FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Smith, JJ Palmer, WE Kattapuram, SV Jensen, ME AF Smith, JJ Palmer, WE Kattapuram, SV Jensen, ME TI Interventional spinal procedures in musculoskeletal radiology: Role in pain management SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Review DE spinal procedures; pain management; facet joint injection; nerve root block; epidural injection ID LOW-BACK-PAIN; PERCUTANEOUS VERTEBROPLASTY; JOINT INJECTION; FACET; METASTASES; CEMENT AB Image-guided procedures have seen explosive growth in the past decade, and spinal interventional procedures directed at back pain are no exception. These interventions may provide valuable diagnostic information regarding the source of the patient's pain, and in many cases provide therapeutic relief of symptoms. Examples of these procedures are facet joint injections, selective and nonselective epidural injections, sacroiliac joint injections, and vertebroplasty. This article discusses general considerations surrounding these techniques, including medication selection. Technical aspects of each procedure are described in detail, with separate discussions of the cervical, thoracic, and lumbar spine applications. While not intended as a substitute for formal training, this information is designed to serve as a reference for both practitioners new to spinal intervention as well as more experienced operators. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Smith, JJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 19 TC 4 Z9 4 U1 1 U2 2 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. PY 1999 VL 16 IS 2 BP 99 EP 112 DI 10.1055/s-0028-1082195 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 209TF UT WOS:000081064400004 ER PT J AU Bird, TD AF Bird, TD TI Risks and benefits of DNA testing for neurogenetic disorders SO SEMINARS IN NEUROLOGY LA English DT Article DE DNA testing; neurogenetic disorders; genetic counseling ID HUNTINGTONS-DISEASE; ABNORMALITIES; DYSTROPHIN; PHENOTYPE; ATAXIA AB DNA testing for mutations in genes causing neurogenetic disorders is becoming a common practice in clinical neurology, The tests are highly sensitive and specific, They are especially valuable in establishing diagnoses in symptomatic patients. These DNA tests are also used in asymptomatic persons at risk for genetic diseases who wish to determine whether or not they have inherited an abnormal gene. There are risks and benefits to such asymptomatic, predictive testing. A number of complex issues need to be considered including precipitation of depression, prenatal diagnosis and testing of children, impact on insurance and employment, legal aspects, possible third-party coercion, and an understanding of each test's limitations. Therefore, these DNA tests need to be used with careful clinical judgment and in the context of each individual patient and family. C1 VA Puget Sound Hlth Care Syst, Geriatr Res Ctr, Seattle, WA 98108 USA. Univ Washington, Dept Neurol, VA Med Ctr, Seattle, WA 98195 USA. Univ Washington, Dept Med, VA Med Ctr, Seattle, WA 98195 USA. RP Bird, TD (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Ctr, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 21 TC 16 Z9 16 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0271-8235 J9 SEMIN NEUROL JI Semin. Neurol. PY 1999 VL 19 IS 3 BP 253 EP 259 DI 10.1055/s-2008-1040841 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 262QB UT WOS:000084077000003 PM 12194381 ER PT J AU Klein, C Breakefield, XO Ozelius, LJ AF Klein, C Breakefield, XO Ozelius, LJ TI Genetics of primary dystonia SO SEMINARS IN NEUROLOGY LA English DT Article DE dystonia; genetics; review ID IDIOPATHIC TORSION DYSTONIA; DOPA-RESPONSIVE DYSTONIA; AUTOSOMAL DOMINANT INHERITANCE; PARKINSONISM SYNDROME LOCUS; CYCLOHYDROLASE-I GENE; FRONTAL-LOBE EPILEPSY; EARLY-ONSET DYSTONIA; ASHKENAZI JEWS; MYOCLONIC DYSTONIA; PAROXYSMAL DYSKINESIA AB Currently, at least 12 types of dystonia can be distinguished on a genetic basis. Advances in the molecular genetics of dystonia have led to the recent identification of a 3-bp deletion in the DYT1 gene, causing early-onset generalized torsion dystonia (TD), and to the detection of mutations in the GTP cyclohydrolase I and the tyrosine hydroxylase genes causing dopa-responsive dystonia (DYT5). A missense change in the D2 dopamine receptor has been shown to be associated with myoclonus-dystonia in one family. In addition, six other dystonia gene loci have been mapped to chromosomal regions, including a locus for a mixed dystonia phenotype (DYT6), one form of focal dystonia (DYT7), two types of paroxysmal dystonia (DYT8, DYT9), X-linked dystonia-parkinsonism (DYT3), and rapid-onset dystonia parkinsonism (DYT12). No positive linkage studies have as yet been reported for autosomal recessive TD (DYT2) and in several other large families with various types of dominantly inherited TD (DYT4), It may be anticipated that the traditional clinical and etiological classifications of dystonia will increasingly be replaced by a genetic one and that the identification of more dystonia genes may lead to a better understanding of these largely nondegenerative disorders. C1 Massachusetts Gen Hosp, Neurol Serv, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Ozelius, LJ (reprint author), AECOM, Mol Genet, 1300 Morris Pk Ave, Bronx, NY 10461 USA. NR 88 TC 15 Z9 16 U1 0 U2 3 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0271-8235 J9 SEMIN NEUROL JI Semin. Neurol. PY 1999 VL 19 IS 3 BP 271 EP 280 DI 10.1055/s-2008-1040843 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 262QB UT WOS:000084077000005 PM 12194383 ER PT J AU Greene, MF AF Greene, MF TI Spontaneous abortions and major malformations in women with diabetes mellitus SO SEMINARS IN REPRODUCTIVE ENDOCRINOLOGY LA English DT Article DE diabetes mellitus; pregnancy; spontaneous abortions; congenital malformations; congenital abnormalities; pregnancy complications ID SERUM ALPHA-FETOPROTEIN; NEURAL-TUBE DEFECTS; FETAL GROWTH DELAY; CONGENITAL-MALFORMATIONS; EARLY-PREGNANCY; GLYCOSYLATED HEMOGLOBIN; MATERNAL HEMOGLOBIN-A1C; UNPLANNED PREGNANCIES; PRENATAL-DIAGNOSIS; GLYCEMIC CONTROL AB Women with insulin dependent diabetes mellitus are at increased risk for both first trimester spontaneous abortions and major congenital malformations when they become pregnant. The magnitudes of both of these risks depend upon the degree of metabolic control of their diabetes in the first trimester. The risks differ in the degree of control necessary to minimize them and the degree to which they can ultimately be reduced. A stricter degree of metabolic control is necessary to avoid spontaneous abortions than major malformations. Although the risks for both complications can be reduced by improved metabolic control, the risk for major malformations remains elevated, when compared to the risk for non-diabetic women, despite good to excellent control. In contrast, good to excellent control does reduce the risk for spontaneous abortions to a rate comparable to that seen in non-diabetic women. Women with insulin dependent diabetes mellitus who are planning pregnancies should be encouraged to achieve the best possible degree of metabolic control prior to and throughout pregnancy. They should be re-assured, however, that perfect control is not necessary to avoid dramatically increased risks for spontaneous abortions and major malformations. C1 Massachusetts Gen Hosp, Vincent Mem Obstet Serv, Div Maternal Fetal Med, Boston, MA 02114 USA. RP Greene, MF (reprint author), Massachusetts Gen Hosp, Vincent Mem Obstet Serv, Div Maternal Fetal Med, Boston, MA 02114 USA. NR 60 TC 64 Z9 65 U1 0 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0734-8630 J9 SEMIN REPROD ENDOCR JI Semin. Reprod. Endocrinol. PY 1999 VL 17 IS 2 BP 127 EP 136 DI 10.1055/s-2007-1016220 PG 10 WC Endocrinology & Metabolism; Obstetrics & Gynecology; Reproductive Biology SC Endocrinology & Metabolism; Obstetrics & Gynecology; Reproductive Biology GA 243YU UT WOS:000083025700004 PM 10528364 ER PT J AU Chang, TI Loeken, MR AF Chang, TI Loeken, MR TI Genotoxicity and diabetic embryopathy: Impaired expression of developmental control genes as a cause of defective morphogenesis SO SEMINARS IN REPRODUCTIVE ENDOCRINOLOGY LA English DT Review DE embryo; diabetes; glucose; neural tube; apoptosis; Pax-3 ID PROGRAMMED CELL-DEATH; PROTEIN-KINASE-C; TUMOR ALVEOLAR RHABDOMYOSARCOMA; FUEL-MEDIATED TERATOGENESIS; CULTURED RAT CONCEPTUS; MOUSE EMBRYOS; CONGENITAL-MALFORMATIONS; SUPEROXIDE-DISMUTASE; OXIDATIVE STRESS; DNA-REPLICATION AB Since the advent of insulin therapy for diabetes mellitus, the survival of mothers with diabetes prior to pergnancy and their offspring has greatly improved. Nevertheless, the observation that the earliest stages of organogenesis can be! impaired in the offspring of women with diabetes raises the question of how abnormal fuel metabolism disturbs embryogenesis. Research into this process has been made possible in recent years by advances in molecular biology which makes it possible to study gene expression in early embryos, and by the availability of genetically engineered mutant mouse strains. Using these approaches, a model is emerging in which elevated glucose, by disturbing expression of genes which regulate embryonic development and cell cycle progression, causes premature cell death of emerging organ structures, thereby causing defective morphogenesis. Investigation into the signaling mechanisms by which excess glucose metabolism exhibits toxic effects on embryo gene expression will explain how diabetic embryopathy occurs on a molecular and cellular level, as well as increase our understanding of the role of metabolic homeostasis in proper embryonic development. C1 Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Sect Mol Biol, Boston, MA 02215 USA. RP Loeken, MR (reprint author), Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Sect Mol Biol, 1 Joslin Pl, Boston, MA 02215 USA. NR 156 TC 26 Z9 26 U1 0 U2 3 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0734-8630 J9 SEMIN REPROD ENDOCR JI Semin. Reprod. Endocrinol. PY 1999 VL 17 IS 2 BP 153 EP 165 DI 10.1055/s-2007-1016222 PG 13 WC Endocrinology & Metabolism; Obstetrics & Gynecology; Reproductive Biology SC Endocrinology & Metabolism; Obstetrics & Gynecology; Reproductive Biology GA 243YU UT WOS:000083025700006 PM 10528366 ER PT J AU Cummings, DE Merriam, GR AF Cummings, DE Merriam, GR TI Age-related changes in growth hormone secretion: Should the somatopause be treated? SO SEMINARS IN REPRODUCTIVE ENDOCRINOLOGY LA English DT Article DE aging; growth hormone (GH, somatotropin); GH deficiency; GH-releasing hormone (GHRH); pituitary ID GH-RELEASING HORMONE; FACTOR-I AXIS; BODY-COMPOSITION; ELDERLY MEN; OLDER MEN; DEFICIENT CHILDREN; CIRCULATING LEVELS; INCREASED RISK; ADULTS; WOMEN AB Growth hormone (GH) secretion declines progressively with aging, and many age-related changes resemble those of the adult GH deficiency (GHD) syndrome, including a decrease in lean body mass; an increase in body fat, especially in the visceral/abdominal compartment; adverse changes in lipoproteins; and a reduction in aerobic capacity. The increase in central obesity can further inhibit GH secretion. GPI replacement is effective in reversing many of these changes in adult GHD, and GH is now FDA approved for treatment of adults with documented GHD or hypopituitarism, although there is still only limited experience with its long-term benefits, side effects, and risks. This early experience with GHD has led to speculation that replacing GH or stimulating its secretion may also be beneficial in normal aging, and to widespread off-label use of GH in this context; however, there are still very few well controlled studies of the effects and side effects of GH or GH secretagogues in aging. All published studies are of 6 months or shorter treatment periods. From this limited experience there is a consensus that GH has effects on body composition, but reports disagree on effects on psychological or physical functional performance. Older adults are much more susceptible to the dose-related side effects of GH, including peripheral edema, carpal tunnel syndrome, and a variable decrease in insulin sensitivity; and it is not known whether chronic GH treatment affects the risk of malignancy or has other long-term risks. Thus while short-term results are somewhat encouraging, the evidence on risks and clinically pertinent benefits is still lacking to support the use of GH in normal aging outside of clinical studies. Ln evaluating patients with clinical features suggesting GHD, which can be quite nonspecific, it is important to assess the presence or absence of true GH deficiency by the context (pituitary disease or its treatment, childhood GHD) and by appropriate GH stimulation tests before considering GH replacement. C1 Univ Washington, Sch Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. RP Merriam, GR (reprint author), VA Puget Sound Hlth Care Syst, A-151,Bldg 18S,Room 5,9600 Vet Blvd SW, Lakewood, WA 98493 USA. NR 72 TC 19 Z9 20 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0734-8630 J9 SEMIN REPROD ENDOCR JI Semin. Reprod. Endocrinol. PY 1999 VL 17 IS 4 BP 311 EP 325 PG 15 WC Endocrinology & Metabolism; Obstetrics & Gynecology; Reproductive Biology SC Endocrinology & Metabolism; Obstetrics & Gynecology; Reproductive Biology GA 312HW UT WOS:000086938700006 PM 10851571 ER PT J AU Jubran, A AF Jubran, A TI Monitoring mechanics during mechanical ventilation SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE resistance; compliance; ventilators ID END-EXPIRATORY PRESSURE; OBSTRUCTIVE PULMONARY-DISEASE; RESPIRATORY-DISTRESS-SYNDROME; AIR-FLOW OBSTRUCTION; ANESTHETIZED PARALYZED HUMANS; CHEST-WALL MECHANICS; COPD PATIENTS; INTRINSIC PEEP; MUSCLE-ACTIVITY; SUPPORT VENTILATION AB Patients with acute respiratory failure necessitating mechanical ventilation have significant abnormalities in pulmonary mechanics, yet formal assessment of their nature is rarely included in clinical decision making, Because of our increased understanding of the pathophysiology, together with the rapid, technological advances, assessment of respiratory mechanics-resistance, compliance, and work of breathing-can be safely and rapidly performed in the intensive care unit (ICU), This chapter provides a review of abnormalities in respiratory mechanics that can be monitored during passive and spontaneous breathing, a description of the methods and techniques, and a summary of clinical observations and applications in critically ill patients. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Hines, IL USA. RP Jubran, A (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Route 111N, Hines, IL 60141 USA. NR 107 TC 2 Z9 2 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1069-3424 J9 SEM RESP CRIT CARE M JI Semin. Respir. Crit. Care Med. PY 1999 VL 20 IS 1 BP 65 EP 79 DI 10.1055/s-2007-1009447 PG 15 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 177CD UT WOS:000079189100008 ER PT J AU Wright, CD AF Wright, CD TI Surgical management of mediastinal tumors and fibrosis SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE mediastinal tumors; mediastinal fibrosis; surgery ID PRIMARY CYSTS; LYMPHOMA; THYMOMA; DIAGNOSIS; ANTERIOR AB Mediastinal tumors are uncommon and often asymptomatic if benign. Tumors have a predilection for arising in one of three mediastinal compartments: the anterior, middle, or posterior. If symptoms are present, they are usually compressive in origin. Computed tomography is almost always the imaging modality of first choice. Benign-appearing lesions are usually resected for cure. Malignant-appearing lesions usually require biopsy by the least invasive route appropriate for the suspected tumor type. Mediastinal fibrosis is thought to be caused by Histoplasma capsulatum most commonly and usually presents with progressive compressive symptoms, Oral antifungal agents have been reported to control the disease. Stenting, superior vena caval bypass, and resectional surgery are sometimes required to palliate obstructive processes. C1 Harvard Med Sch, Boston, MA USA. RP Wright, CD (reprint author), Massachusetts Gen Hosp, Blake 1570,32 Fruit St, Boston, MA 02114 USA. NR 24 TC 0 Z9 1 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1069-3424 J9 SEM RESP CRIT CARE M JI Semin. Respir. Crit. Care Med. PY 1999 VL 20 IS 5 BP 473 EP 481 DI 10.1055/s-2007-1009467 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 250CX UT WOS:000083372400009 ER PT J AU Christiani, DC AF Christiani, DC TI Occupational and environmental lung problems of industrializing countries SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE pneumoconiosis; occupational asthma; developing countries ID TEXTILE WORKERS; PUBLIC-HEALTH; DISEASE; AFRICA; EXPOSURE; CAPE AB Over the past three decades, industrial activity has increased rapidly in developing nations. Industrial growth and intensive agriculture has also increased the health risks faced by workers in the countries by intensifying existing health problems and by introducing new hazards. Many of these hazards pose a threat to respiratory health. This brief report reviews the occupational respiratory problems of industrializing nations and areas for future research. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. NR 38 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 1069-3424 J9 SEM RESP CRIT CARE M JI Semin. Respir. Crit. Care Med. PY 1999 VL 20 IS 6 BP 551 EP 558 DI 10.1055/s-2007-1009474 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 269FV UT WOS:000084466800006 ER PT J AU Nylen, E Muller, B Snider, R Vath, S Wagner, K White, J Zulewski, H Vannier, E Habener, J Becker, K AF Nylen, E Muller, B Snider, R Vath, S Wagner, K White, J Zulewski, H Vannier, E Habener, J Becker, K TI Pathophysiologial significance of calcitonin precursors in sepsis and systemic inflammation SO SHOCK LA English DT Meeting Abstract C1 George Washington Univ, VAMC, Washington, DC USA. Georgetown Univ, Washington, DC USA. Harvard Univ, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 3 Z9 4 U1 0 U2 0 PU BIOMEDICAL PRESS PI AUGUSTA PA 1021 15TH ST, BIOTECH PARK STE 9,, AUGUSTA, GA 30901 USA SN 1073-2322 J9 SHOCK JI Shock PY 1999 VL 12 SU 1 MA 51 BP 14 EP 14 PG 1 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 252BJ UT WOS:000083480600044 ER PT J AU Freebourn, TM Barber, DB Able, AC AF Freebourn, TM Barber, DB Able, AC TI The treatment of immature heterotopic ossification in spinal cord injury with combination surgery, radiation therapy and NSAID SO SPINAL CORD LA English DT Article DE heterotopic ossification; spinal cord injury; nonsteroidal antiinflammatory agents; radiation therapy ID HIP AB Heterotopic ossification (HO) is a frequent complication associated with spinal cord injury. Management of HO consists of a combination of range-of-motion, diphosphonates nonsteroidal antiinflammatory agents, radiation therapy, and in some cases, surgical resection. The appropriate timing of surgical resection has traditionally been based on maturity of the HO. The case presented is that of a 33-year-old male with T8 complete paraplegia who developed HO about the left hip resulting in impaired sitting. The patient underwent successful surgical wedge resection of the HO despite apparent immaturity of the HO. A comprehensive review of the literature is presented which suggests that early resection of immature HO may not be predictive of a higher recurrence rate. C1 Univ Texas, Hlth Sci Ctr, Dept Rehabil Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Spinal Cord Injury Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. RP Barber, DB (reprint author), Univ Texas, Hlth Sci Ctr, Dept Rehabil Med, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 28 TC 28 Z9 28 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD JAN PY 1999 VL 37 IS 1 BP 50 EP 53 DI 10.1038/sj.sc.3100719 PG 4 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 161QZ UT WOS:000078301600010 PM 10025696 ER PT J AU Sigal, EV AF Sigal, EV TI Report from the March research task force - Commissioned by THE MARCH - Coming together to conquer cancer SO STEM CELLS LA English DT Article C1 Massey Canc Ctr, Richmond, VA USA. Duke Univ, Med Ctr, Sch Med, Durham, NC 27706 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Oncol Ctr, Breast Canc Program, Baltimore, MD 21205 USA. Univ Miami, Sch Med, Sylvester Comprehens Canc Ctr, Coral Gables, FL 33124 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Yale Univ, Ctr Canc, New Haven, CT 06520 USA. Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA. RP Sigal, EV (reprint author), 3299 K St NW,Suite 100, Washington, DC 20007 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 1999 VL 17 IS 6 BP 382 EP 419 PG 38 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 261BZ UT WOS:000083989100011 ER PT J AU Shimizu-Sasamata, M Bosque-Hamilton, P Huang, PL Moskowitz, MA Lo, EH AF Shimizu-Sasamata, M Bosque-Hamilton, P Huang, PL Moskowitz, MA Lo, EH TI Attenuated neurotransmitter release and spreading depression-like depolarizations after focal cerebral ischemia in mice lacking the gene for neuronal nitric oxide synthase (nNOS) SO STROKE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1999 VL 30 IS 1 MA 6 BP 232 EP 232 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 155EW UT WOS:000077934200057 ER PT J AU Ay, H Buonanno, FS Schaefer, PW Furie, KL Rordorf, G Gonzalez, RG Kistler, JP Koroshetz, WJ AF Ay, H Buonanno, FS Schaefer, PW Furie, KL Rordorf, G Gonzalez, RG Kistler, JP Koroshetz, WJ TI Clinical and Diffusion-Weighted Imaging characteristics of an identifiable subset of TIA patients with acute infarction. SO STROKE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 7 Z9 7 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1999 VL 30 IS 1 MA 19 BP 235 EP 235 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 155EW UT WOS:000077934200076 ER PT J AU Oliveira, J Ay, H Buonanno, FS Schwamm, LH McDonald, CT Ezzeddine, M Segal, AZ Koroshetz, WJ AF Oliveira, J Ay, H Buonanno, FS Schwamm, LH McDonald, CT Ezzeddine, M Segal, AZ Koroshetz, WJ TI Clinical correlates of acute small subcortical or brainstem infarctions detected by diffusion-weighted MRI SO STROKE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1999 VL 30 IS 1 MA 21 BP 235 EP 235 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 155EW UT WOS:000077934200072 ER PT J AU Segal, AZ Lev, MH Lee, SH Jeffery, F Jonathan, R Putman, CM Budzik, RF Hunter, GJ Rordorf, G Buonanno, F Koroshetz, WJ Gonzalez, G AF Segal, AZ Lev, MH Lee, SH Jeffery, F Jonathan, R Putman, CM Budzik, RF Hunter, GJ Rordorf, G Buonanno, F Koroshetz, WJ Gonzalez, G TI CT-perfusion imaging in acute stroke with MCA stem occlusion: Predicting outcome after intra-arterial (IA) thrombolysis SO STROKE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1999 VL 30 IS 1 MA 98 BP 248 EP 248 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 155EW UT WOS:000077934200149 ER PT J AU Sorensen, AG Wu, O Copen, WA Ay, H Gonzalez, G Finklestein, S AF Sorensen, AG Wu, O Copen, WA Ay, H Gonzalez, G Finklestein, S TI Statistical modeling of acute stroke MRI data can suggest therapeutic efficacy SO STROKE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1999 VL 30 IS 1 MA P52 BP 261 EP 261 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 155EW UT WOS:000077934200229 ER PT J AU Farkas, J Budzik, R Huang-Hellinger, F Schwamm, L Buonanno, F Rordorf, G Koroshetz, W Gonzalez, G Christopher, P AF Farkas, J Budzik, R Huang-Hellinger, F Schwamm, L Buonanno, F Rordorf, G Koroshetz, W Gonzalez, G Christopher, P TI Intra-arterial thrombolysis in hyperacute Stroke SO STROKE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1999 VL 30 IS 1 MA P72 BP 264 EP 264 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 155EW UT WOS:000077934200246 ER PT J AU Egan, RA Lutsep, HL Clark, WM AF Egan, RA Lutsep, HL Clark, WM TI Hereditary resistance to activated protein C and plasma homocysteine screening in patients with retinal artery and vein occlusion and ischemic optic neuropathy SO STROKE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1999 VL 30 IS 1 MA P9 BP 269 EP 269 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 155EW UT WOS:000077934200276 ER PT J AU Singer, RJ Putman, C Budzick, R Choi, IS Huang-Hellinger, F Ogilvy, CS AF Singer, RJ Putman, C Budzick, R Choi, IS Huang-Hellinger, F Ogilvy, CS TI Risks and efficacy of combined endovascular and surgical management of intracranial dural arteriovenous malformations SO STROKE LA English DT Meeting Abstract C1 Lahey Clin, Burlington, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1999 VL 30 IS 1 MA P17 BP 271 EP 271 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 155EW UT WOS:000077934200284 ER PT J AU Kelly, PJ Primavera, J Chang, YC Buonanno, FS Rordorf, G Hedley-White, ET Gonzalez, RG AF Kelly, PJ Primavera, J Chang, YC Buonanno, FS Rordorf, G Hedley-White, ET Gonzalez, RG TI Radiologic-pathologic correlation of diffusion weighted MRI signal abnormality in patients with recent ischemic stroke SO STROKE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1999 VL 30 IS 1 MA P69 BP 279 EP 279 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 155EW UT WOS:000077934200336 ER PT S AU Dwyer, PJ DiMarzio, CA AF Dwyer, PJ DiMarzio, CA BE Nguyen, C TI Hyperspectral imaging for dermal hemoglobin spectroscopy SO SUBSURFACE SENSORS AND APPLICATIONS SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Subsurface Sensors and Applications CY JUL 19-21, 1999 CL DENVER, CO SP SPIE DE oxygen saturation; hemoglobin; reflectance spectroscopy ID SKIN; OPTICS AB It has been shown previously that images collected at selected wavelengths in a sufficiently narrow bandwidth can be used to produce maps of the oxygen saturation of hemoglobin in the dermis. A four-wavelength algorithm has been developed based on a two-layer model of the skin, in which the blood is contained in the lower layer (dermis), while the upper layer attenuates some of the reflection and adds a clutter term. In the present work, the algorithm is compared analytically to simpler algorithms using three wavelengths and based on a single-layer model. It is shown through Monte-Carlo models that, for typical skin, the single-layer model is adequate to analyze data from fiber-optical reflectance spectroscopy, but the two-layer model produces better results for imaging systems. Although the model does not address the full complexity of reflectance of a two-layer skin, it has proven to be sufficient to recover the oxygen saturation, and perhaps other medically relevant information. The algorithm is demonstrated on a suction blister, where the epidermis is removed to reveal the underlying dermis. Applications for this imaging modality exist in dermatology, in surgery and in developing treatment plans for various diseases. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Dwyer, PJ (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, 50 Blossom St,Bartlett Extens Bldg, Boston, MA 02114 USA. NR 7 TC 10 Z9 10 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3238-5 J9 P SOC PHOTO-OPT INS PY 1999 VL 3752 BP 72 EP 82 DI 10.1117/12.365686 PG 11 WC Engineering, Multidisciplinary SC Engineering GA BN95D UT WOS:000083637300009 ER PT S AU Gaudette, TJ DiMarzio, CA Townsend, DJ AF Gaudette, TJ DiMarzio, CA Townsend, DJ BE Nguyen, C TI Interaction of diffusive waves and ultrasound SO SUBSURFACE SENSORS AND APPLICATIONS SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Subsurface Sensors and Applications CY JUL 19-21, 1999 CL DENVER, CO SP SPIE DE Ultrasound Modulation of Light; diffusive optical tomography ID TURBID MEDIA; MODULATION; TOMOGRAPHY; LIGHT AB The interaction of ultrasound with diffusive optical waves holds the promise of improved resolution and depth of penetration for non-ionizing, non-invasive medical imaging. Light offers the ability to make spectroscopic measurements, which can monitor metabolism but, while it can propagate deeply into the body at near infrared wavelengths, it is so strongly scattered in most tissues that imaging is achieved only with measures such as time-resolved or frequency-domain techniques. On the other hand ultrasound has the ability to penetrate deeply with considerably less scattering. We have proposed a mechanism for imaging through the body by mixing diffusive optical waves with focussed ultrasound to produce new, so-called virtual diffusive sources. In the present work, we consider various mechanisms of interaction and report some results suggesting that the interaction in a laboratory phantom is predominantly the result of particle motion rather than variations in the index of refraction of the background medium. This result may be important in development of techniques to maximize the strengths of the virtual sources. C1 Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. RP Gaudette, TJ (reprint author), Massachusetts Gen Hosp, NMR Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3238-5 J9 P SOC PHOTO-OPT INS PY 1999 VL 3752 BP 83 EP 89 DI 10.1117/12.365687 PG 7 WC Engineering, Multidisciplinary SC Engineering GA BN95D UT WOS:000083637300010 ER PT J AU Talcott, JA Stomper, PC Drislane, FW Wen, PY Block, CC Humphrey, CC Lu, C Jolesz, F AF Talcott, JA Stomper, PC Drislane, FW Wen, PY Block, CC Humphrey, CC Lu, C Jolesz, F TI Assessing suspected spinal cord compression - A multidisciplinary outcomes analysis of 342 episodes SO SUPPORTIVE CARE IN CANCER LA English DT Article; Proceedings Paper CT Annual Meeting of the Multinational-Association-of-Supportive-Care-in-Cancer CY MAR 17, 1998 CL SAN ANTONIO, TEXAS SP Multinational Assoc Support Care Canc DE spinal cord compression; risk assessment; spinal neoplasms, secondary ID EPIDURAL METASTASES; BACK PAIN; SURGICAL-TREATMENT; EARLY DIAGNOSIS; CANCER; DECOMPRESSION; STABILIZATION; IRRADIATION; PROGNOSIS; VERTEBRAE AB The object of this work was to evaluate the assessment and document the outcomes of cancer patients with suspected spinal cord compression (SCC). In a retrospective cohort study of 342 episodes of suspected SCC in cancer patients evaluated by computed tomography (CT) of the spine, a multidisciplinary team of neurologists, radiologists, and oncologists assessed the impact of varying the anatomical criterion for SCC and including new SCC diagnosed shortly after definitive radiographical imaging. We developed a logistic regression model to identify independent clinical predictors of SCC, including the natural history of the underlying cancer as well as neurological and radiological risk factors. Management of suspected SCC infrequently involved neurology consultation (21% of episodes). The frequency of SCC increased more than four-fold when the definition was expanded to include epidural cancer rather than spinal cord displacement only (36% vs 8%), and 90-day clinical follow-up identified few new lesions not evident on definitive imaging studies. Clinical information about the course of cancer (documentation and duration of metastatic cancer) added independent predictive information to that yielded by neurological assessment and prior imaging studies in a multiple regression model. The a priori predicted risk of SCC, which ranged from 4% to 87% in this study, may vary enough to affect treatment strategies, although our population may have excluded very-low-risk patients. Consistent anatomical definitions of SCC, clinical follow-up of definitive imaging studies and the addition of information on the natural history of cancer to traditional neurological and radiographical evaluation may all improve clinical assessment of suspected SCC in cancer patients. C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Hosp, Boston, MA 02215 USA. RP Talcott, JA (reprint author), Massachusetts Gen Hosp, Ctr Outcomes Res, B75 230,55 Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [CA01418, CA08242] NR 34 TC 15 Z9 15 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD JAN PY 1999 VL 7 IS 1 BP 31 EP 38 DI 10.1007/s005200050220 PG 8 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 147ZG UT WOS:000077527300007 PM 9926972 ER PT J AU Grillo, HC AF Grillo, HC TI To impart this art: The development of graduate surgical education in the United States SO SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Thorac Surg, Gen Thorac Surg Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Grillo, HC (reprint author), Massachusetts Gen Hosp, Dept Thorac Surg, Gen Thorac Surg Unit, 55 Fruit St, Boston, MA 02114 USA. NR 29 TC 21 Z9 21 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD JAN PY 1999 VL 125 IS 1 BP 1 EP 14 DI 10.1016/S0039-6060(99)70280-1 PG 14 WC Surgery SC Surgery GA 155QK UT WOS:000077957700001 PM 9889790 ER PT J AU Rattner, DW AF Rattner, DW TI Beyond the laparoscope: Minimally invasive surgery in the new millennium SO SURGERY LA English DT Review C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Innovat Minimally Invas Therapy, Boston, MA 02114 USA. RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 8 TC 3 Z9 9 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD JAN PY 1999 VL 125 IS 1 BP 19 EP 22 DI 10.1016/S0039-6060(99)70283-7 PG 4 WC Surgery SC Surgery GA 155QK UT WOS:000077957700004 PM 9889793 ER PT J AU Sheridan, RL Lydon, MM Petras, LM Schomacker, KT Tompkins, RG Glatter, RD Parrish, JA AF Sheridan, RL Lydon, MM Petras, LM Schomacker, KT Tompkins, RG Glatter, RD Parrish, JA TI Laser ablation of burns: Initial clinical trial SO SURGERY LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the American-Burn-Association CY MAR 18-21, 1998 CL CHICAGO, IL SP Amer Burn Assoc ID CARBON-DIOXIDE LASER; BLOOD-LOSS; SKIN INCISIONS; THERMAL-DAMAGE; CO2-LASER; EXCISION; SCALPEL; TRANSFUSION; WOUNDS; GRAFT AB Background. Scanning, high-powered carbon dioxide laser ablation of eschar may facilitate blood conservation in patients with burns. Methods. Twenty-one children with full-thickness burns that required serial excisions were enrolled in a Human Studies Committee approved protocol in which a full-thickness wound was ablated with a rapidly scanned continuous wave carbon dioxide laser system. A control wound was sharply excised and both wounds were immediately autografted. Endpoints were engraftment at 7 days and serial Vancouver scar scores. Results, The children had an average age of 8.3 +/- 1.2 years, weight of 36.3 +/- 4.9 kg, and burn size of 40% +/- 5.1%. The study wounds were ablated with an average energy of 99.2 +/- 5.7 W; there was no bleeding from 19 successfully ablated wounds. Initial engraftment averaged 94.7% +/- 3.5% in the control sites and 94.7% +/- 3.3% in the study sites (P = 1.0). There was no significant difference in Vancouver scar scores at an average follow-up of 32.0 +/- 5.2 weeks. Conclusions. This Pilot study follows a successful trial of this this concept in a porcine model and demonstrates the technical feasibility of laser vaporization of burn eschar in humans with immediate autografting. Further refinement of the technique is required before it can be generally recommended. C1 Shriners Burns Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Burns & Trauma, Dept Surg, Boston, MA USA. Wellman Labs Photomed, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Sheridan, RL (reprint author), Shriners Burns Hosp, 51 Blossom St, Boston, MA 02114 USA. NR 36 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD JAN PY 1999 VL 125 IS 1 BP 92 EP 95 DI 10.1016/S0039-6060(99)70293-X PG 4 WC Surgery SC Surgery GA 155QK UT WOS:000077957700014 PM 9889803 ER PT J AU Shimada, H Alexander, RC Germana, S Sachs, DH LeGuern, C AF Shimada, H Alexander, RC Germana, S Sachs, DH LeGuern, C TI Recombinant retrovirus vectors for the expression of MHC class II heterodimers SO SURGERY TODAY-THE JAPANESE JOURNAL OF SURGERY LA English DT Article DE retrovirus; MHC class II; transcription; tolerance ID MAJOR HISTOCOMPATIBILITY COMPLEX; MEDIATED GENE-TRANSFER; MINIATURE SWINE; BONE-MARROW; REVERSE TRANSCRIPTION; CELLS; CDNA; TRANSPLANTATION; TRANSDUCTION; ALLOGRAFTS AB Class II antigens are critical in determining the fate of vascularized allografts across major histocompatibility differences. We have recently developed a new approach to induce transplantation tolerance in miniature swine by creating MHC class II antigen "molecular chimerism" in bone marrow cells of potential recipients through retrovirus-mediated gene transfer. As part of this project, the ability of a recombinant double expression vector (ZQ32N) to express MHC class II DQA and DQB was investigated. Flow cytometry analyses of ZQ32N transfected virus-producer cells demonstrated the cell surface expression of DQa/DQb heterodimers, thus suggesting a correct transcription, translation, and transport of the swine polypeptides to the cell surface. The analyses of RNA isolated from virus particles produced from ZQ32N transfected virus-producer cells indicated the DQ sequences to be correctly packaged. However, the DQ-negative cells transduced with the ZQ32N retrovirus did not show any DQ-retrovirus surface expression. Southern and Northern blot analyses of ZQ32N transfected and transduced cells strongly suggested DNA rearrangements and deletions which could account for transgene expression loss. An analysis of transduced cell genomes suggested DNA recombinations targeted to homologous sequences within the recombinant provirus, The implications of the sequence instability in designing vectors for gene therapy of organ transplantation are discussed. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Shimada, H (reprint author), Chiba Univ, Sch Med, Dept Surg 2, 1-8-1 Inohana, Chiba 2608670, Japan. FU NHLBI NIH HHS [HL48049]; NIAID NIH HHS [AI33053] NR 42 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0941-1291 J9 SURG TODAY JI Surg. Today-Jpn. J. Surg. PY 1999 VL 29 IS 6 BP 533 EP 541 PG 9 WC Surgery SC Surgery GA 202UH UT WOS:000080670200006 PM 10385368 ER PT S AU Porte, D AF Porte, D BE Hansen, BC Saye, J Wennogle, LP TI Mechanisms for hyperglycemia in the Metabolic Syndrome - The key role of beta-cell dysfunction SO THE METABOLIC SYNDROME X: CONVERGENCE OF INSULIN RESISTANCE, GLUCOSE INTOLERANCE, HYPERTENSION, OBESITY, AND DYSLIPIDEMIAS-SEARCHING FOR THE UNDERLYING DEFECTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on The Metabolic Syndrome X - Convergence of Insulin Resistance, Glucose Intolerance, Hypertension, Obesity, and Dyslipidemias-Searching for the Underlying Defects CY FEB 19-22, 1999 CL JACKSONVILLE, FLORIDA SP New York Acad Sci, Parke Davis Pharmaceut Res Inst, Janssen Res Fdn, Knoll Pharmaceut Co, Novartis Pharma AG, Amer Heart Assoc Council Circulat, Bristol Myers Squibb, Pharmaceut Res Inst, DuPont Pharmaceut Co, GelTex Pharmaceut Inc, Genome Therapeut Corp, Inst Diabet Discovery Inc, Lilly Res Labs, Div Endocrine Res & Clin Invest, Merck Res Labs, Schering Plough Res Inst, Smithkline Beecham Pharmaceut ID DEPENDENT DIABETES-MELLITUS; IMPAIRED GLUCOSE-TOLERANCE; JAPANESE-AMERICAN MEN; INSULIN-SECRETION; TARGETED DISRUPTION; GLUCOKINASE GENE; WEIGHT-GAIN; NIDDM; SENSITIVITY; MICE AB Hyperglycemia in Type 2 diabetes represents a steady-state re-regulation of plasma glucose to a higher-than-normal Level after an overnight fast. The underlying pathophysiology represents an interaction between impaired beta-cell function and peripheral and hepatic insulin resistance which leads to abnormal hepatic glucose production. Subjects with the Metabolic Syndrome are at an increased risk for Type 2 diabetes and often have one or both of these disorders present even when glucose tolerance is normal. Thus, sophisticated measures of beta-cell function and insulin sensitivity demonstrate a high frequency in populations characterized as having a high prevalence of atherosclerosis, central obesity, hypertension, and dyslipidemia with or without impaired glucose tolerance. Hyperglycemia compensates for the impairment of beta-cell function and therefore, in our view, the beta-cell is the critical factor in its development. Hyperinsulinemia, a curvilinear compensation for insulin resistance that is closely correlated with central adiposity, is another important predictor of hyperglycemia. In a Japanese-American population followed for five years, impaired beta-cell function was present at baseline and preceded the accumulation of intraabdominal fat in those who developed Type 2 diabetes five years later. This interaction between these two pathophysiologic abnormalities in this sequence supports the hypothesis that beta-cell dysfunction contributes to the development of central adiposity by reduced CNS insulin signaling. C1 Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Porte, D (reprint author), Vet Affairs Med Ctr, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 27 TC 21 Z9 21 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-207-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 892 BP 73 EP 83 DI 10.1111/j.1749-6632.1999.tb07786.x PG 11 WC Cell Biology; Endocrinology & Metabolism; Multidisciplinary Sciences; Physiology SC Cell Biology; Endocrinology & Metabolism; Science & Technology - Other Topics; Physiology GA BP20K UT WOS:000084392400006 PM 10842653 ER PT S AU Patti, ME AF Patti, ME BE Hansen, BC Saye, J Wennogle, LP TI Nutrient medullation of cellular insulin action SO THE METABOLIC SYNDROME X: CONVERGENCE OF INSULIN RESISTANCE, GLUCOSE INTOLERANCE, HYPERTENSION, OBESITY, AND DYSLIPIDEMIAS-SEARCHING FOR THE UNDERLYING DEFECTS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on The Metabolic Syndrome X - Convergence of Insulin Resistance, Glucose Intolerance, Hypertension, Obesity, and Dyslipidemias-Searching for the Underlying Defects CY FEB 19-22, 1999 CL JACKSONVILLE, FL SP New York Acad Sci, Parke Davis Pharmaceut Res Inst, Janssen Res Fdn, Knoll Pharmaceut Co, Novartis Pharma AG, Amer Heart Assoc Council Circulat, Bristol Myers Squibb, Pharmaceut Res Inst, DuPont Pharmaceut Co, GelTex Pharmaceut Inc, Genome Therapeut Corp, Inst Diabet Discovery Inc, Lilly Res Labs, Div Endocrine Res & Clin Invest, Merck Res Labs, Schering Plough Res Inst, Smithkline Beecham Pharmaceut ID DEPENDENT DIABETES-MELLITUS; FREE FATTY-ACID; GLUCOSE-TRANSPORT SYSTEM; ISOLATED RAT HEPATOCYTES; GLUTAMINE-FRUCTOSE-6-PHOSPHATE AMIDOTRANSFERASE; SKELETAL-MUSCLE; AMINO-ACIDS; IN-VIVO; PERIPHERAL INSULIN; PROTEIN-SYNTHESIS AB Abundant evidence supports a crucial Pole for dietary factors in the induction and maintenance of insulin resistance. At the cellular and tissue level, the availability of substrates for cellular energy production may play an important role in metabolic regulation and, in particular, in determining the response to insulin stimulation. The infusion of amino acids or fatty acids decreases insulin-stimulated glucose disposal in vivo; sustained hyperglycemia also induces insulin resistance. To determine whether nutrients directly affect insulin signaling, we have evaluated the impact of fatty acids, amino acids, and activation of the hexosamine pathway on insulin signaling in both cultured cells and animal models. We demonstrate that fatty acids and amino acids inhibit early post-receptor steps in insulin action, including tyrosine phosphorylation of insulin receptor substrate ORS) proteins and activation of phosphatidylinositol 3-kinase (PI3-kinase), both in vitro and in several in vivo models. Similarly, activation of the hexosamine pathway by infusion of glucosamine also reduces insulin-stimulated phosphorylation of IRS proteins, activation of PI3-kinase, and activation of glycogen synthase. These data suggest that nutrients directly modulate insulin signaling, perhaps via common pathways, and thus contribute to cellular insulin resistance. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Patti, ME (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM pattim@joslab.harvard.edu FU NIDDK NIH HHS [K08 DK 02526-01] NR 68 TC 32 Z9 32 U1 1 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-208-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 892 BP 187 EP 203 DI 10.1111/j.1749-6632.1999.tb07796.x PG 17 WC Cell Biology; Endocrinology & Metabolism; Multidisciplinary Sciences; Physiology SC Cell Biology; Endocrinology & Metabolism; Science & Technology - Other Topics; Physiology GA BP20K UT WOS:000084392400016 PM 10842663 ER PT J AU Fukata, S Kuma, K Sugawara, M AF Fukata, S Kuma, K Sugawara, M TI Granulocyte colony-stimulating factor (G-CSF) does not improve recovery from antithyroid drug-induced agranulocytosis: A prospective study SO THYROID LA English DT Article ID METHIMAZOLE-INDUCED AGRANULOCYTOSIS AB Agranulocytosis is the most serious side effect of antithyroid drug (ATD) therapy. We conducted prospective and randomized studies to examine whether granulocyte colony-stimulating factor (G-CSF) is actually effective for ATD-induced agranulocytosis. Twenty-four patients with Graves' disease who developed agranulocytosis during ATD therapy were randomly divided into a G-CSF group (n = 14) and an untreated group (n = 10). Subcutaneous injection of G-CSF (100 to 250 mu g) was given daily until neutrophil counts rose to greater than 1000/mu L. The untreated group received antibiotic therapy only. Recovery time, which is defined as the number of days required for neutrophil counts to exceed 500/mu L, was monitored by daily complete blood count (CBC). Recovery time in the G-CSF-treated group did not differ from that of the untreated group in those patients with moderate and severe agranulocytosis; thus, prolonged use of G-CSF treatment is generally ineffective for ATD-induced agranulocytosis. C1 Kuma Hosp, Chuo Ku, Kobe, Hyogo 6500011, Japan. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Med Serv, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. RP Fukata, S (reprint author), Kuma Hosp, Chuo Ku, 8-2-35 Shimoyamate Dori, Kobe, Hyogo 6500011, Japan. NR 10 TC 59 Z9 63 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD JAN PY 1999 VL 9 IS 1 BP 29 EP 31 DI 10.1089/thy.1999.9.29 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 164WX UT WOS:000078487500006 PM 10037073 ER PT J AU Dzik, S AF Dzik, S TI Epitope mapping: three-dimensional insights from molecular biology SO TRANSFUSION LA English DT Editorial Material ID EXPRESSION; PROTEIN C1 Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. RP Dzik, S (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, 55 Fruit St, Boston, MA 02114 USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JAN PY 1999 VL 39 IS 1 BP 1 EP 5 PG 5 WC Hematology SC Hematology GA 157FQ UT WOS:000078050300001 PM 9920159 ER PT S AU Ryan, L Molenberghs, G AF Ryan, L Molenberghs, G BE Bailer, AJ Maltoni, C Bailar, JC Belpoggi, F Brazier, JV Soffritti, M TI Statistical methods for developmental toxicity - Analysis of clustered multivariate binary data SO UNCERTAINTY IN THE RISK ASSESSMENT OF ENVIRONMENTAL AND OCCUPATIONAL HAZARDS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT International Workshop on Uncertainty in the Risk Assessment of Environmental and Occupational Hazards CY SEP 24-26, 1998 CL BOLOGNA, ITALY SP European Fdn Oncol & Environm Sci B Ramazzini, Int Stat Inst, Miami Univ, Univ Chicago, Natl Ctr Toxicol Res, NIEHS, NIOSH, Akzo Nobel NV, Reg Agcy Prevent & Envoronm, Agcy Tox Subst & Dis Registry, Collegium Ramazzini, DSM ID GENERALIZED LINEAR-MODELS; GLYCOL DIMETHYL ETHER; REGRESSION-MODELS; LONGITUDINAL DATA; MIXED MODELS; MICE; RESPONSES; OUTCOMES; RATS; TERATOLOGY AB This paper discusses some of the statistical issues that arise from developmental toxicity studies, wherein pregnant mice are exposed to chemicals in order to assess possible adverse effects on developing Fetuses. We begin with a review of some current approaches to risk assessment, based on NOAELs, and provide justification for the use of methods based on dose-response models, Due to the hierarchical nature of the data, such models are more complicated in the present context than, say, in cancer studies. For example, multivariate binary outcomes arise when each fetus in a litter is assessed for the presence of malformations and/or tow birth weight. We describe a multivariate exponential family model that works well for these data and that is flexible in terms of allowing response rates to depend on cluster size. Maximum Likelihood estimation of model parameters and the construction of score tests for dose effect are briefly discussed. Results are illustrated with data from several NTP studies. C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Limburgs Univ Ctr, Ctr Stat, B-3590 Diepenbeek, Belgium. RP Ryan, L (reprint author), Harvard Univ, Sch Publ Hlth, 44 Binney St, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NCI NIH HHS [CA48061] NR 43 TC 4 Z9 4 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-236-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 895 BP 196 EP 211 DI 10.1111/j.1749-6632.1999.tb08086.x PG 16 WC Public, Environmental & Occupational Health; Multidisciplinary Sciences SC Public, Environmental & Occupational Health; Science & Technology - Other Topics GA BP49Z UT WOS:000085328100014 PM 10676418 ER PT J AU Giovannucci, E Platz, EA Stampfer, MJ Chan, A Krithivas, K Kawachi, I Willett, WC Kantoff, PW AF Giovannucci, E Platz, EA Stampfer, MJ Chan, A Krithivas, K Kawachi, I Willett, WC Kantoff, PW TI The CAG repeat within the androgen receptor gene and benign prostatic hyperplasia SO UROLOGY LA English DT Article ID CANCER RISK; TRANSACTIVATION; ASSOCIATION; FINASTERIDE AB Objectives. Shorter CAG repeat lengths in exon 1 of the androgen receptor (AR) gene are associated with a stronger transcriptional activity of the AR and with a higher risk of prostate cancer. Because benign prostatic hyperplasia (BPH) is an androgen-dependent condition, we examined the hypothesis that men with shorter AR gene CAG repeat lengths have an increased risk of developing BPH. Methods. Using data from the Health Professionals Follow-up Study (HPFS), we evaluated the relationship between AR gene CAG repeat length and prevalent BPH, as defined by BPH surgery, by enlarged prostate gland detected by digital rectal examination, and by urinary symptoms as determined by the American Urological Association Symptom Index. Results. The odds ratio for BPH surgery or enlarged prostate gland was 1.92 (95% confidence interval [CI] 1.22 to 3.03; P [trend] = 0.0002), comparing AR gene CAG repeat length of 19 or less to 25 or more. Results were similar for the end points of BPH surgery (P [trend] = 0.002) and for enlarged prostate gland (P [trend] = 0.001), For a six-repeat decrease in CAG repeat length, the odds ratio for having moderate or severe urinary obstructive symptoms from an enlarged prostate gland was 3.62 (95% CI 1.51 to 8.67; P = 0.004). Conclusions. Variability in the AR gene CAG repeat influences the development of symptomatic BPH, particularly in predicting obstructive urinary symptoms. Our findings support further study to establish the appropriate clinical relevance. UROLOGY 53: 121-125, 1999, (C) 1999, Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Giovannucci, E (reprint author), Harvard Univ, Sch Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA55075, CA72036]; NIDDK NIH HHS [DK45779] NR 20 TC 93 Z9 96 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD JAN PY 1999 VL 53 IS 1 BP 121 EP 125 DI 10.1016/S0090-4295(98)00468-3 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 151UR UT WOS:000077739500025 PM 9886600 ER PT J AU Clark, JA Rieker, P Propert, KJ Talcott, JA AF Clark, JA Rieker, P Propert, KJ Talcott, JA TI Changes in quality of life following treatment for early prostate cancer SO UROLOGY LA English DT Article ID HEALTH SURVEY SF-36; OF-LIFE; RADICAL PROSTATECTOMY; CLINICAL-TRIALS; MEDICAL OUTCOMES; END-POINTS; SENSITIVITY; QLQ-C30; SURGERY; THERAPY AB Objectives. To explore the effects of urinary, bowel, and sexual symptoms following treatment for early (nonmetastatic) prostate cancer on health-related quality of life through an examination of the responsiveness of the Medical Outcomes Study Short Form Health Survey (SF-36). Methods. We conducted a prospective observational cohort study of 125 men with early prostate cancer who underwent either radical prostatectomy or radical, external beam radiotherapy. Patients completed questionnaires, which included assessments of urinary, bowel, and sexual symptoms and the SF-36 at the time of their clinical consultation prior to deciding on primary therapy and at 3 and 12-month follow-up, Results. Although cross-sectional analysis showed substantial associations between symptoms and the eight scales of the SF-36 12 months after the initiation of treatment, longitudinal analyses of changes in these scales showed only modest effects. Three scales registered changes associated with the development of new symptoms: General Health Perceptions, Vitality, and Social Function. Role Performance with Emotional Limitations demonstrated a surprising response: slight improvements in men with new symptoms, compared with substantial gains in men who survived treatment without developing new urinary, bower, or sexual symptoms. Overall, the SF-36 demonstrated a pattern of decline at 3 months and recovery to baseline at 12 months. Rather than registering declines in response to increasing symptoms, negative changes occurred primarily in men who presented symptoms prior to treatment and whose symptoms were unchanged 12 months later. Conclusions. The SF-36 is associated with the presence of physical symptoms but demonstrates a complicated pattern of change following treatment and the development of new urinary, bowel, and sexual problems. Multidimensional approaches to the outcomes of treatment for early prostate cancer help to clarify the magnitude of both gains and losses in quality of life. UROLOGY 53: 161-168, 1999. (C) 1999, Elsevier Science Inc. All rights reserved. C1 Edith Nourse Rogers Mem Vet Adm Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Clark, JA (reprint author), Edith Nourse Rogers Mem Vet Adm Hosp, Ctr Hlth Qual Outcomes & Econ Res, 200 Springs Rd, Bedford, MA 01730 USA. NR 37 TC 63 Z9 66 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD JAN PY 1999 VL 53 IS 1 BP 161 EP 168 DI 10.1016/S0090-4295(98)00457-9 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 151UR UT WOS:000077739500031 PM 9886606 ER PT B AU Leaf, A AF Leaf, A BE NavarroLopez, F TI Nutrition science and policy: Implications for Mediterranean diets SO XXI CONGRESS OF THE EUROPEAN SOCIETY OF CARDIOLOGY LA English DT Proceedings Paper CT 21st Congress of the European-Society-of-Cardiology CY AUG 28-SEP 01, 1999 CL BARCELONA, SPAIN SP European Soc Cardiol ID POLYUNSATURATED FATTY-ACIDS; RAT VENTRICULAR MYOCYTES; PREVENTION C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Leaf, A (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY PY 1999 BP 279 EP 285 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BQ43V UT WOS:000088359200042 ER PT J AU Elias, CF Saper, CB Maratos-Flier, E Tritos, NA Lee, C Kelly, J Tatro, JB Hoffman, GE Ollmann, MM Barsh, GS Sakurai, T Yanagisawa, M Elmquist, JK AF Elias, CF Saper, CB Maratos-Flier, E Tritos, NA Lee, C Kelly, J Tatro, JB Hoffman, GE Ollmann, MM Barsh, GS Sakurai, T Yanagisawa, M Elmquist, JK TI Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic area SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE obesity; feeding; arcuate hypothalamic nucleus; melanin-concentrating hormone; orexins ID MELANIN-CONCENTRATING HORMONE; MELANOCYTE-STIMULATING HORMONE; PROOPIOMELANOCORTIN MESSENGER-RNA; NUCLEUS-TRACTUS-SOLITARIUS; OBESE GENE-PRODUCT; NEUROPEPTIDE-Y; RAT-BRAIN; BETA-ENDORPHIN; OB/OB MICE; ALPHA-MSH AB Recent studies have identified several neuropeptide systems in the hypothalamus that are critical in the regulation of body weight. The lateral hypothalamic area (LHA) has long been considered essential in regulating food intake and body weight. Two neuropeptides, melanin-concentrating hormone (MCH) and the orexins (ORX), are localized in the LHA and provide diffuse innervation of the neuraxis, including monosynaptic projections to the cerebral cortex and autonomic preganglionic neurons; Therefore, MCH and ORX neurons may regulate both cognitive and autonomic aspects of food intake and body weight regulation. The arcuate nucleus also is critical in the regulation of body weight, because it contains neurons that express leptin receptors, neuropeptide Y (NPY), alpha-melanin-stimulating hormone (alpha-MSH), and agouti-related peptide (AgRP). In this study, we examined the relationships of these peptidergic systems by using dual-label immunohistochemistry or in situ hybridization in rat, mouse, and human brains. In the normal rat, mouse, and human brain, ORX and MCH neurons make up segregated populations. In addition, we found that AgRP- and NPY-immunoreactive neurons are present in the medial division of the human arcuate nucleus, whereas alpha-MSH-immunoreactive neurons are found in the lateral arcuate nucleus. In humans, AgRP projections were widespread in the hypothalamus, but they were especially dense in the paraventricular nucleus and the perifornical area. Moreover, in both rat and human, MCH and ORX neurons receive innervation from NPY-, AgRP-, and alpha-MSH-immunoreactive fibers. Projections from populations of leptin-responsive neurons in the mediobasal hypothalamus to MCH and ORX cells in the LHA may link peripheral metabolic cues with the cortical mantle and may play a critical role in the regulation of feeding behavior and body weight. J. Comp. Neurol. 402:442-459, 1998. (C) 1998 Wiley-Liss, Inc. C1 Beth Israel Deaconess Med Ctr, Div Endocrinol, Dept Neurol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Tufts Univ, Sch Med, Tupper Res Inst, Div Endocrinol Metab & Mol Med, Boston, MA 02111 USA. Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA. Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94395 USA. Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94395 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94395 USA. Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr, Dept Mol Genet, Dallas, TX 75235 USA. RP Elmquist, JK (reprint author), Beth Israel Deaconess Med Ctr, Div Endocrinol, Dept Neurol, 325 Res N,99 Brookline Ave, Boston, MA 02215 USA. EM jelmquis@bidmc.harvard.edu FU NIMH NIH HHS [MH44694, MH56537]; NINDS NIH HHS [NS33987] NR 81 TC 618 Z9 625 U1 1 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD DEC 28 PY 1998 VL 402 IS 4 BP 442 EP 459 DI 10.1002/(SICI)1096-9861(19981228)402:4<442::AID-CNE2>3.0.CO;2-R PG 18 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 148CB UT WOS:000077534100002 PM 9862320 ER PT J AU Meyerson, M AF Meyerson, M TI Telomerase enzyme activation and human cell immortalization SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT 8th International Congress of Toxicology CY JUL 05-09, 1998 CL PARIS, FRANCE SP Soc Francaise Toxicol DE telomerase; cancer; cell immortalization ID CATALYTIC SUBUNIT GENE; TEMPLATE RNA COMPONENT; TETRAHYMENA-TELOMERASE; SACCHAROMYCES-CEREVISIAE; TERMINAL TRANSFERASE; MAMMALIAN TELOMERASE; YEAST TELOMERASE; EST GENES; PROTEIN; SENESCENCE AB Activity of telomerase, the enzyme that synthesizes the telomere ends of linear eukaryotic chromosomes, is repressed in most normal human somatic cells but induced in most human cancers. Normal human cells that lack telomerase activity progressively lose telomere sequences. In contrast, most immortalized cell lines and malignant human tumors appear to maintain constant telomere length via telomerase activity. Telomerase is composed of at least two subunits, an RNA subunit that templates telomere synthesis, and a catalytic protein subunit. The gene encoding the catalytic protein subunit of telomerase has recently been identified, first in yeast and ciliates and then in humans. This catalytic subunit belongs to the reverse transcriptase family. Studies of telomerase subunits further define a role for telomerase in the control of mammalian cell lifespan. The expression of the human telomerase catalytic subunit gene, hTERT, is induced in immortalized cells and primary tumors. When hTERT is ectopically expressed in hitherto telomerase-negative cells, telomerase enzyme activity appears, and an extended lifespan has been observed in some cells. In contrast, disruption of the mouse telomerase RNA subunit gene, mTERC, results in a delayed failure of cell proliferation. Telomerase activity therefore appears to be necessary for the prolonged survival of mammalian cells. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Meyerson, M (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. EM matthew-meyerson@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012 NR 44 TC 6 Z9 6 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD DEC 28 PY 1998 VL 103 BP 41 EP 45 PG 5 WC Toxicology SC Toxicology GA 164KE UT WOS:000078462400007 ER PT J AU Tilly, JL AF Tilly, JL TI Molecular and genetic basis of normal and toxicant-induced apoptosis in female germ cells SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT 8th International Congress of Toxicology CY JUL 05-09, 1998 CL PARIS, FRANCE SP Soc Francaise Toxicol DE apoptosis; genotoxicant; chemotherapy; germ cell; oocyte; ovary; infertility ID DIEPOXIDE-INDUCED OVOTOXICITY; BAX; EXPRESSION; DEATH; DESTRUCTION; FOLLICLES; BCL-2; OVARY; MICE; RAT AB The union of a healthy egg and a healthy sperm is required for propagation of mammalian species, and thus any factor that disrupts the normal production of female or male gametes is a potential threat to reproductive performance. These hazards to gonadal function are derived from both clinical and environmental sources, and can affect either somatic cell or germ cell lineages, or in some cases both, with equal consequences, i.e. the loss of fertility. Females of the species are particularly at risk to gonadal toxicants since, unlike males, females are born with an irreplaceable stockpile of germ cells in their ovaries at the time of birth. Natural selection processes further dwindle this precious reserve such that by the time of puberty, when eggs could actually be used for fertilization and pregnancy, the number of remaining oocytes has been depleted to less than three-quarters of the starting cohort. In the human female, this completely normal loss of oocytes eventually leads to near-exhaustion of the germ cell reserve around the fifth decade of life, and the menopause ensues. Consequently, exposure of women to potentially damaging agents, such as anti-cancer drugs, industrial chemicals or even cigarette smoke, can have a dramatic and irreparable effect on the ovary by accelerating the natural process of germ cell depletion and, as a direct consequence, advance the time to menopause. This mini-review attempts to bring together these concepts from a molecular biological standpoint, and further offers the hypothesis that many gonadal toxicants exert their effects via modulation of discrete signaling pathways linked to apoptotic cell death in the female germline. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. RP Tilly, JL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, VBK137E-GYN,55 Fruit St, Boston, MA 02114 USA. NR 22 TC 20 Z9 20 U1 0 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD DEC 28 PY 1998 VL 103 BP 497 EP 501 PG 5 WC Toxicology SC Toxicology GA 164KE UT WOS:000078462400079 ER PT J AU Rosen, HR Martin, P AF Rosen, HR Martin, P TI Hepatitis C infection in patients undergoing liver retransplantation SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the American-Society-of-Transplant-Physicians CY MAY 09-13, 1998 CL CHICAGO, ILLINOIS SP Amer Soc Transplant Physicians ID RISK-FACTORS; TRANSPLANT RECIPIENTS AB Background. There is concern that repeat orthotopic liver transplantation in patients with hepatitis C virus (HCV) infection may be associated with poor long-term survival. The specific aims of the current analysis were to determine (1) the prevalence of HCV infection in a large cohort of patients undergoing retransplantation, (2) define the impact of HCV infection on patient survival, and (3) determine the predictors of outcome of HCV-positive patients undergoing retransplantation for graft failure not caused by primary nonfunction. Methods. We analyzed the United Network of Organ Sharing (UNOS) registry data of 1539 adults undergoing orthotopic liver retransplantation between January 1990 and February 1996; 357 patients (23%) were HCV-positive. Results. The prevalence of HCV infection increased significantly from 6.5% in 1990 to 38.4% in 1995 (P<0.0001). Comparing the HCV-positive versus HCV-negative groups, there were no significant differences with regards to age, time to retransplantation, biochemical parameters immediately preceding retransplantation, UNOS registry status mix, or cause of graft failure (% with primary nonfunction). However, Kaplan-Meier analysis demonstrated significantly diminished survival in the HCV-positive group (P=0.0038, log-rank test; relative risk, 1.36; 95% confidence interval: 1.07-1.71). Multivariate logistic regression analysis of the subgroup of HCV-positive patients undergoing retransplantation for graft failure not caused by primary nonfunction identified preoperative serum bilirubin and serum creatinine as significant predictors of outcome. Seven of 207 (3.4%) patients undergoing retransplantation died of recurrent HCV in their second allografts. Conclusion. The prevalence of HCV infection in patients undergoing retransplantation appears to have significantly increased since 1990. HCV infection is an independent risk factor for death after retransplantation, However, acceptable results are attainable in highly selected patients, i.e., those patients without severe hyperbilirubinemia and renal failure, and retransplantation remains the only viable option for patients whose allografts fail because of recurrent disease. C1 Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol, Portland, OR 97207 USA. Univ Calif Los Angeles, Los Angeles, CA USA. United Network Organ Sharing Sci Data Registry, Richmond, VA USA. RP Rosen, HR (reprint author), Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol, 3710 SW US Vet Hosp Rd,POB 1034,P3-GI, Portland, OR 97207 USA. NR 24 TC 94 Z9 94 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 27 PY 1998 VL 66 IS 12 BP 1612 EP 1616 DI 10.1097/00007890-199812270-00007 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 155QU UT WOS:000077958500007 PM 9884247 ER PT J AU Rosen, HR Corless, CL Rabkin, J Chou, S AF Rosen, HR Corless, CL Rabkin, J Chou, S TI Association of cytomegalovirus genotype with graft rejection after liver transplantation SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the American-Society-of-Transplant-Physicians CY MAY 09-13, 1998 CL CHICAGO, ILLINOIS SP Amer Soc Transplant Physicians ID GLYCOPROTEIN-B GENOTYPES; ENVELOPE GLYCOPROTEIN; INTERSTRAIN VARIATION; BONE-MARROW; RECIPIENTS; INFECTION; VIRUS; SEQUENCES; HEPATITIS; VIREMIA AB Background. The envelope glycoprotein gB of human cytomegalovirus (CMV) occurs as one of four main genotypes, Some previous studies have proposed a relationship of CMV gB genotype to the frequency of symptomatic infection and to clinical outcomes in both transplant and human immunodeficiency virus-infected populations. Our aim was to define the distribution of CMV gB genotypes and the impact on acute cellular rejection and graft/patient survival after orthotopic liver transplantation (OLT). Methods. Between October 1988 and December 1996, 325 patients underwent cyclosporine-based OLT at our center. CMV infection was surveyed prospectively and defined as viral isolation from blood or urine; 53 (16%) patients had detectable CMV, Isolates were genotyped by polymerase chain reaction amplification and restriction digest analysis. Results. The distribution of CMV genotypes was: gB1, 19 (36%) patients; gB2, 15 (28%) patients; gB3, 13 (24%) patients; and gB4, 4 (8%) patients. Two patients (4%) had mixed infection (1 + 3, 1 + 4), Age, preOLT diagnosis, use of ganciclovir prophylaxis, basal immunosuppression, mean number of HLA donor/recipient mismatches, and United Network of Organ Sharing status were comparable among patients with different genotypes. Patients with gB1 had a significantly higher mean number of acute rejection episodes (1.52+/-0.30 vs. 0.67+/-0.22; P=0.027). However, there was no difference in rejection severity, including OKT3 usage or FK506 conversion, or development of chronic rejection among patients with different genotypes. The gB genotype did not affect the development of symptomatic or tissue-invasive CMV disease, detected in 15 patients. Actuarial rates of patient (odds ratio [OR] 3.0; confidence interval [CI] 1.49-6.0) and graft (OR 2.57; CI 1.25-5.22) survival were significantly diminished in the group with CMV infection versus those without CMV (P<0.0001 for both), but there was no association with CMV genotype. Conclusions. (1) Patients with CMV infection had significantly reduced patient and graft survival rates at 1 and 5 years after OLT as compared with OLT recipients without CMV infection. (2) CMV genotype gB1 was associated with a higher mean number of acute rejection episodes. C1 Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol, Dept Med, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Dept Surg & Pathol, Portland, OR 97207 USA. RP Rosen, HR (reprint author), Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol, Dept Med, 3710 SW US Vet Hosp Rd,POB 1034,P3-GI, Portland, OR 97207 USA. EM rosen.hugo_R@portland.va.gov FU NIAID NIH HHS [AI 39938] NR 31 TC 36 Z9 40 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 27 PY 1998 VL 66 IS 12 BP 1627 EP 1631 DI 10.1097/00007890-199812270-00010 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 155QU UT WOS:000077958500010 PM 9884250 ER PT J AU Turgeon, N Fishman, JA Basgoz, N Tolkoff-Rubin, NE Doran, M Cosimi, AB Rubin, RH AF Turgeon, N Fishman, JA Basgoz, N Tolkoff-Rubin, NE Doran, M Cosimi, AB Rubin, RH TI Effect of oral acyclovir or ganciclovir therapy after preemptive intravenous ganciclovir therapy to prevent cytomegalovirus disease in cytomegalovirus seropositive renal and liver transplant recipients receiving antilymphocyte antibody therapy SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the American-Society-of-Transplant-Physicians CY MAY 09-13, 1998 CL CHICAGO, ILLINOIS SP Amer Soc Transplant Physicians ID CONTROLLED TRIAL; ANTIGENEMIA; VIRUS; PROPHYLAXIS; INFECTION; ALLOGRAFTS; INTERFERON; EFFICACY; VIREMIA AB Background. Organ transplant recipients who are seropositive for cytomegalovirus (CMV) and who are treated with antilymphocyte antibody (ALA) therapy have a high rate of symptomatic CMV disease. The intravenous administration of ganciclovir therapy once daily during ALA therapy decreased the incidence from 24% to 10% in patients receiving ALA as an induction therapy and from 64% to 22% in those treated for rejection. The present study was undertaken to determine whether a more intensive and sustained antiviral regimen could be more effective. Methods. From April 1995 to December 1997, all CMV seropositive renal and liver transplant, recipients who received ALA therapy were treated with intravenously administered ganciclovir (5 mg/kg/day with dose adjusted for renal dysfunction) for the length of ALA therapy and then with orally administered acyclovir (400 mg three times/day) or ganciclovir (1 gm twice/day) for 3 to 4 months. The incidence of CMV viremia and of CMV disease was determined during the 6 months after completion of ALA therapy. Results. Forty-one patients (35 renal and 6 liver transplant recipients) were studied. CMV disease occurred in 2 patients (4.9%), both of whom were treated for rejection; it occurred in 1 of 21 patients (4.8%) treated with orally administered acyclovir, and in 1 of 20 patients (5%) treated with orally administered ganciclovir. The only patient who developed CMV disease in the ganciclovir group had received only 26 days of oral antiviral therapy. No CMV disease was documented in the group of patients receiving ALA therapy as induction therapy. CMV viremia occurred in three patients in the acyclovir group (14.3%) and in one patient in the ganciclovir group (5%). Among renal transplant recipients only, 1 of 35 patients developed CMV disease (2.9%) and no case of CMV disease was documented in patients treated with orally administered ganciclovir. All six patients receiving two courses of ALA therapy each were free of CMV disease. Toxicity of the regimen was minimal, and antiviral resistance did not develop. Conclusions. Preemptive antiviral therapy with intravenously administered ganciclovir during ALA therapy and then orally administered ganciclovir for 3 to 4 months provides virtually complete protection against the excessive rate of CMV disease that occurs in CMV seropositive allograft recipients receiving ALA therapy. C1 Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Rubin, RH (reprint author), MIT, Clin Res Ctr, Ctr Expt Pharmacol & Therapeut, 40 Amos St,Bldg E18-435, Cambridge, MA 02142 USA. NR 27 TC 21 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 27 PY 1998 VL 66 IS 12 BP 1780 EP 1786 DI 10.1097/00007890-199812270-00036 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 155QU UT WOS:000077958500036 PM 9884276 ER PT J AU Laredo, J Thurer, RL Burke, PA Archer, SY AF Laredo, J Thurer, RL Burke, PA Archer, SY TI A 70-year-old man with an empyema SO LANCET LA English DT Article ID LAPAROSCOPIC CHOLECYSTECTOMY C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg,Div Gen Surg, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg,Div Cardiothorac Surg, Boston, MA 02215 USA. RP Archer, SY (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg,Div Gen Surg, Boston, MA 02215 USA. NR 5 TC 5 Z9 5 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD DEC 26 PY 1998 VL 352 IS 9145 BP 1982 EP 1982 DI 10.1016/S0140-6736(98)09328-3 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 150KA UT WOS:000077663000013 PM 9872249 ER PT J AU Bardales, RH Pitman, MB Stanley, MW Korourian, S Suhrland, MJ AF Bardales, RH Pitman, MB Stanley, MW Korourian, S Suhrland, MJ TI Urine cytology of primary and secondary urinary bladder adenocarcinoma SO CANCER CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT 86th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-08, 1997 CL ORLANDO, FLORIDA SP US & Canadian Acad Pathol DE cytology; urine; urinary bladder; adenocarcinoma; prostate carcinoma; colon carcinoma; breast carcinoma; renal carcinoma ID NEPHROGENIC ADENOMA; CARCINOMA; URETHRA; CANCER AB BACKGROUND. Primary and secondary adenocarcinomas of the urinary bladder are uncommon, and the urine cytology of these tumors has rarely been described. Familiarity with the cytomorphology of these neoplasms may facilitate their detection in urine cytology specimens. METHODS. The authors reviewed 46 urine samples (19 voided, 19 instrumented, and 8 bladder washings) from 41 patients with biopsy-proven primary urinary bladder adenocarcinoma (n = 11) or metastatic adenocarcinoma (n = 35) from the prostate (n = 17), colon (n = 10), breast (n = 3), kidney (n = 3), or uterus (n = 1), or from unknown origin (n = 1). Cytomorphology, the role of cytology, and causes for negative diagnoses were evaluated. RESULTS. Cytologic diagnoses of malignancy, adenocarcinoma not otherwise specified, and adenocarcinoma of a specific type were given in 87%, 28%, and 39% of cases, respectively. Columnar cells, coarse chromatin, and necrosis were found in adenocarcinoma of the colon. Syncytial and acinar arrangements, round or oval nuclei, vesicular chromatin, and prominent nucleoli were commonly found in adenocarcinoma of the prostate. These features permitted us to make a specific diagnosis in 90% of cases of adenocarcinoma of the colon and 41% of cases of adenocarcinoma of the prostate. Cytologic examination failed to lead to a diagnosis of malignancy in 18% of primary adenocarcinoma cases. CONCLUSIONS. A large number of adenocarcinomas of the colon and prostate have sufficient cytologic features to suggest the correct diagnosis in urine samples. The cytomorphology of primary bladder adenocarcinoma is not as easily characterized. The submucosal nature of some metastatic deposits and tumor differentiation influence the diagnostic accuracy. Cancer (Cancer Cytopathol) 1998;84:335-43, (C) 1998 American Cancer Society. C1 Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. John L McClellan Mem Vet Hosp, Little Rock, AR USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Hennepin Cty Med Ctr, Dept Lab Med & Pathol, Minneapolis, MN 55415 USA. Montefiore Med Ctr, Dept Pathol, Bronx, NY 10467 USA. RP Bardales, RH (reprint author), Univ Arkansas Med Sci Hosp, Dept Pathol, 4301 W Markham St, Little Rock, AR 72205 USA. NR 39 TC 30 Z9 33 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD DEC 25 PY 1998 VL 84 IS 6 BP 335 EP 343 DI 10.1002/(SICI)1097-0142(19981225)84:6<335::AID-CNCR4>3.0.CO;2-W PG 9 WC Oncology; Pathology SC Oncology; Pathology GA 155LP UT WOS:000077948700004 PM 9915134 ER PT J AU Hood, JK Silver, PA AF Hood, JK Silver, PA TI Cse1p is required for export of Srp1p/importin-alpha from the nucleus in Saccharomyces cerevisiae SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTPASE-ACTIVATING PROTEIN; MESSENGER-RNA EXPORT; BINDING-PROTEINS; IMPORTIN-BETA; PORE COMPLEX; CHROMOSOME CONDENSATION; TRANSPORT FACTORS; RAN/TC4 HOMOLOG; POLY(A)(+) RNA; YEAST MUTANT AB In metazoan cells, the CAS protein has been shown to function as a recycling factor for the importin-alpha subunit of the classical nuclear localization signal receptor, exporting importin-alpha from the nucleus to allow its participation in multiple rounds of nuclear import. CAS is a member of a family of proteins that bear homology to the larger subunit of the nuclear localization signal receptor, importin-beta, and that are found in all eukaryotes from yeast to humans. Sequence similarity identifies the product of the Saccharomyces cerevisiae CSE1 gene as a potential CAS homologue. Here we present evidence that Cse1p is the functional homologue of GAS: Cse1p is required to prevent accumulation of Srplp/importin-a: in the nucleus, it localizes to the nuclear envelope in a pattern typical of nuclear transport receptors, and it associates in vivo with Srp1p in a nucleotide-specific manner. We show further that mutations in CSE1 and SRP1 have specific effects on their association and on the intracellular localization of Cse1p. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Silver, PA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 46 TC 94 Z9 97 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 25 PY 1998 VL 273 IS 52 BP 35142 EP 35146 DI 10.1074/jbc.273.52.35142 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 151KR UT WOS:000077719700068 PM 9857050 ER PT J AU Friedman, LS AF Friedman, LS TI Helicobacter pylori and nonulcer dyspepsia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MANAGEMENT STRATEGIES; ULCER C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Friedman, LS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 18 TC 29 Z9 30 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 24 PY 1998 VL 339 IS 26 BP 1928 EP 1930 DI 10.1056/NEJM199812243392611 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 150ZN UT WOS:000077696600011 PM 9862951 ER PT J AU Kharbanda, S Yuan, ZM Weichselbaum, R Kufe, D AF Kharbanda, S Yuan, ZM Weichselbaum, R Kufe, D TI Determination of cell fate by c-Abl activation in the response to DNA damage SO ONCOGENE LA English DT Review DE c-Abl; DNA damage; growth arrest; recombination; apoptosis ID PROTEIN-KINASE-C; RADIATION-INDUCED APOPTOSIS; ATAXIA-TELANGIECTASIA GENE; NUCLEAR TYROSINE KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; DROSOPHILA-ABL; GROWTH-FACTOR; SIGNAL-TRANSDUCTION; IONIZING-RADIATION; CATALYTIC SUBUNIT AB The cellular response to DNA damage includes growth arrest and activation of DNA repair, Certain insights into how DNA damage is converted into intracellular signals that control the genotoxic stress response have been derived from the finding that the c-Abl protein tyrosine kinase is activated by ionizing radiation and other DNA-damaging agents. c-Abl associates with the DNA-dependent protein kinase (DNA-PK) and is activated by DNA-PK-dependent phosphorylation, The ataxia telangiectasia mutated (ATM) gene product also contributes to c-Abl activation, The demonstration that c-Abl binds to p53, induces the transactivation function of p53 and activates p21 expression has supported involvement of c-Abl in regulation of the p53-dependent G1 arrest response, Interaction between c-Abl and the Rad51 protein has also provided support for involvement of c-Abl in recombinational repair of DNA strand breaks, Defects in G1 arrest and repair predispose to replication of damaged templates and, in the event of irreparable DNA lesions, induction of apoptosis, The available evidence indicates that c-Abl effects proapoptotic function by a mechanism largely independent of p53, c-Abl also functions as an upstream effector of the proapoptotic JNK/SAPK and p38 MAPK pathways. In addition, c-Abl-dependent inhibition of PI 3-kinase contributes to the induction of apoptosis, The findings thus suggest that, in response to genotoxic stress, c-Abl functions in determining cell fate, that is growth arrest and repair or induction of apoptosis, The physiologic function of c-Abl may reside in control of the cellular response to DNA strand breaks that occur during DNA replication, genetic recombination and gene rearrangements. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 55241, CA29431] NR 177 TC 130 Z9 135 U1 1 U2 5 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 24 PY 1998 VL 17 IS 25 BP 3309 EP 3318 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 157EW UT WOS:000078048200012 PM 9916993 ER PT J AU Gao, YJ Sun, Y Frank, KM Dikkes, P Fujiwara, Y Seidl, KJ Sekiguchi, JM Rathbun, GA Swat, W Wang, JY Bronson, RT Malynn, BA Bryans, M Zhu, CM Chaudhuri, J Davidson, L Ferrini, R Stamato, T Orkin, SH Greenberg, ME Alt, FW AF Gao, YJ Sun, Y Frank, KM Dikkes, P Fujiwara, Y Seidl, KJ Sekiguchi, JM Rathbun, GA Swat, W Wang, JY Bronson, RT Malynn, BA Bryans, M Zhu, CM Chaudhuri, J Davidson, L Ferrini, R Stamato, T Orkin, SH Greenberg, ME Alt, FW TI A critical role for DNA end-joining proteins in both lymphogenesis and neurogenesis SO CELL LA English DT Article ID STRAND BREAK REPAIR; V(D)J RECOMBINATION; LIGASE-IV; GENE RECOMBINATION; MAMMALIAN-CELLS; NERVOUS-SYSTEM; DEFICIENT MICE; IN-VIVO; BCL-X; REARRANGEMENT AB XRCC4 was identified via a complementation cloning method that employed an ionizing radiation (IR)-sensitive hamster cell line. By gene-targeted mutation, we show that XRCC4 deficiency in primary murine cells causes growth defects, premature senescence, IR sensitivity, and inability to support V(D)J recombination. In mice, XRCC4 deficiency causes late embryonic lethality accompanied by defective lymphogenesis and defective neurogenesis manifested by extensive apoptotic death of newly generated postmitotic neuronal cells. We find similar neuronal developmental defects in embryos that lack DNA ligase IV, an XRCC4-associated protein. Our findings demonstrate that differentiating lymphocytes and neurons strictly require the XRCC4 and DNA ligase IV end-joining proteins and point to the general stage of neuronal development in which these proteins are necessary. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Dept Pediat, Boston, MA 02115 USA. Kyushu Univ, Med Inst Bioregulat, Higashi Ku, Fukuoka 812, Japan. Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA. Tufts Univ, Sch Vet Med, Boston, MA 02111 USA. Lankenau Med Res Ctr, Wynnewood, PA 19096 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,Ctr Blood Res, Boston, MA 02115 USA. OI Sekiguchi, JoAnn/0000-0002-7178-4258 FU NIAID NIH HHS [AI01428, AI20047, AI35714] NR 46 TC 465 Z9 472 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD DEC 23 PY 1998 VL 95 IS 7 BP 891 EP 902 DI 10.1016/S0092-8674(00)81714-6 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 152CX UT WOS:000077759100005 PM 9875844 ER PT J AU Chen, HM Engelman, A AF Chen, HM Engelman, A TI The barrier-to-autointegration protein is a host factor for HIV type 1 integration SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RETROVIRUS-LIKE DNA; CONCERTED INTEGRATION; IN-VITRO; INVITRO AB In vivo, retroviral integration is mediated by a large nucleoprotein complex, termed the preintegration complex (PIC), PICs isolated from infected cells display in vitro integration activity, Here, me analyze the roles of different host cell factors in the structure and function of HIV type I (HIV-1) PICs, PICs purified by size exclusion after treatment with high salt lost their integration activity, and adding back an extract from uninfected cells restored this activity. In parallel, the native protein-DNA intasome structure detected at the ends of HIV-1 by Mu-mediated PCR footprinting was abolished by high salt and restored by the crude cell extract. Various purified proteins previously implicated in retroviral PIC function then were analyzed for their effects on the structure and function of salt-treated HIV-1 PICs. Whereas relatively low amounts (5-20 nM) of human barrier-to-autointegration factor (BAF) protein restored integration activity, substantially more (5-10 mu M) human host factor HMG I(Y) was required, Similarly high levels (3-8 mu M) of bovine RNase A, a DNA-binding protein used as a nonspecific control, also restored activity, Mu-mediated PCR footprinting revealed that of these three purified proteins, only BAF restored the native structure of the HIV-1 protein-DNA intasome, We suggest that BAF is a natural host cofactor for HIV-1 integration. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Engelman, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [R01 AI039394, AI39394, R37 AI039394] NR 21 TC 142 Z9 148 U1 0 U2 0 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 DEC 22 PY 1998 VL 95 IS 26 BP 15270 EP 15274 DI 10.1073/pnas.95.26.15270 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 150ZV UT WOS:000077697200025 PM 9860958 ER PT J AU Ho, IC Kim, JHJ Rooney, JW Spiegelman, BM Glimcher, LH AF Ho, IC Kim, JHJ Rooney, JW Spiegelman, BM Glimcher, LH TI A potential role for the nuclear factor of activated T cells family of transcriptional regulatory proteins in adipogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ENHANCER-BINDING-PROTEIN; GLYCOGEN-SYNTHASE KINASE-3; ADIPOCYTE DIFFERENTIATION; GENE-EXPRESSION; 3T3-L1 PREADIPOCYTES; CYCLOSPORINE-A; C/EBP-ALPHA; NF-ATC; CALCINEURIN; STIMULATION AB NFAT (nuclear factor of activated T cells) is a family of transcription factors implicated in the control of cytokine and early immune response gene expression. Recent studies have pointed to a role for NFAT proteins in gene regulation outside of the immune system. Herein we demonstrate that NFAT proteins are present in 3T3-L1 adipocytes and, upon fat cell differentiation, bind to and transactivate the promoter of the adipocyte-specific gene aP2. Further, fat cell differentiation is inhibited by cyclosporin A, a drug shown to prevent NFAT nuclear localization and hence function. Thus, these data suggest a role for NFAT transcription factors in the regulation of the aP2 gene and in the process of adipocyte differentiation. C1 Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Columbia Univ Coll Phys & Surg, Dept Microbiol, New York, NY 10032 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Cell & Mol Biol, Boston, MA 02115 USA. RP Glimcher, LH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 661 Huntington Ave, Boston, MA 02115 USA. EM lglimche@hsph.harvard.edu FU NIAID NIH HHS [AI/AG37833] NR 53 TC 77 Z9 81 U1 0 U2 0 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 DEC 22 PY 1998 VL 95 IS 26 BP 15537 EP 15541 DI 10.1073/pnas.95.26.15537 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 150ZV UT WOS:000077697200071 PM 9861004 ER PT J AU Wang, ZM Yang, H Livingston, DM AF Wang, ZM Yang, H Livingston, DM TI Endogenous E2F-1 promotes timely G(0) exit of resting mouse embryo fibroblasts SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE RB; cell cycle control ID CELL-CYCLE CONTROL; UBIQUITIN-PROTEASOME PATHWAY; TRANSCRIPTION FACTOR E2F-1; TUMOR-SUPPRESSOR PROTEIN; RETINOBLASTOMA PROTEIN; RESTRICTION POINT; S-PHASE; GENE PROMOTER; EXPRESSION; DEGRADATION AB Much evidence strongly suggests a positive role for one or more E2F species in the control of exit from G(0)/G(1). Results described here provide direct evidence that endogenous E2F-1, as predicted, contributes to progression from G(0) to S. By contrast, cycling cells lacking an intact E2F-1 gene demonstrated normal cell cycle distribution. Therefore, E2F-1 exerts a unique function leading to timely G(0) exit of resting cultured primary cells, while at the same time being unnecessary for normal G(1) to S phase progression of cycling cells. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Livingston, DM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 44 TC 34 Z9 37 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 DEC 22 PY 1998 VL 95 IS 26 BP 15583 EP 15586 DI 10.1073/pnas.95.26.15583 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 150ZV UT WOS:000077697200079 PM 9861012 ER PT J AU Barton-Davis, ER Shoturma, DI Musaro, A Rosenthal, N Sweeney, HL AF Barton-Davis, ER Shoturma, DI Musaro, A Rosenthal, N Sweeney, HL TI Viral mediated expression of insulin-like growth factor I blocks the aging-related loss of skeletal muscle function SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CONTRACTILE PROPERTIES; DIFFERENTIATION; GENE; HORMONE; MICE; MEN AB During the aging process, mammals lose up to a third of their skeletal muscle mass and strength. Although the mechanisms underlying this loss are not entirely understood, we attempted to moderate the loss by increasing the regenerative capacity of muscle. This involved the injection of a recombinant adeno-associated virus directing overexpression of insulin-like growth factor I (IGF-I) in differentiated muscle fibers, We demonstrate that the IGF-I expression promotes an average increase of 15% in muscle mass and a 14% increase in strength in young adult mice, and remarkably, prevents aging-related muscle changes in old adult mice, resulting in a 27% increase in strength as compared with uninjected old muscles. Muscle mass and fiber type distributions were maintained at levels similar to those in young adults. We propose that these effects are primarily due to stimulation of muscle regeneration via the activation of satellite cells by IGF-I, This supports the hypothesis that the primary cause of aging-related impairment of muscle function is a cumulative failure to repair damage sustained during muscle utilization. Our results suggest that gene transfer of IGF-I into muscle could form the basis of a human gene therapy for preventing the loss of muscle function associated with aging and may be of benefit in diseases where the rate of damage to skeletal muscle is accelerated. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA. RP Rosenthal, N (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. EM Lsweeney@mail.med.upenn.edu RI Sweeney, H Lee/F-1862-2010; Musaro, Antonio/K-9598-2016 OI Musaro, Antonio/0000-0002-2944-9739 FU NIA NIH HHS [P01-AG13329]; NIAMS NIH HHS [P01-AR/NS43648] NR 26 TC 477 Z9 497 U1 1 U2 15 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 DEC 22 PY 1998 VL 95 IS 26 BP 15603 EP 15607 DI 10.1073/pnas.95.26.15603 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 150ZV UT WOS:000077697200083 PM 9861016 ER PT J AU Kalams, SA Walker, BD AF Kalams, SA Walker, BD TI The critical need for CD4 help in maintaining effective cytotoxic T lymphocyte responses SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Editorial Material ID EPSTEIN-BARR-VIRUS; HEPATITIS-B VIRUS; IMMUNODEFICIENCY-VIRUS; HIV-1 INFECTION; ANTIBODY-RESPONSES; CELL RESPONSES; MICE; DISEASE; SUPPRESSION; THRESHOLDS C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Infect Dis, Charlestown, MA 02129 USA. RP Kalams, SA (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM kalams@helix.mgh.harvard.edu NR 52 TC 505 Z9 511 U1 0 U2 9 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 21 PY 1998 VL 188 IS 12 BP 2199 EP 2204 DI 10.1084/jem.188.12.2199 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 151HA UT WOS:000077713600001 PM 9858506 ER PT J AU Maurer, M Echtenacher, B Hultner, L Kollias, G Mannel, DN Langley, KE Galli, SJ AF Maurer, M Echtenacher, B Hultner, L Kollias, G Mannel, DN Langley, KE Galli, SJ TI The c-kit ligand, stem cell factor, can enhance innate immunity through effects on mast cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE c-kit; innate immunity; mast cells; stem cell factor; tumor necrosis; factor-alpha ID CONNECTIVE-TISSUE TYPE; GROWTH-FACTOR; DEFICIENT W/WV; TNF-ALPHA; MICE; RESPONSES; APOPTOSIS; RECEPTOR; INVIVO; LOCUS AB Mast cells are thought to contribute significantly to the pathology and mortality associated with anaphylaxis and other allergic disorders. However, studies using genetically mast cell-deficient WBB6F(1)-Kit(W)/Kit(W-v) and congenic wild-type (WBB6F(1)(+/+)) mice indicate that mast cells call also promote health, by participating in natural immune responses to bacterial infection. We previously reported that repetitive administration of the c-kit ligand, stem cell factor (SCF), can increase mast cell numbers in normal mice in vivo. In vitro studies have indicated that SCF can also modulate mast cell effector function.. We now report that treatment with SCF can significantly improve the survival of normal C57BL/6 mice in a model of acute bacterial peritonitis, cecal ligation and puncture (CLP). Experiments in mast cell-reconstituted WBB6F1-Kit(W)/Kit(W-v) mice indicate that this effect of SCF treatment reflects, at least in part, the actions of SCF oil mast cells. Repetitive administration of SCF also carl enhance survival in mice that genetically lack tumor necrosis factor (TNF)-alpha, demonstrating that the ability of SCF treatment to improve survival after CLP does not solely reflect effects of SCF on mast cell-dependent (or -independent) production of TNF-alpha, These findings identify c-kit and mast cells as potential therapeutic targets for enhancing innate immune responses. C1 Beth Israel Deaconess Med Ctr E, Dept Pathol, Div Expt Pathol, Boston, MA 02215 USA. Univ Regensburg, Inst Pathol Tumorimmunol, D-93042 Regensburg, Germany. GSF Forschungszentrum Umwelt & Gesundheit, Inst Expt Hamatol, D-81337 Munich, Germany. Hellen Pasteur Inst, Dept Mol Genet, Athens 11521, Greece. Amgen Inc, Thousand Oaks, CA 91320 USA. RP Galli, SJ (reprint author), Beth Israel Deaconess Med Ctr E, Dept Pathol, Div Expt Pathol, Res N 227,POB 15707, Boston, MA 02215 USA. EM sgalli@bidmc.harvard.edu RI Kollias, George/A-7079-2012 OI Kollias, George/0000-0003-1867-3150 FU NCI NIH HHS [CA/AI72074]; NIAID NIH HHS [5 U19 AI41995, AI/GM23900] NR 31 TC 121 Z9 122 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 21 PY 1998 VL 188 IS 12 BP 2343 EP 2348 DI 10.1084/jem.188.12.2343 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 151HA UT WOS:000077713600015 PM 9858520 ER PT J AU Boes, M Prodeus, AP Schmidt, T Carroll, MC Chen, JZ AF Boes, M Prodeus, AP Schmidt, T Carroll, MC Chen, JZ TI A critical role of natural immunoglobulin M in immediate defense against systemic bacterial infection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE natural antibody; immunoglobulin M; complement; bacterial infection; immediate defense ID GROUP-B STREPTOCOCCI; SEPTIC SHOCK; COMPLEMENT COMPONENT; CELL; ANTIBODIES; IMMUNITY; MICE; AUTOANTIBODIES; POLYSACCHARIDE; PERITONITIS AB To evaluate the role of natural immunoglobulin (Ig)M in the immediate response against microbial infection, wt tested mutant mice that are deficient in secreted (s)IgM in an acute peritonitis model induced. by cecal ligation and puncture (CLP). 20% of wild-type mice died within 32 h of CLP, whereas 70% of sIgM-deficient mice died within the same time period, The increased susceptibility was associated with a reduced level of tumor necrosis factor (TNF)-alpha, a decreased neutrophil recruitment and art increased bacterial load in the peritoneum, and elevated levels of endotoxin and proinflammatory cytokines in the circulation. Resistance to CLP by sIgM-deficient mice was restored by reconstitution with polyclonal IgM from normal mouse serum. Reconstitution with a monoclonal IgM specific to phosphatidylcholine, a conserved cell membrane component, has a modest effect but a monoclonal IgM specific to phosphocholine is nut protective. These findings demonstrate a critical role of natural IgM in the immediate defense against severe bacterial infection. C1 MIT, Canc Res Ctr, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02135 USA. RP Chen, JZ (reprint author), MIT, Canc Res Ctr, E17-128,40 Ames St, Cambridge, MA 02139 USA. EM jchen@mit.edu FU NIAID NIH HHS [AI36389, AI39246, AI41762, R01 AI036389, R01 AI039246] NR 36 TC 320 Z9 331 U1 1 U2 16 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 21 PY 1998 VL 188 IS 12 BP 2381 EP 2386 DI 10.1084/jem.188.12.2381 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 151HA UT WOS:000077713600020 PM 9858525 ER PT J AU Maynard, KI Quinones-Hinojosa, A Ogilvy, CS AF Maynard, KI Quinones-Hinojosa, A Ogilvy, CS TI Magnesium plus mexiletine inhibit energy usage and protect retinas against ischemia SO NEUROREPORT LA English DT Article DE energy metabolism; ischemia; metabolic inhibition; neuroprotection; stroke ID CENTRAL-NERVOUS-SYSTEM; CEREBRAL-ISCHEMIA; CNS ISCHEMIA; NEURONS; METABOLISM AB WE determined whether exogenous Mg2+ and/or mexiletine (Mex), which are reported to be neuroprotective agents, reduced neuronal energy requirements and protected against ischemia, using isolated rabbit retinas. Under non-ischemic conditions, Mex (300 mu M) and the combination of Mg2+ (1 mM) plus Mex (300 mu M) significantly reduced glucose utilization, by 19% and 31%, respectively. The combination of Mg2+ plus Mex, but not either agent alone, significantly reduced lactate production (by 18%; p < 0.05). When added during 2 h of ischemia (simulated by the reduction of oxygen from 95% to 15% and of glucose from 6 mM to 1 mM), Mg2+ plus Mex improved the recovery of glucose utilization (p < 0.01), lactate production (p < 0.05) and neuronal function (p < 0.05) for 3 h following return to control (post-ischemia/recovery) conditions. Thus reducing energy demands by blocking functions during temporary ischemia, protects neurons from irreversible functional damage. (C) 1998 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, Neurophysiol Lab, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Maynard, KI (reprint author), Massachusetts Gen Hosp, Neurophysiol Lab, Neurosurg Serv, Edwards 414,55 Fruit St, Boston, MA 02114 USA. FU NINDS NIH HHS [NS01732] NR 22 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD DEC 21 PY 1998 VL 9 IS 18 BP 4141 EP 4144 DI 10.1097/00001756-199812210-00026 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 158QY UT WOS:000078128400030 PM 9926863 ER PT J AU Tesco, G Kim, TW Diehlmann, A Beyreuther, K Tanzi, RE AF Tesco, G Kim, TW Diehlmann, A Beyreuther, K Tanzi, RE TI Abrogation of the presenilin 1 beta-catenin interaction and preservation of the heterodimeric presenilin 1 complex following caspase activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FAMILIAL ALZHEIMERS-DISEASE; IN-VIVO; CAENORHABDITIS-ELEGANS; PROTEOLYTIC CLEAVAGE; APOPTOSIS; BRAIN; ENDOPROTEOLYSIS; PROTEIN; CELLS; OCCUR AB beta-Catenin has previously been shown to interact with presenilin 1 (PS1) in transfected cells. Here we report that beta-catenin co-immunoprecipitates with the endogenous C-terminal fragment of presenilin 1 (PS1-CTF) but not with the endogenous CTF of presenilin 2 (PS2-CTF) in H4 human neuroglioma cells. During staurosporine (STS)-induced cell death, beta-catenin and PS1-CTF undergo a caspase-mediated cleavage. After 12 h of STS treatment, the beta-catenin PS1-CTF interaction is abrogated. While PS1-CTF immunoprecipitated with all caspase-cleaved species of beta-catenin, beta-catenin holoprotein did not co-immunoprecipitate with the "alternative" caspase-derived PS1-CTF (PS1-aCTF). Thus, the abrogation of the beta-catenin PS1-CTF complex was due to caspase cleavage of PS1-CTF. beta-Catenin co-immunoprecipitated with PS1-NTF, but only when PS1-NTF was associated with PS1-CTF, Even though PS1-NTF CTF complex stability was not altered by caspase cleavage, its ability to bind beta-catenin was abolished, Thus, while the PS1-NTF CTF complex is preserved after caspase cleavage, it may no longer be fully functional. C1 Massachusetts Gen Hosp, Genet & Aging Unit, Charlestown, MA 02129 USA. Harvard Med Sch, Charlestown, MA 02129 USA. Zentrum Mol Biol, INF 282, D-69120 Heidelberg, Germany. RP Tanzi, RE (reprint author), Massachusetts Gen Hosp E, Dept Neurol, Genet & Aging Unit, 149 13th St, Charlestown, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu NR 26 TC 58 Z9 59 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 18 PY 1998 VL 273 IS 51 BP 33909 EP 33914 DI 10.1074/jbc.273.51.33909 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 148PZ UT WOS:000077542200007 PM 9852041 ER PT J AU Hocker, M Raychowdhury, R Plath, T Wu, HJ O'Connor, DT Wiedenmann, B Rosewicz, S Wang, TC AF Hocker, M Raychowdhury, R Plath, T Wu, HJ O'Connor, DT Wiedenmann, B Rosewicz, S Wang, TC TI Sp1 and CREB mediate gastrin-dependent regulation of chromogranin A promoter activity in gastric carcinoma cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HISTIDINE-DECARBOXYLASE PROMOTER; PHORBOL 12-MYRISTATE 13-ACETATE; ENTEROCHROMAFFIN-LIKE CELLS; PROTEIN-KINASE; GROWTH-FACTOR; RAT STOMACH; TRANSCRIPTIONAL ACTIVATION; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; CAMP AB Chromogranin A (CgA) is a multifunctional acidic protein that in the stomach is expressed predominantly in enterochromaffin-like cells (ECL cells) where it is regulated by gastrin, In order to investigate the transcriptional response of the mouse CgA (mCgA) promoter to gastrin stimulation, we studied a 4.8-kilobase mCgA promoter-luciferase reporter gene construct in transiently transfected AGS-B cells, 5'-Deletion analysis and scanning mutagenesis of mCgA 5'-flanking DNA showed that a Sp1/Egr-1 site spanning -88 to -77 base pairs (bp) and a cyclic AMP-responsive element (CRE) at -71 to -64 bp are essential for gastrin-dependent mCgA transactivation. Gastrin stimulation increased cellular Sp1 protein levels and Sp1-binding to the mCgA -88 to -77 bp element, as well as binding of CREB to its consensus motif at -71 to -64 bp. Gastrin also stimulated CREB Ser-133 phosphorylation, and abundance of cellular CREB protein levels. Overexpression of either Sp1 or phosphorylated CREB transactivated the mCgA promoter dose dependently, while coexpression of both transcription factors resulted in an additive mCgA promoter response, mCgA -92 to -64 bp, comprising the Sp1/Egr-1 site and the CRE motif, conferred gastrin responsiveness to a heterologous thymidine kinase promoter system, and therefore functions as a "true" enhancer element. This report demonstrates that Sp1 and CREB mediate CCK-B/gastrin receptor-dependent gene regulation, and that the effect of gastrin on the CgA gene is brought about by cooperative action of both transcription factors. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Humboldt Univ, Klinikum Charite, Med Klin Scherpunkt Gastroenterol & Hepatol, D-1086 Berlin, Germany. Free Univ Berlin, Klinikum Benjamin Franklin, D-1000 Berlin, Germany. Univ Calif San Diego, Dept Med, San Diego, CA 92161 USA. Univ Calif San Diego, Ctr Mol Genet, San Diego, CA 92161 USA. RP Wang, TC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 30 Fruit St, Boston, MA 02114 USA. EM Wang@helix.mgh.harvard.edu FU NIDDK NIH HHS [R01 DK 48077] NR 52 TC 52 Z9 54 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 18 PY 1998 VL 273 IS 51 BP 34000 EP 34007 DI 10.1074/jbc.273.51.34000 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 148PZ UT WOS:000077542200020 PM 9852054 ER PT J AU Rosowsky, A Wright, JE Vaidya, CM Bader, H Forsch, RA Mota, CE Pardo, J Chen, CS Chen, YN AF Rosowsky, A Wright, JE Vaidya, CM Bader, H Forsch, RA Mota, CE Pardo, J Chen, CS Chen, YN TI Synthesis and potent antifolate activity and cytotoxicity of B-ring deaza analogues of the nonpolyglutamatable dihydrofolate reductase inhibitor N-alpha-(4-amino-4-deoxypteroyl)-N-delta-hemiphthaloyl-L-ornithine (PT523) SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ANTICANCER DRUG SCREEN; CARCINOMA CELL-LINES; MULTIDRUG-RESISTANT PHENOTYPE; FOLIC-ACID; INTRINSIC RESISTANCE; FOLYLPOLYGLUTAMATE SYNTHETASE; METHOTREXATE POLYGLUTAMATES; PNEUMOCYSTIS-CARINII; INHERENT RESISTANCE; BIOLOGICAL-ACTIVITY AB Six new B-ring analogues of the nonpolyglutamatable antifolate N-alpha-(4-amino-4-deoxypteroyl)-N-delta-hemiphthaloyl-L-ornithine (PT523, 3) were synthesized with a view to determining the effect of modifications at the 5- and/or 8-position on dihydrofolate reductase (DHFR) binding and tumor cell growth inhibition The 5- and 8-deaza analogues were prepared from methyl 2-L-amino-5-phthalimidopentanoate and 4-amino-4-deoxy-N-10-formyl-5-deaza- and -8-deazapteroic acid, respectively. The 5,8-dideaza analogues were prepared from methyl 2-L-[(4-aminobenzoyl)-amino]-5-phthalimidopentanoate and 2,4-diaminoquinazoline-6-carbonitriles. The K-i for inhibition of human DHFR by the 5-deaza and 5-methyl-5-deaza analogues was about the same as that of 3 (0.35 pM), 11-fold lower than that of aminopterin (AMT, 1), and 15-fold lower than that of methotrexate (MTX, 2). However the K-i of the 8-deaza analogue was 27-fold lower than that of 1, and that of the 5,8-dideaza, 5-methyl-5,8-dideaza, and 5-chloro-5,8-dideaza analogues was approximately 50-fold lower. This trend was consistent with the published literature on the corresponding DHFR inhibitors with a glutamate side chain. In colony formation assays against the human head and neck squamous carcinoma cell line SCC25 after 72 h of treatment, the 5- and 8-deaza analogues were approximately as potent as 3, whereas the 5,8-dideaza analogue was 3 times more potent. 5-Methyl and 5-chloro substitution was also favorable, with the 5-methyl-5-deaza analogue being 2.5-fold more potent than the 5-deaza analogue. However the effect of 5-methyl substitution was less pronounced in the 5,8-dideaza analogues than in the 5-deaza analogues. The 5-chloro-5,8-dideaza analogue of 3 was the most active member of the series, with an IC50 = 0.33 nM versus 1.8 nM for 3 and 15 nM for MTX. The 5-methyl-5-deaza analogue of 3 was also tested at the National Cancer Institute against a panel of 50 human tumor cell lines in culture and was consistently more potent than 3, with IC50 values in the low nanomolar to subnanomolar range against most of the tumors. Leukemia and colorectal carcinoma cell lines were generally most sensitive, though good activity was also observed against CNS tumors and carcinomas of the breast and prostate. The results of this study demonstrate that B-ring analogues of 3 inhibit DHFR activity and tumor cell colony formation as well as, or better than, the parent compound. In view of the fact that 3 and its B-ring analogues cannot form polyglutamates, their high cytotoxicity relative to the corresponding B-ring analogues of AMT is noteworthy. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Rosowsky, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA25394, CA70349] NR 50 TC 29 Z9 29 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 17 PY 1998 VL 41 IS 26 BP 5310 EP 5319 DI 10.1021/jm980477+ PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 149LA UT WOS:000077605700017 PM 9857098 ER PT J AU Shimada, M Tritos, NA Lowell, BB Flier, JS Maratos-Flier, E AF Shimada, M Tritos, NA Lowell, BB Flier, JS Maratos-Flier, E TI Mice lacking melanin-concentrating hormone are hypophagic and lean SO NATURE LA English DT Article ID TARGETED DISRUPTION; NEUROPEPTIDE-Y; MESSENGER-RNA; OBESE GENE; LEPTIN; AGOUTI; PROTEIN; WEIGHT AB Feeding is influenced by hypothalamic neuropeptides that promote (orexigenic peptides) or inhibit feeding(1). Of these, neuropeptide Y (NPY) in the arcuate nucleus' and melanin-concentrating hormone (MCH)(3) and orexins/hypocretins(4,5) in the lateral hypothalamus have received attention because their expression is increased during fasting and because they promote feeding when administered centrally. Surprisingly, absence of the orexigenic neuropeptide NPY fails to alter feeding or body weight in normal mice(6). As deficiency of a single component of the pathway that limits food intake (such as leptin or receptors for melanocortin-4)(7,8) causes obesity, it has been suggested that orexigenic signals are more redundant than those limiting food intake(7,8). To define further the physiological role of MCH and to test the redundancy of orexigenic signals, we generated mice carrying a targeted deletion of the MCH gene. MCH-deficient mice have reduced body weight and leanness due to hypophagia (reduced feeding) and an inappropriately increased metabolic rate, despite their reduced amounts of both leptin and arcuate nucleus pro-opiomelanocortin messenger RNA. Our results show that MCH is a critical regulator of feeding and energy balance which acts downstream of leptin and the melanocortin system, and that deletion of a gene encoding a single orexigenic peptide can result in leanness. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02115 USA. RP Maratos-Flier, E (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM emarat@joslab.harvard.edu NR 29 TC 799 Z9 816 U1 2 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 17 PY 1998 VL 396 IS 6712 BP 670 EP 674 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 150YT UT WOS:000077694200052 PM 9872314 ER PT J AU Lloyd-Jones, DM Martin, DO Larson, MG Levy, D AF Lloyd-Jones, DM Martin, DO Larson, MG Levy, D TI Accuracy of death certificates for coding coronary heart disease as the cause of death SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE coronary disease; death certificates; cause of death; mortality; epidemiologic methods ID MORTALITY; AUTOPSY; POPULATION; TRENDS; COMPLETION; STATISTICS; DECLINE; ERRORS; MEN AB Background: Death certificates are widely used in epidemiologic and clinical investigations and for national statistics. Objective: To examine the accuracy of death certificates for coding coronary heart disease as the underlying cause of death. Design: Community-based inception cohort followed since 1948. Setting: Framingham, Massachusetts. Patients: 2683 deceased Framingham Heart Study participants. Measurements: Sensitivity, specificity, and predictive values of the death certificate. The reference standard was cause of death adjudicated by a panel of three physicians. Results: Among 2683 decedents, the death certificate coded coronary heart disease as the underlying cause of death for 942; the physician panel assigned coronary heart disease for 758. The death certificate had a sensitivity of 83.8% (95% CI, 81.1% to 86.4%), positive predictive value of 67.4% (CI, 64.4% to 70.4%), specificity of 84.1% (CI, 82.4% to 85.7%1), and negative predictive value of 92.9% (CI, 91.7% to 94.1 %) for coronary heart disease. The death certificate assigned coronary heart disease in 51.2% of 242 deaths (9.0% of total deaths) for which the physician panel could not determine a ca use. Compared with the physician panel, the death certificate attributed 24.3% more deaths to coronary heart disease overall and more than twice as many deaths to coronary heart disease in decedents who were at least 85 years of age. When deaths that were assigned unknown cause by the physician panel were excluded, the death certificate still assigned more deaths to coronary heart disease (7.9% overall and 43.1% in the oldest age group). Conclusions: Coronary heart disease may be overrepresented as a cause of death on death certificates. National mortality statistics, which are based on death certificate data, may overestimate the frequency of coronary heart disease by 7.9% to 24.3% overall and by as much as twofold in older persons. C1 NHLBI, NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Durham, NC 27710 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Levy, D (reprint author), Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. RI Lloyd-Jones, Donald/C-5899-2009 FU NHLBI NIH HHS [N01-HC-38038] NR 39 TC 276 Z9 279 U1 1 U2 8 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 15 PY 1998 VL 129 IS 12 BP 1020 EP + PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 147DC UT WOS:000077471900004 PM 9867756 ER PT J AU Auer, KL Park, JS Seth, P Coffey, RJ Darlington, G Abo, A McMahon, M DePinho, RA Fisher, PB Dent, P AF Auer, KL Park, JS Seth, P Coffey, RJ Darlington, G Abo, A McMahon, M DePinho, RA Fisher, PB Dent, P TI Prolonged activation of the mitogen-activated protein kinase pathway promotes DNA synthesis in primary hepatocytes from p21(Cip-1/WAF1)-null mice, but not in hepatocytes from p16(INK4a)-null mice SO BIOCHEMICAL JOURNAL LA English DT Article ID ADULT-RAT HEPATOCYTES; CELL-CYCLE ARREST; P53-INDEPENDENT INDUCTION; INDUCED PROLIFERATION; LIVER-REGENERATION; TUMOR SUPPRESSION; INK4A LOCUS; EXPRESSION; GENE; P53 AB In primary rat hepatocytes, prolonged activation of the p42/44 mitogen-activated protein kinase (MAPK) pathway is associated with a decrease in DNA synthesis and increased expression of the cyclin-dependent kinase inhibitor (CKI) proteins p21(Cip-1/WAF1) and p16(INK4a). To evaluate the relative importance of these CKIs in mediating this response, we determined the impact of prolonged MAPK activation on DNA synthesis in primary cultures of hepatocytes derived from mice embryonically deleted (null) for either p21(Cip-1/WAF1) or p16(INK4a). When MAPK was activated in wild-type mouse hepatocytes for 24 h, via infection with a construct to express an inducible oestrogen receptor-Raf-1 fusion protein (Delta Raf: ER), the expression of p21(Cip-1/WAF1) and p16(INK1a) CKI proteins increased, cyclin-dependent kinase 2 (cdk2) and cdk4 activities decreased, and DNA synthesis decreased, Inhibition of RhoA GTPase function increased the basal expression of p21(Cip-1/WAF1) and p27(Kip-1) but not p16(INK4a), and enhanced the ability of MAPK signalling to decrease DNA synthesis. Ablation of the expression of CCAATT enhancer-binding protein alpha (C/EBP alpha), but not of the expression of C/EBP beta, decreased the ability of MAPK signalling to induce p21(Cip-1/WAF1). When MAPK was activated in p16(INK4a)-null hepatocytes for 24 h, the expression of p21(Cip-1/WAF1) increased, cdk2 and cdk4 activities decreased and DNA synthesis decreased. In contrast with these findings, prolonged activation of the MAPK pathway in hepatocytes from p21(Cip-1/WAF1)-null mice enhanced cdk1 and cdk4 activities and caused a large increase in DNA synthesis, despite elevated expression of p16(INK4a). Inhibition of RhoA GTPase activity in p21(Cip-1/WAF1)-null cells partly blunted both the basal levels of DNA synthesis and the ability of prolonged MAPK signalling to increase DNA synthesis. Expression of anti-sense p21(Cip-1/WAF1) in either wild-type or p16(INK4a)-null hepatocytes decreased the ability of prolonged MAPK signalling to increase the expression of P21(Cip-1/WAF1), and permitted MAPK signalling to increase both cdk2 and cdk4 activities and DNA synthesis. These results argue that the ability of prolonged MAPK signalling to inhibit DNA synthesis in hepatocytes requires the expression of p21(Cip-1/WAF1), and that the increased expression of p16(INK4a) has a smaller role in the ability of this stimulus to mediate growth arrest. Our results also suggest that RhoA function can modulate DNA synthesis in primary hepatocytes via the expression of p21(CiP-1/WAF1) and p27(Kip-1). C1 Virginia Commonwealth Univ, Med Coll Virginia, Dept Radiat Oncol, Richmond, VA 23298 USA. NCI, Breast Canc Sect, Med Branch, Bethesda, MD 20892 USA. Vanderbilt Univ, Dept Gastroenterol & Med Oncol, Nashville, TN 37232 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77071 USA. Onyx Pharmaceut, Richmond, CA 94806 USA. Univ Calif San Francisco, Mt Zion Canc Ctr, Canc Res Inst, San Francisco, CA 94115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Columbia Univ Coll Phys & Surg, Dept Urol & Pathol, New York, NY 10032 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. RP Dent, P (reprint author), Virginia Commonwealth Univ, Med Coll Virginia, Dept Radiat Oncol, Richmond, VA 23298 USA. EM pdent@hsc.vcu.edu NR 43 TC 53 Z9 54 U1 0 U2 3 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD DEC 15 PY 1998 VL 336 BP 551 EP 560 PN 3 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 153RW UT WOS:000077847300007 PM 9841865 ER PT J AU Whalen, PJ Bush, G McNally, RJ Wilhelm, S McInerney, SC Jenike, MA Rauch, SL AF Whalen, PJ Bush, G McNally, RJ Wilhelm, S McInerney, SC Jenike, MA Rauch, SL TI The emotional counting Stroop paradigm: A functional magnetic resonance imaging probe of the anterior cingulate affective division SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Research Symposium on Brain Neurocircuitry of Anxiety and Fear - Implications for Clinical Research and Practice CY MAR 26, 1998 CL BOSTON, MA SP Anxiety Disorders Assoc Amer, NIMH, Wyeth Ayerst Labs DE imaging; anxiety disorders; obsessive-compulsive disorder; emotion ID POSTTRAUMATIC-STRESS-DISORDER; OBSESSIVE-COMPULSIVE DISORDER; POSITRON EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; SYMPTOM PROVOCATION; PREFRONTAL CORTEX; THREAT CUES; ANXIETY; TASK; ATTENTION AB Background: The emotional counting Stroop (ecStroop) functional magnetic resonance imaging (fMRI) activation paradigm was designed to recruit the anterior cingulate affective division (ACad). Methods: Nine normal, healthy male and female subjects (mean age 24.2 years) reported via button press the number of neutral and negative words that appeared on a screen while reaction time and fMRI data were acquired. Results: We observed a) greater ACad activation for negative versus neutral words during initial presentation blocks; b) lower overall ACad signal intensity during task performance (i.e. both negative and neutral words) compared to the baseline fixation condition; and c) no reaction time increase to negative versus neutral words. Conclusions: In a companion study of a cognitive version of the counting Stroop (Bush et al 1998), these same 9 subjects a) activated the more dorsal anterior cingulate cognitive division; b) also showed the overall decrease in ACad signal intensity; and c) demonstrated a reliable reaction time effect. Taken together, these data offer a within-group spatial dissociation of AC function based upon information content (i.e., cognitive vs. emotional) and/or presence of behavioral interference. We propose the that ecStroop will be a useful fMRI probe of ACad function in anxiety disorders. Biol Psychiatry 1998;44:1219-1228. (C) 1998 Society of Biological Psychiatry. C1 Massachusetts Gen Hosp, Dept Psychiat, Psychiat Neuroimaging Res Grp, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Psychiat, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Rauch, SL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Psychiat Neuroimaging Res Grp, 13th St,Bldg 149,CNY-9, Charlestown, MA 02129 USA. FU NIMH NIH HHS [MH-01215, MH-16259] NR 49 TC 464 Z9 468 U1 13 U2 50 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 1998 VL 44 IS 12 BP 1219 EP 1228 DI 10.1016/S0006-3223(98)00251-0 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 147JC UT WOS:000077484900005 PM 9861465 ER PT J AU Teoh, G Chen, L Urashima, M Tai, YT Celi, LA Chen, DS Chauhan, D Ogata, A Finberg, RW Webb, IJ Kufe, DW Anderson, KC AF Teoh, G Chen, L Urashima, M Tai, YT Celi, LA Chen, DS Chauhan, D Ogata, A Finberg, RW Webb, IJ Kufe, DW Anderson, KC TI Adenovirus vector-based purging of multiple myeloma cells SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY; VERSUS-HOST DISEASE; RECOMBINANT ADENOVIRUS; HEMATOPOIETIC-CELLS; PERIPHERAL-BLOOD; GENE-TRANSFER; STEM-CELLS; THERAPY; EXPRESSION AB Adenoviruses are efficient gene delivery agents for a variety of neoplasms. In the present study, we have investigated the use of adenoviruses for the delivery of the thymidine kinase (tk) gene into multiple myeloma (MM) cells. We first demonstrated that MM cell lines and MM patient cells express both adenovirus receptors as well as the DF3/MUC1 protein, thus providing a rationale for using adenoviruses to selectively deliver genes under the control of the DF3 promoter. By using an adenoviral construct containing beta-galactosidase (beta-gal) gene driven by the DFB promoter (Ad.DF3-beta gal), we demonstrate greater than 80% transduction efficiency in OCI-My5 and RPMI 8226 MM cell lines at a multiplicity of infection of 1 to 100. Importantly, transduction with the tk gene driven by the DF3 promoter (Ad.DF3-tk) followed by treatment with 50 mu mol/L ganciclovir (GCV) purged greater than or equal to 6 log of contaminating OCI-My5 and RPMI 8226 MM cells within bone marrow mononuclear cells. In contrast, normal human hematopoietic progenitor cell number was unaffected under these conditions. Selectivity of DF3/MUC1 promoter was further confirmed, because Ad.DF3-beta gal or Ad.DF3-tk did not transduce MUC1-negative HeLa cervical carcinoma cells. In addition, GCV treatment of Ad.DFB-tk-transduced RPMI 8226 MM cells did not induce a significant bystander effect. These findings demonstrate that transduction with Ad Vectors using a tumor-selective promoter provides a highly efficient and selective approach for the ex vivo purging of MM cells. (C) 1998 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Singapore Gen Hosp, Dept Haematol, Singapore 0316, Singapore. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu RI Finberg, Robert/E-3323-2010 FU NCI NIH HHS [CA 78378] NR 43 TC 48 Z9 48 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 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 1998 VL 92 IS 12 BP 4591 EP 4601 PG 11 WC Hematology SC Hematology GA 147JR UT WOS:000077566000012 PM 9845525 ER PT J AU Loh, ML Silverman, LB Young, ML Neuberg, D Golub, TR Sallan, SE Gilliland, DG AF Loh, ML Silverman, LB Young, ML Neuberg, D Golub, TR Sallan, SE Gilliland, DG TI Incidence of TEL/AML1 fusion in children with relapsed acute lymphoblastic leukemia SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; THERAPY-RELATED MYELODYSPLASIA; MINIMAL RESIDUAL DISEASE; TEL GENE; CHILDHOOD; T(12-21); TRANSLOCATION; TRANSFORMATION; REARRANGEMENT; CHEMOTHERAPY AB The TEL/AML1 fusion associated with t(12;21)(p13;q22) is the most common gene rearrangement in childhood leukemia, occurring in approximately 25% of pediatric acute lymphoblastic leukemia (ALL), and is associated with a favorable prognosis. For example, a cohort of pediatric patients with ALL retrospectively analyzed for the TEL/AML1 fusion treated on Dana-Farber Cancer Institute (DFCI) ALL Consortium protocols between 1980 to 1991 demonstrated a 100% relapse-free survival in TEL/AML1-positive patients with a median of 8.3 years of follow-up, However, two recent studies analyzing pediatric patients with relapsed ALL have reported the same incidence of the TEL/AML1 rearrangement as in patients with newly diagnosed ALL, suggesting that TEL/AML1 positivity is not a favorable prognostic indicator. To clarify this apparent discrepancy, 48 pediatric patients treated on Dana-Farber Cancer Institute (DFCI) protocols with ALL at first or second relapse were tested for TEL/AML1 using reverse transcriptase-polymerase chain reaction (RT-PCR). The TEL/AML1 fusion was identified in only 1 of 32 analyzable relapsed ALL patients, in concordance with our previous reports of improved disease-free survival in TEL/AML1-positive patients. The low frequency of TEL/AML1-positive patients at relapse is significantly different than that reported in other studies. Although there are several potential explanations for the observed differences in TEL/AML1-positive patients at relapse, it is plausible that relapse-free survival in TEL/AML1-positive patients may be changed with different therapeutic approaches. Taken together, these results support the need for prospective analysis of prognosis in TEL/AML1-positive patients. (C) 1998 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Inst Human Genet, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Gilliland, DG (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Inst Human Genet, 4 Blackfan Circle,Room 421, Boston, MA 02115 USA. FU NCI NIH HHS [CA68484] NR 36 TC 93 Z9 95 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 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 1998 VL 92 IS 12 BP 4792 EP 4797 PG 6 WC Hematology SC Hematology GA 147JR UT WOS:000077566000033 PM 9845546 ER PT J AU Fadeel, B Ahlin, A Henter, JI Orrenius, S Hampton, MB AF Fadeel, B Ahlin, A Henter, JI Orrenius, S Hampton, MB TI Involvement of caspases in neutrophil apoptosis: Regulation by reactive oxygen species SO BLOOD LA English DT Article ID PROGRAMMED CELL-DEATH; CHRONIC GRANULOMATOUS-DISEASE; PHORBOL MYRISTATE ACETATE; POLYMORPHONUCLEAR LEUKOCYTES; DIFFERENTIAL EXPRESSION; OXIDATIVE-METABOLISM; ICE/CED-3 PROTEASE; IN-VITRO; FAS; INHIBITION AB Human neutrophils have a short half-life and are believed to die by apoptosis or programmed cell death both in vivo and in vitro. We found that caspases are activated in a time-dependent manner in neutrophils undergoing spontaneous apoptosis, concomitant with other characteristic features of apoptotic cell death such as morphologic changes, phosphatidylserine (PS) exposure, and DNA fragmentation. The treatment of neutrophils with agonistic anti-fas monoclonal antibodies (MoAbs) significantly accelerated this process, However, in cells treated with the potent neutrophil activator phorbol 12-myristate 13-acetate (PMA), caspase activity was only evident after pharmacologic inhibition of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Similarily, inhibition of the NADPH oxidase in constitutive and Fas/APO-1-triggered apoptosis resulted in increased rather than suppressed levels of caspase activity, suggesting that reactive oxygen species may prevent caspases from functioning optimally in these cells. Moreover, oxidants generated via the NADPH oxidase were essential for PS exposure during PMA-induced cell death, but not for neutrophils undergoing spontaneous apoptosis. We conclude that caspases are an important component of constitutive and Fas/APO-1-triggered neutrophil apoptosis. However, these redox sensitive enzymes are suppressed in activated neutrophils, and an alternate oxidant-dependent pathway is used to mediate PS exposure and neutrophil clearance under these conditions. (C) 1998 by The American Society of Hematology. C1 Karolinska Inst, Inst Environm Med, Div Toxicol, S-10401 Stockholm, Sweden. Karolinska Hosp, Childhood Canc Res Unit, S-10401 Stockholm, Sweden. Karolinska Inst, Sachs Childrens Hosp, Ctr Inflammat Res, Dept Pediat, Stockholm, Sweden. Stockholm Soder Hosp, Stockholm, Sweden. RP Hampton, MB (reprint author), Massachusetts Gen Hosp, 149 13th St, Charlestown, MA 02129 USA. RI Hampton, Mark/A-8490-2008; OI Hampton, Mark/0000-0002-7349-3729 NR 50 TC 254 Z9 259 U1 0 U2 3 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 DEC 15 PY 1998 VL 92 IS 12 BP 4808 EP 4818 PG 11 WC Hematology SC Hematology GA 147JR UT WOS:000077566000035 PM 9845548 ER PT J AU Abner, AL Collins, L Peiro, G Recht, A Come, S Shulman, LN Silver, B Nixon, A Harris, JR Schnitt, SJ Connolly, JL AF Abner, AL Collins, L Peiro, G Recht, A Come, S Shulman, LN Silver, B Nixon, A Harris, JR Schnitt, SJ Connolly, JL TI Correlation of tumor size and axillary lymph node involvement with prognosis in patients with T1 breast carcinoma SO CANCER LA English DT Article DE breast neoplasms; size; prognostic features; radiation therapy ID CANCER PATIENTS; ONE CENTIMETER; SURVIVAL; METASTASES; DISSECTION; RECURRENCE; RELAPSE; LESS AB BACKGROUND. The prognosis of patients with T1 breast carcinoma remains controversial. Some studies have shown a low risk of lymph node metastasis and distant failure whereas others have not, possibly due to differences in the definition of tumor size. In this study, the authors assessed the relation between macroscopic tumor size, microscopic invasive tumor size, axillary lymph node involvement, and prognosis in a group of patients with clinically lymph node negative disease. METHODS, Between 1968 and 1986, 1865 women with American Joint Committee on Cancer clinical Stage I or II infiltrating carcinoma of the breast were treated at the Joint Center for Radiation Therapy with conservative surgery and radiation therapy. The study population was limited to 118 patients with clinically negative axillary lymph nodes for whom the macroscopic pathologic tumor size was identified unambiguously as being less than or equal to 2.0 cm, who underwent an axillary lymph node dissection with at least 6 lymph nodes sampled, and for whom the microscopic size of the invasive component could be determined. The median follow-up time for surviving patients was 134 months (range, 90-208 months]. No patients with pathologically negative axillary lymph nodes received systemic therapy. RESULTS, Macroscopic and microscopic tumor sizes differed by > 5 mm in 17 patients (14%), by 3-5 mm in 24 patients (20%), and by less than or equal to 2 mm in 77 patients (65%). The macroscopic tumor size was smaller than the microscopic size in 37 patients (31%), larger in 55 patients (47%), and equal in 26 patients (22%). Pathologic axillary lymph node involvement was present in 21% of all patients. The risk of lymph node involvement was not significantly different for those patients with tumors less than or equal to 1 cm compared with patients with tumors greater than or equal to 1.1 cm, regardless of whether tumor size was measured by macroscopic or microscopic examination. The 10-year actuarial rate of freedom from distant recurrence (FFDR) was 91% for lymph node negative patients with macroscopic tumors measuring less than or equal to 1.0 cm compared with 77% for patients with macroscopic tumors measuring greater than or equal to 1.1 cm (P = 0.07). When measured microscopically, the rates were 96% and 72%, respectively (P = 0.001). CONCLUSIONS, There often is a discrepancy between microscopic tumor size and macroscopic tumor size. T1 tumors have a substantial risk of axillary lymph node metastasis whether measured macroscopically or microscopically. Among those patients with pathologic lymph node negative tumors who are not treated with systemic adjuvant therapy, microscopic invasive tumor size is a better predictor of 10-year FFDR than macroscopic tumor size. There is a substantial risk of distant failure for patients with tumors whose invasive component microscopically measure greater than or equal to 1.1 cm, whereas the prognosis for patients with tumors that microscopically measured less than or equal to 1 cm is excellent. These results suggest that the microscopic size of the invasive component of breast carcinomas less than or equal to 2.0 cm routinely should be reported. Cancer 1998;83:2502-8, (C) 1998 American Cancer Society. C1 Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA. Brigham & Womens Hosp, Boston, MA USA. RP Abner, AL (reprint author), Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, 330 Brookline Ave, Boston, MA 02215 USA. NR 24 TC 45 Z9 46 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 15 PY 1998 VL 83 IS 12 BP 2502 EP 2508 DI 10.1002/(SICI)1097-0142(19981215)83:12<2502::AID-CNCR14>3.0.CO;2-I PG 7 WC Oncology SC Oncology GA 151QJ UT WOS:000077731700014 PM 9874455 ER PT J AU Scadden, DT Schenkein, DP Bernstein, Z Luskey, B Doweiko, J Tulpule, A Levine, AM AF Scadden, DT Schenkein, DP Bernstein, Z Luskey, B Doweiko, J Tulpule, A Levine, AM TI Immunotoxin combined with chemotherapy for patients with AIDS-related non-Hodgkin's lymphoma SO CANCER LA English DT Article DE AIDS; AIDS-related lymphoma; non-Hodgkin's lymphoma; immunotoxin; monoclonal antibody therapy ID ACQUIRED IMMUNODEFICIENCY SYNDROME; B-CELL LYMPHOMA; ANTI-B4-BLOCKED RICIN; COMBINATION CHEMOTHERAPY; MULTIDRUG-RESISTANT; CONTINUOUS-INFUSION; ANTIBODY THERAPY; TRIAL; TRANSPLANTATION; EXPERIENCE AB BACKGROUND. The objective of this study was to develop and test a combined therapeutic approach for patients with AIDS-related lymphoma (ARL), employing agents with independent mechanisms of action and nonoverlapping toxicity. This study was designed to test the feasibility and tolerance of combining low dose chemotherapy with infusional immunotoxin in the treatment of ARL patients. METHODS. Previously untreated patients received low dose methotrexate, bleomycin, doxorubicin, cyclophosphamide, and vincristine (m-BACOD) on a 21- to 28-day schedule. Patients who did not have progressive disease by Cycle 3 received anti-B4-blocked ricin (anti-B4bR), a murine monoclonal antibody linked to modified ricin, 20 mu g/kg/day for 7 days administered by continuous infusion on an outpatient basis. A repeat cycle of anti-B4-bR was administered during Cycle 4 of chemotherapy based on tolerance. Patients received two cycles of chemotherapy beyond complete remission up to eight cycles. Study endpoints were toxicity, development of human antimurine antibody (HAMA) and human antiricin (HARA), tumor response, and survival. RESULTS. Twenty-six of 44 patients received the immunotoxin therapy. Anti-B4-bR infusion was associated with transaminase elevation (Grade 3) in 14 of 26 patients (58%), and flulike symptoms were common. HAMA or HARA was observed in 8 patients (31%). The overall response rate was 57% (13 complete responses and 12 partial responses). The median survival for all patients was 8.9 months. CONCLUSIONS. This study demonstrates the safety and feasibility of using chemotherapy and immunotoxin therapies in combination and supports their further evaluation to improve the outcomes of patients with ARL. Cancer 1998;83:2580-7. (C) 1998 American Cancer Society. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH Canc Ctr,AIDS Res Ctr, Boston, MA 02129 USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. SUNY Buffalo, Roswell Pk Canc Ctr, Buffalo, NY 14260 USA. Texas Oncol, Houston, TX USA. Harvard Univ, New England Deaconess Hosp, Sch Med, Boston, MA 02215 USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. RP Scadden, DT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH Canc Ctr,AIDS Res Ctr, Room 5212D,Bldg 149,13th St, Boston, MA 02129 USA. FU NCI NIH HHS [R01 CA55520] NR 27 TC 26 Z9 26 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 15 PY 1998 VL 83 IS 12 BP 2580 EP 2587 DI 10.1002/(SICI)1097-0142(19981215)83:12<2580::AID-CNCR25>3.0.CO;2-C PG 8 WC Oncology SC Oncology GA 151QJ UT WOS:000077731700025 PM 9874466 ER PT J AU Nguyen, JT Wu, P Clouse, ME Hlatky, L Terwilliger, EF AF Nguyen, JT Wu, P Clouse, ME Hlatky, L Terwilliger, EF TI Adeno-associated virus-mediated delivery of antiangiogenic factors as an antitumor strategy SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; ADENOASSOCIATED VIRUS; TUMOR-GROWTH; MAMMALIAN-CELLS; VIRAL VECTOR; ANGIOGENESIS; TRANSDUCTION; EXPRESSION; SUPPRESSION; INHIBITION AB Antiangiogenic tumor therapies have recently attracted intense interest for their broad-spectrum action, low toxicity, and, in the case of direct endothelial targeting, an absence of drug resistance. To promote tumor regression and to maintain dormancy, antiangiogenic agents need to be chronically administered. Gene therapy offers a potential may to achieve sustained therapeutic release of potent antiangiogenic substances. As a step toward this goal, me have generated recombinant adeno-associated virus (rAAV) vectors that carry genes coding for angiostatin, endostatin, and an antisense mRNA species against vascular endothelial growth factor (VEGF), These rAAVs efficiently transduced three human tumor cell lines tested. Transduction with an rAAV-encoding antisense VEGF mRNA inhibited the production of endogenous tumor cell VEGF. Conditioned media from cells transduced with this rAAV or with rAAV-expressing endostatin or angiostatin inhibited capillary endothelial cell proliferation in vitro. Antiangiogenic rAAVs may offer a novel gene therapy approach to undermining tumor neovascularization and cancer progression. C1 Dana Farber Canc Inst, JFB, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiol Sci, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Expt Med, Boston, MA 02115 USA. RP Hlatky, L (reprint author), Dana Farber Canc Inst, JFB, Room 523,44 Binney St, Boston, MA 02115 USA. RI wu, Ping /G-8958-2011 NR 21 TC 106 Z9 115 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1998 VL 58 IS 24 BP 5673 EP 5677 PG 5 WC Oncology SC Oncology GA 148HT UT WOS:000077499800011 PM 9865720 ER PT J AU Seftor, REB Seftor, EA Sheng, SJ Pemberton, PA Sager, R Hendrix, MJC AF Seftor, REB Seftor, EA Sheng, SJ Pemberton, PA Sager, R Hendrix, MJC TI maspin suppresses the invasive phenotype of human breast carcinoma SO CANCER RESEARCH LA English DT Article ID CANCER CELLS; SERPIN; EXPRESSION; MAMMARY; ETS AB The recently discovered tumor suppressor gene maspin has been shown to inhibit tumor cell motility, invasion, and metastasis in breast cancer by our laboratories, Nonetheless, the exploitation of maspin as a potential diagnostic and/or therapeutic tool has remained limited due to the lack of knowledge concerning its molecular and biological mechanism(s) of action. The work reported here demonstrates that recombinant maspin (rMaspin) has the ability to induce higher cell surface levels of alpha(5)- and alpha(3)-containing integrins and reduced levels of alpha(2)-, alpha(4)-, alpha(6)-, alpha(v)-, and some beta(1)-containing integrins in the metastatic human breast carcinoma cell line MDA-MB-435 concomitant with its ability to inhibit the invasive process in vitro. Furthermore, treatment of MDA-MB-435 cells with rMaspin results in the selective adhesion of the cell to a fibronectin matrix and conversion from a fibroblastic to a more epithelial-like phenotype, In addition, the ability of rMaspin to inhibit the invasive process can be abrogated with a blocking antibody to the alpha(5)beta(1) integrin, which diminishes the ability of the cells to invade through a fibronectin matrix-containing barrier in vitro, Taken together, these data address the hypothesis that rMaspin reduces the invasive phenotype of MDA-MB-435 cells by altering their integrin profile, particularly alpha(5), which in turn converts these cells to a more Benign epithelial phenotype, with less invasive ability. These data pro,ide new insights into the biological significance of this tumor suppressor gene found in normal mammary epithelium and may form the basis of novel therapeutic strategies in the management of breast carcinoma. C1 Univ Iowa, Dept Anat & Cell Biol, Coll Med, Iowa City, IA 52242 USA. Univ Iowa, Iowa Canc Ctr, Coll Med, Iowa City, IA 52242 USA. Wayne State Univ, Detroit, MI 48201 USA. LXR Biotechnol, Richmond, CA 94804 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hendrix, MJC (reprint author), Univ Iowa, Dept Anat & Cell Biol, Coll Med, 51 Newton Rd,1-100 BSB, Iowa City, IA 52242 USA. FU NCI NIH HHS [CA61253, CA75681] NR 16 TC 130 Z9 134 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1998 VL 58 IS 24 BP 5681 EP 5685 PG 5 WC Oncology SC Oncology GA 148HT UT WOS:000077499800013 PM 9865722 ER PT J AU Gorski, DH Mauceri, HJ Salloum, RM Gately, S Hellman, S Beckett, MA Sukhatme, VP Soff, GA Kufe, DW Weichselbaum, RR AF Gorski, DH Mauceri, HJ Salloum, RM Gately, S Hellman, S Beckett, MA Sukhatme, VP Soff, GA Kufe, DW Weichselbaum, RR TI Potentiation of the antitumor effect of ionizing radiation by brief concomitant, exposures to angiostatin SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; ANGIOGENESIS INHIBITOR; TUMOR-GROWTH; CANCER; METASTASIS; CARCINOMA; PLASMINOGEN; THERAPY; CELLS AB Angiostatin, a proteolytic fragment of plasminogen, inhibits the growth of primary and metastatic tumors by suppressing angiogenesis, When used in combination with ionizing radiation (IR), angiostatin demonstrates potent antitumor synergism, largely caused by inhibition of the tumor microvasculature. We report here the temporal interaction of angiostatin and IR in Lewis lung carcinoma (LLC) tumors growing in the hind limbs of syngeneic mice. Tumors with an initial mean volume of 510 +/- 151 mm(3) were treated with IR alone (20 Gy x 2 doses on days 0 and 1), angiostatin alone (25 md/kg/day divided twice daily) on days 0 through 13, or a combination of the two as follows: (a) IR plus angiostatin (days 0 through 13); (b) IR plus angiostatin (days 0 and 1); and (c) IR Followed by angiostatin beginning on the day after IR completion and given daily thereafter (days 2 through 13), By day 14, tumors in untreated control mice had grown to 6110 +/- 582 mm(3), whereas in mice treated with: (a) IR alone, tumors had grown to 2854 +/- 338 mm(3) (P < 0.05 compared with untreated controls); and (b) angiostatin alone, tumors had grown to 3666 +/- 453 mm(3) (P < 0.05 compared with untreated controls). In combined-treatment groups, in mice treated with: (a) IR plus Longer-course angiostatin, tumors reached 2022 +/- 282 mm(3) (P = 0.036 compared with IR alone); (b) IR followed by angiostatin, tumors reached 2677 +/- 469 mm(3) (P > 0.05 compared with IR alone); and (c) IR plus short-course angiostatin, tumors reached 1032 +/- 78 mm(3) (P < 0.001 compared with IR alone). These findings demonstrate that the efficacy of experimental radiation therapy is potentiated by brief concomitant exposure of the tumor vasculature to angiostatin. C1 Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. Univ Chicago, Dept Surg, Chicago, IL 60637 USA. Northwestern Univ, Dept Med, Div Hematol & Oncol, Chicago, IL 60611 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Renal, Boston, MA 02115 USA. RP Weichselbaum, RR (reprint author), Univ Chicago, Dept Radiat & Cellular Oncol, 5841 S Maryland Ave, Chicago, IL 60637 USA. FU NCI NIH HHS [CA42596] NR 22 TC 164 Z9 172 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1998 VL 58 IS 24 BP 5686 EP 5689 PG 4 WC Oncology SC Oncology GA 148HT UT WOS:000077499800014 PM 9865723 ER PT J AU Zhou, DC Hallam, SJ Lee, SJ Klein, RS Wiernik, PH Tallman, MS Robert, E AF Zhou, DC Hallam, SJ Lee, SJ Klein, RS Wiernik, PH Tallman, MS Robert, E TI Constitutive expression of cellular retinoic acid binding protein II and lack of correlation with sensitivity to all-trans retinoic acid in acute promyelocytic leukemia cells SO CANCER RESEARCH LA English DT Article ID PML-RAR-ALPHA; CRABP-I; MYELOID-LEUKEMIA; MESSENGER-RNA; LINE HL-60; HUMAN SKIN; INDUCTION; DIFFERENTIATION; RESISTANCE; TRANSCRIPTION AB The up-regulation of cellular retinoic acid binding protein-II (CRABP-II) has been invoked as an important mechanism of clinically acquired resistance to all-trans retinoic acid (RA) therapy in acute promyelocytic leukemia (APL), To test this hypothesis, we used quantitative reverse transcription-PCR and fast performance liquid chromatography procedures to examine the levels of CRABP-II mRNA and RA binding activity in APL patient samples. We found that CRABP-II mRNA in APL cells from pretreatment patients (Is = 36) was constitutively expressed at relatively high levels (median, 0.92; range, 0.16-4.13) relative to the level in CRABP-II protein-expressing NB4 cells (arbitrarily set at 1.0 unit). Consistent with this finding, the RA binding activity of CRABP in APL cells from three pretreatment cases (range, 27.2-53.2 fmol/mg protein) was similar to that of NB4 cells (22.6 +/- 5.4 fmol/mg protein). Furthermore, in the pretreatment samples, there was no association between CRABP-II mRNA expression level and APL cellular sensitivity to RA-induced differentiation irt vitro. After 45 days of remission induction therapy on Eastern Cooperative Oncology Group protocol E2491, CRABP-II mRNA was modestly increased from day 0 values in patients treated with either RA (median increase, 0.41) or chemotherapy (median increase, 0.56), and there was no significant difference between the two treatment groups (P = 0.91). In patients studied after relapse from RA therapy (n = 7), there was a significant decline in APL cell sensitivity to RA-induced differentiation in vitro compared with patients after relapse from chemotherapy (n = 5; P = 0.015-0.055 at three RA concentrations tested), but in the RA relapse cases, there was no change from pretreatment levels of CRABP-II mRNA (median, 0.98) or, in three relapse cases studied, of RA protein binding activity (range, 22.1-70.7 fmol/mg protein). Taken together, our data strongly imply that variations in CRABP-II expression and RA binding activity are not causally related to the development of clinically acquired APL cellular RA resistance, but rather, they suggest that constitutive expression of CRABP-II could have a facilitative role in the response of APL cells to RA. C1 Montefiore Med Ctr, Albert Einstein Canc Ctr, Dept Oncol, Bronx, NY 10467 USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. Northwestern Univ, Sch Med, Dept Med, Div Hematol Oncol, Chicago, IL 60611 USA. Eastern Cooperat Oncol Grp, Brookline, MA 02146 USA. RP Zhou, DC (reprint author), Montefiore Med Ctr, Albert Einstein Canc Ctr, Dept Oncol, 11 E 210th St, Bronx, NY 10467 USA. FU NCI NIH HHS [CA 56771] NR 49 TC 18 Z9 19 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1998 VL 58 IS 24 BP 5770 EP 5776 PG 7 WC Oncology SC Oncology GA 148HT UT WOS:000077499800026 PM 9865735 ER PT J AU Sckell, A Safabakhsh, N Dellian, M Jain, RK AF Sckell, A Safabakhsh, N Dellian, M Jain, RK TI Primary tumor size-dependent inhibition of angiogenesis at a secondary site: An intravital microscopic study in mice SO CANCER RESEARCH LA English DT Article ID VASCULAR-PERMEABILITY FACTOR; ENDOTHELIAL GROWTH-FACTOR; MICROVASCULAR PERMEABILITY; CARCINOMA; MICROENVIRONMENT; XENOGRAFTS; MACROPHAGE; ADHESION; VESSELS AB Some primary tumors are capable of suppressing the growth of their metastases by presumably generating antiangiogenic factors such as angiostatin, We hypothesized that the amount of inhibitor(s) released by a tumor increases with tumor growth, We tested this hypothesis by evaluating the relationship between the size of a primary tumor and its ability to inhibit angiogenesis at a secondary site. Furthermore, we characterized the effects of the primary tumor on physiological properties of newly formed vessels at the secondary site. Angiogenesis and physiological properties were measured using intravital microscopy of angiogenic vessels in the gels containing basic fibroblast growth factor placed into cranial windows of immunodeficient mice bearing human prostatic carcinoma (PC-3) in their flank, The PC-3 tumor inhibited angiogenesis in the gels, and surgical resection of tumor reversed this inhibition. The inhibition of angiogenesis 20 days after gel implantation (range, 0-83%) correlated positively (r = 0.625; P < 0.008) with the tumor size on the day of gel implantation (range, 19-980 mm(3)). The primary tumor also suppressed leukocyte-adhesion in angiogenic vessels, thus helping them evade the immune recognition. These results provide an additional rationale for combining antiangiogenic treatment with local therapies. C1 Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, COX 7, Boston, MA 02114 USA. FU NCI NIH HHS [R35-CA56591] NR 25 TC 42 Z9 44 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1998 VL 58 IS 24 BP 5866 EP 5869 PG 4 WC Oncology SC Oncology GA 148HT UT WOS:000077499800038 PM 9865747 ER PT J AU Li, ZG Wu, WP Kemp, O Stephen, M Manolios, N AF Li, ZG Wu, WP Kemp, O Stephen, M Manolios, N TI The interchain disulfide linkage of T-cell antigen receptor-alpha and -beta chains is a prerequisite for T-cell activation SO CELLULAR IMMUNOLOGY LA English DT Article DE TCR; interchain disulfide bond; clonotypic chain interaction; cell surface expression; T-cell activation ID CONSTANT-REGION; SIGNAL-TRANSDUCTION; SURFACE EXPRESSION; TCR-ALPHA; DOMAIN; HETERODIMERS; SUPERANTIGEN; COMPLEXES; CD3; MHC AB Complementary DNAs encoding the T-cell antigen receptor (TCR)-alpha and mutant TCR-beta chains, lacking the interchain disulfide bond-related cysteine, were introduced into a TCR-alpha and -beta protein-deficient T-cell line. TCR-alpha and the mutant TCR-beta chains assembled with the CD3-epsilon, -gamma, -delta, and -zeta subunits and were efficiently transported to the cell surface; however, the hybrid TCR molecules exhibited a diminished response to T-cell activation by major histocompatibility complex-bound antigen, superantigen, and TCR crosslinking. These results suggest that the interchain disulfide bond between the TCR clonotypic chains is not required for TCR assembly and cell surface expression, but it plays an important role in maintaining the functional integrity of the TCR complex. (C) 1998 Academic Press. C1 Royal N Shore Hosp, Dept Rheumatol, Sutton Rheumatism Res Lab, St Leonards, NSW 2065, Australia. Univ Sydney, Dept Med, St Leonards, NSW 2065, Australia. RP Li, ZG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Immunol & AIDS, 44 Binney St,SM722, Boston, MA 02115 USA. NR 52 TC 5 Z9 5 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD DEC 15 PY 1998 VL 190 IS 2 BP 101 EP 111 DI 10.1006/cimm.1998.1383 PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 151QZ UT WOS:000077733300002 PM 9878111 ER PT J AU Yuan, C Beach, KW Smith, LH Hatsukami, TS AF Yuan, C Beach, KW Smith, LH Hatsukami, TS TI Measurement of atherosclerotic carotid plaque size in vivo using high resolution magnetic resonance imaging SO CIRCULATION LA English DT Article DE atherosclerosis; magnetic resonance imaging; plaque; carotid arteries ID ARTERY STENOSIS; IN-VIVO; ULTRASONOGRAPHY; ANGIOGRAPHY AB Background-Current imaging modalities, such as contrast angiography, accurately determine the degree of luminal nan-owing but provide no direct information on plaque size. Magnetic resonance imaging (MRI), however, has potential for noninvasively determining arterial wall area (WA). This study was conducted to determine the accuracy of in vivo MRI for measuring the cross-sectional maximum wall area (MaxWA) of atherosclerotic carotid arteries in a group of patients undergoing carotid endarterectomy. Methods and Results-Fourteen patients scheduled for carotid endarterectomy underwent preoperative carotid MRT using a custom-made phased-array coil. The plaques were excised en bloc and scanned using similar imaging parameters. MaxWA measurements from the ex vivo MRI were used as the reference standard and compared with MaxWA measurements from the corresponding in vivo MR study. Agreement between the in vivo and ex vivo measurement was analyzed using the Bland-Altman method. The paired in vivo and ex vivo MaxWA measurements strongly agreed: the mean difference (in vivo minus ex vivo) in MaxWA was 13.1+/-6.5 mm(2) fur T1-weighted (TIW) imaging (mean MaxWA in vivo=94.7 mm(2), ex vivo=81.6 mm(2)) and 14.1+/-11.7 mm2 for proton density-weighted (PDW) imaging (mean MaxWA in vivo=93.4 mm(2), ex vivo=79.3 mm(2)). Intraobserver and interobserver variability was small, with intraclass correlation coefficients ranging from 0.90 to 0.98. Conclusions-MRI is highly accurate for in vivo measurement of artery WA in atherosclerotic carotid lesions. This imaging technique has potential application monitoring lesion size in studies examining plaque progression and/or regression. C1 VA Puget Sound Hlth Care Syst, Surg Serv 112, Seattle, WA 98108 USA. Univ Washington, Dept Radiol, Seattle, WA 98195 USA. Univ Washington, Div Vasc Surg, Seattle, WA 98195 USA. RP Hatsukami, TS (reprint author), VA Puget Sound Hlth Care Syst, Surg Serv 112, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NHLBI NIH HHS [HL-56874] NR 12 TC 206 Z9 215 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 15 PY 1998 VL 98 IS 24 BP 2666 EP 2671 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 146QX UT WOS:000077442800005 PM 9851951 ER PT J AU Li, J Nishizawa, K An, WQ Hussey, RE Lialios, FE Salgia, R Sunder-Plassmann, R Reinherz, EL AF Li, J Nishizawa, K An, WQ Hussey, RE Lialios, FE Salgia, R Sunder-Plassmann, R Reinherz, EL TI A cdc15-like adaptor protein (CD2BP1) interacts with the CD2 cytoplasmic domain and regulates CD2-triggered adhesion SO EMBO JOURNAL LA English DT Article DE adhesion; CD2; protein tyrosine phosphatase; SH3 domains; signal transduction ID T-CELL ACTIVATION; TYROSINE-PHOSPHORYLATED PROTEINS; FUNCTION-ASSOCIATED ANTIGEN-3; LYMPHOCYTE GLYCOPROTEIN CD2; PHOSPHATASE PTP-PEST; SH3 DOMAIN; ERYTHROCYTE RECEPTOR; SIGNAL-TRANSDUCTION; CRYSTAL-STRUCTURE; FOCAL ADHESIONS AB A human CD2 cytoplasmic tail-binding protein, termed CD2BP1, was identified by an interaction trap cloning method. Expression of CD2BP1 is restricted to hematopoietic tissue, being prominent in T and natural killer (NK) cells, with long (CD2BP1L) and short (CD2BP1S) variants arising by alternative RNA splicing. Both CD2BP1 molecules are homologous to Schizosaccharomyces pombe cdc15, and include a helical domain, variable length intervening PEST sequence and C-terminal SH3 domain. Although the CD2BP1 SH3 domain binds directly to the CD2 sequence, KGPPLPRPRV (amino acids 300-309), its association is augmented markedly by the CD2BP1 N-terminal segment. Upon ligand-induced clustering of surface CD2 molecules, CD2BP1 redistributes from a cytosolic to a surface membrane compartment, co-localizing with CD2, In turn, CD2-stimulated adhesion is down-regulated by CD2BP1, apparently through coupling of the protein tyrosine phosphatase (PTP)-PEST to CD2, These findings offer the first molecular view into the control processes for T cell adhesion. C1 Harvard Med Sch, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Med Sch, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Med Sch, Dept Med, Boston, MA 02115 USA. Harvard Med Sch, Dept Pathol, Boston, MA 02115 USA. RP Reinherz, EL (reprint author), Harvard Med Sch, Dana Farber Canc Inst, Immunobiol Lab, 44 Binney St J318, Boston, MA 02115 USA. FU NIAID NIH HHS [AI21226] NR 93 TC 76 Z9 82 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 15 PY 1998 VL 17 IS 24 BP 7320 EP 7336 DI 10.1093/emboj/17.24.7320 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 153LC UT WOS:000077833700018 PM 9857189 ER PT J AU Kamura, T Sato, S Haque, D Liu, L Kaelin, WG Conaway, RC Conaway, JW AF Kamura, T Sato, S Haque, D Liu, L Kaelin, WG Conaway, RC Conaway, JW TI The Elongin BC complex interacts with the conserved SOCS-box motif present in members of the SOCS, ras, WD-40 repeat, and ankyrin repeat families SO GENES & DEVELOPMENT LA English DT Article DE Elongin BC complex; SOCS box; SOCS-1; Jak/STAT signaling; protein degradation ID TUMOR-SUPPRESSOR GENE; RNA-POLYMERASE-II; TRANSCRIPTION FACTOR-SIII; INDUCED STAT INHIBITOR; F-BOX; PROTEIN; ELONGATION; IDENTIFICATION; ACTIVATION; PRODUCT AB The Elongin BC complex was identified initially as a positive regulator of RNA polymerase II (Pol II) elongation factor Elongin A and subsequently as a component of the multiprotein von Hippel-Lindau (VHL) tumor suppressor complex, in which it participates in both tumor suppression and negative regulation of hypoxia-inducible genes. Elongin B is a ubiquitin-like protein, and Elongin C is a Skp1-like protein that binds to a BC-box motif that is present in both Elongin A and VHL and is distinct from the conserved F-box motif recognized by Skp1. In this report, we demonstrate that the Elongin BC complex also binds to a functional BC box present in the SOCS box, a sequence motif identified recently in the suppressor of cytokine signaling-1 (SOCS-1) protein, as well as in a collection of additional proteins belonging to the SOCS, ras, WD-40 repeat, SPRY domain, and ankyrin repeat families. In addition, we present evidence (1) that the Elongin BC complex is a component of a multiprotein SOCS-1 complex that attenuates Jak/STAT signaling by binding to Jak2 and inhibiting Jak2 kinase, and (2) that by interacting with the SOCS box, the Elongin BC complex can increase expression of the SOCS-1 protein by inhibiting its degradation. These results suggest that Elongin BC is a multifunctional regulatory complex capable of controlling multiple pathways in the cell through interaction with a short degenerate sequence motif found in many different proteins. C1 Oklahoma Med Res Fdn, Howard Hughes Med Inst, Oklahoma City, OK 73104 USA. Oklahoma Med Res Fdn, Program Mol & Cell Biol, Oklahoma City, OK 73104 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73190 USA. RP Conaway, JW (reprint author), Oklahoma Med Res Fdn, Howard Hughes Med Inst, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM conawayj@omrf.ouhsc.edu OI Conaway, Joan/0000-0002-2786-0663 FU NIGMS NIH HHS [GM41628, R01 GM041628, R37 GM041628] NR 42 TC 416 Z9 427 U1 0 U2 11 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD DEC 15 PY 1998 VL 12 IS 24 BP 3872 EP 3881 DI 10.1101/gad.12.24.3872 PG 10 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 153YX UT WOS:000077862200011 PM 9869640 ER PT J AU Yang, YG Dey, BR Sergio, JJ Pearson, DA Sykes, M AF Yang, YG Dey, BR Sergio, JJ Pearson, DA Sykes, M TI Donor-derived interferon gamma is required for inhibition of acute graft-versus-host disease by interleukin 12 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE bone marrow transplantation; lethal irradiation; cytokine; T cell activation; mice ID BONE-MARROW TRANSPLANTATION; T-CELL DEPLETION; IFN-GAMMA; LEISHMANIA-MAJOR; BETA-CHAINS; MICE; IL-12; CYTOKINE; EXPRESSION; RECEPTOR AB We have demonstrated that a single injection of interleukin (IL)-12 on the day of bone marrow transplantation (BMT) inhibits acute graft-versus-host disease (GVHD) in mice. This effect of IL-12 can be diminished by anti-interferon (IFN)-gamma mAb. To determine the mechanism by which IFN-gamma affects IL-12-mediated GVHD protection, we have compared the effect of IL-12 on GVHD in C57BL/6 wild-type (WT) or IFN-gamma gene knockout (GKO) recipients of fully major histocompatibility complex plus minor antigen-mismatched allogeneic BMT from WT or GKO BALBlc mice. Lethal acute GVHD was readily induced in the absence of IFN-gamma, IL-12 inhibited GVHD mortality to a similar extent in WT and GKO recipients of WT allogeneic BMT, However, neither WT nor GKO recipients were protected by IL-12 from GVHD induced by GKO allogeneic BMT. Moreover, the effective inhibition of host-reactive donor T cell activation and expansion that is associated with IL-12-mediated GVHD protection was dependent on the ability of BALB/c donors to produce IFN-gamma. These results demonstrate that (a) acute GVHD can be induced in the absence of IFN-gamma, (b) host IFN-gamma does not play a critical role in IL-12-induced GVHD protection, and (c) the protective effect of IL-12 against GVHD is dependent on the ability of the donor to produce IFN-gamma. C1 Massachusetts Gen Hosp, Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, Surg Serv,Harvard Med Sch, Boston, MA 02129 USA. RP Sykes, M (reprint author), Massachusetts Gen Hosp, Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, Surg Serv,Harvard Med Sch, MGH East,Bldg 149-5102,13th St, Boston, MA 02129 USA. FU PHS HHS [R01 64912] NR 58 TC 127 Z9 130 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC 15 PY 1998 VL 102 IS 12 BP 2126 EP 2135 DI 10.1172/JCI4992 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 151GJ UT WOS:000077712100012 PM 9854048 ER PT J AU Weber, C Springer, TA AF Weber, C Springer, TA TI Interaction of very late antigen-4 with VCAM-1 supports transendothelial chemotaxis of monocytes by facilitating lateral migration SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL-ADHESION MOLECULE-1; LIGAND-BINDING; COUNTER-RECEPTOR; T-CELLS; LYMPHOCYTE MIGRATION; LEUKOCYTE EMIGRATION; PHYSIOLOGICAL FLOW; ENDOTHELIAL-CELLS; HUMAN-NEUTROPHILS; INTEGRIN AVIDITY AB The transient regulation of very late antigen (VLA)-4 avidity by CC chemokines may promote chemotaxis of monocytes across VCAM-1-bearing barriers, whereas late and prolonged activation of VLA-5 may mediate subsequent localization in the extracellular matrix. We demonstrate that interactions of VLA-4 with VCAM-1, fibronectin, or a 40-kDa fragment but not a 120-kDa fragment of fibronectin supported the lateral random migration of isolated blood monocytes induced by CC chemokines, termed chemokinesis. This effect was optimal at intermediate substrate concentrations. Moreover, coimmobilization of VCAM-1 with ICAM-1 allowed better migration than ICAM-1 alone. Chemokinesis on VCAM-1 appeared to be associated with transient regulation of VLA-4 avidity by CC chemokines, given that locking VLA-4 in a high avidity state markedly inhibited migration and the locomotion rate was inversely correlated with the adhesive strength of VLA-4 to VCAM-1 following stimulation with monocyte chemoattractant protein-1. Induction of VCAM-1 expression by endothelial activation with IL-4 improved chemokinesis and lateral migration toward a monocyte chemoattractant protein-1 or a monocyte inflammatory protein-1 alpha gradient on endothelium and increased transendothelial chemotaxis of monocytes by a VLA-4-dependent mechanism. In contrast, endothelial activation with IL-4 did not affect the time required for diapedesis of monocytes itself. Hence, VCAM-1 may facilitate transendothelial chemotaxis by supporting lateral migration of attached monocytes along endothelium. C1 Univ Munich, Klinikum Innenstadt, Inst Prophylaxe Kreislaufkrankheiten, D-80336 Munich, Germany. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Weber, C (reprint author), Univ Munich, Klinikum Innenstadt, Inst Prophylaxe Kreislaufkrankheiten, Pettenkoferstr 9, D-80336 Munich, Germany. OI Weber, Christian/0000-0003-4610-8714 FU NCI NIH HHS [CA31798] NR 56 TC 68 Z9 68 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 DEC 15 PY 1998 VL 161 IS 12 BP 6825 EP 6834 PG 10 WC Immunology SC Immunology GA 146NG UT WOS:000077436400050 PM 9862714 ER PT J AU Morrill, JA Brown, RH Cannon, SC AF Morrill, JA Brown, RH Cannon, SC TI Gating of the L-type Ca channel in human skeletal myotubes: An activation defect caused by the hypokalemic periodic paralysis mutation R528H SO JOURNAL OF NEUROSCIENCE LA English DT Article DE dihydropyridine receptor; L-type calcium channel; human skeletal muscle; cultured cells; familial periodic paralysis; patch clamp ID VOLTAGE-DEPENDENT INACTIVATION; CALCIUM CURRENT ACTIVATION; TWITCH MUSCLE-FIBERS; DIHYDROPYRIDINE RECEPTOR; KINETIC-PROPERTIES; POTASSIUM CHANNEL; CHARGE MOVEMENT; SODIUM-CHANNEL; REPEAT-I; FROG AB The skeletal muscle L-type Ca channel serves a dual role as a calcium-conducting pore and as the voltage sensor coupling t-tubule depolarization to calcium release from the sarcoplasmic reticulum. Mutations in this channel cause hypokalemic periodic paralysis (HypoPP), a human autosomal dominant disorder characterized by episodic failure of muscle excitability that occurs in association with a decrease in serum potassium. The voltage-dependent gating of L-type Ca channels was characterized by recording whole-cell Ca currents in myotubes cultured from three normal individuals and from a patient carrying the HypoPP mutation R528H. We found two effects of the R528H mutation on the L-type Ca current in HypoPP myotubes: (1) a mild reduction in current density and (2) a significant slowing of the rate of activation. We also measured the voltage dependence of steady-state L-type Ca current inactivation and characterized, for the first time in a mammalian preparation, the kinetics of both entry into and recovery from inactivation over a wide range of voltages. The R528H mutation had no effect on the kinetics or voltage dependence of inactivation. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02214 USA. Harvard Univ, Sch Med, Div Med Sci, Program Neurosci, Boston, MA 02214 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02214 USA. RP Cannon, SC (reprint author), Massachusetts Gen Hosp, Dept Neurol, EDR 413A, Boston, MA 02214 USA. FU NIAMS NIH HHS [R01-AR42703] NR 51 TC 48 Z9 50 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 15 PY 1998 VL 18 IS 24 BP 10320 EP 10334 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 149LM UT WOS:000077606800011 PM 9852570 ER PT J AU Ierino, FL Kozlowski, T Siegel, JB Shimizu, A Colvin, RB Banerjee, PT Cooper, DKC Cosimi, AB Bach, FH Sachs, DH Robson, SC AF Ierino, FL Kozlowski, T Siegel, JB Shimizu, A Colvin, RB Banerjee, PT Cooper, DKC Cosimi, AB Bach, FH Sachs, DH Robson, SC TI Disseminated intravascular coagulation in association with the delayed rejection of pig-to-baboon renal xenografts SO TRANSPLANTATION LA English DT Article ID ENDOTHELIAL-CELL ACTIVATION; BONE-MARROW TRANSPLANTATION; THROMBOTIC THROMBOCYTOPENIC PURPURA; SOLUBLE COMPLEMENT RECEPTOR-TYPE-1; PRIMATE CARDIAC XENOGRAFTS; DECAY-ACCELERATING FACTOR; TISSUE FACTOR PATHWAY; HYPERACUTE REJECTION; HUMAN XENOTRANSPLANTATION; HUMAN PLATELETS AB Background. Intravascular fibrin deposition and platelet sequestration occur with porcine xenograft rejection by baboons. Disseminated intravascular coagulopathy may arise either as a direct consequence of the failure to fully deplete xenoreactive natural antibodies and block complement, or because of putative cross-species molecular incompatibilities in this discordant species combination. Methods. Three baboons were conditioned with retrovirally transduced autologous bone marrow to induce tolerance to swine antigens, Xenoreactive natural antibodies and complement were depleted by plasmapheresis and the use of Gal alpha 1-3Gal column adsorptions; baboons were then splenectomized and underwent renal xenografting from inbred, miniature pigs, Soluble complement receptor type-1 with protocol immunosuppression (mycophenolate mofetil, 15-deoxyspergualin, steroids, and cyclosporine) was administered. Results. A bleeding diathesis was clinically evident from days 5 to 12 after transplantation in two baboons, Low levels of circulating C3a, C3d, and iC3b were measured despite the absence of functional circulating complement components. Profound thrombocytopenia with abnormalities in keeping with disseminated intravascular coagulopathy were observed. Prolongation of prothrombin and partial thromboplastin times was accompanied by evidence for tissue factor-mediated coagulation pathways, high levels of thrombin generation (prothrombin fragment F1+2 production and thrombin-antithrombin complex formation), fibrinogen depletion, and production of high levels of the fibrin degradation product D-dimer, Importantly, these disturbances resolved rapidly after the excision of the rejected xenografts in two surviving animals. Histopathological examination of the rejected xenografts confirmed vascular injury, fibrin deposition, platelet deposition, and localized complement activation, Conclusions. Systemic coagulation disturbances are associated with delayed xenograft rejection. C1 Beth Israel Deaconess Med Ctr, Dept Surg, Ctr Immunobiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. BioTransplant Inc, Charlestown, MA 02129 USA. RP Robson, SC (reprint author), Beth Israel Deaconess Med Ctr, Dept Surg, Ctr Immunobiol, Room 370H,99 Brookline Ave, Boston, MA 02215 USA. EM srobson@bidmc.harvard.edu NR 59 TC 90 Z9 90 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 15 PY 1998 VL 66 IS 11 BP 1439 EP 1450 DI 10.1097/00007890-199812150-00006 PG 12 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 150LQ UT WOS:000077666700006 PM 9869084 ER PT J AU Pascual, M Saidman, S Tolkoff-Rubin, N Williams, WW Mauiyyedi, S Duan, JM Farrell, ML Colvin, RB Cosimi, AB Delmonico, FL AF Pascual, M Saidman, S Tolkoff-Rubin, N Williams, WW Mauiyyedi, S Duan, JM Farrell, ML Colvin, RB Cosimi, AB Delmonico, FL TI Plasma exchange and tacrolimus-mycophenolate rescue for acute humoral rejection in kidney transplantation SO TRANSPLANTATION LA English DT Article ID RENAL-ALLOGRAFT REJECTION; PATHOLOGICAL FEATURES; HYPERACUTE REJECTION; ANTIBODY AB Background. Acute renal allograft rejection associated with the development of donor-specific alloantibody (acute humoral rejection, ABR) typically carries a poor prognosis. The best treatment of this condition remains undefined. tk;2Methods. During a Ii-month period, 73 renal transplants were performed. During the first postoperative month, five recipients (6.8%) with AHR were identified. The diagnosis was based on: (1) evidence of severe rejection, resistant to steroid and antilymphocyte therapy; (2) typical pathologic features; and (3) demonstration of donor-specific alloantibody (DSA) in recipient's serum at the time of rejection. Pretransplant donor-specific T- and B-cell cross-matches were negative. Results Plasma exchange (PE, four to seven treatments per patient) significantly decreased circulating DSA to almost pretransplant levels in four of five patients, and improvement in renal function occurred in all patients. One patient had recurrent renal dysfunction in the setting of an increase in circulating DSA A second series of five PE treatments decreased DSA and reversed the rejection episode. Rescue therapy with tacrolimus (initial mean dose: 0.14+/-0.32mg/kg/day) and mycophenolate mofetil (2 g/day) was used in five of five and four of five patients, respectively. With a mean follow-up of 19.6+/-5.6 months, patient and allograft survival are 100%. Renal function remains excellent with a mean current serum creatinine of 1.2+/-0.3 mg/dl. (range: 0.9-1.8mg/dl). Conclusions. Our findings suggest that a therapeutic approach combining PE and tacrolimus-mycophenolate mofetil rescue has the potential to improve the outcome of AHR. C1 Massachusetts Gen Hosp, Renal Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Pascual, M (reprint author), Massachusetts Gen Hosp, Renal Unit, Dept Med, Fruit St,Box MZ70, Boston, MA 02114 USA. NR 26 TC 152 Z9 165 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 15 PY 1998 VL 66 IS 11 BP 1460 EP 1464 DI 10.1097/00007890-199812150-00008 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 150LQ UT WOS:000077666700008 PM 9869086 ER PT J AU Li, R Rieu, P Griffith, DL Scott, D Arnaout, MA AF Li, R Rieu, P Griffith, DL Scott, D Arnaout, MA TI Two functional states of the CD11b A-domain: Correlations with key features of two Mn2+-complexed crystal structures SO JOURNAL OF CELL BIOLOGY LA English DT Article DE integrin activation; A-domain; crystal structure; complement iC3b; G proteins ID INTEGRIN CR3 CD11B/CD18; ARG-GLY-ASP; FUNCTION-ASSOCIATED ANTIGEN-1; NEUTROPHIL INHIBITORY FACTOR; LIGAND-BINDING SITES; I-DOMAIN; DIVALENT-CATION; RECOGNITION SITE; MONOCLONAL-ANTIBODIES; MAC-1 CD11B/CD18 AB In the presence of bound Mn2+, the three-dimensional structure of the ligand-binding A-domain from the integrin CR3 (CD11b/CD18) is shown to exist in the "open" conformation previously described only for a crystalline Mg2+ complex. The open conformation is distinguished from the "closed" form by the solvent exposure of F302, a direct T209-Mn2+ bond, and the presence of a glutamate side chain in the MIDAS site. Approximately 10% of wild-type CD11b A-domain is present in an "active" state (binds to activation-dependent ligands, e.g., iC3b and the mAb 7E3). In the isolated domain and in the holoreceptor, the percentage of the active form can be quantitatively increased or abolished in F302W and T209A mutants, respectively. The iC3b-binding site is located on the MIDAS face and includes conformationally sensitive residues that undergo significant shifts in the open versus closed structures. We suggest that stabilization of the open structure is independent of the nature of the metal ligand and that the open conformation may represent the physiologically active form. C1 Massachusetts Gen Hosp, Dept Med, Renal Unit, Leukocyte Biol & Inflammat Program, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Arnaout, MA (reprint author), Massachusetts Gen Hosp, Dept Med, Renal Unit, Leukocyte Biol & Inflammat Program, 149 13th St,8th Floor, Charlestown, MA 02129 USA. EM arnaout@receptor.mgh.harvard.edu NR 60 TC 111 Z9 111 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 14 PY 1998 VL 143 IS 6 BP 1523 EP 1534 DI 10.1083/jcb.143.6.1523 PG 12 WC Cell Biology SC Cell Biology GA 150CF UT WOS:000077644800009 PM 9852148 ER PT J AU Pillay, SS Renshaw, PF Bonello, CM Lafer, B Fava, M Yurgelun-Todd, D AF Pillay, SS Renshaw, PF Bonello, CM Lafer, B Fava, M Yurgelun-Todd, D TI A quantitative magnetic resonance imaging study of caudate and lenticular nucleus gray matter volume in primary unipolar major depression: relationship to treatment response and clinical severity SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE depressive disorders; neuroanatomy; basal ganglia; fluoxetine response ID NEURO-BEHAVIORAL CHANGES; BASAL GANGLIA; HUNTINGTONS-DISEASE; MOOD DISORDERS; CEREBROSPINAL-FLUID; PARKINSONS-DISEASE; CEREBRAL ANATOMY; METABOLIC RATES; FRONTAL-LOBE; BRAIN AB The authors investigated whether there were differences in caudate and lenticular nucleus volumes in depressed patients relative to comparison subjects, and whether differences in basal ganglia volume were associated with treatment response to fluoxetine. Brain magnetic resonance images were obtained from 38 unipolar depressed patients and 20 matched comparison subjects. Patients were divided into groups of 'responders' and 'non-responders' based on change in the 17-item Hamilton Depression Rating Scale (HDRS) score after a 10-week open trial of fluoxetine, 20 mg/day. There were no group mean differences in caudate and lenticular nucleus volumes between patients and comparison subjects. Female treatment responders tended to have larger caudate nucleus volumes than male 'responders', and also larger right caudate nucleus volumes than their female 'non-responder' counterparts. Baseline HDRS scores correlated negatively with left caudate nucleus volume in depressed patients. Thus, in mild to moderately depressed patients, we were unable to find differences in caudate and lenticular nucleus-gray matter volumes relative to comparison subjects. One possible reason is that caudate nucleus-gray matter volume and severity of depression are inversely correlated, suggesting that severity of depression may be an important covariate when comparing caudate volumes in depressed patients and control subjects. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. McLean Hosp, Psychopharmacol Serv, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. RP Pillay, SS (reprint author), McLean Hosp, Brain Imaging Ctr, 115 Mill St, Belmont, MA 02178 USA. EM spillay@warren.med.harvard.edu RI Lafer, Beny/C-1055-2012; Lafer, Beny/F-9390-2015 OI Lafer, Beny/0000-0002-6132-9999; Lafer, Beny/0000-0002-6132-9999 NR 55 TC 48 Z9 49 U1 2 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD DEC 14 PY 1998 VL 84 IS 2-3 BP 61 EP 74 DI 10.1016/S0925-4927(98)00048-1 PG 14 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 167TF UT WOS:000078649000002 PM 10710164 ER PT J AU Mannion, BA Kolesnikova, TV Lin, SH Wang, S Thompson, NL Hemler, ME AF Mannion, BA Kolesnikova, TV Lin, SH Wang, S Thompson, NL Hemler, ME TI The light chain of CD98 is identified as E16/TA1 protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FUSION REGULATORY PROTEIN-1; MONOCLONAL-ANTIBODY 4F2; AMINO-ACID-TRANSPORT; CELL-SURFACE ANTIGEN; XENOPUS-LAEVIS OOCYTES; HEAVY-CHAIN; ACTIVATION ANTIGEN; MOLECULAR-CLONING; LIVER DEVELOPMENT; RAT-KIDNEY AB The 80/40-kDa CD98 protein. complex was purified using an anti-CD98 heavy chain monoclonal antibody coupled to Sepharose beads. fluted proteins were subjected to preparative SDS-polyacrylamide gel electrophoresis, and protein corresponding to the 40-kDa CD98 light chain was excised. Following proteolysis with trypsin, a peptide fragment was sequenced by mass spectrometry. The nine residues obtained we:re identical to established C-terminal sequences of the human E16 and rat TAI proteins, suggesting that TA1/E16 protein is the CD98 Light chain. Consistent with this, anti-TA1/E16 antibodies specifically immunoblotted the similar to 35-40-kDa light chain present upon immunoprecipitation of the human CD98 complex. Furthermore, anti-CD98 heavy chain antibody specifically co-immunoprecipitated hemagglutinin-tagged light chain from cells transfected with hemagglutinin-tagged E16 cDNA. In conclusion, the CD98 light chain is identical to the TA1/E16 protein, based on partial amino acid sequence identity, antibody crossreactivity, genetic reconstitution evidence, similar molecular size, and comparable cell distribution. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Rhode Isl Hosp, Dept Med, Providence, RI 02903 USA. Rhode Isl Hosp, Dept Pathol, Providence, RI 02903 USA. RP Hemler, ME (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM Martin_Hemler@dfci.harvard.edu FU NCI NIH HHS [CA42368, T32-CA9172] NR 41 TC 60 Z9 60 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 11 PY 1998 VL 273 IS 50 BP 33127 EP 33129 DI 10.1074/jbc.273.50.33127 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 146YY UT WOS:000077462500008 PM 9837878 ER PT J AU Biswas, DK Reddy, PV Pickard, M Makkad, B Pettit, N Pardee, AB AF Biswas, DK Reddy, PV Pickard, M Makkad, B Pettit, N Pardee, AB TI Calmodulin is essential for estrogen receptor interaction with its motif and activation of responsive promoter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAMMARY EPITHELIAL-CELLS; BINDING PROTEIN; DOWN-REGULATION; DNA-BINDING; CYCLIN D1; GENE; INHIBITION; GROWTH; ANTAGONIST; TAMOXIFEN AB Calmodulin (CaM) has been reported to have affinity for the estrogen receptor (ER:), Observations reported here reveal a direct physical interaction between purified CaM and ER, This direct ER-CaM interaction may he an initial event preceding the assembly of ER plus auxiliary proteins into the active ER complex with its DNA motif the estrogen response element. We demonstrate that CaM is an integral component of this complex by using a system reconstituted from purified ER and nuclear extract from ER-negative breast cancer cells and also with ER-depleted nuclear extract of an ER-positive breast cancer cell line. Although CaM is essential for formation of this complex, it is not sufficient, suggesting roles also of auxiliary proteins. CaM also is functionally required for activation of an ER-responsive promoter, in the 17 beta-estradiol-ER pathway of hormone action and regulation of 17 beta-estradiol-responsive gene expression that is associated with proliferation of mammary epithelial cells. C1 Dana Farber Canc Inst, Div Canc Biol, Boston, MA 02115 USA. Henry Ford Hlth Syst, Detroit, MI 48202 USA. RP Biswas, DK (reprint author), Dana Farber Canc Inst, Div Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM biswas@mbcrr.harvard.edu FU NCI NIH HHS [CA61253-06] NR 46 TC 42 Z9 42 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 11 PY 1998 VL 273 IS 50 BP 33817 EP 33824 DI 10.1074/jbc.273.50.33817 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 146YY UT WOS:000077462500102 PM 9837972 ER PT J AU Ruvkun, G Hobert, O AF Ruvkun, G Hobert, O TI The taxonomy of developmental control in Caenorhabditis elegans SO SCIENCE LA English DT Review ID C-ELEGANS; GENE ENCODES; DROSOPHILA; PROTEIN; PATHWAY; FAMILY; HEDGEHOG; MESODERM; NEURONS; MEMBER AB The Caenorhabditis elegans genome sequence was surveyed for transcription factor and signaling gene families that have been shown to regulate development in a variety of species. About 10 to 25 percent of the genes in most of the gene families already have been genetically analyzed in C. elegans, about half of the genes detect probable orthologs in other species, and about 10 to 25 percent of the genes are, at present, unique to C. elegans. Caenorhabditis elegans is also missing genes that are found in vertebrates and other invertebrates. Thus the genome sequence reveals universals in developmental control that are the Legacy of metazoan complexity before the Cambrian explosion, as well as genes that have been more recently invented or Lost in particular phylogenetic lineages. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Genet,Dept Mol Biol, Boston, MA 02114 USA. RP Ruvkun, G (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Genet,Dept Mol Biol, Boston, MA 02114 USA. EM ruvkun@frodo.mgh.harvard.edu OI Hobert, Oliver/0000-0002-7634-2854 NR 63 TC 250 Z9 298 U1 2 U2 10 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 11 PY 1998 VL 282 IS 5396 BP 2033 EP 2041 DI 10.1126/science.282.5396.2033 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 147BB UT WOS:000077467100038 PM 9851920 ER PT J AU Saeki, Y Ichikawa, T Saeki, A Chiocca, EA Tobler, K Ackermann, M Breakefield, XO Fraefel, C AF Saeki, Y Ichikawa, T Saeki, A Chiocca, EA Tobler, K Ackermann, M Breakefield, XO Fraefel, C TI Herpes simplex virus type 1 DNA amplified as bacterial artificial chromosome in Escherichia coli: Rescue of replication-competent virus progeny and packaging of amplicon vectors SO HUMAN GENE THERAPY LA English DT Article ID NEURAL CELLS; EXPRESSION; INFECTION; CLONING; SYSTEM; GENOME AB Herpes simplex virus type 1 (HSV-1)-based amplicon vectors contain only similar to 1% of the 152-kb HSV-1 genome, and consequently, replication and packaging into virions depends on helper functions. These helper functions have been provided conventionally by a helper virus, usually a replication-defective mutant of HSV-1, or more recently, by a set of five cosmids that overlap and represent the genome of HSV-1 deleted for DNA cleavage/packaging signals (pac). In the absence of pac signals, potential HSV-1 genomes that are reconstituted from the cosmids via homologous recombination are not packageable, The resulting amplicon stocks are, therefore, virtually free of contaminating helper virus. To simplify this packing system, the HSV-1 genome was cloned and maintained stably as a single-copy, F plasmid-based bacterial artificial chromosome in E. coli. Such a plasmid containing the HSV-1 genome deleted for the pac signals (fHSV Delta pac) did not generate replication-competent progeny virus on transfection into mammalian cells, but rather, it was able to support the packaging of cotransfected amplicon DNA that contained a functional pac signal. The resulting amplicon vector stocks had titers of up to 10(7) transducing units per milliliter of culture medium and efficiently transduced neural cells in the rat brain, as well as hepatocytes in the rat. The capacity of generating infectious and replication-competent HSV-1 progeny following transfection into mammalian cells was restored after insertion of a pac signal into fHSV Delta pac. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg,Mol Neurooncol Lab, Charlestown, MA 02129 USA. Northwestern Univ, BNBCB, Evanston, IL 60208 USA. Univ Zurich, Inst Virol, CH-8057 Zurich, Switzerland. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Mol Neurogenet Unit, Charlestown, MA 02129 USA. RP Fraefel, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg,Mol Neurooncol Lab, Charlestown, MA 02129 USA. FU NCI NIH HHS [P01CA69246]; NINDS NIH HHS [NS24279] NR 22 TC 165 Z9 168 U1 0 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD DEC 10 PY 1998 VL 9 IS 18 BP 2787 EP 2794 DI 10.1089/hum.1998.9.18-2787 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 150JK UT WOS:000077661600014 PM 9874276 ER PT J AU Reed, MF Liu, VF Ladha, MH Ando, K Griffin, JD Weaver, DT Ewen, ME AF Reed, MF Liu, VF Ladha, MH Ando, K Griffin, JD Weaver, DT Ewen, ME TI Enforced CDK4 expression in a hematopoietic cell line confers resistance to the G1 arrest induced by ionizing radiation SO ONCOGENE LA English DT Article DE CDK4; p53; p21; ionizing radiation ID CYCLIN-DEPENDENT KINASES; P53-DEPENDENT G(1) ARREST; WILD-TYPE P53; RETINOBLASTOMA PROTEIN; HUMAN FIBROBLASTS; GROWTH ARREST; DNA-DAMAGE; ULTRAVIOLET-IRRADIATION; CANCER-CELLS; INHIBITION AB In hematopoietic cells, gamma-irradiation causes a p53-dependent transient G1 phase cell cycle arrest. Various extracellular growth inhibitory signals elicit G1 arrest by targeting CDK4. Here we show that in a myeloid cell line, 32D cl 3, enforced expression of CDK4, but not cyclins D2 nor D3, overrides the gamma-irradiation-induced G1 arrest. CDK4 does not confer resistance to the radiation-induced G2 block observed in parental cells. Ectopic expression of CDK4 overcomes the ionizing radiation-induced inhibition of CDK4 and CDK2 kinase activity. The levels of CDK4 protein do not change after exposure to ionizing radiation in either parental cells or those overexpressing CDK4. Ionizing radiation induces the expression of both p53 and p21, and in cells constitutively synthesizing exogenous CDK4, the return of p53 protein levels to baseline is prolonged. Increased levels of p21 are found associated with CDK4, and not CDK2, in the lines overexpressing CDK4, compared to the parental line, after exposure to ionizing radiation. Enforced expression of CDK4 may therefore overcome a gamma-irradiation-induced G1 arrest through the titration of the CDK inhibitor p21 allowing both CDK4 and CDK2 to remain active. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ewen, ME (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA65842, CA09535] NR 65 TC 17 Z9 19 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 10 PY 1998 VL 17 IS 23 BP 2961 EP 2971 DI 10.1038/sj.onc.1202450 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 146KL UT WOS:000077427800003 PM 9881698 ER PT J AU Counter, CM Hahn, WC Wei, WY Caddle, SD Beijersbergen, RL Lansdorp, PM Sedivy, JM Weinberg, RA AF Counter, CM Hahn, WC Wei, WY Caddle, SD Beijersbergen, RL Lansdorp, PM Sedivy, JM Weinberg, RA TI Dissociation among in vitro telomerase activity, telomere maintenance, and cellular immortalization SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CATALYTIC SUBUNIT GENE; HUMAN FIBROBLASTS; HUMAN-CELLS; EPITHELIAL-CELLS; SENESCENCE; EXPRESSION; CARCINOMA; DYNAMICS; LINE AB The immortalization of human cells is a critical step during tumorigenesis. In vitro, normal human somatic cells must overcome two proliferative blockades, senescence and crisis, to become immortal. Transformation with viral oncogenes extends the life span of human cells beyond senescence. Such transformed cells eventually succumb to crisis, a period of widespread cellular death that has been proposed to be the result of telomeric shortening. We now show that ectopic expression of the telomerase catalytic subunit (human telomerase reverse transcriptase or hTERT) and subsequent activation of telomerase can allow postsenescent cells to proliferate beyond crisis, the last known proliferative blockade to cellular immortality. Moreover, we demonstrate that alteration of the carboxyl terminus of human telomerase reverse transcriptase does not affect telomerase enzymatic activity but impedes the ability of this enzyme to maintain telomeres. Telomerase-positive cells expressing this mutant enzyme fail to undergo immortalization, further tightening the connection between telomere maintenance and immortalization. C1 MIT, Whitehead Inst Biomed Res, Dept Biol, Cambridge, MA 02142 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA. British Columbia Canc Res Ctr, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. RP Weinberg, RA (reprint author), MIT, Whitehead Inst Biomed Res, Dept Biol, 9 Cambridge Ctr,Room 367B, Cambridge, MA 02142 USA. FU NCI NIH HHS [CA 39826]; NIAID NIH HHS [AI29524, R01 AI029524, R21 AI029524]; NIGMS NIH HHS [GM RO1-41690] NR 31 TC 459 Z9 483 U1 1 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 8 PY 1998 VL 95 IS 25 BP 14723 EP 14728 DI 10.1073/pnas.95.25.14723 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146NJ UT WOS:000077436700026 PM 9843956 ER PT J AU Nishizawa, K Freund, C Li, J Wagner, G Reinherz, EL AF Nishizawa, K Freund, C Li, J Wagner, G Reinherz, EL TI Identification of a proline-binding motif regulating CD2-triggered T lymphocyte activation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CYTOPLASMIC DOMAIN; CELL ACTIVATION; SIGNAL TRANSDUCTION; NMR-SPECTROSCOPY; SH3 DOMAIN; WW DOMAIN; CD2; PROTEIN; RESPONSIVENESS; SUPPRESSION AB An intracellular protein termed CD2 binding protein 2 (CD2BP2), which binds to a site containing two PPPGHR segments within the cytoplasmic region of CD2, was identified, Mutagenesis and NMR analysis demonstrated that the CD2 binding region of CD2BP2 includes a 17-aa motif (GPY[orF]xxxxM[orV]xxWxxx GYF), also found in several yeast and Caenorhabditis elegans proteins of unknown function. In Jurkat T cells, over-expression of the isolated CD2BP2 domain binding to CD2 enhances the production of interleukin 2 on crosslinking of CD2 but not the T cell receptor. Hence, a proline-binding module distinct from SH3 and WW domains regulates protein-protein interactions. C1 Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Reinherz, EL (reprint author), Dana Farber Canc Inst, Immunobiol Lab, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI21226, AI27581, R01 AI021226] NR 38 TC 72 Z9 77 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 8 PY 1998 VL 95 IS 25 BP 14897 EP 14902 DI 10.1073/pnas.95.25.14897 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146NJ UT WOS:000077436700057 PM 9843987 ER PT J AU Thomas, GD Sander, M Lau, KS Huang, PL Stull, JT Victor, RG AF Thomas, GD Sander, M Lau, KS Huang, PL Stull, JT Victor, RG TI Impaired metabolic modulation of alpha-adrenergic vasoconstriction in dystrophin-deficient skeletal muscle SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DUCHENNE MUSCULAR-DYSTROPHY; NITRIC-OXIDE SYNTHASE; SENSITIVE POTASSIUM CHANNELS; VASCULAR SMOOTH-MUSCLE; RELAXING FACTOR; MDX MOUSE; CONTRACTILE RESPONSES; CYCLIC-GMP; BLOOD-FLOW; RAT AORTA AB The neuronal isoform of nitric oxide synthase (nNOS) is highly expressed in mammalian skeletal muscle, but its functional role has not been defined. NO has been implicated in the local metabolic regulation of blood flow in contracting skeletal muscle in part by antagonizing sympathetic vasoconstriction. We therefore hypothesized that nNOS in skeletal muscle is the source of the NO mediating the inhibition of sympathetic vasoconstriction in contracting muscle. In the mdr mouse, a model of Duchenne muscular dystrophy in which dystrophin deficiency results in greatly reduced expression of nNOS in skeletal muscle, we found that the normal ability of skeletal muscle contraction to attenuate alpha-adrenergic vasoconstriction is defective. Similar results were obtained in mutant mice that lack the gene encoding nNOS. Together these data suggest a specific role for nNOS in the local metabolic inhibition of cu-adrenergic vasoconstriction in active skeletal muscle. C1 Univ Texas, SW Med Ctr, Dept Internal Med, Div Hypertens, Dallas, TX 75235 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA 02129 USA. Harvard Med Sch, Charlestown, MA 02129 USA. Univ Texas, SW Med Ctr, Dept Physiol, Dallas, TX 75235 USA. RP Thomas, GD (reprint author), Univ Texas, SW Med Ctr, Dept Internal Med, Div Hypertens, 5323 Harry Hines Blvd, Dallas, TX 75235 USA. FU NHLBI NIH HHS [P01-HL-06296, P01 HL006296] NR 42 TC 256 Z9 259 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 8 PY 1998 VL 95 IS 25 BP 15090 EP 15095 DI 10.1073/pnas.95.25.15090 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146NJ UT WOS:000077436700090 PM 9844020 ER PT J AU Gao, JM Niklason, L Langer, R AF Gao, JM Niklason, L Langer, R TI Surface hydrolysis of poly(glycolic acid) meshes increases the seeding density of vascular smooth muscle cells SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article DE surface modification; poly(glycolic acid); cell seeding density; vascular smooth muscle cells; tissue engineering; biomaterials ID BLOOD-VESSEL; POLYMERS; ADHESION; SERUM; ASSAY; VEIN; DNA AB A procedure for surface hydrolysis of poly(glycolic acid) (PGA) meshes was developed to increase cell seeding density and improve attachment of vascular smooth muscle cells. Hydrolysis of PGA in 1N NaOH transformed ester groups on the surface of PGA fibers to carboxylic acid and hydroxyl groups. After hydrolysis, the polymer scaffold retained its original gross appearance and dimensions while the fiber diameter decreased. A plot of fiber diameter versus the hydrolysis time showed a linear relationship, with a rate of decrease in fiber diameter of 0.65 mu m/min. The molecular weight and thermal properties of the polymer did not change significantly following surface hydrolysis. In cell seeding experiments, surface-hydrolyzed mesh was seeded with more than twice as many cells as unmodified PGA mesh. Vascular smooth muscle cells attached to the surface-hydrolyzed PGA mesh both as individual cells and as cell aggregates while only cell aggregates were observed on the unmodified mesh. Control experiments indicated that adsorption of serum proteins onto the surface-hydrolyzed PGA fibers was correlated with the increase in cell seeding density. These results demonstrate that optimization of biomaterial-cell interactions provides a strategy for increasing the initial cell seeding density for the engineering of tissues of high cell density. (C) 1998 John Wiley & Sons, Inc. C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. RP Langer, R (reprint author), MIT, Dept Chem Engn, Cambridge, MA 02139 USA. FU NHLBI NIH HHS [HL03492-02] NR 28 TC 235 Z9 246 U1 2 U2 36 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD DEC 5 PY 1998 VL 42 IS 3 BP 417 EP 424 DI 10.1002/(SICI)1097-4636(19981205)42:3<417::AID-JBM11>3.0.CO;2-D PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 125XK UT WOS:000076262200010 PM 9788505 ER PT J AU Zori, RT Marsh, DJ Graham, GE Marliss, EB Eng, C AF Zori, RT Marsh, DJ Graham, GE Marliss, EB Eng, C TI Germline PTEN mutation in a family with Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE Cowden disease; Bannayan-Riley-Ruvalcaba syndrome; PTEN; thyroid cancer; polyposis; Bannayan-Zonana syndrome; Ruvalcaba-Myhre syndrome ID DISEASE; GENE AB Clinical overlap between Cowden disease and Bannayan-Riley-Ruvalcaba syndrome has rarely been described and identical germline mutations in the PTEN gene have been demonstrated in a few families with Cowden disease and some cases of Bannayan-Riley-Ruvalcaba syndrome. We report on a mother with Cowden disease and a son with Bannayan-Riley-Ruvalcaba syndrome. Mutation analysis of the PTEN gene demonstrated a heterozygous nonsense mutation R130X in both individuals. This might suggest that Cowden disease and Bannayan-Riley-Ruvalcaba syndrome are one causal entity. Am. J. Med. Genet. 80:399-402, 1998. (C) 1998 Wiley-Liss, Inc. C1 Univ Florida, Dept Pediat, JHMHC, Div Genet, Gainesville, FL 32606 USA. Harvard Univ, Sch Med,Dana Farber Canc Inst,Dept Adult Oncol, Charles A Dana Human Canc Genet Unit, Dept Med,Translat Res Lab, Boston, MA 02115 USA. Univ Calgary, Dept Med Genet, Calgary, AB, Canada. McGill Univ, Fac Med, McGill Nutr & Food Sci Ctr, Montreal, PQ, Canada. Univ Cambridge, Canc Res Campaign, Human Canc Genet Res Grp, Cambridge, England. RP Zori, RT (reprint author), Univ Florida, Dept Pediat, JHMHC, Div Genet, POB 100296, Gainesville, FL 32606 USA. RI Marsh, Deborah/I-1491-2014; OI Marsh, Deborah/0000-0001-5899-4931; Eng, Charis/0000-0002-3693-5145 NR 9 TC 73 Z9 75 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD DEC 4 PY 1998 VL 80 IS 4 BP 399 EP 402 DI 10.1002/(SICI)1096-8628(19981204)80:4<399::AID-AJMG18>3.0.CO;2-O PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 144FG UT WOS:000077302900018 PM 9856571 ER PT J AU Du, KY Montminy, M AF Du, KY Montminy, M TI CREB is a regulatory target for the protein kinase Akt/PKB SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOLECULAR-CLONING; CYCLIC-AMP; PHOSPHORYLATION; MICE; GENE; AKT; TRANSLOCATION; TRANSCRIPTION; ACTIVATION; BINDING AB The nuclear factor CREB stimulates the expression of cellular genes following its protein kinase A-mediated phosphorylation at Ser-133. Ser-133 phosphorylation, in turn, activates target gene expression by promoting recruitment of the co-activator CBP, Recent studies showing that CREE and its paralog CREM are required for survival of certain cell types prompted us to examine whether CREB is a nuclear target for activation via the growth factor-dependent Ser/Thr kinase Akt/PKB. When overexpressed in serum-stimulated cells, Akt/PKB potently induced Ser-133 phosphorylation of CREB and promoted recruitment of CBP, Correspondingly, Akt/PKB stimulated target gene expression via CREB in a phospho(Ser-133) dependent manner. Akt/PKB induced CREB activity only in response to serum stimulation, and this effect was suppressed by the phosphatidylinositol 3-kinase inhibitor LY 294002. Our results support the notion that Akt/PKB promotes cell survival, at least in part, by stimulating the expression of cellular genes via the CREB/CBP nuclear transduction pathway. C1 Harvard Univ, Sch Med, Dept Cell Biol, Joslin Diabet Ctr,Res Div, Boston, MA 02215 USA. RP Montminy, M (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Joslin Diabet Ctr,Res Div, Joslin Pl, Boston, MA 02215 USA. NR 21 TC 636 Z9 647 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 4 PY 1998 VL 273 IS 49 BP 32377 EP 32379 DI 10.1074/jbc.273.49.32377 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 144RP UT WOS:000077329100003 PM 9829964 ER PT J AU Yu, GS Lu, YC Gulick, T AF Yu, GS Lu, YC Gulick, T TI Co-regulation of tissue-specific alternative human carnitine palmitoyltransferase I beta gene promoters by fatty acid enzyme substrate SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROLIFERATOR-ACTIVATED RECEPTORS; TRANSCRIPTION FACTORS; MALONYL-COA; RETINOIC ACID; EXPRESSION; OXIDATION; HEART; RAT; MUSCLE; CARBOXYLASE AB Carnitine palmitoyltransferase I (CPT-I) catalyzes the rate-determining step in mitochondrial fatty acid beta-oxidation. CPT-I has two structural genes (alpha and beta) that are differentially expressed among tissues. Our CPT-I beta isolates from a human cardiac cDNA library contained two different extreme 5'-sequences derived from short alternative first untranslated exons that utilize a common splice acceptor site in exon 2. Primer extension identified single dominant start sites for each transcript, and ribonuclease protection assays showed the presence of one 5'-exon in liver, muscle, and heart mRNAs, indicating that the cognate promoter U (upstream/ubiquitous) is active in each of these tissues. By contrast, mRNAs containing the alternative 5'-exon were present only in muscle and heart, indicating a muscle-specific promoter M (muscle). CPT-I beta mRNA levels increased markedly in tissues of fasted rats, when circulating free fatty acid concentrations are elevated. Using CPT-I beta promoter/reporter transient transfection of murine C2C12 myotubes and HepG2 hepatocyte, fatty acids were found to increase promoter activity in a peroxisome proliferator-activated receptor alpha (PPAR alpha)-dependent fashion. A promoter fatty acid response element (FARE) was mapped, mutation of which ablated fatty acid-mediated production of both transcripts. PPAR alpha/retinoid X receptor a formed specific complexes with oligonucleotides containing the FARE, and anti-PPAR alpha antibody shifted nuclear protein-DNA complexes, confirming the role of this factor in regulating the expression of this critical metabolic enzyme gene. The constitutive repressor chicken ovalbumin upstream promoter transcription factor competitively binds at the FARE and modulates fatty acid induction of the promoters. C1 Massachusetts Gen Hosp, Diabet Res Lab, Diabet Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Med Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Gulick, T (reprint author), Massachusetts Gen Hosp, Diabet Res Lab, Diabet Unit, MGH E,CNY 149 8218,149 13th St, Charlestown, MA 02129 USA. EM gulick@helix.mgh.harvard.edu FU NICHD NIH HHS [HD35685] NR 52 TC 77 Z9 80 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 4 PY 1998 VL 273 IS 49 BP 32901 EP 32909 DI 10.1074/jbc.273.49.32901 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 144RP UT WOS:000077329100079 PM 9830040 ER PT J AU Price, ER Horstmann, MA Wells, AG Weilbaecher, KN Takemoto, CM Landis, MW Fisher, DE AF Price, ER Horstmann, MA Wells, AG Weilbaecher, KN Takemoto, CM Landis, MW Fisher, DE TI alpha-melanocyte-stimulating hormone signaling regulates expression of microphthalmia, a gene deficient in Waardenburg syndrome SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR; TYROSINASE GENE; HUMAN HOMOLOG; FACTOR CREB; CYCLIC-AMP; PROTEIN; CAMP; MUTATIONS; KINASE; CELLS AB The pituitary peptide alpha-melanocyte-stimulating hormone (alpha-MSH) stimulates melanocytes to up-regulate cAMP, but the downstream targets of cAMP are not well understood mechanistically. One consequence of alpha-MSH stimulation is increased melanization attributable to induction of pigmentation enzymes, including tyrosinase, which catalyzes a rate-limiting step in melanin synthesis. The tyrosinase promoter is a principle target of the melanocyte transcription factor Microphthalmia (Mi), a factor for which deficiency in humans causes Waardenburg syndrome II. We show here that both alpha-MSH and forskolin, a drug that increases cAMP, stimulate a rapid increase in Mi mRNA and protein levels in both melanoma cell lines and primary melanocytes. This up-regulation requires a cAMP-responsive element within the Mi promoter, and the pathway leading to Mi stimulation is subject to tight homeostatic regulation. Although cAMP signaling is ubiquitous, the Mi promoter was seen to be cAMP-responsive in melanocytes but not in non-melanocytes. Moreover, dominant negative interference with Mi impeded successful alpha-MSH stimulation of tyrosinase, The regulation of Mi expression via alpha-MSH thus provides a direct mechanistic link to pigmentation. In addition, because the human melanocyte and deafness condition Waardenburg syndrome is sometimes caused by haploinsufficiency of Mi, its modulation by alpha-MSH suggests therapeutic strategies targeted at up-regulating the remaining wild type Mi allele. C1 Dana Farber Canc Res Inst, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fisher, DE (reprint author), Dana Farber Canc Res Inst, Dept Pediat Hematol Oncol, 44 Binney St, Boston, MA 02115 USA. NR 38 TC 144 Z9 145 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 4 PY 1998 VL 273 IS 49 BP 33042 EP 33047 DI 10.1074/jbc.273.49.33042 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 144RP UT WOS:000077329100097 PM 9830058 ER PT J AU Hong, M Zhukareva, V Vogelsberg-Ragaglia, V Wszolek, Z Reed, L Miller, BI Geschwind, DH Bird, TD McKeel, D Goate, A Morris, JC Wilhelmsen, KC Schellenberg, GD Trojanowski, JQ Lee, VMY AF Hong, M Zhukareva, V Vogelsberg-Ragaglia, V Wszolek, Z Reed, L Miller, BI Geschwind, DH Bird, TD McKeel, D Goate, A Morris, JC Wilhelmsen, KC Schellenberg, GD Trojanowski, JQ Lee, VMY TI Mutation-specific functional impairments in distinct Tau isoforms of hereditary FTDP-17 SO SCIENCE LA English DT Article ID PAIRED HELICAL FILAMENTS; ALZHEIMERS-DISEASE; SR PROTEINS; PHOSPHORYLATION; LOCALIZATION; SEQUENCES; DEMENTIA AB Tau proteins aggregate as cytoplasmic inclusions in a number of neurodegenerative diseases, including Alzheimer's disease and hereditary frontotemporal dementia and parkinsonism Linked to chromosome 17 (FTDP-17). Over 10 exonic and intronic mutations in the tau gene have been identified in about 20 FTDP-17 families. Analyses of soluble and insoluble tau proteins from brains of FTDP-17 patients indicated that different pathogenic mutations differentially altered distinct biochemical properties and stoichiometry of brain tau isoforms, Functional assays of recombinant tau proteins with different FTDP-17 missense mutations implicated all but one of these mutations in disease pathogenesis by reducing the ability of tau to bind microtubules and promote microtubule assembly. C1 Univ Penn, Sch Med, Dept Pathol & Lab Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. Mayo Clin Jacksonville, Dept Neurol, Jacksonville, FL 32224 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Calif Los Angeles, Reed Neurol Res Ctr, Program Neurogenet, Dept Neurol, Los Angeles, CA 90095 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94110 USA. Ernest Gallo Clin & Res Ctr, San Francisco, CA 94110 USA. Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Dept Pharmacol, Seattle, WA 98195 USA. RP Lee, VMY (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. RI Morris, John/A-1686-2012 NR 21 TC 609 Z9 620 U1 1 U2 13 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 4 PY 1998 VL 282 IS 5395 BP 1914 EP 1917 DI 10.1126/science.282.5395.1914 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 144WG UT WOS:000077338100056 PM 9836646 ER PT J AU Rivier, J Gulyas, J Corrigan, A Martinez, V Craig, AG Tache, Y Vale, W Rivier, C AF Rivier, J Gulyas, J Corrigan, A Martinez, V Craig, AG Tache, Y Vale, W Rivier, C TI Astressin analogues (corticotropin-releasing factor antagonists) with extended duration of action in the rat SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID SOLID-PHASE SYNTHESIS; COMPETITIVE ANTAGONISTS; SECRETION; HORMONE; PEPTIDE; OVINE; POTENCIES AB In earlier reports we identified specific point substitutions (DPhe(12),Nle(21,38)), cyclization strategies [in particular, introduction of lactam rings such as that of cyclo(Glu(30),Lys(33))], and deletions (residues 1-7) in the CRF molecule that led to agonists. We also noted that further deletions (residues 8-14) produced antagonists such as astressin {cyclo(30-33)[DPhe(12),Nle(21,38),Glu(30), Lys(33)]hCRF((12-41))} (1). We hypothesized that the lactam ring promoted conformational stability to yield analogues with increased potency both in vitro and in vivo as compared to that of their linear counterparts. Additionally, we reported that cyclo(30-33)[DPhe(12),Nle(21,38), Glu(30),DHis(32),Lys(33)]hcRF((12-41)) (3) and dicyclo(26-36,30-33)[Ac-Asp(9),DPhe(12),Nle(21,38),Cys(26), Glu(30),Lys(33),Cys(36)]hCRF((9-41)) were ca. twice and 1/100 as potent as astressin, respectively, suggesting a putative turn that encompasses residues 30-33 (previous paper: Koerber et al. J. Med. Chem. 1998, 41). To increase the potency of 1 and/or 3 in vivo, we extended their chain length by one (5-8), two (9, 10), and three (11, 12) residues at the N-terminus and acetylated (6, 8, 10, 12). Of the compounds tested for duration of action (1, 3-6, 8), we found 6 and 8 to be slightly longer-acting than astressin or [DHis32]astressin, while their potencies in vitro were not significantly different from that of 3. Additionally, we introduced C alpha Me-leucine residues in Lieu of leucine at positions 14, 15, 19, 27, and 37 in [DHis(32)]astressin. The analogue [C alpha Me-Leu(27),DHis(32)]astressin (16) was more potent (although not statistically in all cases) than the other four analogues in vitro. While acetylation of the N-terminus of 16 (i.e., 18) or of [C alpha Me-Leu(27)]astressin (i.e., 19) did not have a significant effect on in vitro potency, elongation of the N-terminus by one or three residues in addition to acetylation resulted in cyclo(30-33)[DPhe(12),Nle(21),C alpha Me-Leu(27),Glu(30),DHis(32),Lys(33),Nle(38)]Ac-hCRF((11-41)) (21), cyclo(30-33)[DPhe(12),Nle(21),C alpha Me-Leu(27),Glu(30),Lys(33),Nle(38)]Ac-HCRF(9-41) (22), and cyclo(30-33)[DPhe(12),Nle(21),C alpha Me-Leu(27),Glu(30),DHis(32),Lys(33),Nle(38)]Ac-hCRF((9-41)) (23) that were longer-acting than 6 and 8 (ca. 2 h inhibition of ACTH secretion at 25 mu g/adrenalectomized rat). Analogues 22 and 23 were also more potent than astressin at reversing intracisternal CRF- and abdominal surgery-induced delay of gastric emptying in conscious rats. C1 Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, La Jolla, CA 92037 USA. W Los Angeles Vet Affairs Med Ctr, Digest Dis Res Ctr, CURE, Los Angeles, CA 90073 USA. CEU San Pablo, Sch Vet, Dept Physiol, Valencia, Spain. RP Rivier, J (reprint author), Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [DK-33061, DK-26741]; NIMH NIH HHS [MH-00663] NR 36 TC 34 Z9 35 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 3 PY 1998 VL 41 IS 25 BP 5012 EP 5019 DI 10.1021/jm980426c PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 146ZB UT WOS:000077462800014 PM 9836619 ER PT J AU Cassileth, PA Harrington, DP Appelbaum, FR Lazarus, HM Rowe, JM Paietta, E Willman, C Hurd, DD Bennett, JM Blume, KG Head, DR Wiernik, PH AF Cassileth, PA Harrington, DP Appelbaum, FR Lazarus, HM Rowe, JM Paietta, E Willman, C Hurd, DD Bennett, JM Blume, KG Head, DR Wiernik, PH TI Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; CONSOLIDATION CHEMOTHERAPY; 1ST REMISSION; INTENSIVE CHEMOTHERAPY; POSTREMISSION THERAPY; 4-HYDROPEROXYCYCLOPHOSPHAMIDE; CLASSIFICATION AB Background In young adults with acute myeloid leukemia, intensive chemotherapy during the initial remission improves the long-term outcome, but the role of bone marrow transplantation is uncertain. We compared high-dose cytarabine with autologous or allogeneic marrow transplantation during the first remission of acute myeloid leukemia. Methods Previously untreated adolescents and adults 16 to 55 years of age who had acute myeloid leukemia received standard induction chemotherapy. After complete remission had been achieved, idarubicin (two days) and cytarabine (five days) were administered. Patients with histocompatible siblings were offered allogeneic marrow transplantation, whereas the remaining patients were randomly assigned to receive a single course of high-dose cytarabine or transplantation of autologous marrow treated with perfosfamide (4-hydroperoxycyclophosphamide). Oral busulfan and intravenous cyclophosphamide were used as preparative regimens for both allogeneic and autologous marrow transplantation. The end points were survival from the time of complete remission and disease-free survival. Results In an intention-to-treat analysis, we found no significant differences in disease-free survival among patients receiving high-dose chemotherapy, those undergoing autologous bone marrow transplantation, and those undergoing allogeneic marrow transplantation. The median follow-up was four years. Survival after complete remission was somewhat better after chemotherapy than after autologous marrow transplantation (P = 0.05). There was a marginal advantage in terms of overall survival with chemotherapy as compared with allogeneic marrow transplantation (P = 0.04). Conclusions A postinduction course of high-dose cytarabine can provide equivalent disease-free survival and somewhat better overall survival than autologous marrow transplantation in adults with acute myeloid leukemia. (N Engl J Med 1998;339:1649-56.) (C)1998, Massachusetts Medical Society. C1 Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH USA. Univ Rochester, Ctr Canc, Rochester, NY USA. Montefiore Med Ctr, Albert Einstein Canc Ctr, Bronx, NY 10467 USA. Univ New Mexico, Sch Med, Albuquerque, NM 87131 USA. Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. Stanford Univ Hosp, Stanford, CA 94305 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. RP Cassileth, PA (reprint author), Univ Miami, Sylvester Comprehens Canc Ctr, 1475 NW 12th Ave, Miami, FL 33136 USA. FU NCI NIH HHS [CA38926, CA23318, CA14548] NR 33 TC 433 Z9 448 U1 0 U2 3 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 3 PY 1998 VL 339 IS 23 BP 1649 EP 1656 DI 10.1056/NEJM199812033392301 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 144BX UT WOS:000077294800001 PM 9834301 ER PT J AU Foster, GS AF Foster, GS TI Truth and consequences SO ACADEMIC MEDICINE LA English DT Editorial Material C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Foster, GS (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD DEC PY 1998 VL 73 IS 12 BP 1226 EP 1227 DI 10.1097/00001888-199812000-00009 PG 2 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 150ZT UT WOS:000077697000012 PM 9883195 ER PT J AU Oslin, DW Pettinati, HM Luck, G Semwanga, A Cnaan, A O'Brien, CP AF Oslin, DW Pettinati, HM Luck, G Semwanga, A Cnaan, A O'Brien, CP TI Clinical correlations with carbohydrate-deficient transferrin levels in women with alcoholism SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Research-Society-of-Alcoholism CY JUL, 1998 CL HILTON HEAD ISL, SOUTH CAROLINA SP Res Soc Alcoholism DE alcohol dependence; biological markers; carbohydrate-deficient transferrin ID GAMMA-GLUTAMYL-TRANSFERASE; SERUM TRANSFERRIN; CONSUMPTION; MARKER; ABUSE; POPULATION; DRINKING; SEVERITY; UTILITY; RELAPSE AB Carbohydrate-deficient transferrin (CDT) has received increasing attention as a potential biological marker for heavy drinking or as an objective marker of relapse in patients who are treated for alcohol dependence. Previous studies have demonstrated the utility of CDT among men, but there are fewer and inconsistent reports on the utility of CDT among women, This study reports in a sample of 40 alcohol-dependent women, the association between CDT levels, and several different types of measures of drinking intensity including frequency of heavy drinking, Although the majority of drinking indices correlated with CDT levels in men, among women, CDT levels were significantly correlated with the percentage of days of heavy drinking when heavy drinking day was defined as drinking 6 or more drinks per drinking day, The results also support an association between current menstrual function, CDT levels, and drinking indices, These findings suggest that the pattern of drinking (combining high frequency and high intensity) may be an important determinant of CDT levels in women with alcohol dependence, compared with men. C1 Univ Penn, Ralston Penn Ctr, Ctr Study Addict, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Oslin, DW (reprint author), Univ Penn, Ralston Penn Ctr, Ctr Study Addict, Dept Psychiat, 3615 Chestnut St, Philadelphia, PA 19104 USA. FU NIAAA NIH HHS [AA-09544] NR 25 TC 15 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 1998 VL 22 IS 9 BP 1981 EP 1985 PG 5 WC Substance Abuse SC Substance Abuse GA 153CB UT WOS:000077814500015 PM 9884141 ER PT J AU Banerjee, K Mohr, L Wands, JR de la Monte, SM AF Banerjee, K Mohr, L Wands, JR de la Monte, SM TI Ethanol inhibition of insulin signaling in hepatocellular carcinoma cells SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE insulin receptor substrate-1; ethanol; hepatocellular carcinoma; signal transduction; mitogen-activated protein kinase ID EPIDERMAL GROWTH-FACTOR; RECEPTOR SUBSTRATE-1; PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE PHOSPHORYLATION; RAT ADIPOCYTES; HEPATIC REGENERATION; LIVER-REGENERATION; PHOSPHOLIPASE-C; KINASE FAMILY; FACTOR-I AB Chronic ethanol toxicity impairs liver regeneration, inhibits DNA synthesis, and mutes cellular responses to growth factor stimulation, Previous studies demonstrated that the adverse effects of ethanol are mediated by inhibition of tyrosyl phosphorylation of the insulin receptor and the insulin receptor substrate-type 1 (IRS-1), However, overexpression of IRS-1 leads to increased DNA synthesis and cellular transformation due to constitutive activation of mitogen-activated protein (MAP) kinase, The present study examines the effects of ethanol on insulin signaling through IRS-1 in FOCUS hepatocellular carcinoma cells, which overexpress IRS-l,to determine whether such cells were resistant to the inhibitory effects of ethanol, The results demonstrated that ethanol treatment (100 mM) caused 30 to 50% reductions in the levels of insulin-stimulated tyrosyl phosphorylation of the insulin receptor beta-subunit, tyrosyl phosphorylation of IRS-1, phosphorylation of Erk2, association of phosphatidylinositol-3 kinase with tyrosyl-phosphorylated IRS-1, and MAP kinase and phosphatidylinositol-3 kinase activities. In contrast, ethanol treatment had no effect on epidermal growth factor-stimulated tyrosyl phosphorylation of Shc. Corresponding with the pronounced inhibition of MAP kinase, ethanol treatment resulted in 30 to 50% reductions in the expression levels of two important insulin-responsive genes: glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and proliferating cell nuclear antigen (PCNA). The findings suggest that, in FOCUS hepatocellular carcinoma cells, which overexpress IRS-1, ethanol treatment substantially inhibits IRS-1 and MAP kinase signaling and growth-associated gene expression, but has no effect on Shc phosphorylation, which activates p21(ras) through an IRS-1 independent pathway. C1 Massachusetts Gen Hosp, Ctr Canc, Mol Hepatol Lab, Dept Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc, Mol Hepatol Lab, Dept Pathol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. RP de la Monte, SM (reprint author), Massachusetts Gen Hosp, Ctr Canc, Mol Hepatol Lab, Dept Med, 149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02666, AA-10102] NR 56 TC 38 Z9 38 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 1998 VL 22 IS 9 BP 2093 EP 2101 DI 10.1111/j.1530-0277.1998.tb05921.x PG 9 WC Substance Abuse SC Substance Abuse GA 153CB UT WOS:000077814500030 PM 9884156 ER PT J AU Mahdi, NA Pathan, AZ Harrell, L Leon, MN Lopez, J Butte, A Ferrell, M Gold, HK Palacios, IF AF Mahdi, NA Pathan, AZ Harrell, L Leon, MN Lopez, J Butte, A Ferrell, M Gold, HK Palacios, IF TI Directional Coronary atherectomy for the treatment of Palmaz-Schatz in-stent restenosis SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID THREATENED CLOSURE; ANGIOGRAPHIC OUTCOMES; BALLOON ANGIOPLASTY; FOLLOW-UP; IMPLANTATION; MECHANISMS; EXPERIENCE; 4-YEAR AB Management of in-stent restenosis has become a significant challenge in interventional cardiology. The results of balloon angioplasty have been disappointing due to the high recurrence of restenosis at follow-vp. Debulking of the restenotic tissue within the stents using directional coronary atherectomy (DCA) may offer a therapeutic advantage. We report the immediate clinical and angiographic outcomes and long-term clinical follow-up results of 45 patients (46 lesions), mean age 63 +/- 12 years, 73% men, with ct mean reference diameter of 2.9 +/- 0.6 mm, treated with DCA for symptomatic Palmaz-Schatz in-stent restenosis. DCA was performed successfully in all 46 lesions and resulted In a postprocedural minimal luminal diameter of 2.7 +/- 0.7 mm and a residual diameter stenosis of 17 +/- 10%. There were no in-hospital deaths, Q-wave myocardial infarctions, or emergency coronary artery bypass surgeries. Four patients (9%) suffered a non-Q-wave myocardial infarction. Target lesion revascularization was 28.3% at a mean follow-vp of 10 +/- 4.6 months. Kaplan-Meier event-free survival (freedom from death, myocardial infarction, and repeat target lesion revascularization) was 71.2% and 64.7% at 6 and 12 months after DCA, respectively. Thus, DCA is safe and efficacious for the treatment of Palmaz-Schatz in-stent restenosis. It results in a large postprocedural minimal luminal diameter and a low rate of both target lesion revascularization and combined major clinical evens at follow-vp. (C) 1998 by Excerpta Medica, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiac Unit,Cardiac Catheterizat Lab, Boston, MA 02114 USA. RP Palacios, IF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiac Unit,Cardiac Catheterizat Lab, Bulfinch 105,Fruit St, Boston, MA 02114 USA. EM mahdi.nassei@mgh.harvard.edu; palacios.igor@mgh.harvard.edu NR 27 TC 52 Z9 56 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 1 PY 1998 VL 82 IS 11 BP 1345 EP 1351 DI 10.1016/S0002-9149(98)00639-0 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 145EA UT WOS:000077357000007 PM 9856917 ER PT J AU Kushwaha, SS Narula, J Narula, N Zervos, G Semigran, MJ Fischman, AJ Alpert, NA Dec, GW Gewirtz, H AF Kushwaha, SS Narula, J Narula, N Zervos, G Semigran, MJ Fischman, AJ Alpert, NA Dec, GW Gewirtz, H TI Pattern of changes over time in myocardial blood flow and microvascular dilator capacity in patients with normally functioning cardiac allografts SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; CORONARY VASCULAR RESERVE; ISCHEMIC-HEART-DISEASE; SYMPATHETIC REINNERVATION; TRANSPLANT RECIPIENTS; ARTERY DISEASE; HUMANS; REJECTION; QUANTIFICATION; CIRCULATION AB This study tests the hypothesis that myocardial blood flow and coronary microvascular dilator capacity vary as a function of time after orthotopic heart transplantation in humans. Positron emission tomography measurements of myocardial blood flow were obtained at rest and during adenosine in 24 patients between 1 and 86 months after heart transplantation. At the time of the study all patients were clinically well and had angiographically normal epicardial coronary artery vessels. patients were divided into 3 groups based on time from transplant to positron emission tomography measurement of myocardial blood flow: group 1 to 12 months (n = 9); group 13 to 34 months (n = 8); and group greater than or equal to 37 months (n = 7). Basal myocardial blood flow in group 1 to 12 months (1.86 +/- 1.01 ml/min/g) exceeded (p <0.05) that of group 13 to 34 months (1.17 +/- 0.73) and group greater than or equal to 37 months (0.98 +/- 0.34). In group 13 to 34 months, basal myocardial blood flow and maximal dilator capacity (minimal coronary vascular resistance with adenosine 36 +/- 12 mm Hg/ml/min/g) were comparable to that of normal volunteers (1.01 +/- 0.20 and 37 +/- 9, respectively). In group greater than or equal to 37 months, maximal flow response to adenosine was reduced (2.54 +/- 1.25 vs 3.16 +/- 0.52, respectively, p = 0.06). Maximal dilator capacity in group greater than or equal to 37 months (60 +/- 34) wets impaired versus group 1 to 12 months (36 +/- 10) and group 13 to 34 months (36 +/- 12; both p <0.05) as well as normals (37 +/- 9, p <0.05). During the first year after cardiac transplantation basal myocardial blood flow is elevated out of proportion to external determinants of myocardial oxygen demand, but maximal dilator capacity of the coronary microcirculation is normal. Between 1 and 3 years both basal myocardial blood flow and microvascular function tend to normalize. After 3 years, although basal myocardial blood flow is normal, microvascular dilator capacity is impaired. (C) 1998 by Excerpta Medica, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Nucl Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Gewirtz, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiac Unit, Vincent Burnham 3, Boston, MA 02114 USA. NR 25 TC 12 Z9 12 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 1 PY 1998 VL 82 IS 11 BP 1377 EP 1381 DI 10.1016/S0002-9149(98)00645-6 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 145EA UT WOS:000077357000013 PM 9856923 ER PT J AU Arjmandi, BH Birnbaum, R Goyal, NV Getlinger, MJ Juma, S Alekel, L Hasler, CM Drum, ML Hollis, BW Kukreja, SC AF Arjmandi, BH Birnbaum, R Goyal, NV Getlinger, MJ Juma, S Alekel, L Hasler, CM Drum, ML Hollis, BW Kukreja, SC TI Bone-sparing effect of soy protein in ovarian hormone-deficient rats is related to its isoflavone content SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT 2nd International Symposium on the Role of Soy in Preventing and Treating Chronic Disease CY SEP 15-19, 1996 CL BRUSSELS, BELGIUM SP Alpo Nat Soyfoods, Amer Inst Canc Res, Amer Soybean Assoc, Archer Daniels Midland Co, Cent Soya Co, Foreign Agr Serv, Illinois Soybean Assoc & Illinois Soybean Program Operating Board, Indiana Soybean Dev Council, Infant Formula Council, Iowa Soybean Promot Board, Michigan Soybean Promot Comm, Minnesota Soybean Res & Promot Council, Monsanto Co, Morinaga Nutr Foods Inc, Nebraska Soybean Board, Ohio Soybean Council, Ontario Soybean Growers Mkt Board, Protein Technol Int, Sanitarium Hlth Foods, Sojaxa, Soyfoods Assoc Amer, United Soybean Board, Wyeth Nutr Int DE isoflavones; osteoporosis; ovariectomy; rats; soy protein; bone density; bone formation rate ID OVARIECTOMIZED RAT; ESTROGEN; OSTEOPOROSIS; PROGESTERONE; IPRIFLAVONE; MODEL AB Our previous studies showed that a soy-protein diet prevents ovariectomy-induced bone loss. The purpose of this study was to determine whether isoflavones in soy protein are responsible for this bone-protective effect. Forty-eight 95-d-old Sprague-Dawley rats were divided into 4 groups: sham-operated fed a casein-based diet (SHAM), ovariectomized fed a casein-based diet (OVX+CASEIN), ovariectomized fed soy protein with normal isoflavone content (OVX+SOY), and ovariectomized fed soy protein with reduced isoflavone content (OVX+SOY-). The OVX+SOY group had significantly greater femoral bone density (in g/cm(3) bone vol) than the OVX+CASEIN group, whereas OVX+SOY- was similar to OVX+CASEIN ((x) over bar +/- SD; SHAM, 1.522 +/- 0.041; OVX+CASEIN, 1.449 +/- 0.044; OVX+SOY, 1.497 +/- 0.030; OVX+SOY-, 1.452 +/- 0.030). Ovariectomy resulted in greater bone turnover as indicated by higher serum alkaline phosphatase activity, serum insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations, and urinary hydroxyproline. These increases were not affected by soy with either normal or reduced isoflavone content. Similarly, histomorphometry revealed a greater bone formation rate with ovariectomy, and this was not altered by the soy diets. The findings of this study suggest that isoflavones in soy protein are responsible for its bone-sparing effects. Further studies to evaluate the mechanism of action of isoflavones on bone are warranted. C1 Oklahoma State Univ, Dept Nutr Sci, Stillwater, OK 74078 USA. VA Puget Sound Hlth Care Syst, Res Serv, Amer Lake Div, Tacoma, WA USA. Univ Washington, Sch Med, Dept Med, Seattle, WA USA. Univ Illinois, Dept Human Nutr & Dietet, Chicago, IL 60612 USA. Univ Illinois, Sch Publ Hlth, Div Epidemiol Biostat, Chicago, IL 60612 USA. Iowa State Univ, Dept Food Sci & Human Nutr, Ames, IA 50011 USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. W Side Vet Adm Med Ctr, Dept Med, Chicago, IL 60612 USA. RP Arjmandi, BH (reprint author), Oklahoma State Univ, Dept Nutr Sci, Stillwater, OK 74078 USA. EM arjmand@okstate.edu NR 30 TC 85 Z9 91 U1 2 U2 5 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 1998 VL 68 IS 6 SU S BP 1364S EP 1368S PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 145VM UT WOS:000077392300007 PM 9848500 ER PT J AU Miller, HJ Leong, T Khandekar, JD Greipp, PR Gertz, MA Kyle, RA AF Miller, HJ Leong, T Khandekar, JD Greipp, PR Gertz, MA Kyle, RA TI Paclitaxel as the initial treatment of multiple myeloma - An Eastern Cooperative Oncology Group Study (E1A93) SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE paclitaxel; multiple myeloma; Eastern Cooperative Oncology Group ID IN-VITRO; MELPHALAN; CHEMOTHERAPY; COMBINATION; TAXOL AB The authors assess the activity and toxicity of paclitaxel in previously untreated patients with multiple myeloma. Eighteen patients with previously untreated multiple myeloma were enrolled. Paclitaxel was given in a dose of 250 mg/m(2) by a continuous intravenous infusion for 24 hours every 21 days for four cycles. All patients received granulocyte colony stimulating factor in a dose of 5 mu g/kg each day until the absolute neutrophil count was 10,000/mm(3). All patients were evaluated after four cycles. Four (29%) objective responses were observed in the 14 eligible patients. No complete responses occurred. Three lethal toxicities were observed, two were the result of neutropenic sepsis. Sixty-one percent of patients experienced some type of severe nonhematologic toxicity. Patients who received four cycles of paclitaxel were given further treatment at the discretion of the investigator. The median survival of all eligible patients was 2.8 years, which is comparable with the median survival with melphalan and prednisone of 2.3 years or vincristine, carmustine, melphalan, cylophosphamide, and prednisone of 2.4 years. Paclitaxel in the dosage used in this study has prohibitive toxicity. The four (29%) responses in 14 evaluable untreated patients indicates that paclitaxel is active in the treatment of multiple myeloma. No complete remissions were recorded. Further studies using paclitaxel in a smaller dose, in combination with other agents, or using one of the paclitaxel analogs may be useful in the treatment of multiple myeloma. C1 Northwestern Univ, Evanston Hosp, Evanston, IL 60201 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. RP Miller, HJ (reprint author), 418 Church St, Evanston, IL 60201 USA. FU NCI NIH HHS [CA23318, CA66636, CA13650] NR 14 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD DEC PY 1998 VL 21 IS 6 BP 553 EP 556 DI 10.1097/00000421-199812000-00005 PG 4 WC Oncology SC Oncology GA 146GT UT WOS:000077421500005 PM 9856654 ER PT J AU Cochran, AJ Bailly, C Cook, M Crotty, K McCarthy, S Mihm, M Mooi, W Sagebiel, R AF Cochran, AJ Bailly, C Cook, M Crotty, K McCarthy, S Mihm, M Mooi, W Sagebiel, R TI Recommendations for the reporting of tissues removed as part of the surgical treatment of cutaneous melanoma SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE malignant melanoma; skin ID MALIGNANT-MELANOMA; CLASSIFICATION; THICKNESS; SURVIVAL; MODEL AB The Association of Directors of Anatomic and Surgical Pathology has developed recommendations for the surgical pathology report for common malignant tumors. The recommendations for cutaneous melanoma are reported. C1 Univ Calif Los Angeles, Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. Ctr Leon Berard, F-69373 Lyon, France. Royal Surrey Cty Hosp, Guildford, Surrey, England. Royal Prince Alfred Hosp, Sydney, NSW, Australia. Massachusetts Gen Hosp, Boston, MA 02114 USA. Erasmus Univ, NL-3000 DR Rotterdam, Netherlands. Univ Calif San Francisco, Mt Zion Hosp, San Francisco, CA 94143 USA. RP Cochran, AJ (reprint author), Univ Calif Los Angeles, Sch Med, Dept Pathol & Lab Med, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. NR 12 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD DEC PY 1998 VL 110 IS 6 BP 719 EP 722 PG 4 WC Pathology SC Pathology GA 142AL UT WOS:000077177700002 PM 9844583 ER PT J AU Slominski, A Wortsman, J Nickoloff, B McClatchey, K Mihm, MC Ross, JS AF Slominski, A Wortsman, J Nickoloff, B McClatchey, K Mihm, MC Ross, JS TI Molecular pathology of malignant melanoma SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Review DE melanoma; melanoma markers; progression; pathology; molecular biology ID COMPARATIVE GENOMIC HYBRIDIZATION; MELANOCYTIC TUMOR PROGRESSION; ACRAL LENTIGINOUS MELANOMA; POMC GENE-EXPRESSION; S-PHASE FRACTION; GROWTH-FACTOR; STIMULATING HORMONE; FAMILIAL MELANOMA; L-TYROSINE; L-DOPA C1 Albany Med Coll, Dept Pathol & Lab Med, Albany, NY 12208 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. So Illinois Univ, Dept Med, Springfield, IL USA. Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. RP Ross, JS (reprint author), Albany Med Coll, Dept Pathol & Lab Med, A-81,47 New Scotland Ave, Albany, NY 12208 USA. NR 136 TC 15 Z9 17 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD DEC PY 1998 VL 110 IS 6 BP 788 EP 794 PG 7 WC Pathology SC Pathology GA 142AL UT WOS:000077177700011 PM 9844592 ER PT J AU Klein, C Ozelius, LJ Hagenah, J Breakefield, XO Risch, NJ Vieregge, P AF Klein, C Ozelius, LJ Hagenah, J Breakefield, XO Risch, NJ Vieregge, P TI Search for a founder mutation in idiopathic focal dystonia from northern Germany SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID TORSION DYSTONIA; LINKAGE DISEQUILIBRIUM; PARKINSONS-DISEASE; GENETIC COMPLEXITY; ASHKENAZI JEWS; CHROMOSOME 18P; ADULT-ONSET; FAMILY; TORTICOLLIS; INHERITANCE AB Both the discovery of the DYT1 gene on chromosome 9q34 in autosomal dominant early-onset torsion dystonia and the detection of linkage for one form of adult-onset focal dystonia to chromosome 18p (DYT7) in a family from northern Germany provide the opportunity to further investigate genetic factors in the focal dystonias. Additionally, reports of linkage disequilibrium between several chromosome 18 markers and focal dystonia, both in sporadic patients from northern Germany and in members of affected families from central Europe suggest the existence of a founder mutation underlying focal dystonia in this population. To evaluate the role of these loci in focal dystonia, we tested 85 patients from northern Germany who had primary focal dystonia, both for the GAG deletion in the DYT1 gene on chromosome 9q34 and for linkage disequilibrium at the chromosome 18p markers D18S1105, D18S1098, D18S481, and D18S54. None of these patients had the GAG deletion in the DYT1 gene. Furthermore, Hardy-Weinberg analysis of markers on 18p in our patient population and in 85 control subjects from the same region did not support linkage disequilibrium. Taken together, these results suggest that most cases of focal dystonia in patients of northern German or central European origin are due neither to the GAC deletion in DYT1 nos to a proposed founder mutation on chromosome 18p but must be caused by other genetic or environmental factors. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA USA. Univ Lubeck, Dept Neurol, Lubeck, Germany. Stanford Univ, Dept Genet, Stanford, CA 94305 USA. RP Ozelius, LJ (reprint author), Massachusetts Gen Hosp E, Bldg 149,13th St, Charlestown, MA 02129 USA. EM Ozelius@helix.mgh.harvard.edu FU NHGRI NIH HHS [HG00348]; ONDIEH CDC HHS [ND38485] NR 28 TC 27 Z9 31 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC PY 1998 VL 63 IS 6 BP 1777 EP 1782 DI 10.1086/302143 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 151EL UT WOS:000077707700024 PM 9837831 ER PT J AU Cook, JR Glick, HA Gerth, W Kinosian, B Kostis, JB AF Cook, JR Glick, HA Gerth, W Kinosian, B Kostis, JB TI The cost and cardioprotective effects of enalapril in hypertensive patients with left ventricular dysfunction SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE Studies of Left Ventricular Dysfunction (SOLVD); angiotensin converting enzyme inhibitor; cost-effectiveness; enalapril ID CONGESTIVE-HEART-FAILURE; MODERATE HYPERTENSION; AGENTS; MILD AB This study examined the effect of enalapril on survival, resource use, and cost of care in patients with left ventricular dysfunction and hypertension using a retrospective analysis of patients who participated in the Studies of Left Ventricular Dysfunction (SOLVD). Among the 6797 SOLVD participants, 1917 patients had either elevated systolic (greater than or equal to 140 mm Hg) or diastolic (greater than or equal to 90 mm Hg) blood pressure. Therapy with enalapril was associated with a significant relative risk reduction for mortality (RR = 0.819, 95% CI: 0.68 to 0.98; P = .03). This resulted in a gain of 0.11 years (95% CI: 0.00 to 0.20 years) of survival during the average 2.8 year follow-up for this subgroup and was projected to result in a gain of 2.14 years (95% CI: 0.05 to 4.21 years) during the patient's lifetime. Enalapril significantly reduced the risk of first hospitalization for heart failure by 37%, For all types of hospitalizations, there was an average reduction of 32 hospitalizations per 100 patients treated with enalapril during the trial period (95% CI: 11.8 to 52.2 hospitalizations avoided per 100 patients), resulting in an estimated net savings of $1656 per patient during the trial period (95% CI: increased cost of $191 to savings of $3502). Although the projected lifetime net savings of $1456 was not significant (95% CI: increased cost of $9243 to saving of $12,527), evaluation of the cost per life year saved indicated that enalapril represented a cost-effective strategy. The estimated clinical benefit of enalapril among the hypertensive subgroup in SOLVD supports the recommendation that angiotensin converting enzyme (ACE) inhibitors should be considered as first line pharmacologic therapy for hypertensive patients with left ventricular dysfunction. From both the clinical and economic viewpoints, ACE inhibitors provide important clinical benefits and are cost-effective. (C) 1998 American Journal of Hypertension, Ltd. C1 Merck & Co Inc, Whitehouse Stn, NJ USA. Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Med Serv, Philadelphia, PA USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA. RP Cook, JR (reprint author), Merck Res Labs, 10 Sentry Pkwy BL2-3, Blue Bell, PA 19422 USA. EM cook_john@merck.com NR 29 TC 20 Z9 22 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD DEC PY 1998 VL 11 IS 12 BP 1433 EP 1441 DI 10.1016/S0895-7061(98)00180-0 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 150DM UT WOS:000077647900006 PM 9880125 ER PT J AU Park, IS Kiyomoto, H Alvarez, F Xu, YC Abboud, HE Abboud, SL AF Park, IS Kiyomoto, H Alvarez, F Xu, YC Abboud, HE Abboud, SL TI Preferential expression of insulin-like growth factor binding proteins-1, -3, and -5 during early diabetic renal hypertrophy in rats SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE insulin-like growth factor binding proteins; gene expression; diabetes; kidney ID RIBONUCLEIC-ACID EXPRESSION; OSTEOBLAST-LIKE CELLS; I MESSENGER-RNA; IGF-I; MESANGIAL CELLS; GENE-EXPRESSION; KIDNEY; RECEPTOR; PHOSPHORYLATION; POTENTIATION AB The renal insulin-like growth factor-I (IGF-I) system has been implicated in the pathogenesis of renal hypertrophy, altered hemodynamics, and extracellular matrix expansion associated with early diabetes. The relative abundance of IGF binding proteins (IGFBPs) in the renal microenvironment may modulate IGF-I actions. However, the precise IGFBPs expressed in the glomerular and tubulointerstitial compartments during diabetic renal growth have not been characterized. In the present study, in situ hybridization studies were performed to examine the expression of IGFBP-1 to -6 messenger RNAs (mRNAs) 3, 7, and 14 days after streptozotocin (STZ) injection in rats. In control, nondiabetic kidneys, all six IGFBP mRNAs were differentially expressed with a predominance of IGFBP-5, The onset of renal hypertrophy in STZ-induced diabetes was associated with a rapid and site-specific induction of IGFBP-1, -3, and -5 mRNAs. In contrast, basal expression of IGFBP-5, -4, and -6 mRNAs was not altered in diabetic rats. IGFBP-5 mRNA expression increased in diabetic glomeruli, cortical, and inner medullary peritubular interstitial cells at days 3, 7, and 14. Although normal glomeruli failed to express IGFBP-3, it was induced concomitantly with IGFBP-5 in diabetic glomeruli and cortical peritubular interstitial cells. IGFBP-1 mRNA levels also increased in cortical tubular cells at each time point tested. Peak induction of IGFBP-3 and -5 was observed at day 3, whereas IGFBP-1 was delayed until day 7. IGFBP-1, -3, and -5 mRNA levels declined by day 14, but remained persistently elevated above control. By immunoperoxidase staining, similar alterations in the pattern of IGFBP-3 and -5 protein expression were observed at each time point. The preferential and site-specific increase in IGFBP-1, -3, and -5 suggest that these IGFBPs may regulate the local autocrine and/or paracrine actions of IGF-I and contribute to the pathogenesis of the early manifestations of diabetic nephropathy. (C) 1998 by the National Kidney Foundation, Inc. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Abboud, SL (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIAMS NIH HHS [AR42306]; NIDDK NIH HHS [DK3365, DK43988] NR 44 TC 21 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD DEC PY 1998 VL 32 IS 6 BP 1000 EP 1010 DI 10.1016/S0272-6386(98)70075-7 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 145QY UT WOS:000077383900012 PM 9856516 ER PT J AU Veronikis, DK Nichols, DH Spino, C AF Veronikis, DK Nichols, DH Spino, C TI The Noble-Mengert-Fish operation - Revisited: A composite approach for persistent rectovaginal fistulas and complex perineal defects SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 24th Scientific Meeting of the Society-of-Gynecologic-Surgeons CY MAR 02-04, 1998 CL LAKE BUENA VISTA, FLORIDA SP Soc Gynecol Surgeons DE primary rectovaginal fistula; recurrent or persistent rectovaginal fistula; "cloaca-like" defects; fecal incontinence; complex perineal defects; site-specific defect classification ID REPAIR AB OBJECTIVE: Our aims were to evaluate the full-thickness anterior rectal wail advancement flap in the treatment of primary and recurrent or persistent rectovaginal fistulas, evaluate the surgical exposure for composite repair of site-specific perineal defects, and categorize clinical manifestations of site-specific perineal defects caused by obstetric injury. STUDY DESIGN:This is a prospective study of all patients with fecal incontinence from rectovaginal septal defects and complex perineal obstetric injuries treated by the Noble-Mengert-Fish operation. RESULTS: Thirty-four patients were classified into groups on the basis of site-specific perineal defects. Anatomic success was 94.2%. Functional success was excellent in 76.5%, good in 14.7%, fair in 5.9%, and poor in 2.9%. CONCLUSION: The Noble-Mengert-Fish operation is effective for primary and recurrent or persistent rectovaginal fistulas. The circumanal surgical exposure permits concomitant repair of all perineal defects. C1 St Johns Mercy Med Ctr, Dept Obstet & Gynecol, Sect Urogynecol Reconstruct Plast Surg, St Louis, MO 63141 USA. Brown Univ, Sch Med, Women & Infants Hosp, Dept Obstet & Gynecol,Div Urogynecol Reconstruct, Providence, RI 02912 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Urogynecol Reconstruct Pelv Surg, Vincent Mem Obstet & Gynecol, Boston, MA USA. RP Veronikis, DK (reprint author), St Johns Mercy Med Ctr, Dept Obstet & Gynecol, Sect Urogynecol Reconstruct Plast Surg, 621 S New Ballas Rd,Suite 2002-B, St Louis, MO 63141 USA. NR 19 TC 6 Z9 7 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 1998 VL 179 IS 6 BP 1411 EP 1416 DI 10.1016/S0002-9378(98)70003-1 PN 1 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 151CD UT WOS:000077702500004 PM 9855574 ER PT J AU Taylor, AE AF Taylor, AE TI Understanding the underlying metabolic abnormalities of polycystic ovary syndrome and their implications SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT Conference on Polycystic Ovary Syndrome - Metabolic Challenges and New Treatment Options CY MAY 10, 1998 CL NEW ORLEANS, LOUISIANA SP UMDNJ Robert Wood Johnson Med Sch DE cardiovascular risk factors; insulin resistance; obesity; polycystic ovary syndrome ID BODY-FAT DISTRIBUTION; IMPAIRED GLUCOSE-TOLERANCE; HORMONE-BINDING GLOBULIN; CORONARY-ARTERY DISEASE; DEPENDENT DIABETES-MELLITUS; ADIPOSE-TISSUE DISTRIBUTION; INSULIN-RECEPTOR GENE; HYPERANDROGENIC WOMEN; RISK-FACTORS; POSTPRANDIAL THERMOGENESIS AB Women with polycystic ovary syndrome have an increased rate of obesity, with a propensity toward abdominal deposition of body fat. Independent of obesity, at least half of affected women have insulin resistance. To understand the mechanisms of insulin resistance in polycystic ovary syndrome, it is necessary to understand normal insulin signaling. Women with polycystic ovary syndrome have normal binding of insulin to its receptor but have decreased activation of events downstream of the receptor. This insulin resistance occurs mostly in the peripheral tissues (muscle and fat cells), and results in increased pancreatic insulin secretion to maintain normal glucose levels. Obese women with polycystic ovary syndrome have a relative defect in insulin secretion. At least 20% of obese patients with polycystic ovary syndrome have glucose intolerance or diabetes, versus about 5% of the healthy age-matched population. Obesity and insulin resistance probably increase the risk of cardiovascular disease in women with polycystic ovary syndrome. The metabolic features of polycystic ovary syndrome are important health risk factors and need to be considered seriously, even if the patient seeks treatment for other concerns. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Taylor, AE (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, 55 Fruit St,BHX-5, Boston, MA 02114 USA. NR 65 TC 15 Z9 15 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 1998 VL 179 IS 6 SU S BP S94 EP S100 DI 10.1016/S0002-9378(98)70239-X PN 2 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 154MT UT WOS:000077893400003 PM 9855615 ER PT J AU Gukovsky, I Gukovskaya, AS Blinman, TA Zaninovic, V Pandol, SJ AF Gukovsky, I Gukovskaya, AS Blinman, TA Zaninovic, V Pandol, SJ TI Early NF-kappa B activation is associated with hormone-induced pancreatitis SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE pancreatic acinar cell; interleukin-6; KC; I kappa B ID NECROSIS-FACTOR-ALPHA; TRANSCRIPTION FACTOR; GENE-EXPRESSION; INFLAMMATORY MEDIATORS; OXYGEN RADICALS; ACINAR-CELLS; MECHANISM; BINDING; INTERLEUKIN-8; CYTOKINES AB Inflammation and cell death are critical to pathogenesis of acute pancreatitis. Here we show that transcription factor nuclear factor-kappa B (NF-kappa B), which regulates these processes, is activated and plays a role in rat cerulein pancreatitis. NF-kappa B was strongly activated in the pancreas within 30 min of cerulein infusion; a second phase of NF-kappa B activation was prominent at 3-6 h. This biphasic kinetics could result from observed transient degradation of the inhibitory protein I kappa B alpha and slower but sustained degradation of I kappa B beta. The hormone also caused NF-kappa B translocation and I kappa B degradation in vitro in dispersed pancreatic acini. Both p65/p50 and p50/p50, but not c-Rel, NF-kappa B complexes were manifest in pancreatitis and in isolated acini. Coinfusion of CCK JMV-180, which abolishes pancreatitis, prevented cerulein-induced NF-kappa B activation. The second but not early phase of NF-kappa B activation was inhibited by a neutralizing tumor necrosis factor-alpha antibody. Antioxidant N-acetylcysteine (NAC) blocked NF-kappa B activation and significantly improved parameters of pancreatitis. In particular, NAC inhibited intrapancreatic trypsin activation and mRNA expression of cytokines interleukin-6 and KC, which were dramatically induced by cerulein. The results suggest that NF-kappa B activation is an important early event that may contribute to inflammatory and cell death responses in acute pancreatitis. C1 W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Dept Surg, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA 90073 USA. RP Gukovsky, I (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Med, Bldg 258,Rm 340,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 56 TC 167 Z9 178 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD DEC PY 1998 VL 275 IS 6 BP G1402 EP G1414 PG 13 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 151XR UT WOS:000077746400024 PM 9843778 ER PT J AU Schulze-Lohoff, E Hugo, C Rost, S Arnold, S Gruber, A Brune, B Sterzel, RB AF Schulze-Lohoff, E Hugo, C Rost, S Arnold, S Gruber, A Brune, B Sterzel, RB TI Extracellular ATP causes apoptosis and necrosis of cultured mesangial cells via P2Z/P2X(7) receptors SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE purinergic receptors; nucleotides; tumor suppressor p53 ID GLOMERULAR CELLS; P-2Z RECEPTOR; IN-VITRO; DEATH; P53; PROLIFERATION; P2X(7); RAT; PURINOCEPTORS; FIBROBLASTS AB Mesangial cells undergo cell death both by apoptosis and necrosis during glomerular disease. Since nucleotides are released from injured and destroyed cells in the glomerulus, we examined whether extracellular ATP and its receptors may regulate cell death of cultured mesangial cells. Addition of extracellular ATP (300 mu M to 5 mM) to cultured rat mesangial cells for 90 min caused a 5.8-fold increase in DNA fragmentation (terminal deoxynucleotidyl transferase assay) and a 4.2-fold increase in protein levels of the tumor suppressor p53, which is thought to regulate apoptosis. Apoptotic DNA fragmentation was confirmed by the diphenylamine assay and by staining with the DNA-specific fluorochrome Hoechst 33258. The necrotic markers, release of lactate dehydrogenase and uptake of trypan blue, were not positive before 3 h of ATP addition. The effects of ATP on DNA fragmentation and p53 expression were reproduced by the purinergic P2Z/P2X(7) receptor agonist, 3'-O-(4-benzoylbenzoyl)-ATP, and inhibited by the P2Z/P2X(7) receptor blocker, oxidized ATP. Transcripts encoding the P2Z/P2X(7) receptor were expressed by cultured mesangial cells as determined by Northern blot analysis. P2Z/P2X(7) receptor-associated pore formation in the plasma membrane was demonstrated by the Lucifer yellow assay. We conclude that activation of P2Z/P2X(7) receptors by extracellular ATP causes apoptosis and necrosis of cultured mesangial cells. Activation of purinergic P2Z/P2X(7) receptors may play a role C1 Univ Erlangen Nurnberg, Med Klin 4, Nephrol Lab, D-91054 Erlangen, Germany. RP Schulze-Lohoff, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Rm 4002,149 13th St, Charlestown, MA 02129 USA. NR 45 TC 123 Z9 124 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD DEC PY 1998 VL 275 IS 6 BP F962 EP F971 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 151XX UT WOS:000077746900014 PM 9843914 ER PT J AU Witzgall, R Obermuller, N Bolitz, U Calvet, JP Cowley, BD Walker, C Kriz, W Gretz, N Bonventre, JV AF Witzgall, R Obermuller, N Bolitz, U Calvet, JP Cowley, BD Walker, C Kriz, W Gretz, N Bonventre, JV TI Kid-1 expression is high in differentiated renal proximal tubule cells and suppressed in cyst epithelia SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE renal development; renal cell carcinoma; polycystic kidney disease; gene regulation; transcriptional repression ID POLYCYSTIC KIDNEY-DISEASE; TRANSCRIPTION FACTOR; UROGENITAL DEVELOPMENT; GENE-EXPRESSION; MURINE MODEL; TSC2 GENE; RAT MODEL; EKER RAT; PROTEINS; MOUSE AB The cDNA coding for the transcriptional repressor protein Kid-1 was cloned in a screen for zinc finger proteins, which are regulated during renal development and after renal ischemia. Kid-1 mRNA levels increase in the course of postnatal renal development and decrease after acute renal injury caused by ischemia or administration of folic acid. We have raised a monoclonal anti-Kid-1 antibody and demonstrate that the Kid-1 protein is strongly expressed in the proximal tubule of the adult rat kidney. During nephron development, the Kid-1 protein appears after the S-shaped body stage concomitantly with the brush-border enzyme alkaline phosphatase. In two animal models of polycystic kidney disease, the expression of Kid-1 is downregulated. The loss of expression of Kid-1 in cyst wall cells correlates with the loss of alkaline phosphatase histochemical staining. Kid-1 mRNA levels are also reduced in rodent renal cell carcinomas, another condition characterized by epithelial cell dedifferentiation and increased proliferation. We propose that Kid-1 plays an important role during the differentiation of the proximal tubule. C1 Univ Heidelberg, Inst Anat & Cell Biol 1, D-69120 Heidelberg, Germany. Univ Heidelberg, Klinikum Mannheim, Med Res Ctr, D-68167 Mannheim, Germany. Univ Kansas, Med Ctr, Kansas City, KS 66160 USA. Univ Texas, Md Anderson Canc Ctr, Smithville, TX 78957 USA. Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Witzgall, R (reprint author), Univ Heidelberg, Inst Anat & Cell Biol 1, Neuenheimer Feld 307, D-69120 Heidelberg, Germany. FU NIDDK NIH HHS [DK-39773] NR 41 TC 13 Z9 13 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD DEC PY 1998 VL 275 IS 6 BP F928 EP F937 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 151XX UT WOS:000077746900010 PM 9843910 ER PT J AU Oelberg, DA Kacmarek, RM Pappagianopoulos, PP Ginns, LC Systrom, DM AF Oelberg, DA Kacmarek, RM Pappagianopoulos, PP Ginns, LC Systrom, DM TI Ventilatory and cardiovascular responses to inspired He-O-2 during exercise in chronic obstructive pulmonary disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID SKELETAL-MUSCLE METABOLISM; LUNG-DISEASE; RESPIRATORY-FAILURE; AIRWAY-OBSTRUCTION; UPRIGHT EXERCISE; LACTIC-ACIDOSIS; HELIUM-OXYGEN; IMPAIRMENT; COPD; HEMODYNAMICS AB Blunted maximum cardiac output and systemic OZ extraction could constitute primary limits to exercise in severe chronic obstructive pulmonary disease (COPD) or they could simply reflect cessation of exercise because of abnormal pulmonary mechanics. To determine which is the case, eight consecutive patients with severe COPD (FEV1 = 0.56 +/- 0.04 L, mean +/- SEM), five of whom had alpha 1-antiprotease deficiency, performed two incremental cycling tests while breathing N-2-O-2 or He-O-2. Expired gases and (V) over dotE were measured, and radial and pulmonary arterial blood was simultaneously sampled each minute. Peak exercise (V) over dotE was higher with He-O-2 than with N-2-O-2 (25.5 +/- 2.2 versus 19.3 +/- 1.5 L/min, p = 0.002) and Pa-CO2 was lower (42 +/- 2 versus 46 +/- 2 mm Hg, p = 0.0003). (V) over dot O(2)max improved only modestly (594 +/- 75 versus 514 +/- 54 ml/min, p = 0.04), and was accompanied by an increase in peak exercise Ca-O2 (18.7 +/- 0.9 versus 17.6 +/- 0.9 ml/dl, p = 0.02). Peak Fick cardiac output was decreased (39 +/- 3% pred) and C (V) over bar(O2), was elevated (130 +/- 10% pred), and neither improved with He-OZ (p > 0.05 for each). Abnormal peak exercise cardiac output and systemic O-2 extraction in severe COPD cannot be fully accounted for by limiting pulmonary mechanics and may contribute to exercise Intolerance. C1 Harvard Univ, Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Resp Care Serv, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Systrom, DM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Pulm & Crit Care Unit, Bulfinch 148,32 Fruit St, Boston, MA 02114 USA. NR 39 TC 41 Z9 41 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC PY 1998 VL 158 IS 6 BP 1876 EP 1882 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 147RP UT WOS:000077511800028 PM 9847281 ER PT J AU Morrell, MJ Arabi, Y Zahn, B Badr, MS AF Morrell, MJ Arabi, Y Zahn, B Badr, MS TI Progressive retropalatal narrowing preceding obstructive apnea SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID AIRWAY CLOSING PRESSURES; SLEEP-APNEA; LUNG-VOLUME; NORMAL MEN; OCCLUSION; PATHOGENESIS; VELOPHARYNX; RESISTANCE; PATENCY; PHARYNX AB Pharyngeal occlusion during obstructive apnea is thought to be an inspiratory-related event; however, occlusion also occurs in the absence of negative intrathoracic pressure. We hypothesized that inspiratory-related pharyngeal occlusion would be preceded by significant expiratory narrowing. Eight sleeping patients with obstructive apnea were studied. Pharyngeal caliber, airflow, and esophageal pressure (Pes) were simultaneously monitored during three to four consecutive breaths preceding occlusion (between 3 and 22 events were studied per subject). Relative changes in retropalatal airway cross-sectional area (CSA) were determined from fiberoptic images (five frames per second) normalized to the maximum CSA. During inspiration, CSA was significantly reduced only during the breath immediately preceding the apnea (Group mean CSA +/- SEM: 51 +/- 8% at the start of inspiration compared with 37 +/- 8% at midinspiration). During expiration, for all breaths there was an initial significant increase in CSA compared with the nadir CSA during the preceding inspiration (CSA: breath-3, 57 +/- 10% to 79 +/- 3%; breath-2, 59 +/- 8% to 76 +/- 4%; breath-1, 37 +/- 8% to 64 +/- 8%), followed by a significant narrowing at end-expiration compared with the peak CSA during that expiration (CSA: breath-3, 79 +/- 3% to 62 +/- 6%; breath-2, 76 +/- 4% to 50 +/- 10%; breath-1, 64 +/- 8% to 36 +/- 10%). Occlusion occurred at a pressure significantly less than that generated during the previous unoccluded breath (Pes: breath-1, -10.8 +/- 2.9 cm H2O; occlusion, -8.2 +/- 1.9 cm H2O). These results show that expiratory narrowing produced a significant reduction of CSA at end-expiration prior to obstructive apnea. C1 Univ Wisconsin, William S Middleton Mem Vet Hosp, Dept Med, Madison, WI 53706 USA. Univ Wisconsin, Sch Med, Dept Prevent Med, John Rankin Lab Pulm Med, Madison, WI 53706 USA. RP Morrell, MJ (reprint author), Royal Brompton Hosp, Imperial Coll Sch Med, Natl Heart & Lung Inst, Sleep & Ventilat Unit, S Block,Sydney St, London SW3 6NP, England. NR 33 TC 70 Z9 71 U1 0 U2 2 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC PY 1998 VL 158 IS 6 BP 1974 EP 1981 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 147RP UT WOS:000077511800042 PM 9847295 ER PT J AU Thrall, JH AF Thrall, JH TI Directions in radiology for the next millennium SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Massachusetts Gen Hosp, Dept Radiol, MZ-FND 216,14 Fruit St, Boston, MA 02114 USA. NR 10 TC 8 Z9 9 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 1998 VL 171 IS 6 BP 1459 EP 1462 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 140XB UT WOS:000077114000003 PM 9843271 ER PT J AU Bowers, SP Pearlman, NW McIntyre, RC Finlayson, CA Huerd, S AF Bowers, SP Pearlman, NW McIntyre, RC Finlayson, CA Huerd, S TI Cost-effective management of gynecomastia SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT Southwestern-Surgical-Congress 50th Annual Meeting CY APR 19-22, 1998 CL SAN ANTONIO, TEXAS SP SW Surg Congress ID IDIOPATHIC GYNECOMASTIA; CELL TUMORS; MEN AB BACKGROUND: Routine endocrine screening of idiopathic gynecomastia has been advocated, but may not be cost effective. We carried out a cost-benefit analysis of this approach. METHODS: A retrospective study (1992 to 1997) of 87 adult males with symptomatic gynecomastia was performed. RESULTS: Thirty-four (39%) patients had extrinsic causes; 53 (61%) were considered idiopathic. Forty-five idiopathic cases underwent endocrine testing: beta human chorionic gonadotropin alone, 16; and beta human chorionic gonadotropin, LH, estradiol, testosterone +/- testicular ultrasound, 29. One (2%) occult Leydig cell testicular tumor was detected. Forty-four patients had normal studies and remain well after local excision. CONCLUSION: Routine endocrine evaluation of idiopathic gynecomastia is rarely productive; such testing is best done selectively. Am J Surg. 1998;176:638-641. (C) 1998 by Excerpta Medica, Inc. C1 Univ Colorado, Hlth Sci Ctr, Dept Surg, Denver, CO 80262 USA. Denver VA Med Ctr, Denver, CO USA. RP Pearlman, NW (reprint author), Univ Hosp, Dept Surg, Box C311,4200 E 9th Ave, Denver, CO 80262 USA. NR 19 TC 21 Z9 23 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD DEC PY 1998 VL 176 IS 6 BP 638 EP 640 DI 10.1016/S0002-9610(98)00281-5 PG 3 WC Surgery SC Surgery GA 159FG UT WOS:000078160800082 PM 9926805 ER PT J AU Dull, RO Peterfreund, RA AF Dull, RO Peterfreund, RA TI Variations in the composition of spinal anesthetic solutions: The effects of drug addition order and preparation methods SO ANESTHESIA AND ANALGESIA LA English DT Article; Proceedings Paper CT 48th Annual Meeting of American-Society-of-Anesthesiologists CY OCT 16-23, 1997 CL SAN DIEGO, CA SP Amer Soc Anesthesiol ID CESAREAN-SECTION; INTRATHECAL FENTANYL; PROLONGING RECOVERY; EPINEPHRINE; BUPIVACAINE; LIDOCAINE; ANALGESIA; MORPHINE; SUFENTANIL; TETRACAINE AB Adjuvants such as opioids or epinephrine are commonly added in small volumes to multicomponent spinal anesthetic solutions. In this study, we tested the hypothesis that final adjuvant concentrations vary depending on the devices and techniques used to prepare the anesthetic solution. We compared two aspiration devices, the filter needle and the filter straw, in a laboratory study. Two techniques for drawing up and estimating adjuvant volumes were assessed, as was variation in the composition of a model spinal anesthetic solution resulting from intra- and interindividual variability. A model hyperbaric anesthetic solution consisting of tetracaine, dextrose, and methylene blue (MB) as a small-volume tracer solution was studied. The components were drawn up into a syringe through one of two commercially supplied aspiration devices, a filter straw or a filter needle. The effect of the order of aspiration of the components into the syringe was measured by determining the MB concentration in the final solution by optical absorbance. Ten experienced anesthesiologists then prepared samples of the test solution using one of two different techniques to estimate tracer volume in the aspiration syringe. In comparison studies, the MB tracer was added to the hyperbaric solution with a tuberculin syringe. The order of aspiration of the solution components had a large effect on the final concentration of the MB tracer in the ultimate mixture. Variation in the MB concentration was on the order of four- to fivefold. Effects were larger for the filter straw compared with the filter needle. A comparison of 10 anesthesiologists revealed large intra- and interindividual variations in the final composition of the model anesthetic solution. The concentration of tracer added to the mixture with a tuberculin syringe approximated the planned yield. We conclude that the devices and techniques used to prepare mixtures of drugs for delivery to the cerebrospinal fluid may influence the concentrations of drugs in the anesthetic and, thus, the dose supplied to the patient receiving spinal anesthesia. Variation in clinical effects of spinal anesthetics may be attributable, in part, to variation in the composition of the anesthetic. Implications: This laboratory study demonstrates the potential for large variation in the composition of spinal anesthetic mixtures. C1 Harvard Univ, Dept Anesthesia & Crit Care, Clin 314D, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA. RP Harvard Univ, Dept Anesthesia & Crit Care, Clin 314D, Massachusetts Gen Hosp,Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM Peterfreund@etherdome.mgh.harvard.edu NR 27 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD DEC PY 1998 VL 87 IS 6 BP 1326 EP 1330 DI 10.1097/00000539-199812000-00021 PG 5 WC Anesthesiology SC Anesthesiology GA 142AP UT WOS:000077178000021 PM 9842821 ER PT J AU Abdi, S Lee, DH Chung, JM AF Abdi, S Lee, DH Chung, JM TI The anti-allodynic effects of amitriptyline, gabapentin, and lidocaine in a rat model of neuropathic pain SO ANESTHESIA AND ANALGESIA LA English DT Article ID TACTILE ALLODYNIA; HYPERALGESIA; INJECTIONS; NEURONS AB The management of patients with neuropathic pain is challenging. There are only a few reports regarding the acute effects of the commonly used adjuvant drugs amitriptyline (AMI), gabapentin (GBP), and lidocaine (LDC) on neuropathic pain behaviors in animal models. Thus, the purpose of this study was to investigate the acute effects of AMI, GBP, and LDC on behavioral signs of mechanical allodynia and the site of action of these drugs using a rat model of neuropathic pain. Under general anesthesia with halothane, neuropathic injury was produced in rats by tightly ligating the left L5 and L6 spinal nerves. In Experiment 1,baseline mechanical allodynia data were recorded, and the animals were randomly divided into five groups: Group 1 received saline intraperitoneally (IP), Group 2 received AMI (1.5 mg/kg TP); Group 3 received GBP (50 mg/kg IP), Group 4 received an IV saline infusion for 10 min, and Group 5 received LDC (10-mg/kg IV infusion) for 10 min. Measurements of mechanical allodynia were repeated 0.5, 1, 2, and 4 h and 1, 3, and 7 days after treatment. In Experiment 2, rats were prepared similarly to the first experiment, and a single unit activity of continuous discharges of injured afferent fibers was recorded from the left L5 fascicles before and until 1 h after treatment. All animals developed neuropathic pain behavior within 7 days after surgery. All three tested drugs were effective in increasing the threshold for mechanical allodynia as early as 30 min after treatment, and the effect lasted for at least 1 h. Furthermore, AMI and LDC reduced the rate of continuing discharges of injured afferent fibers, whereas GBP did not influence these discharges. Our findings clearly demonstrate an attenuation of neuropathic pain behavior in rats treated with AMI, GBP, or LDC. Finally, the site of action of LDC seems to be primarily in the periphery, and that of GBP is exclusively central, whereas that of AMI seems to have both peripheral and central components. Implications: In the present study, we examined the effectiveness of three drugs commonly used for the treatment of neuropathic pain. Systemic injections of amitriptyline, gabapentin, or lidocaine produced pain-relieving effects in this established model for neuropathic pain in rats, which supports their clinical use in managing patients with neuropathic pain syndromes. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Univ Texas, Med Branch, Dept Anesthesia, Galveston, TX 77550 USA. Univ Texas, Med Branch, Dept Anat & Neurosci, Galveston, TX 77550 USA. Univ Texas, Med Branch, Dept Physiol, Galveston, TX 77550 USA. Univ Texas, Med Branch, Dept Biophys, Galveston, TX 77550 USA. Univ Texas, Med Branch, Inst Marine Biomed, Galveston, TX 77550 USA. RP Abdi, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 32 Fruit St, Boston, MA 02114 USA. EM abdi@etherdome.mgh.harvard.edu FU NINDS NIH HHS [NS 31680, NS 11255] NR 32 TC 188 Z9 191 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD DEC PY 1998 VL 87 IS 6 BP 1360 EP 1366 DI 10.1097/00000539-199812000-00027 PG 7 WC Anesthesiology SC Anesthesiology GA 142AP UT WOS:000077178000027 PM 9842827 ER PT J AU Schwartz, MD Lerman, C Audrain, J Cella, D Rimer, B Stefanek, M Garber, J Lin, TH Vogel, V AF Schwartz, MD Lerman, C Audrain, J Cella, D Rimer, B Stefanek, M Garber, J Lin, TH Vogel, V TI The impact of a brief problem-solving training intervention for relatives of recently diagnosed breast cancer patients SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article ID PSYCHOLOGICAL DISTRESS; UNIPOLAR DEPRESSION; RANDOMIZED TRIAL; FAMILY HISTORY; RISK; WOMEN; STRESS; SYMPTOMS; ADHERENCE; THERAPY AB Previous studies have found high levels of psychological distress in women who have a family history of breast cancer We evaluated a brief Problem-Solving Training (PST) intervention designed to reduce distress among women with a first-degree relative recently diagnosed with this disease. Participants were randomly assigned to either the PST group (N = 144) or a General Health Counseling (GHC) control group (N = 197). At baseline, these groups did not differ on any sociodemographic, risk factor or psychological distress variables. We evaluated the impact of PST relative to GHC, at the three-month follow-lip assessment using a 2 (treatment group) x 2 (time of assessment) mixed factor analysis of variance (ANOVA). Although there were significant decreases in both cancer-specific and general distress in both the PST and GHC groups, the magnitude of these decreases did not differ However when PST participants were divided into those who regularly practiced the PST techniques and those who did not, significant differences emerged. Participants who regularly practiced the PST techniques had significantly greater decreases in cancer-specific distress [Impact of Event Scale (IEs) intrusion and avoidance subscales] compared to infrequent practicers and GHC participants. Effects on general distress were not found. Additional studies are needed to identify ways to promote the practice of PST techniques and to evaluate other psychosocial interventions for female relatives of breast cancer patients. C1 Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Duke Univ, Ctr Comprehens Canc, Durham, NC 27706 USA. Univ Maryland, Med Ctr, College Pk, MD 20742 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA. RP Schwartz, MD (reprint author), Georgetown Univ, Med Ctr, 2233 Wisconsin Ave NW,Suite 535, Washington, DC 20007 USA. FU NCI NIH HHS [KO7 CA65597, R01 CA63605] NR 27 TC 37 Z9 38 U1 1 U2 4 PU SOC BEHAVIORAL MEDICINE PI MIDDLETON PA 7611 ELMWOOD AVE, STE 201, MIDDLETON, WI 53562-3161 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD WIN PY 1998 VL 20 IS 1 BP 7 EP 12 DI 10.1007/BF02893803 PG 6 WC Psychology, Multidisciplinary SC Psychology GA 116TW UT WOS:000075741800002 PM 9755346 ER PT J AU Hooper, DC AF Hooper, DC TI Expanding uses of fluoroquinolones: Opportunities and challenges SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID COMMUNITY-ACQUIRED PNEUMONIA; INFECTIONS; MULTICENTER; RESISTANCE; ADULTS C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. NR 20 TC 33 Z9 33 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 1 PY 1998 VL 129 IS 11 BP 908 EP 910 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 143DF UT WOS:000077239200012 PM 9867736 ER PT J AU Barry, MJ AF Barry, MJ CA Patient Outcomes Res Team Prostatic Dis TI PSA screening for prostate cancer: The current controversy - a viewpoint SO ANNALS OF ONCOLOGY LA English DT Article DE mass screening; prostatic neoplasia; prostate-specific antigen ID RADICAL PROSTATECTOMY; STAGE-I; ANTIGEN; TRIAL AB Prostate cancer is an important health problem. Randomized trials have not yet proven whether or not screening with prostate-specific antigen measurements reduces morbidity or mortality. The potential for overtreatment of prostate cancers not destined to cause future mortality, the uncertainty about the benefits of aggressive treatment of screen-detected cancers, and the relatively high costs of prostate cancer screening programs are all areas of concern. A shared approach to decisions about screening individual patients pending better evidence is one strategy for clinicians to consider in dealing with this controversial problem. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Med Unit, Boston, MA 02114 USA. RP Barry, MJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Med Unit, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM barry.michael@mgh.harvard.edu FU AHRQ HHS [HS08397] NR 20 TC 19 Z9 19 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 1998 VL 9 IS 12 BP 1279 EP 1282 PG 4 WC Oncology SC Oncology GA 162EC UT WOS:000078331700010 PM 9932155 ER PT J AU Goodman, CM Cohen, V Thornby, J Netscher, D AF Goodman, CM Cohen, V Thornby, J Netscher, D TI The life span of silicone gel breast implants and a comparison of mammography, ultrasonography, and magnetic resonance imaging in detecting implant rupture: A meta-analysis SO ANNALS OF PLASTIC SURGERY LA English DT Article ID DIAGNOSIS; SONOGRAPHY; ULTRASOUND; TISSUE; MR AB Because of the growing concern surrounding the integrity and life span of silicone gel breast implants and the reported variations in the diagnostic accuracy of various imaging techniques in identifying ruptured implants, the authors undertook a meta-analysis of articles in the scientific literature to examine these concerns. They were able to include reports from the literature that detailed the condition and removal of 1,099 breast implants during the past 7 years. The median life span of a silicone gel implant was estimated to be 16.4 years. Of the implants, 79.1% were intact at 10 years, falling to 48.7% by 15 years. The sensitivities and specificities of three imaging modalities used in the diagnosis of implant rupture (mammography, ultrasonography, and magnetic resonance imaging [MRI]) were also evaluated and compared statistically in an effort to discover which of the three techniques might serve as the most reliable screening tool in the diagnosis of gel implant rupture. The sensitivity of mammography for finding a ruptured implant is 28.4% with a specificity of 92.9%. Ultrasonography has a sensitivity and specificity of 59.0% and 76.8% respectively compared with MRI, which was 78.1% and 80.0% respectively. For implants in place for 10 years, one would need to image 3.3 implants by ultrasound to identify a single possible rupture. However, because of the 76.8% specificity, 8.1 implants would need to be imaged to find a confirmed intraoperative rupture. This was similar to MRI, in which 3.1 implants would need to be imaged to detect one suspected rupture, and 6.1 implants would need to be imaged to find one intraoperatively confirmed rupture. The authors do not recommend either ultrasound or MRI as a screening tool based on their meta-analysis. C1 Baylor Coll Med, Div Plast Surg, Houston, TX 77030 USA. Dept Vet Affairs Med Ctr, Houston, TX USA. RP Netscher, D (reprint author), 6560 Fannin,Suite 800, Houston, TX 77030 USA. NR 26 TC 34 Z9 34 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD DEC PY 1998 VL 41 IS 6 BP 577 EP 585 DI 10.1097/00000637-199812000-00001 PG 9 WC Surgery SC Surgery GA 147DT UT WOS:000077473500001 PM 9869129 ER PT J AU Mathisen, DJ Kuo, EY Hahn, CW Moncure, AC Wain, JC Grillo, HC Hurford, WE Wright, CD AF Mathisen, DJ Kuo, EY Hahn, CW Moncure, AC Wain, JC Grillo, HC Hurford, WE Wright, CD TI Inhaled nitric oxide for adult respiratory distress syndrome after pulmonary resection SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 26-28, 1998 CL NEW ORLEANS, LOUISIANA SP Soc Thorac Surgeons ID LUNG RESECTION; EDEMA AB Background. The adult respiratory distress syndrome (ARDS) developing after pulmonary resection is usually a lethal complication. The etiology of this serious complication remains unknown despite many theories. Intubation, aspiration bronchoscopy, antibiotics, and diuresis have been the mainstays of treatment. Mortality rates from ARDS after pneumonectomy have been reported as high as 90% to 100%. Methods. In 1991, nitric oxide became clinically available. We instituted an aggressive program to treat patients with ARDS after pulmonary resection. Patients were intubated and treated with standard supportive measures plus inhaled nitric oxide at 10 to 20 parts/million. While being ventilated, all patients had postural changes to improve ventilation/perfusion matching and management of secretions. Systemic steroids were given to half of the patients. Results. Ten consecutive patients after pulmonary resection with severe ARDS (ARDS score = 3.1 +/- 0.04) were treated. The mean ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen at initiation of treatment was 95 +/- 13 mm Hg (mean +/- SEM) and improved immediately to 128 +/- 24 mm Hg, a 31% +/- 8% improvement (p < 0.05). The ratio improved steadily over the ensuing 96 hours. Chest x-rays improved in all patients and normalized in 8. No adverse reactions to nitric oxide were observed. Conclusions. We recommend the following treatment regimen for this lethal complication: intubation at the first radiographic sign of ARDS; immediate institution of inhaled nitric oxide (10 to 20 parts per million); aspiration bronchoscopy and postural changes to improve management of secretions and ventilation/perfusion matching; diuresis and antibiotics; and consideration of the addition of intravenous steroid therapy. (C) 1998 by The Society of Thoracic Surgeons. C1 Massachusetts Gen Hosp, Div Gen Thorac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. RP Mathisen, DJ (reprint author), Massachusetts Gen Hosp, Div Gen Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 21 TC 27 Z9 33 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 1998 VL 66 IS 6 BP 1894 EP 1901 DI 10.1016/S0003-4975(98)01167-9 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 161NG UT WOS:000078294900007 PM 9930465 ER PT J AU Borodyansky, L Li, YZ Pardee, AB Li, CJ AF Borodyansky, L Li, YZ Pardee, AB Li, CJ TI Apoptosis in non-proliferating cells: implications for viral infection and tumourigenesis SO APOPTOSIS LA English DT Article DE AIDS; apoptosis; cell cycle; cell quiescence; HIV-1 infection; tumourigenesis ID C-MYC; GROWTH-FACTOR; HIV-1 INFECTION; TAT PROTEIN; ACTIVATION; FIBROBLASTS; LYMPHOCYTES; INDUCTION; DEATH; MACROPHAGES AB To date much attention has been focused on regulation of apoptosis in proliferating cells. However, recent evidence shows that regulation of apoptosis in quiescent tissue plays an important role in homeostasis of the organism. This review examines the implications of apoptosis of quiescent cells for both tumourigenesis and viral infection such as HIV. In this article we propose a dual role for cellular activation in the homeostasis regulation. In this model cellular mitogens not only activate quiescent cells into the active cell cycle, but under certain conditions, loss of quiescence may result in apoptosis. The loss of quiescence-associated apoptosis may play a significant role in tumourigenesis and viral infections. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Cell Growth & Regulat, Boston, MA 02115 USA. RP Li, CJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Cell Growth & Regulat, 44 Binney St, Boston, MA 02115 USA. NR 33 TC 2 Z9 2 U1 0 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1360-8185 J9 APOPTOSIS JI Apoptosis PD DEC PY 1998 VL 3 IS 6 BP 381 EP 385 DI 10.1023/A:1009693517181 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 215XA UT WOS:000081407700001 PM 14646470 ER PT J AU Bigby, M AF Bigby, M TI Snake oil for the 21st century SO ARCHIVES OF DERMATOLOGY LA English DT Article ID CONTROLLED CLINICAL-TRIAL; CARBON-DIOXIDE LASER; HYPERTROPHIC SCARS; SILICONE GEL; DOUBLE-BLIND; KELOIDS; CIMETIDINE; THERAPY; WARTS; CONDYLOMATA AB Dermatology has been associated with quackery for at least a century. The dictionary defines a quack as "a pretender to medical knowledge or skill; ignorantly or falsely pretending to cure."(1) The term quack is derived from quacksalver, or one who quacks like a duck in promoting his salves.' Quacksalvers hacked many potions, including snake oil, with claims that it cured everything from dermatitis to rheumatism. With the current promulgation of skin "products" and their promotion and even sale by dermatologists, and the use of treatments of no proven efficacy, this association between dermatology and quackery is set to continue well into the 21st century. The list of offending treatments includes silicone gel sheets and Onion extract cream (Mederma) for keloids, alpha-hydroxy acid creams and peels, topical ascorbic acid and phytonadione, "laser resurfacing," and cimetidine for warts, to name only a few. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Cutaneous Biol Res Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bigby, M (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Dermatol, Boston, MA 02115 USA. NR 24 TC 16 Z9 16 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD DEC PY 1998 VL 134 IS 12 BP 1512 EP 1514 DI 10.1001/archderm.134.12.1512 PG 3 WC Dermatology SC Dermatology GA 149TP UT WOS:000077622100002 PM 9875187 ER PT J AU Bigby, M AF Bigby, M TI Evidence-based medicine in a nutshell - A guide to finding and using the best evidence in caring for patients SO ARCHIVES OF DERMATOLOGY LA English DT Review ID TOENAIL TINEA INFECTION; USERS GUIDES; ORAL TERBINAFINE; CLINICAL-TRIALS; POSTMARKETING SURVEILLANCE; MYOCARDIAL-INFARCTION; ANTIFUNGAL AGENTS; DIAGNOSTIC-TEST; HELP ME; ONYCHOMYCOSIS AB Evidence-based medicine is the use of the best current evidence in making decisions about the care of individual patients. Practicing EBM requires recognition that in most encounters with patients, questions arise that should be answered to provide the patient with the best available medical care. Asking well-built clinical questions that contain 4 elements-a patient or problem, an intervention, a comparison intervention (if necessary), and an outcome-is an important step in practicing EBM. Once appropriate questions have been formulated, the best source for finding most types of best evidence is by searching the MEDLINE database by computer. MEDLINE searches have inherent software and operator limitations that make their reliability quite variable. One should be aware of these limitations and improve one's skills in searching. The Cochrane Collaboration Controlled Clinical Trials Registry contains more than 190 000 controlled clinical trials and is the best source of evidence about treatment. The quality (strength) of evidence is based on a hierarchy of evidence: results of systematic reviews of well-designed clinical studies, results of 1 or more well-designed clinical studies, results of large case series, expert opinion, and personal experience. Once the best evidence has been found, the EBM approach involves critically appraising the quality of the evidence, determining its magnitude and precision, and applying it to the specific patient. Guidelines to critically appraise and apply evidence are available. The clinical question, best evidence, and its critical appraisal should be saved in a format that can be easily retrieved for future use. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Dermatol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Cutaneous Biol Res Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bigby, M (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Dermatol, 330 Brookline Ave, Boston, MA 02215 USA. EM mbigby@bidmc.harvard.edu NR 79 TC 41 Z9 41 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD DEC PY 1998 VL 134 IS 12 BP 1609 EP 1618 DI 10.1001/archderm.134.12.1609 PG 10 WC Dermatology SC Dermatology GA 149TP UT WOS:000077622100018 PM 9875202 ER PT J AU Rumelt, S Hogan, NR Rubin, PAD Jakobiec, FA AF Rumelt, S Hogan, NR Rubin, PAD Jakobiec, FA TI Four-eyelid sebaceous cell carcinoma following irradiation SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID OCULAR ADNEXA; GLAND AB Background: Sebaceous cell carcinoma is a distinctive tumor of the eyelid associated with a high rate of metastasis and mortality. Involvement of both upper and lower lids has been described; however, involvement of all 4 eyelids is extremely rare. Objective: To describe the evaluation and diagnosis of the clinicopathologic features in a 74-year-old patient with 4-eyelid sebaceous carcinoma and a history of whole face irradiation for eczema. Methods: Bilateral eyelid, conjunctiva, map, and fine needle biopsy of enlarged, submandibular lymph node specimens were stained with hematoxylin-eosin and oil-red-O for light microscopy and fresh-frozen sections were evaluated by electron microscopy. Results: The biopsy specimens from the eyelids and conjunctiva showed sebaceous carcinoma cells in the meibomian glands and scattered within the conjunctival epithelium. The cells were moderately well differentiated. Similar cells stained with oil-red-O were found in the submandibular lymph nodes. Conclusions: The appearance of bilateral sebaceous carcinoma supports the concept of simultaneous occurrence of multiple primaries in specific patients, especially after radiation therapy. Patients with a history of facial irradiation and atypical eyelid lesions should be evaluated for malignant tumors such as sebaceous carcinoma. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ophthalm Pathol & Oncol Unit,Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Eye Plast Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Orbit Ctr, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ophthalm Pathol & Oncol Unit,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 10 TC 14 Z9 14 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD DEC PY 1998 VL 116 IS 12 BP 1670 EP 1672 PG 3 WC Ophthalmology SC Ophthalmology GA 149TT UT WOS:000077622400023 PM 9869803 ER PT J AU Shin, J AF Shin, J TI P62 and the sequestosome, a novel mechanism for protein metabolism SO ARCHIVES OF PHARMACAL RESEARCH LA English DT Review DE P62; sequestosome; ubiqitination; protein metabolism ID PHOSPHOTYROSINE-INDEPENDENT LIGAND; SH2 DOMAIN; MULTIUBIQUITIN CHAINS; BINDING PROTEINS; P56(LCK); KINASE; PROTEASOME; COMPONENT; SEQUENCE; GROWTH AB In addition to selecting proteins for degradation by the 26S proteasome, ubiqitination appears to serve other regulatory functions, including for endosomal/lysosomal targeting, protein translocation, and enzyme modification. Currently, little is known how multiubiquitin chains are recognized by these cellular mechanisms. Within the 26S proteasome, one subunit (Mcb1/S5a) has been identified that has affinity for multiubiquitin chains and may function as a ubiquitin receptor. We recently found that a non-proteasomal protein p62 also preferentially binds multiubiquitin chains and forms a novel cytoplasmic structure "sequestosome" which serves as a storage place for ubiquitinated proteins. In the present manuscript, the role and regulation of p62 in relation to the sequestosomal function will be reviewed. C1 Dana Farber Canc Inst, Div Tumor Virol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Shin, J (reprint author), Dana Farber Canc Inst, Div Tumor Virol, 44 Binney St, Boston, MA 02115 USA. NR 35 TC 77 Z9 80 U1 0 U2 0 PU PHARMACEUTICAL SOCIETY KOREA PI SEOUL PA 1489-3 SUHCHO-DONG, SUHCHO-KU, SEOUL 137-071, SOUTH KOREA SN 0253-6269 J9 ARCH PHARM RES JI Arch. Pharm. Res. PD DEC PY 1998 VL 21 IS 6 BP 629 EP 633 DI 10.1007/BF02976748 PG 5 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 148TV UT WOS:000077549800002 PM 9868528 ER PT J AU Choe, H AF Choe, H TI Chemokine receptors in HIV-1 and SIV infection SO ARCHIVES OF PHARMACAL RESEARCH LA English DT Review DE chemokine; receptor; HIV; SIV; CCR5; transmembrane segment; CXCR4 ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN; CD4-POSITIVE CELLS; T-LYMPHOCYTES; AIDS VIRUS; CCR5; TYPE-1; ENTRY; CORECEPTOR; COFACTOR AB Seven transmembrane segment (7TMS) receptors for chemokines and related molecules have been demonstrated to be essential, in addition to CD4, for HIV and SIV infection. The beta-chemokine receptor CCR5 is the primary, perhaps sole, coreceptor for HIV-1: during the early and chronic phases of infection, and supports infection by most primary HIV-1 and many SIV isolates. Late-stage primary and laboratory-adapted HIV-1, HIV-2, and SIV isolates can use other 7TMS receptors. CXCR4 appears especially important in late-stage HIV infection; several related receptors can also be used. The specificity of SIV viruses is similar. Commonalities among these receptors, combined with analyses of mutated molecules, indicate that discrete, conformationally-dependent sites on the chemokine receptors determine their association with the third variable and conserved regions of viral envelope glycoproteins. These studies are useful for elucidating the mechanism and molecular determinants of HIV-1 entry, and of inhibitors to that entry. C1 Dana Farber Canc Inst, Div Tumor Virol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Choe, H (reprint author), Dana Farber Canc Inst, Div Tumor Virol, 44 Binney St, Boston, MA 02115 USA. NR 38 TC 15 Z9 15 U1 1 U2 3 PU PHARMACEUTICAL SOCIETY KOREA PI SEOUL PA 1489-3 SUHCHO-DONG, SUHCHO-KU, SEOUL 137-071, SOUTH KOREA SN 0253-6269 J9 ARCH PHARM RES JI Arch. Pharm. Res. PD DEC PY 1998 VL 21 IS 6 BP 634 EP 639 DI 10.1007/BF02976749 PG 6 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 148TV UT WOS:000077549800003 PM 9868529 ER PT J AU Krebs, DE Jette, AM Assmann, SF AF Krebs, DE Jette, AM Assmann, SF TI Moderate exercise improves gait stability in disabled elders SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article ID NURSING-HOME RESIDENTS; OLDER PERSONS; LOCOMOTOR ACTIVITIES; REACTION-TIME; BALANCE; STRENGTH; HEALTH; MUSCLE; WOMEN; KNEE AB Background: Decreased muscle strength impedes elders' functional performance in daily activities such as gait. The mechanisms whereby increased strength improves gait are unknown. Methods: A prospective, blinded, randomized trial of moderate intensity strength exercise was conducted and its impact was measured on functional mobility during gait in 132 functionally limited elders. Lower extremity strength was measured, including hip abductor, hip extensor, and knee extensor strength. Of the 132 subjects, 120 subjects (mean age, 75.1 yrs) completed 6 months of elastic band resistance training at least 3 times a week or served as no-exercise controls. Results: Subjects increased their lower extremity strength in the exercise and control groups, by 17.6% and 7.3% (p < .01), respectively. Gait stability improved significantly more in the exercise group than in the control group (p < .05). Increases in forward gait velocity were not significantly different between groups. Peak mediolateral velocity and base of support improved in the exercise group, but not in the control group. Change in lower extremity strength correlated significantly but weakly with many of the gait variables. Conclusions: Gait stability, especially mediolateral steadiness, improved in the exercise group but not in the control group. These results show that even moderate strength gains benefit gait performance in elders and thus provide a sound basis for encouraging low-intensity strength training for elders with functional limitations. (C) 1998 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 Massachusetts Gen Hosp, Inst Hlth Profess, Biomot Lab, Boston, MA 02114 USA. Boston Univ, Coll Hlth & Rehabil Sci, Boston, MA 02215 USA. New England Res Inst, Watertown, MA 02172 USA. RP Krebs, DE (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, Biomot Lab, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. FU NIA NIH HHS [P50AG11669, R01AG12561] NR 27 TC 95 Z9 96 U1 6 U2 14 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD DEC PY 1998 VL 79 IS 12 BP 1489 EP 1495 DI 10.1016/S0003-9993(98)90408-7 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 146GW UT WOS:000077421800001 PM 9862288 ER PT J AU Allen, DN Aldarondo, F Goldstein, G Huegel, SG Gilbertson, M van Kammen, DP AF Allen, DN Aldarondo, F Goldstein, G Huegel, SG Gilbertson, M van Kammen, DP TI Construct validity of neuropsychological tests in schizophrenia SO ASSESSMENT LA English DT Article DE schizophrenia; neuropsychological tests; WAIS-R; WMS-R; WCST; CPT ID WORKING-MEMORY; ATTENTION; WAIS; PERFORMANCE; DEFICITS; TASK AB Validity studies of neuropsychological tests have typically examined individuals with neurological disorders. The present study was designed to investigate the construct validity of neuropsychological measures in patients with schizophrenia. We used Wechsler Adult Intelligence Scale-Revised (WAIS-R) factor scores that were generated from the population of interest as marker variables in the present analysis. The current study included 39 patients with schizophrenia who were evaluated with a battery of neuropsychological tests assessing attention, memory, and abstract reasoning abilities. Pearson correlations indicated significant relationships between (a) WAIS-R Verbal Comprehension factor and tests of sustained attention, verbal memory and remote memory; (b) WAIS-R Perceptual Organization factor and tests of visual memory and abstraction and problem solving; and (c) WAIS-R Freedom From Distractibility factor and neuropsychological measures of attention and concentration. These results provide support for the construct validity of the neuropsychological tests in patients with schizophrenia, and indicate that these tests evaluate essentially the same constructs in patients with schizophrenia as they do for patients with structural neurological disorders. C1 VA Pittsburgh Healthcare Syst, Highland Dr Div 151R, Pittsburgh, PA 15206 USA. VA Med Ctr, Manchester, NH USA. Robert Wood Johnson Pharmaceut Res Inst, Princeton, NJ USA. RP Allen, DN (reprint author), VA Pittsburgh Healthcare Syst, Highland Dr Div 151R, 7180 Highland Dr, Pittsburgh, PA 15206 USA. FU NIMH NIH HHS [R01MH44-841] NR 42 TC 4 Z9 4 U1 5 U2 6 PU PSYCHOLOGICAL ASSESSMENT RESOURCES INC PI ODESSA PA PO BOX 998, ODESSA, FL 33556 USA SN 1073-1911 J9 ASSESSMENT JI Assessment PD DEC PY 1998 VL 5 IS 4 BP 365 EP 374 DI 10.1177/107319119800500406 PG 10 WC Psychology, Clinical SC Psychology GA 147CC UT WOS:000077469500006 PM 9835660 ER PT J AU Nikolova, L Soman, K Nichols, JC Daniel, DS Dickey, BF Hoffenberg, S AF Nikolova, L Soman, K Nichols, JC Daniel, DS Dickey, BF Hoffenberg, S TI Conformationally variable Rab protein surface regions mapped by limited proteolysis and homology modelling SO BIOCHEMICAL JOURNAL LA English DT Article ID SMALL GTPASE RAB5; ENDOCYTIC MEMBRANE-FUSION; HETEROTRIMERIC G-PROTEIN; SWITCH-II REGION; CRYSTAL-STRUCTURE; EXCHANGE FACTOR; GERANYLGERANYL TRANSFERASE; ENDOPLASMIC-RETICULUM; NUCLEOTIDE EXCHANGE; NUCLEIC-ACIDS AB Tryptic proteolysis of the small GTPases Rab4 and Rab5 is a multi-step, nucleotide-dependent process. Using N-terminal peptide sequencing, matrix-assisted laser desorption ionization-time-of-flight MS and molecular modelling, we identified the three initial sites of proteolysis in Rab5 as Arg-4, Arg-81 and Arg-197. Arg-4 and Arg-81 lie within regions previously implicated in Rab5 endocytic function, and Arg-197 lies in a region involved in membrane targeting. Topologically, Arg-81 lies within the conformationally variable Switch II region shown to be important for protein-protein interactions of other GTPases. Homology modelling studies on Rab5 indicate that the Arg-81 side chain is buried in the Rab5 GTP conformation, but is solvent-accessible in the GDP conformation, explaining the dependence of proteolysis on nucleotides. Peptide mapping of Rab4 was performed to take advantage of additional scissile bonds within Switch II to determine more precisely the limits of the nucleotide-dependent protease-accessible region. The Rab4 cleavage sites corresponded to Arg-81 and Pro-87 of Rab5, and taken together with the finding that Rab5 was not cleaved at Arg-91 this analysis defines an eight-residue surface-exposed conformationally variable region lying in the centre of Switch II. A sequence comparison of Rab proteins shows these eight residues to have a loosely conserved motif that we term Switch II(v) for its relative variability. C-terminal to Switch II(v) is a highly conserved Rab-specific YYRGA motif that we term Switch II(c) for its constant sequence. N-terminal to Switch II(v) is a sequence-invariant G-domain involved in nucleotide binding and hydrolysis, We propose that the Rab Switch II(v) region imparts specificity to nucleotide-dependent protein-protein interactions. C1 Houston VA Med Ctr, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol Physiol & Biophys, Houston, TX 77030 USA. Rice Univ, Dept Biochem & Cell Biol, Houston, TX 77005 USA. RP Hoffenberg, S (reprint author), Tanox Biosyst Inc, 10301 Stella Link, Houston, TX 77025 USA. EM shoffenberg@tanox.com RI Soman, Kizhake/C-2028-2012 FU NHLBI NIH HHS [HL43161] NR 46 TC 6 Z9 6 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD DEC 1 PY 1998 VL 336 BP 461 EP 469 PN 2 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 151QH UT WOS:000077731600027 PM 9820825 ER PT J AU Takahashi, K Takahashi, F Tanabe, KK Takahashi, H Fukuchi, Y AF Takahashi, K Takahashi, F Tanabe, KK Takahashi, H Fukuchi, Y TI The carboxyl-terminal fragment of osteopontin suppresses arginine-glycine-asparatic acid-dependent cell adhesion SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL LA English DT Article DE osteopontin; adhesion; carboxyl-terminal; fragment; thrombin cleavage; RGD; fibroblast; fusion protein ID THROMBIN-CLEAVAGE; NEOPLASTIC TRANSFORMATION; MONOCLONAL-ANTIBODY; GENE-EXPRESSION; METASTASIS; MIGRATION; CD44; MACROPHAGES; DOMAIN; PHOSPHOPROTEIN AB Osteopontin (OPN) is a secreted glycoprotein implicated in cell adhesion. It contains the arginine-glycine-asparatic acid (RGD) cell adhesive domain and the thrombin cleavage sequence. Although thrombin cleavage of OPN has been shown to be of physiological importance, the function of C-terminal OFN fragment cleaved by thrombin remains unknown. To determine its role, we performed cell adhesion assays using glutathione S-transferase-OPN fusion protein fragments and full-length OPN fusion protein. The N-terminal fragment containing RGD motif promoted enhanced adhesion of mouse and human fibroblasts by 2.9 and 2.8 folds in comparison with full-length OPN, respectively. The enhanced adhesion of both cells mediated by N-terminal fragment was significantly suppressed by addition of C-terminal fragment lacking RGD motif that has less cell adhesive property than full-length OPN. These results suggest that the C-terminal domain may play a pivotal role in regulating OPN functions by suppressing the RGD-dependent cell adhesion. C1 Juntendo Univ, Sch Med, Dept Resp Med, Bunkyo Ku, Tokyo 113, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Boston, MA 02114 USA. RP Takahashi, K (reprint author), Juntendo Univ, Sch Med, Dept Resp Med, Bunkyo Ku, 2-1-1 Hongo, Tokyo 113, Japan. EM k-m3540@ma.kcom.ne.jp FU NCI NIH HHS [CA64454] NR 46 TC 24 Z9 28 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1039-9712 J9 BIOCHEM MOL BIOL INT JI Biochem. Mol. Biol. Int. PD DEC PY 1998 VL 46 IS 6 BP 1081 EP 1092 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 155WB UT WOS:000077968400002 PM 9891840 ER PT J AU Slack, F Ruvkun, G AF Slack, F Ruvkun, G TI Heterochronic genes in development and evolution SO BIOLOGICAL BULLETIN LA English DT Article; Proceedings Paper CT Workshop on Genetic Regulatory Networks in Embryogenesis and Evolution CY JUN 11-14, 1997 CL MARINE BIOL LAB, WOODS HOLE, MASSACHUSETTS SP Marine Biol Lab, Ctr Adv Studies Space Life Sci, NASA HO MARINE BIOL LAB ID C-ELEGANS; LIN-4 C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Slack, F (reprint author), Harvard Univ, Sch Med, Dept Genet, Wellman 8, Boston, MA 02114 USA. EM ruvkun@frodo.mgh.harvard.edu OI Slack, Frank/0000-0001-8263-0409 FU NIGMS NIH HHS [R01 GM44619, GM18663] NR 9 TC 7 Z9 7 U1 0 U2 3 PU MARINE BIOLOGICAL LABORATORY PI WOODS HOLE PA 7 MBL ST, WOODS HOLE, MA 02543 USA SN 0006-3185 J9 BIOL BULL JI Biol. Bull. PD DEC PY 1998 VL 195 IS 3 BP 375 EP 376 DI 10.2307/1543152 PG 2 WC Biology; Marine & Freshwater Biology SC Life Sciences & Biomedicine - Other Topics; Marine & Freshwater Biology GA 158XL UT WOS:000078142700018 PM 9924779 ER PT J AU Hobert, O Ruvkun, G AF Hobert, O Ruvkun, G TI A common theme for LIM homeobox gene function across phylogeny? SO BIOLOGICAL BULLETIN LA English DT Article; Proceedings Paper CT Workshop on Genetic Regulatory Networks in Embryogenesis and Evolution CY JUN 11-14, 1997 CL MARINE BIOL LAB, WOODS HOLE, MASSACHUSETTS SP Marine Biol Lab, Ctr Adv Studies Space Life Sci, NASA HO MARINE BIOL LAB ID C-ELEGANS; EXPRESSION; PATHWAY; NEURONS; SYSTEM C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Hobert, O (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. OI Hobert, Oliver/0000-0002-7634-2854 NR 12 TC 20 Z9 20 U1 0 U2 0 PU MARINE BIOLOGICAL LABORATORY PI WOODS HOLE PA 7 MBL ST, WOODS HOLE, MA 02543 USA SN 0006-3185 J9 BIOL BULL JI Biol. Bull. PD DEC PY 1998 VL 195 IS 3 BP 377 EP 380 DI 10.2307/1543153 PG 4 WC Biology; Marine & Freshwater Biology SC Life Sciences & Biomedicine - Other Topics; Marine & Freshwater Biology GA 158XL UT WOS:000078142700019 PM 9924780 ER PT J AU Tsai, GC Yang, PC Chung, LC Lange, N Coyle, JT AF Tsai, GC Yang, PC Chung, LC Lange, N Coyle, JT TI D-serine added to antipsychotics for the treatment of schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE D-serine; N-methyl-D-aspartate; glutamate; schizophrenia; treatment ID TREATMENT-RESISTANT SCHIZOPHRENIA; MOUSE HIPPOCAMPAL-NEURONS; CENTRAL-NERVOUS-SYSTEM; ENDOGENOUS D-SERINE; FREE D-ASPARTATE; NMDA-RECEPTOR; RAT-BRAIN; NEGATIVE SYMPTOMS; D-CYCLOSERINE; GLYCINE SITE AB Background: Hypofunction of N-methyl-D-aspartate (NMDA) subtype glutamate receptor has been implicated in the pathophysiology of schizophrenia. D-serine is a full agonist of the glycine site of NMDA receptor, all endogenous cotransmitter enriched in corticolimbic regions and distributed in parallel with NMDA receptor. Supplementation of D-serine may improve the symptoms of schizophrenia. Methods: Thirty-one Taiwanese schizophrenic patients enrolled in a 6-week double-blind, placebo-controlled trial of D-serine (30 mg/kg/day), which was added to their stable antipsychotic regimens. Of these, 28 completed the trial, Measures of clinical efficacy, side effects, and serum levels of amino acids and D-serine were determined every other week. Wisconsin Card Sorting Test (WCST) was performed at the beginning and end of the trial. Results: Patients who received D-serine treatment revealed significant improvements in their positive, negative, and cognitive symptoms as well as some performance in WCST. D-serine levels at week 4 and 6 significantly predicted the improvements. D-serine was well tolerated and no significant side effects were noted. Conclusions: The significant improvement with the D-serine further supports the hypothesis of NMDA receptor hypofunction in schizophrenia. Given the effects of D-serine on positive symptoms, a trial of D-serine alone in schizophrenia should be considered. (C) 1998 Society: of Biological Psychiatry. C1 Massachusetts Gen Hosp, Dept Psychiat, Lab Mol & Dev Neurosci, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Kaohsiung Med Sch, Dept Psychiat, Kaohsiung, Taiwan. RP Tsai, GC (reprint author), MGH CNY, Dept Psychiat, Lab Mol & Dev Neurosci, Room 254,149 13th St, Charlestown, MA 02129 USA. NR 64 TC 431 Z9 442 U1 2 U2 22 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 1 PY 1998 VL 44 IS 11 BP 1081 EP 1089 DI 10.1016/S0006-3223(98)00279-0 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 141BN UT WOS:000077122900004 PM 9836012 ER PT J AU Goggins, WB Finkelstein, DM Schoenfeld, DA Zaslavsky, AM AF Goggins, WB Finkelstein, DM Schoenfeld, DA Zaslavsky, AM TI A Markov chain Monte Carlo EM algorithm for analyzing interval-censored data under the Cox proportional hazards model SO BIOMETRICS LA English DT Article DE cancer; HIV; missing data; rank-based inference; survival ID LIKELIHOOD; AIDS AB This paper proposes a Monte Carlo EM (MCEM) algorithm for fitting the proportional hazards model for interval-censored failure-time data. The algorithm generates orderings of the failures from their probability distribution under the model. We maximize the average of the log-likelihoods from these completed data sets to obtain updated parameter estimates. As with the standard Cox model, this algorithm does not require the estimation of the baseline hazard function. The performance of the algorithm is evaluated using simulations, and the method is applied to data from AIDS and cancer studies. Our results indicate that our method produced more precise and unbiased estimates than methods of right and midpoint imputation. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Finkelstein, DM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. FU NCI NIH HHS [CA 74302]; NIAID NIH HHS [N0-AI 95030] NR 18 TC 34 Z9 35 U1 0 U2 3 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 1998 VL 54 IS 4 BP 1498 EP 1507 DI 10.2307/2533674 PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 154PZ UT WOS:000077898700024 PM 9883548 ER PT J AU Busch, NA Yarmush, ML Toner, M AF Busch, NA Yarmush, ML Toner, M TI A theoretical formalism for aggregation of peroxidized lipids and plasma membrane stability during photolysis SO BIOPHYSICAL JOURNAL LA English DT Article ID ANTIBODY-TARGETED PHOTOLYSIS; CIS-PARINARIC ACID; PHOTODYNAMIC THERAPY; ERYTHROCYTE-MEMBRANES; BLADDER-CANCER; PROTOPORPHYRIN; PEROXIDATION; CHLORIN; LIPOSOMES; MECHANISM AB The objective of this investigation was to examine, from a theoretical perspective, the mechanism underlying the lysis of plasma membranes by photoinduced, chemically mediated damage such as is found in photolysis. Toward this end, a model is presented which relates the membrane lifetime to the thermodynamic parameters of the membrane components based upon the kinetic theory of aggregate formation. The formalism includes a standard birth/death process for the formation of damaged membrane components (i.e., peroxidized lipids) as well as a terminating condensation process for the formation of aggregates of peroxidized plasma membrane lipids. Our theory predicts that 1) the membrane lifetime is inversely correlated with predicted rate of membrane damage; 2) an upper limit on the duration of membrane damage exists, above which the mean and variance of the membrane lifetime is independent of further membrane damage; and 3) both the mean and variance of the time of membrane lifetime distribution are correlated with the number of sites that may be damaged to form a single membrane defect. The model provides a framework to optimize the lysis of cell membranes by photodynamic therapy. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Cambridge, MA 02139 USA. Shriners Burn Hosp, Cambridge, MA 02139 USA. RP Toner, M (reprint author), Shriners Res Ctr, 1 Kendall Sq,Bldg 1400W, Cambridge, MA 02139 USA. EM mtoner@sbi.org FU NIGMS NIH HHS [GM-07035] NR 53 TC 6 Z9 6 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD DEC PY 1998 VL 75 IS 6 BP 2956 EP 2970 PG 15 WC Biophysics SC Biophysics GA 144BZ UT WOS:000077295000032 PM 9826616 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 costs and cost-effectiveness of unrelated donor bone marrow transplantation for chronic phase chronic myelogenous leukemia SO BLOOD LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; IMPROVED SURVIVAL; CHEMOTHERAPY; INTERFERON AB Unrelated donor transplantation prolongs survival in some patients with chronic myelogenous leukemia (CML) in chronic phase. However, there are growing concerns about the intensive resources required for this procedure given health care budget constraints. To address this issue, we conducted a study of the costs and cost-effectiveness of unrelated donor transplantation for chronic phase CML. The costs of transplantation were derived from 157 patients from the Brigham and Women's Hospital (BWH) and the Fred Hutchinson Cancer Research Center (FHCRC). Estimates of the effectiveness of transplantation were taken from our previous work using data from the International Bone Marrow Transplant Registry and the National Marrow Donor Program. The median cost of the first 6 months of care including donor identification, marrow collection, patient hospitalization for transplantation and all outpatient medications and readmissions through 6 months postmarrow infusion was $178,500 (range, $85,000 to $462,400) and the mean was $196,200. Mean costs for patients surviving beyond 6 months posttransplant were significantly lower than for patients dying within that period ($189,700 v $211,000, respectively, P = .03). Posttransplant follow-up costs were high for months 6 to 18, then decreased. The incremental cost-effectiveness of transplantation within 1 year of diagnosis versus cr-interferon therapy without transplant in the base case of a 35-year-old patient was $51,800/quality-adjusted life year (QALY) gained. Sensitivity analysis showed that most ratios were between $50,000 to $100,000/QALY or within the intermediate zone of acceptable cost-effectiveness ratios. (C) 1998 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Lee, SJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Ctr Outcomes & Policy Res, 454 Brookline Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA75267-01] NR 30 TC 43 Z9 45 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 1998 VL 92 IS 11 BP 4047 EP 4052 PG 6 WC Hematology SC Hematology GA 142HH UT WOS:000077194300009 PM 9834208 ER PT J AU Przepiorka, D Phillips, GL Ratanatharathorn, V Cottler-Fox, M Sehn, LH Antin, JH LeBherz, D Awwad, M Hope, J McClain, JB AF Przepiorka, D Phillips, GL Ratanatharathorn, V Cottler-Fox, M Sehn, LH Antin, JH LeBherz, D Awwad, M Hope, J McClain, JB TI A phase II study of BTI-322, a monoclonal anti-CD2 antibody, for treatment of steroid-resistant acute graft-versus-host disease SO BLOOD LA English DT Article ID HUMAN T-CELLS; LYMPHOCYTE-T; ACUTE GVHD; RENAL-TRANSPLANTATION; CD2; RECEPTOR; ANTIGEN; ACTIVATION; HYPORESPONSIVENESS; PROTEIN AB BTI-322, a rat monoclonal IgG2b directed against the CD2 antigen on T cells and natural killer (NK) cells, blocks primary and memory alloantigen proliferative responses in vitro. We have evaluated the pharmacokinetics and safety of BTI-322 during treatment of 20 transplant recipients with steroid-refractory acute graft-versus-host disease (GVHD). Treatment consisted of BTI-322 by intravenous (IV) bolus or 30-minute infusion at approximately 0.1 mg/kg/d for 10 days in addition to continuing high-dose steroids and tacrolimus or cyclosporine. Pharmacokinetic sampling was performed in 10 patients; the t(1/2) +/- SE was 9.1 +/- 1.3 hours, the C-max was 2,549 +/- 291 ng/mL, the Vd was 3.97 +/- 0.95 L, and the Vd/kg was 0.05 +/- 0.01 L/kg. Ten patients experienced transient dyspnea sometimes accompanied by nausea, vomiting, diarrhea, and tachycardia shortly after the initial bolus dose of drug, but serious drug-related adverse events were not seen during the remainder of the infusions. At the end of treatment (day 11), there were six patients with complete responses and five with a reduction in grade of GVHD for a total response rate of 55% (95% confidence interval [CI], 32% to 77%), Antibodies targeting CD2 may be active in the treatment of acute GVHD, and evaluation of a humanized form of BTI-322 is warranted. (C) 1998 by The American Society of Hematology. C1 Medimmune Inc, Gaithersburg, MD 20878 USA. BioTransplant Inc, Charlestown, MA USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. Univ Kentucky, Albert B Chandler Med Ctr, Lexington, KY 40536 USA. Univ Texas, Md Anderson Canc Ctr, Houston, TX USA. RP Przepiorka, D (reprint author), Baylor Coll Med, Ctr Cell & Gene Therapy, 6621 Fannin St,MC3-3320, Houston, TX 77030 USA. EM donnap@bcm.tmc.edu FU NCI NIH HHS [CA16672] NR 31 TC 45 Z9 45 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 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 1998 VL 92 IS 11 BP 4066 EP 4071 PG 6 WC Hematology SC Hematology GA 142HH UT WOS:000077194300012 PM 9834211 ER PT J AU Berger, G Hartwell, DW Wagner, DD AF Berger, G Hartwell, DW Wagner, DD TI P-selectin and platelet clearance SO BLOOD LA English DT Article ID GRANULE MEMBRANE PROTEIN-140; CIRCULATING PLASMA-PROTEIN; WEIBEL-PALADE BODIES; IN-VIVO; ACTIVATED PLATELETS; ENDOTHELIAL-CELLS; RABBIT PLATELETS; DEFICIENT MICE; STORAGE; ADHESION AB P-selectin is an adhesion receptor for leukocytes expressed by activated platelets and endothelial cells. To assess a possible role of P-selectin in platelet clearance, we adapted an in vivo biotinylation technique in mice. Wild-type and P-selectin-deficient mice were infused with N-hydroxysuccinimido biotin, The survival of biotinylated platelets was followed by flow cytometry after labeling with fluorescent streptavidin. Both wild-type and P-selectin-deficient platelets presented identical life spans of about 4.7 days, suggesting that P-selectin does not play a role in platelet turnover. When biotinylated platelets were isolated, activated with thrombin, and reinjected into mice, the rate of platelet clearance was unchanged. In contrast, storage of platelets at 4 degrees C caused a significant reduction in their life span in vivo but again no significant differences were observed between the two genotypes. The infused thrombin-activated platelets rapidly lost their surface P-selectin in circulation, and this loss was accompanied by the simultaneous appearance of a 100-kD P-selectin fragment in the plasma. This observation suggests that the platelet membrane P-selectin was shed by cleavage. In conclusion, this study shows that P-selectin, despite its binding to leukocytes, does not mediate platelet clearance. However, the generation of a soluble form of P-selectin on platelet activation may have biological implications in modulating leukocyte recruitment or thrombus growth. (C) 1998 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [P01 HL56949] NR 60 TC 199 Z9 203 U1 2 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 1998 VL 92 IS 11 BP 4446 EP 4452 PG 7 WC Hematology SC Hematology GA 142HH UT WOS:000077194300053 PM 9834252 ER PT J AU Beland, JL Adler, H Del-Pan, NC Kozlow, W Sung, J Fanslow, W Rimm, IJ AF Beland, JL Adler, H Del-Pan, NC Kozlow, W Sung, J Fanslow, W Rimm, IJ TI Recombinant CD40L treatment protects allogeneic murine bone marrow transplant recipients from death caused by herpes simplex virus-1 infection SO BLOOD LA English DT Article ID VERSUS-HOST REACTION; T-CELLS; INTERSTITIAL PNEUMONITIS; DISEASE; SUPPRESSION; ANTIBODY; ANTIGEN; MICE; IMMUNODEFICIENCY; ALLOREACTIVITY AB Posttransplant infection associated with host immune deficiency is the major cause of nonrelapse mortality of human bone marrow transplant recipients. In a new murine model of posttransplant infection, allogeneic bone marrow transplant recipients were infected with herpes simplex virus-1 (HSV-1) via intraperitoneal inoculation 12 weeks after transplantation. Allogeneic transplant recipients with graft-versus-host disease (GVHD) had significantly increased mortality from HSV-1 encephalitis, with deficiencies of both specific anti-HSV-1 antibody and total serum IgG2a. GVHD mice displayed a Th2 cytokine profile (increased interleukin-4 [IL-4] and decreased interferon-gamma) and decreased lipopolysaccharide (LPS) responses, suggesting that both T-cell and B-cell defects contributed to the impaired production of antibody. Because passive transfer of hyperimmune serum protected mice from HSV-1 infection, we hypothesized that CD40 ligand (CD40L), which induces B-cell maturation, would protect mice from HSV-1 infection, CD40L-treated GVHD mice showed elevated IgG2a levels and increased survival compared with vehicle-treated transplant recipients. (C) 1998 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Immunex Corp, Seattle, WA USA. RP Rimm, IJ (reprint author), Genet Inst, 87 Cambridge Pk Dr, Cambridge, MA 02140 USA. FU NCI NIH HHS [P01-CA39542] NR 37 TC 9 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 1998 VL 92 IS 11 BP 4472 EP 4478 PG 7 WC Hematology SC Hematology GA 142HH UT WOS:000077194300056 PM 9834255 ER PT J AU Boucher, Y Brekken, C Netti, PA Baxter, LT Jain, RK AF Boucher, Y Brekken, C Netti, PA Baxter, LT Jain, RK TI Intratumoral infusion of fluid: estimation of hydraulic conductivity and implications for the delivery of therapeutic agents SO BRITISH JOURNAL OF CANCER LA English DT Article DE human tumour xenografts; intratumoral fluid infusion; hydraulic conductivity; compliance; interstitial fluid pressure ID INTERSTITIAL PRESSURE; MONOCLONAL-ANTIBODIES; SOLID TUMORS; BLOOD-FLOW; MACROMOLECULES; CONVECTION; TISSUE; BRAIN; COEFFICIENT; TRANSPORT AB We have developed a new technique to measure in vivo tumour tissue fluid transport parameters (hydraulic conductivity and compliance) that influence the systemic and intratumoral delivery of therapeutic agents. An infusion needle approximating a point source was constructed to produce a radially symmetrical fluid source in the centre of human tumours in immunodeficient mice. At constant flow, the pressure gradient generated in the tumour by the infusion of fluid (Evans blue-albumin in saline) was measured asa function of the radial position with micropipettes connected to a servo-null system. To evaluate whether the fluid infused was reabsorbed by blood vessels. infusions were also performed after circulatory arrest. In the colon adenocarcinoma LS174T with a spherically symmetrical distribution of Evans blue-albumin, the median hydraulic conductivity in vivo and after circulatory arrest at a flow rate of 0.1 mu l min(-1) was, respectively, 1.7x10(-7) and 2.3x10(-7) cm(2) mmHg(-1) s. Compliance estimates were 35 mu l mmHg(-1) in vivo, and 100 mu l mmHg(-1) after circulatory arrest. In the sarcoma HSTS 26T, hydraulic conductivity and compliance were not calculated because of the asymmetric distribution of the fluid infused. The technique will be helpful in identifying strategies to improve the intratumoral and systemic delivery of gene targeting vectors and other therapeutic agents. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Boucher, Y (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab, Boston, MA 02114 USA. OI NETTI, PAOLO/0000-0002-2435-7181 FU NCI NIH HHS [R35 CA56591] NR 32 TC 59 Z9 60 U1 0 U2 5 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD DEC PY 1998 VL 78 IS 11 BP 1442 EP 1448 DI 10.1038/bjc.1998.705 PG 7 WC Oncology SC Oncology GA 139EX UT WOS:000077015900009 PM 9836476 ER PT J AU Wickramashinghe, SN Spearing, RL Hill, GR AF Wickramashinghe, SN Spearing, RL Hill, GR TI Congenital dyserythropoiesis with intererythroblastic chromatin bridges and ultrastructurally-normal erythroblast heterochromatin: a new disorder SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE congenital dyserythropoiesis; basophilic stippling; macrocytes; internuclear chromatin bridges; serum thymidine kinase activity ID ANEMIA TYPE-I; THALASSEMIA AB Two non-anaemic subjects, a father and daughter, with a new form of congenital dyserythropoiesis are reported. The features of their disorder are: (1) an abnormal blood film with basophilic stippling of red cells and oral macrocytes, (2) various dysplastic changes in the erythroblasts, including internuclear chromatin bridges, (3) ultrastructurally-normal erythroblast heterochromatin, (4) normal serum thymidine kinase activity and (5) a probable autosomal dominant inheritance. The last three features distinguish this disorder from CDA type I. C1 Imperial Coll Sch Med, Dept Haematol, London W2 1PG, England. Canterbury Hlth Labs, Christchurch, New Zealand. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Wickramashinghe, SN (reprint author), Imperial Coll Sch Med, Dept Haematol, St Marys Campus,Norfolk Pl, London W2 1PG, England. RI Hill, Geoffrey/O-2630-2016 OI Hill, Geoffrey/0000-0003-2994-0429 NR 8 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC 1 PY 1998 VL 103 IS 3 BP 831 EP 834 PG 4 WC Hematology SC Hematology GA 146XD UT WOS:000077457400036 PM 9858240 ER PT J AU Febbo, PG Kantoff, PW Giovannucci, E Brown, M Chang, G Hennekens, CH Stampfer, M AF Febbo, PG Kantoff, PW Giovannucci, E Brown, M Chang, G Hennekens, CH Stampfer, M TI Debrisoquine hydroxylase (CYP2D6) and prostate cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID OXIDATION; LOCUS; GENE; SUSCEPTIBILITY; POLYMORPHISMS; METABOLISM; 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE; IDENTIFICATION; HUMANS; DEFECT AB The p450 hepatic microsomal enzyme system metabolizes exogenous drugs and carcinogens. Debrisoquine hydroxylase (CYP2D6), one member of the p450 hemoproteins, has polymorphic expression leading to poor metabolism of debrisoquine and similar compounds in approximately 7% of Caucasians, The genetic locus for this enzyme has been characterized, and the mutations responsible for the slowed metabolism have been identified. Epidemiological studies of the CYP2D6 phenotype suggest an association between the normal or rapid metabolism phenotype and increased risk of lung and bladder cancer. Preliminary data have also suggested an association with prostate cancer (CaP), We used a PCR-based assay to investigate possible associations between the CYP2D6 B allele, the most common genetic mutation responsible for the poor metabolism phenotype, and CaP, Using genomic DNA isolated from peripheral blood, we genetically typed 571 men with CaP and 767 matched controls, all participants in the Physician's Health Study, Relative to men homozygous for the wad-type allele, heterozygotes for the B allele have an odds ratio of 1.19 (95% confidence interval, 0.94-1.51) for CaP, and men homozygous for the B allele have an odds ratio of 1.37 (95% confidence interval, 0.86-2.20). When analyzed as a trend over zero, one, or two copies of the B allele, there emerges a possible association between the B allele and an increased risk of CaP of borderline statistical significance (P = 0.07). C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Physicians Hlth Study, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Kantoff, PW (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. RI Myles, Brown/B-6906-2008; OI Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [CA58684, CA42182, CA72036] NR 29 TC 21 Z9 21 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 1998 VL 7 IS 12 BP 1075 EP 1078 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 146HU UT WOS:000077423900002 PM 9865424 ER PT J AU Rutter, JL Mitchell, TI Buttice, G Meyers, J Gusella, JF Ozelius, LJ Brinckerhoff, CE AF Rutter, JL Mitchell, TI Buttice, G Meyers, J Gusella, JF Ozelius, LJ Brinckerhoff, CE TI A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter creates an Ets binding site and augments transcription SO CANCER RESEARCH LA English DT Article ID GENE-EXPRESSION; HUMAN FIBROBLASTS; COLLAGENASE GENE; INTERSTITIAL COLLAGENASE; GROWTH-FACTOR; AP-1 SITE; COMPLEX; FAMILY; CANCER; CELLS AB Matrix metalloproteinases (MMPs) facilitate cellular invasion by degrading the extracellular matrix, and their regulation is partially dependent on transcription. Binding sites for members of the Ets family of transcription factors are present within MMP promoters and are potent positive regulators. We report a single nucleotide polymorphism at -1607 bp in the MMP-1 promoter, where an additional guanine (G) creates an Ets binding site, 5'-GGA-3'. This polymorphism displays significantly higher transcription in normal fibroblasts and in melanoma cells than the 1 G polymorphism, and it binds substantially more nuclear extract and recombinant ETS-1, Analysis of control DNAs from the Center d'Etude du Polymorphisme Humain pedigrees reveals that this polymorphism is not a mutation, with a frequency of the 2 G polymorphism at 30%, In contrast, in eight tumor cell Lines, this frequency increased to 62.5% (P < 0.0001). Thus, this MMP-1 polymorphism contributes to increased transcription, and cells expressing the 2 G polymorphism may provide a mechanism for more aggressive matrix degradation, thereby facilitating cancer progression. C1 Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Pharmacol & Toxicol, Hanover, NH 03756 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Med, Hanover, NH 03756 USA. Inst Biol Lille, F-59021 Lille, France. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Brinckerhoff, CE (reprint author), Dartmouth Med Sch, Dept Med & Biochem, Hanover, NH 03755 USA. OI Rutter, Joni/0000-0002-6502-2361 FU NIAMS NIH HHS [AR-26599]; NINDS NIH HHS [NS-24279]; OHS HRSA HHS [ST32-CA09658] NR 23 TC 405 Z9 421 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 1998 VL 58 IS 23 BP 5321 EP 5325 PG 5 WC Oncology SC Oncology GA 144YL UT WOS:000077343400015 PM 9850057 ER PT J AU Momma, T Hamblin, MR Wu, HC Hasan, T AF Momma, T Hamblin, MR Wu, HC Hasan, T TI Photodynamic therapy of orthotopic prostate cancer with benzoporphyrin derivative: Local control and distant metastasis SO CANCER RESEARCH LA English DT Article ID CANINE PROSTATE; HEMATOGENOUS DISSEMINATION; SKIN PHOTOSENSITIVITY; RADICAL PROSTATECTOMY; LIGHT PENETRATION; TUMOR-METASTASIS; IN-SITU; CELLS; MODEL; RECURRENCE AB This is the first report of photodynamic therapy (PDT) in an orthotopic prostate tumor model and shows that PDT combined with surgery (tumor bed sterilization) gave significant local control of the primary tumor and significant reduction in distant metastases. By contrast, either treatment alone (surgery or PDT) gave relatively poorer local control, and PDT gave a significant increase in the mean number of lung metastases, The MatLyLu variant of the Dunning 3327 rat prostate cancer cell line, which has been selected to be metastatic to lymph nodes and lungs, was injected into the ventral lobe of the rat prostate. After 7 days, tumors were either treated by surgical removal of the ventral lobe, PDT with liposomal benzoporphyrin derivative monoacid ring A, or a combination of surgery, followed by PDT of the tumor bed. Results after 21 days showed a reduction in prostate tumor weight in all groups compared with controls, which became highly significant only for the combination group (17% of control mean tumor weight; P < 0.001; 7 of 13 clinical complete responses). The combination treatment also led to a reduction in lymph node metastasis and reductions in both the frequency and mean number of lung metastases compared with other treatment groups. The PDT-alone group, however, had a mean number of lung metastases per animal, which was nine times the control group and 34 times the combination group. These findings suggest that a tumor bed sterilization approach may be promising for locally advanced prostate cancer and suggest that factors other than local control may need to be evaluated when considering PDT for primary prostate cancer. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Hasan, T (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Wellman Labs Photomed, WEL 224, Boston, MA 02114 USA. OI Hamblin, Michael/0000-0001-6431-4605 NR 64 TC 77 Z9 79 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 1998 VL 58 IS 23 BP 5425 EP 5431 PG 7 WC Oncology SC Oncology GA 144YL UT WOS:000077343400033 PM 9850075 ER PT J AU Prabhu, SD AF Prabhu, SD TI Ryanodine and the left ventricular force-interval and relaxation-interval relations in closed-chest dogs: insights on calcium handling SO CARDIOVASCULAR RESEARCH LA English DT Article DE myocardial contraction; ventricular function; calcium; sarcoplasmic reticulum; dog ID END-SYSTOLIC PRESSURE; SARCOPLASMIC-RETICULUM; INTRACELLULAR CALCIUM; CONSCIOUS DOGS; MECHANICAL RESTITUTION; FREQUENCY RELATION; MYOCARDIUM; MUSCLE; CONTRACTION; EXCITATION AB Objective: Although the myocardial force-interval and relaxation-interval relations are considered to be mechanical expressions of myocardial Ca2+ handling, correlation of these phenomena with altered Ca2+ kinetics in the intact state is limited. Thus, I sought to determine the impact of selective impairment of physiologic sarcoplasmic reticulum Ca2+ release, achieved by the use of the drug ryanodine, on these relations in the intact animal. Methods: Twelve dogs instrumented with left ventricular manometers and piezoelectric dimension crystals were studied before and after ryanodine (4 mu g/kg intravenously). End-systolic elastance was measured at paced heart rates of 120-180 bpm to determine the force-frequency response. Mechanical restitution and relaxation restitution were determined by measuring contractile (single beat elastance) and relaxation (peak negative dP/dt) responses for beats delivered at graded extrasystolic intervals, with normalized responses expressed as a function of extrasystolic interval. Results: Ryanodine accelerated mechanical restitution (time constant 60.3+/-3.9 versus 81.7+/-10.1 ms, p<0.05) and reduced maximal contractile response (107.5+/- 2.1 versus 122.1+/-5.7%, p<0.05), slowed early relaxation restitution (time constant 65.5+/-13.8 versus 36.8+/-3.8 ms, p<0.05) without changing late relaxation restitution kinetics, and amplified the force-frequency response (end-systolic elastance, 180 bpm, 19.4+/-4.3 versus 11.4+/-1.2 mm Hg/ml, p<0.05). Conclusions: These findings suggest that in the intact animal, Ca2+ handling by the sarcoplasmic reticulum is a primary determinant of mechanical restitution and early relaxation restitution, but not late relaxation restitution. Conversely, ryanodine induced augmentation of the force-frequency response indicates a central role for sarcolemmal Ca2+ influx in producing frequency potentiation. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Med Cardiol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Prabhu, SD (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med Cardiol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. RI Prabhu, Sumanth/D-5223-2009 NR 36 TC 6 Z9 6 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD DEC PY 1998 VL 40 IS 3 BP 483 EP 491 DI 10.1016/S0008-6363(98)00201-6 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 149LZ UT WOS:000077607900010 PM 10070488 ER PT J AU Strauss, GM AF Strauss, GM TI The AtBCs of lung cancer screening SO CHEST LA English DT Editorial Material ID FOLLOW-UP; SURVIVAL; PROGRAM C1 Univ Massachusetts Mem Hlth Care, Div Hematol & Oncol, Sch Med, Worcester, MA 01605 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Strauss, GM (reprint author), Univ Massachusetts Mem Hlth Care, Div Hematol & Oncol, Sch Med, Mem Campus,119 Belmont St, Worcester, MA 01605 USA. NR 14 TC 5 Z9 5 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 1998 VL 114 IS 6 BP 1502 EP 1505 DI 10.1378/chest.114.6.1502 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 149PF UT WOS:000077613600002 PM 9872175 ER PT J AU Huizenga, HF Ramsey, SD Albert, RK AF Huizenga, HF Ramsey, SD Albert, RK TI Estimated growth of lung volume reduction surgery among Medicare enrollees - 1994 to 1996 SO CHEST LA English DT Article DE hospital charges; length of stay; lung volume reduction surgery; Medicare ID EMPHYSEMA AB Objective: To estimate the number of lung volume reduction surgery procedures performed on Medicare enrollees from 1994 to 1996, Design: Statistical analysis of national Medicare claims data. Patients: All Medicare enrollees with emphysema having claims records for pulmonary resection procedures from January 1, 1993, through December 31, 1996. Main outcome measure: Estimated number of lung volume reduction procedures performed per month fi om July 1994 through December 1996. Results: An estimated 1,212 lung volume reduction procedures were performed on Medicare enrollees between July 1994 and December 1995 (95% confidence interval, 1,012 to 1,408), Nearly one half of these procedures were performed in the last 3 months of 1995, At the time Health Care Financing Administration announced that it would suspend reimbursement for the procedure (December 1995), lung volume reduction surgery was being performed in 37 states. The number of claims per month decreased from a peak of 169 in December 1995, to 11 in March 1996, Average Medicare reimbursement per procedure was $31,398. Conclusions: Lung volume reduction surgery for patients increased rapidly following its reintroduction in 1994. The growth of lung volume reduction surgery demonstrates that widespread adoption and utilization of a surgical procedure can occur in the absence of data from controlled clinical trials. Medicare expenditures for lung volume reduction surgery were an estimated $30 million to $50 million. Performing the surgery for all current Medicare patients who meet the appropriate clinical criteria would cost an estimated $1 billion. C1 Vet Adm Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Div Gen Internal Med, Seattle, WA 98195 USA. Univ Washington, Hlth Serv, Seattle, WA 98195 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Denver Hlth Med Ctr, Div Pulm & Crit Care Med, Denver, CO USA. Denver Hlth Med Ctr, Dept Internal Med, Denver, CO USA. RP Huizenga, HF (reprint author), Vet Affairs Puget Sound Hlth Care Syst, GIMC, 1660 S Colombian Way, Seattle, WA 98108 USA. NR 8 TC 18 Z9 18 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 1998 VL 114 IS 6 BP 1583 EP 1587 DI 10.1378/chest.114.6.1583 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 149PF UT WOS:000077613600019 PM 9872192 ER PT J AU Mann, DL Willerson, JT AF Mann, DL Willerson, JT TI Left ventricular assist devices and the failing heart - A bridge to recovery, a permanent assist device, or a bridge too far? SO CIRCULATION LA English DT Editorial Material DE editorials; heart-assist device; heart failure; ventricles ID BETA-ADRENERGIC-BLOCKADE; HISTOLOGIC-CHANGES; SUPPORT; FAILURE; CARDIOMYOPATHY C1 Baylor Coll Med, Cardiol Sect, Dept Med, Vet Adm Med Ctr,Winters Ctr Heart Failure Res, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, St Lukes Episcopal Hosp, Texas Heart Inst,Dept Med, Houston, TX USA. RP Mann, DL (reprint author), VA Med Ctr, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM dmann@bcm.tmc.edu OI Mann, Douglas /0000-0002-2516-0145 NR 18 TC 41 Z9 41 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 1 PY 1998 VL 98 IS 22 BP 2367 EP 2369 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 143VQ UT WOS:000077278100004 PM 9832479 ER PT J AU Miller, LG Goetz, MB AF Miller, LG Goetz, MB TI Response: What is the relevance of antiretroviral therapy that does not include protease inhibitors? SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; HIV-INFECTED PATIENTS; CD4 CELL COUNTS; CUBIC MILLIMETER; CONTROLLED TRIAL; VIRUS INFECTION; ZIDOVUDINE; AIDS; RECOMMENDATIONS; COMBINATION C1 W Los Angeles Vet Affairs Med Ctr, Infect Dis Sect, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Goetz, MB (reprint author), W Los Angeles Vet Affairs Med Ctr, Infect Dis Sect, 111F,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 24 TC 2 Z9 2 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC PY 1998 VL 27 IS 6 BP 1386 EP 1387 DI 10.1086/515031 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 148UU UT WOS:000077552300008 PM 9868647 ER PT J AU Oringer, RJ Palys, MD Iranmanesh, A Fiorellini, JP Haffajee, AD Socransky, SS Giannobile, WV AF Oringer, RJ Palys, MD Iranmanesh, A Fiorellini, JP Haffajee, AD Socransky, SS Giannobile, WV TI C-telopeptide pyridinoline cross-links (ICTP) and periodontal pathogens associated with endosseous oral implants SO CLINICAL ORAL IMPLANTS RESEARCH LA English DT Article DE pyridinoline cross-links; periodontal pathogens; diagnosis; gingival crevicular fluid; dental implants; periodontal disease ID GINGIVAL CREVICULAR FLUID; I COLLAGEN; CARBOXYTERMINAL TELOPEPTIDE; FAILING IMPLANT; BONE; DEGRADATION; DISEASE; SERUM; MICROBIOTA; FRAGMENTS AB `Detection of periodontal or peri-implant sites exhibiting progressing disease or those at risk of deterioration has proven difficult. Pyridinoline crosslinked carboxyterminal telopeptide of type I collagen (ICTP), a marker specific for bone degradation found in gingival crevicular fluid (GCF), has been associated with both bone and attachment loss in periodontitis and may be useful for predicting disease activity. The aim of this cross-sectional study was to examine the relationship between ICTP levels and subgingival species around implants and teeth from 20 partially and 2 fully edentulous patients. GCF and plaque samples were collected from the mesiobuccal site of each implant and tooth. Radioimmunoassay techniques were utilized to determine GCF ICTP levels. Plaque samples were analyzed utilizing checkerboard DNA-DNA hybridization. Traditional clinical parameters were assessed. Seventy-one implants and 370 teeth from 22 subjects were examined. ICTP levels and subgingival plaque composition were not significantly different between implants and teeth. Implant sites colonized by Prevotella intermedia, Capnocytophaga gingivalis, Fusobacterium nucleatum ss vincentii, and Streptococcus gordonii exhibited odds ratios of 12.4, 9.3, 8.1, and 6.7, respectively of detecting ICTP. These results suggest a relationship between elevated ICTP levels at implant sites and some species associated with disease progression. Longitudinal studies are necessary to determine whether elevated ICTP levels may predict the development of peri-implant bone loss. C1 Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Forsyth Dent Ctr, Boston, MA 02115 USA. RP Giannobile, WV (reprint author), Univ Michigan, Sch Dent, Dept Periodont Prevent Geriatr, 1101 N Univ Ave, Ann Arbor, MI 48109 USA. OI Giannobile, William/0000-0002-7102-9746 FU NIDCR NIH HHS [DE 04881, P50 DE004881-200005, P30 DE011814-029002, P30 DE011814-020001, P30 DE11814] NR 25 TC 37 Z9 37 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0905-7161 J9 CLIN ORAL IMPLAN RES JI Clin. Oral Implant. Res. PD DEC PY 1998 VL 9 IS 6 BP 365 EP 373 DI 10.1034/j.1600-0501.1996.090602.x PG 9 WC Dentistry, Oral Surgery & Medicine; Engineering, Biomedical SC Dentistry, Oral Surgery & Medicine; Engineering GA 144EC UT WOS:000077300000002 PM 11429938 ER PT J AU Manner, PA Rubash, HE Herndon, JH AF Manner, PA Rubash, HE Herndon, JH TI Prospectus - Future trends in transfusion SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID ACUTE NORMOVOLEMIC HEMODILUTION; AUTOLOGOUS BLOOD-TRANSFUSION; LIPOSOME-ENCAPSULATED HEMOGLOBIN; TOTAL JOINT ARTHROPLASTY; KNEE ARTHROPLASTY; POSTOPERATIVE AUTOTRANSFUSION; MEDIASTINAL BLOOD; SPINAL SURGERY; RED-CELLS; REINFUSION AB There are several emerging trends in perioperative transfusion that are promising in terms of clinical practice. These include modifications in transfusion practice, changes in blood bank procedures and philosophy, the use of autologous transfusion methods, and the development of new artificial blood substitutes. Refinement of current techniques will continue, and will be driven by several factors. The most significant recent changes in surgical practice relating to blood transfusion include a decreased reliance on the use of arbitrary transfusion triggers, and the increased use of various forms of autologous transfusion. Other clinical changes have been less obvious, such as changes in blood bank management practice. Similar factors drive the development of blood conservation strategies and artificial blood substitutes or O-2 carriers. Both will play a role in reducing perioperative blood loss. The most likely scenarios involve use of blood substitutes in conjunction with various methods of blood conservation. Recent advances in blood banking have made the donor blood supply safer than ever before. Progress in the clinical setting and in the laboratory have widened the possibilities for treatment of perioperative blood loss, with attention to minimizing risk and cost, and maintaining safety for the patient. C1 Univ Pittsburgh, Med Ctr, Dept Orthopaed Surg, Adult Reconstruct Serv, Pittsburgh, PA 15213 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA USA. Harvard Univ, Sch Med, Partners Dept Orthopaed Surg, Boston, MA USA. RP Manner, PA (reprint author), Univ Pittsburgh, Med Ctr, Dept Orthopaed Surg, Adult Reconstruct Serv, 3471 5th Ave,Suite 1010, Pittsburgh, PA 15213 USA. NR 98 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 1998 IS 357 BP 101 EP 115 PG 15 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 153UH UT WOS:000077850700015 PM 9917706 ER PT J AU Lee, FYI Hazan, EJ Kloen, P Wolfe, MA Mankin, HJ AF Lee, FYI Hazan, EJ Kloen, P Wolfe, MA Mankin, HJ TI Reconstruction of the shoulder joint using an acetabular allograft - A report of two cases SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID DESMOPLASTIC FIBROMA; LIMB SALVAGE; BONE; TUMORS; GIRDLE AB Wide resection of tumors involving the glenoid region of the scapula compromises a center of motion in the shoulder joint and can cause significant loss of function. Two patients with aggressive tumor of the scapula were treated with wide resection and reconstruction using an osteoarticular acetabular allograft, The ball and socket geometry of the newly reconstructed joint and secure reattachment of soft tissues in the allograft provided a stable shoulder joint. The functional results of the two patients were 87 % and 93 %, respectively according to the Musculoskeletal Tumor Society system. In a select group of patients with locally aggressive lesions of the scapula, a surgical reconstruction with an osteoarticular allograft would yield satisfactory functional and cosmetic results. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Orthopaed Oncol Unit, Boston, MA 02114 USA. RP Mankin, HJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Orthopaed Oncol Unit, Boston, MA 02114 USA. NR 17 TC 6 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 1998 IS 357 BP 116 EP 121 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 153UH UT WOS:000077850700016 PM 9917707 ER PT J AU Lee, FYI Gebhardt, MC Keel, SB Rosenthal, DI AF Lee, FYI Gebhardt, MC Keel, SB Rosenthal, DI TI A discrete soft tissue mass in the distal thigh of a 29-year-old man SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Orthopaed Oncol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Gebhardt, MC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Orthopaed Oncol Unit, GRB 606, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 1998 IS 357 BP 247 EP + PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 153UH UT WOS:000077850700032 PM 9917723 ER PT J AU Whalen, PJ AF Whalen, PJ TI Fear, vigilance, and ambiguity: Initial neuroimaging studies of the human amygdala SO CURRENT DIRECTIONS IN PSYCHOLOGICAL SCIENCE LA English DT Article ID NICTITATING-MEMBRANE RESPONSE; POSTTRAUMATIC-STRESS-DISORDER; EMOTIONAL FACIAL EXPRESSIONS; POSITRON-EMISSION-TOMOGRAPHY; CENTRAL NUCLEUS LESIONS; REFLEX FACILITATION; NEURONAL-ACTIVITY; ACTIVATION; RECOGNITION; STIMULATION C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02139 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Whalen, PJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 13th St,Bldg 149,CNY-9, Charlestown, MA 02139 USA. EM paulw@nmr.mgh.harvard.edu NR 79 TC 464 Z9 466 U1 5 U2 38 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0963-7214 J9 CURR DIR PSYCHOL SCI JI Curr. Dir. Psychol. PD DEC PY 1998 VL 7 IS 6 BP 177 EP 188 DI 10.1111/1467-8721.ep10836912 PG 12 WC Psychology, Multidisciplinary SC Psychology GA 196ZT UT WOS:000080340700003 ER PT J AU Adams, PD Kaelin, WG AF Adams, PD Kaelin, WG TI Negative control elements of the cell cycle in human tumors SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR E2F; DNA-DAMAGE CHECKPOINT; SKELETAL-MUSCLE CELLS; WILD-TYPE P53; RETINOBLASTOMA PROTEIN; ATAXIA-TELANGIECTASIA; INK4A LOCUS; APOPTOSIS; PHOSPHORYLATION; GENE AB The retinoblastoma protein and p53 are both cell-cycle regulators and are, directly or indirectly, inactivated in the majority of human tumors. Recent studies have provided new mechanistic insights into how these proteins regulate cell growth in response to various intracellular and extracellular signals. C1 Univ Penn, Fox Chase Canc Ctr, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Adams, PD (reprint author), Univ Penn, Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19104 USA. NR 66 TC 36 Z9 36 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LE, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD DEC PY 1998 VL 10 IS 6 BP 791 EP 797 DI 10.1016/S0955-0674(98)80123-3 PG 7 WC Cell Biology SC Cell Biology GA 146XL UT WOS:000077458500017 PM 9914179 ER PT J AU Bucalo, BD Moy, RL AF Bucalo, BD Moy, RL TI Quantitative comparison of inflammatory infiltrate and linear contraction in human skin treated with 90-mu s pulsed and 900-mu s dwell time carbon dioxide lasers SO DERMATOLOGIC SURGERY LA English DT Article AB BACKGROUND. Skin resurfacing With 90-mu s pulse duration carbon dioxide (CO2) resurfacing lasers has been reported to have shorter duration of erythema compared with skin resurfacing with 900-mu s dwell time lasers.(1) The presence of inflammatory infiltrate following resurfacing may correlate with the persistance of this erythema. Furthermore, skin treated with the 90-mu s pulse duration laser and the 900-mu s dwell time lasers both result in equivalent improvement of rhytids in the treated skin.(1) OBJECTIVE. TO quantitative the inflammatory cell infiltrate and linens contraction of skin treated with the 90-mu s pulsed and 900-mu s dwell time CO2 lasers at intervals of 2 and 4 weeks after treatment. MATERIALS AND METHODS. Volunteers were recruited from patients who were planning to undergo full face laser resurfacing under general anesthesia. Informed consent was obtained from all volunteers. In the posterior auricular areas of all volunteers, four separate rectangular areas were marked using a skin marking pen and a template. Two rectangular areas behind the right ear were treated with 6 passes of the 90-mu s laser and two rectangular areas behind the left ear were treated with the 900-mu s dwell time laser. The resurfaced areas were wiped with a moist cotton swab and then patted dry with dry gauze between passes. Contraction measurements of the resurfaced areas were taken before and immediately after laser treatment and again at 2 and 4 weeks following treatment. Punch biopsies were also performed at 2 and 4 weeks after treatment iii ail area of skin different from where contraction measurements were taken. RESULTS. The number of inflammatory cells present in the skill at 2 and 4 weeks after laser resurfacing are greater for skin resurfaced With a 900-mu s dwell time laser than a 90-mu s pulse time laser. Linear contraction of skin immediately after treatment was 18% greater with the 900-mu s dwell time laser than with the 90-mu s pulsed laser. The difference in the amount of contraction produced by the lasers tended to decrease over time. At 4 weeks there was a 10% difference in mean linear contraction between the two laser types. CONCLUSION. Increased numbers of inflammatory cells in skin resurfaced with the 900-mu s dwell time laser may explain the observed persistence of erythema associated with the 900-mu s dwell time laser. Measurable linear contraction produced by the 900-mu s dwell time laser was initially 18% greater than the 90-mu s pulse laser. This difference tends to decrease over time. (C) 1998 by the American Society for Dermatologic Surgery, Inc. C1 Univ Calif Los Angeles, Div Dermatol, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Bucalo, BD (reprint author), 100 UCLA Med Plaza,Suite 590, Los Angeles, CA 90024 USA. NR 4 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD DEC PY 1998 VL 24 IS 12 BP 1314 EP 1316 PG 3 WC Dermatology; Surgery SC Dermatology; Surgery GA 149QC UT WOS:000077615800005 PM 9865195 ER PT J AU Moy, RL Bucalo, B Lee, MH Wieder, J Chalet, MD Ostad, A Dishell, WD AF Moy, RL Bucalo, B Lee, MH Wieder, J Chalet, MD Ostad, A Dishell, WD TI Skin resurfacing of facial rhytides and scars with the 90-mu s short pulse CO2 laser - Comparison to the 900-mu s dwell time CO2 lasers and clinical experience SO DERMATOLOGIC SURGERY LA English DT Article ID CARBON-DIOXIDE LASER; THERMAL-DAMAGE; DURATION; CO2-LASER AB BACKGROUND. Carbon dioxide lasers that produce either short pulses or scanned continuous beams have been used for skin resurfacing to improve wrinkles or scars. Using a high peak power, short pulse CO2 laser can produce clinically effective results with minimal thermal damage. OBJECTIVE. TO evaluate the effectiveness Of skin resurfacing using the 90-mu s pulse duration CO2 laser compared to other laser systems. Erythema, healing time, complications, and histological measurement of the depth of ablation and thermal damage per pass with this system were also assessed. METHODS. Forty-one patients with facial rhytides and scars underwent resurfacing With a 90 mu sec pulse duration CO2 laser. Using patient survey, patients were evaluated for effectiveness of therapy, healing time, and complication rates. Comparisons of histologic and clinical findings Were made with different short pulse CO2 lasers. RESULTS. Healing time, duration Of erythema, and post-operative pain were less with the 90 mu s pulse CO2 laser than With the 900-mu s dwell time and 950-mu s pulse duration lasers, while effectiveness teas comparable. Complications were few with the 90-mu s pulse laser, including three patients (9.1%) developing hyperpigmentation. One pass with the 90-mu s pulse duration CO2 laser produced 100 mu m Of ablation With 17 mu m of thenrml damage. Ablation and damage were additive so that, by six passes, ablation depth was 350 mu m and depth of thermal damage Was 63 mu m. This thermal damage is less than that reported with lasers having a longer pulse duration or dwell time with comparable depths of vaporization. CONCLUSION. Treatment with the 90-mu s pulse duration laser results in a more rapid healing time and shorter duration erythema. The clinical improvements in wrinkles and sun damage were comparable. The 90-mu s pulse duration laser provides an effective, predictable, and safe means of improving facial rhytides and scars. (C) 1998 by the American Society for Dermatologic Surgery, Inc. C1 Univ Calif Los Angeles, Div Dermatol, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Moy, RL (reprint author), 100 UCLA Med Plaza,Suite 590, Los Angeles, CA 90024 USA. NR 9 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD DEC PY 1998 VL 24 IS 12 BP 1390 EP 1396 PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 149QC UT WOS:000077615800024 PM 9865210 ER PT J AU Drummond, IA Majumdar, A Hentschel, H Elger, M Solnica-Krezel, L Schier, AF Neuhauss, SCF Stemple, DL Zwartkruis, F Rangini, Z Driever, W Fishman, MC AF Drummond, IA Majumdar, A Hentschel, H Elger, M Solnica-Krezel, L Schier, AF Neuhauss, SCF Stemple, DL Zwartkruis, F Rangini, Z Driever, W Fishman, MC TI Early development of the zebrafish pronephros and analysis of mutations affecting pronephric function SO DEVELOPMENT LA English DT Article DE zebrafish; pronephros; kidney; nephron; fleer; pao pao tang; double bubble ID MICE LACKING GDNF; POLYCYSTIC KIDNEY-DISEASE; TUMOR SUPPRESSOR GENE; WILMS-TUMOR; UROGENITAL DEVELOPMENT; ALPORT SYNDROME; HOMEOBOX GENE; EXPRESSION; SYSTEM; XENOPUS AB The zebrafish pronephric kidney provides a simplified model of nephron development and epithelial cell differentiation which is amenable to genetic analysis, The pronephros consists of two nephrons with fused glomeruli and paired pronephric tubules and ducts. Nephron formation occurs after the differentiation of the pronephric duct with both the glomeruli and tubules being derived from a nephron primordium. Fluorescent dextran injection experiments demonstrate that vascularization of the zebrafish pronephros and the onset of glomerular filtration occurs between 40 and 48 hpf. We isolated fifteen recessive mutations that affect development of the pronephros. All have visible cysts in place of the pronephric tubule at 2-2.5 days of development. Mutants were grouped in three classes: (1) a group of twelve mutants with defects in body axis curvature and manifesting the most rapid and severe cyst formation involving the glomerulus, tubule and duct, (2) the fleer mutation with distended glomerular capillary loops and cystic tubules, and (3) the mutation pao pao tang with a normal glomerulus and pronephric tubules, double bubble was analyzed as a representative of mutations that perturb the entire length of the pronephros and body axis curvature. Cyst formation begins in the glomerulus at 40 hpf at the time when glomerular filtration is established suggesting a defect associated with the onset of pronephric function. Basolateral membrane protein targeting in the pronephric duct epithelial cells is also severely affected, suggesting a failure in terminal epithelial cell differentiation and alterations in electrolyte transport. These studies reveal the similarity of normal pronephric development to kidney organogenesis in all vertebrates and allow for a genetic dissection of genes needed to establish the earliest renal function. C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. MPI Dortmund, Max Planck Inst Mol Physiol, D-44026 Dortmund, Germany. Univ Heidelberg, Inst Anat & Zellbiol, D-69120 Heidelberg, Germany. RP Drummond, IA (reprint author), Massachusetts Gen Hosp, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [R01 DK53093-01] NR 64 TC 261 Z9 273 U1 0 U2 23 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 DEC PY 1998 VL 125 IS 23 BP 4655 EP 4667 PG 13 WC Developmental Biology SC Developmental Biology GA 151VW UT WOS:000077742200008 PM 9806915 ER PT J AU Vasir, B Aiello, LP Yoon, KH Quickel, RR Bonner-Weir, S Weir, GC AF Vasir, B Aiello, LP Yoon, KH Quickel, RR Bonner-Weir, S Weir, GC TI Hypoxia induces vascular endothelial growth factor gene and protein expression in cultured rat islet cells SO DIABETES LA English DT Article ID PERMEABILITY FACTOR; IN-VITRO; TRANSPLANTED ISLETS; PANCREATIC-ISLETS; RETINAL PERICYTES; FACTOR FAMILY; ANGIOGENESIS; INSULIN; LANGERHANS; INDUCTION AB The formation of new microvasculature by capillary sprouting at the site of islet transplantation is crucial for the long-term survival and function of the graft. Vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen with potent angiogenic and vascular permeability-inducing properties, may be a key factor in modulating the revascularization of islets after transplantation. In this study, me examined the gene expression of VEGF mRNA in three tumor cell Lines and in isolated whole and dispersed rat islets in vitro by Northern blot hybridization in normoxic (5% CO2, 95% humidified air) and hypoxic (1% O-2, 5% CO2, 94% N-2) culture conditions. Increased expression of VEGF mRNA was observed in beta-TC3, RAW 264.7, and IC-21 tumor cell lines when subjected to hypoxia. With isolated whole islets in normoxic culture, a threefold increase in VEGF mRNA (P < 0.001) was seen at 48 h as compared with freshly isolated islets. This response was similar to the 3.8-fold increase observed with islets subjected to hypoxia. Dispersed rat islet cell clusters cultured on Matrigel for 24 h under hypoxic conditions showed a 3.4-fold increase (P < 0.01) in VEGF mRNA compared with those cultured in normoxia. This correlated with increased VEGF secretion as determined by enzyme-linked immunosorbent assay. Immunohistochemical studies revealed the presence of increased expression of VEGF protein near the center of islets after 24 h of normoxic culture. Islet cell clusters on Matrigel showed intense cellular localization of VEGF in both beta-cells and non-beta-cens. These findings suggest that rat islet cells, when subjected to hypoxia during the first few days after transplantation, may act as a major source of VEGF, thereby initiating revascularization and maintaining the vascular permeability of the grafted islets. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Beetham Eye Inst, Boston, MA USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA USA. RP Weir, GC (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM weirg@joslab.harvard.edu FU NEI NIH HHS [EY-10827]; NIDDK NIH HHS [DK-36836, DK-50657] NR 66 TC 99 Z9 100 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 1998 VL 47 IS 12 BP 1894 EP 1903 DI 10.2337/diabetes.47.12.1894 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 142KP UT WOS:000077199800011 PM 9836521 ER PT J AU Bao, S Kennedy, A Wojciechowski, B Wallace, P Ganaway, E Garvey, WT AF Bao, S Kennedy, A Wojciechowski, B Wallace, P Ganaway, E Garvey, WT TI Expression of mRNAs encoding uncoupling proteins in human skeletal muscle - Effects of obesity and diabetes SO DIABETES LA English DT Article ID BROWN ADIPOSE-TISSUE; ENERGY-EXPENDITURE; GENE-EXPRESSION; THERMOGENESIS; INSULIN; GLUCOSE; MEDIATOR; HOMOLOG; LEPTIN AB To explore the potential role of the uncoupling protein (UCP) family in human obesity and diabetes, we have used the reverse transcription-polymerase chain reaction to quantify UCP mRNA expression in human skeletal muscle. Levels of mRNA for UCP2, and for both short (UCP3S) and long (UCP3L) forms of UCP3, were highly correlated in individuals, indicating that gene transcription of these UCPs may be coordinately regulated by common mechanisms. In normal glucose-tolerant individuals, muscle UCP2 mRNA levels mere positively correlated with percentage of body fat and with BMI (r = 0.6 and P < 0.05 for both). UCP3S mRNA levels were also positively correlated with percentage of body fat (r = 0.52, P < 0.05), and UCP3L mRNA tended to increase as a function of obesity (0.05 < P < 0.1). UCP mRNA levels, however were not correlated with resting metabolic rate. UCP3S and UCP3L mRNA levels (P < 0.05) and the UCP2 mRNA level (P = 0.09) were increased by 1.8- to 2.7-fold in type 2 diabetes, an effect that could not be explained by obesity. No significant difference was found for UCP2, UCP3S, or UCP3L mRNA levels between insulin-sensitive and insulin-resistant nondiabetic subgroups. We conclude that 1) skeletal muscle mRNA levels encoding UCP2 and UCP3 are correlated among individuals and may be coordinately regulated; 2) UCP3 expression is not regulated by differential effects on UCP3L and UCP3S forms of the mRNA; and 3) UCP mRNA expression tends to increase in muscle as a function of obesity but not of resting metabolic rate or insulin resistance, and is increased in patients with type 2 diabetes. C1 Med Univ S Carolina, Div Endocrinol, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Garvey, WT (reprint author), Med Univ S Carolina, Div Endocrinol, Dept Med, 171 Ashley Ave, Charleston, SC 29425 USA. EM garveywt@musc.edu FU NCRR NIH HHS [M01-RR-1070]; NIDDK NIH HHS [DK-38765, DK-47461] NR 26 TC 71 Z9 72 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 1998 VL 47 IS 12 BP 1935 EP 1940 DI 10.2337/diabetes.47.12.1935 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 142KP UT WOS:000077199800017 PM 9836527 ER PT J AU Mayfield, JA Reiber, GE Sanders, LJ Janisse, D Pogach, LM AF Mayfield, JA Reiber, GE Sanders, LJ Janisse, D Pogach, LM TI Preventive foot care in people with diabetes SO DIABETES CARE LA English DT Review ID PERIPHERAL VASCULAR-DISEASE; LOWER-EXTREMITY AMPUTATION; LIMITED JOINT MOBILITY; PLANTAR PRESSURE DISTRIBUTION; TOE BLOOD-PRESSURE; RISK-FACTORS; ARTERIAL-DISEASE; NEUROPATHIC FOOT; SENSORY NEUROPATHY; AUTONOMIC NEUROPATHY C1 Indiana Univ, Bowen Res Ctr, Dept Family Practice, Indianapolis, IN USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res Ctr, Seattle, WA USA. Vet Affairs Med Ctr, Lebanon, PA USA. Med Coll Wisconsin, Dept Phys Med & Rehabil, Milwaukee, WI 53226 USA. Vet Affairs Med Ctr, E Orange, NJ USA. RP Mayfield, JA (reprint author), Indiana Univ, Long Hosp, Bowen Res Ctr, Dept Family Med, 1110 W Michigan St,Room 200, Indianapolis, IN 46202 USA. NR 200 TC 206 Z9 217 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD DEC PY 1998 VL 21 IS 12 BP 2161 EP 2177 DI 10.2337/diacare.21.12.2161 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 141UP UT WOS:000077162900020 PM 9839111 ER PT J AU Testa, MA Simonson, DC Turner, RR AF Testa, MA Simonson, DC Turner, RR TI Valuing quality of life and improvements in glycemic control in people with type 2 diabetes SO DIABETES CARE LA English DT Article; Proceedings Paper CT Workshop on the Worldwide Burden of Diabetes CY DEC 06-07, 1996 CL PHOENIX, AZ SP Amylin Pharmaceut Inc ID OF-LIFE; ANTIHYPERTENSIVE THERAPY; MELLITUS; INSULIN; HYPOGLYCEMIA; HYPERGLYCEMIA; ENALAPRIL; SYMPTOMS; IDDM AB Outcomes research is used increasingly for assessing the health economic benefits of new therapeutic programs and interventions. The measurement properties of the outcomes assessment tools are important. If overlooked, they can mislead health care administrators and caregivers regarding the importance and value of these programs and interventions. We reviewed the literature and conducted two analyses to determine the absolute, relative, and operative quality-of-life ranges for people with type 2 diabetes. Quality of life and fasting blood glucose and HMI, concentrations were measured at baseline and at 4, 8, and 12 weeks of treatment in 569 men and women randomized to either glipizide gastrointestinal therapeutic system (GITS) or placebo in a double-blind, multicenter clinical trial. A subgroup of 290 patients completed a diabetes-specific health states questionnaire at endpoint (week 12 or early termination) rating 10 health-state descriptions on a health thermometer scale ranging from 0 (death) to 100 (full health). Health losses at the higher end of the scale had a greater negative utility than did comparable losses at lower health states, indicating patients' strong preferences for maintaining asymptomatic or mildly symptomatic conditions. patients rated their current health state at 83.4 +/- 0.8% of full health and indicated that a loss of 27 points below this value would prevent them from living and working as they currently do. The calibration analysis applied to the quality-of-life scales suggested that the targeted range for clinical investigation and quality-of-care evaluation must be more narrowly focused. Effect sizes as seemingly small as 2% (0.25 responsiveness units) on the absolute scare can correspond to quality-of-life losses of 15-20% on the personal operative scale. Differences in glycemic control clearly affected quality of life. Those patients with the best HbA(1c) responses (decreasing 1.5% or more from baseline) versus those with the worst responses (increasing 1.5% or more from baseline) were separated by 0.6 responsiveness units for the overall quality-of-life summary measure. The calibration analysis suggested that this degree of better glycemic control provides a nearly 50% gain in quality of life according to personal expectations within the operative range. In conclusion, general measures of quality of life may be too crude and insensitive to capture the important gains in health outcomes due to new therapeutic interventions and programs in diabetes. Quality-of-care evaluations for diabetes are at risk of favoring inferior programs with lower costs simply because gains or losses in health outcomes go undetected. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Brigham & Womens Hosp,Dept Med, Boston, MA 02115 USA. Phase V Technol, Wellesley, MA USA. RP Testa, MA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. EM testa@sdac.harvard.edu FU AHRQ HHS [R01 HS07767] NR 38 TC 30 Z9 32 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD DEC PY 1998 VL 21 SU 3 BP C44 EP C52 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 143MT UT WOS:000077260000013 PM 9850489 ER PT J AU Morgan, DG Kulkarni, RN Hurley, JD Wang, ZL Wang, RM Ghatei, MA Karlsen, AE Bloom, SR Smith, DM AF Morgan, DG Kulkarni, RN Hurley, JD Wang, ZL Wang, RM Ghatei, MA Karlsen, AE Bloom, SR Smith, DM TI Inhibition of glucose stimulated insulin secretion by neuropeptide Y is mediated via the Y1 receptor and inhibition of adenylyl cyclase in RIN 5AH rat insulinoma cells SO DIABETOLOGIA LA English DT Article DE neuropeptide Y; Y1 receptor; insulin secretion; insulinoma cells ID ISLET AMYLOID POLYPEPTIDE; PEPTIDE-YY; FUNCTIONAL EXPRESSION; DEXAMETHASONE TREATMENT; PANCREATIC-POLYPEPTIDE; GLUCAGON-SECRETION; PARACRINE ROLE; G-PROTEIN; CLONING; RELEASE AB Neuropeptide Y (NPY) has been shown to inhibit insulin secretion from the islets of Langerhans. We show that insulin secretion in the insulinoma cell line RIN 5AH is inhibited by NPY. I-125-Peptide YY (PYY) saturation and competition-binding studies using NPY fragments and analogues on membranes prepared from this cell line show the presence of a single class of NPY receptor with a Y1 receptor subtype-like profile. Inhibition of insulin secretion in this cell line by NPY fragments and analogues also shows a Y1 receptor-like profile. Both receptor binding and inhibition of insulin secretion showed the same orders of potency with NPY > [Pro(34)] NPY > NPY 3-36 > > NPY 13-36. The Y1 receptor antagonist, BIBP 3226, blocks NPY inhibition of insulin secretion from, and inhibits I-125-PYY binding to, RIN 5AH cells. Northern blot analysis using a Y1-receptor specific probe shows that NPY Y1 receptors are expressed by RIN 5AH cells. Y5 receptors are not expressed in this cell line. Neuropeptide Y inhibition of insulin secretion is blocked by incubation with pertussis toxin, implying that the effect is via a G-protein (G(i) or G(o)) coupled receptor. Neuropeptide Y inhibits the activation of adenylyl cyclase by isoprenaline in RIN 5AH. cell lysates, and the stimulation of cAMP by glucagon-like peptide-1 (7-36) amide (GLP-1). It also blocks insulin secretion stimulated by GLP-1, but not by dibutyryl cyclic AMP. Hence, we suggest that NPY inhibits insulin secretion from RIN SAH cells via a Y1 receptor linked through G(i) to the inhibition of adenylyl cyclase. C1 Univ London Imperial Coll Sci Technol & Med, Sch Med, Hammersmith Hosp, ICSM Endocrine Unit, London W12 0HH, England. Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Cellular & Mol Physiol, Boston, MA 02115 USA. Harvard Univ, Inst Med, Dept Expt Med, Boston, MA 02115 USA. Steno Diabet Ctr, DK-2820 Gentofte, Denmark. RP Smith, DM (reprint author), Univ London Imperial Coll Sci Technol & Med, Sch Med, Hammersmith Hosp, ICSM Endocrine Unit, Du Cane Rd, London W12 0HH, England. NR 44 TC 55 Z9 55 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD DEC PY 1998 VL 41 IS 12 BP 1482 EP 1491 DI 10.1007/s001250051095 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 145CA UT WOS:000077352400011 PM 9867216 ER PT J AU Shellito, PC AF Shellito, PC TI Complications of abdominal stoma surgery SO DISEASES OF THE COLON & RECTUM LA English DT Review DE colostomy; ileostomy; colostomy complications; ileostomy complications; peristomal hernia; colostomy closure; ileostomy closure ID LOOP TRANSVERSE COLOSTOMY; TEMPORARY FECAL DIVERSION; EARLY LOCAL COMPLICATIONS; POUCH-ANAL ANASTOMOSIS; LIFE-TABLE ANALYSIS; HARTMANN PROCEDURE; ULCERATIVE-COLITIS; PARASTOMAL HERNIAS; INTESTINAL STOMAS; CLINIC EXPERIENCE AB PURPOSE: This study was undertaken to review and summarize the complications of ileostomy and colostomy creation and subsequent closure. METHODS: The English-language medical literature for at least the past 15 years was reviewed comprehensively. RESULTS: Complications of surgery for the creation of end, loop, and "end loop" stomas are presented. Technical factors, which might influence complication rates, are discussed. Optimal management of ostomy complications is presented, especially for peristomal hernias. Similarly, techniques and complications for stoma closure are analyzed. CONCLUSIONS: Stoma creation is not a trivial undertaking; careful surgical technique minimizes complications (which are relatively frequent), and promotes good ostomy function. Peristomal hernias are difficult to cure permanently. The morbidity of ileostomy and colostomy closure is also appreciable. C1 Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Shellito, PC (reprint author), Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. NR 113 TC 103 Z9 111 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD DEC PY 1998 VL 41 IS 12 BP 1562 EP 1572 DI 10.1007/BF02237308 PG 11 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 147GL UT WOS:000077480700019 PM 9860339 ER PT J AU Lipsky, BA AF Lipsky, BA TI Pexiganan acetate - A viewpoint SO DRUGS LA English DT Editorial Material C1 Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Lipsky, BA (reprint author), Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PD DEC PY 1998 VL 56 IS 6 BP 1053 EP 1053 DI 10.2165/00003495-199856060-00012 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 150DY UT WOS:000077649100013 ER PT J AU Rosenbek, JC Robbins, J Willford, WO Kirk, G Schiltz, A Sowell, TW Deutsch, SE Milanti, FJ Ashford, J Gramigna, GD Fogarty, A Dong, K Rau, MT Prescott, TE Lloyd, AM Sterkel, MT Hansen, JE AF Rosenbek, JC Robbins, J Willford, WO Kirk, G Schiltz, A Sowell, TW Deutsch, SE Milanti, FJ Ashford, J Gramigna, GD Fogarty, A Dong, K Rau, MT Prescott, TE Lloyd, AM Sterkel, MT Hansen, JE TI Comparing treatment intensities of tactile-thermal application SO DYSPHAGIA LA English DT Article DE dysphagia treatment; thermal stimulation; stroke rehabilitation; dysphagia; deglutition; deglutition disorders ID DYSPHAGIA; STROKE AB The purpose of this study was to investigate the relationships of four intensities of tactile-thermal application (TTA) to changes in duration of stage transition (DST) and performance on a newly designed scale of penetration and aspiration by groups of patients made dysphagic by stroke. Patients were randomly assigned to receive 150, 300, 450, or 600 trials of TTA during each of 2 weeks. Data on the time required to provide such treatment, the actual number of trials clinicians were able to provide, and on the influence of the four intensities are provided. No single intensity emerged as the most therapeutic. It is suggested that subsequent studies with larger groups include intensities between 300 and 550. C1 UNIV WISCONSIN,WILLIAM S MIDDLETON MEM VET HOSP,SCH MED,DEPT MED,MADISON,WI 53705. VET ADM MED CTR,COOPERAT STUDIES PROGRAM,COORDINATING CTR,PERRY POINT,MD. AURORA REG MED CTR,AURORA,CO. VET ADM MED CTR,LITTLE ROCK,AR. VET ADM MED CTR,LONG BEACH,CA. HINES VA HOSP,HINES,IL. VET ADM MED CTR,NASHVILLE,TN. VET ADM MED CTR,BROCKTON,MA. VET ADM MED CTR,N CHICAGO,IL. VET ADM MED CTR,PORTLAND,OR. VET ADM MED CTR,DENVER,CO. RICHARD L RONDEBUSH VET MED CTR,INDIANAPOLIS,IN. VET ADM MED CTR,RENO,NV. VA PUGET SOUND HLTH CARE SYST,SEATTLE,WA. RP Rosenbek, JC (reprint author), UNIV WISCONSIN,WILLIAM S MIDDLETON MEM VET HOSP,SCH MED,DEPT NEUROL,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. NR 10 TC 36 Z9 37 U1 1 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0179-051X J9 DYSPHAGIA JI Dysphagia PD WIN PY 1998 VL 13 IS 1 BP 1 EP 9 DI 10.1007/PL00009542 PG 9 WC Otorhinolaryngology SC Otorhinolaryngology GA YJ970 UT WOS:A1998YJ97000001 PM 9391220 ER PT J AU Cook, IA O'Hara, R Uijtdehaage, SHJ Mandelkern, M Leuchter, AF AF Cook, IA O'Hara, R Uijtdehaage, SHJ Mandelkern, M Leuchter, AF TI Assessing the accuracy of topographic EEG mapping for determining local brain function SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE positron emission tomography; cerebral perfusion; montage; quantitative EEG ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; QUANTITATIVE EEG; ELECTRICAL-ACTIVITY; ALZHEIMERS-DISEASE; INFARCTION; DEMENTIA; ELECTROENCEPHALOGRAPHY; SPECT; POWER AB Objective: There has been considerable discussion regarding the accuracy of topographic electroencephalographic (EEG) maps for assessing local cerebral function. We performed this study to test the accuracy of EEG mapping by examining the association between electrical activity and the perfusion under each electrode as another measure of local cerebral function. Methods: EEG mapping was performed simultaneously with (H2O)-O-15 positron emission tomography (PET) scanning in 6 normal adult subjects, both at rest and during a simple motor task. EEG data were processed using 3 different montages; two EEG power measures (absolute and relative power) were examined. Results: Relative power had much stronger associations with perfusion than did absolute power. In addition, calculating power for bipolar electrode pairs and averaging power over electrode pairs sharing a common electrode yielded stronger associations with perfusion than data from referential or single source montages. Conclusions: These findings indicate (1) that topographic EEG mapping can accurately reflect local brain function in a way that is comparable to other methods, and (2) that the choice of EEG measure and montage have a significant influence on the degree with which maps reflect this local activity and function. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Calif Los Angeles, Sch Med, Neuropsychiat Inst & Hosp, Quantitat EEG Lab, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. W Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. RP Cook, IA (reprint author), Univ Calif Los Angeles, NPI, 760 Westwood Plaza, Los Angeles, CA 90024 USA. EM icook@ucla.edu OI Uijtdehaage, Sebastian/0000-0001-8598-4683 FU NIA NIH HHS [P30-AG10123]; NIMH NIH HHS [R01-MH40705, K02-MH01165] NR 32 TC 134 Z9 138 U1 0 U2 6 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0013-4694 J9 ELECTROEN CLIN NEURO JI Electroencephalogr. Clin. Neurophysiol. PD DEC PY 1998 VL 107 IS 6 BP 408 EP 414 DI 10.1016/S0013-4694(98)00092-3 PG 7 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA 155DD UT WOS:000077930100005 PM 9922086 ER PT J AU Bottcher, B Tsuji, N Takahashi, H Dyson, MR Zhao, S Crowther, RA Murray, K AF Bottcher, B Tsuji, N Takahashi, H Dyson, MR Zhao, S Crowther, RA Murray, K TI Peptides that block hepatitis B virus assembly: analysis by cryomicroscopy, mutagenesis and transfection SO EMBO JOURNAL LA English DT Article DE difference imaging; electron cryomicroscopy; hepatitis B virus; peptide inhibitors; virus assembly ID ELECTRON CRYOMICROSCOPY; ENVELOPE PROTEINS; BINDING-SITE; CORE ANTIGEN; INHIBITION; SEQUENCES; PARTICLES; SELECTION; PHAGE; RNA AB Peptides selected to bind to hepatitis B virus (HBV) core protein block interaction with the long viral surface antigen (L-HBsAg) in vitro. High resolution electron cryomicroscopy showed that one such peptide binds at the tips of the spikes of the core protein shell, The peptides contain two basic residues; changing either of two acidic residues at the spike tip to an alanine greatly reduced the binding affinity, Transfection of hepatoma cells with a replication-competent HBV plasmid gave significantly reduced production of virus in the presence of peptide, in a dose-dependent manner. These experiments show that the interaction of L-HBsAg with core particles is critical for HBV assembly, and give proof of principle for its disruption in vivo by small molecules. C1 MRC, Mol Biol Lab, Cambridge CB2 2QH, England. Univ Edinburgh, Inst Cell & Mol Biol, Edinburgh EH9 3JR, Midlothian, Scotland. Harvard Univ, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Murray, K (reprint author), MRC, Mol Biol Lab, Hills Rd, Cambridge CB2 2QH, England. RI Bottcher, Bettina/E-9397-2010 OI Bottcher, Bettina/0000-0002-7962-4849 FU NIDDK NIH HHS [NIDDK 4331] NR 28 TC 63 Z9 66 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 1 PY 1998 VL 17 IS 23 BP 6839 EP 6845 DI 10.1093/emboj/17.23.6839 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 149VA UT WOS:000077625600008 PM 9843489 ER PT J AU Kim, B Leventhal, PS White, MF Feldman, EL AF Kim, B Leventhal, PS White, MF Feldman, EL TI Differential regulation of insulin receptor substrate-2 and mitogen-activated protein kinase tyrosine phosphorylation by phosphatidylinositol 3-kinase inhibitors in SH-SY5Y human neuroblastoma cells SO ENDOCRINOLOGY LA English DT Article ID GROWTH-FACTOR-I; NECROSIS-FACTOR-ALPHA; PHOSPHOINOSITIDE 3-KINASE; SIGNAL-TRANSDUCTION; NEURITE OUTGROWTH; SERINE/THREONINE PHOSPHORYLATION; SH3 DOMAIN; MAP-KINASE; IRS-1; WORTMANNIN AB Insulin-like growth factor I (IGF-I) is a potent neurotropic factor promoting the differentiation and survival of neuronal cells. SH-SY5Y human neuroblastoma cells are a well characterized in vitro model of nervous system growth. We report here that IGF-I stimulated the tyrosine phosphorylation of the type I IGF receptor (IGF-IR) and insulin receptor substrate-2 (IRS-2) in a time- and concentration-dependent manner. These cells lacked IRS-1. After being tyrosine phosphorylated, IRS-2 associated transiently with downstream signaling molecules, including phosphatidylinositol 3-kinase (PI 3-K) and Grb2. Treatment of the cells with PI 3-K inhibitors (wortmannin and LY294002) increased IGF-I-induced tyrosine phosphorylation of IRS-2. We also observed a concomitant increase in the mobility of IRS-2, suggesting that PI 3-K mediates or is required for IRS-2 serine/threonine phosphorylation, and that this phosphorylation inhibits IRS-2 tyrosine phosphorylation. Treatment with PI 3-K inhibitors induced an increased association of IRS-2 with Grb2, probably as a result of the increased IRS-2 tyrosine phosphorylation. However, even though the PI 3-K inhibitors enhanced the association of Grb2 with IRS-2, these compounds suppressed IGF-I-induced mitogen-activated protein kinase activation and neurite outgrowth. Together, these results indicate that although PI 3-K participates in a negative regulation of IRS-2 tyrosine phosphorylation, its activity is required for IGF-IR-mediated mitogen-activated protein kinase activation and neurite outgrowth. C1 Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA. Univ Michigan, Program Neurosci, Ann Arbor, MI 48109 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Feldman, EL (reprint author), Univ Michigan, Dept Neurol, 4414 Kresge 3,200 Zina Pitcher Pl, Ann Arbor, MI 48109 USA. EM efeldman@umich.edu NR 55 TC 32 Z9 32 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1998 VL 139 IS 12 BP 4881 EP 4889 DI 10.1210/en.139.12.4881 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 140TG UT WOS:000077104000015 PM 9832424 ER PT J AU Delahaye, L Mothe-Satney, I Myers, MG White, MF Van Obberghen, E AF Delahaye, L Mothe-Satney, I Myers, MG White, MF Van Obberghen, E TI Interaction of insulin receptor substrate-1 (IRS-1) with phosphatidylinositol 3-kinase: Effect of substitution of serine for alanine in potential IRS-1 serine phosphorylation sites SO ENDOCRINOLOGY LA English DT Article ID HIGH-EFFICIENCY TRANSFORMATION; P85 ALPHA-GENE; PROTEIN-KINASE; TYROSINE PHOSPHORYLATION; REGULATORY SUBUNIT; SIGNAL-TRANSDUCTION; CELLS; YEAST; TRANSLOCATION; ADIPOCYTES AB Serine and threonine phosphorylation has been shown to downregulate insulin signaling at multiple steps, including the receptor and downstream molecules such as insulin receptor substrate-1 (IRS-1). To further address the mechanism of this regulation at the level of IRS-1, we constructed a double serine mutant of IRS-1: S662A/S731A-IRS-1. The serines 662 and 731 mutated to alanine are surrounding tyrosines Y658 and Y727, respectively. These tyrosines are comprised in YXXM motifs, which are potential binding sites for the p85 alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase. In a first series of experiments using the yeast two-hybrid system, we show that IRS-1 interacts with p85 alpha, and this interaction depends on tyrosine phosphorylation, as shown with the IRS-1 mutant F18 and 3Y-IRS-1. F18-IRS-1 contains 18 potential tyrosine phosphorylation sites mutated to phenylalanine; three of them, i.e. Y608, 628, and 658, which are potential binding sites for p85 alpha, have been added back in the 3Y-IRS-1 mutant. The tyrosine phosphorylation of IRS-1, which is required for the interaction with p85 alpha, is thought to occur via endogenous yeast kinases that phosphorylate IRS-1 at least on these PI 3-kinase-binding sites. Next, we show that not only p85 alpha but also p55(PIK), another regulatory subunit of PI 3-kinase, interacts with IRS-1 in yeast. Interestingly, for both regulatory subunits their interaction with IRS-1 is up-regulated by mutating serines 662 and 731 on IRS-1. In a previous study we found that insulin-stimulated PI 3-kinase activity was increased not only in the presence of S662A/S731A-IRS-1 but also under resting conditions compared with the activity seen with WT-IRS-1. Here we demonstrate in 293-EBNA cells overexpressing S662A/S731A-IRS-1 that insulin-stimulated protein kinase B activity is not augmented, whereas without insulin treatment, basal activity is increased compared with that in cells overexpressing wild-type IRS-1. In conclusion, we have shown that 1) potential serine phosphorylation sites on IRS-1, which are adjacent to YXXM binding motifs for PI S-kinase, negatively regulate binding of IRS-1 to PI 3-kinase regulatory subunits; and 2) these modulations affect protein kinase B activity. C1 Fac Med, INSERM U145, F-06107 Nice 2, France. Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Biol & Biochem Sci, Boston, MA 02115 USA. RP Delahaye, L (reprint author), Fac Med, INSERM U145, Ave Valombrose, F-06107 Nice 2, France. EM delahaye@unice.fr OI MOTHE-SATNEY, ISABELLE/0000-0002-2693-8385 NR 36 TC 35 Z9 35 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1998 VL 139 IS 12 BP 4911 EP 4919 DI 10.1210/en.139.12.4911 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 140TG UT WOS:000077104000019 PM 9832428 ER PT J AU Lanske, B Divieti, P Kovacs, CS Pirro, A Landis, WJ Krane, SM Bringhurst, FR Kronenberg, HM AF Lanske, B Divieti, P Kovacs, CS Pirro, A Landis, WJ Krane, SM Bringhurst, FR Kronenberg, HM TI The parathyroid hormone (PTH)/PTH-related peptide receptor mediates actions of both ligands in murine bone SO ENDOCRINOLOGY LA English DT Article ID OSTEOBLAST-LIKE CELLS; MATRIX GLA-PROTEIN; COMPLEMENTARY DEOXYRIBONUCLEIC ACIDS; MESSENGER RIBONUCLEIC-ACIDS; RAT OSTEOSARCOMA CELLS; PTH/PTHRP RECEPTOR; TRANSCRIPTIONAL REGULATION; OSTEOPONTIN PRODUCTION; CYTOSOLIC CALCIUM; PTH RECEPTOR AB PTH and PTH-related peptide (PTHrP) have been shown to bind to and activate the same PTH/PTHrP receptor. Recent studies have demonstrated, however, the presence of additional receptors specific for each ligand. We used the PTHrP and PTH/PTHrP receptor gene knock-out models to investigate whether this receptor mediates the actions of both ligands in bone. The similar phenotype of the PTHrP (-/-) and PTH/PTHrP receptor(-/-) animals in the growth plate of the tibia suggests that this receptor mediates the actions of PTHrP. Electron microscopic studies have confirmed the accelerated differentiation and disordered organization of chondrocytes, with the accumulation of large amounts of dispersed glycogen granules in the cytoplasm of proliferative and maturing cells of both genotypes. The contrasting growth plate mineralization patterns of the PTHrP( -/-) and PTH/PTHrP receptor(-/-) mice, however, suggest that the actions of PTHrP and the PTH/PTHrP receptor are not identical. Studies using calvariae from PTH/PTHrP receptor (-/-) embryos demonstrate that this receptor solely mediates the ability of PTH and PTHrP to stimulate adenylate cyclase in bone and to stimulate, bone resorption. Furthermore, we show that osteoblasts of PTH/PTHrP receptor (-/-) animals, but not PTHrP (-/-) animals, have decreased levels of collagenase 3, osteopontin, and osteocalcin messenger RNAs. The PTH/PTHrP receptor, therefore, mediates distinct physiologic actions of both PTH and PTHrP. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Childrens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Arthrit Unit, Boston, MA 02114 USA. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Wellmann 5, Boston, MA 02114 USA. EM kronenberg.henry@mgh.harvard.edu OI Kovacs, Christopher/0000-0002-5219-9993 NR 54 TC 58 Z9 58 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1998 VL 139 IS 12 BP 5194 EP 5204 DI 10.1210/en.139.12.5194 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 140TG UT WOS:000077104000051 PM 9832460 ER PT J AU Hayes, FJ Seminara, SB Crowley, WF AF Hayes, FJ Seminara, SB Crowley, WF TI Hypogonadotropic hypogonadism SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; FOLLICLE-STIMULATING-HORMONE; LINKED KALLMANN SYNDROME; ADRENAL HYPOPLASIA CONGENITA; HUMAN CHORIONIC-GONADOTROPIN; GNRH-DEFICIENT MEN; FREE ALPHA-SUBUNIT; LUTEINIZING-HORMONE; X-CHROMOSOME; KAL GENE AB This article outlines the changing pattern of gonadotropin-releasing hormone (GnRH)-induced gonadotropin secretion across sexual development, a knowledge of which is critical to understanding GnRH secretion in pathologic states such as hypogonadotropic hypogonadism. The clinical presentation, differential diagnosis, and treatment of hypogonadotropic hypogonadism in humans are discussed. Particular emphasis is placed on the contribution of frequent sampling studies of gonadotropin secretion and genetic studies to understanding the pathophysiology and clinical heterogeneity of isolated GnRH deficiency in humans. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hayes, FJ (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Bartlett Hall Ext 5,Fruit St, Boston, MA 02114 USA. FU NICHD NIH HHS [P30 HD028138, R01 HD015788, T32 HD007396, U54 HD028138] NR 94 TC 23 Z9 25 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD DEC PY 1998 VL 27 IS 4 BP 739 EP + DI 10.1016/S0889-8529(05)70039-6 PG 26 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 146RQ UT WOS:000077444600002 PM 9922906 ER PT J AU Taylor, AE AF Taylor, AE TI Polycystic ovary syndrome SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Review ID GONADOTROPIN-RELEASING-HORMONE; FOLLICLE-STIMULATING-HORMONE; DEPENDENT DIABETES-MELLITUS; CORONARY-ARTERY DISEASE; INSULIN-RECEPTOR GENE; GROWTH FACTOR-I; LUTEINIZING-HORMONE; OBESE WOMEN; HYPERANDROGENIC WOMEN; ADRENAL-HYPERPLASIA AB Polycystic ovary syndrome is a syndrome and not a disease. It reflects multiple potential etiologies and variable clinical presentations that are reviewed in this article. In addition to menstrual dysfunction and hyperandrogenism, women with polycystic ovary syndrome also may have hypothalamic-pituitary abnormalities, polycystic ovaries on pelvic ultrasonography, infertility, obesity, and insulin resistance. A familial pattern occurs in some cases, suggesting a genetic component to the disorder. The three major pathophysiologic hypotheses that have been proposed to explain the clinical findings of the disorder as well as treatment options are reviewed in this article. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Taylor, AE (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX-5,55 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR-01066]; NICHD NIH HHS [R29HD33509, U5U HD29164] NR 135 TC 61 Z9 66 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD DEC PY 1998 VL 27 IS 4 BP 877 EP + DI 10.1016/S0889-8529(05)70045-1 PG 27 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 146RQ UT WOS:000077444600008 PM 9922912 ER PT J AU Cabrero, JG Freeman, GJ Reiser, H AF Cabrero, JG Freeman, GJ Reiser, H TI The murine Cd48 gene: allelic polymorphism in the IgV-like region SO EUROPEAN JOURNAL OF IMMUNOGENETICS LA English DT Article ID T-CELL ACTIVATION; ANTIGEN; MOUSE; CD2; COMPLEX; SGP-60 AB The murine CD48 molecule is a member of the immunoglobulin superfamily which regulates the activation of T lymphocytes. Prior cloning experiments using mRNA from two different mouse strains had yielded discrepant sequences within the IgV-like domain of murine CD48. To resolve this issue, we have directly sequenced genomic DNA of 10 laboratory strains and two inbred strains of wild origin. The results of our analysis reveal an allelic polymorphism within the IgV-like domain of murine CD48. C1 Hammersmith Hosp, Imperial Coll, Sch Med, Dept Immunol,Div Med, London W12 0NN, England. Fdn Jimenez Diaz, Unidad Invest, E-28040 Madrid, Spain. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Reiser, H (reprint author), Hammersmith Hosp, Imperial Coll, Sch Med, Dept Immunol,Div Med, Du Cane Rd, London W12 0NN, England. FU Wellcome Trust NR 12 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0960-7420 J9 EUR J IMMUNOGENET JI Eur. J. Immunogenet. PD DEC PY 1998 VL 25 IS 6 BP 421 EP 423 DI 10.1046/j.1365-2370.1998.00136.x PG 3 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 165BQ UT WOS:000078499300007 PM 9949948 ER PT J AU Chang, L AF Chang, L TI The association of functional gastrointestinal disorders and fibromyalgia SO EUROPEAN JOURNAL OF SURGERY LA English DT Article DE irritable bowel syndrome; fibromyalgia ID IRRITABLE-BOWEL-SYNDROME; PAIN PERCEPTION; FIBROSITIS; SLEEP; CLASSIFICATION; DYSFUNCTION; STIMULATION; DISTENSION; TOLERANCE; DYSPEPSIA AB Previous epidemiological studies have confirmed the clinical impression that functional gastrointestinal disorders typically overlap with fibromyalgia (FM) in the same patient, suggesting a common etiology. FM syndrome occurs in up to 60% of patients with functional bowel disorders. Up to 50% of patients with a diagnosis of FM syndrome complain of symptoms characteristic of functional dyspepsia and 70% have symptoms of IBS. These two conditions have common clinical characteristics: (1) the majority of patients associate stressful life events with the initiation or exacerbation of symptoms, (2) the majority of patients complain of disturbed sleep and fatigue, (3) psychotherapy and behavioral therapies are efficacious in treating symptoms, and (4) low-dose tricyclic antidepressant medication can improve symptoms. Despite these similarities, their perceptual responses to both somatic and visceral stimuli differ. While FM patients characteristically exhibit somatic hyperalgesia, IBS patients without coexistent FM have somatic hypoalgesia to mechanical stimuli. Visceral distention studies have also demonstrated perceptual alterations in patients with IBS and FM although these findings appear to differ in the two conditions. Further studies will help explore the mechanisms which are responsible for the similarities and differences in clinical symptoms and physiologic parameters seen in IBS and FM. C1 W Los Angeles VA Med Ctr, CURE, Neuroenter Dis Program, Los Angeles, CA 90073 USA. RP Chang, L (reprint author), W Los Angeles VA Med Ctr, CURE, Neuroenter Dis Program, Bldg 115,Room 223,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 45 TC 1 Z9 1 U1 0 U2 1 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 1102-4151 J9 EUR J SURG JI Eur. J. Surg. PD DEC PY 1998 VL 164 SU 583 BP 32 EP 36 DI 10.1080/11024159850191210 PG 5 WC Surgery SC Surgery GA 162HQ UT WOS:000078340400006 ER PT J AU Naliboff, BD Balice, G Mayer, EA AF Naliboff, BD Balice, G Mayer, EA TI Psychosocial moderators of quality of life in irritable bowel syndrome SO EUROPEAN JOURNAL OF SURGERY LA English DT Article DE irritable bowel syndrome; quality of life; assessment AB Irritable Bowel Syndrome (IBS) is a chronic disorder with symptoms that range in intensity from mild and infrequent to severe and continuous. Similarly the impact of IBS on Quality of Life (QOL) measures can range from very small to disabling. In a very simple model one might expect a change in symptom intensity or frequency to be reflected in a similar change in QOL. However, a variety of other factors may alter this straightforward and unidirectional relationship between symptomatic treatment and QOL improvement. This paper presents several classes of these potential. moderator variables in QOL outcome in IBS, as well as specific models of symptom, moderator, QOL relationships that can be investigated in future research. An illustrative example of a regression approach to analysis of psychosocial moderator variables indicates both psychosocial measures, and symptom severity, independently contribute to the prediction of QOL in IBS. C1 W Los Angeles VA Med Ctr, Neuroenter Dis Program, CURE,Dept Med, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. W Los Angeles VA Med Ctr, Neuroenter Dis Program, CURE,Dept Physiol, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. W Los Angeles VA Med Ctr, Neuroenter Dis Program, CURE,Dept Psychiat, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Naliboff, BD (reprint author), W Los Angeles VA Med Ctr, Neuroenter Dis Program, CURE,Dept Med, Digest Dis Res Ctr, Bldg 115,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 4 TC 1 Z9 1 U1 0 U2 2 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 1102-4151 J9 EUR J SURG JI Eur. J. Surg. PD DEC PY 1998 VL 164 SU 583 BP 57 EP 59 PG 3 WC Surgery SC Surgery GA 162HQ UT WOS:000078340400010 ER PT J AU Bester, H Allchorne, AJ Woolf, CJ AF Bester, H Allchorne, AJ Woolf, CJ TI Recovery of C-fiber-induced extravasation following peripheral nerve injury in the rat SO EXPERIMENTAL NEUROLOGY LA English DT Article DE primary sensory neurons; nerve crush; degeneration; regeneration; cell death; axotomy ID GENE-RELATED PEPTIDE; NEUROGENIC PLASMA EXTRAVASATION; PRIMARY SENSORY NEURONS; DORSAL-ROOT GANGLION; PRIMARY AFFERENT NEURONS; SUBSTANCE-P; SCIATIC-NERVE; GROWTH-FACTOR; SPINAL-CORD; CRUSH INJURY AB Peripheral nerve injury leads to substantial alterations in injured sensory neurons. These include cell death, phenotypic modifications, and regeneration. Primary sensory neurons have recently been shown not to die until a time beyond 4 months following a nerve crush or ligation and this loss is, moreover, limited to cells with unmyelinated axons, the C-fibers, The late loss of C-fibers may be due to a lack of target reinnervation during the regenerative phase. In order to investigate this, we have used a particular peripheral function, unique to C-fibers, as a measure of peripheral reinnervation: an increase in capillary permeability on antidromic activation of C-fibers, i.e., neurogenic extravasation, This was investigated in rats that had received a nerve crush injury 1 to 50 weeks earlier. Some recovery of the capacity of C-fibers to generate extravasation was detected at 8-10 weeks, which increased further at 12-14 weeks, and then plateaued at this level with no further recovery at 30 or 50 weeks. In intact and damaged sciatic nerves, A beta-fibers never induced extravasation. These findings are compatible with the hypothesis that those C-fibers which make it back to their peripheral targets do not subsequently die and those that do not, may die, (C) 1998 Academic Press. C1 UCL, Dept Anat & Dev Biol, London WC1E 6BT, England. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Neuronal Plastic Res Grp, Charlestown, MA 02129 USA. RP Bester, H (reprint author), UCL, Dept Anat & Dev Biol, Medawar Bldg,Gower St, London WC1E 6BT, England. FU Wellcome Trust NR 60 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD DEC PY 1998 VL 154 IS 2 BP 628 EP 636 DI 10.1006/exnr.1998.6953 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 157TW UT WOS:000078078600032 PM 9878197 ER PT J AU Madsen, JR MacDonald, P Irwin, N Goldberg, DE Yao, GL Meiri, KF Rimm, IJ Stieg, PE Benowitz, LI AF Madsen, JR MacDonald, P Irwin, N Goldberg, DE Yao, GL Meiri, KF Rimm, IJ Stieg, PE Benowitz, LI TI Tacrolimus (FK506) increases neuronal expression of GAP-43 and improves functional recovery after spinal cord injury in rats SO EXPERIMENTAL NEUROLOGY LA English DT Article DE tacrolimus; FK506; GAP-43; immunophilin; spinal cord injury; neurite outgrowth; sprouting; photothrombotic lesion ID PERIPHERAL-NERVE INJURY; PROTEIN GAP-43; IMMUNOSUPPRESSANT FK506; MESSENGER-RNA; AXONAL REGENERATION; GROWTH; CELLS; METHYLPREDNISOLONE; PHOSPHORYLATION; BRAIN AB Tacrolimus (FK506), a widely used immunosuppressant drug, has neurite-promoting activity in cultured PC12 cells and peripheral neurons. The present study investigated whether tacrolimus affects the expression of the neuronal growth-associated protein, GAP-43, as well as functional recovery after photothrombotic spinal cord injury in the rat. In injured animals receiving tacrolimus, the number of neurons expressing GAP-43 mRNA and protein approximately doubled compared to that in injured animals receiving vehicle alone. This increase in GAP-BE-positive cells was paralleled by a significant improvement in neurological function evaluated by open-field and inclined plane tests. Another FKBP-18 ligand (V-10,367) had similar effects on GAP-43 expression and functional outcome, indicating that the observed effects of tacrolimus do not involve inhibition of the phosphatase calcineurin. Thus, tacrolimus, a drug which is already approved for use in humans, as well as other FKBP-12 ligands which do not inhibit calcineurin, could potentially enhance functional outcome after CNS injury in humans. (C) 1998 Academic Press. C1 Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. SUNY Hlth Sci Ctr, Dept Pharmacol, Syracuse, NY 13210 USA. Childrens Hosp, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Childrens Hosp, Dept Neurosurg, 300 Longwood Ave, Boston, MA 02115 USA. EM madsen_j@al.tch.harvard.edu FU NINDS NIH HHS [NS01471] NR 43 TC 85 Z9 93 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD DEC PY 1998 VL 154 IS 2 BP 673 EP 683 DI 10.1006/exnr.1998.6974 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 157TW UT WOS:000078078600037 PM 9878202 ER PT J AU Sun, BM DeSalles, AAF Medin, PM Solberg, TD Hoebel, B Felder-Allen, M Krahl, SE Ackermann, RF AF Sun, BM DeSalles, AAF Medin, PM Solberg, TD Hoebel, B Felder-Allen, M Krahl, SE Ackermann, RF TI Reduction of hippocampal-kindled seizure activity in rats by stereotactic radiosurgery SO EXPERIMENTAL NEUROLOGY LA English DT Article DE radiosurgery; kindling; epilepsy; hippocampus; rats ID CEREBRAL ARTERIOVENOUS-MALFORMATIONS; MOSSY FIBERS; EPILEPSY; IRRADIATION; RADIOTHERAPY; NEURONS; MODEL; BRAIN AB Radiosurgery may provide an alternative therapy for intractable epilepsy by eliminating or modifying abnormally active pacemaker neurons in epileptic foci. In the present study, the effect of radiosurgery on rat hippocampal kindling was examined. Rats received daily hippocampal stimulus trains until they were fully kindled. They then underwent radiosurgery of the kindled focus, receiving a single-dose of 0-, 10-, or 40-Gy. The 40-Gy group demonstrated are acute decrease in seizure threshold (3-5 days). Three months after radiosurgery, the threshold for seizures increased and the duration of afterdischarges decreased in the 40-Gy radiosurgery group compared to controls. The changes to both seizure threshold and afterdischarge duration were not significant in the 10-Gy group. These data suggest that radiosurgery is an effective means of reducing the epileptogenic activity of seizure foci. (C) 1998 Academic Press. C1 Univ Calif Los Angeles, Sch Med, Div Neurosurg, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Div Radiat Oncol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Neurosurg Serv, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Serv Neurol, Los Angeles, CA USA. RP Sun, BM (reprint author), Univ Calif Los Angeles, Sch Med, Div Neurosurg, Los Angeles, CA 90024 USA. NR 30 TC 20 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD DEC PY 1998 VL 154 IS 2 BP 691 EP 695 DI 10.1006/exnr.1998.6935 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 157TW UT WOS:000078078600039 PM 9878204 ER PT J AU Fass, R Naliboff, B Higa, L Johnson, C Kodner, A Munakata, J Ngo, JM Mayer, EA AF Fass, R Naliboff, B Higa, L Johnson, C Kodner, A Munakata, J Ngo, JM Mayer, EA TI Differential effect of long-term esophageal acid exposure on mechanosensitivity and chemosensitivity in humans SO GASTROENTEROLOGY LA English DT Article ID GASTROESOPHAGEAL REFLUX DISEASE; NONCARDIAC CHEST PAIN; BALLOON DISTENSION; SENSORY PERCEPTION; VISCERAL PAIN; HYPERALGESIA; SENSITIVITY; SENSITIZATION; INFLAMMATION; NEURONS AB Background & Aims: Chronic tissue injury in the esophagus associated with gastroesophageal reflux disease may result in sensitization of afferent pathways mediating mechanosensitivity and chemosensitivity. The aim of this study was to evaluate the sensitivity to intraluminal acid and to distention of the esophagus in patients with mild-to-moderate gastroesophageal reflux disease. Methods: Perceptual responses to intraluminal acid perfusion and to esophageal distention and pressure volume relationships were evaluated in 10 healthy volunteers and in 11 patients. Mechanosensitivity was evaluated with a barostat using unbiased distention protocols and verbal descriptor ratings of sensations. Chemosensitivity to acid was determined at baseline and after a 1-month treatment of acid suppression. Results: Patients showed enhanced perception of acid perfusion but not of esophageal distension. Chemosensitivity but not mechanosensitivity was correlated with reflux symptoms and with the degree of endoscopical ly shown tissue injury at baseline. Tissue injury was not associated with altered compliance. Conclusions: Mild-to-moderate chronic tissue injury in gastroesophageal reflux disease differentially affects mechanosensitive and chemosensitive afferent pathways. Chronic acid reflux by itself is not likely to play a role in reported esophageal hypersensitivity to distention in patients with noncardiac chest pain. C1 Univ Calif Los Angeles, Sch Med,Digest Dis Res Ctr,Dept Med, W Los Angeles Vet Affairs Med Ctr, Ctr Ulcer Res & Educ,Neuroenter Dis Program, Los Angeles, CA 90073 USA. Vet Affairs Med Ctr, Tucson, AZ USA. RP Mayer, EA (reprint author), Univ Calif Los Angeles, Sch Med,Digest Dis Res Ctr,Dept Med, W Los Angeles Vet Affairs Med Ctr, Ctr Ulcer Res & Educ,Neuroenter Dis Program, Bldg 115,Room 223,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK 48351] NR 39 TC 204 Z9 208 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 1998 VL 115 IS 6 BP 1363 EP 1373 DI 10.1016/S0016-5085(98)70014-9 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 144BW UT WOS:000077294700013 PM 9834263 ER PT J AU Mackay, F Browning, JL Lawton, P Shah, SA Comiskey, M Bhan, AK Mizoguchi, E Terhorst, C Simpson, SJ AF Mackay, F Browning, JL Lawton, P Shah, SA Comiskey, M Bhan, AK Mizoguchi, E Terhorst, C Simpson, SJ TI Both the lymphotoxin and tumor necrosis factor pathways are involved in experimental murine models of colitis SO GASTROENTEROLOGY LA English DT Article ID CD4(+) T-CELLS; INFLAMMATORY BOWEL-DISEASE; ALPHA-DEFICIENT MICE; INDUCE WASTING DISEASE; GERMINAL-CENTERS; INTESTINAL INFLAMMATION; SCID MICE; MONOCLONAL-ANTIBODIES; TRANSGENIC MICE; DISTINCT ROLES AB Background & Aims: Membrane lymphotoxin (LT) alpha/beta, a member of the tumor necrosis factor (INF) family of immune regulatory molecules, is involved both in the development of secondary lymphoid tissues and the maintenance of organized lymphoid tissues in the adult, Defects observed in the mucosal immune system in animals with a genetically disrupted LT alpha/beta pathway coupled with the expression of LT alpha/beta in activated T cells motivated an examination of the importance of this pathway in experimental colitis; Methods: Soluble LTP receptor (LT beta R) immunoglobulin fusion protein was used to inhibit the LT alpha/beta/light axis in two independent rodent models of colitis: CD45RB(hi) CD4(+)-reconstituted SCID mice and bone marrow-transplanted tg epsilon 26 mice (BM --> tg epsilon 26). Results: Treatment with LT beta R immunoglobulin attenuated the development of both the clinical and histological manifestations of the disease in these two murine models of colitis. Given the success of TNF inhibitors in the treatment of human Crohn's disease, the effects of LT beta R immunoglobulin have been compared with antibody to TNF in the BM --> tg epsilon 26 model, and both treatments were equally efficacious, Conclusions: The LT pathway plays a role in the development of colitis as important as that of the TNF system and, therefore, represents a potential novel intervention point for the treatment of inflammatory bowel disease. C1 Biogen, Dept Immunol Inflammat & Cell Biol, Cambridge, MA 02142 USA. Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Mackay, F (reprint author), Biogen, Dept Immunol Inflammat & Cell Biol, 12 Cambridge Ctr, Cambridge, MA 02142 USA. EM fabienne_mackay@bigen.com RI Mackay, Fabienne/B-7440-2008; OI Mackay, Fabienne/0000-0002-6074-2693; Browning, Jeffrey/0000-0001-9168-5233 FU NIDDK NIH HHS [P30DK-433-51, R01DK47677-01, R01DK52510] NR 67 TC 119 Z9 119 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 1998 VL 115 IS 6 BP 1464 EP 1475 DI 10.1016/S0016-5085(98)70025-3 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 144BW UT WOS:000077294700024 PM 9834274 ER PT J AU Mohr, L Tanaka, S Wands, JR AF Mohr, L Tanaka, S Wands, JR TI Ethanol inhibits hepatocyte proliferation in insulin receptor substrate 1 transgenic mice SO GASTROENTEROLOGY LA English DT Article ID RAT-LIVER REGENERATION; GROWTH-FACTOR-I; HUMAN HEPATOCELLULAR-CARCINOMA; PLECKSTRIN HOMOLOGY DOMAINS; FACTOR-BINDING PROTEIN-1; HEPATIC REGENERATION; SIGNAL-TRANSDUCTION; PHOSPHATIDYLINOSITOL-3 KINASE; TYROSINE PHOSPHORYLATION; PARTIAL-HEPATECTOMY AB Background & Aims: Long-term ethanol consumption is known to impair the ability of the liver to regenerate, but the molecular mechanisms are poorly understood. Multiple growth factors promote hepatocyte proliferation, some of which involve the insulin receptor substrate 1 (IRS-1)-mediated signal transduction pathway. To explore effects of ethanol on the IRS-1 signal liver growth in vivo, studies in transgenic mice overexpressing IRS-1 in the liver were performed because these mice show constitutive activation of the downstream signal transduction pathways leading to enhanced hepatocyte proliferation. Methods: Tyrosyl phosphorylation of IRS-1 and subsequent protein-protein interactions were examined in liver lysates from animals fed ethanol or control diet. Activity of phosphatidylinositol-3 kinase (Pl3K) and mitogen-activated protein kinase (MAPK) was assessed by specific enzymatic assays. Hepatocyte proliferation was measured by incorporation of [H-3]thymidine into liver DNA. Results: Tyrosyl phosphorylation of IRS-1, association of IRS-1 with Pl3K, and activation of downstream Pl3K and MAPK pathways were greatly reduced as a result of long-term ethanol consumption, Ethanol virtually abolished the enhanced hepatocyte DNA synthesis induced by expression of the IRS-1 transgene, Conclusions: Altered transmission of growth signals through the IRS-1-mediated signal transduction cascade may represent a molecular mechanism of how ethanol inhibits hepatocyte proliferation. C1 Massachusetts Gen Hosp, Ctr Canc, Mol Hepatol Lab, Charlestown, MA 02129 USA. Kyushu Univ, Med Inst Bioregulat, Dept Surg, Beppu, Oita, Japan. RP Wands, JR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Mol Hepatol Lab, 149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02666, AA-10102] NR 63 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 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 1998 VL 115 IS 6 BP 1558 EP 1565 DI 10.1016/S0016-5085(98)70036-8 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 144BW UT WOS:000077294700035 PM 9834285 ER PT J AU Brugge, WR AF Brugge, WR TI Endoscopic ultrasonography: The current status SO GASTROENTEROLOGY LA English DT Article ID FINE-NEEDLE ASPIRATION; ESOPHAGEAL CANCER; COMPUTED-TOMOGRAPHY; ULTRASOUND; CARCINOMA; ENDOSONOGRAPHY; BIOPSY; DIAGNOSIS; INVASION; TUMORS C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Blake 452C, Boston, MA 02114 USA. EM Brugge.william@mgh.harvard.edu NR 37 TC 40 Z9 44 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 1998 VL 115 IS 6 BP 1577 EP 1583 DI 10.1016/S0016-5085(98)70039-3 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 144BW UT WOS:000077294700038 PM 9834288 ER PT J AU Jutabha, R Jensen, DM Machicado, G Hirabayashi, K AF Jutabha, R Jensen, DM Machicado, G Hirabayashi, K TI Randomized controlled studies of Injection Gold Probes compared with monotherapies for hemostasis of bleeding canine gastric ulcers SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID ENDOSCOPIC LOCAL INJECTION; PEPTIC-ULCER; HEATER PROBE; HEMORRHAGE; THERAPY; TRIAL; ELECTROCOAGULATION; SCLEROTHERAPY; COAGULATION; VARICES AB Background: There is a significant interest in combination therapy using endoscopic epinephrine injection and thermal coagulation for nonvariceal hemostasis. The purpose of the study was to compare the relative effectiveness, ease of use, and safety of new Injection Gold Probes to other hemostasis techniques in three randomized, controlled laboratory studies of bleeding canine gastric ulcers. Methods: Fifteen dogs with prehepatic portal hypertension were heparinized and bleeding gastric ulcers were induced with jumbo biopsy forceps. Three different prototypes of Injection Gold Probes were compared with monotherapy (thermal, electrocoagulation, or epinephrine injection alone), control, or combination therapy with separate injector and thermal probes. The treatment times, total number of pulses or injections, volume of epinephrine injected, and ease of applications were recorded. Gastric ulcer size, ulcer healing, and complications were evaluated at 1 and 4 weeks. Results: All endoscopic treatments were effective for acute hemostasis compared with control. Thermal coagulation alone was the fastest treatment to perform. The performance of the first Injection Gold Probe prototype was restricted by its small-gauge needle. The second and third Injection Gold Probe prototypes had a larger-gauge needle and irrigation channel which made them faster and easier to use than separate injection catheters and thermal probes. Conclusions: The advantages of Injection Gold Probes were the ability to irrigate, inject, and coagulate without probe removal. Combination therapy did not increase treatment-related complications compared with monotherapies. C1 Univ Calif Los Angeles, Ctr Hlth Sci, Div Digest Dis, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Ctr Hlth Sci, Ctr Ulcer Res & Educ, Digest Dis Res Ctr, Los Angeles, CA 90095 USA. W Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. RP Jutabha, R (reprint author), Univ Calif Los Angeles, Ctr Hlth Sci, Div Digest Dis, Dept Med, CHS 44-133, Los Angeles, CA 90095 USA. NR 31 TC 9 Z9 10 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD DEC PY 1998 VL 48 IS 6 BP 598 EP 605 DI 10.1016/S0016-5107(98)70042-2 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 149WG UT WOS:000077628800007 PM 9852450 ER PT J AU Holland, EC Hively, WP DePinho, RA Varmus, HE AF Holland, EC Hively, WP DePinho, RA Varmus, HE TI A constitutively active epidermal growth factor receptor cooperates with disruption of G(1) cell-cycle arrest pathways to induce glioma-like lesions in mice SO GENES & DEVELOPMENT LA English DT Article DE EGFR; gliomagenesis; cell cycle arrest ID EGFR GENE AMPLIFICATION; WNT-1 TRANSGENIC MICE; GLIOBLASTOMA-MULTIFORME; MAMMARY CARCINOGENESIS; CDK4 AMPLIFICATION; TUMOR SUPPRESSION; INK4A LOCUS; EXPRESSION; P53; DELETION AB The epidermal growth factor receptor (EGFR) gene is amplified or mutated in 30%-50% of human gliobastoma multiforme (GBM). These mutations are associated usually with deletions of the INK4a-ARF locus, which encodes two gene products (p16(INK4a) and p19(ARF)) involved in cell-cycle arrest and apoptosis. We have investigated the role of EGFR mutation in gliomagenesis, using avian retroviral vectors to transfer a mutant EGER gene to glial precursors and astrocytes in transgenic mice expressing tv-a, a gene encoding the retrovirus receptor. TVA, under control of brain cell type-specific promoters. We demonstrate that expression of a constitutively active, mutant form of EGER in cells in the glial lineage can induce lesions with many similarities to human gliomas. These lesions occur more frequently with gene transfer to mice expressing tv-a from the progenitor-specific nestin promoter than to mice expressing tv-a from the astrocyte-specific glial fibrillary acidic protein (GFAP) promoter, suggesting that tumors arise more efficiently from immature cells in the glial lineage. Furthermore, EGFR-induced gliomagenesis appears to require additional mutations in genes encoding proteins involved in cell-cycle arrest pathways. We have produced these combinations by simultaneously infecting tv-a transgenic mice with vectors carrying cdk4 and EGFR or by infecting tv-a transgenic mice bearing a disrupted INK4a-ARF locus with the EGFR-carrying vector alone. Moreover, EGFR-induced gliomagenesis does not occur in conjunction with p53 deficiency, unless the mice are also infected with a vector carrying cdk4. The gliomagenic combinations of genetic lesions required in mice are similar to those found in human gliomas. C1 NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Holland, EC (reprint author), MD Anderson Cancer Ctr, Dept Neurosurg, Houston, TX 77030 USA. EM eholland@notes.mdacc.tmc.edu FU NEI NIH HHS [EY11267] NR 41 TC 334 Z9 342 U1 1 U2 7 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD DEC 1 PY 1998 VL 12 IS 23 BP 3675 EP 3685 DI 10.1101/gad.12.23.3675 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 149WU UT WOS:000077630000006 PM 9851974 ER PT J AU Sorensen, G Hunt, MK Cohen, N Stoddard, A Stein, E Phillips, J Baker, F Combe, C Hebert, J Palombo, R AF Sorensen, G Hunt, MK Cohen, N Stoddard, A Stein, E Phillips, J Baker, F Combe, C Hebert, J Palombo, R TI Worksite and family education for dietary change: the Treatwell 5-a-Day program SO HEALTH EDUCATION RESEARCH LA English DT Article ID COMMUNITY-HEALTH PROMOTION; CANCER PREVENTION; VEGETABLE INTAKE; UNITED-STATES; INTERVIEW SURVEY; ESTIMATE FRUIT; NUTRITION; FAT; PATTERNS; MODELS AB The National Cancer Institute's '5-a-Day for Better Health Campaign' is examining the efficacy of interventions in increasing the consumption of fruits and vegetables to five or more servings a day, This paper presents the study design, intervention and baseline survey results of the Treatwell 5-a-Day project, a randomized, controlled worksite-based intervention study. Twenty-two community health centers were randomly assigned to either a Minimal Intervention, Worksite Intervention or Worksite Plus Family Intervention, The Worksite Intervention included participation of employee advisory boards, programs aimed at individual behavior change and programs aimed at changes in the worksite environment. The Worksite Plus Family Intervention incorporated family-focused interventions into the worksite program, including a learn-at-home program, family newsletter, family festival and materials mailings. A self-administered survey was conducted prior to randomization (mean response rate: 87%, n = 1359), Twenty-three percent reported consuming five or more servings of fruits and vegetables a day. Consumption of fruits and vegetables was directly associated with level of household support for healthy eating. The Treatwell 5-a-Day intervention model has the potential to enhance existing worksite-based intervention through incorporation of its family focus, especially given the association of household support with individual eating habits. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Univ Massachusetts, Sch Publ Hlth, Amherst, MA 01003 USA. Univ Massachusetts, Sch Med, Worcester, MA 02655 USA. Massachusetts Dept Publ Hlth, Boston, MA 02108 USA. RP Sorensen, G (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [5 R01 CA59728] NR 84 TC 29 Z9 29 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1153 J9 HEALTH EDUC RES JI Health Educ. Res. PD DEC PY 1998 VL 13 IS 4 BP 577 EP 591 DI 10.1093/her/13.4.577 PG 15 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 151AD UT WOS:000077698000010 PM 10345908 ER PT J AU Yamaoka, Y Kodama, T Kita, M Imanishi, J Kashima, K Graham, DY AF Yamaoka, Y Kodama, T Kita, M Imanishi, J Kashima, K Graham, DY TI Relationship of vacA genotypes of Helicobacter pylori to cagA status, cytotoxin production, and clinical outcome SO HELICOBACTER LA English DT Article ID VACUOLATING CYTOTOXIN; PEPTIC-ULCER; DUODENAL-ULCER; GASTRIC-CANCER; GENE; STRAINS; EXPRESSION; INFECTION; DISEASE; JAPAN AB Background. Mosaicism in vacA alleles with three distinct families of vacA signal sequences (sla, s1b and s2) and two distinct families of middle region alleles (ml and m2) has been reported. It was suggested that the vacA sla genotype was closely associated with duodenal ulcer disease and with high cytotoxin production. The aim of this study was to evaluate the role of vacA genotyping with respect to gastric inflammation and injury, cytotoxin activity, and clinical presentation. Methods. H. pylori from patients with gastritis, peptic ulcer disease, or gastric cancer were characterized by vacA typing by polymerase chain reaction (PCR) and DNA sequencing. In vitro cytotoxin activity was assessed by vacuolation assay using Vero cells as well as with Hela cells. Results. Four hundred ninety-one strains were tested. vacA genotype s1a/m1 was present in more than 95% of strains independent of presentation with gastritis, peptic ulcer, or gastric cancer. No vacA genotype was associated with high average cytotoxin activity. The s2/m2 isolates had low or absent cytotoxin activity. All cagA negative strains (n = 18) were sla strains and both s2/m2 strains were cagA positive. One strain that was a recombinant of mi and m2 strains was identified and had low cytotoxin activity. The nucleotide and amino acid sequences between original mi strains and Japanese mi strains (new mi strains) were about 85% and 81%, respectively. Strains with the new mi genotype had nucleotide and amino acid sequences similarity of more than 96%. There was no difference in cytotoxin activity between strains with the Western type mi and the new type mi genotype. Conclusion. In this as in other reported studies (approximate to 1500 patients overall) vacA genotype was strongly but not exclusively associated with the presence of cagA. Overall, the studies did not support a role for vacA genotyping in relation to cytotoxin activity, virulence, histologic finding, or risk of a particular H. pylori disease. vacA genotype sl is likely to be a surrogate marker for the presence of the cag pathogenicity. C1 Vet Affairs Med Ctr 111D, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Kyoto Prefectural Univ Med, Dept Internal Med 3, Kyoto 602, Japan. Kyoto Prefectural Univ Med, Dept Microbiol, Kyoto 602, Japan. RP Yamaoka, Y (reprint author), Vet Affairs Med Ctr 111D, Dept Med, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 42 TC 100 Z9 106 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD DEC PY 1998 VL 3 IS 4 BP 241 EP 253 DI 10.1046/j.1523-5378.1998.08056.x PG 13 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 149HX UT WOS:000077600000003 PM 9844065 ER PT J AU Van Cott, EM Laposata, M AF Van Cott, EM Laposata, M TI Laboratory evaluation of hypercoagulable states SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID FACTOR-V-LEIDEN; ACTIVATED PROTEIN-C; DEEP-VEIN THROMBOSIS; ADDITIONAL RISK FACTOR; COAGULATION-FACTOR-V; VENOUS THROMBOSIS; S DEFICIENCY; ANTITHROMBIN-III; PLASMA HOMOCYSTEINE; MYOCARDIAL-INFARCTION AB The number of well-characterized hereditary and acquired hypercoagulable conditions is increasing, such that in many thrombophilic patients, the laboratory can now identify a hypercoagulable condition. This review describes the currently known hypercoagulable states that predispose patients to venous, and in some instances, arterial thrombosis. For each condition, the discussion includes the incidence, magnitude of the thrombotic risk in the general population in comparison with symptomatic families, synergistic interactions among the various hypercoagulable conditions, molecular pathogenesis, and interpretation of laboratory test results. In addition, recommendations for laboratory testing are summarized. C1 Massachusetts Gen Hosp, Div Lab Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Coagulat Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Van Cott, EM (reprint author), Massachusetts Gen Hosp, Div Lab Med, Gray Jackson 235,Fruit St, Boston, MA 02114 USA. NR 117 TC 39 Z9 40 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD DEC PY 1998 VL 12 IS 6 BP 1141 EP + DI 10.1016/S0889-8588(05)70047-2 PG 27 WC Oncology; Hematology SC Oncology; Hematology GA 155DV UT WOS:000077931700002 PM 9922930 ER PT J AU Neufeld, EJ AF Neufeld, EJ TI Update on genetic risk factors for thrombosis and atherosclerotic vascular disease SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID CORONARY HEART-DISEASE; COAGULATION-FACTOR-VII; PROTHROMBIN GENE; VENOUS THROMBOSIS; 3'-UNTRANSLATED REGION; MYOCARDIAL-INFARCTION; ARTERY DISEASE; METHYLENETETRAHYDROFOLATE REDUCTASE; APOLIPOPROTEIN(A) GENE; CARDIOVASCULAR-DISEASE AB The strong familial occurrence of venous and arterial thromboembolic disease has prompted ongoing research to identify novel risk factors. Polymorphisms in the factor VII and prothrombin genes are related to increased thrombosis, but the mechanism of increased risk remains to be elucidated. Elevated levels of plasma homocysteine and of the variant lipoprotein(a) particle also contribute to increased thrombotic risk, due in part to polymorphisms in the apolipoprotein(a) gene and the gene for methylene tetrahydrofolate reductase. C1 Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Neufeld, EJ (reprint author), Childrens Hosp, Div Pediat Hematol Oncol, Enders 720,300 Longwood Ave, Boston, MA 02115 USA. RI Neufeld, Ellis/F-9331-2011 NR 74 TC 13 Z9 13 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD DEC PY 1998 VL 12 IS 6 BP 1193 EP + DI 10.1016/S0889-8588(05)70049-6 PG 18 WC Oncology; Hematology SC Oncology; Hematology GA 155DV UT WOS:000077931700004 PM 9922932 ER PT J AU Calverley, DC Roth, GJ AF Calverley, DC Roth, GJ TI Antiplatelet therapy - Aspirin, ticlopidine/clopidogrel, and anti-integrin agents SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID LOW-DOSE ASPIRIN; VEIN-GRAFT PATENCY; CORONARY-BYPASS GRAFTS; DOUBLE-BLIND TRIAL; UNSTABLE ANGINA; RANDOMIZED TRIAL; MYOCARDIAL-INFARCTION; PLATELET-FUNCTION; INTERMITTENT CLAUDICATION; ATRIAL-FIBRILLATION AB Aspirin is the most widely employed antithrombotic agent in use today and has a proven role in the prevention and acute management of atherosclerosis-associated arterial thrombotic events. More recently developed antiplatelet agents have been found to have specific prophylactic roles associated with percutaneous coronary intervention and other clinical settings. This article outlines pharmacologic considerations and current clinical knowledge relevant to the use of aspirin, ticlopidine, clopidogrel, and the GPIIbIIIa antagonists in the management of thrombotic disorders. C1 Univ So Calif, Div Hematol, Los Angeles, CA 90033 USA. Univ Washington, Div Hematol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Hematol Sect, Seattle, WA USA. RP Calverley, DC (reprint author), Univ So Calif, Div Hematol, 1441 Eastlake Ave,MS 34, Los Angeles, CA 90033 USA. NR 123 TC 8 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD DEC PY 1998 VL 12 IS 6 BP 1231 EP + DI 10.1016/S0889-8588(05)70051-4 PG 20 WC Oncology; Hematology SC Oncology; Hematology GA 155DV UT WOS:000077931700006 PM 9922934 ER PT J AU Huang, JN Shimamura, A AF Huang, JN Shimamura, A TI Low-molecular-weight heparins SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID DEEP-VEIN THROMBOSIS; INTRAVENOUS UNFRACTIONATED HEPARIN; ACUTE ISCHEMIC STROKE; ELECTIVE HIP-SURGERY; RANDOMIZED CLINICAL-TRIALS; KNEE REPLACEMENT SURGERY; CORONARY-ARTERY DISEASE; DOUBLE-BLIND TRIAL; LOW-DOSE HEPARIN; VENOUS THROMBOSIS AB Low-molecular-weight heparins (LMWH) are a new group of parenteral anticoagulants. They represent a major clinical advance in anticoagulation since the identification of unfractionated heparin (UFH) in 1922 and the introduction of the synthetic coumarin derivative, warfarin, in 1948. Their predictable pharmacokinetics, increased bioavailability, and longer plasma half-lift allow for once- or twice-daily dosing and eliminate the need for routine laboratory monitoring. This simplified administration stands to alter the clinical practice of anticoagulation. This review highlights recent clinical trials and focuses on studies comparing LMWH with the other two major anticoagulants: UFH and coumadin. C1 Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Div Hematol, Boston, MA 02115 USA. RP Huang, JN (reprint author), Dana Farber Canc Inst, Div Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NICHD NIH HHS [K08-HD01203] NR 90 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD DEC PY 1998 VL 12 IS 6 BP 1251 EP + DI 10.1016/S0889-8588(05)70052-6 PG 33 WC Oncology; Hematology SC Oncology; Hematology GA 155DV UT WOS:000077931700007 PM 9922935 ER PT J AU DiMichele, D Neufeld, EJ AF DiMichele, D Neufeld, EJ TI Hemophilia - A new approach to an old disease SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID FACTOR-VIII CONCENTRATE; HEPATITIS-C VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; PURITY FACTOR-VIII; RECOMBINANT FACTOR-VIII; PURIFIED FACTOR-IX; PREVIOUSLY UNTREATED PATIENTS; PASTEURIZED FACTOR-VIII; COAGULATION FACTOR-IX; CHRONIC LIVER-DISEASE AB Hemophilia is a bleeding disorder resulting from a congenital deficiency in either factor VIII or IX. Recent major advances in diagnostic techniques and replacement-factor therapy are already in widespread use. Yet, at a time when the cure of hemophilia is rapidly becoming more probable than possible, issues of optimal and cost-effective care of both the disease and its complications are still being grappled with. This article discusses the past, present, and future of the diagnosis and therapy of hemophilia, and explores therapeutic dilemmas and strategies most pertinent to its treatment today. C1 New York Presbyterian Hosp, Cornell Med Ctr, Reg Comprehens Hemophilia Diagnost & Treatment Ct, New York, NY USA. New York Presbyterian Hosp, Cornell Med Ctr, Dept Pediat, Div Pediat Hematol Oncol, New York, NY USA. Cornell Univ Med Coll, Dept Pediat, New York, NY USA. Childrens Hosp, Div Pediat Hematol Oncol, Thrombosis Serv, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP DiMichele, D (reprint author), Cornell Univ, Med Ctr, New York Hosp, Reg Comprehens Hemophilia Treatment Ctr, 525 E 68th St, New York, NY 10021 USA. RI Neufeld, Ellis/F-9331-2011 NR 172 TC 30 Z9 31 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD DEC PY 1998 VL 12 IS 6 BP 1315 EP + DI 10.1016/S0889-8588(05)70054-X PG 31 WC Oncology; Hematology SC Oncology; Hematology GA 155DV UT WOS:000077931700009 PM 9922937 ER PT J AU Flieder, DB Moran, CA Travis, WD Koss, MN Mark, EJ AF Flieder, DB Moran, CA Travis, WD Koss, MN Mark, EJ TI Pleuro-pulmonary endometriosis and pulmonary ectopic deciduosis: A clinicopathologic and immunohistochemical study of 10 cases with emphasis on diagnostic pitfalls SO HUMAN PATHOLOGY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 28-MAR 06, 1998 CL BOSTON, MASSACHUSETTS SP US & Canadian Acad Pathol DE endometriosis; deciduosis; lung; pleura; catamenial pneumothorax; hemorrhage ID CATAMENIAL PNEUMOTHORAX; THORACIC ENDOMETRIOSIS; LUNG; HEMOPTYSIS; METASTASES; MALIGNANCY; NEOPLASMS; SARCOMA AB The clinical and pathological features of nine cases of pleuropulmonary endometriosis and the first case of pulmonary ectopic deciduosis are presented. The patients were all women between the ages of 27 and 74 years (median, 36 years) who presented with symptoms of catamenial pleural pain, shortness of breath, hemoptysis, or radiographically detected lung masses. Clinically, six patients were multiparous, one patient had pelvic endometriosis, and four patients had undergone prior pelvic surgical procedures, including dilatation and curettage. Radiographically, eight patients had pulmonary infiltrates or nodules, and four patients had pneumothorax. Three cases involved the visceral pleura and one case the parietal pleura. The other six cases, including the single case of ectopic deciduosis, involved the lung parenchyma. Histologically, the single or multifocal lesions were well circumscribed or infiltrative, nodular, cystic, or nodulocystic, and showed the characteristic features of proliferative or secretory endometrium with numerous mullerian metaplastic changes. Mucin stains were negative in five cases of endometriosis and in the single case of ectopic deciduosis. Immunohistochemical studies were performed in these same six cases using antibodies to epithelial, mesenchymal, vascular, and neuroendocrine markers. The glandular epithelium was decorated with antibodies to pan-cytokeratin, CK7, BER-EP4, ER, and PR, whereas the stromal cells showed positive staining for vimentin, actin, smooth muscle actin, desmin, ER, and PR. Follow-up information obtained in seven patients showed all women without recurrences after 1 to 20 years. The current study highlights the importance of recognizing intrathoracic endometriosis and ectopic deciduosis and properly assessing small biopsy specimens to avoid a misdiagnosis of malignancy. C1 Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Flieder, DB (reprint author), Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, 6825 NW 16th St, Washington, DC 20306 USA. NR 53 TC 60 Z9 63 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD DEC PY 1998 VL 29 IS 12 BP 1495 EP 1503 DI 10.1016/S0046-8177(98)90021-1 PG 9 WC Pathology SC Pathology GA 147QD UT WOS:000077576800022 PM 9865838 ER PT J AU Agarwal, S Rao, A AF Agarwal, S Rao, A TI Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation SO IMMUNITY LA English DT Article ID TRANSCRIPTION FACTOR GATA-3; INTERFERON-GAMMA GENE; LOCUS-CONTROL REGION; MURINE IL-4 GENE; TH2 CELLS; HYPERSENSITIVE SITE; ERYTHROID-CELLS; INTERLEUKIN-4; ACTIVATION; RESPONSES AB Differentiating cells undergo programmed alterations in their patterns of gene expression, which are often regulated by structural changes in chromatin. Here we demonstrate that T cell differentiation results in long-range changes in the chromatin structure of effector cytokine genes, which persist in resting Th1 and Th2 cells in the absence of further stimulation. Differentiation of naive T helper cells into mature Th2 cells is associated with chromatin remodeling of the IL-4 and IL-13 genes, whereas differentiation into Th1 cells evokes remodeling of the IFN gamma but not IL-4 or IL-13 genes. IL-4 locus remodeling is accompanied by demethylation and requires both antigen stimulation and STAT6 activation. We propose that chromatin remodeling of cytokine gene loci is functionally associated with productive T cell differentiation and may explain the coordinate regulation of Th2 cytokine genes. C1 Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, Boston, MA 02115 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA42471]; NIAID NIH HHS [P01 AI35297] NR 70 TC 533 Z9 544 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 1998 VL 9 IS 6 BP 765 EP 775 DI 10.1016/S1074-7613(00)80642-1 PG 11 WC Immunology SC Immunology GA 153MJ UT WOS:000077836600002 PM 9881967 ER PT J AU Wong, SM Carroll, PA Rahme, LG Ausubel, FM Calderwood, SB AF Wong, SM Carroll, PA Rahme, LG Ausubel, FM Calderwood, SB TI Modulation of expression of the ToxR regulon in Vibrio cholerae by a member of the two-component family of response regulators SO INFECTION AND IMMUNITY LA English DT Article ID TYPHIMURIUM INVASION GENES; VIRULENCE FACTORS; ESCHERICHIA-COLI; PSEUDOMONAS-SYRINGAE; OUTER-MEMBRANE; TRANSCRIPTIONAL ACTIVATOR; SIGNAL TRANSDUCTION; GACA GENE; PROTEIN; COLONIZATION AB The ToxRS system in Vibrio cholerae plays a central role in the modulation of virulence gene expression in response to environmental stimuli. An integration of multiple signalling inputs mediated by ToxR, -S, and -T controls virulence gene expression leading to cholera toxin (CT) production. Recently, we identified a new virulence locus, varA (virulence associated regulator), in classical V. cholerae O1 that positively controls transcription of tcpA, the major subunit of the toxin-coregulated pilus (TCP) and the production of CT, two key factors in cholera pathogenesis. The varA locus is a homolog of gacA (originally described for the soil organism Pseudomonas fluorescens), which encodes a conserved global regulator belonging to the family of two-component signal transducing molecules. GacA homologs in a number of diverse gram-negative pathogenic bacterial species have been implicated in controlling the production of diverse virulence factors. varA mutants showed reduced levels of tcpA message and TcpA protein, lacked visible signs of autoagglutination (a phenotype associated with functional TCP), produced decreased levels of CT, and were attenuated in colonizing infant mice. Transcription of varA appears to be independent of ToxR, and overexpression of the regulators tcpPH and toxT from plasmids in the varA mutant restored wild-type levels of CT production and the ability to autoagglutinate. varA represents an additional modulating factor in the coordinate expression of virulence factors in V. cholerae. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Shriners Burns Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Calderwood, SB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. FU NIAID NIH HHS [R01 AI34968, T32 AI007061, T32 AI007410, T32 AI07410, T32AI07061] NR 55 TC 56 Z9 59 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 1998 VL 66 IS 12 BP 5854 EP 5861 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 142BG UT WOS:000077179600035 PM 9826365 ER PT J AU Stout, JE Lin, YSE Goetz, AM Muder, RR AF Stout, JE Lin, YSE Goetz, AM Muder, RR TI Controlling Legionella in hospital water systems: Experience with the superheat-and-flush method and copper-silver ionization SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID NOSOCOMIAL LEGIONNAIRES-DISEASE; PNEUMOPHILA AB OBJECTIVE: To evaluate the effect of copper-silver ionization on Legionella colonization and nosocomial legionnaires' disease and to compare the efficacy of metal ions versus the superheat-and-flush method of disinfection. DESIGN: Prospective determination over a 36-month period of copper and silver ion concentrations in the recirculating hot-water system, Legionella colonization of the hospital water distribution system, and cases of nosocomial legionnaires' disease. Retrospective comparison of results with the previous 13 years, during which the superheat-and-flush method was used. SETTING: The Pittsburgh Veterans' Affairs Health Care System (University Drive Division) acute-care hospital. INTERVENTION: Three copper-silver ionization systems were installed on the hot water distribution system in November 1994. RESULTS: The average number of cases of legionnaires' disease per year and the percentage of distal sites positive for Legionella pneumophila for the superheat-and-flush method versus the copper-silver ionization method was six cases with 15% positivity versus two cases with 4% positivity, respectively. The reduction in Legionella colonization after copper-silver ionization was significant (P<.05) compared to the superheat and flush. Mean copper and silver ion concentrations (mg/L) were 0.29 and 0.054 hom hot-water tanks, and 0.17 and 0.04 from distal outlets, respectively. CONCLUSIONS: We conclude that a properly maintained and monitored copper-silver ionization system was more effective than the superheat-and-flush method for reducing the recovery of Legionella from the hospital water distribution system. C1 Vet Affairs Pittsburgh Hlth Care Syst, Special Pathogens Lab, Univ Dr Div, Pittsburgh, PA USA. Vet Affairs Pittsburgh Hlth Care Syst, Infect Dis Sect, Univ Dr Div, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Muder, RR (reprint author), Vet Adm Med Ctr, Infect Dis Sect, Univ Dr C, Pittsburgh, PA 15240 USA. NR 15 TC 71 Z9 72 U1 0 U2 4 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD DEC PY 1998 VL 19 IS 12 BP 911 EP 914 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 148DC UT WOS:000077536700008 PM 9872527 ER PT J AU Mortlock, NJ Schleis, T AF Mortlock, NJ Schleis, T TI Outpatient parenteral antimicrobial therapy technology SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID INFUSION DEVICES AB Health care costs are continuing to spiral upward despite government and public insistence on cost containment. To meet the challenge, medical professionals and organizations are seeking opportunities for cost reduction and alternatives for delivery health care. This article discusses the tools that allow the effective delivery of care using the outpatient parenteral antimicrobial therapy (OPAT) model. C1 Infect Dis NW PS, Spokane, WA 99204 USA. Sacred Heart Med Ctr, Spokane, WA USA. Deaconess Med Ctr, Spokane, WA USA. Valley Gen Med Ctr, Spokane, WA USA. NW Med Specialties PLLC, Serv Pharm, Tacoma, WA USA. RP Mortlock, NJ (reprint author), Infect Dis NW PS, 105 W 8th Ave,Suite 350, Spokane, WA 99204 USA. NR 44 TC 6 Z9 6 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD DEC PY 1998 VL 12 IS 4 BP 861 EP + DI 10.1016/S0891-5520(05)70025-8 PG 19 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 148CN UT WOS:000077535400005 PM 9888027 ER PT J AU Manilay, JO Waneck, GL Sykes, M AF Manilay, JO Waneck, GL Sykes, M TI Altered expression of Ly-49 receptors on NK cells developing in mixed allogeneic bone marrow chimeras SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE repertoire development; tolerance; transplantation ID NATURAL-KILLER-CELLS; CLASS-I MHC; INHIBITORY RECEPTORS; PECULIAR IMMUNOBIOLOGY; MONOCLONAL-ANTIBODIES; HEMATOPOIETIC-CELLS; MULTIGENE FAMILY; GRAFT-REJECTION; MOUSE; MICE AB Ly-49 molecules are used by NK cells to distinguish 'self' from 'non-self', but the determinants of Ly-49 expression that allow this distinction to be made are not understood. The education of NK cells for self/non-self recognition was studied In murine mixed allogeneic bone marrow chimeras, in which NK cells are of both host and donor origin. Marked alterations in Ly-49 receptor expression were observed on both host and donor NK cells developing in BALB/c --> B6 mixed chimeras. Ly-49A and Ly-49G2 expression was lower on host B6 NK cells of mixed chimeras compared to non-transplanted B6 controls. Among donor BALB/c NK cells, Ly-49C expression levels were reduced, but the proportion of Ly-49C(+) cells was increased, whereas Ly-49G2 expression was up-regulated compared to non-transplanted BALB/c controls. Thus, Ly-49 expression on donor and host NK cells developing post-bone marrow transplantation evolves toward the expression pattern of the host and donor strains respectively due to the presence of the allogeneic MHC, In vitro functional NK cell assays showed that donor NK cells in mixed chimeras were not tolerant to host antigens and that host NK cells were not tolerant to the donor. Our data are consistent with a model in which MHC expression in the environment has a dominant down-regulating effect on the expression of Ly-49 molecules that recognize those MHC molecules, regardless of whether they are self or allogeneic. This down-regulation, combined with the limited repertoire of Ly-49 molecules, may not be sufficient to allow NK cells to be tolerant of MHC antigens of a fully MHC-mismatched allogenic strain. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Surg Serv,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Surg Serv,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, MGH E,Bldg 149,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [T32 HL 07623-11A1, 5 F31 HL09733-02, R01 HL49915] NR 53 TC 28 Z9 28 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD DEC PY 1998 VL 10 IS 12 BP 1943 EP 1955 DI 10.1093/intimm/10.12.1943 PG 13 WC Immunology SC Immunology GA 153LM UT WOS:000077834600021 PM 9885916 ER PT J AU Proctor, SP Heeren, T White, RF Wolfe, J Borgos, MS Davis, JD Pepper, L Clapp, R Sutker, PB Vasterling, JJ Ozonoff, D AF Proctor, SP Heeren, T White, RF Wolfe, J Borgos, MS Davis, JD Pepper, L Clapp, R Sutker, PB Vasterling, JJ Ozonoff, D TI Health status of Persian Gulf War veterans: self-reported symptoms, environmental exposures and the effect of stress SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Gulf War veterans; health symptoms; environmental exposures; stress ID DISORDER AB Background Most US troops returned home from the Persian Gulf War (PGW) by Spring 1991 and many began reporting increased health symptoms and medical problems soon after. This investigation examines the relationships between several Gulf-service environmental exposures and health symptom reporting, and the role of traumatic psychological stress on the exposure-health symptom relationships. Methods Stratified, random samples of two cohorts of PGW veterans, from the New England area (n = 220) and from the New Orleans area (n = 71), were selected from larger cohorts being followed longitudinally since arrival home from the Gulf. A group of PGW-era veterans deployed to Germany (n = 50) served as a comparison group. The study protocol included questionnaires, a neuropsychological test battery an environmental interview, and psychological diagnostic interviews. This report focuses on self-reported health symptoms and exposures of participants who completed a 52-item health symptom checklist and a checklist of environmental exposures. Results The prevalence of reported symptoms was greater in both Persian Gulf-deployed cohorts compared to the Germany cohort, Analyses of the body-system symptom scores (BSS), weighted to account for sampling design, and adjusted by age, sex, and education, indicated that Persian Gulf-deployed veterans were more likely to report neurological, pulmonary, gastrointestinal, cardiac, dermatological, musculoskeletal, psychological and neuropsychological system symptoms than Germany veterans. Using a priori hypotheses about the toxicant effects of exposure to specific toxicants, the relationships between self-reported exposures and body-system symptom groupings were examined through multiple regression analyses, controlling for war-zone exposure and post-traumatic stress disorder (PTSD). Self-reported exposures to pesticides, debris from Scuds, chemical and biological warfare (CBW) agents, and smoke from tent heaters each were significantly related to increased reporting of specific predicted BSS groupings. Conclusions Veterans deployed to the Persian Gulf have higher self-reported prevalence of health symptoms corn-pared to PGW veterans who were deployed only as far as Germany. Several Gulf-service environmental exposures are associated with increased health symptom reporting involving predicted body-systems, after adjusting for war-zone stressor exposures and PTSD. C1 Boston Environm Hazards Ctr 116B4, Boston, MA 02130 USA. Boston Univ, Sch Publ Hlth Epidemiol & Biostat, Boston, MA USA. Boston Univ, Sch Publ Hlth Environm Hlth, Boston, MA USA. Boston Univ, Sch Med Neurol, Boston, MA USA. VAMC, Psychol Serv, Boston, MA USA. Odense Univ, Dept Environm Med, Odense, Denmark. VAMC, Natl Ctr PTSD, Boston, MA USA. Boston Univ, Sch Med Psychiat, Boston, MA USA. John Snow Inst Inc, Boston, MA USA. VAMC, Psychol Serv, New Orleans, LA USA. Tulane Univ, Sch Med Psychiat & Neurol, New Orleans, LA 70118 USA. VAMC, Med Serv, Boston, MA USA. RP Proctor, SP (reprint author), Boston Environm Hazards Ctr 116B4, 150 S Huntington Ave, Boston, MA 02130 USA. OI Clapp, Richard/0000-0001-8174-0825; Ozonoff, David/0000-0002-4281-4171 NR 43 TC 139 Z9 140 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD DEC PY 1998 VL 27 IS 6 BP 1000 EP 1010 DI 10.1093/ije/27.6.1000 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 166XJ UT WOS:000078602900013 PM 10024195 ER PT J AU Kemppainen, JK O'Brien, L Corpuz, B AF Kemppainen, JK O'Brien, L Corpuz, B TI The behaviors of AIDS patients toward their nurses SO INTERNATIONAL JOURNAL OF NURSING STUDIES LA English DT Article DE critical incident technique; HIV/AIDS; patient-provider interaction ID CRITICAL INCIDENT TECHNIQUE; CARE AB The purpose of this study is to identify the behavioral responses of hospitalized patients with HIV/AIDS to nursing care providers. The critical incident technique, developed by Flanagan (1954) was used to obtain a listing of the behavioral responses. Patients were asked to recall brief descriptions of caregiving events. A purposive sample included 118 men and women with HIV/AIDS from broad socioeconomic and cultural backgrounds. A total of 273 critical incidents yielded a listing of 393 behaviors. The analysis of data was facilitated by a computer program which allowed for the creation of coding systems and refinement of coded items into behavioral response categories. The inductive content analysis yielded 10 major response categories: participate, anger, appreciate, come close, stay away, match respect, match disrespect, dependent, complaint, and self care. In the largest category, 41% of the patients described ways in which they participate actively in their nursing care. These behavioral responses sharply contrast with current literature which continues to place a negative emphasis on the attitudes and behaviors of nurses. One third of the patients listed angry behaviors which were directed at nurses. Behavioral descriptions of anger reflected increased irritability with advancing illness, intense psychological responses toward an AIDS diagnosis, or a violent and angry style of relating to others in street settings. Two of the response categories describe the reciprocal nature of nurse-patient interactions. By becoming aware of patient responses, nurses will obtain a greater understanding of what changes would influence outcomes in patient behavior. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. San Francisco VA Med Ctr, San Francisco, CA USA. San Francisco State Univ, Sch Nursing, San Francisco, CA 94132 USA. RP Kemppainen, JK (reprint author), VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. FU NIMH NIH HHS [R03-MH54934-01] NR 21 TC 16 Z9 17 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0020-7489 J9 INT J NURS STUD JI Int. J. Nurs. Stud. PD DEC PY 1998 VL 35 IS 6 BP 330 EP 338 DI 10.1016/S0020-7489(98)00047-9 PG 9 WC Nursing SC Nursing GA 148CV UT WOS:000077536000004 PM 9871823 ER PT J AU Yang, JM Lee, J Southern, JF Warshaw, AL Dhanak, E Lewandrowski, KB AF Yang, JM Lee, J Southern, JF Warshaw, AL Dhanak, E Lewandrowski, KB TI Measurement of pS2 protein in pancreatic cyst fluids - Evidence for a potential role of pS2 protein in the pathogenesis of mucinous cystic tumors SO INTERNATIONAL JOURNAL OF PANCREATOLOGY LA English DT Article DE pS2 protein; growth factor; pancreas; cystic tumor; mucinous cystic neoplasm; cyst fluid ID EPIDERMAL GROWTH-FACTOR; HUMAN SPASMOLYTIC POLYPEPTIDE; FACTOR RECEPTOR; FACTOR-ALPHA; CARCINOEMBRYONIC ANTIGEN; DIFFERENTIAL-DIAGNOSIS; FACTOR-I; CANCER; EXPRESSION; NEOPLASMS AB Conclusion. Elevated levels of the growth factor pS2 protein in the cyst fluids of mucinous cystic tumors correlate with earlier observations using immunohistochemical techniques showing that pS2 protein is expressed by these tumors. The markedly elevated levels of pS2 protein compared to normal plasma values suggest that this growth factor may be important in the pathogenesis of pancreatic mucinous cystic tumors. Background. Cystic lesions of the pancreas include inflammatory pseudocysts, serous cystadenomas, and mucinous cystic tumors, some of which are malignant. Previous studies using immunohistochemical techniques have shown that virtually all pancreatic mucinous tumors express pS2 protein. pS2 protein is a growth factor that is believed to be important in the normal process of inflammation and repair. We measured pS2 protein and other growth factors in pancreatic cyst fluids to assess their potential pathophysiologic and diagnostic significance. Methods. Levels of pS2 protein were measured in 54 pancreatic cyst fluids by radioimmunoassay. The growth factors, epidermal growth factor (EGF), transforming growth factor-cc (TGF-a), and insulin-like growth factors I and II (IGF-I, IGF-II) were measured in 22 cyst fluids using commercial immunoassays. Results. Mucinous cysts exhibited significantly higher levels of cyst fluid pS2 protein than nonmucinous lesions, including pseudocysts and serous cystadenomas (median: 78,303 pg/mL; range: 218-361,176 pg/mL vs median: 886 pg/mL; range: 0-14,206 pg/mL; p = 0.0001). The level of pS2 in mucinous tumors was markedly higher than plasma values (median: 392 pg/mL). Levels of pS2 protein in malignant mucinous lesions tended to be higher than those in benign mucinous cysts, but this difference was not statistically significant (median: 88,817 vs 64,350 pg/mL; p = 0.159). Levels of other growth factors, including EGF, TGF-alpha, IGF-I, and IGF-II, did not discriminate among the different cyst types, and the values were within normal plasma ranges. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Lewandrowski, KB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Gray 5, Boston, MA 02114 USA. NR 29 TC 5 Z9 5 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0169-4197 J9 INT J PANCREATOL JI Int. J. Pancreatol. PD DEC PY 1998 VL 24 IS 3 BP 181 EP 186 PG 6 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 149WX UT WOS:000077630400003 PM 9873952 ER PT J AU Shulman, LN Tarbell, NJ Storen, E Marcus, K Mauch, PM AF Shulman, LN Tarbell, NJ Storen, E Marcus, K Mauch, PM TI Low-dose total body irradiation and G-CSF without hematopoietic stem cell support in the treatment of relapsed or refractory acute myelogenous leukemia (AML), or AML in second or subsequent remission SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE total body irradiation; granulocyte-colony-stimulating factor (G-CSF); acute myelogenous leukemia ID COLONY-STIMULATING FACTOR; ACUTE MYELOID-LEUKEMIA; BONE-MARROW TRANSPLANTATION; RECOVERY; IL-6 AB Purpose: Patients with relapsed acute myelogenous leukemia (AML), who are not eligible for bone marrow transplantation, have a poor prognosis when treated with chemotherapy alone. Total body irradiation (TBI) is an effective modality against AML when used in doses of 1000-1400 cGy with hematopoietic stem cell support. We undertook a phase I study of TBI with granulocyte-colony-stimulating factor (G-CSF) support, without stem cell support in patients with AML either in relapse or second or subsequent remission. Methods and Materials: Patients with relapsed AML, or AML in second or subsequent remission were treated in a phase I study of TBI followed by G-CSF, The first dose level was 200 cGy, After the initial cohort of patients it was clear that patients with overt leukemia did not benefit from this treatment, and subsequent patients were required to be in remission at the time of TBI. Results: Eleven patients were treated, 4 in overt relapse, and 7 in remission. 200 cGy was used in all, and dose escalation was not possible due to prolonged thrombocytopenia in all patients but one. Neutrophil recovery was adequate in those patients who remained in remission after TBI. Patients with overt leukemia had transient reduction in blast counts, but rapid recurrence of their leukemia. Patients treated in remission had short remissions, with the exception of one patient who is in remission 32 months after treatment, Conclusion: There is some antileukemic effect of TBT even at 200 cGy, though this dose appears to be too low to help a significant number of patients. If TBI is to be escalated without stem cell support, then a thrombopoietic agent will need to be used. (C) 1998 Elsevier Science Inc. C1 Brigham & Womens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. RP Shulman, LN (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 12 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD DEC 1 PY 1998 VL 42 IS 5 BP 1113 EP 1117 DI 10.1016/S0360-3016(98)00344-7 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 149GU UT WOS:000077597400026 PM 9869237 ER PT J AU Harper, SL Foster, CS AF Harper, SL Foster, CS TI The ocular manifestations of rheumatoid disease SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID ACUTE ANTERIOR UVEITIS; PERIPHERAL ULCERATIVE KERATITIS; ANKYLOSING-SPONDYLITIS; CLINICAL MANIFESTATIONS; CATARACT-SURGERY; SICCA SYNDROME; ARTHRITIS; SCLERITIS; EPISCLERITIS; CHILDREN C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Harper, SL (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 84 TC 17 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1998 VL 38 IS 1 BP 1 EP 19 DI 10.1097/00004397-199803810-00003 PG 19 WC Ophthalmology SC Ophthalmology GA ZB975 UT WOS:000072527100002 PM 9532469 ER PT J AU Shiuey, Y Foster, CS AF Shiuey, Y Foster, CS TI Peripheral ulcerative keratitis and collagen vascular disease SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID RELAPSING POLYCHONDRITIS; WEGENERS GRANULOMATOSIS; RHEUMATOID-ARTHRITIS; REVISED CRITERIA; SCLERITIS; CLASSIFICATION C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Shiuey, Y (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 17 TC 11 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1998 VL 38 IS 1 BP 21 EP 32 DI 10.1097/00004397-199803810-00004 PG 12 WC Ophthalmology SC Ophthalmology GA ZB975 UT WOS:000072527100003 PM 9532470 ER PT J AU Nguyen, QD Foster, CS AF Nguyen, QD Foster, CS TI Systemic lupus erythematosus and the eye SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Review ID BILATERAL INTERNUCLEAR OPHTHALMOPLEGIA; SUBSEQUENT PULSE CYCLOPHOSPHAMIDE; SEROUS RETINAL-DETACHMENT; ACQUIRED BROWNS-SYNDROME; SJOGRENS-SYNDROME; NERVOUS-SYSTEM; ANTIPHOSPHOLIPID ANTIBODIES; ANTICARDIOLIPIN ANTIBODIES; RHEUMATIC DISEASES; OCCLUSIVE DISEASE C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Nguyen, QD (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 105 TC 18 Z9 19 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1998 VL 38 IS 1 BP 33 EP 60 DI 10.1097/00004397-199803810-00005 PG 28 WC Ophthalmology SC Ophthalmology GA ZB975 UT WOS:000072527100004 PM 9532471 ER PT J AU Krzystolik, M Power, WJ Foster, CS AF Krzystolik, M Power, WJ Foster, CS TI Diagnostic and therapeutic challenges of sarcoidosis SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID ANGIOTENSIN-CONVERTING ENZYME; TRANSBRONCHIAL LUNG-BIOPSY; LOW-DOSE METHOTREXATE; OCULAR SARCOIDOSIS; CONJUNCTIVAL BIOPSY; PROLACTIN RECEPTORS; OPTIMAL NUMBER; CYCLOSPORIN-A; GALLIUM SCAN; SERUM C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Krzystolik, M (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 56 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1998 VL 38 IS 1 BP 61 EP 76 DI 10.1097/00004397-199803810-00006 PG 16 WC Ophthalmology SC Ophthalmology GA ZB975 UT WOS:000072527100005 PM 9532472 ER PT J AU Tolentino, MJ Adamis, AP AF Tolentino, MJ Adamis, AP TI Angiogenic factors in the development of diabetic iris neovascularization and retinopathy SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; PIGMENT EPITHELIAL-CELLS; VASCULAR-PERMEABILITY FACTOR; FACTOR-BETA; FACTOR-I; RETINAL CAPILLARIES; ALDOSE REDUCTASE; BOVINE PITUITARY; TGF-BETA; INSULIN C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Tolentino, MJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 92 TC 15 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1998 VL 38 IS 1 BP 77 EP 94 DI 10.1097/00004397-199803810-00007 PG 18 WC Ophthalmology SC Ophthalmology GA ZB975 UT WOS:000072527100006 PM 9532473 ER PT J AU Yoo, SH Adamis, AP AF Yoo, SH Adamis, AP TI Retinal manifestations of aging SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID MACULAR DEGENERATION; BRUCHS MEMBRANE; MORPHOMETRIC ANALYSIS; AGE; CELLS; PHYSIOLOGY; LIPOFUSCIN; ACUITY; DRUSEN; RPE C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Yoo, SH (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 47 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1998 VL 38 IS 1 BP 95 EP 101 DI 10.1097/00004397-199803810-00008 PG 7 WC Ophthalmology SC Ophthalmology GA ZB975 UT WOS:000072527100007 PM 9532474 ER PT J AU Coday, MP Dallow, RL AF Coday, MP Dallow, RL TI Managing Graves' orbitopathy SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID THYROID-ASSOCIATED OPHTHALMOPATHY; T2 RELAXATION-TIME; ENDOCRINE OPHTHALMOPATHY; ORBITAL IRRADIATION; CIGARETTE-SMOKING; OPTIC NEUROPATHY; DISEASE; THERAPY; PREDNISONE; SURGERY C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Coday, MP (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 60 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1998 VL 38 IS 1 BP 103 EP 115 DI 10.1097/00004397-199803810-00009 PG 13 WC Ophthalmology SC Ophthalmology GA ZB975 UT WOS:000072527100008 PM 9532475 ER PT J AU Watkins, LM Rubin, PAD AF Watkins, LM Rubin, PAD TI Metastatic tumors of the eye and orbit SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID OPTIC-NERVE; CARCINOMA; MANAGEMENT; DIAGNOSIS; DISEASE C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Watkins, LM (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 38 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1998 VL 38 IS 1 BP 117 EP 128 DI 10.1097/00004397-199803810-00010 PG 12 WC Ophthalmology SC Ophthalmology GA ZB975 UT WOS:000072527100009 PM 9532476 ER PT J AU Davis, EA Rizzo, JF AF Davis, EA Rizzo, JF TI Ocular manifestations of multiple sclerosis SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID VISUAL EVOKED-POTENTIALS; WHITE-MATTER LESIONS; ACUTE OPTIC NEURITIS; CEREBROSPINAL-FLUID; BODY-TEMPERATURE; CORTICOSTEROIDS; ABNORMALITIES; NEUROPATHY; DIAGNOSIS; FEATURES C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Davis, EA (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 47 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1998 VL 38 IS 1 BP 129 EP 139 DI 10.1097/00004397-199803810-00011 PG 11 WC Ophthalmology SC Ophthalmology GA ZB975 UT WOS:000072527100010 PM 9532477 ER PT J AU Vinals, AF Kenyon, KR AF Vinals, AF Kenyon, KR TI Corneal manifestations of metabolic diseases SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID CONJUNCTIVA; DYSTROPHY C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Vinals, AF (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 41 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1998 VL 38 IS 1 BP 141 EP 153 DI 10.1097/00004397-199803810-00012 PG 13 WC Ophthalmology SC Ophthalmology GA ZB975 UT WOS:000072527100011 PM 9532478 ER PT J AU Harris, EW Loewenstein, JI Azar, D AF Harris, EW Loewenstein, JI Azar, D TI Vitamin A deficiency and its effects on the eye SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID RETINOL-BINDING PROTEIN; TRANSPORT; RECEPTOR; GENE C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Harris, EW (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 50 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1998 VL 38 IS 1 BP 155 EP 161 DI 10.1097/00004397-199803810-00013 PG 7 WC Ophthalmology SC Ophthalmology GA ZB975 UT WOS:000072527100012 PM 9532479 ER PT J AU Burk, SE Jakobiec, FA AF Burk, SE Jakobiec, FA TI Metabolic syndromes with ocular and renal consequences SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID NEPHROPATHIC CYSTINOSIS; ALPORTS-SYNDROME; PRIMARY HYPEROXALURIA; CYSTEAMINE; CLONE; GENE C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Burk, SE (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 36 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1998 VL 38 IS 1 BP 163 EP 176 DI 10.1097/00004397-199803810-00014 PG 14 WC Ophthalmology SC Ophthalmology GA ZB975 UT WOS:000072527100013 PM 9532480 ER PT J AU Kim, RY Loewenstein, JI AF Kim, RY Loewenstein, JI TI Systemic diseases manifesting as exudative retinal detachment SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID LUPUS-ERYTHEMATOSUS; RHEUMATOID-ARTHRITIS; HYPERTENSIVE RETINOPATHY; MANIFESTATIONS; CYCLOPHOSPHAMIDE; PREGNANCY; SCLERITIS; OCCLUSION; LEUKEMIA; LESIONS C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Kim, RY (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 100 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1998 VL 38 IS 1 BP 177 EP 195 DI 10.1097/00004397-199803810-00015 PG 19 WC Ophthalmology SC Ophthalmology GA ZB975 UT WOS:000072527100014 PM 9532481 ER PT J AU You, TT Young, LHY AF You, TT Young, LHY TI Retinal manifestations of gastrointestinal conditions SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Review ID SYNDROME ARTERIOHEPATIC DYSPLASIA; FAMILIAL ADENOMATOUS POLYPOSIS; CANCER-ASSOCIATED RETINOPATHY; INFLAMMATORY BOWEL-DISEASE; OCULAR FUNDUS LESIONS; HEPATO-RENAL SYNDROME; PSEUDOXANTHOMA-ELASTICUM; WHIPPLES DISEASE; CARCINOEMBRYONIC ANTIGEN; ALAGILLE SYNDROME C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP You, TT (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 120 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1998 VL 38 IS 1 BP 197 EP 220 DI 10.1097/00004397-199803810-00016 PG 24 WC Ophthalmology SC Ophthalmology GA ZB975 UT WOS:000072527100015 PM 9532482 ER PT J AU An, BB Adamis, AP AF An, BB Adamis, AP TI Chlamydial ocular diseases SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID POLYMERASE CHAIN-REACTION; TRACHOMATIS INFECTION; ORAL IMMUNIZATION; DIAGNOSIS; INFANTS; STRAIN; TWAR C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP An, BB (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 53 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1998 VL 38 IS 1 BP 221 EP 230 DI 10.1097/00004397-199803810-00017 PG 10 WC Ophthalmology SC Ophthalmology GA ZB975 UT WOS:000072527100016 PM 9532483 ER PT J AU Rowe, SG Durand, M AF Rowe, SG Durand, M TI Blackflies and whitewater: Onchocerciasis and the eye SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID WEST-AFRICA; OCULAR ONCHOCERCIASIS; IVERMECTIN; VOLVULUS; RESPONSES; INFECTION; IMMUNITY; ANTIGEN; CHORIORETINOPATHY; HUMANS C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Rowe, SG (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 31 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1998 VL 38 IS 1 BP 231 EP 240 DI 10.1097/00004397-199803810-00018 PG 10 WC Ophthalmology SC Ophthalmology GA ZB975 UT WOS:000072527100017 PM 9532484 ER PT J AU Ryan-Graham, MA Durand, M Pavan-Langston, D AF Ryan-Graham, MA Durand, M Pavan-Langston, D TI AIDS and the anterior segment SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Review ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY-SYNDROME; MYCOBACTERIUM-AVIUM COMPLEX; HERPES-ZOSTER OPHTHALMICUS; POLYMERASE CHAIN-REACTION; SQUAMOUS-CELL CARCINOMA; MICROSPORIDIAL KERATOCONJUNCTIVITIS; VIRUS-INFECTION; OCULAR MANIFESTATIONS; KAPOSIS-SARCOMA C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Ryan-Graham, MA (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 104 TC 4 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1998 VL 38 IS 1 BP 241 EP 263 DI 10.1097/00004397-199803810-00019 PG 23 WC Ophthalmology SC Ophthalmology GA ZB975 UT WOS:000072527100018 PM 9532485 ER PT J AU Graham, K Pinnolis, M AF Graham, K Pinnolis, M TI AIDS and the posterior segment SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Review ID CYTOMEGALO-VIRUS RETINITIS; IMMUNE-DEFICIENCY-SYNDROME; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; RETINAL NECROSIS SYNDROME; PNEUMOCYSTIS-CARINII CHOROIDITIS; DIHYDROXY PROPOXYMETHYL GUANINE; TERM INTRAVITREAL GANCICLOVIR; VARICELLA-ZOSTER VIRUS; CMV RETINITIS; OCULAR MANIFESTATIONS C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Graham, K (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 113 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1998 VL 38 IS 1 BP 265 EP 280 DI 10.1097/00004397-199803810-00020 PG 16 WC Ophthalmology SC Ophthalmology GA ZB975 UT WOS:000072527100019 PM 9532486 ER PT J AU Frank, H Loewe, R Loewe, C Oberhuber, G Schwaighofer, B Huber, K Weissleder, R AF Frank, H Loewe, R Loewe, C Oberhuber, G Schwaighofer, B Huber, K Weissleder, R TI Efficacy of thrombolytic therapy in pulmonary embolism determined by MION-enhanced MRA - An experimental study in rabbits SO INVESTIGATIVE RADIOLOGY LA English DT Article DE pulmonary embolism; MR-angiography; magnetic resonance (MR); contrast enhancement; thrombolysis; animal study ID TISSUE PLASMINOGEN-ACTIVATOR; CONTRAST AGENT; IRON-OXIDE; UROKINASE; REGIMEN; TRIAL; ANGIOGRAPHY; INFUSION; ANIMALS; HEPARIN AB RATIONALE AND OBJECTIVES. This study determined whether contrast-enhanced magnetic resonance angiography could he used as a noninvasive imaging technique to determine the therapeutic effect and endpoint in thrombolysis of acute pulmonary embolism in an animal model. METHODS. New Zealand white rabbits (n = 18) were anesthetized and mechanically ventilated. Single (n = 12 emboli) or dual (n = 12 emboli in 6 animals) pulmonary emboli were created by injecting autologous thrombi through a right internal jugular venous approach. Three-dimensional time of flight (TOF) magnetic resonance angiograms were obtained after intravenous administration of 2 mg Fe of a long circulating monocrystalline iron oxide. Animals then received 5000 IU heparin and 1.3 mg recombinant tissue plasminogen activator/kg intravenously, and magnetic resonance angiography was repeated 30 minutes and 60 minutes after initiation of thrombolytic therapy. RESULTS. MION-enhanced magnetic resonance angiography accurately detected pulmonary emboli in all rabbits, Thrombolysis during the observation period was successful in 8 of the 18 animals. In animals with a single embolus, the revascularization rate was 50% (6 of 12 emboli), The rate was 33% (4 of 12 emboli) in animals with multiple emboli. Magnetic resonance angiography allowed determination of thrombus resolution or thrombus persistence. CONCLUSIONS. It was feasible to diagnose pulmonary embolism accurately in this experimental study and to monitor thrombolysis of pulmonary emboli by MION-enhanced magnetic resonance angiography. C1 Univ Vienna, Dept Internal Med 2, Div Cardiol, A-1090 Vienna, Austria. Univ Vienna, Dept Clin Pathol, A-1010 Vienna, Austria. Evangel Krankenhaus, Dept Radiol, Vienna, Austria. Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02115 USA. RP Frank, H (reprint author), Univ Vienna, Dept Internal Med 2, Div Cardiol, Waehringer Guertel 18-20, A-1090 Vienna, Austria. NR 29 TC 9 Z9 9 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD DEC PY 1998 VL 33 IS 12 BP 853 EP 857 DI 10.1097/00004424-199812000-00002 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 142EM UT WOS:000077187000002 PM 9851818 ER PT J AU Henry, K Erice, A Tierney, C Balfour, HH Fischl, MA Kmack, A Liou, SH Kenton, A Hirsch, MS Phair, J Martinez, A Kahn, JO AF Henry, K Erice, A Tierney, C Balfour, HH Fischl, MA Kmack, A Liou, SH Kenton, A Hirsch, MS Phair, J Martinez, A Kahn, JO CA AIDS Clinical Trial Grp 193A Study Team TI A randomized, controlled, double-blind study comparing the survival benefit of four different reverse transcriptase inhibitor therapies (three-drug, two-drug, and alternating drug) for the treatment of advanced AIDS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE AIDS; antiretroviral therapy; CD4 lymphocyte count; didanosine; HIV-1 RNA; nevirapine; reverse transcriptase inhibitors survival; zalcitabine; zidovudine ID IMMUNODEFICIENCY-VIRUS INFECTION; PLACEBO-CONTROLLED TRIAL; CD4 CELL COUNTS; CUBIC MILLIMETER; ANTIRETROVIRAL THERAPY; COMBINATION THERAPY; HIV-1 INFECTION; CLINICAL-TRIALS; ZIDOVUDINE; DIDANOSINE AB Objective: The primary objective was to compare the effects of dual or triple combinations of HN-I reverse transcriptase inhibitors with respect to survival. The time to new HIV disease progression or death, toxicities, the change in CD4 cells, and plasma HIV-1 RNA concentrations in a subset of study subjects were evaluated. Design: This was a multicenter randomized, double-blind: placebo-controlled study. Setting: The study was conducted among 42 adult AIDS Clinical Trials Group sites and 7 National Hemophilia Foundation centers. Patients: 1313 HIV-infected patients with CD4 counts less than or equal to 50 cells/mm(3) participated in this study, which was conducted from June 1993 to June 1996. Intervention: Patients were randomized to one of four daily regimens containing 600 mg of zidovudine: zidovudine alternating monthly with 400 mg didanosine; zidovudine plus 2.25 mg of zalcitabine; zidovudine plus 400 mg of didanosine; or zidovudine plus 400 mg of didanosine plus 400 mg of nevirapine (triple therapy). Main Outcome Measures: The main outcome was survival (i.e., time to death). Results: A significant difference in survival time was found between the four treatment groups, favoring those assigned to triple therapy (p = .02). A significant difference was also found in the delay of disease progression or death among the four treatment arms favoring the group assigned to triple therapy(p = .002). Baseline CD4 cell counts and plasma HIV-1 RNA concentrations as well as changes of CD4 counts at week 8 predicted survival for subjects in the virology substudy. Conclusions: In the pre-protease inhibitor era, a combination of triple reverse transcriptase inhibitors prolonged life and delayed disease progression in AIDS patients with advanced immune suppression. C1 Univ Minnesota, Minneapolis, MN 55455 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Miami Univ, Sch Med, Miami, FL USA. Frontier Sci Data Management Ctr, Amherst, NY USA. AIDS Clin Trials Grp, Operat Ctr, Rockville, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Northwestern Univ, Sch Med, Chicago, IL USA. NIAID, Div Aids, Rockville, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Henry, K (reprint author), Reg Hosp, HIV Program, 640 Jackson,Suite 125, St Paul, MN 55101 USA. EM henry02@karloff.fstrf.org NR 40 TC 44 Z9 47 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD DEC 1 PY 1998 VL 19 IS 4 BP 339 EP 349 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 140CZ UT WOS:000077070300004 PM 9833742 ER PT J AU Kloen, P Burke, DW Chew, FS Mildrum, R AF Kloen, P Burke, DW Chew, FS Mildrum, R TI Radiographic pseudochondrocalcinosis in early failure of a cemented total knee replacement SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total knee arthroplasty; osteolysis; polymethylmethacrylate debris ID HIP-REPLACEMENT; POLYETHYLENE AB We observed a case of early-onset osteolysis in a cemented total knee arthroplasty. Preoperative radiographs suggested numerous radiopaque particles covering the polyethylene insert. Findings at the time of revision confirmed the presence of small radiopaque polymethylmethacrylate particles on the bearing surface of the tibial insert, presumably leading to early failure of the knee arthroplasty. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Burke, DW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Wang ACC 535,15 Parkman St, Boston, MA 02114 USA. OI Chew, Felix/0000-0003-2711-2013 NR 12 TC 1 Z9 1 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD DEC PY 1998 VL 13 IS 8 BP 953 EP 957 DI 10.1016/S0883-5403(98)90206-6 PG 5 WC Orthopedics SC Orthopedics GA 151ZD UT WOS:000077749900019 PM 9880192 ER PT J AU Ring, D Jupiter, JB Simpson, NS AF Ring, D Jupiter, JB Simpson, NS TI Monteggia fractures in adults SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID RADIAL HEAD; REPLACEMENT; LESIONS AB The records concerning ten consecutive years of experience with Monteggia fractures in adult patients at a level-one trauma center were retrospectively reviewed. Forty-eight patients who had been followed for a minimum of two years (average, 6.5 years; range, two to fourteen years) were identified. There were twenty-five women and twenty-three men, and the average age was fifty-two years (range, eighteen to eighty-eight years). According to the classification of Bado, there were seven type-I, thirty-eight type-II, one type-III, and two type-IV injuries. Twenty-six patients (68 percent) who had a Bado type-II fracture had an associated fracture of the radial head; ten of these patients also had a fracture of the coronoid process as a single large fragment. The ulna was fixed with a tension band-wire construct supplemented with screws in three patients (all of whom had a Bado type-II fracture). An ulnar diaphyseal fracture was fixed with an intramedullary Steinmann pin in one patient. The remaining patients had fixation with a plate and screws. The fracture of the radial head was treated with either complete or partial excision of the fragments in twelve patients (with replacement with a silicone prosthesis in two), open reduction and internal fixation in ten patients, and no intervention in four patients. Nine patients, all of whom had a Bado type-II fracture, needed a reoperation within three months after the initial operation; five had revision of a loose ulnar fixation device, three had resection of the radial head, and one had removal of a wire that had migrated from the radial head into the elbow articulation. Other important complications included proximal radioulnar synostosis in three patients, ulnar malunion in three, posterolateral rotatory instability of the ulnohumeral joint in one, and instability of the distal radioulnar joint in one. At the most recent follow-up examination, which was performed after all of the reoperations and reconstructive procedures had been done, the average score according to the system of Broberg and Morrey was 86 points (range, 15 to 100 points). The result was excellent for eighteen patients, good for twenty-two, fair for two, and poor for six. Six of the eight patients who had an unsatisfactory (fair or poor) result had had a Bado type-II fracture with a concomitant fracture of the radial head. These unsatisfactory results were related to a malunited fracture of the coronoid process in two patients, a proximal radioulnar synostosis in one, a malunited fracture of the coronoid process and a proximal radioulnar synostosis in one, a malunion of the ulna in one, and painfully restricted rotation of the forearm after operative fixation of a comminuted fracture of the radial head in one. The other two unsatisfactory results were in a patient who had had a Bado type-I fracture and in one who had had a Bado type-IV fracture. The results of the present series are much better than those reported in most earlier studies, suggesting that stable anatomical fixation of the ulnar fracture (including associated fracture fragments of the coronoid process) with a plate and screws inserted with use of current techniques of fixation leads to a satisfactory result in most adults who have a Monteggia fracture. The posterior (Bado type-II) fracture is the most common type of Monteggia fracture in adults. Problems with the elbow related to fractures of the coronoid process and the radial head, which are common with Bado type-II Monteggia fractures, remain the most challenging elements in the treatment of these injuries. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, ACC 527,15 Parkman St, Boston, MA 02114 USA. NR 48 TC 95 Z9 105 U1 0 U2 4 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD DEC PY 1998 VL 80A IS 12 BP 1733 EP 1744 PG 12 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 151FJ UT WOS:000077709800003 PM 9875931 ER PT J AU Herndon, JH AF Herndon, JH TI Subspecialty training during residency and the ideal academic fellowship SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. RP Herndon, JH (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, 55 Fruit St,Gray 624, Boston, MA 02114 USA. NR 0 TC 5 Z9 5 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 1998 VL 80A IS 12 BP 1836 EP 1838 PG 3 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 151FJ UT WOS:000077709800017 PM 9875944 ER PT J AU Divieti, P Lanske, B Kronenberg, HM Bringhurst, FR AF Divieti, P Lanske, B Kronenberg, HM Bringhurst, FR TI Conditionally immortalized murine osteoblasts lacking the type 1 PTH/PTHrP receptor SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 07-11, 1996 CL SEATTLE, WASHINGTON SP Amer Soc Bone & Mineral Res ID PARATHYROID-HORMONE RECEPTOR; MESSENGER RIBONUCLEIC-ACIDS; RAT OSTEOSARCOMA CELLS; PHOSPHOLIPASE-C; INTRACELLULAR CALCIUM; ALKALINE-PHOSPHATASE; SIGNAL-TRANSDUCTION; OSTEO-SARCOMA; EXPRESSION; PEPTIDE AB Osteoblasts synthesize and mineralize bone matrix and are principal target cells for parathyroid hormone (PTH), The type 1 PTH/PTH-related protein (PTHrP) receptor (PTH1R), cloned from rat osteoblastic cells, activates multiple intracellular signaling mechanisms, The specific roles of these PTH1R signals, or of responses to other types of PTH receptors that may be expressed, in regulating osteoblast function are incompletely understood. Use of established mammalian osteoblastic cell lines has led to much understanding of PTH action in bone, although such cells are of neoplastic origin or have other characteristics that compromise their validity as models of normal osteoblasts, To examine the role of the PTH1R in osteoblast biology, we have isolated a series of clonal murine calvarial osteoblastic cell lines that are only conditionally immortalized, via expression of a transgene encoding the tsA58 temperature-sensitive SV40 large T antigen, and that lack both functional alleles of the PTH1R gene. When cultured under nontransforming conditions, these cells stopped proliferating expressed a series of characteristic osteoblastic genes (including the nonfunctional remnant of the PTH1R gene), and, after 3-4 weeks, produced mineralized bone nodules in a manner that was regulated by 1,25 dihydroxyvitamin D-3 but not by PTH(1-84), Cyclic AMP measurements revealed no evidence of expression of alternate species of Gs-linked PTH receptors, Stable transfection with PTH1R cDNA reconstituted both PTH binding and adenylyl cyclase activation, increased basal osteocalcin expression, and supported PTH stimulation of c-Fos expression and matrix mineralization. These conditionally transformed, PTH1R(-/-) clonal osteoblastic cell lines should prove useful for studies of the regulation of osteoblast differentiation and function by both endogenous nonclassical species of PTH (or PTHrP) receptors and mutant signal-selective PTH1Rs. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Divieti, P (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Wellman 5, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK47038, DK11794] NR 49 TC 35 Z9 35 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD DEC PY 1998 VL 13 IS 12 BP 1835 EP 1845 DI 10.1359/jbmr.1998.13.12.1835 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 141GE UT WOS:000077134300007 PM 9844101 ER PT J AU Reddy, S Devlin, R Menaa, C Nishimura, R Choi, SJ Dallas, M Yoneda, T Roodman, GD AF Reddy, S Devlin, R Menaa, C Nishimura, R Choi, SJ Dallas, M Yoneda, T Roodman, GD TI Isolation and characterization of a cDNA clone encoding a novel peptide (OSF) that enhances osteoclast formation and bone resorption SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID TRANSFORMING GROWTH-FACTOR; HUMAN MARROW CULTURES; MULTINUCLEATED CELLS; PROTEINS; ACID; SRC AB Using an expression cloning approach, we identified and cloned a novel intracellular protein produced by osteoclasts that indirectly induces osteoclast formation and bone resorption, termed OSF. Conditioned media from 293 cells transiently transfected with the 0.9 kb OSF cDNA clone stimulated osteoclast-like cell formation in both human and murine marrow cultures in the presence or absence 10(-9) M 1,25-dihydroxyvitamin D-3. In addition, conditioned media from 293 cells transfected with the OSF cDNA clone enhanced the stimulatory effects of 1,25(OH)(2)D-3 on bone resorption in the fetal rat long bone assay. In situ hybridization studies using antisense oligomers showed expression of OSF mRNA in highly purified osteoclast-like cells from human giant cell tumors of the bone. Northern blot analysis demonstrated ubiquitous expression of a 1.3 kb mRNA that encodes OSF in multiple human tissues. Sequence analysis showed the OSF cDNA encoded a 28 kD peptide that contains a c-Src homology 3 domain (SH3) and ankyrin repeats, suggesting that it was not a secreted protein, but that it was potentially involved in cell signaling. Consistent with these data, immunoblot analysis using rabbit antisera against recombinant OSF demonstrated OSF expression in cell lysates but not in the culture media. Furthermore, recombinant OSF had a high affinity for c-Src, an important regulator of osteoclast activity. Taken together, these data suggest that OSF is a novel intracellular protein that indirectly enhances osteoclast formation and osteoclastic bone resorption through the cellular signal transduction cascade, possibly through its interactions with c-Src or other Src-related proteins. J Cell Physiol 177.636-645, 1998. (C) 1998 Wiley-Liss, Inc. C1 Vet Adm Med Ctr, Dept Med Hematol Endocrinol, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Osaka Univ, Dept Biochem, Osaka, Japan. RP Roodman, GD (reprint author), Audie L Murphy Mem Vet Hosp, Res Serv 151, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NIA NIH HHS [AG 39529]; NIADDK NIH HHS [AM 35188]; NIAMS NIH HHS [AR41336] NR 18 TC 35 Z9 36 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD DEC PY 1998 VL 177 IS 4 BP 636 EP 645 DI 10.1002/(SICI)1097-4652(199812)177:4<636::AID-JCP14>3.0.CO;2-H PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 144DZ UT WOS:000077299700014 PM 10092216 ER PT J AU So, GM Herbert, MR Dooling, EC Buonanno, F Kosofsky, BE Ebb, D AF So, GM Herbert, MR Dooling, EC Buonanno, F Kosofsky, BE Ebb, D TI Multifocal embolic strokes following cardiac surgery in a protein C-deficient child SO JOURNAL OF CHILD NEUROLOGY LA English DT Article ID CONGENITAL HEART-DISEASE; S DEFICIENCY; THROMBOSIS; INFANTS; ASSOCIATION; PREVALENCE; NEWBORN; STATE; RISK C1 Univ Texas, SW Med Ctr, Div Neurol, Dallas, TX 75235 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA USA. RP So, GM (reprint author), Univ Texas, SW Med Ctr, Div Neurol, Dallas, TX 75235 USA. NR 22 TC 2 Z9 2 U1 0 U2 0 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD DEC PY 1998 VL 13 IS 12 BP 629 EP 631 PG 3 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 150NJ UT WOS:000077670800007 PM 9881534 ER PT J AU Eng, C Marsh, DJ Robinson, BG Chow, CW Patton, MA Southey, MC Venter, DJ Ponder, BAJ Milla, PJ Smith, VV AF Eng, C Marsh, DJ Robinson, BG Chow, CW Patton, MA Southey, MC Venter, DJ Ponder, BAJ Milla, PJ Smith, VV TI Germline RET codon 918 mutation in apparently isolated intestinal ganglioneuromatosis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MEDULLARY-THYROID CARCINOMA; ENDOCRINE NEOPLASIA TYPE-2; PROTOONCOGENE; 2B; DISEASE C1 Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Med, Dept Adult Oncol,Charles A Dana Human Canc Genet, Boston, MA 02115 USA. Royal N Shore Hosp, Dept Endocrinol, Kolling Inst Med Res, Mol Genet Lab, St Leonards, NSW 2006, Australia. Univ Sydney, Dept Med, Sydney, NSW 2006, Australia. Royal Childrens Hosp, Dept Anat Pathol, Melbourne, Vic, Australia. Peter MacCallum Canc Inst, Dept Pathol, Melbourne, Vic 3052, Australia. Peter MacCallum Canc Inst, Dept Res, Melbourne, Vic 3052, Australia. St George Hosp, Sch Med, Dept Med Genet, London SW7 0RE, England. Univ Cambridge, Canc Res Campaign, Human Canc Genet Res Grp, Cambridge CB2200, England. Great Ormond St Hosp Sick Children, Dept Histopathol, London, England. Great Ormond St Hosp Sick Children, Gastroenterol Unit, London, England. Inst Child Hlth, London WC1N 3JH, England. RP Eng, C (reprint author), Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, 420 W 12th Ave,690MRF, Columbus, OH 43210 USA. RI Smith, Virpi/C-2159-2008; Marsh, Deborah/I-1491-2014; OI Marsh, Deborah/0000-0001-5899-4931; Eng, Charis/0000-0002-3693-5145 NR 13 TC 10 Z9 10 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 DEC PY 1998 VL 83 IS 12 BP 4191 EP 4194 DI 10.1210/jc.83.12.4191 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 145FB UT WOS:000077359400003 PM 9851750 ER PT J AU Grinspoon, S Corcoran, C Stanley, T Katznelson, L Klibanski, A AF Grinspoon, S Corcoran, C Stanley, T Katznelson, L Klibanski, A TI Effects of androgen administration on the growth hormone-insulin-like growth factor I axis in men with acquired immunodeficiency syndrome wasting SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SOMATOMEDIN-C CONCENTRATIONS; PROTEIN RESTRICTION; BODY-COMPOSITION; VIRUS-INFECTION; TESTOSTERONE; BINDING; MASS; SECRETION; CHILDREN; HUMANS AB It is unknown whether hypogonadism contributes to decreased insulin-like growth factor I (IGF-I) production and/or how testosterone administration may effect the GH-IGF-I axis in human immunodeficiency virus (HIV)-infected men with the acquired immunodeficiency syndrome (AIDS) wasting syndrome (AWS). In this study, we investigate the GH-IGF-I axis in men with the AWS and determine the effects of testosterone on GH secretory dynamics, pulse characteristics determined from overnight frequent sampling, arginine stimulation, and total and free IGF-I levels. Baseline GH-IGF-I parameters in hypogonadal men with AWS (n = 51) were compared before testosterone administration (300 mg, im, every 3 weeks vs. placebo for 6 months) with cross-sectional data obtained in two age-matched control groups: eugonadal men with AIDS wasting (n = 10) and healthy age-matched normal men (n = 15). The changes in GH-IGF-I parameters were then compared prospectively in testosterone- and placebo-treated patients. Mean overnight GH levels [1.8 +/- 0.3 and 2.4 +/- 0.3 vs. 0.90 +/- 0.1 mu g/L (P = 0.04 and P = 0.003 vs, healthy controls)] and pulse frequency [0.35 +/- 0.06 and 0.37 +/- 0.02 vs. 0.22 +/- 0.03 pulses/h (P = 0.06 and P = 0.002 vs, healthy controls)] were comparably elevated in the eugonadal and hypogonadal HIV-positive groups, respectively, compared to those in the healthy control group. No significant differences in pulse amplitude, interpulse interval, or maximal GH stimulation to arginine administration (0.5 g/kg, iv) were seen between either the eugonadal and hypogonadal HIV-positive or healthy control patients. In contrast, IGF-I levels were comparably decreased in both HIV-positive groups compared to the healthy control group [143 +/- 16 and 165 +/- 14 vs. 216 +/- 14 mu g/L (P = 0.004 and P = 0.02 vs. healthy controls)]. At baseline, before treatment with testosterone, overnight GH levels were inversely correlated with IGF-I (r = -0.42; P = 0.003), percent ideal body weight (r = -0.36; P = 0.012), albumin (r = -0.37; P = 0.012), and fat mass (r = -0.52; P = 0.0002), whereas IGF-I levels correlated with free testosterone (r = 0.35; P = 0.011) and caloric intake (r = 0.32; P = 0.023) in the hypogonadal HIV-positive men. In a stepwise regression model, albumin (P = 0.003) and testosterone (P = 0.011) were the only significant predictors of GH [mean GH (mu g/L) = -1.82 x albumin (g/dL) + 0.003 x total testosterone (mu g/L) + 6.5], accounting for 49% of the Variation in GH. Mean overnight GH levels decreased significantly in the testosterone-treated patients compared to those in the placebo-treated hypogonadal patients (-0.9 +/- 0.3 vs. 0.2 +/- 0.4 mu g/L; P = 0.020). In contrast, no differences in IGF-I or free IGF-I were observed in response to testosterone administration. The decrement in mean overnight GH in response to testosterone treatment was inversely associated with increased fat-free mass (r = -0.49; P = 0.024), which was the only significant variable in a stepwise regression model for change in GH [change in mean GH (mu g/L) = -0.197 x kg fat-free mass - 0.53] and accounted for 27% of the variation in the change in GH. In this study, we demonstrate increased basal GH secretion and pulse frequency in association with reduced IGF-I concentrations, consistent with GH resistance, among both hypogonadal and eugonadal men with AIDS wasting. Testosterone administration decreases GH in hypogonadal men with AIDS wasting. The change in GH is best predicted by and is inversely related to the magnitude of the change in lean body mass in response to testosterone administration. These data demonstrate that among hypogonadal men with the AWS, testosterone administration has a significant effect on the GH axis. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. FU NCRR NIH HHS [MO1-RR-01066]; NIDDK NIH HHS [R01-DK-49302, F32-DK-09218] NR 29 TC 22 Z9 22 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 DEC PY 1998 VL 83 IS 12 BP 4251 EP 4256 DI 10.1210/jc.83.12.4251 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 145FB UT WOS:000077359400014 PM 9851759 ER PT J AU Eng, C Thomas, GA Neuberg, DS Mulligan, LM Healey, CS Houghton, C Frilling, A Raue, F Williams, ED Ponder, BAJ AF Eng, C Thomas, GA Neuberg, DS Mulligan, LM Healey, CS Houghton, C Frilling, A Raue, F Williams, ED Ponder, BAJ TI Mutation of the RET proto-oncogene is correlated with RET immunostaining in subpopulations of cells in sporadic medullary thyroid carcinoma SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; SOMATIC MUTATIONS; DISEASE PHENOTYPE; TYROSINE KINASE; CODON 883; MEN 2A; TYPE-2; EXPRESSION; SEQUENCE; TISSUES AB Mutations in the RET proto-oncogene, which encodes a receptor tyrosine kinase, are associated with the pathogenesis of medullary thyroid carcinoma (MTC). Somatic mutations in RET, predominantly at codon 918, and very rarely at codon 883, have been found in a proportion of sporadic MTC. Fire have previously shown that approximately 80% of sporadic MTCs had at least one subpopulation with a somatic RET mutation. Uneven distribution of somatic mutation within a single tumor or among metastases from a single individual was notable. In the present study, we sought to correlate RET expression, as demonstrated by RET immunohistochemistry, with mutation status in sporadic MTC for each tumor. Seventy evaluable subpopulations, belonging to 28 unrelated sporadic cases, comprising primary MIC and metastases, were immunostained with two different polyclonal antibodies raised against the C-terminus of RET. The regional presence of codon 918 or 883 seemed to coincide with increased RET immunopositivity in at least 62 of 70 (89%, P < 0.000001 tumor subpopulations. The reasons for this concordance are not entirely clear but could be related to either RNA or protein stability. Preliminary studies have suggested that the presence of somatic codon 918 mutation in MTC has a prognostic significance. If these preliminary results prove true, then given our data, we can further explore the feasibility of RET immunocytochemistry as a rapid assessment for the presence of somatic codon 918 for molecular diagnostic and prognostic purposes. C1 Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA. Univ Cambridge, Canc Res Campaign, Human Canc Genet Res Grp, Cambridge CB2 2QQ, England. Univ Cambridge, Dept Histopathol, Cambridge CB2 2QQ, England. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Adult Oncol, Charles A Dana Human Canc Genet Unit, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Queens Univ, Dept Pathol, Kingston, ON K7L 3N6, Canada. Queens Univ, Dept Paediat, Kingston, ON K7L 3N6, Canada. Univ Hamburg, Univ Krankenhaus, Chirurg Klin, D-2000 Hamburg 20, Germany. Heidelberg Univ, Med Klin & Poliklin, Innere Med Abt 1, D-69118 Heidelberg, Germany. RP Eng, C (reprint author), Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, 690C Med Res Facil,420 W 12th Ave, Columbus, OH 43210 USA. EM eng-1@medctr.osu.edu OI Eng, Charis/0000-0002-3693-5145 NR 23 TC 22 Z9 23 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 DEC PY 1998 VL 83 IS 12 BP 4310 EP 4313 DI 10.1210/jc.83.12.4310 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 145FB UT WOS:000077359400024 PM 9851769 ER PT J AU Solomon, KR Kurt-Jones, EA Saladino, RA Stack, AM Dunn, IF Ferretti, M Golenbock, D Fleisher, GR Finberg, RW AF Solomon, KR Kurt-Jones, EA Saladino, RA Stack, AM Dunn, IF Ferretti, M Golenbock, D Fleisher, GR Finberg, RW TI Heterotrimeric G proteins physically associated with the lipopolysaccharide receptor CD14 modulate both in vivo and in vitro responses to lipopolysaccharide SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE lipopolysaccharide; G proteins; signal transduction; monocytes/macrophages; endotoxin shock ID GPI-ANCHORED PROTEINS; G-BETA-GAMMA; SIGNAL-TRANSDUCTION; TYROSINE KINASES; BINDING PROTEIN; CELL-SURFACE; DETERGENT INSOLUBILITY; ALKALINE-PHOSPHATASE; COUPLED RECEPTORS; MEMBRANE DOMAINS AB Septic shock induced by lipopolysaccharide (LPS) triggering of cytokine production from monocytes/macrophages is a major cause of morbidity and mortality. The major monocyte/macrophage LPS receptor is the glycosylphosphatidylinositol (GPI)-anchored glycoprotein CD14. Here we demonstrate that CD14 coimmunoprecipitates with G(i)/G(o) heterotrimeric G proteins. Furthermore, we demonstrate that heterotrimeric G proteins specifically regulate CD14-mediated, LPS-induced mitogen-activated protein kinase (MAPK) activation and cytokine production in normal human monocytes and cultured cells. We report here that a G protein binding peptide protects rats from LPS-induced mortality, suggesting a functional linkage between a GPI-anchored receptor and the intracellular signaling molecules with which it is physically associated. C1 Dana Farber Canc Inst, Infect Dis Unit, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Boston Univ, Med Ctr, Dept Med, Maxwell Finland Lab Infect Dis, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Finberg, RW (reprint author), Dana Farber Canc Inst, Infect Dis Unit, 44 Binney St, Boston, MA 02115 USA. RI Finberg, Robert/E-3323-2010 FU NIAID NIH HHS [T32 AI 07061-19]; NIGMS NIH HHS [R01 GM54060] NR 62 TC 84 Z9 91 U1 0 U2 1 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 1998 VL 102 IS 11 BP 2019 EP 2027 DI 10.1172/JCI4317 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 146PY UT WOS:000077440600016 PM 9835628 ER PT J AU Iwen, PC Rupp, ME Bishop, MR Rinaldi, MG Sutton, DA Tarantolo, S Hinrichs, SH AF Iwen, PC Rupp, ME Bishop, MR Rinaldi, MG Sutton, DA Tarantolo, S Hinrichs, SH TI Disseminated aspergillosis caused by Aspergillus ustus in a patient following allogeneic peripheral stem cell transplantation SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID LIPOSOMAL AMPHOTERICIN-B; INVASIVE ASPERGILLOSIS; FUNGAL-INFECTIONS; IMMUNOCOMPROMISED PATIENTS; BONE-MARROW; THERAPY; ENDOCARDITIS; EPIDEMIOLOGY; DISEASE AB The first case of disseminated aspergillosis caused by Aspergillus ustus in an allogeneic peripheral stem cell transplant patient is described. The patient, a 46-year-old female with a history of myelodysplastic syndrome, underwent high-dose chemotherapy and total body irradiation prior to transplantation. She was released from the hospital 49 days posttransplant (p.t.) in a stable condition with an absolute neutrophil count (ANC) of 2,700 cells per yl. Multiple antimicrobial agents, including itraconazole (ITR), were prescribed during hospitalization and at the time of discharge. Three days after discharge, the patient was readmitted with hemorrhagic cystitis, persistent thrombocytopenia, and bilateral pulmonary consolidation, although no fever was present. The ANC at the time of readmission was 3,500, Upon detection of a pulmonary nodule (day 67 p.t.), a bronchoalveolar lavage was performed; the lavage fluid was positive for both cytomegalovirus and parainfluenza virus and negative for fungus. The patient was placed on ganciclovir, A biopsy specimen from a leg lesion also noted on day 67 p.t. revealed septate hyphae consistent with Aspergillus species, and a culture subsequently yielded Aspergillus ustus. Confirmation detection of A. ustus was made by demonstration of characteristic reproductive structures with the presence of Hulle cells. On day 67 p.t., ITR was discontinued and liposomal amphotericin B (AMB) was initiated. The patient's condition worsened, and she died 79 days p.t. At the time of autopsy, septate hyphae were present in heart, thyroid, and lung tissues, with lung tissue culture positive ford. ustus. In vitro susceptibility testing indicated probable resistance to AMB but not to ITR, This case supports the need for the development of rapid methods to determine antifungal susceptibility. C1 Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Internal Med, Omaha, NE 68198 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, Fungus Testing Lab, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Iwen, PC (reprint author), Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, 600 S 42nd St, Omaha, NE 68198 USA. NR 30 TC 27 Z9 27 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 1998 VL 36 IS 12 BP 3713 EP 3717 PG 5 WC Microbiology SC Microbiology GA 140CP UT WOS:000077069400054 PM 9817905 ER PT J AU Wu, C Vasconcelles, M DePiro, P Van den Abbeele, A Rakusin, A Bechard, K Skarin, A AF Wu, C Vasconcelles, M DePiro, P Van den Abbeele, A Rakusin, A Bechard, K Skarin, A TI Primary cardiac angiosarcoma presenting as a malignant pericardial effusion SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HEART C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Wu, C (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC PY 1998 VL 16 IS 12 BP 3913 EP 3915 PG 3 WC Oncology SC Oncology GA 144RE UT WOS:000077328200025 PM 9850037 ER PT J AU Schlozman, SC AF Schlozman, SC TI Upper-extremity self-amputation and replantation: 2 case reports and a review of the literature SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID MUTILATION; PENIS AB Background: Patients who deliberately amputate I or more of their own extremities present a unique set of challenges for the entire treatment team. Decisions regarding replantation of the amputated extremity must be made quickly and the psychiatrist is involved early in the care of these difficult patients. Surgical staff may feel that replantation surgery is inappropriate for such patients, although there is limited literature addressing this issue. Therefore, the psychiatrist must also address the strong feelings that such patients generate in nonpsychiatric caregivers. Method: Two cases of deliberate upper-extremity self-amputation are discussed, and the world literature on self-amputation and replantation from 1966 to the present, identified via a MEDLINE search, using the key words self-amputation, self-inflicted, upper extremity, and amputation, is reviewed. Results: There have been Il reported cases (plus 2 in the current report) of deliberate upper-extremity amputation in the last 30 years. All patients have been psychotic, and many of the case reports note that patients with this presentation are rarely suicidal. Instead, the amputation usually stems from psychotically driven feelings of guilt and concrete religious preoccupations. Patients who undergo replantation often are pleased with the reattachment, and both psychiatric and surgical outcomes appear to benefit from prompt and aggressive psychiatric treatment. Conclusion: Patients who deliberately amputate one or more of their extremities can be unsettling as well as challenging. The psychiatrist must coordinate diagnosis and treatment among multiple services to ensure the best possible outcome. As replantation surgery becomes more common, the psychiatric implications of surgical reattachment are of increasing importance. More cases need to be described to better understand the best treatment options for this particular patient population. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. RP Schlozman, SC (reprint author), Harvard Univ, Sch Med, Dept Psychiat, 15 Parkman St,WACC-725, Boston, MA 02114 USA. NR 22 TC 32 Z9 35 U1 0 U2 5 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 1998 VL 59 IS 12 BP 681 EP 686 DI 10.4088/JCP.v59n1207 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 158LL UT WOS:000078116900007 PM 9921703 ER PT J AU Amsterdam, JD Garcia-Espana, F Fawcett, J Quitkin, FM Reimherr, FW Rosenbaum, JF Schweizer, E Beasley, C AF Amsterdam, JD Garcia-Espana, F Fawcett, J Quitkin, FM Reimherr, FW Rosenbaum, JF Schweizer, E Beasley, C TI Efficacy and safety of fluoxetine in treating bipolar II major depressive episode SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID AFFECTIVE-DISORDERS; MANIA; ANTIDEPRESSANTS; STABILITY; UNIPOLAR; ILLNESS AB As many as 45% of patients with major depressive episode also meet DSM-TV criteria for bipolar II (BP II) disorder. Although some clinicians advocate using a mood stabilizer in treating BP II depression, antidepressant monotherapy has been less well studied in this disorder. As part of a prospective, placebo-controlled, relapse-prevention study in 839 patients, the efficacy and safety of short- and long-term fluoxetine treatment in patients with BP II major depression compared with patients with unipolar (UP) major depression was retrospectively examined. Eighty-nine BP II patients (mean age, 41 +/- 11 years) were compared with 89 age- and gender-matched UP patients and with 661 unmatched UP patients (mean age, 39 +/- 11 years). All received short-term fluoxetine therapy at 20 mg daily for up to 12 weeks. Complete remission was defined as a final Hamilton Rating Scale for Depression score less than or equal to 7 by meek 9 that was then maintained for 3 additional weeks. Remitted patients were then randomly assigned to receive double-blind treatment with one of the following: (1) fluoxetine 20 mg daily for 52 weeks; (2) fluoxetine for 38 weeks, then placebo for 14 weeks; (3) fluoxetine for 14 weeks, then placebo for 38 weeks; or (4) placebo for 52 weeks. Antidepressant efficacy mas similar in BP and UP patients during short-term therapy. Discontinuation for lack of efficacy was lower in BP II (5%) than in UP (12%) patients (p = not significant [NS]), whereas dropouts for adverse events mere similar in BP II(11%) and UP (9%) patients. During longterm relapse-prevention therapy, relapse rates mere similar in BP II and UP patients (p = NS) During short-term fluoxetine therapy, three BP II (3.8%) versus no matched UP (p = NS) and 0.3% unmatched UP (p = 0.01) patients had a "manic switch." During long-term fluoxetine therapy, one (2%) BP II and three (1%) unmatched UP patients (one taking placebo) had a manic switch (p = NS). In conclusion, fluoxetine may be a safe and effective antidepressant monotherapy for the shortterm treatment of BP II depression with a relatively low manic switch rate. Fluoxetine may also be effective in relapse-prevention therapy in patients with BP II disorder. C1 Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL USA. New York State Psychiat Inst, New York, NY USA. Univ Utah, Sch Med, Salt Lake City, UT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Lilly Res Labs, Indianapolis, IN USA. RP Amsterdam, JD (reprint author), Univ Sci Ctr, Depress Res Unit, 8th Floor,3600 Market St, Philadelphia, PA 19104 USA. OI Beasley, Charles/0000-0001-8743-7691 NR 29 TC 121 Z9 126 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD DEC PY 1998 VL 18 IS 6 BP 435 EP 440 DI 10.1097/00004714-199812000-00003 PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 146JJ UT WOS:000077425300003 PM 9864074 ER PT J AU Lytton, WW AF Lytton, WW TI Adapting a feedforward heteroassociative network to Hodgkin-Huxley dynamics SO JOURNAL OF COMPUTATIONAL NEUROSCIENCE LA English DT Article DE associative memory; inhibition; artificial neural network; hippocampus ID DEPOLARIZATION-INDUCED SUPPRESSION; CAT VISUAL-CORTEX; PIRIFORM CORTEX; PYRAMIDAL CELLS; GABAERGIC INHIBITION; DENTATE GYRUS; NEURONS; MEMORY; OSCILLATIONS; RESPONSES AB Using the original McCulloch-Pitts notion of simple on and off spike coding in lieu of rate coding, an Anderson-Kohonen artificial neural network (ANN) associative memory model was ported to a neuronal network with Hodgkin-Huxley dynamics. In the ANN, the use of 0/1 (no-spike/spike) units introduced a cross-talk term that had to be compensated by introducing balanced feedforward inhibition. The resulting ANN showed good capacity and fair selectivity (rejection of unknown input vectors). Translation to the Hodgkin-Huxley model resulted in a network that was functional but not at all robust. Evaluation of the weaknesses of this network revealed that it functioned far better using spike timing, rather than spike occurrence, as the code. The algorithm requires a novel learning algorithm for feedforward inhibition that could be sought physiologically. C1 Univ Wisconsin, William S Middleton Mem Vet Hosp, Dept Neurol, Madison, WI 53706 USA. Univ Wisconsin, William S Middleton Mem Vet Hosp, Neurosci Training Program, Madison, WI 53706 USA. RP Lytton, WW (reprint author), Univ Wisconsin, William S Middleton Mem Vet Hosp, Dept Neurol, 1300 Univ Ave,MSC 1715, Madison, WI 53706 USA. EM billl@neurosim.wisc.edu NR 64 TC 6 Z9 7 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0929-5313 J9 J COMPUT NEUROSCI JI J. Comput. Neurosci. PD DEC PY 1998 VL 5 IS 4 BP 353 EP 364 DI 10.1023/A:1026456411040 PG 12 WC Mathematical & Computational Biology; Neurosciences SC Mathematical & Computational Biology; Neurosciences & Neurology GA 153JC UT WOS:000077829100001 PM 9877019 ER PT J AU Wang, M Dobeck, JM Sorkin, BC Skobe, Z AF Wang, M Dobeck, JM Sorkin, BC Skobe, Z TI Adenomatous polyposis coli protein is expressed in alternate stages of the ameloblast life cycle SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE adenomatous polyposis coli protein; APC; ameloblasts; odontogenesis; enamel; catenins; E-cadherin ID TUMOR-SUPPRESSOR PROTEIN; CELL-ADHESION MOLECULE; CYTOPLASMIC DOMAIN; CATENIN COMPLEX; APC GENE; CADHERIN AB Mutations of the adenomatous polyposis coli gene protein (APC) are associated with familial polyposis and also sporadic colon adenomas, both preconditions to cancer formation. Some familial polyposis patients also develop Gardner's syndrome, a condition characterized by supernumerary teeth, mandibular osteomas, and other maladies. We investigated participation of APC in normal tooth development. Using a monoclonal antibody to study APC expression in the forming rat incisor, we found no APC staining in differentiating ameloblasts, then strong staining in secreting ameloblasts and stratum intermedium cells, followed by cells in the transition stage which did not stain. Intense APC staining resumes in maturation-stage ameloblasts and proximal papillary cells. APC staining disappears again in reduced ameloblasts at the conclusion of amelogenesis. APC staining was not seen in any other odontogenic cells. We report a unique system in which APC expresssion is upregulated and downregulated twice during the normal life cycle of ameloblasts. APC, therefore, is important in the normal maturation of both colonic epithelium and odontogenic epithelium. At this point, we cannot rule out any of the known functions of APC, which include: modulation of cell adhesion by binding to catenin, regulation of beta-catenin as a differentiative signaling molecule, and promotion of microtubule assembly. In this respect, the rat incisor enamel organ provides a unique tissue for studying the regulation and functions of APC. C1 Forsyth Dent Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Skobe, Z (reprint author), Forsyth Dent Ctr, 140 Fenway, Boston, MA 02115 USA. OI Sorkin, Barbara/0000-0001-8198-6921 NR 20 TC 9 Z9 9 U1 0 U2 5 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD DEC PY 1998 VL 77 IS 12 BP 1979 EP 1982 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 142PL UT WOS:000077209000005 PM 9839785 ER PT J AU Keen, A AF Keen, A TI Diagnosis and treatment of sociopaths and clients with sociopathic traits. SO JOURNAL OF FAMILY VIOLENCE LA English DT Book Review C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15208 USA. RP Keen, A (reprint author), VA Pittsburgh Healthcare Syst, VA Med Ctr Highland Dr,7180 Highland Dr, Pittsburgh, PA 15208 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7482 J9 J FAM VIOLENCE JI J. Fam. Violence PD DEC PY 1998 VL 13 IS 4 BP 445 EP 446 DI 10.1023/A:1022883405163 PG 2 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 142YZ UT WOS:000077229500008 ER PT J AU Ritholz, MD Jacobson, AM AF Ritholz, MD Jacobson, AM TI Living with hypoglycemia SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE hypoglycemia; type 1 diabetes; narrative research ID DEPENDENT DIABETES-MELLITUS; RECURRENT EPISODES; CHRONIC ILLNESS; IMPAIRMENT; IDDM AB OBJECTIVE: To increase understanding of the everyday experiences of hypoglycemia for patients with type 1 diabetes through the use of a narrative research approach. SETTING:Center for diabetes treatment and research. DESIGN: Cross-sectional assessment using a narrative research approach. PATIENTS/PARTICIPANTS: Twenty outpatients (aged 21-30 years) diagnosed with type 1 diabetes for at least 10 years. MEASUREMENTS AND MAIN RESULTS: Experiences of hypoglycemia were investigated during in-depth, semistructured interviews that were tape-recorded, transcribed, and analyzed to identify common themes. Self-report measures of depression (Revised Hamilton Rating Scale for Depression) and anxiety (State-Trait Anxiety Inventory) also were administered. Subjects reported the following common themes: interpersonal conflict including fears of dependency and loss of control and problems addressing concerns about hypoglycemia with significant others; difficulty making sense of their hypoglycemic behaviors in relation to their usual ways of functioning; and perceived lack of understanding by others, including physicians, about the emotional experiences of hypoglycemia. Subjects were neither clinically depressed nor anxious. CONCLUSIONS: These findings suggest that type 1 diabetes patients' experiences of hypoglycemia negatively affect their interpersonal relationships and views of themselves. Hypoglycemia also was described as an extremely private experience that was rarely discussed with others. Patient education and professional support in the treatment of hypoglycemia are recommended to enhance treatment decision making for patients with type 1 diabetes. C1 Childrens Hosp, Joslin Diabet Ctr, Behav & Mental Hlth Res Sect, Boston, MA 02115 USA. RP Ritholz, MD (reprint author), Joslin Diabet Ctr, Behav & Mental Hlth Unit, 1 Joslin Pl, Boston, MA 02215 USA. NR 42 TC 26 Z9 26 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 1998 VL 13 IS 12 BP 799 EP 804 DI 10.1046/j.1525-1497.1998.00243.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 148GD UT WOS:000077496000002 PM 9844077 ER PT J AU Li, CH Breton, S Morrison, R Cannon, CL Emma, F Sanchez-Olea, R Bear, C Strange, K AF Li, CH Breton, S Morrison, R Cannon, CL Emma, F Sanchez-Olea, R Bear, C Strange, K TI Recombinant pI(Cln) forms highly cation-selective channels when reconstituted into artificial and biological membranes SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article DE cell volume; swelling-activated anion channels; planar lipid bilayer; liposomes; recombinant protein ID RESISTANCE P-GLYCOPROTEIN; XENOPUS-OOCYTES; CHLORIDE CHANNEL; EXPRESSION; CONDUCTANCE; INSERTION; PROTEIN; BINDING; FUSION AB pI(Cln) has been proposed to be the swelling-activated anion channel responsible for I-Cl,I- swell, or a channel regulator. We tested the anion channel hypothesis by reconstituting recombinant pI(Cln) into artificial and biological membranes. Single channels were observed when pI(Cln) was reconstituted into planar lipid bilayers. In the presence of symmetrical 300 mM KCI, the channels had a high open probability and a slope conductance of 48 pS, and were outwardly rectifying. Reduction of trans KCl to 50 mM shifted the reversal potential by -31.2 +/- 0.06 mV, demonstrating that the channel is at least seven times more selective for cations than for anions. Consistent with this finding, channel conductance was unaffected by substitution of Cl- with glutamate, but was undetectable when K+ was replaced by N-methyl-d-glucamine. Reconstitution of pI(Cln) into liposomes increased Rb-86(+) uptake by three- to fourfold, but had no effect on Cl-36(-) uptake. Phosphorylation of pI(Cln) with casein kinase II or mutation of Gig, G56, and G58 to alanine decreased channel open probability and Rb-86(+) uptake. When added to the external medium bathing Sf9 cells, pI(Cln) inserted into the plasma membrane and increased cell cation permeability. Taken together, these observations demonstrate that channel activity is due to pI(Cln) and not minor contaminant proteins. However, these findings do not support the hypothesis that pI(Cln) is the anion-selective I-Cl,I- swell channel. The observed cation channel activity may reflect an as yet to be defined physiological function of pI(Cln), or may be a consequence of in vitro reconstitution of purified, recombinant protein. C1 Vanderbilt Univ, Sch Med, Dept Anesthesiol, Anesthesiol Res Div, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37232 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Univ Toronto, Hosp Sick Children, Div Cell Biol, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Physiol, Toronto, ON M5G 1X8, Canada. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02129 USA. RP Strange, K (reprint author), Vanderbilt Univ, Sch Med, Dept Anesthesiol, Anesthesiol Res Div, 504 Oxford House,1313 21st Ave S, Nashville, TN 37232 USA. EM kevin.strange@mcmail.vanderbilt.edu RI Cannon, Carolyn/A-4402-2008; Emma, Francesco/H-2116-2012 FU NIDDK NIH HHS [DK-51610, R01 DK051610]; NINDS NIH HHS [NS-30591] NR 29 TC 37 Z9 37 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD DEC PY 1998 VL 112 IS 6 BP 727 EP 736 DI 10.1085/jgp.112.6.727 PG 10 WC Physiology SC Physiology GA 145EE UT WOS:000077357400005 PM 9834142 ER PT J AU Camicioli, R Oken, BS Sexton, G Kaye, JA Nutt, JG AF Camicioli, R Oken, BS Sexton, G Kaye, JA Nutt, JG TI Verbal fluency task affects gait in Parkinson's disease with motor freezing SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article ID DUAL-TASK; SIMULTANEOUS MOVEMENTS; BIMANUAL MOVEMENTS; ALZHEIMERS-DISEASE; IGNITION FAILURE; PERFORMANCE; WALKING; ATTENTION; FALLS; DISORDERS AB We examined the effects of a simultaneous verbal fluency task on walking in Parkinson's disease (PD) patients with freezing of gait (PD-F) compared to nonfreezing patients (PD-NF) or control subjects (C). Effects of antiparkinsonian medications on gait in PD-F were examined. PD-F patients exhibited a greater increase in the number of steps to complete the walk with verbal fluency, even when the effect of medication was taken into account (mean increase +/- SD): PD-F = 4.2 +/- 4.6, n = 10; PD-NF = 0.1 +/- 1.6, n = 9; C = 1.5 +/- 1.5, n = 19; P =.007. Medications improved walking in PD-F patients by decreasing the number of steps, the time to walk, and freezing. PD-F patients may be more dependent on attention for walking. C1 Oregon Hlth Sci Univ, Dept Neurol, Aging & Alzheimer Dis Ctr, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. RP Camicioli, R (reprint author), Oregon Hlth Sci Univ, Dept Neurol, Aging & Alzheimer Dis Ctr, CR131,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. OI Kaye, Jeffrey/0000-0002-9971-3478; Camicioli, Richard/0000-0003-2977-8660 FU NCRR NIH HHS [3M01-RR00334-30S1]; NIA NIH HHS [AG08017] NR 43 TC 80 Z9 83 U1 2 U2 6 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD WIN PY 1998 VL 11 IS 4 BP 181 EP 185 PG 5 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 185KH UT WOS:000079667800003 PM 10230996 ER PT J AU Systrom, DM Pappagianopoulos, P Fishman, RS Wain, JC Ginns, LC AF Systrom, DM Pappagianopoulos, P Fishman, RS Wain, JC Ginns, LC TI Determinants of abnormal maximum oxygen uptake after lung transplantation for chronic obstructive pulmonary disease SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID LEFT-VENTRICULAR FUNCTION; SKELETAL-MUSCLE; HEMOGLOBIN CONCENTRATION; ANAEROBIC THRESHOLD; OXIDATIVE CAPACITY; EXERCISE; RECIPIENTS; RESPONSES; CYCLOSPORINE; SINGLE AB Background: Single lung transplantation for chronic obstructive pulmonary disease relieves a ventilatory limit to incremental exercise, but maximum oxygen uptake remains abnormal. The purpose of this study was to define the relative contributions of Pick principle variables to abnormal aerobic capacity after lung transplantation. Methods: Twelve paired incremental cardiopulmonary exercise test results obtained before and 3 to 6 months after single lung transplantation for chronic obstructive pulmonary disease were compared. Results: Maximum workload neatly doubled after operation (42.5 +/- 4.2 vs 25.5 +/- 4.7 watts, P <.05). Peak exercise minute ventilation increased (32.8 +/- 3.3 vs 21 +/- 2.4 L/min, n = 11, P <.05), but maximum oxygen uptake remained markedly abnormal after transplantation (46.6% +/- 4.4% vs 32.1% +/- 2.9% predicted, P <.05, n = 8). Peak exercise cardiac output was normal (11.0 +/- 1.4 L/min, 89% predicted), but arterial - mixed venous oxygen content difference at peak exercise was only half of normal (7.2 +/- 0.61 mL/dL), as a result in part of the failure of mixed venous oxygen saturation to fall normally (peak exercise SVO2 = 49.8% +/- 2.8%). Conclusions: Lung transplantation for chronic obstructive pulmonary disease relieves a ventilatory limit to exercise, but maximum aerobic capacity remains abnormal, in part because of abnormal systemic O-2 extraction. C1 Harvard Univ, Massachusetts Gen Hosp, Pulm & Crit Care Unit, Cardiopulm Exercise Lab,Sch Med, Boston, MA 02114 USA. RP Systrom, DM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Pulm & Crit Care Unit, Cardiopulm Exercise Lab,Sch Med, Bulfinch 1, Boston, MA 02114 USA. FU NHLBI NIH HHS [KO8 HL2593-03, HL-07354] NR 43 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 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD DEC PY 1998 VL 17 IS 12 BP 1220 EP 1230 PG 11 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 151YA UT WOS:000077747200011 PM 9883764 ER PT J AU Hirano, T Fujimoto, J Ueki, T Yamamoto, H Takeuchi, M Okamoto, E Takahashi, H Morisita, R Sawa, Y Kaneda, Y AF Hirano, T Fujimoto, J Ueki, T Yamamoto, H Takeuchi, M Okamoto, E Takahashi, H Morisita, R Sawa, Y Kaneda, Y TI HVJ-liposome mediated gene transfer into hepatocytes in vitro SO JOURNAL OF HEPATOLOGY LA English DT Article DE HVJ-liposome; in vivo gene transduction; partial hepatectomy ID ADULT-RAT LIVER; NUCLEAR-PROTEIN; SENDAI VIRUS; IN-VIVO; EXPRESSION; THERAPY; INVIVO; DNA; HEPATITIS; DISEASES AB Background/Aims: The efficient transduction of appropriate target cells will be critical for gene therapy. We evaluated the suitability of hemagglutinating virus of Japan (HVJ)-liposome-mediated gene transfer for gene therapy of liver diseases. Methods: The Escherichia coli beta-galactosidase (beta-gal) gene was introduced into rat liver by HVJ-liposome to examine gene transfer efficacy and persistence of expression with or without partial hepatectomy prior to transfection. Results: About 30% of hepatocytes were transduced after portal vein injection. Gene expression was transient, with only 2% of hepatocytes expressing beta-gal after 4 weeks. However, partial hepatectomy performed 24 h prior to injection resulted in persistently high levels of beta-gal for 4 weeks after injection. A 247-bp beta-gal polymerase chain reaction fragment transcript was detected in livers of transfected rats, but not in livers of control rats. The rat livers following gene transfer were histologically normal, and serum glutamic-pyruvic transaminase was not found to be elevated in rats. Conclusions: Our results demonstrate that HVJ-liposome-mediated gene transfer produced high gene transduction and persistent gene expression in the liver. C1 Hyogo Coll Med, Dept Surg 1, Nishinomiya, Hyogo 663, Japan. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Osaka Univ, Sch Med, Dept Geriatr Med, Osaka 553, Japan. Osaka Univ, Sch Med, Dept Surg 1, Osaka 553, Japan. Osaka Univ, Sch Med, Inst Mol & Cellular Biol, Osaka 553, Japan. RP Fujimoto, J (reprint author), Hyogo Coll Med, Dept Surg 1, 1-1 Mukogawacho, Nishinomiya, Hyogo 663, Japan. NR 23 TC 14 Z9 14 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD DEC PY 1998 VL 29 IS 6 BP 910 EP 914 DI 10.1016/S0168-8278(98)80118-9 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 146PU UT WOS:000077440200007 PM 9875637 ER PT J AU Barrett, JD Zhang, ZS Zhu, JH Lee, DBN Ward, HJ Jamgotchian, N Hu, MS Fredal, A Giordani, M Eggena, P AF Barrett, JD Zhang, ZS Zhu, JH Lee, DBN Ward, HJ Jamgotchian, N Hu, MS Fredal, A Giordani, M Eggena, P TI Erythropoietin upregulates angiotensin receptors in cultured rat vascular smooth muscle cells SO JOURNAL OF HYPERTENSION LA English DT Article DE recombinant human erythropoietin; cultured vascular smooth muscle cells; angiotensin II receptor messenger RNA ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; GENE-EXPRESSION; BLOOD-PRESSURE; INDUCED HYPERTROPHY; HYPERTENSIVE RATS; AT(1) RECEPTOR; BINDING-SITES; MESSENGER-RNA; DNA-SYNTHESIS; GROWTH AB Objective Plasma renin is not elevated in recombinant human erythropoietin (rhEPO)-induced hypertension but angiotensin converting enzyme inhibitors reduce blood pressure in both human and animal studies. Since rhEPO elevates renin and angiotensinogen messenger RNAs in angiotensin II target tissues such as the aorta, we explored the actions of rhEPO on renin-angiotensin system-related gene transcription of cultured rat vascular smooth muscle cells. Design and methods To separate direct actions of rhEPO from those mediated secondarily by potential activation of the renin-angiotensin system, vascular smooth muscle cells were cultured with rhEPO and enalapril to inhibit the angiotensin converting enzyme and losartan to inhibit angiotensin II type 1 receptors, Results Vascular smooth muscle cells cultured with rhEPO (6-8 units/ml) demonstrated elevations (40-120%) in messenger RNAs of the renin-angiotensin system (renin, angiotensinogen, angiotensin receptor types 1 and 2) and increased levels of several messenger RNAs known to respond to angiotensin It (transforming growth factor-p, insulin-like growth factor-II, epidermal growth factor, c-fos and platelet-derived growth factor). In contrast, cells cultured in the presence of rhEPO and enalapril or losartan showed elevations of messenger RNA for only the two types of angiotensin II receptor. This increase was higher than that obtained when cells were cultured with rhEPO or either antagonist alone. The increase in specific binding of angiotensin II to cells cultured in the presence of rhEPO and enalapril or rhEPO and losartan paralleled the changes in receptor messenger RNA. Conclusions rhEPO exerts its primary action on vascular smooth muscle cells via an increase in angiotensin receptor messenger RNA, resulting in a parallel increase in angiotensin II receptor expression. We suggest that increased receptor expression secondarily mediates the expression of other renin-angiotensin system messenger RNAs, which leads to angiotensin Ii-responsive gene transcription. The elevation in angiotensin II receptors, as observed in response to rhEPO, may provide a mechanism by which other forms of renin-dependent hypertension are initiated. (C) Lippincott Williams & Wilkins. C1 Vet Adm Greater Los Angeles Hlth Care Syst, Vasc Pharmacol Lab 111H 1, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, San Fernando Valley Program, Los Angeles, CA USA. Univ Calif Los Angeles, Drew Med Ctr, Los Angeles, CA USA. RP Barrett, JD (reprint author), Vet Adm Greater Los Angeles Hlth Care Syst, Vasc Pharmacol Lab 111H 1, 16111 Plummer St, Sepulveda, CA 91343 USA. FU NHLBI NIH HHS [T32HL07656-11] NR 35 TC 25 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD DEC PY 1998 VL 16 IS 12 BP 1749 EP 1757 DI 10.1097/00004872-199816120-00007 PN 1 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 146FH UT WOS:000077417800007 PM 9869008 ER PT J AU Agostini, C Cassatella, M Zambello, R Trentin, L Gasperini, S Perin, A Piazza, F Siviero, M Facco, M Dziejman, M Chilosi, M Qin, SX Luster, AD Semenzato, G AF Agostini, C Cassatella, M Zambello, R Trentin, L Gasperini, S Perin, A Piazza, F Siviero, M Facco, M Dziejman, M Chilosi, M Qin, SX Luster, AD Semenzato, G TI Involvement of the IP-10 chemokine in sarcoid granulomatous reactions SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACTIVE PULMONARY SARCOIDOSIS; LUNG LYMPHOCYTES-T; ALVEOLAR MACROPHAGES; GAMMA-INTERFERON; INDUCIBLE PROTEIN-10; ENDOTHELIAL-CELLS; CYTOKINE RANTES; EXPRESSION; GENE; INTERLEUKIN-2 AB The accumulation of T cells and monocytes at sites of ongoing inflammation represents the earliest step in the series of events that lead to granuloma formation in sarcoidosis, In this study, we evaluated the pulmonary production off IFN-inducible protein 10 (IP-10), a CXC chemokine that stimulates the directional migration of activated T cells, Striking levels of IP-10 were demonstrated in the bronchoalveolar lavage (BAL) fluid of 24 patients with pulmonary sarcoidosis and lymphocytic alveolitis, as compared with patients with inactive disease or control subjects. A positive correlation was demonstrated between IP-10 levels and the number of sarcoid CD45R0(+)/CD4(+) cells in the BAL, Immunochemistry, performed with an anti-human IP-10 polyclonal Ab in lymph nodes displaying prominent sarcoid granulomas, showed that cells bearing IP-10 were mainly epithelioid cells and CD68(+) macrophages located inside granulomatous areas. Macrophages recovered from the BAL of sarcoid patients stained positive for IP-10 protein. Furthermore, alveolar macrophages isolated from sarcoid patients with T cell alveolitis and cultured for 24 h in presence of IFN-gamma secreted definite levels of IP-10 capable of inducing T cell chemiotaxis, Interestingly, alveolar lymphocytes recovered from patients with active sarcoidosis were CD4(+) T cells expressing Th1 cytokines (IL-2 and IFN-gamma) and high levels of CXCR3, Taken together, these data suggest the potential role of IP-10 in regulating the migration and activation of T cells toward sites of sarcoid inflammatory process and the consequent granuloma formation. C1 Univ Padua, Sch Med, Dept Clin & Expt Med, I-35128 Padua, Italy. Univ Verona, Sch Med, Inst Gen Pathol, Dept Pathol, I-37100 Verona, Italy. LeukoSite Inc, Res & Discovery, Inst Gen Pathol, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02129 USA. RP Semenzato, G (reprint author), Univ Padua, Sch Med, Dept Clin & Expt Med, Via Giustiniani 2, I-35128 Padua, Italy. RI Agostini, Carlo/J-3103-2012; TRENTIN, LIVIO/J-7676-2016; Semenzato, Gianpietro/J-7727-2016; Piazza, Francesco/K-6695-2016 OI Agostini, Carlo/0000-0001-7786-3574; TRENTIN, LIVIO/0000-0003-1222-6149; Semenzato, Gianpietro/0000-0002-6061-4595; Piazza, Francesco/0000-0002-2831-623X FU NCI NIH HHS [CA69212] NR 34 TC 139 Z9 142 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1998 VL 161 IS 11 BP 6413 EP 6420 PG 8 WC Immunology SC Immunology GA 142NQ UT WOS:000077206900082 PM 9834133 ER PT J AU Malley, R DeVincenzo, J Ramilo, O Dennehy, PH Meissner, HC Gruber, WC Sanchez, PJ Jafri, H Balsley, J Carlin, D Buckingham, S Vernacchio, L Ambrosino, DM AF Malley, R DeVincenzo, J Ramilo, O Dennehy, PH Meissner, HC Gruber, WC Sanchez, PJ Jafri, H Balsley, J Carlin, D Buckingham, S Vernacchio, L Ambrosino, DM TI Reduction of respiratory syncytial virus (RSV) in tracheal aspirates in intubated infants by use of humanized monoclonal antibody to RSV F protein SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Academic-Society/Ambulatory-Pediatric-Association CY MAY 01-05, 1998 CL NEW ORLEANS, LOUISIANA SP Pediat Acad Soc, Ambulatory Pediat Assoc ID IMMUNE GLOBULIN; TRACT INFECTION; YOUNG-CHILDREN; INTRAVENOUS IMMUNOGLOBULIN; HIGH-RISK; RIBAVIRIN; DISEASE; THERAPY AB Thirty-five children <2 years of age mechanically ventilated for respiratory syncytial virus (RSV) infection were randomized to receive an intravenous infusion of 15 mg/kg MEDI-493 or placebo. RSV concentration was measured in tracheal secretions by plaque assay before and at 24-h intervals after treatment. The reduction in tracheal RSV concentration from day 0 to day 1 (-1.7 +/- 0.28 vs, -0.6 +/- 0.21 log(10) pfu/mL; P = .004) and from day 0 to day 2 (-2.5 +/- 0.26 vs. -1.0 +/- 0.41 log(10) pfu/mL; P = .012) was significantly greater in the MEDI-493 group than in the placebo group. RSV concentration in nasal aspirates did not differ significantly between the groups, No significant differences were observed in the tracheal aspirate white blood cell count, or myeloperoxidase or eosinophilic cationic protein concentration, or in measures of disease severity between the groups. Thus, treatment with 15 mg/kg MEDI-493 intravenously was well-tolerated and significantly reduced RSV concentration in tracheal aspirates of children with respiratory failure due to RSV. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. New England Med Ctr, Div Pediat Infect Dis, Boston, MA 02111 USA. Univ Tennessee, Memphis, TN USA. Lebonheur Childrens Med Ctr, Memphis, TN USA. Vanderbilt Univ, Med Ctr, Div Pediat Infect Dis, Nashville, TN USA. Univ Texas, SW Med Ctr, Div Pediat Infect Dis, Dallas, TX USA. Hasbro Childrens Hosp, Div Pediat Infect Dis, Providence, RI USA. Medimmune, Gaithersburg, MD USA. RP Malley, R (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, D820D,44 Binney St, Boston, MA 02115 USA. EM malley@a1.tch.harvard.edu OI Dennehy, Penelope/0000-0002-2259-5370; Vernacchio, Louis/0000-0002-2012-5404 NR 24 TC 133 Z9 136 U1 1 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1998 VL 178 IS 6 BP 1555 EP 1561 DI 10.1086/314523 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 147AU UT WOS:000077466700001 PM 9815203 ER PT J AU Tritos, NA Weinrib, S Kaye, TB AF Tritos, NA Weinrib, S Kaye, TB TI Endocrine manifestations of Erdheim-Chester disease (a distinct form of histiocytosis) SO JOURNAL OF INTERNAL MEDICINE LA English DT Article DE adrenal; diabetes insipidus; Erdheim-Chester disease; histiocytosis X; hypothalamus; pituitary ID GROWTH FACTOR-I; DIABETES-INSIPIDUS; RETROPERITONEAL XANTHOGRANULOMA; RENAL-FAILURE; MR IMAGES; PITUITARY; DYSFUNCTION; CHILDREN; PATIENT; BONE AB Erdheim-Chester disease (ECD) is a disorder of unclear aetiology, characterized by exuberant histiocyte proliferation and a variable clinical course. We report the case of a woman with multiorgan involvement secondary to ECD. Central diabetes insipidus (CDI), hyperprolactinaemia, gonadotropin insufficiency and decreased insulinlike growth factor I levels were present, suggesting hypothalamic-pituitary dysfunction. The high-intensity signal of the posterior pituitary on T1-weighted images was absent on magnetic resonance imaging, but no sellar mass lesions or stalk thickening were apparent. Additionally. our patient had bilateral adrenal enlargement. Even though ECD is a rare cause of neuroendocrine dysfunction or adrenal enlargement, it should be considered in patients with these disorders in the setting of multiorgan disease. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Lahey Hitchcock Clin, Endocrinol Sect, Burlington, MA USA. Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA USA. RP Tritos, NA (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM nicholas-tritos@joslin.harvard.edu NR 36 TC 30 Z9 31 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD DEC PY 1998 VL 244 IS 6 BP 529 EP 535 DI 10.1111/j.1365-2796.1998.00389.x PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 153MN UT WOS:000077837000012 PM 9893107 ER PT J AU Whitbourn, RJ Oesterle, SN AF Whitbourn, RJ Oesterle, SN TI State of the art: Trans- and percutaneous myocardial revascularization SO JOURNAL OF INTERVENTIONAL CARDIOLOGY LA English DT Article ID TRANSMYOCARDIAL LASER REVASCULARIZATION; CHANNELS AB Traditional approaches to improve myocardial perfusion in patients with coronary artery disease previously have applied methods to restore blood flow through the existing coronary vessels. In contrast laser myocardial revascularization techniques rely on the creation of new myocardial channels to produce effects leading to improved perfusion and reduction in angina. Laser transmyocardial revascularization (TMR) is performed via open thoracotomy to access the epicardial surface, is relatively safe, and appears to have a beneficial effect on myocardial perfusion. Percutaneous myocardial revascularization (PMR), however, uses transmission of laser energy along a flexible, fiber-optic catheter, thus permitting creation of laser channels from the endocardial surface of the left ventricle via a femoral artery approach. Tissue responses to lasers are dependent upon the energy used and its means of delivery, thermal, mechanical, or chemical effects of laser channel creation may all impact on the myocardium, although stimulation of angiogenic growth factors, with consequent neovascularization appears to be the principal underlying mechanism responsible for improvement in myocardial perfusion. Patients with severe, chronic angina refractory to drug therapies and in whom standard surgical or angioplasty revascularization approaches are not possible may be candidate for TMR or PMR techniques. Clinical studies of TMR have described reductions in angina class, hospital admissions, and the number of myocardial myocardial perfusion defects. PMR studies have reported improvements in angina class, increased exercise duration, and trends toward improvement in radionuclide perfusion defects. Randomized trials are underway and will provide more definitive insights into the future clinical role of laser myocardial revascularization techniques. C1 St Vincents Hosp, Dept Cardiol, Melbourne, Vic, Australia. RP Oesterle, SN (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. NR 29 TC 0 Z9 0 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 0896-4327 J9 J INTERV CARDIOL JI J. Interv. Cardiol. PD DEC PY 1998 VL 11 IS 6 BP 609 EP 613 DI 10.1111/j.1540-8183.1998.tb00175.x PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 141NU UT WOS:000077150700015 ER PT J AU Lee, S McAuliffe, DJ Flotte, TJ Kollias, N Doukas, AG AF Lee, S McAuliffe, DJ Flotte, TJ Kollias, N Doukas, AG TI Photomechanical transcutaneous delivery of macromolecules SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE photoacoustics; shock waves; stress waves; transdermal drug delivery ID TRANSDERMAL DRUG-DELIVERY; IN-VITRO; IONTOPHORETIC DELIVERY; STRESS WAVES; ULTRASOUND; MEMBRANE; ELECTROPORATION; SONOPHORESIS; PERMEATION; SKIN AB Transcutaneous drug delivery has been the subject of intensive research. In certain situations, rapid transcutaneous delivery is very desirable. A mechanical (stress) pulse generated by a single laser pulse was shown to transiently increase the permeability of the stratum corneum in vivo. The barrier function of the stratum corneum recovers within minutes. The increased permeability during these few minutes allows macromolecules to diffuse through the stratum corneum into the viable (40 kDa dextran and 20 nm latex particles) were deposited into the skin using a photomechanical pulse generated by a single 23 ns laser pulse. This treatment can potentially be utilized in therapies that currently require occlusive dressings for hours or day(s). C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. RP Lee, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Wellman Labs Photomed, 55 Fruit St,Mail Stop WEL224, Boston, MA 02114 USA. NR 24 TC 68 Z9 75 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 1998 VL 111 IS 6 BP 925 EP 929 DI 10.1046/j.1523-1747.1998.00415.x PG 5 WC Dermatology SC Dermatology GA 145PT UT WOS:000077381000002 PM 9856797 ER PT J AU Evens, R Shultz, LD Dranoff, G Fuller, JA Kamdar, SJ AF Evens, R Shultz, LD Dranoff, G Fuller, JA Kamdar, SJ TI CSF-1 regulation of Il6 gene expression by murine macrophages: a pivotal role for GM-CSF SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE resident peritoneal macrophages lipopolysaccharide; interleukin-2; interferon-gamma ID COLONY-STIMULATING FACTOR; MOUSE MACROPHAGES; PROGENITOR CELLS; INTERLEUKIN-6; MONOCYTE; IL-6; ENDOTOXIN; PATHWAYS; MICE; LPS AB We test the hypothesis that the monocyte-macrophage colony-stimulating factor (CSF-1 or M-CSF) plays a major role in the inflammatory responses of M phi by acting as a priming agent that heightens their responsiveness to secondary stimulation by other mediators. We previously reported that CSF-1 induced peritoneal M phi (PM phi) to transcribe several genes including interleukin-6 (Il6) and,granulocyte-macrophage colony-stimulating factor (Csfgm), It was reported that the 116 and Csfgm genes were individually regulated by different pathways but it was not clear to what extent the two genes interacted during M phi-mediated inflammatory responses, We now show that CSF-1 induces the release of bioactive GM-CSF from mouse resident PM phi. GM-CSF induces 116 gene expression and synergizes with CSF-1 to induce the release of large amounts of IL-6, PM phi from C57BL/6J-Csfgm(null) mice were shown to release minimal IL-6 in response to CSF-1 and to express a much reduced response to the highly stimulatory combination of CSF-1 and Lipopolysaccharide (LPS). Exogenous recombinant GM-CSF restored the IL-6 response of GM-CSF null PM phi to a great extent but not completely, As controls, three other recombinant proteins were tested but of these only tumor necrosis factor alpha (TNF-alpha) was shown to synergize with both CSF-1 and GM-CSF, Using PM phi from mice deficient in the expression of the Il6 gene, it was shown that they released two- to threefold more GM-CSF in response to CSF-1 than their control counterparts, However, an exogenous supply of recombinant IL-6 had no effect on GM-CSF release, The data indicate that the pathways regulating 116 gene expression are under the control of a complex network of cytokine interactions involving at least CSF-1, GM-CSF, and TNF-alpha, with the added possibility that IL-6 may exert modulatory activity within this network. C1 Jackson Lab, Bar Harbor, ME 04609 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Evens, R (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. NR 22 TC 1 Z9 1 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD DEC PY 1998 VL 64 IS 6 BP 810 EP 816 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 145EL UT WOS:000077358000015 ER PT J AU Klivenyi, P Beal, MF Ferrante, RJ Andreassen, OA Wermer, M Chin, MR Bonventre, JV AF Klivenyi, P Beal, MF Ferrante, RJ Andreassen, OA Wermer, M Chin, MR Bonventre, JV TI Mice deficient in group IV cytosolic phospholipase A(2) are resistant to MPTP neurotoxicity SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE MPTP; free radicals; arachidonic acid; phospholipase; Parkinson's disease ID BRAIN INJURY; SUPEROXIDE; ACTIVATION; POTENTIATION; RECEPTORS; MECHANISM; APOPTOSIS; ISCHEMIA; NEURONS; DAMAGE AB Phospholipase A, (PLA,) enzymes are critical regulators of prostaglandin and leukotriene synthesis, and they may also play an important role in the generation of intracellular free radicals. The group IV cytosolic form of phospholipase A, (cPLA(2)) is regulated by changes in intracellular calcium concentration, and the enzyme preferentially acts to release arachidonic acid esterified at the sn-2 position of phospholipids. We examined the susceptibility of mice carrying a targeted mutation of the cPLA(2) gene to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. Mutant mice have no functional cPLA2 activity. Mice that were homozygous for the mutation (cPLA(2)(-/-)) were significantly resistant to MPTP-induced dopamine depletion as compared with littermate control (cPLA(2)(-/-)) and heterozygous mice (cPLA(2)(+/-)). These findings provide evidence that cPLA(2) plays a role in MPTP neurotoxicity and suggest that cPLA(2) may play a role in the development of Parkinson's disease in humans. C1 Massachusetts Gen Hosp, Serv Neurol, Neurochem Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. Dept Vet Affairs, Bedford, MA USA. RP Beal, MF (reprint author), Massachusetts Gen Hosp, Serv Neurol, Neurochem Lab, WRN 408,32 Fruit St, Boston, MA 02114 USA. FU NINDS NIH HHS [NS37102, NS10828, NS31579] NR 20 TC 99 Z9 102 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 1998 VL 71 IS 6 BP 2634 EP 2637 PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 139QH UT WOS:000077040400046 PM 9832165 ER PT J AU Bogdanov, MB Ferrante, RJ Kuemmerle, S Klivenyi, P Beal, MF AF Bogdanov, MB Ferrante, RJ Kuemmerle, S Klivenyi, P Beal, MF TI Increased vulnerability to 3-nitropropionic acid in an animal model of Huntington's disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Huntington's disease; 3-nitropropionic acid; free radicals; oxidative damage; transgenic mice; mitochondria ID EXCITOTOXICITY IN-VIVO; TRANSGENIC MICE; DYSFUNCTION AB There is substantial evidence for both metabolic dysfunction and oxidative damage in Huntington's disease(HD). In the present study, we used in vivo microdialysis to measure the conversion of 4-hydroxybenzoic acid to 3,4-dihydroxybenzoic acid (3,4-DHBA) as a measure of hydroxyl radical production in a transgenic mouse model of HD, as well as in littermate controls. The conversion of 4-hydroxybenzoic acid to 3,4-DHBA was unchanged in the striatum of transgenic HD mice at baseline. Following administration of the mitochondrial toxin 3-nitropropionic acid (3-NP), there were significant increases in 3,4-DHBA generation in both control and transgenic HD mice, and the increases in the transgenic HD mice were significantly greater than those in controls. Furthermore, administration of 3-NP produced significantly larger striatal lesions in transgenic HD mice than in littermate controls. The present results show increased sensitivity to the mitochondrial toxin 3-NP in transgenic HD mice, which suggests metabolic dysfunction in this mouse model of HD. C1 Massachusetts Gen Hosp, Serv Neurol, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. VA Med Ctr, Geriatr Res Educ Clin Ctr, Bedford, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. RP Beal, MF (reprint author), Massachusetts Gen Hosp, Serv Neurol, Neurochem Lab, WRN 408,32 Fruit St, Boston, MA 02114 USA. FU NINDS NIH HHS [NS31579, NS32365, NS37102] NR 15 TC 68 Z9 68 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 1998 VL 71 IS 6 BP 2642 EP 2644 PG 3 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 139QH UT WOS:000077040400048 PM 9832167 ER PT J AU Brecher, K Hochberg, FH Louis, DN de la Monte, S Riskind, P AF Brecher, K Hochberg, FH Louis, DN de la Monte, S Riskind, P TI Case report of unusual leukoencephalopathy preceding primary CNS lymphoma SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article DE primary lymphoma; central nervous system; demyelinating disease ID NERVOUS-SYSTEM LYMPHOMA; RETICULUM-CELL SARCOMA; MULTIPLE-SCLEROSIS; BRAIN AB A previously healthy 35 year old woman presented with bilateral uveitus associated with multiple, evolving, non-enhancing white matter lesions consistent with a progressive leukoencephalopathy such as multiple sclerosis. Thirty months after her initial presentation, she was diagnosed with primary CNS lymphoma and died 14 months later. The unusual clinical course preceding the diagnosis suggests that a demyelinating disease may have preceded, and possibly heralded, the development of primary CNS lymphoma. Cases of "sentinel lesions" heralding the diagnosis of primary CNS lymphoma have been reported, and this case further corroborates such instances and raises further issues regarding possible neoplastic transformation occurring in inflammatory diseases such as multiple sclerosis. C1 Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Brecher, K (reprint author), Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10021 USA. EM brecherk@mskcc.org NR 20 TC 28 Z9 29 U1 1 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD DEC PY 1998 VL 65 IS 6 BP 917 EP 920 DI 10.1136/jnnp.65.6.917 PG 4 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 146FK UT WOS:000077418200021 PM 9854972 ER PT J AU Knowles, RB Gomez-Isla, T Hyman, BT AF Knowles, RB Gomez-Isla, T Hyman, BT TI A beta associated neuropil changes: Correlation with neuronal loss and dementia SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer disease; amyloid beta protein; neuropil threads; neurofibrillary tangles; neurofilament proteins ID PRECURSOR PROTEIN GENE; ALZHEIMERS-DISEASE; SENILE PLAQUES; NEUROFIBRILLARY TANGLES; AMYLOID PLAQUES; DEPOSITION; MUTATION; CORTEX; A-BETA-42; PATHOLOGY AB Although genetic studies clearly implicate beta-amyloid peptide (A beta) as a pathogenic agent in Alzheimer disease (AD), it is puzzling that the total amount of A beta immunoreactivity does not correlate closely with neuronal loss or degree of dementia. We hypothesized that A beta deposits could vary in the extent to which they disrupt the neuropil, and that the degree to which this occurs might then correlate with the degree of dementia. We used 3 dimensional triple immunofluorescent confocal microscopy to examine the fine structural relationships between A beta deposits and neurites in their vicinity. In non demented elderly, A beta deposits were porous structures with numerous normal appearing processes coursing through them. In AD, dendrites within A beta deposits, compared with dendrites in the surrounding neuropil, were likely to have decreased SMI32 immunoreactivity and increased Alz-50 immunoreactivity. We found that the degree to which A beta deposits disrupt the neuropil, as assessed by local loss of SMI32 immunoreactivity, correlates closely with the amount of neuronal loss and with duration of dementia. These observations support the hypothesis that a subset of A beta deposits contribute directly to neural system failure in AD. C1 Massachusetts Gen Hosp East, Alzheimer Dis Res Unit, Charlestown, MA 02129 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp East, Alzheimer Dis Res Unit, 149 13th St,Room 6405, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG08487, AG05134] NR 35 TC 58 Z9 61 U1 0 U2 2 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD DEC PY 1998 VL 57 IS 12 BP 1122 EP 1130 DI 10.1097/00005072-199812000-00003 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 150EU UT WOS:000077651200003 PM 9862634 ER PT J AU Stemmer-Rachamimov, AO Ino, Y Lim, ZY Jacoby, LB MacCollin, M Gusella, JF Ramesh, V Louis, DN AF Stemmer-Rachamimov, AO Ino, Y Lim, ZY Jacoby, LB MacCollin, M Gusella, JF Ramesh, V Louis, DN TI Loss of the NF2 gene and merlin occur by the tumorlet stage of schwannoma development in neurofibromatosis 2 SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE merlin; neurofibromatosis 2; NF2; Schwann cell; schwannoma ID MOLECULAR-GENETICS; SPECIMENS AB Loss of the neurofibromatosis 2 (NF2) gene-encoded protein merlin is a universal finding in sporadic and NF2-associated schwannomas. Certain NF2 patients may develop numerous minute Schwann cell tumorlets of the spinal nerve roots in addition to larger, frank schwannomas and thereby provide an opportunity to investigate the timing of NF2 gene/merlin loss in Schwann cell tumorigenesis. We studied an NF2 patient with a germline NF2 gene frameshift mutation who had many Schwann cell tumorlets and schwannomas. Loss of heterozygosity studies of DNA from microdissected specimens showed allelic loss of the NF2 region of chromosome 22q in tumorlets as well as schwannomas. Immunohistochemistry further demonstrated loss of merlin expression in tumorlets as well as schwannomas, with intact expression in adjacent nerve. Thus, loss of both NF2 alleles and merlin occur early in Schwann cell tumorigenesis, before the tumorlet stage. The study of tumorlets and schwannomas in such patients may also provide an opportunity to elucidate mechanisms responsible for the subsequent growth of Schwann cell lesions into symptomatic tumors. C1 Massachusetts Gen Hosp, Mol Neurooncol Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurosurg, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Genet, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Louis, DN (reprint author), Massachusetts Gen Hosp, Mol Neurooncol Lab, CNY6,149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA51410]; NINDS NIH HHS [NS24279] NR 9 TC 15 Z9 15 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD DEC PY 1998 VL 57 IS 12 BP 1164 EP 1167 DI 10.1097/00005072-199812000-00008 PG 4 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 150EU UT WOS:000077651200008 PM 9862639 ER PT J AU Kaufer, D Cummings, JL Christine, D AF Kaufer, D Cummings, JL Christine, D TI Differential neuropsychiatric symptom responses to tacrine in Alzheimer's disease: Relationship to dementia severity SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article; Proceedings Paper CT 7th Annual Meeting of the American-Neuropsychiatric-Association CY OCT 12-15, 1995 CL PITTSBURGH, PENNSYLVANIA SP Amer Neuropsychiat Assoc ID LEWY-BODY DEMENTIA; CHOLINERGIC HYPOTHESIS; BEHAVIORAL-CHANGES; TETRAHYDROAMINOACRIDINE; DIAGNOSIS; PSYCHOSIS; CORTEX; HALLUCINATIONS; DELUSIONS; DEFICITS AB Neuropsychiatric symptom responses to tacrine were investigated in an open-label study of Alzheimer's outpatients. Forty subjects were stratified into three groups (Mild, Moderate, and Severe) based on Mini-Mental State Examination scores. A significant reduction in total Neuropsychiatric Inventory score across all subjects was principally attributable to changes in the Moderate group. Apathy and disinhibition symptoms were significantly reduced overall. Whereas other symptoms showed differential responses in Mild and Severe subjects, all symptoms improved in Moderate subjects. These findings suggest that disease severity may significantly influence neuropsychiatric symptom responses to tacrine. Putative mechanisms underlying the observed pattern of responses are explored. C1 Univ Pittsburgh, Med Ctr, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Behav Neurosci Sect, Psychiat Serv, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Nursing Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. RP Kaufer, D (reprint author), Univ Pittsburgh, Med Ctr, Sch Med, Dept Psychiat, 4 W ADRC,200 Lothrop St, Pittsburgh, PA 15213 USA. FU NIA NIH HHS [AG10123, AG10533] NR 51 TC 51 Z9 51 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD WIN PY 1998 VL 10 IS 1 BP 55 EP 63 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZD354 UT WOS:000072676800008 PM 9547467 ER PT J AU Luo, Y Kim, R Gabuzda, D Mi, S Collins-Racie, LA Lu, ZJ Jacobs, KA Dorf, ME AF Luo, Y Kim, R Gabuzda, D Mi, S Collins-Racie, LA Lu, ZJ Jacobs, KA Dorf, ME TI The CXC-chemokine, H174: expression in the central nervous system SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE AIDS dementia; astrocytes; chemoattractant; interferon; multiple sclerosis ID INTERFERON-INDUCIBLE PROTEIN-10; LYMPHOCYTE CHEMOATTRACTANT; T-LYMPHOCYTES; INTERLEUKIN-8; CYTOKINES; IP-10; GAMMA; RECEPTOR; CELLS; GENE AB H174 is a new member of the CXC-chemokine family. A cDNA probe containing the entire H174 coding region recognized a predominant inducible transcript of approximately 1.5 kb expressed in interferon (IFN) activated astrocytoma and monocytic cell lines. H174 message can be induced following IFN-alpha, IFN-beta, or IFN-gamma stimulation. H174 message was also detected in IFN treated cultures of primary human astrocytes, but was absent in unstimulated astrocytes. H174, like IP10 and Mig, lacks the ELR sequence associated with the neutrophil specificity characteristic of most CXC-chemokines. Preliminary experiments suggest H174,IP10 and Mig are independently regulated. Recombinant H174 is a weak chemoattractant for monocyte-like cells. H174 can also stimulate calcium flux responses. The data support the classification of H174 as a member of a subfamily of interferon-gamma inducible non-ELR CXC-chemokines. Brain tissues were obtained at autopsy from one patient with AIDS dementia, one patient with multiple sclerosis, and two normal control patients. H174 and Mig ig were detected by RT-PCR in brain tissue cDNA derived from the patients with pathological conditions associated with activated astrocytes but not in cDNA from control specimens. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Genet Inst, Cambridge, MA 02140 USA. RP Dorf, ME (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. FU NCI NIH HHS [CA67416]; NINDS NIH HHS [NS37284, NS 37277] NR 32 TC 8 Z9 8 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD DEC PY 1998 VL 4 IS 6 BP 575 EP 585 DI 10.3109/13550289809114224 PG 11 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 161BM UT WOS:000078268100001 PM 10065899 ER PT J AU Walker, WA Duffy, LC AF Walker, WA Duffy, LC TI Diet and bacterial colonization: Role of probiotics and prebiotics SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Review DE Bifidobacteria; Lactobacilli; prebiotics; probiotics; intestinal colonization; adhesion ID LACTIC-ACID BACTERIA; METHOTREXATE-INDUCED ENTEROCOLITIS; BIFIDOBACTERIUM-LONGUM; GASTROINTESTINAL-TRACT; ANTIGENOTOXIC PROPERTIES; LACTOBACILLUS-REUTERI; COLONIC MICROBIOTA; MUCOSAL BARRIER; FERMENTED MILK; FECAL FLORA AB The intestinal mucosa functions as a defensive barrier that limits dietary antigen transport and microbial pathogens from colonizing enterocytes. The potential role of lactic acid bacteria, specifically Bifidobacteria, in probiotic and prebiotic functional food supplements is reviewed in the context of bacterial colonization, adherence, and disease prevention. This article reviews the mechanisms of action and optimization of methods that will lead to a new generation of biotic products with enhanced biologic properties and well-being foods. (J. Nutr. Biochem. 9:668-675, 1998) (C) Elsevier Science Inc. 1998. C1 SUNY Buffalo, Childrens Hosp Buffalo, Sch Med & Biomed Sci, Dept Pediat, Buffalo, NY 14209 USA. Harvard Univ, Massachusetts Gen Hosp, Childrens Hosp,Sch Med, Combined Program Pediat Gastroenterol & Nutr, Boston, MA USA. RP Duffy, LC (reprint author), SUNY Buffalo, Childrens Hosp Buffalo, Sch Med & Biomed Sci, Dept Pediat, 888 Delaware Ave, Buffalo, NY 14209 USA. NR 76 TC 68 Z9 77 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD DEC PY 1998 VL 9 IS 12 BP 668 EP 675 DI 10.1016/S0955-2863(98)00058-8 PG 8 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 147VP UT WOS:000077518400001 ER PT J AU Padungtod, C Lasley, BL Christiani, DC Ryan, LM Xu, XP AF Padungtod, C Lasley, BL Christiani, DC Ryan, LM Xu, XP TI Reproductive hormone profile among pesticide factory workers SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; LUTEINIZING-HORMONE; ORGANOPHOSPHORUS COMPOUNDS; TESTOSTERONE; MEN; ESTRADIOL; PARATHION; MOUSE; CELLS AB Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels, as well as urinary levels of FSH, LH, and E1C, a metabolite of testosterone, were measured to investigate the adverse reproductive effects of organophosphate pesticides among Chinese factory workers who were occupationally exposed to ethylparathion and methamidophos. Thirty-four exposed workers were randomly chosen and recruited from a large pesticide factory, and 44 unexposed workers were selected from a nearby textile factory. A quantitative pesticide exposure assessment was performed among a subset of the exposed and unexposed workers. Information on potential confounders was collected in an interview. A single blood sample was collected at the end of a work shift, when each subject also donated a semen sample. Three first-voided urine samples were collected from each worker on 3 consecutive days. Urinary p-nitrophenol level at 1 hour after the work shift correlated with serum (r = 0.71, P < 0.01) and urinary (r = 0.51, P = 0.04) FSH levels. Stratifying by the subjects' exposure status, we found a significant negative correlation among the exposed group between urinary FSH level and sperm count (r = -0.61, P < 0.01) and between urinary FSH level and sperm concentration (r = -0.53, P = 0.03). Pesticide exposure alone was significantly associated with serum LH level (beta [coefficient of exposure effect] = 0.79; 95% confidence interval [CI] = 0.42, 1.16) but not with serum FSH or testosterone or with any urinary hormone levels. With adjustment for age, rotating shift work, current cigarette smoking, and current alcohol consumption, exposure significantly increased the serum LH level by 1.1 mIU/mL (95% CI = 0.34, 1.82). Meanwhile, the serum FSH level was slightly elevated (beta [coefficient of exposure effect] = 1.38; 95% CI = -0.09, 2.85) and the serum testosterone level was decreased (beta = -55.13; 95% CI = -147.24, 37) with increased pesticide exposure. Age and rotating shift work appeared to act as confounders. We conclude the organophosphate pesticides have a small effect on male reproductive hormones, suggestive of a secondary hormonal disturbance after testicular damage. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Program Populat Genet, Boston, MA 02115 USA. Univ Calif Davis, Inst Toxicol & Environm Hlth, Davis, CA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. RP Xu, XP (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, 665 Huntington Ave,FXB-101, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 37 TC 39 Z9 45 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD DEC PY 1998 VL 40 IS 12 BP 1038 EP 1047 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 151LM UT WOS:000077721600002 PM 9871879 ER PT J AU Abelson, M Howes, J George, M AF Abelson, M Howes, J George, M TI The conjunctival provocation test model of ocular allergy: Utility for assessment of an ocular corticosteroid, loteprednol etabonate SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID CHALLENGE MODEL; LEVOCABASTINE; EFFICACY; PLACEBO; SAFETY AB Two studies were conducted using the conjunctival provocation test (CPT) model of ocular allergy. The objective of the first study was to evaluate the sensitivity of the CPT model to a topical corticosteroid. Selected was loteprednol etabonate 0.5%, previously found effective in the treatment of ocular allergy and inflammation. The study was a randomized double-masked, placebo-controlled, paired-comparison of loteprednol etabonate 0.5% (LE), b.i.d. or q.i.d. Sixty subjects who had a minimum pre-determined allergic response received LE in one eye and placebo in the fellow eye for 28 days from Day 7 to Day 35. Antigen challenges were carried out on Days 0, 7 (baseline), 21 and 35. The primary endpoints were interocular differences in itching and mean redness (the average of ciliary, conjunctival and episcleral vessel beds). LE (either b.i.d. or q.i.d.) was significantly more effective than placebo for reducing mean redness and itching. No clinical or statistically significant changes in intraocular pressure were observed. Based upon the results of Study 1, we used the CPT model to aid in the selection of a concentration of loteprednol etabonate for subsequent studies in environmental seasonal allergic conjunctivitis. This was a randomized double-masked, placebo-controlled, paired-comparison of loteprednol etabonate 0.1%, 0.2% and 0.3%, q.i.d in 88 subjects. The dosing and testing regimen was similar to the first portion of the study. Loteprednol etabonate, 0.1%, 0.2% and 0.3%, was numerically superior to the placebo in reducing mean redness and itching. At the 20-minute post allergen challenge, the 0.1% concentration was significantly superior (p < 0.05) to the placebo on Visit 4 (2 and 4 hour challenge) in reducing the mean redness; however, LE was only numerically superior in relieving itching. The 0.2% concentration was significantly superior (p < 0.05) to the placebo in the reduction of mean redness and itching on Visit 3 (Day 21) and in reduction of mean redness on Visit 4 (4 hour challenge). The 0.3% concentration was significantly superior (p < 0.05) to the placebo in the reduction of mean redness on all visits, and statistically significant in the reduction of itching on Visit 4 (4 hour challenge). While there were some elevations of IOP with LE 0.2%, they were not clinically significant. In conclusion, the CPT model of ocular allergy is useful in the evaluation of corticosteroids. Furthermore, based upon a dose-response study in this model, 0.2% loteprednol etabonate was selected for further evaluation in environmental seasonal allergic conjunctivitis studies. C1 Ophthalm Res Associates, N Andover, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Pharmos Corp, Alachua, FL USA. RP Howes, J (reprint author), Precis Pharmaceut, 13709 Progress Blvd,Box 34, Alachua, FL 32615 USA. NR 16 TC 27 Z9 27 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1080-7683 J9 J OCUL PHARMACOL TH JI J. Ocular Pharmacol. Ther. PD DEC PY 1998 VL 14 IS 6 BP 533 EP 542 DI 10.1089/jop.1998.14.533 PG 10 WC Ophthalmology; Pharmacology & Pharmacy SC Ophthalmology; Pharmacology & Pharmacy GA 145YX UT WOS:000077401000005 PM 9867336 ER PT J AU Donoff, RB Todd, R Elovic, A Gallagher, GT Chou, MY Wong, DTW AF Donoff, RB Todd, R Elovic, A Gallagher, GT Chou, MY Wong, DTW TI Prediction of human oral cancer radiation responsiveness by histone (H3) mRNA in situ hybridization: A preliminary report SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID S-PHASE CELLS; MESSENGER-RNA; INSITU HYBRIDIZATION; MEDICAL PROGRESS; LABELING INDEX; PROLIFERATION; CARCINOMA; HEAD; NECK; EPITHELIUM AB Purpose: Cell cycle kinetics are believed to be a key determinant in radiation responsiveness; However, histomorphologic analysis remains an unreliable method of identifying proliferating cells. In this study, the fraction of cells undergoing division within oral cancer biopsy samples was used to predict the responsiveness of the tumor to radiation therapy. Patients and Methods: Eighteen cases of T1 or T2 squamous cell carcinoma of the floor of the mouth with known clinical outcomes were identified. All were treated at the Massachusetts General Hospital with external beam radiation therapy alone. The fraction of proliferating cells was determined using in situ hybridization of histone (H3) mRNA expression. Tissue viability and mRNA status was verified using in situ hybridization for beta-actin mRNA expression. Results: Matching the fraction of oral tumor cells positively labeled for histone (H3) mRNA (histone labeling index or HLI) with the actual clinical outcome showed that the HLI of radioresponsive oral tumors (12 cases) was 0.336 +/- 0.185 (-34% +/- 19%), whereas that for radioresistant oral tumors (six cases) was 0.088 +/- 0.078 (-9% +/- 7.8%). Using t-test statistical analysis for unpaired simples showed that the difference in HLI between the two groups was significantly different (P = .0068). Conclusions: It is concluded that the use of in situ detection of histone (H3) mRNA may be a useful adjunctive criterion in the choice of treatment for human oral cancer. C1 Harvard Univ, Sch Dent Med, Div Oral Pathol, Dept Oral Med & Diagnost Sci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Chung Shan Med & Dent Coll, Sch Dent, Chung Shan, Taiwan. RP Wong, DTW (reprint author), Harvard Univ, Sch Dent Med, Div Oral Pathol, Dept Oral Med & Diagnost Sci, 188 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [R03 CA56325]; NIDCR NIH HHS [R29 DE11983, R01 DE08680] NR 28 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD DEC PY 1998 VL 56 IS 12 BP 1410 EP 1416 DI 10.1016/S0278-2391(98)90406-2 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 144EB UT WOS:000077299900014 PM 9846539 ER PT J AU Cornford, EM AF Cornford, EM TI Presentation of the 1998 recipient of the American Society of Parasitologists' mentor award, Dr Austin J. Macinnis SO JOURNAL OF PARASITOLOGY LA English DT Biographical-Item C1 W Los Angeles Vet Affairs Med Ctr, SW Reg Vet Adm Epilepsy Ctr, Neuropharmacol Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA. RP Cornford, EM (reprint author), W Los Angeles Vet Affairs Med Ctr, SW Reg Vet Adm Epilepsy Ctr, Neuropharmacol Lab, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC PARASITOLOGISTS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 0022-3395 J9 J PARASITOL JI J. Parasitol. PD DEC PY 1998 VL 84 IS 6 BP 1078 EP 1080 PG 3 WC Parasitology SC Parasitology GA 157XV UT WOS:000078087700005 PM 9920294 ER PT J AU Guevara, LF Strack, S AF Guevara, LF Strack, S TI An examination of Millon's dimensional and stylistic descriptions of normal personality SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article AB Millon's new dimensional conceptualization of personality, as measured by the Millon Index of Personality Styles (MIPS; Millon, 1994), was linked to his traditional taxonomy of normal personality styles as assessed by the Personality Adjective Check List (PACL; Strack, 1987, 1991b). Participants were 61 male and 87 female college students (N= 148). At the bivariate level, PACL scales were most strongly associated with MIPS interpersonal behavior scales and least associated with MIPS cognitive-style scales. Similar PACL and MIPS interpersonal style measures were correlated highest with each other in 6 of 8 comparisons, whereas PACL personalities were reliably associated with MIPS measures of Millon's 3 basic axes. A factor analysis of combined scales yielded 4 principal components that accounted for 70% of the variance. The first 3 of these linked PACL scales in a predictable manner with all 3 MIPS measurement domains. A 4th factor, which loaded only MIPS scales, appeared to measure an artistic personality style. Results indicated that the MIPS retains Millon's original stylistic descriptions of normal personality while providing unique measures of his 3 bipolar axes and 8 Jungian cognitive styles (Jung, 1936/1971). C1 US Dept Vet Affairs, Outpatient Clin, Psychol Serv 116B, Los Angeles, CA 90012 USA. Calif Sch Profess Psychol, Los Angeles, CA USA. RP Strack, S (reprint author), US Dept Vet Affairs, Outpatient Clin, Psychol Serv 116B, 351 E Temple St, Los Angeles, CA 90012 USA. NR 24 TC 2 Z9 3 U1 0 U2 1 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD DEC PY 1998 VL 71 IS 3 BP 337 EP 348 DI 10.1207/s15327752jpa7103_4 PG 12 WC Psychology, Clinical; Psychology, Social SC Psychology GA 159EM UT WOS:000078158900004 ER PT J AU Cacciola, JS Rutherford, MJ Alterman, AI McKay, JR Mulvaney, FD AF Cacciola, JS Rutherford, MJ Alterman, AI McKay, JR Mulvaney, FD TI Long-term test-retest reliability of personality disorder diagnoses in opiate dependent patients SO JOURNAL OF PERSONALITY DISORDERS LA English DT Article ID FOLLOW-UP; AGREEMENT AB This investigation reports the two year test-retest reliability of DSM-III-R personality disorder (PD) diagnoses in a sample of 219 patients with opiate dependence-admitted to methadone treatment. Different MA/PhD interviewers at each assessment used a semistructured diagnostic interview for PD, the Structured interview for DSM-III-R Personality Disorders (SIDP-R), to make their diagnoses. The reliability of any PD diagnosis versus no PD-was fair (kappa = .51). The reliability for any specific PD (weighted kappa = .31) was poor. Antisocial (kappa = .45) and sadistic (kappa = .42), were the only specific PDs for which at least fair reliability was achieved. At the cluster level, only Cluster B had fair reliability (kappa = .47). The intraclass correlation coefficients between number of criteria for the specific PDs at the two evaluation points were consistently higher (range .22 to .62.) than were the corresponding kappas for categorical diagnoses. In that the base rates for most of the PDs were low and agreement of no diagnosis tended to be high, percent exact agreement for the specific PDs typically exceeded 90%. Increasing the base rate by lowering the diagnostic threshold, or examining more severe cases by raising the diagnostic threshold, did not consistently effect reliability. Reasons for the low kappa coefficients and the implications for PD research are discussed. C1 Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Ctr Studies Addict,TRC,Dept Psychiat, Philadelphia, PA 19104 USA. RP Cacciola, JS (reprint author), Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Ctr Studies Addict,TRC,Dept Psychiat, 3900 Chestnut St, Philadelphia, PA 19104 USA. NR 11 TC 14 Z9 14 U1 0 U2 1 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0885-579X J9 J PERS DISORD JI J. Pers. Disord. PD WIN PY 1998 VL 12 IS 4 BP 332 EP 337 PG 6 WC Psychiatry SC Psychiatry GA 154GA UT WOS:000077879400004 PM 9891287 ER PT J AU Adebanjo, OA Igietseme, J Huang, CLH Zaidi, M AF Adebanjo, OA Igietseme, J Huang, CLH Zaidi, M TI The effect of extracellularly applied divalent cations on cytosolic Ca2+ in murine Leydig cells: evidence for a Ca2+-sensing receptor SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID ISOLATED RAT OSTEOCLASTS; CALCIUM-RECEPTOR; BONE-RESORPTION; CALCITONIN; ACTIVATION; SECRETION; CLONING; AGONIST; MUSCLE; CA-2+ AB 1. The effect of extracellularly applied divalent cations upon cytosolic Ca2+ levels ([Ca2+]) was investigated in fura-2-loaded mouse Leydig (TM3) cells. 2. The extracellular application of Ca2+ (2.5-15 mM) or Ni2+ (0.5-5 mM) elicited concentration-dependent elevations in cytosolic [Ca2+] that were followed by decays to baseline levels. Extracellular Mg2+ (0.8-15 mM) failed to influence cytosolic [Ca2+]. 3. Conditioning applications of Ca2+ (2.5-10 mM), Mg2+ (2.5-15 mM) or Ni2+ (0.5-5 mM) all attenuated the cytosolic Ca2+ response to a subsequent test application of 5 mM [Ni2+]. 4. The amplitude of Ni2+-induced cytosolic Ca2+ signals remained constant in low-Ca2+ solutions. Such findings suggest a participation of Ca2+ release from intracellular stores. In parallel, depletion of Ca2+ stores by either ionomycin (5 mu M, in low-Ca2+ solutions) or thapsigargin (4 mu M) abolished or attenuated Ni2+-induced Ca2+ transients. 5. Ionomycin (5 mu M) elevated cytosolic [Ca2+] in Ca2+-free solutions even after prior Ni2+ application, indicating the presence of Ni2+-insensitive stores. 6. Caffeine (250 and 500 mu M) elevated cytosolic [Ca2+] and attenuated Ni2+-induced Ca2+ release. Furthermore, TM3 cells stained intensely with a specific anti-ryanodine receptor antiserum, Ab(34). These findings suggest that Ca2+ release is regulated by ryanodine receptors. 7. Both membrane depolarization and hyperpolarization, brought about by changes in extracellular [K+] ([K+](e)) in the presence of valinomycin (5 mu M), altered the waveform of the Ni2+-induced cytosolic Ca2+ signal. Hyperpolarization, in addition, diminished the response magnitude. Such voltage-induced response modulation localizes the regulatory events to the Leydig cell plasma membrane. 8. We propose the existence of a cell surface divalent cation (Ca2+) receptor in Leydig cells, the activation of which triggers Ca2+ fluxes through ryanodine receptors. C1 Vet Affairs Med Ctr, Ctr Osteoporosis & Skeletal Aging, Geriatr & Extended Care Serv, Philadelphia, PA 19104 USA. Allegheny Univ Hlth Sci, Med Coll Penn, Hahnemann Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. Morehouse Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30310 USA. Univ Cambridge, Physiol Lab, Cambridge CB2 3EG, England. RP Zaidi, M (reprint author), Vet Affairs Med Ctr, Ctr Osteoporosis & Skeletal Aging, Geriatr & Extended Care Serv, Univ & Woodland Ave, Philadelphia, PA 19104 USA. RI Huang, Christopher/A-6248-2008 FU NCRR NIH HHS [RR03034, G12 RR003034]; NIA NIH HHS [R01 AG 14917-02]; NIAID NIH HHS [AI41231, R01 AI041231] NR 36 TC 24 Z9 25 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD DEC 1 PY 1998 VL 513 IS 2 BP 399 EP 410 DI 10.1111/j.1469-7793.1998.399bb.x PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 150JG UT WOS:000077661300008 PM 9806991 ER PT J AU Naliboff, BD Munakata, J Chang, L Mayer, EA AF Naliboff, BD Munakata, J Chang, L Mayer, EA TI Toward a biobehavioral model of visceral hypersensitivity in irritable bowel syndrome SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Editorial Material ID FUNCTIONAL DYSPEPSIA; INTESTINAL MOTILITY; CHEST PAIN; PERCEPTION; DISTENSION; COLON; HYPERALGESIA; STIMULATION; SENSITIVITY; MODULATION C1 Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Neuroenter Dis Program,CURE, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Neuroenter Dis Program,CURE, Dept Physiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Neuroenter Dis Program,CURE, Dept Psychol, Los Angeles, CA 90073 USA. RP Naliboff, BD (reprint author), Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Neuroenter Dis Program,CURE, Dept Med, Bldg 115-CURE,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM naliboff@ucla.edu FU NIDDK NIH HHS [DK48351] NR 47 TC 25 Z9 25 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD DEC PY 1998 VL 45 IS 6 BP 485 EP 492 PG 8 WC Psychiatry SC Psychiatry GA 137FA UT WOS:000076903100001 PM 9859851 ER PT J AU Lipsky, LPE Abramson, SB Crofford, L Dubois, RN Simon, LS van de Putte, LBA AF Lipsky, LPE Abramson, SB Crofford, L Dubois, RN Simon, LS van de Putte, LBA TI The classification of cyclooxygenase inhibitors SO JOURNAL OF RHEUMATOLOGY LA English DT Editorial Material ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ALZHEIMERS-DISEASE; GASTROINTESTINAL-TRACT; RHEUMATOID-ARTHRITIS; SELECTIVE-INHIBITION; COLORECTAL-CANCER; ASPIRIN USE; NSAID USE; RISK; EXPRESSION C1 Univ Texas, SW Med Ctr, Harold C Simmons Arthrit Res Ctr, Div Rheumat Dis,Internatl COX2 Study Grp, Dallas, TX 75235 USA. NYU, Sch Med, Dept Rheumatol, Hosp Joint Dis, New York, NY 10001 USA. Univ Michigan, Med Ctr, Div Rheumatol, Ann Arbor, MI 48109 USA. Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37023 USA. Vanderbilt Univ, Med Ctr, Dept GI & Cell Biol, Nashville, TN 37023 USA. Harvard Univ, Sch Med, Beth Israel Deaconness Med Ctr, Div Rheumatol, Boston, MA 02114 USA. Univ Nijmegen Hosp, Div Rheumatol, NL-6500 HB Nijmegen, Netherlands. RP Lipsky, LPE (reprint author), Univ Texas, SW Med Ctr, Harold C Simmons Arthrit Res Ctr, Div Rheumat Dis,Internatl COX2 Study Grp, Dallas, TX 75235 USA. RI Crofford, Leslie/J-8010-2013 NR 52 TC 71 Z9 80 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD DEC PY 1998 VL 25 IS 12 BP 2298 EP 2303 PG 6 WC Rheumatology SC Rheumatology GA 143WN UT WOS:000077280600003 PM 9858421 ER PT J AU Puria, S Allen, JB AF Puria, S Allen, JB TI Measurements and model of the cat middle ear: Evidence of tympanic membrane acoustic delay SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID FINITE-ELEMENT METHOD; INPUT IMPEDANCE; REFLECTION COEFFICIENT; FREQUENCY-RESPONSE; EARDRUM; COCHLEA AB In order to better understand the mechanics of tympanic membrane (TM) transduction at frequencies above a few kHz, the middle-ear (ME) impedance measured near the tympanic membrane is studied for three anesthetized cat ears after widely opening the ME cavities (MEC). Three conditions were measured: intact ossicles, drained cochlea, and disarticulated stapes. When the cochlear load is removed from the ME by disarticulating the stapes, the impedance magnitude varies by about +/-25 dB in the 5- to 30-kHz range, with peaks and valleys at intervals of approximate to 5 kHz. These measurements suggest middle-ear standing waves. It is argued that these standing waves reside in the TM. In contrast, the magnitude of the impedance for the intact case varies by less than +/-10 dB, indicating that for this case the standing waves are damped by the cochlear load. Since the measurements were made within 2 mm of the TM, standing waves in the ear canal can be ruled out at these frequencies. Although the ME cavities were widely opened, reflections from the ME cavity walls or surrounding structures could conceivably result in standing waves. However, this possibility is ruled out by model predictions showing that such large standing waves in the ME cavity space would also be present in the intact case, in disagreement with the observation that standings waves are damped by cochlear loading. As a first-order approximation; the standing waves are modeled by representing the TM as a lossless transmission line with a frequency-independent delay of 36 mu s. The delay was estimated by converting the impedance data to reflectance and analyzing the reflectance group delay. In the model the ossicles are represented as lumped-parameter. elements. In contrast to previous models, the distributed and lumped parameter model of the ME is consistent with the measured impedance for all three conditions in the 200-Hz to 30-kHz region. Also in contrast with previous models, the ear-canal impedance is not mass dominated for frequencies above a few kHz. Finally, the present model is shown to be consistent, at high frequencies, with widely accepted transfer functions between (i) the stapes displacement and ear-canal pressure, (ii) the vestibule pressure and ear-canal pressure, and (iii) the umbo velocity and ear-canal volume velocity. An improved understanding of TM mechanics is important to improve hearing aid transducer design, ear-plug design, as well as otoacoustic emissions research. (C) 1998 Acoustical Society of America. [S0001-4966(98)02812-4]. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. RP Puria, S (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [DC00073, P01 DC00119, R03 DC02677] NR 58 TC 86 Z9 86 U1 0 U2 6 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD DEC PY 1998 VL 104 IS 6 BP 3463 EP 3481 DI 10.1121/1.423930 PG 19 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 145JM UT WOS:000077367500039 PM 9857506 ER PT J AU Kimmel, SE Sekeres, MA Berlin, JA Ellison, N DiSesa, VJ Strom, BL AF Kimmel, SE Sekeres, MA Berlin, JA Ellison, N DiSesa, VJ Strom, BL TI Risk factors for clinically important adverse events after protamine administration following cardiopulmonary bypass SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CARDIAC-SURGERY; HEPARIN NEUTRALIZATION; VASECTOMIZED MEN; SULFATE; ANAPHYLAXIS; INSULIN; CATHETERIZATION; PRETREATMENT; HYPOTENSION; COMPLEMENT AB Objectives. The purpose of this study was to determine risk factors for adverse events following protamine administration after cardiopulmonary bypass. Background. Intravenous protamine administration is associated with a risk of severe systemic reactions. However, risk factors for these events have not been well delineated, thus hampering development of preventive strategies. Methods. A case-control study nested within a cohort of consecutive patients undergoing surgery requiring cardiopulmonary bypass was performed. The primary case definition included those events (pulmonary hypertensive and systemic hypotensive) occurring within 10 min of protamine administration in the absence of other measurable causes of hemodynamic compromise. Results. Comparing the 53 cases to the 223 control subjects, three risk factors mere independently associated with events (multivariable odds ratio [95% confidence interval]): neutral protamine Hagedorn insulin use (8.18 [2.08, 32.2]); fish allergy (24.5 [1.24, 482.3]), and a history of nonprotamine medication allergy (2.97 [1.25, 7.07]). These risk factors demonstrated an increasingly strong association with progressively more specific case definitions. An estimated 39% of cardiopulmonary bypass patients had one or more of these risk factors. Prior intravenous protamine, central venous pressure prior to protamine, preoperative ejection fraction and the need for inotropes when coming off bypass did not exhibit statistically significant associations with events tall p > 0.15). Prior protamine allergy was associated specifically with an increased risk of pulmonary hypertension (multivariable odds ratio 189; 95% confidence interval 1.3, 2,856). Conclusions. Immunologic factors are important in predisposing individuals to protamine reactions, and a substantial proportion of patients are at considerably increased risk. Strategies to reduce the risk of protamine-associated events are needed. (J Am Coll Cardiol 1998;32:1916-22) (C) 1998 by the American College of Cardiology. C1 Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Med, Div Cardiovasc, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Hosp Univ Penn, Dept Anesthesia, Philadelphia, PA 19104 USA. Allegheny Univ E Falls, Dept Surg, Div Cardiothorac Surg, Philadelphia, PA USA. RP Kimmel, SE (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 717 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM kimmel@cceb.med.upenn.edu FU NHLBI NIH HHS [K08-HL03021] NR 47 TC 39 Z9 41 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC PY 1998 VL 32 IS 7 BP 1916 EP 1922 DI 10.1016/S0735-1097(98)00484-7 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 145WW UT WOS:000077396200019 PM 9857872 ER PT J AU Lee, SJ Zelen, M AF Lee, SJ Zelen, M TI Scheduling periodic examinations for the early detection of disease: Applications to breast cancer SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE early detection programs; periodic screening ID LEAD TIME; MORTALITY AB This article develops and extends previous investigations on stochastic models for selecting examination schedules targeted at earlier diagnosis of chronic diseases. The general aim is to provide guidelines for public health programs in the choice of examination schedules. The main features of such schedules are the initial age to begin a scheduled examination program, the intervals between subsequent examinations, and the number of examinations. Our basic model consists of three health states: a disease-free or nondetectable state; a preclinical state, in which an individual has disease but is asymptomatic and is unaware of it; and a clinical state in which the disease has been diagnosed by routine methods. The aim of early detection programs is to identify individuals in a preclinical local state, which may result in higher cure rates or longer survival. We introduce two basic ideas that either individually or together can lead to satisfactory examinations schedules. The threshold method constructs examination schedules so that the probability of an individual being in the preclinical state is always bounded by a preselected value. The concept of schedule sensitivity is the ratio of the expected number of cases diagnosed on scheduled examinations to the expectation of the total number of cases. Combining the threshold and schedule sensitivity methods enables an assessment of the trade-offs with regard to the initial age at examination and cost per case found. All of these methods are extended to high-risk populations. The schedule sensitivity, cost per case diagnosed on a scheduled exam, and the total cost can be calculated for any early detection program. This enables comparisons of different strategies. We illustrate the applicability of our methods to scheduling examinations for female breast cancer. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lee, SJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM sjlee@jimmy.harvard.edu NR 27 TC 33 Z9 33 U1 0 U2 6 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD DEC PY 1998 VL 93 IS 444 BP 1271 EP 1281 DI 10.2307/2670042 PG 11 WC Statistics & Probability SC Mathematics GA 143XE UT WOS:000077282200003 ER PT J AU Ibrahim, JG Ryan, LM Chen, MH AF Ibrahim, JG Ryan, LM Chen, MH TI Using historical controls to adjust for covariates in trend tests for binary data SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Gibbs sampling; historical data; likelihood ratio test; logistic regression; posterior distribution; prior distribution; score test ID GENERALIZED LINEAR-MODELS; BAYESIAN-ANALYSIS; CARCINOGENICITY; INFORMATION; SELECTION AB Historical data often play an important role in helping interpret the results of a current study. This article is motivated primarily by one specific application: the analysis of data from rodent carcinogenicity studies. By proposing a suitable informative prior distribution on the relationship between control outcome data and covariates, we derive modified trend test statistics that incorporate historical control information to adjust for covariate effects. Frequentist and fully Bayesian methods are presented, and novel computational techniques are developed to compute the test statistics. Several attractive theoretical and computational properties of the proposed priors are derived. In addition, a semiautomatic elicitation scheme for the priors is developed. Our approach is used to modify a widely used prevalence test for carcinogenicity studies. The proposed methodology is applied to data from a National Toxicology Program carcinogenicity experiment and is shown to provide helpful insight on the results of the analysis. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Worcester Polytech Inst, Dept Math Stat, Worcester, MA 01609 USA. RP Ibrahim, JG (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 35 TC 41 Z9 42 U1 0 U2 1 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD DEC PY 1998 VL 93 IS 444 BP 1282 EP 1293 DI 10.2307/2670043 PG 12 WC Statistics & Probability SC Mathematics GA 143XE UT WOS:000077282200004 ER PT J AU Adak, S AF Adak, S TI Time-dependent spectral analysis of nonstationary time series SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE cross-validation; fast algorithms; local stationarity; time-frequency analysis; tree-based methods ID SEGMENTATION AB Modeling of nonstationary stochastic time series has found wide applications in speech processing, biomedical signal processing, seismology, and failure detection. Data from these fields have often been modeled as piecewise stationary processes with abrupt changes, and their time-varying spectral features have been studied with the help of spectrograms. A general class of piecewise locally stationary processes is introduced here that allows both abrupt and smooth changes in the spectral characteristics of the nonstationary time series. It is shown that this class of processes behave as approximately piecewise stationary processes and can be used to model various naturally occuring phenomena. An adaptive segmentation method of estimating the time-dependent spectrum is proposed for this class of processes. The segmentation procedure uses binary trees and windowed spectra to nonparametrically and adaptively partition the data into approximately stationary intervals. Results of simulation studies demonstrate that the method has excellent ability to adapt to the rate at which the spectrum is changing. Applications of the method to speech signals and earthquake data are considered. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Adak, S (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. NR 30 TC 60 Z9 60 U1 0 U2 7 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD DEC PY 1998 VL 93 IS 444 BP 1488 EP 1501 DI 10.2307/2670062 PG 14 WC Statistics & Probability SC Mathematics GA 143XE UT WOS:000077282200023 ER PT J AU Kilic, T Pamir, MN Budd, S Ozek, MM Erzen, C AF Kilic, T Pamir, MN Budd, S Ozek, MM Erzen, C TI Grading and hemodynamic follow-up study of arteriovenous malformations with transcranial Doppler ultrasonography SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE arteriovenous malformations; grading; hemodynamics; transcranial Doppler ultrasonography ID SONOGRAPHY; HEMORRHAGE; STEAL; EMBOLIZATION; ULTRASOUND; BRAIN; AVMS AB This study presents and tests the clinical validity of a hemodynamic grading system that depends on noninvasive transcranial Doppler ultrasonographic parameters. The suggested transcranial Doppler-based grading system was compared with the Spetzler-Martin anatomic grading for prognosticative validity and clinical dependability. We concluded the following: (1) The pulsatility index was shown to be a more dependable transcranial Doppler parameter in the clinical evaluation of an arteriovenous malformation because of two reasons: preoperative pulsatility index findings inversely correlated with arteriovenous malformation volume, and the pulsatility index returned to normal values before the mean blood flow velocity did. Therefore, hemodynamic arteriovenous malformation grading can be based on the pulsatility index. (2) A transcranial Doppler-based hemodynamic arteriovenous malformation grading system correlated highly with the Spetzler-Martin grading in predicting postoperative neurologic deficits and adverse radiologic findings. (3) The presented grading system may contribute to the standardization and quantification of the hemodynamic changes during multidisciplinary management of arteriovenous malformations. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Blacks Res Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, CNS Res Inst, Boston, MA 02115 USA. Marmara Univ, Inst Neurol Sci, Istanbul, Turkey. RP Kilic, T (reprint author), Dana Farber Canc Inst, 44 Binney St,Smith Bldg 1010, Boston, MA 02115 USA. OI Pamir, M Necmettin/0000-0002-5958-8625 NR 32 TC 10 Z9 11 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD DEC PY 1998 VL 17 IS 12 BP 729 EP 738 PG 10 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 142DU UT WOS:000077185300001 PM 9849944 ER PT J AU Chang, JJ Shinohara, K Bhargava, V Presti, JC AF Chang, JJ Shinohara, K Bhargava, V Presti, JC TI Prospective evaluation of lateral biopsies of the peripheral zone for prostate cancer detection SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; biopsy ID SYSTEMATIC SEXTANT BIOPSIES; CORE BIOPSIES AB Purpose: We evaluate the usefulness of adding 4 lateral biopsies of the peripheral zone to the routine sextant biopsy regimen for prostate cancer. Materials and Methods: A total of 273 consecutive patients referred for abnormal digital rectal examination and/or prostate specific antigen 4 ng./ml. or greater underwent transrectal ultrasound and systematic biopsy. Lateral biopsies of the peripheral zone taken just medial to the lateral border of the prostate were added to the routine lesion directed and systematic sextant biopsy regimen. Comparisons between positive and negative biopsy groups as well as among various biopsy schemes were performed. Results: Of the patients 44% had cancer on biopsy (121 of 273). While routine sextant biopsies detected 82% of cancers, 77% (17 of 22) of missed cancers were detected on lateral biopsies. Overall, lateral biopsies detected 70% of cancers, and tended to be positive in patients with small prostates and high grade tumors. A significant correlation was found between hypoechoic lesions on transrectal ultrasound and positive lateral biopsies (Fisher's exact test p = 0.0005). Cancer was found in 74 of 147 patients with lesions on transrectal ultrasound (50%). Routine sextant biopsies detected 76% of cancers (56 of 74 patients) while lateral biopsies detected 80% (59). Of these patients 15 (20%) had positive lateral and negative sextant biopsies. Routine sextant biopsies detected 91% of cancers in 121 patients without lesions on ultrasound (43 of 47). Conclusions: The addition of lateral peripheral zone biopsies increases the sensitivity for cancer detection while nearly eliminating the need for lesion directed biopsies. C1 Univ Calif San Francisco, Sch Med, Dept Urol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, Dept Pathol, San Francisco, CA 94143 USA. San Francisco Vet Adm Med Ctr, San Francisco, CA USA. RP Chang, JJ (reprint author), Univ Calif San Francisco, Sch Med, Dept Urol, San Francisco, CA 94143 USA. NR 12 TC 126 Z9 131 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD DEC PY 1998 VL 160 IS 6 BP 2111 EP 2114 DI 10.1016/S0022-5347(01)62254-7 PN 1 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 136TP UT WOS:000076875500043 PM 9817334 ER PT J AU Stoughton, J Nath, RL Abbott, WM AF Stoughton, J Nath, RL Abbott, WM TI Comparison of simultaneous electroencephalographic and mental status monitoring during carotid endarterectomy with regional anesthesia SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 12th Annual Meeting of the Eastern-Vascular-Society CY MAY 01-03, 1998 CL NEWPORT, RHODE ISLAND SP Eastern Vasc Soc ID LOCAL-ANESTHESIA; PERIOPERATIVE COMPLICATIONS; GENERAL-ANESTHESIA; CEREBRAL-ISCHEMIA; ARTERY SURGERY; BLOOD-FLOW AB Purpose: This study examines the accuracy of intraoperative electro encephalographic (EEG) monitoring for the detection of cerebral ischemia by comparing EEG with simultaneous mental status evaluation (MSE) during carotid endarterectomy in awake patients. Methods: Between 1994 and 1997, 208 consecutive carotid endarterectomies were prospectively evaluated for cerebral function during surgery with simultaneous MSE and EEG monitoring. Regional anesthesia (RA), which consisted of superficial cervical block, was chosen preferentially in 75% of the cases, with general anesthesia (GA) reserved for the patients who did not fulfill the criteria for RA. When available, 8-channel EEG monitoring was performed (59% with RA and 55% with GA). Results: The EEG was a reliable predictor in comparison with MSE in most but not ail cases of cerebral ischemia. Significant neurologic changes were noted using MSE in 4 of 89 patients (4.5%) that were not detected using EEG (false negative results). Conversely, 6 of 89 cases (6.7%) showed unilateral slowing without associated changes in MSE (false positive results). For the awake patients, 21 of 150 cases (14%) showed MSE changes that required a shunt. By contrast, 9 of 32 GA cases (28%) shorted EEG changes that would have led to shunting (P = NS). In the RA group, there were no strokes versus 3 of 58 cases (5.2%) with strokes in the GA group. Two of 150 cases (0.1%) had transient ischemic attacks in the RA group. There was 1 myocardial infarction in the GA group; no deaths occurred in this series. Conclusion: EEG monitoring yielded a significant number of false positive (6.7%) and false negative (4.5%) results in the detection of neurologic deficits when compared with MSE in the awake patients. In this series, the preferential use of RA resulted in less shunt use and was possibly associated with a lower stroke rate. C1 Lawrence Mem Hosp, Dept Surg, Medford, MA USA. Lawrence Mem Hosp, Dept Surg, Winchester, MA USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Stoughton, J (reprint author), 101 Main St,Ste 211, Medford, MA 02155 USA. NR 28 TC 38 Z9 39 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 1998 VL 28 IS 6 BP 1014 EP 1021 DI 10.1016/S0741-5214(98)70027-8 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 148QN UT WOS:000077543600012 PM 9845652 ER PT J AU Kaur, A Grant, RM Means, RE McClure, H Feinberg, M Johnson, RP AF Kaur, A Grant, RM Means, RE McClure, H Feinberg, M Johnson, RP TI Diverse host responses and outcomes following simian immunodeficiency virus SIVmac239 infection in sooty mangabeys and rhesus macaques SO JOURNAL OF VIROLOGY LA English DT Article ID CD38 ANTIGEN EXPRESSION; T-CELL RESPONSES; LOW VIRAL LOAD; NONHUMAN-PRIMATES; HIV-1 INFECTION; DISEASE PROGRESSION; SIV/SMM REPLICATION; VACCINE PROTECTION; PERIPHERAL-BLOOD; TYPE-1 INFECTION AB Sooty mangabeys naturally infected with simian immunodeficiency virus (SIV) do not develop immunodeficiency despite the presence of viral loads of 10(5) to 10(7) RNA copies/ml. To investigate the basis of apathogenic SIV infection in sooty mangabeys, three sooty mangabeys and three rhesus macaques were inoculated intravenously with SIVmac239 and evaluated longitudinally for 1 year. SIVmac239 infection of sooty mangabeys resulted in 2- to 4-log-lower viral loads than in macaques and did not reproduce the high viral loads observed in natural SIVsmm infection. During acute SIV infection, polyclonal cytotoxic T-lymphocyte (CTL) activity coincident with decline in peak plasma viremia was observed in both macaques and mangabeys; 8 to 20 weeks later, CTL activity declined in the macaques but was sustained and broadly directed in the mangabeys. Neutralizing antibodies to SIVmac239 were detected in the macaques but not the mangabeys. Differences in expression of CD38 on CD8(+) T lymphocytes or in the percentage of naive phenotype T cells expressing CD45RA and CD62L-selection did not correlate with development of AIDS in rhesus macaques. In macaques, the proportion of CD4(+) T lymphocytes expressing CD25 declined during SIV infection, while in mangabeys, CD25-expressing CD4+ T lymphocytes increased. Longitudinal evaluation of cytokine secretion by flow cytometric analysis of unstimulated lymphocytes revealed elevation of interleukin-2 and gamma interferon in a macaque and only interleukin-10 in a concurrently infected mangabey during acute SIV infection. Differences in host responses following experimental SIVmac239 infection may be associated with the divergent outcome in sooty mangabeys and rhesus macaques. C1 Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA. Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Microbiol, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA 02114 USA. Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Emory Univ, Yerkes Reg Primate Res Ctr, Div Res Resources, Atlanta, GA 30322 USA. Emory Univ, Yerkes Reg Primate Res Ctr, Div Microbiol & Immunol, Atlanta, GA 30322 USA. Emory Univ, Dept Med, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. RP Johnson, RP (reprint author), Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Immunol, 1 Pine Hill Dr,POB 9102, Southborough, MA 01772 USA. FU NCRR NIH HHS [P51 RR000165, K26 RR000168, P51 RR000168, RR 00168, RR 0165]; NIAID NIH HHS [AI 38559, P30 AI027763] NR 75 TC 126 Z9 126 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1998 VL 72 IS 12 BP 9597 EP 9611 PG 15 WC Virology SC Virology GA 137AW UT WOS:000076892100020 PM 9811693 ER PT J AU Verdolini, K Chan, R Titze, IR Hess, M Bierhals, W AF Verdolini, K Chan, R Titze, IR Hess, M Bierhals, W TI Correspondence of electroglottographic closed quotient to vocal fold impact stress in excised canine larynges SO JOURNAL OF VOICE LA English DT Article DE intraglottal SI; intraglottal impact stress; vocal folds; closed quotient; electroglottography; excised larynx ID CONTACT AREA AB The purpose of this study was to explore the possible use of the electroglottographic closed quotient (EGG CQ) as a noninvasive estimate of vocal fold impact stress (SI). Two excised canine larynges were used. Each larynx was mounted and vocal fold oscillation was induced using a humidified air source. Twentyseven experimental trials were conducted for each larynx. Trials involved variations in vocal process gap, vocal fold elongation, and subglottic pressure. Simultaneous measures were made of vocal fold SI at the midpoint of the membranous vocal folds, and EGG CQ (dimensionless ratio). The results indicated that when threshold and saturation effects were excluded, the SI and the CQ were strongly related (Linear correlation r = .83 and .96 for the two individual larynges, and .81 for the combined data). Within the region of linear relation, an increase of .15 in the CQ corresponded to about 1 kPa increase in SI for the combined data. Discussion focuses on possible clinical implications and the likely reasons for threshold and saturation phenomena. C1 Harvard Univ, Sch Med, Div Otol & Laryngol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Voice & Speech Lab, Boston, MA 02114 USA. MGH, Inst Hlth Profess, Boston, MA USA. Beth Israel Deaconess Med Ctr, Voice Speech Swallowing Div, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Iowa, Dept Speech Pathol & Audiol, Iowa City, IA 52242 USA. Natl Ctr Voice & Speech, Iowa City, IA 52242 USA. Wilbur James Gould Voice Res Ctr, Denver, CO USA. Free Univ Berlin, Dept Audiol & Phoniatr, D-1000 Berlin, Germany. Free Univ Berlin, Acoust Res Lab, D-1000 Berlin, Germany. RP Verdolini, K (reprint author), Voice & Speech Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [P60DC00976] NR 25 TC 19 Z9 19 U1 1 U2 1 PU SINGULAR PUBLISHING GROUP INC PI SAN DIEGO PA 401 WEST A ST, STE 325, SAN DIEGO, CA 92101-7904 USA SN 0892-1997 J9 J VOICE JI J. Voice PD DEC PY 1998 VL 12 IS 4 BP 415 EP 423 DI 10.1016/S0892-1997(98)80050-7 PG 9 WC Otorhinolaryngology SC Otorhinolaryngology GA 163DN UT WOS:000078387700003 PM 9988028 ER PT J AU Sanchez, CP Salusky, IB Kuizon, BD Abdella, P Juppner, H Goodman, WG AF Sanchez, CP Salusky, IB Kuizon, BD Abdella, P Juppner, H Goodman, WG TI Growth of long bones in renal failure: Roles of hyperparathyroidism, growth hormone and calcitriol SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the American-Society-of-Nephrology CY NOV 02-06, 1997 CL SAN ANTONIO, TEXAS SP Amer Soc Nephrol DE growth plate cartilage; chondrocyte proliferation; nephrectomy; childhood growth; renal osteodystrophy ID I IGF-I; PARATHYROID-HORMONE; CARTILAGE GROWTH; UREMIC RATS; RECEPTOR; PLATE; EXPRESSION; CULTURES; CHILDREN; PEPTIDE AB Background The treatment of secondary hyperparathyroidism (2 degrees HPT) associated with chronic renal failure adversely affects skeletal growth. Methods. We assessed epiphyseal growth plate morphology by quantitative histology and measured mRNA levels for selected markers of chondrocyte proliferation and differentiation by in situ hybridization in the growth plate cartilage of subtotally nephrectomized rats with either mild or advanced 2 degrees HPT. Results. The width of the growth plate cartilage in the proximal tibia and mRNA levels for PTH/PTHrP receptor were unchanged in rats with mild 2 degrees HPT, however, they were markedly less in nephrectomized rats with advanced 2 degrees HPT than in intact controls. Treatment with growth hormone 10 IU/kg/day increased growth plate thickness both in mild and in advanced 2 degrees HPT and raised mRNA levels for type II and type X collagen in rats with advanced 2 degrees HPT. The administration of calcitriol 50 ng/kg/day attenuated these responses in animals with advanced 2 degrees HPT. Overall, PTH/PTHrP receptor mRNA levels did not correspond to the serum levels of PTH indicating that PTH/PTHrP receptor expression is down-regulated in renal failure by a PTH-independent mechanism. Conclusion. Calcitriol counteracts the trophic actions of growth hormone on epiphyseal growth plate cartilage and modifies chondrocyte differentiation in vivo, and these mechanisms may contribute to disturbances in longitudinal bone growth in renal failure. C1 Univ Calif Los Angeles, Sch Med, Div Pediat Nephrol, Dept Pediat, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Sanchez, CP (reprint author), Univ Calif Los Angeles, Sch Med, Div Pediat Nephrol, Dept Pediat, A2-383 MDCC,10833 Le Conte Ave, Los Angeles, CA 90095 USA. FU NCRR NIH HHS [RR-00865, M01-RR-00865]; NIDDK NIH HHS [DK-35423] NR 26 TC 56 Z9 56 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 1998 VL 54 IS 6 BP 1879 EP 1887 DI 10.1046/j.1523-1755.1998.00199.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 141EE UT WOS:000077129000008 PM 9853253 ER PT J AU Wackym, PA King, WA Barker, FG Poe, DS AF Wackym, PA King, WA Barker, FG Poe, DS TI Endoscope-assisted vestibular neurectomy SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT 101st Annual Meeting of the American-Laryngological-Rhinological-and-Otological-Society CY MAY 11-13, 1998 CL PALM BEACH, FLORIDA SP Amer Laryngol Rhinol & Otol Soc Inc ID MENIERES-DISEASE; SURGERY; HEARING; ANATOMY AB Objective/Hypothesis: In some instances endoscopes offer better visualization than the microscope and frequently allow less invasive surgery. This study was undertaken 60 determine whether endoscopy is safe and effective during neurectomy of the vestibular nerve. Method: Ten patients with intractable unilateral Meniere's disease underwent a retrosigmoid craniotomy for neurectomy of the vestibular nerve. Endoscopy with a Hopkins telescope was used during each procedure to study posterior fossa anatomic relationships and to assist the neurectomy, Preoperative and postoperative audiometric evaluation was performed in all patients undergoing vestibular neurectomy. Nine of these patients had preoperative electronystagmography, and four patients completed postoperative electronystagmography. The 1995 American Academy of Otolaryngology-Head and Neck Surgery's Committee on Hearing and Equilibrium guidelines for the diagnosis and evaluation of therapy in Meniere's disease were used, Results: Complete neurectomy was achieved in all 10 patients. Endoscopy allowed improved identification of the nervus intermedius and the facial, cochlear, and vestibular nerves and adjacent neurovascular relationships without the need for significant retraction of the cerebellum or brainstem. In addition, endoscopic identification of the cleavage plane between the cochlear and vestibular nerves medial to or within the internal auditory canal (n = 3) was not made with the 0-degree endoscope; however, identification was made with the 30- or 70-degree endoscope in all cases. In all patients with Meniere's disease, elimination of the recurrent episodes of vertigo (n = 10) or otolithic crisis of Tumarkin (n = 1) was achieved. Conclusions: Posterior fossa endoscopy can be performed safely. Endoscope-assisted neurectomy of the vestibular nerve may offer some advantages over standard microsurgery including increased visualization, more complete neurectomy, minimal cerebellar retraction, and a lowered risk of cerebrospinal fluid leakage. C1 Med Coll Wisconsin, Dept Otolaryngol & Commun Sci, Milwaukee, WI 53226 USA. Mt Sinai Sch Med, Dept Neurosurg, New York, NY USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Wackym, PA (reprint author), Med Coll Wisconsin, Dept Otolaryngol & Commun Sci, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. NR 27 TC 18 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD DEC PY 1998 VL 108 IS 12 BP 1787 EP 1793 DI 10.1097/00005537-199812000-00005 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 145TF UT WOS:000077386900005 PM 9851492 ER PT J AU Paietta, E Racevskis, J Bennett, JM Neuberg, D Cassileth, PA Rowe, JM Wiernik, PH AF Paietta, E Racevskis, J Bennett, JM Neuberg, D Cassileth, PA Rowe, JM Wiernik, PH CA Eastern Cooperative Oncology Grp TI Biologic heterogeneity in Philadelphia chromosome-positive acute leukemia with myeloid morphology: the Eastern Cooperative Oncology Group experience SO LEUKEMIA LA English DT Article DE acute leukemia; Philadelphia chromosome; myeloid; FAB; immunophenotype ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE LYMPHOCYTIC-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; MIXED LINEAGE LEUKEMIA; EXPRESSION; MONOSOMY-7; ABL; IMMUNOPHENOTYPE; TRANSCRIPTS; BREAKPOINT AB Evaluable karyotypes were available in 776 of 1148 adult patients who were entered on acute myeloid leukemia (AML) treatment protocols of the Eastern Cooperative Oncology Group. Among these, we found seven patients (0.9%) with t(9;22)(q34;q11), the philadelphia (Ph) chromosome, in bone marrow metaphases. Ail fulfilled the FAB criteria for AML (three M0, two M1, two M2), although one patient presented with an additional, distinct lymphoid blast cell population. Chromosomal aberrations in addition to the Ph chromosome were seen in four patients (including two cases of monosomy 7). Molecular analysis by polymerase chain reaction in four patients tested revealed variable BCR/ABL transcript forms (ela2, b2a2, b3a2, b2a3+e1a2). By immunophenotyping, all seven patients were myeloid based on the overall antigen expression pattern. However, all but one demonstrated lymphoid-associated antigens on the myeloid blast cells. The six evaluable patients failed to respond to treatment with a standard anthracycline/cytosine arabinoside-containing regimen. We conclude that the incidence of the Ph chromosome in AML is very low. Although both genotypically and phenotypically heterogenous, Ph chromosome-positive AML, represents a clinically distinct entity with poor outcome. C1 Montefiore Med Ctr, Dept Oncol, Bronx, NY 10467 USA. Albert Einstein Canc Ctr, Dept Oncol, Bronx, NY 10461 USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. Univ Rochester, Div Med Oncol, Rochester, NY USA. Univ Miami, Dept Hematol Oncol, Div Canc Biol, Miami, FL 33152 USA. Eastern Cooperat Grp, Brookline, MA USA. RP Paietta, E (reprint author), Montefiore Med Ctr, Dept Oncol, 111 E 210Th St, Bronx, NY 10467 USA. FU NCI NIH HHS [CA23318, CA14958, CA21115] NR 37 TC 49 Z9 50 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD DEC PY 1998 VL 12 IS 12 BP 1881 EP 1885 DI 10.1038/sj.leu.2401229 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 148YY UT WOS:000077563400005 PM 9844918 ER PT J AU Kelly, K AF Kelly, K TI Choosing a wheelchair: A guide for optimal independence. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kelly, K (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD DEC PY 1998 VL 123 IS 20 BP 144 EP 144 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 148BH UT WOS:000077532000234 ER PT J AU Dennie, J Mandeville, JB Boxerman, JL Packard, SD Rosen, BR Weisskoff, RM AF Dennie, J Mandeville, JB Boxerman, JL Packard, SD Rosen, BR Weisskoff, RM TI NMR imaging of changes in vascular morphology due to tumor angiogenesis SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE angiogenesis; morphology; susceptibility NMR ID ENDOTHELIAL GROWTH-FACTOR; CEREBRAL BLOOD-VOLUME; MAGNETIC-SUSCEPTIBILITY; MALIGNANT GLIOMA; BRAIN-TUMORS; MR CONTRAST; IN-VIVO; PERMEABILITY; RAT; MICROVASCULATURE AB Tumor-sprouted vessels are greater in both number and diameter in comparison to their healthy counterparts, A novel technique based on magnetic susceptibility contrast mechanisms that are sensitive to varying sizes of blood vessels is presented to measure differences between the relaxation rates (1/T-2 and 1/T-2*) in a rat glioma model and normal cerebral cortex. Delta R2 and Delta R2*, the differences between relaxation rates precontrast and postcontrast agent injection, were measured for an intravascular equilibrium contrast agent (MION) at various echo times. Since Delta R2*/Delta R2 increases as vessel size increases, this ratio can be used as a measure of the average vessel size within an ROI or a voxel, The stability and longevity of the contrast agent within the vasculature were verified (n = 2 trials), and the ratio of Delta R2*/Delta R2 between the tumor and normal cortex was measured to be 1.9 +/- 0.2 (n = 4, echo time = 20 ms, and susceptibility difference (Delta chi) approximate to 10(-6)). This ratio compared favorably to a predicted ratio determined using histologically determined vessel sizes and theoretical Monte Carlo modeling results (1.9 +/- 0.1). Maps of the ratio of Delta R2*/Delta R2 were also made on a pixel-by-pixel basis. These techniques support the hypothesis that susceptibility contrast MRI can provide useful quantitative metrics of in vivo tumor vascular morphology. C1 Massachusetts Gen Hosp, Dept Radiol, NMR Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. MIT, Dept Nucl Engn, Cambridge, MA 02139 USA. Johns Hopkins Univ, Sch Med, Dept Radiol & Radiol Sci, Baltimore, MD USA. RP Rosen, BR (reprint author), Massachusetts Gen Hosp, NMR Ctr, 2nd Floor,Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [P01-CA48729, R01-CA40303]; NHLBI NIH HHS [R01-HL39810] NR 37 TC 248 Z9 253 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD DEC PY 1998 VL 40 IS 6 BP 793 EP 799 DI 10.1002/mrm.1910400602 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 141MP UT WOS:000077148000001 PM 9840821 ER PT J AU Glowacki, J Yates, K Little, G Mizuno, S AF Glowacki, J Yates, K Little, G Mizuno, S TI Induced chondroblastic differentiation of human fibroblasts by three-dimensional culture with demineralized bone matrix SO MATERIALS SCIENCE & ENGINEERING C-BIOMIMETIC AND SUPRAMOLECULAR SYSTEMS LA English DT Article DE human fibroblasts; demineralization; osteoinduction ID HUMAN DERMAL FIBROBLASTS; CHONDROINDUCTION; COLLAGEN; DEFECTS AB Demineralized bone powder (DBP) implanted in vivo induces endochondral bone formation (osteoinduction). Connective tissue cells migrate to the powders and they begin to produce cartilage matrix. Subsequently, vascularization is stimulated and the cartilage is replaced by bone and marrow. Demineralized bone implants have been used clinically for a variety of osseous reconstructive applications. We designed a novel three-dimensional (3-D) device to examine the mechanism of chondroinduction in vitro. Normal human dermal fibroblasts (hDFs) were cultured in 3-D collagen sponges with and without DBP. The cells migrated through the collagen lattice and they attached to and spread onto particles of demineralized bone. Cells vicinal to the DBP produced cartilage matrix proteoglycans, Induced cells expressed cartilage-specific gene products, type II collagen and aggrecan. Control hDFs did not produce cartilage matrix when cultured in plain collagen sponges. This experimental system has the potential to reveal mechanisms of gene activation and other early steps in postnatal chondro/osteoinduction. Further, these results suggest that it may be possible to engineer human cartilage for transplantation by culturing autogenous dermal fibroblasts with a chondroinductive agent. (C) 1998 Published by Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Skeletal Biol Res Ctr, Boston, MA 02114 USA. EM glow@ortho.bwh.harvard.edu NR 15 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-4931 J9 MAT SCI ENG C-BIO S JI Mater. Sci. Eng. C-Biomimetic Supramol. Syst. PD DEC PY 1998 VL 6 IS 4 BP 199 EP 203 DI 10.1016/S0928-4931(98)00051-4 PG 5 WC Materials Science, Multidisciplinary SC Materials Science GA 153WT UT WOS:000077856800002 ER PT J AU Mizuno, S Ushida, T Tateishi, T Glowacki, J AF Mizuno, S Ushida, T Tateishi, T Glowacki, J TI Effects of physical stimulation on chondrogenesis in vitro SO MATERIALS SCIENCE & ENGINEERING C-BIOMIMETIC AND SUPRAMOLECULAR SYSTEMS LA English DT Article DE chondrogenesis; cartilage; stimuli ID CHONDROCYTE BIOSYNTHETIC RESPONSE; ARTICULAR-CARTILAGE; HYDROSTATIC-PRESSURE; PROTEOGLYCAN SYNTHESIS; CULTURED CHONDROCYTES; EXTRACELLULAR-MATRIX; DIARTHRODIAL JOINTS; DYNAMIC COMPRESSION; CHONDROITIN SULFATE; METABOLIC RESPONSE AB In cartilage, chondrocytes are embedded in an extracellular matrix composed of water, soluble constituents, and insoluble polymers. The physical stimulation of weight-bearing is known to influence the development, maturation, and degeneration of cartilage. The effects of osmotic and swelling pressure, oxygen tension, and hydrostatic pressure as well as interstitial fluid flow are modulated by compression of the solid cartilage matrix. These physical and physicochemical stimuli may be useful to engineer replacement cartilage. We summarize the effects of these stimuli and propose new methods to apply them. Our novel three-dimensional pressure/perfusion culture system has potential for improving in vitro engineering of autogenous cartilage. (C) 1998 Published by Elsevier Science S.A. All rights reserved. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. Minist Int Trade & Ind, Agcy Ind Sci & Technol, Natl Inst Interdisciplinary Res, 3D Tissue Engn Grp, Tsukuba, Ibaraki 305, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Skeletal Biol Res Ctr, Boston, MA 02114 USA. EM mizuno@ortho.bwh.harvard.edu NR 67 TC 23 Z9 23 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-4931 J9 MAT SCI ENG C-BIO S JI Mater. Sci. Eng. C-Biomimetic Supramol. Syst. PD DEC PY 1998 VL 6 IS 4 BP 301 EP 306 DI 10.1016/S0928-4931(98)00068-X PG 6 WC Materials Science, Multidisciplinary SC Materials Science GA 153WT UT WOS:000077856800018 ER PT J AU Tsunenaga, M Adachi, E Amano, S Burgeson, RE Nishiyama, T AF Tsunenaga, M Adachi, E Amano, S Burgeson, RE Nishiyama, T TI Laminin 5 can promote assembly of the lamina densa in the skin equivalent model SO MATRIX BIOLOGY LA English DT Article DE basement membrane; lamina densa; laminin 5; skin equivalent ID EPIDERMAL BASEMENT-MEMBRANE; HUMAN KERATINOCYTES; BASAL LAMINA; VII COLLAGEN; INTEGRIN RECEPTORS; ANCHORING FIBRILS; EPITHELIAL-CELLS; IV COLLAGEN; DIFFERENTIATION; FIBROBLASTS AB Skin equivalents were prepared by culturing human keratinocytes on the surface of type I collagen gel contracted by human skin fibroblasts (dermal equivalents) and by raising the gel to an air-liquid interface. A stratified squamous epithelium was formed with a well-differentiated cornified layer at the top of keratinocyte layers within 7 days after plating of the keratinocytes on the dermal equivalents. Although major basement membrane components such as collagens IV and VII and laminin 5: were detected immunohistochemically at the dermal-epidermal junction, a lamina densa was rarely observed by electron microscopy even in 14-day skin equivalents. When laminin 5 (1, 5 or 20 mu g/ml) was added to the culture medium on day 7 through day 14, types IV and VII collagens at the dermal-epidermal junction stained more strongly by immunohistochemistry compared with the control. Patches of lamina densa were present along the epidermal-dermal junction, and vesicles containing electron-opaque sheets approximately 0.6 mu m in diameter that reacted with anti-collagen IV antibody were also observed in basal keratinocytes in 14-day skin equivalents by electron microscopy. Morphometric analysis showed that the total length of lamina densa along the dermal-epidermal junction as well as in the vesicles increased up to 180%, 230% or 520% of control cultures by the addition of laminin 5 (1, 5 or 20 mu g/ml, respectively). These results suggest that laminin 5 accelerates formation of the lamina densa along the dermal-epidermal junction of the skin equivalents, depending on the concentration of laminin 5 supplemented exogenously. C1 Shiseido Life Sci Res Ctr, Kanazawa Ku, Yokohama, Kanagawa 2368643, Japan. Kitasato Univ, Postgrad Med Sch, Dept Mol Morphol, Sagamihara, Kanagawa 228, Japan. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Harvard Med Sch, Charlestown, MA USA. RP Nishiyama, T (reprint author), Shiseido Life Sci Res Ctr, Kanazawa Ku, 2-12-1 Fukuura, Yokohama, Kanagawa 2368643, Japan. RI Nishiyama, Toshio/C-5434-2013 NR 35 TC 39 Z9 41 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD DEC PY 1998 VL 17 IS 8-9 BP 603 EP 613 DI 10.1016/S0945-053X(98)90111-1 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 168RA UT WOS:000078705300006 PM 9923653 ER PT J AU Paganetti, H AF Paganetti, H TI Monte Carlo method to study the proton fluence for treatment planning SO MEDICAL PHYSICS LA English DT Article DE proton therapy ID DOSE CALCULATIONS; RADIOTHERAPY; ALGORITHM; PENUMBRA; MODEL AB The proton beam at the Hahn Meitner Institute (HMI) in Berlin will be used for proton therapy of eye melanoma in the near future. As part of the pre-therapeutic studies, Monte Carlo calculations have been performed to investigate the primary fluence distribution of the proton beam including the influence of scattering foils, range shifters, modulator wheels, and collimators. Any material in the beam path will modify the therapeutic beam because of energy loss, multiple scattering, range straggling, and nuclear reactions. The primary fluence information is a pre-requisite for most pencil-beam treatment planning algorithms. The measured beam penumbra has been used as one of the parameters to characterize a proton beam for further calculations in a treatment has been used as one of However, this phenomenological quantity represents only indirect information about the properties of the proton beam. In this work, an alternative parameterization of the beam exiting the vacuum window of the accelerator, as well as the beam right in front of the patient collimator, is introduced. A beam is fully characterized if one knows (for instance from Monte Carlo simulations) the particle distribution in energy, position, and angle, i.e., the phase space distribution. Therefore, parameters derived from this distribution can provide an alternative input in treatment planning algorithms. In addition, the method of calculation is introduced as a tool to investigate the influence of modifications in the beam delivery system on the behavior of the therapeutic proton beam. (C) 1998 American Association of Physicists in Medicine. [S0094-2405(98)02012-4]. C1 Hahn Meitner Inst Kernforsch Berlin GmbH, ATT, D-14109 Berlin, Germany. RP Paganetti, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 16 TC 28 Z9 28 U1 0 U2 3 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD DEC PY 1998 VL 25 IS 12 BP 2370 EP 2375 DI 10.1118/1.598447 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 149YX UT WOS:000077635700016 PM 9874829 ER PT J AU Huang, RY Lian, JP Robinson, D Badwey, JA AF Huang, RY Lian, JP Robinson, D Badwey, JA TI Neutrophils stimulated with a variety of chemoattractants exhibit rapid activation of p21-activated kinases (Paks): Separate signals are required for activation and inactivation of Paks SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-KINASE; POLYMORPHONUCLEAR LEUKOCYTES; TYROSINE PHOSPHORYLATION; CALCIUM MOBILIZATION; CHEMOTACTIC FACTORS; CYTOSKELETAL ACTIN; ADAPTER PROTEIN; L-SELECTIN; MYOSIN-I; RECEPTOR AB Activation of the p21-activated protein kinases (Paks) was compared in neutrophils stimulated with a wide variety of agonists that bind to receptors coupled to heterotrimeric G proteins. Neutrophils stimulated with sulfatide, a ligand for the L-selectin receptor, or the chemoattractant fMet-Leu-Phe (fMLP), platelet-activating factor, leukotriene B-4, interleukin-8, or the chemokine RANTES exhibited a rapid and transient activation of the 63- and 69-kDa Paks. These kinases exhibited maximal activation,vith each of these agonists within 15 s followed by significant inactivation at 3 min. In contrast, neutrophils treated with the chemoattractant and anaphylatoxin C5a exhibited a prolonged activation (>15 min) of these Paks even though the receptor for this ligand may activate the same overall population of complex G proteins as the fMLP receptor, Addition of fMLP to neutrophils already stimulated with C5a resulted in the inactivation of the 63- and 69-kDa Paks. Optimal activation of Paks could be observed at concentrations of these agonists that elicited only shape changes and chemotaxis in neutrophils. While all of the agonists listed above triggered quantitatively similar activation of the 63- and 69-kDa Paks, fMLP was far superior to the other stimuli in triggering activation of the c-Jun N-terminal kinase (JNK) and the p38 mitogen-activated protein kinase (MAPK). These data indicate that separate signals are required for activation and inactivation of Paks and that, in contrast to other cell types, activated Pak does not trigger activation of JNK or p38-MAPK in neutrophils. These results are consistent with the recent hypothesis that G-protein-coupled receptors may initiate signals independent of those transmitted by the alpha and beta gamma subunits of complex G proteins. C1 Boston Biomed Res Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Arthritis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02114 USA. RP Badwey, JA (reprint author), Boston Biomed Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM badwey@disperri.bbri.harvard.edu FU NIAID NIH HHS [AI23323]; NIAMS NIH HHS [AR43518]; NIDDK NIH HHS [DK50015] NR 69 TC 50 Z9 51 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1998 VL 18 IS 12 BP 7130 EP 7138 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 140QK UT WOS:000077099700024 PM 9819399 ER PT J AU Li, YQ Bharti, A Chen, DS Gong, JL Kufe, D AF Li, YQ Bharti, A Chen, DS Gong, JL Kufe, D TI Interaction of glycogen synthase kinase 3 beta with the DF3/MUC1 carcinoma-associated antigen and beta-catenin SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CELL-CELL ADHESION; TRANSCRIPTION FACTOR LEF-1; TUMOR-SUPPRESSOR PROTEIN; MONOCLONAL-ANTIBODY DF3; POLYPOSIS-COLI PROTEIN; APC GENE-PRODUCT; E-CADHERIN; XENOPUS EMBRYOS; WINGLESS SIGNAL; ALPHA-CATENIN AB The DF3/MUC1 mucin-like glycoprotein is highly overexpressed in human carcinomas. Recent studies have demonstrated that the cytoplasmic domain of MUC1 interacts with beta-catenin. Here we show that MUC1 associates with glycogen synthase kinase 3 beta (GSK3 beta). GSK3 beta binds directly to an STDRSPYE site in MUC1 and phosphorylates the serine adjacent to proline, Phosphorylation of MUC1 by GSK3 beta decreases binding of MUC1 to beta-catenin in vitro and in vivo. GSK3 beta-mediated phosphorlylation of MUC1 had no apparent effect on beta-catenin levels or the transcriptional coactivation function of beta-catenin, The results, however, demonstrate that MUC1 expression decreases binding of beta-catenin to the E-cadherin cell adhesion molecule. Negative regulation of the beta-catenin-MUC1 interaction by GSK3 beta is associated with restoration of the complex between beta-catenin and E-cadherin. These findings indicate that GSK3 beta decreases the interaction of MUC1 with beta-catenin and that overexpression of MUC1 in the absence of GSK3 beta activity inhibits formation of the E-cadherin-beta-catenin complex. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu NR 62 TC 193 Z9 198 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1998 VL 18 IS 12 BP 7216 EP 7224 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 140QK UT WOS:000077099700033 PM 9819408 ER PT J AU Alani, RM Hasskarl, L Munger, K AF Alani, RM Hasskarl, L Munger, K TI Alterations in cyclin-dependent kinase 2 function during differentiation of primary human keratinocytes SO MOLECULAR CARCINOGENESIS LA English DT Article DE cell-division cycle; carcinogenesis; phosphorylation ID RETINOBLASTOMA GENE-PRODUCT; CELL-CYCLE; DNA-REPLICATION; E7 ONCOPROTEIN; TGF-BETA; TERMINAL DIFFERENTIATION; POTENTIAL MEDIATOR; CDK6 INHIBITOR; PROTEIN; P21 AB Terminal differentiation of epithelial cells is intimately linked to cell-cycle withdrawal. The tight coupling of these two processes is critical to maintenance of epidermal tissue homeostasis and is frequently disrupted in squamous cell carcinoma. To identify possible molecular targets of epithelial carcinogenesis, we investigated the regulatory pathways that couple cellular differentiation and proliferation in primary cultures of human keratinocytes and found that the cyclin-dependent kinase inhibitors (CKls) p21(cip1/waf1) and p27(kip1) were induced early during differentiation of human keratinocytes, whereas p15(ink4B) was induced later in differentiation. The induction of p21(cip1/waf1) was mediated by both transcriptional and non-transcriptional mechanisms, and the activities of cyclin A/cyclin-dependent kinase (cdk) 2 and cyclin E/cdk2 complexes were specifically inhibited during keratinocyte differentiation. In contrast, p21(cip1/waf1) did not associate with cdk4, and the activities of cdk4 complexes remained unchanged. Hence, our results support the model that multiple CKls participate in linking cellular proliferation and differentiation in human keratinocytes by specific modulation of cdk2 activity. (C) 1998 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Canc Biol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. RP Munger, K (reprint author), Harvard Univ, Sch Med, Dept Pathol, 200 Longwood Ave,Goldenson Bldg,Room 113, Boston, MA 02115 USA. OI Munger, Karl/0000-0003-3288-9935 FU NCI NIH HHS [CA 66980]; NIAMS NIH HHS [K08 AR01975-01A1, T32 AR07098-21] NR 70 TC 16 Z9 17 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD DEC PY 1998 VL 23 IS 4 BP 226 EP 233 DI 10.1002/(SICI)1098-2744(199812)23:4<226::AID-MC5>3.0.CO;2-N PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 150AP UT WOS:000077640500005 PM 9869451 ER PT J AU Gu, HH Pratt, JC Burakoff, SJ Neel, BG AF Gu, HH Pratt, JC Burakoff, SJ Neel, BG TI Cloning of p97/Gab2, the major SHP2-binding protein in hematopoietic cells, reveals a novel pathway for cytokine-induced gene activation SO MOLECULAR CELL LA English DT Article ID COLONY-STIMULATING FACTOR; TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; PHOSPHATIDYLINOSITOL 3'-KINASE; PROMOTER ACTIVATION; POSITIVE REGULATOR; SH2 DOMAIN; C-FOS; RECEPTOR; KINASE AB Several components in cytokine signaling remain unidentified. We report the cloning and initial characterization of one such component, p97, a widely expressed scaffolding protein distantly related to Drosophila DOS and mammalian Gab1. Upon cytokine, growth factor, or antigen receptor stimulation, p97 becomes tyrosyl phosphorylated and associates with several SH2 domain-containing proteins, including SHP2. Expression of p97 mutants unable to bind SHP2 blocks cytokine-induced c-fos promotor activation, inhibiting Elk1-mediated and STAT5-medieted transactivation. Surprisingly, such mutants do not inhibit MAPK activation. Our results identify p97 as an important regulator of receptor signaling that controls a novel pathway to immediate-early gene activation and suggest multiple functions for SHP2 in cytokine receptor signaling. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Dept Med, Div Hematol Oncol,Canc Biol Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat,Div Pediat Oncol, Boston, MA 02115 USA. RP Gu, HH (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Dept Med, Div Hematol Oncol,Canc Biol Program, Boston, MA 02115 USA. EM hgu@bidmc.harvard.edu FU NCI NIH HHS [CA70758]; NIDDK NIH HHS [P01-DK50654, R01-DK50693] NR 51 TC 243 Z9 247 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD DEC PY 1998 VL 2 IS 6 BP 729 EP 740 DI 10.1016/S1097-2765(00)80288-9 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 153WQ UT WOS:000077856600003 PM 9885561 ER PT J AU Kwon, J Imbalzano, AN Matthews, A Oettinger, MA AF Kwon, J Imbalzano, AN Matthews, A Oettinger, MA TI Accessibility of nucleosomal DNA to V(D)J cleavage is modulated by RSS positioning and HMG1 SO MOLECULAR CELL LA English DT Article ID GLUCOCORTICOID RESPONSE ELEMENT; MOBILITY-GROUP PROTEINS; RAG2 PROTEINS; IN-VITRO; RECOMBINATION; GENE; CHROMATIN; INITIATION; 12/23-RULE; MECHANISM AB B and T cell receptor gene assembly by V(D)J recombination is tightly regulated during lymphoid development. The mechanisms involved in this regulation are poorly understood, Mere we show that nucleosomal DNA is refractory to V(D)J cleavage. However, the presence of HMG1, a chromatin-associated nonhistone DNA-binding protein, stimulates V(D)J cleavage of nucleosomal templates, This HMG1 stimulation is differentially affected by the rotational or translational positioning of the recombination signal sequence on the histone octamer, with cleavage of the 12 bp spacer RSS showing sensitivity to rotational position and the 23 bp spacer RSS affected by its displacement from the dyad. These results suggest that V(D)J recombination call be modulated by controlling substrate accessibility and cleavage at the level of an individual nucleosome. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Univ Massachusetts, Med Ctr, Dept Cell Biol, Worcester, MA 01655 USA. RP Oettinger, MA (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM oettinger@frodo.mgh.harvard.edu FU NIGMS NIH HHS [GM48405, GM58026] NR 36 TC 131 Z9 132 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD DEC PY 1998 VL 2 IS 6 BP 829 EP 839 DI 10.1016/S1097-2765(00)80297-X PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 153WQ UT WOS:000077856600012 PM 9885570 ER PT J AU Ogg, S Ruvkun, G AF Ogg, S Ruvkun, G TI The C-elegans PTEN homolog, DAF-18, acts in the insulin receptor-like metabolic signaling pathway SO MOLECULAR CELL LA English DT Article ID CAENORHABDITIS-ELEGANS; DAUER FORMATION; FAMILY MEMBER; LIFE-SPAN; GENE; LONGEVITY; KINASE; 3-KINASE; DIAPAUSE; CLONING AB An insulin-like signaling pathway, From the DAF-2 receptor, the AGE-I phosphoinositide 3-kinase, and the AKT-1/AKT-2 serine/threonine kinases to the DAF-16 Fork head transcription factor, regulates the metabolism, development, and life span of Caenorhabditis elegans. Inhibition of daf-18 gene activity bypasses the normal requirement for AGE-I and partially bypasses the need for DAF-P signaling. The suppression of age-1 mutations by a daf-18 mutation depends an AKT-1/AKT-2 signaling, showing that DAF-18 acts between AGE-1 and the AKT input to DAF-16 transcriptional regulation. daf-18 encodes a homolog of the human turner suppressor PTEN (MMAC1/TEP1), which has 3-phosphatase activity toward phosphatidylinositol 3,4,5-trisphosphate (PIP3). DAF-18 PTEN may normally limit AKT-1 and AKT-2 activation by decreasing PIP3, levels. The action of daf-18 in this metabolic control pathway suggests that mammalian PTEN may modulate insulin signaling and may be variant in diabetic: pedigrees. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, 50 Blossom St, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu FU NIA NIH HHS [AG05790, AG14161] NR 36 TC 273 Z9 281 U1 0 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD DEC PY 1998 VL 2 IS 6 BP 887 EP 893 DI 10.1016/S1097-2765(00)80303-2 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 153WQ UT WOS:000077856600018 PM 9885576 ER PT J AU Brown, RH AF Brown, RH TI SOD1 aggregates in ALS: Cause, correlate or consequence? SO NATURE MEDICINE LA English DT Editorial Material ID AMYOTROPHIC-LATERAL-SCLEROSIS; SUPEROXIDE-DISMUTASE; MUTATIONS; MUTANT; GENE C1 Massachusetts Gen Hosp, Day Neuromuscular Res Lab, Charlestown, MA 02129 USA. RP Brown, RH (reprint author), Massachusetts Gen Hosp, Day Neuromuscular Res Lab, Charlestown, MA 02129 USA. EM brown@helix.mgh.harvard.edu NR 11 TC 49 Z9 50 U1 1 U2 3 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 1998 VL 4 IS 12 BP 1362 EP 1364 DI 10.1038/3945 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 144VW UT WOS:000077336900026 PM 9846568 ER PT J AU Tate, S Benn, S Hick, C Trezise, D John, V Mannion, RJ Costigan, M Plumpton, C Grose, D Gladwell, Z Kendall, G Dale, K Bountra, C Woolf, CJ AF Tate, S Benn, S Hick, C Trezise, D John, V Mannion, RJ Costigan, M Plumpton, C Grose, D Gladwell, Z Kendall, G Dale, K Bountra, C Woolf, CJ TI Two sodium channels contribute to the TTX-R sodium current in primary sensory neurons SO NATURE NEUROSCIENCE LA English DT Article ID ROOT GANGLION NEURONS C1 Glaxo Wellcome Res & Dev Ltd, Med Res Ctr, Gene Funct Unit, Stevenage SG1 2NY, Herts, England. Glaxo Wellcome Res & Dev Ltd, Neurosci Unit, Stevenage SG1 2NY, Herts, England. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Univ London Univ Coll, Dept Anat & Dev Biol, London WC1E 6BT, England. RP Tate, S (reprint author), Glaxo Wellcome Res & Dev Ltd, Med Res Ctr, Gene Funct Unit, Stevenage SG1 2NY, Herts, England. FU Wellcome Trust NR 13 TC 227 Z9 231 U1 2 U2 5 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD DEC PY 1998 VL 1 IS 8 BP 653 EP 655 DI 10.1038/3652 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 144PR UT WOS:000077323400006 PM 10196578 ER PT J AU Tonini, M Fiori, E Balestra, B Spelta, V D'Agostino, G Di Nucci, A Brecha, NC Sternini, C AF Tonini, M Fiori, E Balestra, B Spelta, V D'Agostino, G Di Nucci, A Brecha, NC Sternini, C TI Endomorphin-1 and endomorphin-2 activate mu-opioid receptors in myenteric neurons of the guinea-pig small intestine SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Article DE endomorphin-l; endomorphin-2; mu-opioid receptors; opioid receptor antagonists; longitudinal muscle myenteric plexus preparation; guinea-pig ileum ID BINDING; ANTAGONISTS; INHIBITION; POTENT; BRAIN AB The novel opioid tetrapeptides, endomorphin-1 and endomorphin-2, recently isolated from bovine and human brain bind with high affinity and selectivity to central mu-opioid receptors. In the digestive tract, a comprehensive pharmacological analysis of the receptors involved in endomorphin action has not been reported. In this study, we analyzed the effects of endomorphin-1 and endomorphin-2 on longitudinal muscle-myenteric plexus preparations (LMMPs) from the guinea-pig ileum. Both peptides (30 pM-1 mu M) inhibited (-log EC50 values: 8.61 and 8.59, respectively) the amplitude of electrically-induced twitch contractions in a concentration-dependent fashion, up to its abolition. Conversely, in unstimulated LMMPs, they failed to affect contractions to applied acetylcholine (100 nM). In stimulated LMMPs, the highly selective mu-opioid receptor antagonist, D-Phe-Cys-Tyr-D-Trp-Om-Thr-Pen-Thr-NH2 (CTOP), caused a concentration-dependent (30 nM-1 mu M), parallel rightward shift of endomorphin-1 and endomorphin-2 inhibitory curves, without depression of their maximum. Following Schild analysis, calculated pA(2) values were 7.81 and 7.85, respectively, with slopes not different from unity. Concentration-response curves to both peptides were not affected by 30 nM naltrindole (a selective delta-receptor antagonist) or 30 nM nor-binaltorphimine (a selective kappa-receptor antagonist). These results demonstrate that endomorphins selectively activate mu-opioid receptors located on excitatory myenteric plexus neurons, and that they act as full agonists. C1 Univ Pavia, Dept Internal Med & Therapeut, Div Pharmacol & Toxicol, I-27100 Pavia, Italy. Univ Pavia, Fac Pharm, Inst Pharmacol, I-27100 Pavia, Italy. Univ Calif Los Angeles, Sch Med, CURE Digest Dis Res Ctr, Div Digest Dis,Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Neurobiol, Brain Res Inst, Los Angeles, CA 90073 USA. W Los Angeles Vet Adm Med Ctr, Los Angeles, CA 90073 USA. RP Tonini, M (reprint author), Univ Pavia, Dept Internal Med & Therapeut, Div Pharmacol & Toxicol, Piazza Botta 10, I-27100 Pavia, Italy. FU NIDDK NIH HHS [DK 41301, DK 54155] NR 18 TC 29 Z9 29 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD DEC PY 1998 VL 358 IS 6 BP 686 EP 689 DI 10.1007/PL00005313 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 147WH UT WOS:000077520200014 PM 9879730 ER PT J AU Bernstein, HG Keilhoff, G Seidel, B Stanarius, A Huang, PL Fishman, MC Reiser, M Bogerts, B Wolf, G AF Bernstein, HG Keilhoff, G Seidel, B Stanarius, A Huang, PL Fishman, MC Reiser, M Bogerts, B Wolf, G TI Expression of hypothalamic peptides in mice lacking neuronal nitric oxide synthase: Reduced beta-END immunoreactivity in the arcuate nucleus SO NEUROENDOCRINOLOGY LA English DT Article DE nitric oxide synthase; molecular neuroendocrinology; neurophysin; corticotropin-releasing hormone; pro-opiomelanocortin; beta-endorphin; immunocytochemistry; in situ hybridization; mouse ID CORTICOTROPIN-RELEASING HORMONE; PARAVENTRICULAR NUCLEUS; MAGNOCELLULAR NEURONS; NADPH-DIAPHORASE; RAT; PITUITARY; BRAIN; INVOLVEMENT; VASOPRESSIN; OXYTOCIN AB The gas nitric oxide (NO) is an important messenger in brain signaling. Along with many other functions, NO is thought to influence the expression and/or release of various hypothalamic hormones (corticotropin-releasing hormone (CRH), gonadotropin-releasing hormone (GnRH) and vasopressin). To learn more about the role of NO in neuroendocrine mechanisms, we studied in mutant mice lacking neuronal isoform of NO synthase (nNOS) the cellular expression of CRH, neurophysin (the carrier protein of vasopressin/oxytocin) and proopiomelanocortin (POMC), as well as of the POMC-derived peptides beta-endorphin (beta-END), alpha-melanocyte-stimulating hormone (alpha-MSH) and corticotropin (ACTH) by use of immunohistochemistry and in situ hybridization. Additionally, the remaining NO-generating capacities of the nNOS minus mice were investigated by NADPH-diaphorase histochemistry and citrulline immunohistochemistry as well as by immunohistochemical localization and Western blot analysis of endothelial NOS (eNOS) and nNOS isoforms. Amongst all hypothalamic peptides under investigation, only beta-END was found to be altered in mutant mice. A morphometric analysis of beta-END producing neurons of the arcuate nucleus revealed that significantly less cells were immunoreactive in mutant mice, whereas the expression of the precursor POMC as well as of other POMC-derived peptides was found to be unchanged. In addition to that, fewer beta-END-immunoreactive fibers were found in the paraventricular nucleus of nNOS minus mice in comparison to wild-type animals. Hence, the reduction of hypothalamic beta-END is probably a posttranslational event that might reflect a disturbed endorphinergic innervation of those hypothalamic neurons which normally express nNOS. C1 Univ Magdeburg, Dept Psychiat, D-39120 Magdeburg, Germany. Univ Magdeburg, Inst Med Neurobiol, D-39120 Magdeburg, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. RP Bernstein, HG (reprint author), Univ Magdeburg, Dept Psychiat, Leipziger Str 44, D-39120 Magdeburg, Germany. EM hans-gert.bernstein@medizin.uni-magdeburg.de NR 37 TC 25 Z9 25 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD DEC PY 1998 VL 68 IS 6 BP 403 EP 411 DI 10.1159/000054390 PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 152WH UT WOS:000077799800006 PM 9873204 ER PT J AU Hosler, BA Sapp, PC Berger, R O'Neill, G Bejaoui, K Ben Hamida, M Hentati, F Chin, W McKenna-Yasek, D Haines, JL Patterson, D Horvitz, HR Brown, RH AF Hosler, BA Sapp, PC Berger, R O'Neill, G Bejaoui, K Ben Hamida, M Hentati, F Chin, W McKenna-Yasek, D Haines, JL Patterson, D Horvitz, HR Brown, RH TI Refined mapping and characterization of the recessive familial amyotrophic lateral sclerosis locus (ALS2) on chromosome 2q33 SO NEUROGENETICS LA English DT Article DE amyotrophic lateral sclerosis; yeast artificial chromosome contig; mapping ID YEAST ARTIFICIAL CHROMOSOMES; MULTILOCUS LINKAGE ANALYSIS; RADIATION HYBRID MAP; HUMAN GENOME; XANTHINE DEHYDROGENASE; MOLECULAR-CLONING; ALDEHYDE OXIDASE; RAPID METHOD; GENE; CONSTRUCTION AB Amyotrophic lateral sclerosis (ALS) is a progressive degenerative neuromuscular disease that shows familial, autosomal dominant inheritance in 10%-15% of cases. Previous genetic analysis of one large family linked a recessive form of familial ALS (FALS-AR type 3) to the chromosome 2q33-35 region. Using additional polymorphic markers, we have narrowed the size of the linked region to approximately 1.7 cM by linkage and haplotype analysis. We have also established a yeast artificial chromosome contig across the locus that covers an approximate physical distance of 3 million bases. Based on this contig, genes and expressed sequences that map near the 2q33 region have been examined to determine whether they are located within this ALS2 candidate locus. Five identified genes and 34 expressed sequence tags map within the region defined by crossover analysis and merit further consideration as candidate genes for this disease. C1 Massachusetts Gen Hosp, Serv Neurol, Cecil B Day Lab Neuromuscular Res, Cambridge, MA 02139 USA. MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. Eleanor Roosevelt Inst Canc Res, Denver, CO 80206 USA. Inst Natl Neurol, Tunis 1006, Tunisia. Vanderbilt Univ, Med Ctr, Nashville, TN 37232 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. RP Brown, RH (reprint author), Massachusetts Gen Hosp, Serv Neurol, Cecil B Day Lab Neuromuscular Res, MGH-E,Bldg 149,13th St, Cambridge, MA 02139 USA. RI Haines, Jonathan/C-3374-2012 FU NINDS NIH HHS [1F32NS10064-01, 1PO1NS31248-02] NR 48 TC 19 Z9 19 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1364-6745 J9 NEUROGENETICS JI Neurogenetics PD DEC PY 1998 VL 2 IS 1 BP 34 EP 42 DI 10.1007/s100480050049 PG 9 WC Genetics & Heredity; Clinical Neurology SC Genetics & Heredity; Neurosciences & Neurology GA 162NN UT WOS:000078353400004 PM 9933298 ER PT J AU Neary, D Snowden, JS Gustafson, L Passant, U Stuss, D Black, S Freedman, M Kertesz, A Robert, PH Albert, M Boone, K Miller, BL Cummings, J Benson, DF AF Neary, D Snowden, JS Gustafson, L Passant, U Stuss, D Black, S Freedman, M Kertesz, A Robert, PH Albert, M Boone, K Miller, BL Cummings, J Benson, DF TI Frontotemporal lobar degeneration - A consensus on clinical diagnostic criteria SO NEUROLOGY LA English DT Article ID SLOWLY PROGRESSIVE APHASIA; NON-ALZHEIMER TYPE; MOTOR-NEURON DISEASE; GENERALIZED DEMENTIA; LANGUAGE IMPAIRMENT; EMISSION TOMOGRAPHY; PICKS DISEASE; ATROPHY; FEATURES; PET AB Objective: To improve clinical recognition and provide research diagnostic criteria for three clinical syndromes associated with frontotemporal lobar degeneration. Methods: Consensus criteria for the three prototypic syndromes-frontotemporal dementia, progressive nonfluent aphasia, and semantic dementia-were developed by members of an international workshop on frontotemporal lobar degeneration. These criteria build on earlier published clinical diagnostic guidelines for frontotemporal dementia produced by some of the workshop members. Results: The consensus criteria specify core and supportive features for each of the three prototypic clinical syndromes and provide broad inclusion and exclusion criteria for the generic entity of frontotemporal lobar degeneration. The criteria are presented in lists, and operational definitions for features are provided in the text. Conclusions: The criteria ought to provide the foundation for research work into the neuropsychology, neuropathology, genetics, molecular biology, and epidemiology of these important clinical disorders that account for a substantial proportion of cases of primary degenerative dementia occurring before the age of 65 years. C1 Manchester Royal Infirm, Dept Neurol, Manchester M13 9WL, Lancs, England. Univ Lund Hosp, Lund, Sweden. Baycrest Ctr Geriatr Care, Rotman Res Inst, Toronto, ON, Canada. Univ Toronto, Toronto, ON, Canada. Univ Western Ontario, London, ON, Canada. Univ Nice, Sch Med, F-06108 Nice 2, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. RP Neary, D (reprint author), Manchester Royal Infirm, Dept Neurol, Oxford Rd, Manchester M13 9WL, Lancs, England. OI Black, Sandra/0000-0001-7093-8289; Snowden, Julie/0000-0002-3976-4310 FU NIA NIH HHS [AG 10123]; Wellcome Trust NR 48 TC 3068 Z9 3180 U1 15 U2 129 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 1998 VL 51 IS 6 BP 1546 EP 1554 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 147DX UT WOS:000077473900009 PM 9855500 ER PT J AU Kelly, PJ Toker, DE McDonald, CT Niles, J AF Kelly, PJ Toker, DE McDonald, CT Niles, J TI Granulomatous compressive thoracic myelopathy as the initial manifestation of Wegener's granulomatosis SO NEUROLOGY LA English DT Article ID INVOLVEMENT C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neuropathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. RP Kelly, PJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Wang ACC 835,Fruit St, Boston, MA 02114 USA. RI Newman-Toker, David/C-6083-2008 OI Newman-Toker, David/0000-0003-2789-4115 NR 7 TC 8 Z9 8 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 1998 VL 51 IS 6 BP 1769 EP 1770 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 147DX UT WOS:000077473900060 PM 9855551 ER PT J AU Hsueh, YP Sheng, M AF Hsueh, YP Sheng, M TI Eph receptors, ephrins, and PDZs gather in neuronal synapses SO NEURON LA English DT Editorial Material ID FASCICLIN-II C1 Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA 02114 USA. RP Hsueh, YP (reprint author), Howard Hughes Med Inst, Boston, MA 02114 USA. OI Hsueh, Yi-Ping/0000-0002-0866-6275 NR 11 TC 14 Z9 14 U1 0 U2 0 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 1998 VL 21 IS 6 BP 1227 EP 1229 DI 10.1016/S0896-6273(00)80641-8 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 154VR UT WOS:000077910600004 PM 9883715 ER PT J AU Fox, JW Lamperti, ED Eksioglu, YZ Hong, SE Feng, YY Graham, DA Scheffer, IE Dobyns, WB Hirsch, BA Radtke, RA Berkovic, SF Huttenlocher, PR Walsh, CA AF Fox, JW Lamperti, ED Eksioglu, YZ Hong, SE Feng, YY Graham, DA Scheffer, IE Dobyns, WB Hirsch, BA Radtke, RA Berkovic, SF Huttenlocher, PR Walsh, CA TI Mutations in filamin 1 prevent migration of cerebral cortical neurons in human periventricular heterotopia SO NEURON LA English DT Article ID ACTIN-BINDING PROTEIN; GENE; KINASE; IDENTIFICATION; MACROPHAGES; ABP-280; REGION; LOCUS; MICE; XQ28 AB Long-range, directed migration is particularly dramatic in the cerebral cortex, where postmitotic neurons generated deep in the brain migrate to form layers with distinct form and function. In the X-linked dominant human disorder periventricular heterotopia (PH), many neurons fail to migrate and persist as nodules lining the ventricular surface. Females with PH present with epilepsy and other signs, including patent ductus arteriosus and coagulopathy, while hemizygous males die embryonically. We have identified the PH gene as filamin I (FLN1), which encodes an actin-cross-linking phosphoprotein that transduces ligand-receptor binding into actin reorganization, and which is required for locomotion of many cell types. FLN1 shows previously unrecognized, high-level expression in the developing cortex, is required for neuronal migration to the cortex, and is essential for embryogenesis. C1 Harvard Inst Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Div Neurogenet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Univ Melbourne, Dept Neurol, Austin & Repatriat Med Ctr, Heidelberg, Vic 3084, Australia. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Human Genet, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. Duke Univ, Med Ctr, Div Neurol, Durham, NC 27710 USA. Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. RP Walsh, CA (reprint author), Harvard Inst Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Div Neurogenet, Boston, MA 02115 USA. EM cwalsh@bidmc.harvard.edu RI Scheffer, Ingrid/G-1668-2013; OI Scheffer, Ingrid/0000-0002-2311-2174; Berkovic, Samuel/0000-0003-4580-841X; Dobyns, William/0000-0002-7681-2844 FU NINDS NIH HHS [R01 NS35129] NR 56 TC 500 Z9 512 U1 2 U2 11 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 1998 VL 21 IS 6 BP 1315 EP 1325 DI 10.1016/S0896-6273(00)80651-0 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 154VR UT WOS:000077910600014 PM 9883725 ER PT J AU Tootell, RBH Hadjikhani, N Hall, EK Marrett, S Vanduffel, W Vaughan, JT Dale, AM AF Tootell, RBH Hadjikhani, N Hall, EK Marrett, S Vanduffel, W Vaughan, JT Dale, AM TI The retinotopy of visual spatial attention SO NEURON LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; SELECTIVE ATTENTION; NEURAL MECHANISMS; CEREBRAL-CORTEX; HUMAN BRAIN; VISUOSPATIAL ATTENTION; EXTRASTRIATE CORTEX; FUNCTIONAL-ANALYSIS; BLOOD-FLOW; AREAS V1 AB We used high-field (3T) functional magnetic resonance imaging (fMRI) to label cortical activity due to visual spatial attention, relative to flattened cortical maps of the retinotopy and visual areas from the same human subjects. In the main task, the visual stimulus remained constant, but covert visual spatial attention was varied in both location and load. In each of the extrastriate retinotopic areas, we found MR increases at the representations of the attended target. Similar but smaller increases were found in V1. Decreased MR levels were found in the same cortical locations when attention was directed at retinotopically different locations. In and surrounding area MT+, MR increases were lateralized but not otherwise retinotopic. At the representation of eccentricities central to that of the attended targets, prominent MR decreases occurred during spatial attention. C1 Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. RP Tootell, RBH (reprint author), Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. RI Hadjikhani, Nouchine/C-2018-2008; Dale, Anders/A-5180-2010; OI Hadjikhani, Nouchine/0000-0003-4075-3106; Marrett, Sean/0000-0001-8179-6511 FU NEI NIH HHS [EY07980] NR 64 TC 447 Z9 452 U1 4 U2 19 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 1998 VL 21 IS 6 BP 1409 EP 1422 DI 10.1016/S0896-6273(00)80659-5 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 154VR UT WOS:000077910600022 PM 9883733 ER PT J AU Hsu, DW Efird, JT Hedley-Whyte, ET AF Hsu, DW Efird, JT Hedley-Whyte, ET TI MIB-1(Ki-67) index and transforming growth factor-alpha (TGF alpha) immunoreactivity are significant prognostic predictors for meningiomas SO NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY LA English DT Article DE meningioma; MIB-1; transforming growth factor-alpha; proliferative index; immunocytochemistry ID MONOCLONAL-ANTIBODY KI-67; HUMAN-BRAIN-TUMORS; CELL NUCLEAR ANTIGEN; PROLIFERATING CELLS; INTRACRANIAL MENINGIOMA; SURGICAL-TREATMENT; LABELING INDEXES; FACTOR RECEPTORS; HUMAN GLIOMAS; MOUSE UTERUS AB Mitotic index > 6, proliferating cell nuclear antigen (PCNA) index > 5%, high tumour grade and absence of progesterone receptors (PR) are significant predictors for poor outcome in meningiomas, Since MIB-1 (Ki-67) is a more specific cell proliferation marker, and overexpression of TGF-alpha is also associated with tumour progression, we compared the prognostic significance of these factors with the other indices. Intracranial meningiomas from 21 men and 36 women (age 54.5 +/- 1.7, mean +/- SEM) were classified as 24 benign, 24 atypical and nine malignant. Twenty-one of the 57 tumours recurred (mean interval to recurrence was 57.3 +/- 13.1 months). The mean follow-up period for patients without tumour recurrence was 81.9 +/- 8.7 months. MIB-1 labelling index (LI) was expressed as percentage of labelled nuclei to total tumour nuclei counted in the most densely labelled areas. Analysis of variance revealed significant differences between tumour grades for MIB-1 labelling indices (0.75 +/- 0.21 for benign, 3.2 +/- 0.57 for atypical, 6.04 +/- 1.48 for malignant: P less than or equal to 0.0066), and between malignant and non-malignant meningiomas for TGF alpha staining scores (P less than or equal to 0.029). MIB-1 LI also correlated with mitotic and PCNA indices (P less than or equal to 0.0001), but not with age of the patients. Male patients had higher tumour MIB-1 LI than females (P less than or equal to 0.0128). Univariate analysis indicated that MIB-1 LI > 3%, TGF alpha score > 4 (scoring scale 0-5), mitotic index > 6, and negative PR status were significant factors for worse outcome. Higher MIB-1 LI, TGF alpha score and mitotic index as continuous variables were also significant negative predictors. With multivariate analysis, both MIB-1 LI and TGF alpha score remained significant factors when paired with all other variables: TGF alpha or MIB-1 LI, respectively, mitosis, PCNA, tumour grade, PR status, age, sex, postoperative radiation therapy. We conclude that MIB-1 LI and TGF alpha score are important independent prognostic indicators for patients with meningiomas. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hsu, DW (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 3, Boston, MA 02114 USA. NR 52 TC 61 Z9 64 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0305-1846 J9 NEUROPATH APPL NEURO JI Neuropathol. Appl. Neurobiol. PD DEC PY 1998 VL 24 IS 6 BP 441 EP 452 PG 12 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 153QX UT WOS:000077844800003 PM 9888154 ER PT J AU Peskind, ER Elrod, R Dobie, DJ Pascualy, M Petrie, E Jensen, C Brodkin, K Murray, S Veith, RC Raskind, MA AF Peskind, ER Elrod, R Dobie, DJ Pascualy, M Petrie, E Jensen, C Brodkin, K Murray, S Veith, RC Raskind, MA TI Cerebrospinal fluid epinephrine in Alzheimer's disease and normal aging SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE epinephrine; adrenergic; cerebrospinal fluid; Alzheimer's disease; yohimbine; clonidine; aging ID TYROSINE-HYDROXYLASE ACTIVITY; ADRENERGIC-RECEPTORS; RAT-BRAIN; NEURONS; PLASMA; NOREPINEPHRINE; YOHIMBINE; CATECHOLAMINES; PROPRANOLOL; DYSFUNCTION AB Central nervous system (CNS) adrenergic systems are involved in regulation of behavior and blood pressure. The effects of Alzheimer's disease (AD) and normal aging on resting CNS adrenergic activity were estimated by measuring cerebrospinal fluid (CSF) epinephrine (EPI) concentrations in 74 persons with AD, 42 cognitively normal healthy older persons, and 54 healthy young persons. The responsiveness of CSF EPI to the alpha-2 adrenergic antagonist yohimbine and the alpha-2 adrenergic agonist clonidine teas measured in smaller subject groups. Resting CSF EPI was higher in AD than in older or young subjects, and increased with dementia severity in AD subjects. There was Mo relationship between resting CSF EPI and blood pressure. CSF EPI increased following yohimbine in AD and older subjects but not in young subjects. CSF EPI was unaffected by clonidine in all subject groups. The agitation increase following yohimbine was substantially greater in AD subjects than in older or young subjects. CNS adrenergic activity seems increased in AD, may further increase as AD progresses, and may be involved in the pathophysiology of agitation. (C) 1998 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. C1 VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. Mental Hlth Serv, Seattle, WA USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Peskind, ER (reprint author), VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, 166 MIRECC,1660 S Columbian Way, Seattle, WA 98108 USA. NR 32 TC 27 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 1998 VL 19 IS 6 BP 465 EP 471 DI 10.1016/S0893-133X(98)00054-2 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 128TX UT WOS:000076423600002 PM 9803422 ER PT J AU Andreassen, OA Ferrante, RJ Beal, MF Jorgensen, HA AF Andreassen, OA Ferrante, RJ Beal, MF Jorgensen, HA TI Oral dyskinesias and striatal lesions in rats after long-term co-treatment with haloperidol and 3-nitropropionic acid SO NEUROSCIENCE LA English DT Article DE neuroleptics; energy impairment; vacuous chewing movements; neurodegeneration; basal ganglia; tardive dyskinesia ID VACUOUS CHEWING MOVEMENTS; TARDIVE-DYSKINESIA; OXIDATIVE STRESS; EXTRACELLULAR GLUTAMATE; NEURONS; SCHIZOPHRENIA; PERSISTENT; AGE; PATHOPHYSIOLOGY; MECHANISMS AB The pathophysiologic basis of tardive dyskinesia remains unclear. It has been proposed that tardive dyskinesia may be a result of excitotoxic neurodegeneration in the striatum caused by a neuroleptic-induced increase in striatal glutamate release and impaired energy metabolism To investigate this hypothesis, haloperidol decanoate (38 mg/kg/four weeks intramuscularly) and the succinate dehydrogenase inhibitor 3-nitropropionic acid (8 mg/kg/day via subcutaneous osmotic mini-pumps), were administered alone or together for 16 weeks to four-months-old rats. Control rats received sesame oil intramuscularly and had empty plastic tubes subcutaneously. Vacuous chewing movements, a putative analogue to human tardive dyskinesia, were recorded during and after drug treatment. Haloperidol alone, 3-nitropropionic acid alone, and 3-nitropropionic acid+haloperidol treatments induced an increase in vacuous chewing movements. However, Vacuous chewing movements were more pronounced and appeased earlier in rats treated with 3-nitropropionic acid+haloperidol. After drug withdrawal, increases in vacuous chewing movements persisted for 16 weeks in the haloperidol alone and 3-nitropropionic acid+haloperidol group and for four weeks in the 3-nitropropionic acid alone group. Brains from each group were analysed for histopathological alterations. Bilateral striatal lesions were present only in rats with high levels of vacuous chewing movements in the 3-nitropropionic acid+haloperidol-treated rats. Nerve cell depletion and astrogliosis were prominent histopathologic features. There was selective neuronal sparing of both large- and medium-sized aspiny striatal neurons. These results suggest that mild mitochondrial impairment in combination with neuroleptics results in striatal excitotoxic neurodegeneration which may underlie the development of persistent vacuous chewing movements in rats and possibly irreversible tardive dyskinesia in humans. (C) 1998 IBRO. Published by Elsevier Science Ltd. C1 Univ Bergen, Sandviken Hosp, Dept Physiol, Bergen, Norway. Univ Bergen, Sandviken Hosp, Dept Psychiat, Bergen, Norway. Bedford VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bedford, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Andreassen, OA (reprint author), Univ Bergen, Dept Physiol, Arstadveien 19, N-5009 Bergen, Norway. FU NIA NIH HHS [1P30AG13846, AG12922]; NINDS NIH HHS [NS35255] NR 46 TC 29 Z9 29 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD DEC PY 1998 VL 87 IS 3 BP 639 EP 648 DI 10.1016/S0306-4522(98)00160-2 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 126AJ UT WOS:000076270200012 PM 9758230 ER PT J AU Nguyen, QD Foster, CS AF Nguyen, QD Foster, CS TI Ciliary body melanoma masquerading as chronic uveitis SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article; Proceedings Paper CT American-Uveitis-Society Meeting CY OCT 27, 1997 CL SAN FRANCISCO, CALIFORNIA SP Amer Uveitis Soc DE ciliary body; melanoma; masquerade; uveitis AB Purpose: To report a case of ciliary body melanoma that masqueraded as chronic uveitis. Methods: A patient experienced persistent unilateral panuveitis and elevated intraocular pressure. Inflammation and pressure worsened after cataract extraction and lens implantation. Diagnostic vitrectomy was non-revealing. Results: Repeat vitrectomy and lens implant removal revealed a ciliary body mass, suggestive of melanoma. Ultrasonography and clinical evaluation by the retinal oncologists supported this diagnosis. The uveitis persisted despite aggressive medical treatments, including methotrexate. Proton beam irradiation of the melanoma led to resolution of uveitis and restoration of normal intraocular pressure. Conclusion: Ciliary body melanoma can present as chronic uveitis and refractory glaucoma. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. NR 3 TC 7 Z9 7 U1 0 U2 0 PU AEOLUS PRESS PI BUREN PA PO BOX 740, 4116 ZJ BUREN, NETHERLANDS SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD DEC PY 1998 VL 6 IS 4 BP 253 EP 256 DI 10.1076/ocii.6.4.253.4031 PG 4 WC Ophthalmology SC Ophthalmology GA 159NX UT WOS:000078181300006 PM 9924921 ER PT J AU Grossbard, ML Multani, PS AF Grossbard, ML Multani, PS TI Clinical status and optimal use of rituximab for B-cell lymphomas - The McLaughlin et al article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MONOCLONAL-ANTIBODY; THERAPY; IDEC-C2B8; SENSITIZES C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Grossbard, ML (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI HUNTINGTON PA 17 PROSPECT ST, HUNTINGTON, NY 11743 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD DEC PY 1998 VL 12 IS 12 BP 1769 EP 1770 PG 2 WC Oncology SC Oncology GA 151NT UT WOS:000077727400016 ER PT J AU Hallberg, K Hammarstrom, KJ Falsen, E Dahlen, G Gibbons, RJ Hay, DI Stromberg, N AF Hallberg, K Hammarstrom, KJ Falsen, E Dahlen, G Gibbons, RJ Hay, DI Stromberg, N TI Actinomyces naeslundii genospecies 1 and 2 express different binding specificities to N-acetyl-beta-D-galactosamine, whereas Actinomyces odontolyticus expresses a different binding specificity in colonizing the human mouth SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE Actinomyces; adhesion; acidic proline-rich protein; saliva ID PROLINE-RICH PROTEINS; ROOT SURFACE CARIES; VISCOSUS T14V; DENTAL PLAQUE; COAGGREGATION; FIMBRIAE; STRAINS; HEMAGGLUTINATION; POLYMORPHISMS; BACTERIOLOGY AB A total of 102 strains of Actinomyces were isolated from teeth, buccal mucosa and tongue in eight individuals. The isolates were characterized by multivariate statistical analyses of phenotypic characteristics, serotyping and binding to linked galactosamine (N-acetyl-beta-D-galactosamine) and acidic proline-rich protein structures. Based on these characteristics, isolates were classified into three major groups: (i) Isolates of Actinomyces ces naeslundii genospecies 2 were the dominant species on teeth and buccal mucosa and bound commonly to N-acetyl-beta-D-galactosamine (63 of 63 isolates) and acidic proline-rich proteins (63 of 63 isolates), regardless of tissue origin. They all exhibited a N-acetyl-beta-D-galactosamine binding specificity signified by N-acetyl-beta-D-galactosamine-inhibitable coaggregation with the streptococcal strains LVG1. GVE1. 24892 and MPBI; (ii) Isolates of A. naeslundii gnospecies 1 were prevalent on teeth in certain individuals and bound commonly to N-acetyl-beta-D-galactosamine (20 of 20 isolates), but less commonly to acidic proline-rich proteins (5 of 20 isolates). They all possessed another iv-acetyl-P-D-galactosamine specificity, i.e. N-acetyl-beta-D-galactosamine-inhibitable coaggregation with the same streptococcal strains except for strain MPB 1; (iii) Isolates of Actinomyces ccs odontolyticus, the dominant species on the tongue(l7 of 19 isolates), bound commonly to unknown structures on streptococci (17 of 19 isolates) but rarely to N-acetyl-beta-D-galactosamine (2 of 19 isolates) or acidic proline-rich proteins (3 of 19 isolates). In conclusion A. naeslundii genospecies 1 and 9 exhibit different patterns of N-acetyl-beta-D-galactosamine and acidic proline-rich protein specificities to colonize dental and buccal mucosa surfaces, whereas A. odontolyticus utilizes another specificity to colonize the tongue. C1 Umea Univ, Dept Cariol, S-90187 Umea, Sweden. Univ Gothenburg, Dept Periodontol, Gothenburg, Sweden. Univ Gothenburg, Dept Oral Microbiol, Gothenburg, Sweden. Forsyth Dent Ctr, Boston, MA 02115 USA. Univ Gothenburg, Culture Collect, Gothenburg, Sweden. RP Stromberg, N (reprint author), Umea Univ, Dept Cariol, S-90187 Umea, Sweden. NR 47 TC 22 Z9 22 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 1998 VL 13 IS 6 BP 327 EP 336 PG 10 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA 139YW UT WOS:000077059700001 PM 9872107 ER PT J AU Wang, MB Billings, KR Venkatesan, N Hall, FL Srivatsan, ES AF Wang, MB Billings, KR Venkatesan, N Hall, FL Srivatsan, ES TI Inhibition of cell proliferation in head and neck squamous cell carcinoma cell lines with antisense cyclin D1 SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT 99th Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 16-22, 1995 CL NEW ORLEANS, LOUISIANA SP Amer Acad Otolaryngol Head & Neck Surg ID MOLECULAR-CLONING; ONCOGENE; CANCER; GENE; AMPLIFICATION; EXPRESSION; CHROMOSOME-11Q13; PHOSPHORYLATION; PROTEIN; REGION AB Cyclin D1 and cyclin G are essential regulatory factors in the progression of the cell cycle from GO through G1 and S phase. Aberrations in expression of these cyclins may lead to dysregulated cellular proliferation that could result in neoplasia. Amplification and overexpression of cyclin D1 have been observed in many human cancers, whereas cyclin G is a new cyclin recently described in osteosarcoma cells. This study was performed to determine whether these cyclins were amplified in head and neck squamous cell carcinoma (HNSCC) tumors. Polymerase chain reaction of DNA extracted from 22 HNSCC primary tumors and three HNSCC cell lines did not reveal amplification of cyclin D1 in any of the tumor samples. Southern blot analysis identified amplification of cyclin D1 in a single tumor. Amplification of cyclin G was not observed in any of the tumors by Southern blot hybridization with a cyclin G probe. HNSCC cell lines transfected with antisense cyclin D1 were tested for cell proliferation by the incorporation of H-3-thymidine into cells grown in serum-free media. By 72 hours of incubation, there was a greater than 30% reduction in proliferation of cells transfected with antisense cyclin D1 as compared with non-transfected control cells. The results indicate that cyclin D1 may play an important role in the growth and proliferation of HNSCC cells. C1 Univ Calif Los Angeles, Med Ctr, Div Head & Neck Surg, Sch Med,W Los Angeles Vet Adm Med Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Surg, W Los Angeles Vet Adm Med Ctr, Los Angeles, CA 90095 USA. Childrens Hosp Los Angeles, Div Orthoped Surg, Los Angeles, CA 90027 USA. RP Wang, MB (reprint author), Univ Calif Los Angeles, Med Ctr, Div Head & Neck Surg, Sch Med,W Los Angeles Vet Adm Med Ctr, CHS 62-132,10833 LeConte Ave, Los Angeles, CA 90095 USA. NR 23 TC 27 Z9 27 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 1998 VL 119 IS 6 BP 593 EP 599 DI 10.1016/S0194-5998(98)70017-8 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 146CE UT WOS:000077409400007 PM 9852531 ER PT J AU Bhattacharyya, N Norris, CM Colevas, AD Chasse, TA AF Bhattacharyya, N Norris, CM Colevas, AD Chasse, TA TI Intramucosal spread of malignant melanoma of the oral cavity SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID MUCOSAL MELANOMA; HEAD; NECK C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. New England Deaconess Hosp, Dept Otolaryngol, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bhattacharyya, N (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 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 1998 VL 119 IS 6 BP 711 EP 711 PG 1 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 146CE UT WOS:000077409400033 PM 9852557 ER PT J AU Zupancic, JAF Richardson, DK AF Zupancic, JAF Richardson, DK TI Characterization of the triage process in neonatal intensive care SO PEDIATRICS LA English DT Article DE economics; resource utilization; infant; newborn; neonatal intensive care; cost analysis ID RESPIRATORY-DISTRESS-SYNDROME; BIRTH-WEIGHT INFANTS; COST; SURFACTANT; THERAPY; CHARGES; SYSTEM; INDEX AB Objective. Despite intense interest in allocation of resources to neonatal intensive care, no description exists of resource use by the large numbers of newborns admitted for triage, the process of short-term evaluation and management of infants after delivery. This study characterized the triage phase of neonatal cave with respect to infant demographics, risk factors for illness, and the course of the hospital admission. We hypothesized that triage infants were responsible for a significant fraction of total intensive care resource utilization, and that patterns of use were predictable. Design. Cross-sectional cost analysis of prospectively collected data. Participants. Data were collected prospectively on 2486 inborn infants admitted to two neonatal intensive care units (NICUs) for <24 hours and subsequently discharged to routine care. Over the 11-month study period, these two hospitals delivered 15 097 live births and admitted a further 1837 infants for nontriage NICU care. Interventions. On a 50% random subsample, we calculated severity of illness using the Score for Neonatal Acute Physiology (SNAP) and applied a NICU resource checklist. Daily NICU workload was estimated according to the number and labor intensity of NICU admissions using Medicus and SNAP. Charges were obtained from patient-level item charge records and converted to costs using Medicare ratios of costs to charges. Length of stay (LOS) and costs for triage were correlated with diagnoses, perinatal descriptors, severity of illness, and markers of concurrent NICU workload using stepwise regression. Results, Mean birth weight for triage infants was 3367 g (standard deviation, 600 g) and mean gestational age 39.1 weeks (standard deviation, 1.8 weeks). The predominant reasons for evaluation were exclusion of sepsis (34%), birth complications including meconium aspiration, perinatal depression and trauma (24%), and transitional respiratory distress (23%). Severity illness, as measured by SNAP, was minimal, with 70% having scores of 0, indicating no derangement. Only 6% experienced depressed 5-minute Apgar scores (<7), and 80% required no delivery room resuscitation. The most frequent forms of resource use were antibiotic administration (34%), placement of a peripheral intravenous line (40%), cardiac monitoring (53%) and external warming (26%), Median LOS was 102 minutes, corresponding over the study period to 2% of total NICU hours but 7% of NICU days charged. Median cost was $870, with aggregate costs accounting for a total of 9.5% of total NICU costs. In the multivariate model, LOS was increased by respiratory diagnosis or hypoglycemia, severity of illness, lower gestational age, the need for intravenous placement, daytime shift, hospital, and lower acuity of concurrent NICU admissions (R-2 = 0.24). Conclusions. Neonatal triage is a low-acuity but time-intensive process that contributes significantly to total resource use by newborns because of the large numbers of infants involved. Both LOS and costs are affected not only by infant medical characteristics but also by nonmedical markers of unit structure, which may be amenable to change. This source of resource consumption should be recognized in future assessments of costs associated with neonatal intensive care. C1 Harvard Univ, Sch Med,Brigham & Womens Hosp, Beth Israel Deaconness Med Ctr, Dept Newborn Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Maternal & Child Hlth, Boston, MA 02115 USA. RP Richardson, DK (reprint author), Harvard Univ, Sch Med,Brigham & Womens Hosp, Beth Israel Deaconness Med Ctr, Dept Newborn Med, 330 Brookline Ave, Boston, MA 02115 USA. FU AHRQ HHS [R01 HS06123] NR 25 TC 19 Z9 20 U1 2 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD DEC PY 1998 VL 102 IS 6 BP 1432 EP 1436 DI 10.1542/peds.102.6.1432 PG 5 WC Pediatrics SC Pediatrics GA 144JR UT WOS:000077311500015 PM 9832581 ER PT J AU Pogue, BW Redmond, RW Trivedi, N Hasan, T AF Pogue, BW Redmond, RW Trivedi, N Hasan, T TI Photophysical properties of tin ethyl etiopurpurin I (SnET2) and tin octaethylbenzochlorin (SnOEBC) in solution and bound to albumin SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID PHOTODYNAMIC THERAPY; CELL; RAT AB The photophysical characteristics of two second-generation PDT photosensitizers, tin ethyl etiopurpurin I (SnET2) and tin octaethylbenzochlorin (SnOEBC), have been measured in homogeneous solution and when bound to bovine serum albumin (BSA), The ground state and triplet state absorption spectra have been characterized, as have triplet lifetimes and quantum yields for intersystem crossing, singlet oxygen formation and photobleaching. In total, these parameters provide a complete set of data that can be used to quantitatively compare the photosensitizing efficiencies of these molecules. The photobleaching quantum yield of SnET2 is increased dramatically when it is bound to BSA, thus limiting the production of singlet oxygen at incident fluences above 1 J/cm(2). In contrast, the quantum yield of photobleaching of SnOEBC is at least an order of magnitude lower than that of SnET2 under these conditions and does not significantly limit the photosensitization process for typical in vivo or in vitro fluences. This difference is expected to play a significant role in determining the relative photosensitizing ability of these compounds in vivo. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02114 USA. Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. RP Hasan, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02114 USA. FU NCI NIH HHS [R01 CA68524] NR 22 TC 32 Z9 36 U1 0 U2 1 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 1998 VL 68 IS 6 BP 809 EP 815 DI 10.1111/j.1751-1097.1998.tb05288.x PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 148QU UT WOS:000077544100005 PM 9867030 ER PT J AU McWatters, HG Saunders, DS AF McWatters, HG Saunders, DS TI Maternal temperature has different effects on the photoperiodic response and duration of larval diapause in blow fly (Calliphora vicina) strains collected at two latitudes SO PHYSIOLOGICAL ENTOMOLOGY LA English DT Article DE Calliphora vicina; critical daylength; geographical variation; larval diapause; maternal effect; photoperiodic response; temperature effects ID ROBINEAU-DESVOIDY DIPTERA; GEOGRAPHIC-VARIATION; REPRODUCTIVE DIAPAUSE; DROSOPHILA-TRIAURARIA; SENSITIVE STAGE; INDUCTION; INTENSITY; MOTH AB The blow fly Calliphora vicina Robineau-Desvoidy (Diptera: Calliphoridae) has a wide distribution across northern and temperate Europe. It has a facultative, maternally-induced larval diapause in response go short days. The photoperiodic response, measured at 15 and 20 degrees C, of two populations was compared. A southern population (originating at 51 degrees N) was sensitive to temperature at all daylengths; the incidence of diapause was greatly reduced at 20 degrees C compared with 15 degrees C. The photoperiodic response of a northern population (from 65 degrees N) was sensitive to temperature only in long days; in short days (< 14 h of light) the response of this strain was identical at each temperature. Variation in parental photoperiod and temperature were found to affect the duration of larval diapause, indicating a role for maternal effects in diapause intensity as well as incidence. However, the between-strain variation was greater than that within strains, indicating qualitative differences in diapause response. These differences may arise from the ecological conditions at the points of origin of the two strains. The northern strain from the harsher climate has a more intense diapause that follows a relatively temperature-insensitive photoperiodic response. In contrast, the southern strain has a shallow diapause and its photoperiodic response may be overridden by the experience of concurrent high temperature. C1 Univ Edinburgh, Inst Cell Anim & Populat Biol, Edinburgh, Midlothian, Scotland. RP McWatters, HG (reprint author), Massachusetts Gen Hosp, Lab Dev Chronobiol, Jackson 1226, Boston, MA 02114 USA. NR 37 TC 19 Z9 20 U1 4 U2 14 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0307-6962 J9 PHYSIOL ENTOMOL JI Physiol. Entomol. PD DEC PY 1998 VL 23 IS 4 BP 369 EP 375 DI 10.1046/j.1365-3032.1998.00101.x PG 7 WC Entomology SC Entomology GA 145FL UT WOS:000077360300010 ER PT J AU Rosenblatt, MR Olmstead, RE Iwamoto-Schaap, PN Jarvik, ME AF Rosenblatt, MR Olmstead, RE Iwamoto-Schaap, PN Jarvik, ME TI Olfactory thresholds for nicotine and menthol in smokers (abstinent and nonabstinent) and nonsmokers SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE olfaction; thresholds; nicotine; menthol; smoking; abstinence; odors ID NASAL PUNGENCY; PERCEPTION; CIGARETTES; TITRATION; SMOKING; ODOR AB Nonsmokers and smokers were compared for olfactory sensitivity to two odors associated with cigarettes: nicotine and menthol. Smokers were tested twice-while nonabstinent, and after 16-20 h of smoking abstinence. Smokers showed a higher olfactory threshold for nicotine than did nonsmokers, but the same threshold for menthol. Furthermore, when the smokers were abstinent, they showed a lower olfactory threshold for nicotine than when they were nonabstinent, but again, the same threshold for menthol. These results suggest a nicotine specific olfactory deficit in smokers that is reduced during abstinence. (C) 1998 Elsevier Science Inc. C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Psychopharmacol Unit, Los Angeles, CA 90073 USA. RP Olmstead, RE (reprint author), Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. NR 17 TC 11 Z9 12 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD DEC 1 PY 1998 VL 65 IS 3 BP 575 EP 579 DI 10.1016/S0031-9384(98)00193-0 PG 5 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 150HW UT WOS:000077659900023 PM 9877426 ER PT J AU Kosslyn, SM Thompson, WL Gitelman, DR Alpert, NM AF Kosslyn, SM Thompson, WL Gitelman, DR Alpert, NM TI Neural systems that encode categorical versus coordinate spatial relations: PET investigations SO PSYCHOBIOLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; HEMISPHERIC-SPECIALIZATION; CEREBRAL LATERALIZATION; HUMAN BRAIN; REPRESENTATIONS; ATTENTION; OBJECT; SIMULATIONS; NETWORK; MEMORY AB Participants received three sets of trials while regional cerebral blood flow was assessed using positron emission tomography (PET). In one set, the baseline, they responded when they detected a horizontal bar with an X either above or below it. In another set, the categorical spatial relations judgment condition, they decided whether the X was above or below the bar. In the third set, the coordinate spatial relations judgment condition, they decided whether the X was within 0.5 in, of the bar. In Experiment 1, the precise locations of the bars and X marks were varied, which required participants to focus attention selectively. Consistent with previous behavioral and neuropsychological findings, the left hemisphere was generally more activated during the categorical judgment task than during the coordinate judgment task, whereas the right hemisphere was generally more activated during the coordinate judgment task. In addition, these apparently simple tasks drew on large and different networks of areas. Experiment 2 was the same as Experiment 1 except that the stimuli were always in the same position and were presented very briefly. Three areas in the right parietal lobe were activated more by the coordinate task than by the categorical task in both experiments. In contrast, in neither experiment were any common areas activated more by the categorical task than by the coordinate task. C1 Harvard Univ, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NW Med Sch, Chicago, IL USA. RP Kosslyn, SM (reprint author), 830 William James Hall,33 Kirkland St, Cambridge, MA 02138 USA. NR 40 TC 72 Z9 74 U1 0 U2 0 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 USA SN 0889-6313 J9 PSYCHOBIOLOGY JI Psychobiology PD DEC PY 1998 VL 26 IS 4 BP 333 EP 347 PG 15 WC Psychology; Psychology, Multidisciplinary SC Psychology GA 163FA UT WOS:000078391900005 ER PT J AU Butler, SF Newman, FL Cacciola, JS Frank, A Budman, SH McLellan, AT Ford, S Blaine, J Gastfriend, D Moras, K Salloum, IM Barber, JP AF Butler, SF Newman, FL Cacciola, JS Frank, A Budman, SH McLellan, AT Ford, S Blaine, J Gastfriend, D Moras, K Salloum, IM Barber, JP TI Predicting Addiction Severity Index (ASI) Interviewer Severity Ratings for a computer-administered ASI SO PSYCHOLOGICAL ASSESSMENT LA English DT Article ID LINEAR-MODELS; RELIABILITY; VALIDITY AB The Addiction Severity Index (ASI) is a reliable and valid measure of problem severity among addicted patients. Concerns have been raised about the reliability of the Interviewer Severity Rating (ISR), a summary score for each of 7 domains. As part of an effort to build a computer-administered ASI, regression equations were developed to predict the ISR. Repeated resampling of a large dataset, consisting of 1,124 ASIs conducted by trained interviewers, permitted derivation of stable regression equations predicting the ISR for each ASI domain from patients' answers to preselected interview items. The resulting 7 Predicted Severity Ratings (PSRs) were tested on 8, standardized vignettes, with "gold standard," expert-generated ISRs. Reliabilities compared well with those of intensively trained interviewers. The PSRs could provide an alternative to potentially unreliable interviewer ratings, enhancing the ASI's role in treatment planning and treatment matching and make possible a computer-administered version of the ASI. C1 Innovat Training Syst, Newton, MA 02159 USA. Florida Int Univ, Hlth Serv Adm, Sch Policy & Management, Miami, FL 33199 USA. Vet Affairs Med Ctr, Dept Psychiat, Philadelphia, PA USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Swarthmore Coll, Psychol Serv, Swarthmore, PA 19081 USA. Brookside Hosp, Nashua, NH USA. NIDA, Treatment Res Branch, Lexington, KY 40583 USA. Massachusetts Gen Hosp, Addict Serv, Dept Psychiat, Boston, MA 02114 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Penn, Dept Psychiat, Ctr Psychotherapy Res, Philadelphia, PA 19104 USA. RP Butler, SF (reprint author), Innovat Training Syst, 199 Wells Ave,Suite 108, Newton, MA 02159 USA. EM sfbutler@aol.com OI Butler, Stephen/0000-0002-6132-5883; barber, jacques/0000-0002-8762-2595 NR 22 TC 18 Z9 18 U1 1 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD DEC PY 1998 VL 10 IS 4 BP 399 EP 407 DI 10.1037/1040-3590.10.4.399 PG 9 WC Psychology, Clinical SC Psychology GA 155RJ UT WOS:000077959900008 ER PT J AU Itzhak, Y Ali, SF Martin, JL Black, MD Huang, PL AF Itzhak, Y Ali, SF Martin, JL Black, MD Huang, PL TI Resistance of neuronal nitric oxide synthase-deficient mice to cocaine-induced locomotor sensitization SO PSYCHOPHARMACOLOGY LA English DT Article DE cocaine; locomotor activity; sensitization; nitric oxide; knockout mice ID INDUCED BEHAVIORAL SENSITIZATION; LONG-TERM POTENTIATION; EXCITATORY AMINO-ACIDS; NUCLEUS-ACCUMBENS; REVERSE TOLERANCE; AMPHETAMINE; DOPAMINE; MK-801; BRAIN; GLUTAMATE AB In brain, nitric oxide (NO) is considered as a retrograde messenger involved in synaptic plasticity. The present study was undertaken to investigate whether mice lacking the neuronal nitric oxide synthase (nNOS) gene are protected from cocaine-induced behavioral sensitization. Mice were administered, IP, either saline or cocaine (15 mg/kg) for 5 days. Sensitization was determined as an increase in cocaine-induced locomotor activity on day 5 compared with day 1 and an amplified response of cocaine-experienced mice to a challenge cocaine injection given after a 10-day drug free period (e.g., on day 15). To investigate the development of a context-dependent locomotion (conditioning), the responses of cocaine- and saline-experienced mice to a saline injection were determined on day 17. Male homozygote nNOS(-/-) mice were sensitive to the acute effect of cocaine (15 mg/kg) on day 1; however, they developed neither a sensitized response to cocaine ion day 5 and 15! nor a conditioned locomotion. Female homozygote nNOS(-/-) mice neither were responsive to 15 mg/kg cocaine on day 1, 5 and 15, nor did they develop a conditioned locomotion. In contrast, the same cocaine regimen delivered to male and female heterozygote nNOS(+/-) mice, and wild type mice (B6 J/sv129, C57BL/6 and sv129) resulted in sensitization to cocaine-induced locomotor activity and context-dependent locomotion. Investigation of [H-3]cocaine disposition in the striatum and frontal cortex of the mice revealed neither gender nor strain differences in the drug disposition. Also, no major difference in striatal dopaminergic markers between homozygote nNOS(-/-) and wild type mice was observed. The most significant distinction, however, was the finding that nNOS(-/-) mice are completely deficient in striatal nNOS binding sites. Taken together, our results suggest that the resistance of homozygote nNOS(-/-) mice to cocaine-induced behavioral sensitization is primarily due to the deletion of the nNOS gene. Considering the role of NO in synaptic plasticity, it is conceivable that reduced brain NOS activity blunts the processes that underlie the development of sensitization to cocaine. C1 Univ Miami, Sch Med, Dept Biochem & Mol Biol, Miami, FL 33101 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Itzhak, Y (reprint author), Univ Miami, Sch Med, Dept Biochem & Mol Biol, POB 016129, Miami, FL 33101 USA. FU NIDA NIH HHS [R01DA08584]; NINDS NIH HHS [NS33335] NR 34 TC 44 Z9 45 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD DEC PY 1998 VL 140 IS 3 BP 378 EP 386 DI 10.1007/s002130050779 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 147EP UT WOS:000077475600015 PM 9877018 ER PT J AU Allen, JP Mattson, ME Miller, WR Tonigan, JS Connors, GJ Rychtarik, RG Randall, CL Anton, RF Kadden, RM Litt, M Cooney, NL DiClemente, CC Carbonari, J Zweben, A Longabaugh, RH Stout, RL Donovan, D Babor, TF DelBoca, FK Rounsaville, BJ Carroll, KM Wirtz, PW AF Allen, JP Mattson, ME Miller, WR Tonigan, JS Connors, GJ Rychtarik, RG Randall, CL Anton, RF Kadden, RM Litt, M Cooney, NL DiClemente, CC Carbonari, J Zweben, A Longabaugh, RH Stout, RL Donovan, D Babor, TF DelBoca, FK Rounsaville, BJ Carroll, KM Wirtz, PW CA Project MATCH Res Grp TI Therapist effects in three treatments for alcohol problems SO PSYCHOTHERAPY RESEARCH LA English DT Article ID PROBLEM DRINKERS; COUNSELOR; BEHAVIOR; DRINKING; SUCCESS; MOTIVATION; OUTCOMES AB Prior research indicates that therapist effects can be sizeable in substance-abuse treatment. Therapist differences were examined within a multisite (N = 1726) randomized trial of three psychosocial treatments for alcohol problems: twelve-step facilitation (TSF), cognitive-behavioral skills training (CBT), and motivational enhancement therapy (MET). Therapists (N = 80) were nested within treatments, selected and trained for expertise in a specific approach. This report describes: (1) differences in therapist characteristics across the three treatments; (2) the magnitude of therapist effects within each treatment; and (3) exploratory analyses of therapist attributes associated with successful outcomes. Therapist characteristics differed between TSF and the other two conditions. Significant therapist effects were found in client satisfaction and outcomes, even after covarying for effects of treatment sites and client baseline characteristics. Specific therapist attributes were predictive of client outcomes. Outlier therapists whose caseloads showed unusually poor outcomes accounted for most of the observed effects. C1 NIAAA, Sci Commun Branch, Bethesda, MD 20892 USA. Univ New Mexico, Albuquerque, NM 87131 USA. Res Inst Addict, Buffalo, NY USA. Med Univ S Carolina, Charleston, SC 29425 USA. Vet Affairs Med Ctr, Charleston, SC 29403 USA. Univ Connecticut, Sch Med, Farmington, CT USA. Vet Affairs Connecticut Healthcare Syst, New Haven, CT USA. Yale Univ, Sch Med, New Haven, CT USA. Univ Houston, Houston, TX USA. Univ Wisconsin, Milwaukee, WI 53201 USA. Brown Univ, Providence, RI 02912 USA. Univ Washington, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Connecticut, Farmington, CT USA. Yale Univ, New Haven, CT USA. George Washington Univ, Washington, DC USA. RP Allen, JP (reprint author), NIAAA, Sci Commun Branch, Willco Bldg,Suite 409,6000 Execut Blvd, Bethesda, MD 20892 USA. RI Carroll, Kathleen/A-7526-2009; Cooney, Ned/C-5176-2014; OI Cooney, Ned/0000-0001-6698-8312; Carroll, Kathleen/0000-0003-3263-3374; Litt, Mark/0000-0002-8319-6090 NR 70 TC 87 Z9 87 U1 3 U2 13 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 1050-3307 J9 PSYCHOTHER RES JI Psychother. Res. PD WIN PY 1998 VL 8 IS 4 BP 455 EP 474 PG 20 WC Psychology, Clinical SC Psychology GA 148QE UT WOS:000077542700007 ER PT J AU Hahnfeldt, P Hlatky, L AF Hahnfeldt, P Hlatky, L TI Cell resensitization during protracted dosing of heterogeneous cell populations SO RADIATION RESEARCH LA English DT Article ID RADIATION-INDUCED APOPTOSIS; IONIZING-RADIATION; SUBLETHAL DAMAGE; MODEL; TUMOR; REDISTRIBUTION; CYCLE; RADIOTHERAPY; REPAIR; NUMBER AB When a tumor or other heterogeneous cell population is acutely exposed to ionizing radiation (or, for that matter, to chemotherapeutic agents or hyperthermia), cells that happen to be more sensitive will be preferentially removed, leaving behind a population more resistant as a whole. However, under broadly applicable assumptions, we here demonstrate mathematically that there is a natural tendency of the postirradiation population to recover from the irradiation in such a manner as to restore its original sensitivity composition, i.e. to undergo "resensitization". An important consequence in radiotherapy is that, if a fixed total radiation dose is delivered in a more protracted manner, e.g. as several fractions or as a continuous dose at low dose rate, resensitization occurring over the course of dose delivery will result in greater cell killing than would otherwise have occurred. That is, for a cell population with any form of diversity in radiosensitivity, the influence of redistribution is to make any prolonged dose more damaging than an acute dose of the same magnitude. This tendency toward an "inverse dose-rate effect" may be masked in practice by countervailing effects, such as repair of sublethal damage, but the tendency is demonstrated to hold under very general circumstances, being a consequence of cell-cell diversity and the dynamic response of the cell population to treatment. (C) 1998 by Radiation Research Society. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Joint Ctr Radiat Therapy, Boston, MA 02215 USA. RP Hahnfeldt, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Joint Ctr Radiat Therapy, 330 Brookline Ave, Boston, MA 02215 USA. NR 27 TC 19 Z9 19 U1 0 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 1998 VL 150 IS 6 BP 681 EP 687 DI 10.2307/3579891 PG 7 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 142CT UT WOS:000077182900010 PM 9840188 ER PT J AU Goldberg, SN Hahn, PF Halpern, EF Fogle, RM Gazelle, GS AF Goldberg, SN Hahn, PF Halpern, EF Fogle, RM Gazelle, GS TI Radio-frequency tissue ablation: Effect of pharmacologic modulation of blood flow on coagulation diameter SO RADIOLOGY LA English DT Article DE blood, flow dynamics; interventional procedures, technology; liver, US; radiofrequency (RF) ablation; liver, blood supply ID LASER-DOPPLER FLOWMETRY; LIVER METASTASES; RADIOFREQUENCY; PERFUSION; HALOTHANE; RAT; CATECHOLAMINES; HEPATOTOXICITY; TEMPERATURE; ISOFLURANE AB PURPOSE: To determine whether vasoactive pharmacologic agents can alter radio-frequency (RF)-induced coagulation necrosis by modulating hepatic blood flow. MATERIALS AND METHODS: RF ablation was performed in normal, in vivo porcine liver with 1.5-cm internally cooled electrodes and a standardized RF application (ie, 500 mA for 10 minutes). Ablation was performed without (n = 9) and with pharmacologic modulation of blood flow with halothane (n = 7), vasopressin (n = 6), or epinephrine (n = 7). Laser Doppler techniques were used to quantify changes in hepatic blood flow. Remote thermometry was also performed. Blood flow was correlated with both induced coagulation necrosis and tissue temperatures. RESULTS: Halothane reduced mean blood flow (+/- SD) to 46.1% +/- 8.5 of normal, and vasopressin increased mean blood flow to 132.7% +/- 13.9. Epinephrine caused increased hepatic blood flow centrally (171.1% +/- 31.7) but not peripherally (102.8% +/- 15.4). Mean coagulation diameter was 1.4 cm +/- 0.3 with vasopressin, 2.2 cm +/- 0.4 with normal blood flow, and 3.2 cm +/- 0.1 with halothane (P < .01). After epinephrine infusion, mean coagulation measured 2.3 cm +/- 0.3 peripherally and 1.4 cm +/- 0.5 centrally (P < .01). A linear correlation between coagulation diameter and blood flow was demonstrated (r(2) = 0.78). Temperatures 10 and 15 mm from the electrode correlated with both blood flow and coagulation diameter (r(2) = 0.65 and 0.60, respectively). CONCLUSION: The coagulation necrosis achieved for a standardized RF application correlates with relative tissue perfusion. Pharmacologic reduction of blood flow during thermally mediated percutaneous ablation may induce greater coagulation necrosis. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Goldberg, SN (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA. NR 36 TC 169 Z9 183 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 1998 VL 209 IS 3 BP 761 EP 767 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 141XM UT WOS:000077169600031 PM 9844671 ER PT J AU Rao, PM Rhea, JT AF Rao, PM Rhea, JT TI Colonic diverticulitis: Evaluation of the arrowhead sign and the inflamed diverticulum for CT diagnosis SO RADIOLOGY LA English DT Article DE colon, CT; colon, diverticula; computed tomography (CT), helical ID BARIUM ENEMA; APPENDICITIS; TOMOGRAPHY; DISEASE AB PURPOSE: To determine the frequency of visualization of the arrowhead sign and an inflamed diverticulum on abdominal computed tomographic (CT) scans in patients with acute colonic diverticulitis and to assess the specificity of these signs. MATERIALS AND METHODS: One hundred fifty consecutive patients suspected of having diverticulitis prospectively underwent helical CT after the administration of contrast material by means of an enema. Sixty-four patients (43%) had a final clinical diagnosis of colonic diverticulitis. Each scan was reviewed for the arrowhead sign, an arrowhead-shaped collection of contrast material within focal colonic wall thickening, and for an inflamed diverticulum, a rounded, paracolic outpouching centered within fat stranding. RESULTS: The arrowhead sign was noted at CT in 17 (27%) of the 64 patients with diverticulitis. An inflamed diverticulum was noted in 21 patients (33%) at CT, with either calcium or similar high-attenuation material in 10 (48%) of the 21 patients, soft-tissue attenuation in six patients (29%), air attenuation in four patients (19%), and barium attenuation in one patient (5%). Neither sign was demonstrated in patients with alternative conditions (100% specificity). CONCLUSION: The arrowhead sign and:an inflamed diverticulum are occasional, specific CT signs of colonic diverticulitis. Their identification can add diagnostic specificity to CT Of acute colonic processes. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Rao, PM (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 14 TC 27 Z9 28 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 1998 VL 209 IS 3 BP 775 EP 779 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 141XM UT WOS:000077169600033 PM 9844673 ER PT J AU Yim, JH Siegel, BA DeBenedetti, MK Norton, JA Lairmore, TC Doherty, GM AF Yim, JH Siegel, BA DeBenedetti, MK Norton, JA Lairmore, TC Doherty, GM TI Prospective study of the utility of somatostatin-receptor scintigraphy in the evaluation of patients with multiple endocrine neoplasia type 1 SO SURGERY LA English DT Article; Proceedings Paper CT 19th Annual Meeting of the American-Association-of-Endocrine-Surgeons CY APR 26-28, 1998 CL ORLANDO, FLORIDA SP Amer Assoc Endocrine Surgeons ID TUMORS AB Background. Neuroendocrine tumors (NETs) are a potentially lethal component of multiple endocrine neoplasia type 1 (MEN 1). Somatostatin receptor scintigraphy (SRS) can be used to localize NETs and evaluate patients for extraduodenopancreatic disease; its utility in managing MEN 1 is undefined. Methods. All patients with MEN 1 evaluated by SRS from April 1994 to November 1997 are reported. SRS findings were correlated with other imaging studies and operative findings. Results. Thirty-seven SRS studies were performed in 29 patients with MEN I. SRS identified occult tumor in 36 % (4/11) of patients with only biochemical evidence of NET; 2 patients went on to resection. SRS showed tumor in 79% (15/19) of patients with computed tomography (CT)-demonstrated tumor; 30 % (6/20) of the SRS lesions were occult on CT. Conversely, 55 % (16/29) of CT-identified lesions were occult on SRS. SRS found distant disease in 21% (6/29) of patients. In patients who had previous operations, SRS found tumor in 40% (4/10) of patients, again with both new positive and false-negative results compared with other imaging SRS also had 3 important false-positive results, including 2 patient who had laparotomy with no tumor identified. Conclusions. SRS is useful in identifying otherwise occult NETs in patients with MEN 1 and can substantially alter management. However SRS also has significant false-positive and false-negative results that demand correlation with other studies. C1 Washington Univ, Dept Surg, Sect Endocrine & Oncol Surg, St Louis, MO 63110 USA. Washington Univ, Div Nucl Med, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. San Francisco Vet Adm Med Ctr, San Francisco, CA USA. RP Doherty, GM (reprint author), Washington Univ, Dept Surg, Sect Endocrine & Oncol Surg, Box 8109,660 S Euclid Ave, St Louis, MO 63110 USA. FU NCI NIH HHS [5P01-CA53524] NR 10 TC 23 Z9 23 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1998 VL 124 IS 6 BP 1037 EP 1042 DI 10.1067/msy.1998.92553 PG 6 WC Surgery SC Surgery GA 145UA UT WOS:000077388700024 PM 9854580 ER PT J AU Norton, JA Doherty, GM Fraker, DL Alexander, R Doppman, JL Venzon, DJ Gibril, F Jensen, RT AF Norton, JA Doherty, GM Fraker, DL Alexander, R Doppman, JL Venzon, DJ Gibril, F Jensen, RT TI Surgical treatment of localized gastrinoma within the liver: A prospective study SO SURGERY LA English DT Article; Proceedings Paper CT 19th Annual Meeting of the American-Association-of-Endocrine-Surgeons CY APR 26-28, 1998 CL ORLANDO, FLORIDA SP Amer Assoc Endocrine Surgeons ID ZOLLINGER-ELLISON SYNDROME; SOMATOSTATIN-RECEPTOR SCINTIGRAPHY; PANCREATIC ENDOCRINE TUMORS; GASTROENTEROPANCREATIC TUMORS; AGGRESSIVE RESECTION; SURGERY; METASTASES; MANAGEMENT AB Background. Studies demonstrate that liver metastases of gastrinoma significantly reduce survival. Methods. Since 1982 we have prospectively studied 213 patients with Zollinger-Ellison syndrome. For this report the results of surgery for localized liver gastrinoma were analyzed. Results. Zollinger-Ellison syndrome was diagnosed biochemically in all patients and acid output was controlled with medications. Imaging studies demonstrated liver gastrinoma in 69 patients (32 %). Fifty-two had diffuse unresectable disease, whereas 17 (10 %) had localized disease. All patients with localized liver gastrinoma and 2 patients with diffuse disease who needed surgery are the subject of this report. Major hepatic lobectomy was performed in 10 patients and wedge resections in 9. Three patients had apparent liver primary gastrinomas and 16 had metastatic disease. Seventeen of 19 patients were able to have all identifiable gastrinoma resected. Extrahepatic tumor was also removed at the same procedure. Extirpation of liver gastrinoma required hepatic lobectomy in 10 patients and wedge resections in the others. Five-year survival was 85 %. Five of 17 completely resected patients (29 %) remained disease free. Conclusions, Resectable localized liver gastrinoma is rare. Primary liver gastrinomas can occur Surgical resection of localized liver gastrinoma provides a cure rate similar to that of extrahepatic gastrinoma and an excellent long-term survival. C1 San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. NCI, Surg Branch, Surg Metab Sect, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. NIDDKD, Digest Dis Branch, Bethesda, MD 20892 USA. RP Norton, JA (reprint author), San Francisco Vet Affairs Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. RI Venzon, David/B-3078-2008 NR 25 TC 39 Z9 41 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1998 VL 124 IS 6 BP 1145 EP 1152 DI 10.1067/msy.1998.93110 PG 8 WC Surgery SC Surgery GA 145UA UT WOS:000077388700056 PM 9854596 ER PT J AU Nakajima, S Atsumi, H Metcalf, DC Yoshimine, T Jolesz, FA Black, PM Kikinis, R AF Nakajima, S Atsumi, H Metcalf, DC Yoshimine, T Jolesz, FA Black, PM Kikinis, R TI A simple method of scalp localization using multiplanar reconstruction of MR images - Technical note SO SURGICAL NEUROLOGY LA English DT Article DE craniotomy; MRI; multiplanar reconstruction; scalp localization ID BRAIN-LESIONS; FRAMELESS; RESECTION AB BACKGROUND Image-based scalp localization methods currently used are complex and not standardized. The authors have developed a simple yet accurate method for craniotomy localization using multiplanar reconstruction (MPR) algorithms. METHODS In this method, the goal is to localize a projected point (defined as T) of the center of the lesion on the scalp. An oblique coronal plane is reformatted using a patient's magnetic resonance (MR) images with MPR algorithms to include both the center of the lesion and bilateral external auditory meati. Then the distance between T and the ipsilateral external auditory meatus or sagittal suture (defined as S) is measured along the scalp contour in the plane. The distance between the bregma and S is also measured. These distances are used for scalp localization, using a tape measure in the operating room. RESULTS We have had successful scalp localization in six clinical cases, It took about 3 min to measure each distance on the MR console. CONCLUSION This method for craniotomy planning using MPR algorithms is simple and sufficiently accurate. (C) 1998 by Elsevier Science Inc. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol,Surg Planning Lab, Boston, MA 02215 USA. Osaka Univ, Dept Neurosurg, Osaka, Japan. Harvard Univ, Sch Med,Joint Ctr Radiat Therapy,Childrens Hosp, Dana Farber Canc Inst,Brigham & Womens Hosp, Brain Tumor Ctr,Div Neurosurg, Boston, MA 02115 USA. RP Nakajima, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol,Surg Planning Lab, 75 Francis St, Boston, MA 02215 USA. FU NCI NIH HHS [P01 CA67165-02] NR 8 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PD DEC PY 1998 VL 50 IS 6 BP 597 EP 599 DI 10.1016/S0090-3019(97)00436-9 PG 3 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 151RX UT WOS:000077735400031 PM 9870823 ER PT J AU Vogel, D Carter, PB AF Vogel, D Carter, PB TI Pharmacology and the older person: Effects on communication SO TOPICS IN GERIATRIC REHABILITATION LA English DT Article ID ALZHEIMERS-DISEASE; DEPRESSION; DELIRIUM AB Neurophysiology and neuropharmacology are reviewed, followed by a discussion of how drugs work in the nervous system. The effects of aging on pharmacokinetics, the study of how drugs move in the body, are discussed. Disorders that affect communication of older persons are presented along with a review of the drugs used to manage these disorders. The desired effects as well as side effects of the drugs are addressed. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Our Lady Lake Univ, Dept Commun Disorders, San Antonio, TX 78285 USA. S Texas Vet Healthcare Syst, Extended Care Geriatr, San Antonio, TX USA. RP Vogel, D (reprint author), Our Lady Lake Univ, Dept Commun Disorders, San Antonio, TX 78285 USA. NR 24 TC 1 Z9 1 U1 0 U2 0 PU ASPEN PUBL INC PI FREDERICK PA 7201 MCKINNEY CIRCLE, FREDERICK, MD 21704 USA SN 0882-7524 J9 TOP GERIATR REHABIL JI Top. Geriatr. Rehabil. PD DEC PY 1998 VL 14 IS 2 BP 76 EP 86 PG 11 WC Gerontology; Rehabilitation SC Geriatrics & Gerontology; Rehabilitation GA 137HP UT WOS:000076908900008 ER PT J AU Wright, LS Kornguth, SE Oberley, TD Siegel, FL AF Wright, LS Kornguth, SE Oberley, TD Siegel, FL TI Effects of lead on glutathione S-transferase expression in rat kidney: A dose-response study SO TOXICOLOGICAL SCIENCES LA English DT Article DE rat; kidney; glutathione S-transferase; lead; HPLC ID ANTIOXIDANT ENZYMES; QUINONE REDUCTASE; P GENE; LIVER; ISOENZYMES; 3-METHYLCHOLANTHRENE; IMMUNOLOCALIZATION; BINDING AB Glutathione S-transferases (GST, EC 2.5.1.18) are a family of phase II detoxification enzymes involved in the conjugation of glutathione to a highly diverse group of compounds. The purpose of this study was to evaluate the dose-response effects of lead acetate administration on the expression of rat kidney GST. Sprague-Dawley rats were injected with doses of lead acetate ranging from 0.11 to 114 mg/kg (0.3 to 300 mu mol/kg) for three consecutive days and sacrificed 24 h later. Kidney GST activity, GST isoform HPLC profiles, blood lead analysis, and electron microscopy were performed. A dose of 1.1 mg/kg lead acetate resulted in a blood lead level of 26 mu g/dl and produced a significant increase in GST activity which continued to increase with dose up to 38 mg/kg. Morphological changes were detected at 3.8 mg/kg and increasing severity of cellular damage paralleled dose, blood lead levels, and changes in body weight. Individual GST isoforms exhibited different thresholds and maxima; rGSTP1 and rGSTM1 had thresholds of 1.1 and 3.8 mg/kg, respectively, very similar rates of increase with dose, and a maximum yield that was 450% above control at a dose of 38 mg/kg for both enzymes, rGSTA1 and rGSTA3 showed similar thresholds (1.1 mg/kg) and maximal fold increase (275%) but varied in the relative response to each dose. These results indicate that renal GST increases occur at lead levels which are environmentally significant, that these changes precede cellular damage, and suggest that GST may serve as a tissue biomarker of lead exposure. (C) 1998 Society of Toxicology. C1 Univ Wisconsin, Waisman Ctr, Mol & Genet Sci Unit, Madison, WI 53705 USA. Univ Wisconsin, Dept Biomol Chem, Madison, WI 53705 USA. Univ Wisconsin, Dept Neurol, Madison, WI 53705 USA. Univ Wisconsin, Dept Pediat, Madison, WI 53705 USA. Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53705 USA. William S Middleton Mem Vet Hosp, Madison, WI USA. RP Siegel, FL (reprint author), Univ Wisconsin, Waisman Ctr, Mol & Genet Sci Unit, 1500 Highland Ave, Madison, WI 53705 USA. EM siegel@waisman.wisc.edu FU NICHD NIH HHS [HD03352]; NINDS NIH HHS [NS24669] NR 29 TC 18 Z9 19 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 1998 VL 46 IS 2 BP 254 EP 259 DI 10.1093/toxsci/46.2.254 PG 6 WC Toxicology SC Toxicology GA 167FX UT WOS:000078622800005 PM 10048128 ER PT J AU Sykes, M Ohdan, H Manilay, JO Wekerle, T Yang, YG AF Sykes, M Ohdan, H Manilay, JO Wekerle, T Yang, YG TI Hematopoietic chimerism and tolerance of T cells, B cells, and NK cells SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 3rd International Conference on New Trends in Clinical and Experimental Immunosuppression CY FEB 12-15, 1998 CL GENEVA, SWITZERLAND ID BONE-MARROW TRANSPLANTATION; NONLETHAL PREPARATIVE REGIMEN; ANTIBODY MAB INJECTIONS; WHOLE-BODY IRRADIATION; MIXED CHIMERISM; NONMYELOABLATIVE REGIMEN; THYMIC IRRADIATION; INDUCTION; MECHANISM C1 Massachusetts Gen Hosp, Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, Surg Serv, Boston, MA 02129 USA. RP Sykes, M (reprint author), Massachusetts Gen Hosp, Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, Surg Serv, MGH E,Bldg 149-5102, Boston, MA 02129 USA. FU NHLBI NIH HHS [R01 HL49915] NR 17 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD DEC PY 1998 VL 30 IS 8 BP 4020 EP 4020 DI 10.1016/S0041-1345(98)01325-6 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 149EW UT WOS:000077593000031 PM 9865282 ER PT J AU Allan, JS Slisz, JK Vesga, L Arn, JS Yamada, K Sachs, DH Madsen, JC AF Allan, JS Slisz, JK Vesga, L Arn, JS Yamada, K Sachs, DH Madsen, JC TI Enhanced efficacy of repeated anti-CD8 monoclonal antibody therapy by high-dose cyclosporine treatment SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 3rd International Conference on New Trends in Clinical and Experimental Immunosuppression CY FEB 12-15, 1998 CL GENEVA, SWITZERLAND ID SUPPRESSION; SWINE C1 Harvard Univ, Sch Med, Div Cardiovasc Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02115 USA. RP Madsen, JC (reprint author), Massachusetts Gen Hosp, Dept Surg, Cardiac Surg Unit, Boston, MA 02114 USA. FU NHLBI NIH HHS [R01-HL54211] NR 9 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD DEC PY 1998 VL 30 IS 8 BP 4062 EP 4063 DI 10.1016/S0041-1345(98)01340-2 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 149EW UT WOS:000077593000044 PM 9865295 ER PT J AU Slack, FJ Ruvkun, G AF Slack, FJ Ruvkun, G TI A novel repeat domain that is often associated with RING finger and B-box motifs SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID ZINC-FINGER; RAR-ALPHA; PROTEIN; SEQUENCE; TRANSLOCATION; T(15-17); ELEGANS; PML C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Slack, FJ (reprint author), Harvard Univ, Sch Med, Dept Genet, Blossom St, Boston, MA 02114 USA. OI Slack, Frank/0000-0001-8263-0409 NR 15 TC 111 Z9 115 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD DEC PY 1998 VL 23 IS 12 BP 474 EP 475 DI 10.1016/S0968-0004(98)01299-7 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 148LT UT WOS:000077507300011 PM 9868369 ER PT J AU Wang, JH AF Wang, JH TI The insulin connection: Dorothy Hodgkin and the Beijing Insulin Group SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wang, JH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 8 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD DEC PY 1998 VL 23 IS 12 BP 497 EP 500 DI 10.1016/S0968-0004(98)01313-9 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 148LT UT WOS:000077507300017 PM 9868375 ER PT J AU Newcomb, R Pierce, AR Kano, T Meng, W Bosque-Hamilton, P Taylor, L Curthoys, N Lo, EH AF Newcomb, R Pierce, AR Kano, T Meng, W Bosque-Hamilton, P Taylor, L Curthoys, N Lo, EH TI Characterization of mitochondrial glutaminase and amino acids at prolonged times after experimental focal cerebral ischemia SO BRAIN RESEARCH LA English DT Article DE stroke; ischemia; excitotoxicity; neurodegeneration; glutaminase; delayed neuronal damage ID METHYL-D-ASPARTATE; EXTRACELLULAR GLUTAMATE; ARTERY OCCLUSION; NEURONAL DEATH; BRAIN-TISSUE; RAT; CULTURES; RELEASE; CORTEX; METABOLISM AB The mitochondrial enzyme glutaminase is a significant contributor to extracellular glutamate after neuronal injury in vitro [R. Newcomb, X. Sun, L. Taylor, N. Curthoys, R.G. Giffard, Increased production of extracellular glutamate by the mitochondrial glutaminase following neuronal death, J. Biol. Chem. 272 (1997) 11276-11282.]. As a step towards characterizing the role of the enzyme in neuronal injury in vivo, glutaminase activity was measured in central and peripheral regions of the ischemic distribution in rat brain at 6, 24, and 48 h after permanent focal ischemia. Although glutaminase activity decreases in the central ischemic area, significant activity remains in peripheral areas of evolving damage, even after 24 and 48 h ischemia. Western blots show no detectable change in glutaminase molecular weight or total immunoreactivity, regardless of the degree of inactivation. Significant amounts of glutamine remain in ischemic tissue at prolonged times after focal ischemia, while reductions in tissue amounts of glutamate are highly correlated with decreases in glutaminase activity. In vivo microdialysis probes were inserted into the ischemic periphery after 24 h focal ischemia. Glutamate is significantly elevated in these dialysates. Perfusion of the glutaminase substrate glutamine and the enzyme activator phosphate results in further and specific elevations in dialysate glutamate. In sum, significant mitochondrial,glutaminase activity remains in the periphery of the ischemic lesion at 24 and 48 h, where it can contribute directly to elevated extracellular glutamate. Inactivation of the glutaminase in central areas of the ischemic lesion does not involve significant proteolytic degradation, and likely involves a specific molecular event. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Elan Pharmaceut Inc, Menlo Park, CA 94025 USA. Colorado State Univ, Dept Biochem & Mol Biol, Ft Collins, CO 80523 USA. Harvard Univ, Sch Med, Neuroprotect Res Lab, Dept Neurol,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. RP Newcomb, R (reprint author), Elan Pharmaceut Inc, 3760 Haven Ave, Menlo Park, CA 94025 USA. FU NIDDK NIH HHS [DK37124]; NINDS NIH HHS [NS32806, R43 NS35406] NR 44 TC 25 Z9 27 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 30 PY 1998 VL 813 IS 1 BP 103 EP 111 DI 10.1016/S0006-8993(98)01006-3 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 142HF UT WOS:000077194100014 PM 9824679 ER PT J AU Wiley, HS Woolf, MF Opresko, LK Burke, PM Will, B Morgan, JR Lauffenburger, DA AF Wiley, HS Woolf, MF Opresko, LK Burke, PM Will, B Morgan, JR Lauffenburger, DA TI Removal of the membrane-anchoring domain of epidermal growth factor leads to intracrine signaling and disruption of mammary epithelial cell organization SO JOURNAL OF CELL BIOLOGY LA English DT Article DE epidermal growth factor; autocrine; intracrine; receptors; epithelium ID CANINE KIDNEY-CELLS; FACTOR-ALPHA; FACTOR RECEPTOR; EGF RECEPTOR; TGF-ALPHA; ERBB RECEPTORS; FIBROMA VIRUS; FACTOR FAMILY; MICE LACKING; FACTOR GENE AB Autocrine EGF-receptor (EGFR) ligands are normally made as membrane-anchored precursors that are proteolytically processed to yield mature, soluble peptides. To explore the function of the membrane anchoring domain of EGF, we expressed artificial EGF genes either with or without this structure in human mammary epithelial cells (HMEC). These cells require activation of the EGFR for cell proliferation. We found that HMEC expressing high levels of membrane-anchored EGF grew at a maximal rate that was not increased by exogenous EGF, but could be inhibited by anti-EGFR antibodies. In contrast, when cells expressed EGF lacking the membrane-anchoring domain (sEGF), their proliferation rate, growth at clonal densities, and receptor substrate phosphorylation were not affected by anti-EGFR antibodies. The sEGF was found to be colocalized with the EGFR within small cytoplasmic vesicles. It thus appears that removal of the membrane-anchoring domain converts autocrine to intracrine signaling. Significantly, sEGF inhibited the organization of HMEC on Matrigel, suggesting that spatial restriction of EGF access to its receptor is necessary for organization. Our results indicate that an important role of the membrane-anchoring domain of EGFR ligands is to restrict the cellular compartments in which the receptor is activated. C1 Univ Utah, Sch Med, Dept Pathol, Div Cell Biol & Immunol, Salt Lake City, UT 84132 USA. Harvard Univ, Massachusetts Gen Hosp, Surg Serv, Cambridge, MA 02139 USA. Shriners Burn Unit, Cambridge, MA 02139 USA. MIT, Div Bioengn & Environm Hlth, Cambridge, MA 02139 USA. RP Wiley, HS (reprint author), Univ Utah, Sch Med, Dept Pathol, Div Cell Biol & Immunol, Salt Lake City, UT 84132 USA. OI Morgan, Jeffrey/0000-0002-7546-3443; Wiley, Steven/0000-0003-0232-6867 FU NCI NIH HHS [P30 CA042014, 5P30 CA 42014] NR 81 TC 46 Z9 46 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV 30 PY 1998 VL 143 IS 5 BP 1317 EP 1328 DI 10.1083/jcb.143.5.1317 PG 12 WC Cell Biology SC Cell Biology GA 145XU UT WOS:000077398300016 PM 9832559 ER PT J AU Clement, MV Ponton, A Pervaiz, S AF Clement, MV Ponton, A Pervaiz, S TI Apoptosis induced by hydrogen peroxide is mediated by decreased superoxide anion concentration and reduction of intracellular milieu SO FEBS LETTERS LA English DT Article DE hydrogen peroxide; superoxide anion; apoptosis; caspase; cellular redox state ID CELL-DEATH; POLY(ADP-RIBOSE) POLYMERASE; OXYGEN; FAS; ACIDIFICATION; LUMINESCENCE; GLUTATHIONE; MECHANISMS; DISULFIDE; DISMUTASE AB Hydrogen peroxide (H2O2) is considered to be a mediator of apoptotic cell death but the mechanism by which it induces apoptosis is unclear, Here, me show that cells undergoing apoptosis from exposure to H2O2 display a significant decrease in intracellular concentration of superoxide (O-2(-)) which is associated with a reduction of the intracellular milieu, as measured by an increase in the GSH/GSSG ratio and a decrease in intracellular pH, The notion that a decrease in intracellular O-2(-) concentration triggers apoptosis is supported by the observation that H2O2-mediated apoptosis could be retarded in cells in which the intracellular O-2(-) concentration is maintained at or above the cellular baseline level by inhibition of the major O-2(-) scavenger superoxide dismutase (Cu/Zn SOD), Taken together, our observations indicate that a decrease in the intracellular O-2(-) concentration, reduction and acidification of the intracellular milieu constitute a signal for H2O2-mediated apoptosis, thereby inducing a reductive as opposed to an oxidative stress. (C) 1998 Federation of European Biochemical Societies. C1 Natl Univ Singapore, Inst Med, Oncol Res Inst, Clin Res Ctr 02 01, Singapore 119260, Singapore. Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Natl Univ Singapore, Dept Physiol, Singapore 119260, Singapore. RP Clement, MV (reprint author), Natl Univ Singapore, Inst Med, Oncol Res Inst, Clin Res Ctr 02 01, Block MD11,10 Kent Ridge Crescent, Singapore 119260, Singapore. RI Pervaiz, Shazib/C-4188-2015 NR 30 TC 137 Z9 140 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 27 PY 1998 VL 440 IS 1-2 BP 13 EP 18 DI 10.1016/S0014-5793(98)01410-0 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 145AK UT WOS:000077348700003 PM 9862415 ER PT J AU Krukonis, ES Dersch, P Eble, JA Isberg, RR AF Krukonis, ES Dersch, P Eble, JA Isberg, RR TI Differential effects of integrin alpha chain mutations on invasin and natural ligand interaction SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-ADHESION; PLATELET INTEGRIN; BINDING-SITE; GPIIB-IIIA; G-PROTEIN; RECEPTOR; SUBUNIT; DOMAIN; IDENTIFICATION; FIBRONECTIN AB To determine if recognition of the Yersinia pseudotuberculosis invasin protein and natural substrates requires identical integrin residues, a region of the human alpha(3) integrin chain predicted to be involved in substrate adhesion was targeted for mutation. One point mutation located in a region of the third N-terminal repeat of the alpha(3) chain, alpha(3)-W220A, failed to promote adhesion to the natural alpha(3)beta(1) substrate epiligrin but maintained near wild type levels of adhesion to invasin, A second nearby mutation, alpha(3)-Y218A, which showed no detectable adhesion to epiligrin, was only partially attenuated for invasin binding as well as invasin-mediated bacterial uptake. A third substitution, alpha(3)-D154A, predicted to be in the second N-terminal repeat not known to be implicated in cell adhesion, was competent for invasin-promoted adhesion events and appeared to encode a receptor of increased activity, as it had a higher efficiency than wild type receptor for adhesion to epiligrin, Cell lines expressing this derivative were not recognized by a function blocking anti-alpha(3) antibody, indicating that the second and third repeats of the alpha(3) chain are either closely linked in space or the second repeat can modulate activity of the third. Differential effects on substrate adhesion do not appear to be associated with all integrin alpha chain mutations, as alpha(4) chain mutations affecting the divalent cation binding domains depressed adhesion to invasin to a significant extent. C1 Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. Howard Hughes Med Inst, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Isberg, RR (reprint author), Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, 136 Harrison Ave M&V 409, Boston, MA 02111 USA. FU NIAID NIH HHS [R01-AI23538, T32-AI07422]; NIDDK NIH HHS [1 P30DK39428] NR 38 TC 26 Z9 26 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 27 PY 1998 VL 273 IS 48 BP 31837 EP 31843 DI 10.1074/jbc.273.48.31837 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 142NR UT WOS:000077207000033 PM 9822651 ER PT J AU Kantoff, P Giovannucci, E Brown, M AF Kantoff, P Giovannucci, E Brown, M TI The androgen receptor CAG repeat polymorphism and its relationship to prostate cancer SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Article ID BULBAR MUSCULAR-ATROPHY; N-TERMINAL DOMAIN; GENE; RISK; TRANSACTIVATION; EXPANSION; SIZE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. RP Kantoff, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. EM philip-kantoff@dfci.harvard.edu RI Myles, Brown/B-6906-2008 NR 25 TC 39 Z9 41 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD NOV 26 PY 1998 VL 1378 IS 3 BP C1 EP C5 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA 150CZ UT WOS:000077646500001 PM 9875243 ER PT J AU Disatnik, MH Dhawan, J Yu, Y Beal, MF Whirl, MM Franco, AA Rando, TA AF Disatnik, MH Dhawan, J Yu, Y Beal, MF Whirl, MM Franco, AA Rando, TA TI Evidence of oxidative stress in mdx mouse muscle: Studies of the pre-necrotic state SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE muscular dystrophy; mdx mouse; antioxidant enzyme; free radicals; oxidative stress ID DUCHENNE-MUSCULAR-DYSTROPHY; NITRIC-OXIDE SYNTHASE; SKELETAL-MUSCLE; SUPEROXIDE-DISMUTASE; LIPID-PEROXIDATION; ANTIOXIDANT ENZYMES; ANIMAL-MODELS; DAMAGE; MICE; ACID AB Considerable evidence indicates that free radical injury may underlie the pathologic changes in muscular dystrophies from mammalian and avian species. We have investigated the role of oxidative injury in muscle necrosis in mice with a muscular dystrophy due to a defect in the dystrophin gene (the mdr strain). In order to avoid secondary consequences of muscle necrosis, all experiments were done on muscle prior to the onset of the degenerative process (i.e. during the 'pre-necrotic' phase) which lasted up to 20 days of age in the muscles examined. In pre-necrotic mdx muscle, there was an induction of expression of genes encoding antioxidant enzymes, indicative of a cellular response to oxidative stress. In addition, the levels of lipid peroxidation were greater in mdx muscle than in the control. Since the free radical nitric oxide (NO.) has been shown to mediate oxidative injury in various disease states, and because dystrophin has been shown to form a complex with the enzyme nitric oxide synthase, we examined pre-necrotic mdx muscle for evidence of NO.-mediated injury by measuring cellular nitrotyrosine formation. By both immunohistochemical and electrochemical analyses, no evidence of increased nitrotyrosine levels in mdx muscle was detected. Therefore, although no relationship with NO.-mediated toxicity was found, we found evidence of increased oxidative stress preceding the onset of muscle cell death in dystrophin-deficient mice. These results lend support to the hypothesis that free radical-mediated injury may contribute to the pathogenesis of muscular dystrophies. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Dept Vet Affairs, Palo Alto, CA 94303 USA. Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Serv Neurol, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Rando, TA (reprint author), Dept Vet Affairs, Palo Alto, CA 94303 USA. EM rando@stanford.edu NR 53 TC 114 Z9 114 U1 0 U2 4 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 26 PY 1998 VL 161 IS 1 BP 77 EP 84 DI 10.1016/S0022-510X(98)00258-5 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 149KW UT WOS:000077605200013 PM 9879685 ER PT J AU Holstege, FCP Jennings, EG Wyrick, JJ Lee, TI Hengartner, CJ Green, MR Golub, TR Lander, ES Young, RA AF Holstege, FCP Jennings, EG Wyrick, JJ Lee, TI Hengartner, CJ Green, MR Golub, TR Lander, ES Young, RA TI Dissecting the regulatory circuitry of a eukaryotic genome SO CELL LA English DT Article ID RNA-POLYMERASE-II; TRANSCRIPTION FACTOR IIE; TATA-BINDING PROTEIN; C-TERMINAL DOMAIN; SACCHAROMYCES-CEREVISIAE; BASAL TRANSCRIPTION; GENE-EXPRESSION; NUCLEOSOMAL DNA; MESSENGER-RNAS; IN-VIVO AB Genome-wide expression analysis was used to identify genes whose expression depends on the functions of key components of the transcription initiation machinery in yeast. Components of the RNA polymerase II holoenzyme, the general transcription factor TFIID, and the SAGA chromatin modification complex were found to have roles in expression of distinct sets of genes. The results reveal an unanticipated level of regulation which is superimposed on that due to gene-specific transcription factors, a novel mechanism for coordinate regulation of specific sets of genes when cells encounter limiting nutrients, and evidence that the ultimate targets of signal transduction pathways can be identified within the initiation apparatus. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Univ Massachusetts, Med Ctr, Howard Hughes Med Inst, Program Mol Med, Worcester, MA 01605 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Young, RA (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. RI Young, Richard/F-6495-2012 OI Young, Richard/0000-0001-8855-8647 NR 65 TC 1419 Z9 1447 U1 2 U2 32 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD NOV 25 PY 1998 VL 95 IS 5 BP 717 EP 728 DI 10.1016/S0092-8674(00)81641-4 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 143KD UT WOS:000077253700018 PM 9845373 ER PT J AU Guo, ZM Heydari, A Richardson, A AF Guo, ZM Heydari, A Richardson, A TI Nucleotide excision repair of actively transcribed versus nontranscribed DNA in rat hepatocytes: Effect of age and dietary restriction SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE DNA repair; hepatocytes; rat; aging; dietary restriction ID IRRADIATED MAMMALIAN-CELLS; PYRIMIDINE DIMERS; LIFE-SPAN; ULTRAVIOLET-LIGHT; FINE-STRUCTURE; DHFR GENE; DAMAGE; MICE; EXPRESSION; EFFICIENT AB The ability of primary cultures of rat hepatocytes to remove cyclobutane pyrimidine dimers (CPDs) from DNA fragments containing the transcriptionally active albumin gene and the transcriptionally inactive embryonic myosin heavy chain (MHCemb) and H-ras fragments as well as the genome overall was measured. At all UV doses studied, more CPDs were observed in the three DNA fragments and the genome overall in hepatocytes isolated from old (24-month-old) rats fed ad libitum than in young (6-month-old) rats fed ad libitum or old rats fed a calorie-restricted diet. The cultured hepatocytes preferentially removed CPDs from the albumin fragment compared to the genome overall or the MHCemb and H-ras fragments. The rate of repair (12 h after UV irradiation) of the albumin fragment was approximately 40% less in hepatocytes isolated from old rats than from young rats; this was due to a decrease in repair of the transcribed strand of this fragment, and dietary restriction prevented this decrease. The extent of repair (24 h after UV irradiation) of the MHCemb and H-ras fragments as well as the genome overall was reduced approximately 40% with age, and this decrease was reversed by dietary restriction, (C) 1998 Academic Press. C1 Univ Texas, Ctr Geriatr Res Educ & Clin, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. RP Richardson, A (reprint author), Audie L Murphy Mem Vet Hosp, GRECC 182, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NIA NIH HHS [P0I AG14674] NR 59 TC 48 Z9 50 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 1998 VL 245 IS 1 BP 228 EP 238 DI 10.1006/excr.1998.4269 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 145DY UT WOS:000077356800026 PM 9828120 ER PT J AU March, JS Biederman, J Wolkow, R Safferman, A Mardekian, J Cook, EH Cutler, NR Dominguez, R Ferguson, J Muller, B Riesenberg, R Rosenthal, M Sallee, FR Wagner, KD AF March, JS Biederman, J Wolkow, R Safferman, A Mardekian, J Cook, EH Cutler, NR Dominguez, R Ferguson, J Muller, B Riesenberg, R Rosenthal, M Sallee, FR Wagner, KD TI Sertraline in children and adolescents with obsessive-compulsive disorder - A multicenter randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID DOUBLE-BLIND; CLOMIPRAMINE TREATMENT; PLACEBO; DESIPRAMINE; INHIBITORS; FLUOXETINE AB Context.-The serotonin reuptake inhibitors are the treatment of choice for patients with obsessive-compulsive disorder; however, empirical support for this assertion has been weaker for children and adolescents than far adults. Objective.-To evaluate the safety and efficacy of the selective serotonin reuptake inhibitor sertraline hydrochloride in children and adolescents with obsessive-compulsive disorder. Design.-Randomized, double-blind, placebo-controlled trial. Patients.-One hundred eighty-seven patients: 107 children aged 6 to 12 years and 80 adolescents aged 13 to 17 years randomized to receive either sertraline (53 children, 39 adolescents) or placebo (54 children, 41 adolescents). Setting.-Twelve US academic and community clinics with experience conducting randomized controlled trials. Intervention.-Sertraline hydrochloride was titrated to a maximum of 200 mg/d during the first 4 weeks of double-blind therapy, after which patients continued to receive this dosage of medication for 8 move weeks. Control patients received placebo. Main Outcome Measures.-The Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), the National institute of Mental Health Global Obsessive ;Compulsive Scale (NIMH GOCS), and the NIMH Clinical Global Impressions of Severity of Illness (CGI-S) and Improvement (CGI-I) rating scales. Results.-In intent-to-treat analyses, patients treated with sertraline showed significantly greater improvement than did placebo-treated patients on the CY-BOCS (adjusted mean, -6.8 vs -3.4, respectively; P = .005), the NIMH GOCS (-2.2 vs -1.3, respectively; P = .02), and the CGI-I (2.7 vs 3.3, respectively; P = .002) scales. Significant differences in efficacy between sertraline and placebo emerged at week 3 and persisted for the duration of the study. Based on CGI-I ratings at end point, 42% of patients receiving sertraline and 26% of patients receiving placebo were very much or much improved. Neither age nor sex predicted response to treatment. The incidence of insomnia, nausea, agitation, and tremor were significantly greater in patients receiving sertraline; 12 (13%) of 92 sertraline-treated patients and 3 (3.2%) of 95 placebo-treated patients discontinued prematurely because of adverse medical events (P =.02). No clinically meaningful abnormalities were apparent on vital sign determinations, laboratory findings, or electrocardiographic measurements. Conclusion.-Sertraline appears to be a safe and effective short-term treatment for children and adolescents with obsessive-compulsive disorder. C1 Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Psychol, Durham, NC 27710 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Pfizer Inc, New York, NY USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Univ Chicago, Dept Psychol, Chicago, IL 60637 USA. Calif Clin Trials, Beverly Hills, CA USA. Univ Miami, Dept Psychiat, Miami, FL 33152 USA. Tulane Univ, Dept Psychiat, New Orleans, LA 70118 USA. Biobehav Res Ctr, Decatur, GA USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Univ Texas, Med Branch, Dept Psychiat, Galveston, TX 77550 USA. RP March, JS (reprint author), Duke Univ, Med Ctr, Dept Psychiat, Box 3527, Durham, NC 27710 USA. EM jsmarch@acpub.duke.edu OI Cook, Edwin/0000-0002-5848-5114 NR 33 TC 266 Z9 270 U1 2 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 25 PY 1998 VL 280 IS 20 BP 1752 EP 1756 DI 10.1001/jama.280.20.1752 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 140HF UT WOS:000077081400030 PM 9842950 ER PT J AU Croce, K Freedman, SJ Furie, BC Furie, B AF Croce, K Freedman, SJ Furie, BC Furie, B TI Interaction between soluble P-selectin and soluble P-selectin glycoprotein ligand 1: Equilibrium binding analysis SO BIOCHEMISTRY LA English DT Article ID GRANULE MEMBRANE-PROTEIN; GROWTH-FACTOR DOMAINS; ADHESION MOLECULES; FUNCTIONAL-CHARACTERIZATION; TYROSINE SULFATION; PLASMA-MEMBRANE; AMINO-TERMINUS; IN-VIVO; T-CELLS; GMP-140 AB Leukocyte rolling in the vasculature is mediated by the interaction of endothelial P-selectin and leukocyte P-selectin glycoprotein ligand 1 (PSGL-1). Since cell-cell interaction mediated by P-selectin and PSGL-1 is cooperative and complex, we have developed a model system to examine the binding of P-selectin to PSGL-1 in a soluble system. Equilibrium binding analyses were performed with truncated forms of soluble human P-selectin and dimeric PSGL-1, both lacking the transmembrane domain and both produced in Chinese hamster ovary (CHO) cells. Soluble PSGL-1 (sPSGL-1), which contains no tryptophan residues and exhibits no intrinsic fluorescence, was harvested from CHO cells cotransfected with either fucosyltransferase III (sPSGL-1/Fuc-TIII) or fucosyltransferase VII (sPSGL-1/Fuc-TVII). Both fucosylation isoforms of sPSGL-1 bound to sP-selectin. The interaction of sP-selectin and sPSGL-1 was studied by monitoring changes in the intrinsic fluorescence of sP-selectin upon binding to sPSGL-1. Binding of sPSGL-1 to sP-selectin in the presence of calcium caused an increase in tryptophan fluorescence that could be reversed by the addition of ethylenediaminetetraacetic acid (EDTA). The fluorescence enhancement of sP-selectin by sPSGL-1 was used to generate binding isotherms, and these data were fined to a bimolecular binding model. The binding constant, K-d, for the binding of sPSGL-1/Fuc-TIII and sPSGL-1/Fuc-TVII to sP-selectin was 3 +/- 2 nM and 80 +/- 44 nM, respectively. Monomeric sP-selectin bound to dimeric sPSGL-1 with a 2:1 stoichiometry. In a system in which both protein species are soluble and lack transmembrane domains, these results indicate high-affinity interaction between P-selectin and PSGL-1. Furthermore, the fucosylation pattern of PSGL-1 can affect its affinity for P-selectin. These binding constants can be used to explore models of cell adhesion in flow systems. C1 Res E BIDMC, Ctr Hemostasis & Thrombosis Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. RP Furie, B (reprint author), Res E BIDMC, Ctr Hemostasis & Thrombosis Res, Boston, MA 02215 USA. FU NHLBI NIH HHS [HL51926] NR 47 TC 31 Z9 32 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 24 PY 1998 VL 37 IS 47 BP 16472 EP 16480 DI 10.1021/bi981341g PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 144UZ UT WOS:000077334800005 PM 9843413 ER PT J AU Stankewich, MC Tse, WT Peters, LL Ch'ng, Y John, KM Stabach, PR Devarajan, P Morrow, JS Lux, SE AF Stankewich, MC Tse, WT Peters, LL Ch'ng, Y John, KM Stabach, PR Devarajan, P Morrow, JS Lux, SE TI A widely expressed beta III spectrin associated with Golgi and cytoplasmic vesicles SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ENDOPLASMIC-RETICULUM; MEMBRANE-TRANSPORT; RAT-LIVER; IN-VITRO; GENE; IDENTIFICATION; ISOFORM; COMPLEX; MUSCLE; BINDS AB Spectrin is an important structural component of the plasma membrane skeleton. Heretofore-unidentified isoforms of spectrin also associate with Golgi and other organelles. We have discovered another member of the P-spectrin gene family by homology searches of the GenBank databases and by 5' rapid amplification of cDNA ends of human brain cDNAs. Collectively, 7,938 nucleotides of contiguous clones are predicted to encode a 271,293-Da protein, called pm spectrin, with conserved actin-, protein 4.1-, and ankyrin-binding domains, membrane association domains 1 and 2, a spectrin dimer self-association site, and a pleckstrinhomology domain. beta III spectrin transcripts are concentrated in the brain and present in the kidneys, liver, and testes and the prostate, pituitary, adrenal, and salivary glands. All of the tested tissues contain major 9.0-kb and minor 11.3-kb transcripts. The human pm spectrin gene (SPTBN2) maps to chromosome 11q13 and the mouse gene (Spnb3) maps to a syntenic region close to the centromere on chromosome 19. Indirect immunofluorescence studies of cultured cells using antisera specific to human pm spectrin reveal a Golgi-associated and punctate cytoplasmic vesicle-like distribution, suggesting that beta III spectrin associates with intracellular organelles. This distribution overlaps that of several Golgi and vesicle markers, including mannosidase II, p58, trans-Golgi network (TGN)38, and beta-COP and is distinct from the endoplasmic reticulum markers calnexin and Bip. Liver Golgi membranes and other vesicular compartment markers cosediment in vitro with beta III spectrin. beta III spectrin thus constitutes a major component of the Golgi and vesicular membrane skeletons. C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Yale Univ, Dept Pathol, New Haven, CT 06520 USA. Yale Univ, Dept Pediat, New Haven, CT 06520 USA. RP Lux, SE (reprint author), Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. EM lux@rascal.med.harvard.edu NR 48 TC 99 Z9 101 U1 0 U2 0 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 24 PY 1998 VL 95 IS 24 BP 14158 EP 14163 DI 10.1073/pnas.95.24.14158 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 142GE UT WOS:000077191200032 PM 9826670 ER PT J AU Cohen, BA Colas, P Brent, R AF Cohen, BA Colas, P Brent, R TI An artificial cell-cycle inhibitor isolated from a combinatorial Library SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RANDOM PEPTIDE LIBRARIES; PHAGE DISPLAY; RETINOBLASTOMA PROTEIN; DEPENDENT KINASES; S-PHASE; REVERSE 2-HYBRID; RNA-POLYMERASE; MOUSE GENOME; SELECTION; ACTIVATION AB Understanding the genetic networks that operate inside cells will require the dissection of interactions among network members. Here we describe a peptide aptamer isolated from a combinatorial library that distinguishes among such interactions. This aptamer binds to cyclin-dependent kinase 2 (Cdk2) and inhibits its kinase activity. In contrast to naturally occurring inhibitors, such as p21(Cip1), which inhibit the activity of Cdk2 on all its substrates, inhibition by pep8 has distinct substrate specificity. We show that the aptamer binds to Cdk2 at or near its active site and that its mode of inhibition is competitive. Expression of pep8 in human cells retards their progression through the G(1) phase of the cell cycle. Our results suggest that the aptamer inhibits cell-cycle progression by blocking the activity of Cdk2 on substrates needed for the G(1)-to-S transition. This work demonstrates the feasibility of selection of artificial proteins to perform functions not developed during evolution. The ability to select proteins that block interactions between a gene product and some partners but not others should make sophisticated genetic manipulations possible in human cells and other currently intractable systems. C1 Inst Mol Sci, Berkeley, CA 94704 USA. Ecole Normale Super Lyon, Lab Biol Mol & Cellulaire, F-69364 Lyon 07, France. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Brent, R (reprint author), Inst Mol Sci, 2168 Shattuck Ave, Berkeley, CA 94704 USA. EM brent@molsci.org NR 50 TC 93 Z9 95 U1 1 U2 2 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 24 PY 1998 VL 95 IS 24 BP 14272 EP 14277 DI 10.1073/pnas.95.24.14272 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 142GE UT WOS:000077191200052 PM 9826690 ER PT J AU Bertrand, P Tishkoff, DX Filosi, N Dasgupta, R Kolodner, RD AF Bertrand, P Tishkoff, DX Filosi, N Dasgupta, R Kolodner, RD TI Physical interaction between components of DNA mismatch repair and nucleotide excision repair SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SACCHAROMYCES-CEREVISIAE MSH2; TRANSCRIPTION-COUPLED REPAIR; BREAK-INDUCED RECOMBINATION; NONREPLICATING PHAGE DNA; ESCHERICHIA-COLI; SPECIFICALLY BINDS; BASE DAMAGE; TUMOR-CELLS; YEAST; PROTEINS AB Nucleotide excision repair (NER) and DNA mismatch repair are required for some common processes although the biochemical basis for this requirement is unknown. Saccharomyces cerevisiae RAD14 was identified in a two-hybrid screen using MSH2 as "bait," and pairwise interactions between MSH2, and RAD1, RAD2, RAD3, RAD10, RAD14, and RAD25 subsequently were demonstrated by two-hybrid analysis. MSH2 coimmunoprecipitated specifically with epitope-tagged versions of RAD2, RAD10, RAD14, and RAD25. MSH2 and RAD10 were found to interact in msh3 msh6 and mlh1 pms1 double mutants, suggesting a direct interaction with MSH2. Mutations in MSH2 increased the UV sensitivity of NER-deficient yeast strains, and msh2 mutations were epistatic to the mutator phenotype ob served in NER deficient strains. These data suggest that MSH2 and possibly other components of DNA mismatch repair exist in a complex with NER proteins, providing a biochemical and genetical basis for these proteins to function in common processes. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Charles A Dana Div Human Canc Genet, Boston, MA 02115 USA. RP Bertrand, P (reprint author), Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, CMME 3080,9500 Gilman Dr, La Jolla, CA 92093 USA. FU NIGMS NIH HHS [GM50006, R01 GM050006] NR 60 TC 102 Z9 102 U1 0 U2 7 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 24 PY 1998 VL 95 IS 24 BP 14278 EP 14283 DI 10.1073/pnas.95.24.14278 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 142GE UT WOS:000077191200053 PM 9826691 ER PT J AU Levelt, CN Mizoguchi, E Huang, X Zacks, R Bhan, AK Tonegawa, S AF Levelt, CN Mizoguchi, E Huang, X Zacks, R Bhan, AK Tonegawa, S TI Inhibition of intrathymic T cell development by expression of a transgenic antagonist peptide SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE thymus; positive selection ID POSITIVE SELECTION; NEGATIVE SELECTION; LYMPHOCYTES-T; RECEPTOR; THYMOCYTES; LIGANDS; THYMUS; MICE; ACTIVATION; AGONIST AB The mature T cell receptor (TCR) repertoire is shaped by positive- and negative-selection events taking place during T cell development. These events are regulated by interactions between the TCR and major histocompatibility complex molecules presenting self-peptides. It has been shown that many antagonist peptides are efficient at mediating positive selection. In this study we analyzed the effects of a transgene encoding an antagonist peptide (influenza NP34) that is presented by H-2D(b) in a Tap-1-independent fashion in mice expressing the influenza NP68-specific TCR F5. We find that the transgenic peptide does not mediate positive or negative selection in F5(+)Tap-1(-/-) mice, but inhibits maturation of CD8(+) single positive thymocytes in F5(+)Tap-1(+) mice without inducing signs of negative selection. We conclude that antagonism of antigen recognition occurs not only at the level of mature T cells but also in T cell development. C1 MIT, Ctr Canc Res, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. RP Levelt, CN (reprint author), MIT, Ctr Canc Res, Room E17-353,40 Ames St, Cambridge, MA 02139 USA. EM clevelt@wccf.mit.edu FU NCI NIH HHS [CA53874]; NIDDK NIH HHS [DK43551, DK47677, R01 DK047677] NR 46 TC 15 Z9 15 U1 0 U2 0 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 24 PY 1998 VL 95 IS 24 BP 14349 EP 14354 DI 10.1073/pnas.95.24.14349 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 142GE UT WOS:000077191200065 PM 9826703 ER PT J AU Frenette, PS Subbarao, S Mazo, IB von Andrian, UH Wagner, DD AF Frenette, PS Subbarao, S Mazo, IB von Andrian, UH Wagner, DD TI Endothelial selectins and vascular cell adhesion molecule-1 promote hematopoietic progenitor homing to bone marrow SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID P-SELECTIN; STROMAL CELLS; LYMPHOCYTE; MICE; EXPRESSION; CHEMOATTRACTANT; SUSCEPTIBILITY; RECONSTITUTION; INTERLEUKIN-3; DEFICIENT AB The adhesive mechanisms allowing hemato poietic progenitor cells (HPC) homing to the bone marrow (BM) after BM transplantation are poorly understood. We investigated the role of endothelial selectins and vascular cell adhesion molecule-1 (VCAM-1) in this process. Lethally irradiated recipient mice deficient in both P-and E-selectins (P/E-/-), reconstituted with minimal numbers (less than or equal to 5 x 10(4)) of wild-type BM cells, poorly survived the procedure compared with wild-type recipients. Excess mortality in P/E-/- mice, after a lethal dose of irradiation, was likely caused by a defect of HPC homing. Indeed, we observed that the recruitment of HPC to the BM was reduced in P/E-/- animals, either splenectomized or spleen-intact. Homing into the BM of P/E-/- recipient mice was further compromised when a function-blocking VCAM-1 antibody was administered. Circulating HPC, 14 hr after transplantation, were greatly in creased in P/E-/- mice treated with anti-VCAM-1 compared with P/E-/- mice treated with just IgG or wild-type mice treated with either anti-VCAM-1 or IgG. Our results indicate that endothelial selectins play an important role in HPC homing to the BM, Optimal recruitment of HPC after lethal doses of irradiation requires the combined action of both selectins and VCAM-1 expressed on endothelium of the BM. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Frenette, PS (reprint author), CUNY Mt Sinai Sch Med, Dept Med, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM paul.frenette@smtplink.mssm.edu RI von Andrian, Ulrich/A-5775-2008; Frenette, Paul/J-8272-2012 FU NHLBI NIH HHS [P01 HL 56949, P01 HL056949] NR 33 TC 243 Z9 250 U1 0 U2 2 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 24 PY 1998 VL 95 IS 24 BP 14423 EP 14428 DI 10.1073/pnas.95.24.14423 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 142GE UT WOS:000077191200078 PM 9826716 ER PT J AU Peabody, JW Luck, J AF Peabody, JW Luck, J TI How far down the managed care road? A comparison of primary care outpatient services in a Veterans Affairs medical center and a capitated multispecialty group practice SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID VA AB Background: Under increasing pressure to provide more efficient, higher-quality care, the Department of Veterans Affairs (VA) is expanding primary care and implementing other managed care techniques. To assess the magnitude of performance improvement possible in the VA and to investigate potential barriers to implementation of new techniques, we compared a VA facility with similar managed care organizations on specific managed care performance benchmarks. Methods and Data Collection: Detailed case studies of a large VA medical center and a large capitated multispecialty group practice in the same region were carried out. Various qualitative and quantitative data were collected between October 1, 1994, and September 30. 1997. Unstructured and semistructured interviews, participant and direct observations, document review, electronic data abstractions, and patient surveys were used to collect the data. Results: Patients in the VA medical center were poorer (average income, $13 300 per year), older (36.5% aged 65 years and older), and more likely to be homeless (10.5%). The VA patients saw more specialists and made more emergency department visits than managed care patients. Although the VA had better electronic information flows, its providers saw fewer patients, had more unscheduled visits, and received fewer consultant reports, and its patients waited longer. Inpatient utilization was also higher (length of stay averaged 8 days) among VA primary care patients. Conclusions: On many dimensions the VA did not compare favorably with the efficiency or lower utilization of the capitated managed care practice. Part of the reason must be attributed to the VA's multiple missions, which include teaching and research; another reason is the VA's role to be a service provider to all eligible veterans regardless of sociodemographic or health characteristics. Whether these differences are also caused by different case mix, or differences in socioeconomic status of patients, surprisingly is not well understood. This hampers future efforts to use managed care techniques to improve the operation of the VA. C1 Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. RP Peabody, JW (reprint author), Rand Corp, 1700 Main St, Santa Monica, CA 90407 USA. NR 16 TC 18 Z9 18 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 23 PY 1998 VL 158 IS 21 BP 2291 EP 2299 DI 10.1001/archinte.158.21.2291 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 139TK UT WOS:000077045600001 PM 9827780 ER PT J AU Miller, KW Addona, GH Kloczewiak, MA AF Miller, KW Addona, GH Kloczewiak, MA TI Approaches to proving there are general anesthetic sites on ligand gated ion channels SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT 5th International Conference on Molecular and Cellular Mechanisms of Anaesthesia CY JUN 18-20, 1997 CL UNIV CALGARY, CALGARY, CANADA HO UNIV CALGARY DE anesthetic; action; ligand gated ion channels ID NICOTINIC ACETYLCHOLINE-RECEPTOR; BINDING-SITE; TORPEDO; ALCOHOLS; ALKANOLS; GABA(A); STATE; AFFINITY; CHAIN AB (1) There are at least two broad classes of general anesthetic action on the anesthetic-sensitive ligand gated superfamily of ion channels. (2) First, some channels may be inhibited upon opening. Pharmacology, kinetics and site directed mutagenesis all suggest that inhibition is mediated by a site on the acetylcholine receptor probably located in the channel lumen. (3) Second, the agonist's concentration-response curve may be shifted to the left without affecting the maximum response. (4) This effect does not saturate with anesthetic concentration and might involve partial occupancy of many low affinity sites, mechanism consistent with the observation that the conformation changes accompanying channel gating involve most structural features of the receptor and its surrounding environment. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Miller, KW (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM k_miller@helix.mgh.harvard.edu NR 30 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 EI 1879-3169 J9 TOXICOL LETT JI Toxicol. Lett. PD NOV 23 PY 1998 VL 101 BP 139 EP 147 PG 9 WC Toxicology SC Toxicology GA 160EL UT WOS:000078217400022 ER PT J AU Raines, DE AF Raines, DE TI Conformational transitions of the nicotinic acetylcholine receptor as a model for anesthetic actions on ligand-gated ion channels: single and sequential mixing stopped-flow fluorescence studies SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT 5th International Conference on Molecular and Cellular Mechanisms of Anaesthesia CY JUN 18-20, 1997 CL UNIV CALGARY, CALGARY, CANADA HO UNIV CALGARY DE general anesthetic; nonanesthetic compounds; nicotinic acetylcholine receptor; fluorescence studies ID TORPEDO-MARMORATA; CHOLINERGIC RECEPTOR; AGONIST; DESENSITIZATION; KINETICS; BINDING; MEMBRANES; SITES AB (1) The effects of general anesthetic and nonanesthetic compounds on nicotinic acetylcholine receptor (nAcChoR) desensitization kinetics were characterized with stopped-flow fluorescence spectroscopy. (2) Anesthetics were found to increase the apparent rate of agonist-induced desensitization and shift the receptor equilibrium towards the desensitized state. (3) In contrast, nonanesthetics had little effect on either the apparent rate of desensitization or receptor equilibrium. (4) Octanol, but not isoflurane, decreases the rate of agonist dissociation from resting state nAcChoRs. (5) These results suggest that anesthetics alter nAcChoR desensitization kinetics by increasing either agonist binding affinity to the resting state or the channel opening probability. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Raines, DE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 32 Fruit St, Boston, MA 02114 USA. EM raines@etherdome.mgh.harvard.edu NR 19 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 EI 1879-3169 J9 TOXICOL LETT JI Toxicol. Lett. PD NOV 23 PY 1998 VL 101 BP 163 EP 168 PG 6 WC Toxicology SC Toxicology GA 160EL UT WOS:000078217400025 ER PT J AU Forman, SA AF Forman, SA TI Direct interactions of anesthetics and nonanesthetics with the nicotinic acetylcholine receptor pore SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT 5th International Conference on Molecular and Cellular Mechanisms of Anaesthesia CY JUN 18-20, 1997 CL UNIV CALGARY, CALGARY, CANADA HO UNIV CALGARY DE anesthetic site; nAChR pore; binding; cation translocation ID MEYER-OVERTON HYPOTHESIS; NONCOMPETITIVE ANTAGONIST; ION CHANNELS; BINDING-SITE; AMINO-ACIDS; MECHANISMS; MUTATIONS AB (1) We review evidence that anesthetics inhibit peripheral nAChR cation translocation by binding directly to a protein site in the transmembrane pore. (2) This site is near the middle of the pore-forming M2 domains on alpha and beta subunits, but further from the homologous portions of gamma and delta subunits. (3) Interactions between both anesthetics and nonanesthetics with the nAChR pore site are determined primarily by hydrophobic forces rather than steric factors. (4) Anesthetics and nonanesthetics display different state-dependent accessibility to this site, suggesting a mechanism for the different in vivo actions of these two classes of drugs. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Forman, SA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, CLN-3, Boston, MA 02114 USA. NR 25 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD NOV 23 PY 1998 VL 101 BP 169 EP 178 PG 10 WC Toxicology SC Toxicology GA 160EL UT WOS:000078217400026 ER PT J AU Hill, JS Yang, D Nikazy, J Curtiss, LK Sparrow, JT Wong, H AF Hill, JS Yang, D Nikazy, J Curtiss, LK Sparrow, JT Wong, H TI Subdomain chimeras of hepatic lipase and lipoprotein lipase - Localization of heparin and cofactor binding SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SUBSTRATE-SPECIFICITY; DENSITY-LIPOPROTEIN; HUMAN-PLASMA; DOMAIN; IDENTIFICATION; RESIDUES; PROTEIN; PHOSPHOLIPIDS; TRIGLYCERIDE; EVOLUTION AB To specify and localize carboxyl-terminal domain functions of human hepatic lipase (HL) and human lipoprotein lipase (LPL), two subdomain chimeras were created in which portions of the carboxyl-terminal domain were exchanged between the two lipases, The first chimera (HL-LPLC1) was composed of residues 1-344 of human HL, residues 331-388 of human LPL, and residues 415-476 of human HL, The second chimera (HL-LPLC2) consisted of just two segments, residues 1-414 of human HL and residues 389-448 of human LPL, These chimeric constructs effectively divided the HL C-terminal domain into halves, with corresponding LPL sequences either in the first or second portion of that domain, Both chimeras were lipolytically active and hydrolyzed triolein emulsions to a similar extent compared with native HL and LPL, Heparin-Sepharose chromatography demonstrated that HL-LPLC1 and HL-LPLC2 eluted at 0.80 and 1.3 M NaCl, respectively, elution positions that corresponded to native HL and LPL, Hence, substitution of LPL sequences into the HL carboxyl-terminal domain resulted in the production of functional lipases, but with distinct heparin binding properties. In addition, HL-LPLC2 trioleinase activity was responsive to apoC-II activation, although the -fold stimulation was less than that observed with native LPL, Moreover, an apoC-II fragment (residues 44-79) was specifically cross-linked to LPL and HL-LPLC2, but not to HL or HL-LPLC1. Finally, both chimeras hydrolyzed phospholipid with a specific activity similar to that of HL, which was unaffected by the presence of apoC-II, These findings indicated that in addition to a region found within the amino-terminal domain of LPL, apoC-II also interacted with the last half of the carboxyl-terminal domain (residues 389-448) to achieve maximal lipolytic activation. In addition, the relative heparin affinity of HL and LPL was determined by the final 60 carboxyl-terminal residues of each enzyme. C1 W Los Angeles Vet Affairs Med Ctr, Lipid Res Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Vasc Biol, La Jolla, CA 92037 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Methodist Hosp, Houston, TX 77030 USA. RP Wong, H (reprint author), W Los Angeles Vet Affairs Med Ctr, Lipid Res Lab, Bldg 113,Rm 312,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NHLBI NIH HHS [HL28481] NR 29 TC 42 Z9 42 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 20 PY 1998 VL 273 IS 47 BP 30979 EP 30984 DI 10.1074/jbc.273.47.30979 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 141HG UT WOS:000077136900022 PM 9812994 ER PT J AU Burks, DJ Wang, J Towery, H Ishibashi, O Lowe, D Riedel, H White, MF AF Burks, DJ Wang, J Towery, H Ishibashi, O Lowe, D Riedel, H White, MF TI IRS pleckstrin homology domains bind to acidic motifs in proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INSULIN-RECEPTOR SUBSTRATE-1; PHOSPHOTYROSINE-DEPENDENT INTERACTION; 2-HYBRID SYSTEM; HIGH-AFFINITY; NPEY MOTIF; ASSOCIATION; NUCLEOLIN; DYNAMIN; REGION; KINASE AB Using a yeast two-hybrid system, we identified several proteins that interact with the PH domains in IRS-1 and IRS-2, including Lon protease, myeloblast protein, and nucleolin, Although the roles of these molecules in insulin action are not yet known, each protein contained an acidic motif that interacted with the PH domain of IRS-2. However, only the acidic motif in nucleolin bound to IRS-1, suggesting that the PH domain in IRS-1 and IRS-2 are not identical. Moreover, synthetic peptides based on the acidic motif in Lon protease and myeloblast protein inhibited the binding of nucleolin to the PH domain of IRS-2 but not to the PH domain of IRS-1, confirming the selectivity of these PH domains. The ability to bind acidic motifs may be a specific function of the PH domain in IRS proteins, because the PH domains in beta ARK, phospholipase C gamma, or spectrin did not bind nucleolin. In 32D cells, nucleolin bound to both IRS-1 and IRS-2, and expression of the acidic motif of nucleolin inhibited insulin-stimulated tyrosine phosphorylation of IRS-1 and IRS-2, These results suggest that the binding of acidic motifs to the PH domain of IRS-1 and IRS-2 disrupts coupling to the activated insulin receptor. Our results are consistent with the hypothesis that the PH domain in the IRS proteins may ordinarily bind acidic peptide motifs in membrane proteins or other acidic membrane elements that couple IRS proteins to activated membrane receptors. C1 Harvard Univ, Joslin Diabet Ctr, Sch Med, Howard Hughes Med Inst, Cambridge, MA 02138 USA. Wayne State Univ, Sch Med, Dept Biol Sci, Detroit, MI 48202 USA. Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI 48202 USA. Toyama Med & Pharmaceut Univ, Dept Med 1, Toyama 93001, Japan. RP White, MF (reprint author), Harvard Univ, Joslin Diabet Ctr, Sch Med, Howard Hughes Med Inst, 1 Joslin Pl, Cambridge, MA 02138 USA. FU NIDDK NIH HHS [DK43808] NR 40 TC 57 Z9 57 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 20 PY 1998 VL 273 IS 47 BP 31061 EP 31067 DI 10.1074/jbc.273.47.31061 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 141HG UT WOS:000077136900033 PM 9813005 ER PT J AU Wechsler, H Rigotti, NA Gledhill-Hoyt, J Lee, H AF Wechsler, H Rigotti, NA Gledhill-Hoyt, J Lee, H TI Increased levels of cigarette use among college students - A cause for national concern SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID UNITED-STATES; SMOKING; PREVALENCE; INITIATION; DRINKING AB Context.-Adolescent smoking prevalence is tracked annually and has increased since 1991. In contrast, little is known about trends in smoking among college students, a group that has previously been more resistant to tobacco use than other young adults. Objective.-To examine changes in cigarette smoking among college students between 1993 and 1997 and among different types of students and colleges. Design.-Seif-administered survey (Harvard School of Public Health College Alcohol Study). Setting.-One hundred sixteen nationally representative 4-year colleges. Subjects.-A total of 15 103 randomly selected students in 1993 (70% response rate) and 14 251 students in 1997 (60% response rate). Main Outcome Measures.-Self-reports of cigarette smoking in the past 30 days and in the past year, age at smoking first cigarette, and number of attempts to quit. Results.-Over 4 years, the prevalence of current (30-day) cigarette smoking rose by 27.8%, from 22.3% to 28.5% (P<.001). The increase was observed in 99 of 116 colleges and was statistically significant(P<.05) in 27 (23%) of them. Current smoking increased across all student subgroups (defined by sex, race/ ethnicity, and year in school) and in all types of colleges. Smoking is rising faster in public schools (from 22.0% to 29.3%) than in private schools (from 22.9% to 26.8%). Eleven percent of college smokers had their first cigarette and 28% began to smoke regularly at or after age 19 years, by which time most were already in college. Half of current smokers tried to quit in the previous year; 18% had made 5 or more attempts to quit. Conclusions.-Cigarette use is increasing on campuses nationwide in all subgroups and types of colleges. Substantial numbers of college students are both starting to smoke regularly and trying to stop. National efforts to reduce smoking should be extended to college students. C1 Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Div Gen Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Calif Los Angeles, Ctr Vaccine Res, Los Angeles, CA USA. RP Wechsler, H (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, 677 Huntington Ave, Boston, MA 02115 USA. NR 29 TC 287 Z9 290 U1 3 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 18 PY 1998 VL 280 IS 19 BP 1673 EP 1678 DI 10.1001/jama.280.19.1673 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 138PD UT WOS:000076980700032 PM 9831998 ER PT J AU Silberstein, S Schlenstedt, G Silver, PA Gilmore, R AF Silberstein, S Schlenstedt, G Silver, PA Gilmore, R TI A role for the DnaJ homologue Scj1p in protein folding in the yeast endoplasmic reticulum SO JOURNAL OF CELL BIOLOGY LA English DT Article DE glycosylation; endoplasmic reticulum; chaperones; heat-shock protein 70; oligosaccharides ID SACCHAROMYCES-CEREVISIAE OLIGOSACCHARYLTRANSFERASE; MOLECULAR CHAPERONE; SECRETORY PROTEINS; GENE DISRUPTIONS; SHUTTLE VECTORS; ATPASE ACTIVITY; KARYOGAMY GENE; SEC PROTEINS; TRANSLOCATION; BIP AB Members of the eukaryotic heat shock protein 70 family (Hsp70s) are regulated by protein cofactors that contain domains homologous to bacterial DnaJ. Of the three DnaJ homologues in the yeast rough endoplasmic reticulum (RER; Scj1p, Sec63p, and Jem1p), Scj1p is most closely related to DnaJ, hence it is a probable cofactor for Kar2p, the major Hsp70 in the yeast RER. However, the physiological role of Scj1p has remained obscure due to the lack of an obvious defect in Kar2p-mediated pathways in scj1 null mutants. Here, we show that the Delta scj1 mutant is hypersensitive to tunicamycin or mutations that reduce N-linked glycosylation of proteins. Although maturation of glycosylated carboxypeptidase Y occurs with wild-type kinetics in Delta scj1 cells, the transport rate for an unglycosylated mutant carboxypeptidase Y (CPY) is markedly reduced. Loss of Scj1p induces the unfolded protein response pathway, and results in a cell wall defect when combined with an oligosaccharyltransferase mutation. The combined loss of both Scj1p and Jem1p exaggerates the sensitivity to hypoglycosylation stress, leads to further induction of the unfolded protein response pathway, and drastically delays maturation of an unglycosylated reporter protein in the RER. We propose that the major role for Scj1p is to cooperate with Kar2p to mediate maturation of proteins in the RER lumen. C1 Univ Massachusetts, Sch Med, Dept Biochem & Mol Biol, Worcester, MA 01655 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Univ Massachusetts, Sch Med, Dept Biochem & Mol Biol, 55 Lake Ave N, Worcester, MA 01655 USA. EM reid.gilmore@banyan.ummed.edu FU NIGMS NIH HHS [GM43768, GM47385, R01 GM043768] NR 64 TC 61 Z9 63 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD NOV 16 PY 1998 VL 143 IS 4 BP 921 EP 933 DI 10.1083/jcb.143.4.921 PG 13 WC Cell Biology SC Cell Biology GA 141NJ UT WOS:000077149800005 PM 9817751 ER PT J AU Hartwell, DM Mayadas, TN Berger, G Frenette, PS Rayburn, H Hynes, RO Wagner, DD AF Hartwell, DM Mayadas, TN Berger, G Frenette, PS Rayburn, H Hynes, RO Wagner, DD TI Role of P-selectin cytoplasmic domain in granular targeting in vivo and in early inflammatory responses SO JOURNAL OF CELL BIOLOGY LA English DT Article DE P-selectin; granular targeting; platelets; endothelium; cytoplasmic domain ID HUMAN-ENDOTHELIAL-CELLS; NECROSIS-FACTOR-ALPHA; WEIBEL-PALADE BODIES; LEUKOCYTE-ADHESION MOLECULE-1; REGULATED SECRETORY PATHWAY; MEMBRANE-PROTEIN GMP-140; GROWTH-FACTOR DOMAINS; DEFICIENT MICE; NEUTROPHIL ADHESION; PLASMA-MEMBRANE AB P-selectin is an adhesion receptor for leukocytes expressed on activated platelets and endothelial cells. The cytoplasmic domain of P-selectin was shown in vitro to contain signals required for both the sorting of this protein into storage granules and its internalization from the plasma membrane. To evaluate in vivo the role of the regulated secretion of P-selectin, we have generated a mouse that expresses P-selectin lacking the cytoplasmic domain (Delta CT mice). The deletion did not affect the sorting of P-selectin into alpha-granules of platelets but severely compromised the storage of P-selectin in endothelial cells. Unstored P-selectin was proteolytically shed from the plasma membrane, resulting in increased levels of soluble P-selectin in the plasma. The Delta CT-P-selectin appeared capable of mediating cell adhesion as it supported leukocyte rolling in the mutant mice. However, a secretagogue failed to upregulate leukocyte rolling in the Delta CT mice, indicating an absence of a releasable storage pool of P-selectin in the endothelium. Furthermore, the neutrophil influx into the inflamed peritoneum was only 30% of the wildtype level 2 h after stimulation. Our results suggest that different sorting mechanisms for P-selectin are used in platelets and endothelial cells and that the storage pool of P-selectin in endothelial cells is functionally important during early stages of inflammation. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Frenette, Paul/J-8272-2012 FU NHLBI NIH HHS [HL 41484, F32 HL009264, HL 53756, R01 HL053756]; NINDS NIH HHS [NS 33296] NR 69 TC 76 Z9 78 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV 16 PY 1998 VL 143 IS 4 BP 1129 EP 1141 DI 10.1083/jcb.143.4.1129 PG 13 WC Cell Biology SC Cell Biology GA 141NJ UT WOS:000077149800021 PM 9817767 ER PT J AU Burock, MA Buckner, RL Woldorff, MG Rosen, BR Dale, AM AF Burock, MA Buckner, RL Woldorff, MG Rosen, BR Dale, AM TI Randomized event-related experimental designs allow for extremely rapid presentation rates using functional MRI SO NEUROREPORT LA English DT Article DE event-related; fMRI; hemodynamic response; overlap; rapid presentation; visual stimulation ID CORTEX; TRIALS AB Previous studies have shown that hemodynamic response overlap severely limits the maximum presentation rate with event-related functional MRI (fMRI) using fixed intertrial experimental designs. Here we demonstrate that the use of randomized experimental designs can largely overcome this limitation, thereby allowing for event-related fMRI experiments with extremely rapid presentation rates. In the first experiment, fMRI time courses were simulated using a fixed intertrial interval design with intervals of 16, 3, and 1 s, and using a randomized design having the same mean intertrial intervals. We found that using fixed intertrial interval designs the transient information decreased with decreasing intertrial intervals, whereas using randomized designs the transient information increased with decreasing mean intertrial intervals. In a second experiment, fMRI data were collected from two subjects using a randomized paradigm with visual hemifield stimuli presented randomly every 500 ms. Robust event-related activation maps and hemodynamic response estimates were obtained. These results demonstrate the feasibility of performing event-related fMRI experiments with rapid, randomized paradigms identical to those used in electrophysiological and behavioral studies, thereby expanding the applicability of event-related fMRI to a whole new range of cognitive neurosciences questions and paradigms. NeuroReport 9: 3735-3739 (C) 1998 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Boston, MA 02129 USA. Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02129 USA. Washington Univ, Dept Psychol, St Louis, MO 63130 USA. Univ Texas, Hlth Sci Ctr, Res Imaging Ctr, San Antonio, TX 78284 USA. RP Dale, AM (reprint author), Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Bldg 149,13th St, Boston, MA 02129 USA. RI Dale, Anders/A-5180-2010 NR 17 TC 375 Z9 377 U1 2 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD NOV 16 PY 1998 VL 9 IS 16 BP 3735 EP 3739 DI 10.1097/00001756-199811160-00030 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 148FE UT WOS:000077493400034 PM 9858388 ER PT J AU Levy, WC Cerqueira, MD Harp, GD Johannessen, KA Abrass, IB Schwartz, RS Stratton, JR AF Levy, WC Cerqueira, MD Harp, GD Johannessen, KA Abrass, IB Schwartz, RS Stratton, JR TI Effect of endurance exercise training on heart rate variability at rest in healthy young and older men SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID RISK; BAROREFLEX; AGE; BRADYCARDIA; INFARCTION; BALANCE AB Heart rate variability (HRV) (SD of the RR interval), an index of parasympathetic tone, was measured at rest and during exercise in 13 healthy older men (age 60 to 82 years) and 11 healthy young men (age 24 to 32 years) before and after 6 months of aerobic exercise training. Before exercise training, the older subjects had a 47% lower HRV at rest compared with the young subjects (31 +/- 5 ms vs 58 +/- 4 ms, p = 0.0002), During peak exercise, the older subjects had less parasympathetic withdrawal than the young subjects (-45% vs -84%, p = 0.0001), Six months of intensive aerobic exercise training increased maximum oxygen consumption by 21% in the alder group and 17% in the young group (analysis of variance: overall training effect, p = 0.0001; training effect in young vs old, p = NS), Training decreased the heart rate at rest in both the older (-9 beats/min) and the young groups (-5 beats/min, before vs after, p = 0.0001), Exercise training increased HRV at rest (p = 0.009) by 68% in the older subjects (31 +/- 5 ms to 52 +/- 8 ms) and by 17% in the young subjects (58 +/- 4 ms to 68 +/- 6 ms). Exercise training Increases parasympathetic tone at rest in both the healthy older and young men, which may contribute to the reduction in mortality associated with regular exercise. (C) 1998 by Excerpta Medica, Inc. C1 Univ Washington, Seattle, WA 98195 USA. Seattle Vet Affairs Med Ctr, Dept Radiol, Div Nucl Med, Seattle, WA USA. Seattle Vet Affairs Med Ctr, Dept Med, Div Cardiol, Seattle, WA USA. Seattle Vet Affairs Med Ctr, Dept Med, Div Geriatr, Seattle, WA USA. RP Stratton, JR (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98109 USA. EM jrs@u.washington.edu FU NIA NIH HHS [AG 06581, K12AG00503] NR 30 TC 126 Z9 134 U1 5 U2 18 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 15 PY 1998 VL 82 IS 10 BP 1236 EP 1241 DI 10.1016/S0002-9149(98)00611-0 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 139AL UT WOS:000077005200015 PM 9832101 ER PT J AU Hung, J Koelling, T Semigran, MJ Dec, GW Levine, RA Di Salvo, TG AF Hung, J Koelling, T Semigran, MJ Dec, GW Levine, RA Di Salvo, TG TI Usefulness of echocardiographic determined tricuspid regurgitation in predicting event-free survival in severe heart failure secondary to idiopathic-dilated cardiomyopathy or to ischemic cardiomyopathy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID VENTRICULAR EJECTION FRACTION; DOPPLER COLOR-FLOW; TWO-DIMENSIONAL ECHOCARDIOGRAPHY; EXERCISE AB Tricuspid regurgitation (TR) is often a consequence of right ventricular (RV) dilation and hypokinesia.(1) The finding of TR may therefore provide an indirect measure of RV systolic dysfunction. The threefold purpose of the present study of patients with severe heart failure referred for cardiac transplant evaluation was to determine if echocardiographically detected TR is (1) associated with RV systolic dysfunction, (2) predicts event-free survival, and (3) compares favorably in prognostic value to peak VO2. C1 Harvard Univ, Heart Failure & Transplantat Ctr, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Di Salvo, TG (reprint author), Massachusetts Gen Hosp, MGH Heart Failure Ctr, Bigelow 628,55 Fruit St, Boston, MA 02114 USA. NR 8 TC 58 Z9 58 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 15 PY 1998 VL 82 IS 10 BP 1301 EP + DI 10.1016/S0002-9149(98)00624-9 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 139AL UT WOS:000077005200030 PM 9832116 ER PT J AU Strom, BL Abrutyn, E Berlin, JA Kinman, JL Feldman, RS Stolley, PD Levison, ME Korzeniowski, OM Kaye, D AF Strom, BL Abrutyn, E Berlin, JA Kinman, JL Feldman, RS Stolley, PD Levison, ME Korzeniowski, OM Kaye, D TI Dental and cardiac risk factors for infective endocarditis - A population-based, case-control study SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE endocarditis, bacterial; heart valve disease; dental care; antibiotics; risk factors ID MITRAL-VALVE PROLAPSE; AMERICAN-HEART-ASSOCIATION; BACTERIAL-ENDOCARDITIS; ANTIBIOTIC-PROPHYLAXIS; PREVENTION; CRITERIA; RECOMMENDATIONS; EFFICACY AB Background: Although antibiotic prophylaxis against infective endocarditis is recommended, the true risk factors for infective endocarditis are unclear. Objective: To quantitate the risk for endocarditis from dental treatment and cardiac abnormalities. Design: Population-based, case-control study Setting: 54 hospitals in the Philadelphia area. Patients: Persons with community-acquired infective endocarditis not associated with intravenous drug use were compared with community residents, matched by age, sex, and neighborhood of residence. Measurements: Information on demographic characteristics, host risk factors, and dental treatment was obtained from structured telephone interviews, dental records, and medical records. Results: During the preceding 3 months, dental treatment was no more frequent among case-patients than controls (adjusted odds ratio, 0.8 [95% CI, 0.4 to 1.5]). Of 273 case-patients, 104 (38%) knew of previous cardiac lesions compared with 17 controls (6%) (adjusted odds ratio, 16.7 [Cl, 7.4 to 37.4]). Case-patients more often had a history of mitral valve prolapse (adjusted odds ratio, 19.4 [Cl, 6.4 to 58.4]), congenital heart disease (adjusted odds ratio, 6.7 [Cl, 2.3 to 19.4]), cardiac valvular surgery (adjust ed odds ratio 74.6 [CI, 12.5 to 447]), rheumatic fever (adjusted odds ratio, 13.4 [CI, 4.5 to 39.5]), and heart murmur without other known cardiac abnormalities (adjusted odds ratio, 4.2 [CI, 2.0 to 8.9]). Among case-patients with known cardiac lesions-the target of prophylaxis - dental therapy was significantly (P = 0.03) less common than among controls (adjusted odds ratio, 0.2 [Cl, 0.04 to 0.7] over 3 months). Few participants received prophylactic antibiotics. Conclusions: Dental treatment does not seem to be a risk factor for infective endocarditis, even in patients with valvular abnormalities, but cardiac valvular abnormalities are strong risk factors. Few cases of infective endocarditis would be preventable with antibiotic prophylaxis, even with 100% effectiveness assumed. Current policies for prophylaxis should be reconsidered. C1 Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Allegheny Univ Hlth Sci, Dept Med, Philadelphia, PA 19102 USA. Allegheny Univ Hlth Sci, Sch Publ Hlth, Philadelphia, PA 19102 USA. Univ Maryland, Baltimore, MD 21201 USA. RP Strom, BL (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 824 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. FU NHLBI NIH HHS [R01 HL 39000] NR 29 TC 237 Z9 245 U1 1 U2 68 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 15 PY 1998 VL 129 IS 10 BP 761 EP + PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 138QW UT WOS:000076984800001 PM 9841581 ER PT J AU Freedman, R AF Freedman, R TI Biological phenotypes in the genetics of schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material C1 Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. RP Freedman, R (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Campus Box C-268-71,4200 E 9th Ave, Denver, CO 80262 USA. NR 2 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 1998 VL 44 IS 10 BP 939 EP 940 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 137WA UT WOS:000076938700001 PM 9821557 ER PT J AU Faraone, SV Biederman, J AF Faraone, SV Biederman, J TI Neurobiology of attention-deficit hyperactivity disorder SO BIOLOGICAL PSYCHIATRY LA English DT Review DE ADHD; genetics; neuroimaging; neurotransmitters; adversity ID DOPAMINE TRANSPORTER; RISK-FACTORS; FAMILIAL ASSOCIATION; NOVELTY SEEKING; CIGARETTE-SMOKING; GENETIC-ANALYSIS; THYROID-HORMONE; RECEPTOR LOCUS; DRUG-USE; NICOTINE AB Attention-deficit hyperactivity disorder (ADHD) is an early-onset clinically heterogeneous disorder of inattention, hyperactivity, and impulsivity. Family, twin, adoption, segregation analysis, and molecular genetic studies show that is has a substantial genetic component. Although their results are still tentative, molecular genetic studies suggest that three genes may increase the susceptibility to ADHD: the D4 dopamine receptor gene, the dopamine transporter gene, and the D2 dopamine receptor gene. Studies of environmental adversity have implicated pregnancy and delivery complications, marital distress, family dysfunction, and low social class. The pattern of neuropsychological deficits found in ADHD children implicate executive functions and working memory; this pattern is similar to what has been found among adults with frontal lobe damage, which suggests that the frontal cortex or regions projecting to the frontal cortex are dysfunctional in at least some ADHD children. Moreover neuroimaging studies implicate frontosubcortical pathways in ADHD. Notably, these pathways are rich in catecholamines, which have been implicated in ADHD by the mechanism of action of stimulants-the class of drugs that effectively treats many ADHD children. Yet human studies of the catecholamine hypothesis of ADHD have produced conflicting results, perhaps due to the insensitivity of peripheral measures. (C) 1998 Society of Biological Psychiatry. C1 Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit Acc 725, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit Acc 725, Fruit St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 NR 84 TC 382 Z9 393 U1 11 U2 59 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 1998 VL 44 IS 10 BP 951 EP 958 DI 10.1016/S0006-3223(98)00240-6 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 137WA UT WOS:000076938700003 PM 9821559 ER PT J AU Peskind, ER Jensen, CF Pascualy, M Tsuang, D Cowley, D Martin, DC Wilkinson, CW Raskind, MA AF Peskind, ER Jensen, CF Pascualy, M Tsuang, D Cowley, D Martin, DC Wilkinson, CW Raskind, MA TI Sodium lactate and hypertonic sodium chloride induce equivalent panic incidence, panic symptoms, and hypernatremia in panic disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE panic disorder; sodium lactate; hypertonic saline; vasopressin; cortisol; sodium ID PITUITARY-ADRENOCORTICAL UNRESPONSIVENESS; ATRIAL-NATRIURETIC-FACTOR; CEREBROSPINAL-FLUID; ATTACKS; ANXIETY; VASOPRESSIN; INFUSION; SECRETION; SENSITIVITY; YOHIMBINE AB Background: Although experimental induction of panic by infusion of 0.5 mol/L sodium lactate in persons with panic disorder was described three decades ago, the mechanism underlying this observation remains unclear Here we asked if the rapid administration of the large sodium load contained in the 0.5-mol/L sodium lactate infusion might be involved in panic induction. Methods: We compared in panic disorder and healthy subjects behavioral, electrolyte, endocrine, and acid-base responses to three double-blind randomly ordered equal volume 20-min infusions: 0.5 mol/L sodium lactate, hypertonic saline (3% sodium chloride), and normal saline placebo. Results: Sodium lactate (0.5 mol/L) and hypertonic saline produced the same high incidence of panic and equivalent increases in panic symptoms, serum sodium, and plasma vasopressin in the panic disorder subjects. Neither hyper tonic infusion increased cortisol or adrenacorticotropin. Na normal subject experienced panic in any condition. The 0.5-mol/L sodium lactate infusion induced alkalosis, whereas hypertonic saline and normal saline induced a mild acidosis. Conclusions: Hypertonic sodium solution containing either chloride or lactate anion induces panic in panic disorder. The large sodium loads delivered by hypertonic saline and 0.5 mol/L sodium lactate may be involved in the mechanism of panic induction. Published by Society of Biological Psychiatry. C1 VA Puget Sound Hlth Care Syst, MIRECC 16, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Epidemiol & Biostat, Seattle, WA 98195 USA. RP Peskind, ER (reprint author), VA Puget Sound Hlth Care Syst, MIRECC 16, 1660 S Columbian Way, Seattle, WA 98108 USA. RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 NR 50 TC 29 Z9 30 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 1998 VL 44 IS 10 BP 1007 EP 1016 DI 10.1016/S0006-3223(98)00053-5 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 137WA UT WOS:000076938700009 PM 9821565 ER PT J AU Gazda, H Lipton, JM Niemeyer, CM Vlachos, A Rokicka-Milewska, R Ohara, A Ploszynska, A Webber, A Nathan, DG Beggs, AH Sieff, CA AF Gazda, H Lipton, JM Niemeyer, CM Vlachos, A Rokicka-Milewska, R Ohara, A Ploszynska, A Webber, A Nathan, DG Beggs, AH Sieff, CA TI Diamond-Blackfan anemia is genetically heterogeneous. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. CUNY Mt Sinai Sch Med, Div Pediat Hematol Oncol, New York, NY 10029 USA. Univ Freiburg, Childrens Hosp, Freiburg, Germany. Warsaw Sch Med, Dept Pediat Hematol Oncol, Warsaw, Poland. Univ Gdansk, Dept Pediat Hematol Oncol, PL-80952 Gdansk, Poland. Toho Univ, Sch Med, Dept Pediat, Tokyo, Japan. NR 0 TC 2 Z9 2 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 3043 BP 16B EP 16B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121400057 ER PT J AU Kupfer, G Garcia-Higuera, I D'Andrea, AD AF Kupfer, G Garcia-Higuera, I D'Andrea, AD TI Identification of nuclear proteins that bind to the Fanconi anemia proteins, FAA and FAC. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 3050 BP 17B EP 17B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121400064 ER PT J AU Kupfer, G Naf, D Garcia-Higuera, I Yamashita, T Cheng, A Tipping, A Morgan, N Mathew, CG D'Andrea, AD AF Kupfer, G Naf, D Garcia-Higuera, I Yamashita, T Cheng, A Tipping, A Morgan, N Mathew, CG D'Andrea, AD TI A patient-derived mutant form of the Fanconi Anemia protein, FAA, is defective in nuclear translocation. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat, Boston, MA 02115 USA. Univ Tokyo, Inst Med Sci, Tokyo, Japan. UMDS, Guys Hosp, Div Med & Mol Genet, London, 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 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 3051 BP 18B EP 18B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121400065 ER PT J AU Means, RT Middleton, T van Laer, A AF Means, RT Middleton, T van Laer, A TI Elevated serum protein nitrotyrosine content is associated with increased marrow iron stores in anemic patients. SO BLOOD LA English DT Meeting Abstract C1 Ralph H Johnson VA Med Ctr, Charleston, SC USA. Med Univ S Carolina, Charleston, SC 29425 USA. RI Means, Robert/A-4454-2008 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 3058 BP 19B EP 19B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121400072 ER PT J AU Naf, D Kupfer, GM Suliman, A Lambert, K D'Andrea, AD AF Naf, D Kupfer, GM Suliman, A Lambert, K D'Andrea, AD TI Functional activity of the Fanconi anemia protein, FAA, requires FAC binding and nuclear localization. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 3059 BP 20B EP 20B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121400073 ER PT J AU Yamashita, T Kupfer, GM Naf, D Suliman, A Joenje, H Asano, S D'Andrea, AD AF Yamashita, T Kupfer, GM Naf, D Suliman, A Joenje, H Asano, S D'Andrea, AD TI The Fanconi Anemia pathway requires FAA phosphorylation and FAA/FAC nuclear accumulation. SO BLOOD LA English DT Meeting Abstract C1 Univ Tokyo, Inst Med Sci, Tokyo, Japan. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat, Boston, MA 02115 USA. Free Univ Amsterdam, Dept Human Genet, Amsterdam, Netherlands. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 3085 BP 26B EP 26B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121400099 ER PT J AU Poznansky, MC Olszak, I Silva-Arietta, S Foxall, R Piascik, A Van Gorder, M Adams, G Scadden, DT AF Poznansky, MC Olszak, I Silva-Arietta, S Foxall, R Piascik, A Van Gorder, M Adams, G Scadden, DT TI Hematopoiesis in the developing human: Comparative immunophenotype and function of CD34+ cells derived from multiple hematopoietic tissues. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 227 BP 57A EP 57A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300224 ER PT J AU Poznansky, MC Olszak, I Foxall, R Piascik, A Luster, AD Scadden, DT AF Poznansky, MC Olszak, I Foxall, R Piascik, A Luster, AD Scadden, DT TI Chemokine receptor expression and chemotaxis of CD34+ cells isolated from the human fetal hematopoietic system. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 226 BP 57A EP 57A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300223 ER PT J AU Cheng, T Shen, H Rodrigues, N Scadden, DT AF Cheng, T Shen, H Rodrigues, N Scadden, DT TI TGF-beta 1 induced cell cycle arrest of hematopoietic cells is independent of p21. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 245 BP 62A EP 62A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300242 ER PT J AU Ryder, JW Wu, SC Hamilton, E Hunter, S Anderson, SM AF Ryder, JW Wu, SC Hamilton, E Hunter, S Anderson, SM TI Downregulation of tyrosine phosphorylation and intracellular signalling pathways in cells expressing a constitutively activated mutant form of the common beta subunit of the GM-CSF, IL-3 and IL-5 receptors. SO BLOOD LA English DT Meeting Abstract C1 Denver VA Med Ctr, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 259 BP 65A EP 65A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300256 ER PT J AU Grabowski, EF Carter, C Tsukurov, O Conroy, N Abbott, WM Orkin, RW AF Grabowski, EF Carter, C Tsukurov, O Conroy, N Abbott, WM Orkin, RW TI A comparison of the tissue factor pathway in human umbilical vein and adult saphenous vein endothelial cells. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 3309 BP 77B EP 77B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121400325 ER PT J AU Zhou, M Gu, L Abshire, T Homans, A Billett, AL Yeager, AM Findley, HW AF Zhou, M Gu, L Abshire, T Homans, A Billett, AL Yeager, AM Findley, HW TI Induction of NFkB-p65/RelA protein by MDM2 in childhood acute lymphoblastic leukemia (ALL) cells: A novel mechanism by which MDM2 confers resistance to chemotherapy and poor prognosis. SO BLOOD LA English DT Meeting Abstract C1 Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA. Univ Vermont, Coll Med, Burlington, VT USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 328 BP 81A EP 81A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300325 ER PT J AU Sillaber, C Sattler, M Merchav, S Frank, DA Griffin, JD AF Sillaber, C Sattler, M Merchav, S Frank, DA Griffin, JD TI BCR/ABL kinase activity and the C-terminus of STAT5 are required for BCR/ABL STAT5 interaction. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 367 BP 90A EP 90A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300364 ER PT J AU Ilaria, RL de Aos, IE Rumjantsev, S Varticovski, L Van Etten, RA AF Ilaria, RL de Aos, IE Rumjantsev, S Varticovski, L Van Etten, RA TI The SH2 domain of BCR/ABL is required for induction of CML-like disease in mice but not for activation of phosphatidylinositol-3 kinase. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Tufts Univ, St Elizabeths Hosp, Sch Med, Boston, MA 02135 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 377 BP 92A EP 92A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300374 ER PT J AU Hideshima, T Chauhan, D Teoh, G Raje, N Treon, SP Ogata, A Anderson, KC AF Hideshima, T Chauhan, D Teoh, G Raje, N Treon, SP Ogata, A Anderson, KC TI Signaling by Kaposi's sarcoma-associated herpesvirus (KSHV) encoded viral interleukin-6 (vIL-6) in human IL-6 (hIL-6) dependent cell lines. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Hyogo Coll Med, Dept Internal Med, Nishinomiya, Hyogo, Japan. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 390 BP 95A EP 95A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300387 ER PT J AU Raje, N Gong, J Chauhan, D Teoh, G Avigan, D Wu, Z Chen, D Treon, SP Webb, I Kufe, D Anderson, KC AF Raje, N Gong, J Chauhan, D Teoh, G Avigan, D Wu, Z Chen, D Treon, SP Webb, I Kufe, D Anderson, KC TI Bone marrow (BM) and peripheral blood (PB) dendritic cells (DC's) from patients with multiple myeloma (MM) are the phenotypically and functionally normal despite the detection of Kaposi's sarcoma herpes virus (KSHV) gene sequences. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 389 BP 95A EP 95A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300386 ER PT J AU Treon, SP Maimonis, P Chauhan, D Raje, N Teoh, G Belch, AR Pilarski, LM Anderson, KC AF Treon, SP Maimonis, P Chauhan, D Raje, N Teoh, G Belch, AR Pilarski, LM Anderson, KC TI Soluble MUC-1 (sMUC-1) is elevated in multiple myeloma (MM) bone marrow (BM) plasma and inhibits T cell proliferation. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Chiron Diagnost Corp, Walpole, MA USA. Univ Alberta, Cross Canc Inst, Edmonton, AB, Canada. NR 0 TC 4 Z9 4 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 411 BP 100A EP 100A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300408 ER PT J AU Teoh, G Tai, YT Greenfield, EA Nguyen, KA Lee, JF Chauhan, D Treon, SP Raje, N Hideshima, T Anderson, KC AF Teoh, G Tai, YT Greenfield, EA Nguyen, KA Lee, JF Chauhan, D Treon, SP Raje, N Hideshima, T Anderson, KC TI Tumor rejection antigen 1 (GRP94) expression is induced by CD40 ligand activation of multiple myeloma cells and mediates allogeneic T cell reactivity. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. 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 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 412 BP 101A EP 101A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300409 ER PT J AU Berenson, J Webb, I Henick, K Vescio, R Swift, R Anderson, K Seaman, J AF Berenson, J Webb, I Henick, K Vescio, R Swift, R Anderson, K Seaman, J TI A phase II dose-ranging trial of single-agent pamidronate for relapsed/refractory multiple myeloma. SO BLOOD LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Novartis Pharmaceut, E Hanover, NJ USA. 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 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 436 BP 107A EP 107A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300432 ER PT J AU Schultze, JL Anderson, KA Gilleece, MH Michalak, S Hickey, A Webb, I Gribben, JG Nadler, LM AF Schultze, JL Anderson, KA Gilleece, MH Michalak, S Hickey, A Webb, I Gribben, JG Nadler, LM TI Autologous adoptive T cell transfer for a patient with plasma cell leukemia: Results of a pilot phase I trial. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 0 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 446 BP 109A EP 109A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300442 ER PT J AU Pozansky, M Levechio, J Oiszak, I Silva-Arietta, S Porter-Brooks, J Brody, K Adams, G Ramstedt, U Marasco, W Scadden, DT AF Pozansky, M Levechio, J Oiszak, I Silva-Arietta, S Porter-Brooks, J Brody, K Adams, G Ramstedt, U Marasco, W Scadden, DT TI Inhibition of HIV replication and growth advantage of CD4+ T-cells and monocytes derived from CD34+ cells transduced with an intracellular antibody directed against HIV-1 tat. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 584 BP 145A EP 145A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300580 ER PT J AU Nisbet-Brown, E Pulsipher, M Sieff, C Guinan, E Jungles, S Chung, M Mulligan, R D'Andrea, AD AF Nisbet-Brown, E Pulsipher, M Sieff, C Guinan, E Jungles, S Chung, M Mulligan, R D'Andrea, AD TI Enhanced clonigenic survival of primary bone marrow progenitor cells from Fanconi Anemia patients following retroviral-mediated gene transfer SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Genet, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 607 BP 150A EP 151A PN 1 PG 2 WC Hematology SC Hematology GA 141AW UT WOS:000077121300602 ER PT J AU Zhu, A Raymond, R Zheng, X Westrick, R Furie, BC Furie, B Kaufman, RJ Ginsburg, D AF Zhu, A Raymond, R Zheng, X Westrick, R Furie, BC Furie, B Kaufman, RJ Ginsburg, D TI Abnormalities of development and hemostasis in gamma-carboxylase deficient mice. SO BLOOD LA English DT Meeting Abstract C1 Univ Michigan, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, BIDMC, Boston, MA 02115 USA. NR 0 TC 4 Z9 4 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 611 BP 152A EP 152A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300606 ER PT J AU Sezaki, N Ishimaru, F Nakayama, H Fujii, N Nakase, K Harada, M Shipp, MA AF Sezaki, N Ishimaru, F Nakayama, H Fujii, N Nakase, K Harada, M Shipp, MA TI The type1 CD10/neutral endopeptidase 24.11 promoter: Differentiation stage-specific regulation by SP1. SO BLOOD LA English DT Meeting Abstract C1 Okayama Univ, Dept Med, Okayama 700, Japan. Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 3642 BP 155B EP 155B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121400661 ER PT J AU Adra, CN Iyengar, AR Syed, FA Donato, JL Lin, SR Hu, W Cheng, T Scadden, DT Shirakawa, T Lim, B AF Adra, CN Iyengar, AR Syed, FA Donato, JL Lin, SR Hu, W Cheng, T Scadden, DT Shirakawa, T Lim, B TI Gene structure, sequence, fine expression analysis and cellular localization of HTm4, a CD20/Fc epsilon RI beta homologue and a candidate gene for atopy. SO BLOOD LA English DT Meeting Abstract C1 Univ Oxford, Oxford OX1 2JD, England. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 658 BP 163A EP 163A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300653 ER PT J AU Bussel, J Guinan, E Blanchette, V Parham, A AF Bussel, J Guinan, E Blanchette, V Parham, A TI Amegakaryocytic thrombocytopenia (AMT): A survey of natural history and outcome. SO BLOOD LA English DT Meeting Abstract C1 New York Hosp, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Amgen Inc, Thousand Oaks, CA 91320 USA. NR 0 TC 2 Z9 2 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 715 BP 177A EP 177A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300711 ER PT J AU Kwack, K Saffaripour, S Denis, C Wagner, DD Schaub, RG AF Kwack, K Saffaripour, S Denis, C Wagner, DD Schaub, RG TI Recombinant human interleukin-11 increases plasma von Willebrand factor (vWF) and factor VIII concentration in mice. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Genet Inst, Cambridge, MA 02140 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 748 BP 185A EP 185A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300744 ER PT J AU Methia, N Denis, C Wagner, DD AF Methia, N Denis, C Wagner, DD TI Carboxypeptidase E is expressed in endothelial cells but is not involved in von Willebrand factor targeting to the regulated pathway. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 750 BP 185A EP 185A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300746 ER PT J AU Vyas, P Ault, K Jackson, CW Orkin, SH Shivdasani, RA AF Vyas, P Ault, K Jackson, CW Orkin, SH Shivdasani, RA TI Consequences of GATA-1 deficiency in megakaryocytes and platelets. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Maine Med Ctr, Res Inst, S Portland, ME USA. St Jude Childrens Res Hosp, Dept Expt Hematol, Memphis, TN 38105 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 791 BP 195A EP 195A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300787 ER PT J AU Li, J Kuter, DJ AF Li, J Kuter, DJ TI Cloning and functional characterization of a novel c-mpl variant expressed in CD34 cells, megakaryocytes and platelets. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hematol Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 853 BP 209A EP 209A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300849 ER PT J AU Yang, C Kuter, DJ AF Yang, C Kuter, DJ TI Regulation of circulating thrombopoietin (TPO) levels in the rut during thrombocytopenia; translating TPO mRNA is not altered. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hematol Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 855 BP 210A EP 210A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300851 ER PT J AU Kamel-Reid, S Hummel, JL Wells, RA Dube, ID Licht, JD AF Kamel-Reid, S Hummel, JL Wells, RA Dube, ID Licht, JD TI Deregulation of NPM and PLZF in a variant t(5;17) case of acute promyelocytic leukemia. SO BLOOD LA English DT Meeting Abstract C1 Toronto Hosp, Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M5T 2S8, Canada. Toronto Hosp, Princess Margaret Hosp, Dept Lab Med, Toronto, ON M5T 2S8, Canada. Univ Toronto, Toronto, ON, Canada. Sunnybrook Hlth Sci Ctr, Lab Med, Toronto, ON, Canada. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA USA. Mt Sinai Sch Med, Derald H Ruttenberg Canc Ctr, New York, NY USA. Mt Sinai Sch Med, Dept Med, New York, NY USA. Mt Sinai Sch Med, Dept Mol Biol, New York, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 864 BP 212A EP 212A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300860 ER PT J AU Liu, LQ Ilaria, R Van Etten, RA Zhang, DE AF Liu, LQ Ilaria, R Van Etten, RA Zhang, DE TI A novel ubiquitin protease in hematopoietic cell differentiation. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Beth Israel Deaconess Med Ctr,Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 877 BP 215A EP 215A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300873 ER PT J AU Neumann, CA Wen, ST Van Etten, RA AF Neumann, CA Wen, ST Van Etten, RA TI Role of the c-Abl tyrosine kinase in the cellular response to oxidative stress. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 879 BP 215A EP 215A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300875 ER PT J AU Donovan, JW Ladetto, M Gribben, JG AF Donovan, JW Ladetto, M Gribben, JG TI A novel method for assessing the dynamics of residual disease in B-cell malignancies by real-time quantitative PCR. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 913 BP 223A EP 223A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300909 ER PT J AU Nichols, KE Levitz, S Shannon, KE Wahrer, DCR Bell, DW Chang, G Hegde, S Neuberg, D Shafman, T Tarbell, NJ Mauch, P Ishioka, C Haber, DA Diller, L AF Nichols, KE Levitz, S Shannon, KE Wahrer, DCR Bell, DW Chang, G Hegde, S Neuberg, D Shafman, T Tarbell, NJ Mauch, P Ishioka, C Haber, DA Diller, L TI Heterozygous germline ATM mutations do not contribute to radiation-associated malignancies after Hodgkin's disease. SO BLOOD LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Tohoku Univ, Sendai, Miyagi 980, 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 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 3977 BP 228B EP 228B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121400997 ER PT J AU Fisher, DC van den Abbeele, A Singer, S Michalak, S Hickey, A Webb, I Nadler, LM Schultze, JL AF Fisher, DC van den Abbeele, A Singer, S Michalak, S Hickey, A Webb, I Nadler, LM Schultze, JL TI Phase I trial with CD40-activated follicular lymphoma cells: A novel cellular vaccine strategy for B cell malignancies. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 0 TC 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1010 BP 247A EP 247A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301006 ER PT J AU Suzuki, S Hanada, S Ishitsuka, K Uozumi, K Utsunomiya, A Takeuchi, S Arima, T Takahashi, H AF Suzuki, S Hanada, S Ishitsuka, K Uozumi, K Utsunomiya, A Takeuchi, S Arima, T Takahashi, H TI Human lymphocytes activated by chimeric SF-25 monoclonal antibody induce apoptosis of HTLV-1 infected T-cell lines resistant against anti-Fas, TNF alpha and IFN gamma. SO BLOOD LA English DT Meeting Abstract C1 Kagoshima Univ, Dept Internal Med 2, Kagoshima 8908520, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, GI Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1014 BP 248A EP 248A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301010 ER PT J AU Guo, XYD Wang, T Liu, F Savinov, S Loewe, R Kufe, D Austin, D Deisseroth, A AF Guo, XYD Wang, T Liu, F Savinov, S Loewe, R Kufe, D Austin, D Deisseroth, A TI Use of computational chemistry to design small molecular weight chemical inhibitors of the ABL tyrosine specific protein kinase in the P210bcrabl oncoprotein for therapy of CML SO BLOOD LA English DT Meeting Abstract C1 Yale Canc Ctr, New Haven, CT USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1036 BP 253A EP 253A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301030 ER PT J AU Ladetto, M Donovan, JW Schlossman, R Anderson, K Gribben, JG AF Ladetto, M Donovan, JW Schlossman, R Anderson, K Gribben, JG TI Limitations of quantitative detection of immunoglobulin heavy chain (IgH) gene rearrangements in multiple myeloma (MM) patients using real-time PCR SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1056 BP 258A EP 258A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301050 ER PT J AU Raje, N Kica, G Chauhan, D Teoh, G Treon, SP Hideshima, T Wally, J Zhang, Y Comenzo, RL Anderson, KC AF Raje, N Kica, G Chauhan, D Teoh, G Treon, SP Hideshima, T Wally, J Zhang, Y Comenzo, RL Anderson, KC TI Detection of Kaposi's sarcoma-associated herpesvirus (KSHV) gene sequences in amyloidosis (AL) SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Boston Med Ctr, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1072 BP 261A EP 261A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301066 ER PT J AU Andrews, D Kawai, T Weymouth, D Saidman, S Wee, SL Boskovic, S Ko, D Abrahamiam, G Hong, H Colvin, RB Sykes, M Sachs, DH Cosimi, AB AF Andrews, D Kawai, T Weymouth, D Saidman, S Wee, SL Boskovic, S Ko, D Abrahamiam, G Hong, H Colvin, RB Sykes, M Sachs, DH Cosimi, AB TI Donor hematopoietic microchimerism is associated with graft acceptance in a Cynomolgus monkey model of combined bone marrow and solid organ transplantation SO BLOOD LA English DT Meeting Abstract ID CHIMERISM; TOLERANCE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Unit,Dept Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Blood Transfus Serv, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1083 BP 264A EP 264A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301076 ER PT J AU Cooke, KR Hill, G Gerbitz, A Kobzik, L Crawford, JM Brinson, Y Ferrara, JLM AF Cooke, KR Hill, G Gerbitz, A Kobzik, L Crawford, JM Brinson, Y Ferrara, JLM TI Hyporesponsiveness of donor accessory cells to LPS reduces the severity of TNF alpha mediated lung disease after experimental bone marrow transplantation. SO BLOOD LA English DT Meeting Abstract C1 Yale Sch Med, Dept Pathol, New Haven, CT USA. Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1091 BP 266A EP 266A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301084 ER PT J AU Gazitt, Y Freytes, C Callander, N Tsai, TW Alsina, M Anderson, J Cruz, J Alvarez, R Montgomery, W Devore, P McGrath, M West, G AF Gazitt, Y Freytes, C Callander, N Tsai, TW Alsina, M Anderson, J Cruz, J Alvarez, R Montgomery, W Devore, P McGrath, M West, G TI Successful stem cell mobilization with high dose of G-CSP alone for patients failing first round of mobilization. SO BLOOD LA English DT Meeting Abstract C1 Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. 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 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1112 BP 271A EP 271A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301105 ER PT J AU Henick, K Vescio, R Scott, S Lee, M Schiller, G Berenson, J AF Henick, K Vescio, R Scott, S Lee, M Schiller, G Berenson, J TI The use of pamidronate prior to autologous peripheral blood stem cell transplant does not impact mobilization or engraftment in multiple myeloma patients. SO BLOOD LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1120 BP 273A EP 273A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301113 ER PT J AU Cruz, JC Alsina, M Anderson, J Mundy, GR Yoneda, T Roodman, GD AF Cruz, JC Alsina, M Anderson, J Mundy, GR Yoneda, T Roodman, GD TI Effect of ibandronate in an in vivo model of multiple myeloma. SO BLOOD LA English DT Meeting Abstract C1 Vet Adm Med Ctr, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. 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 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 4186 BP 275B EP 275B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121401209 ER PT J AU Callander, N Garaz, C Cruz, J Litofsky, I Freytes, C Tsai, T Anderson, J Alsina, M Holle, L AF Callander, N Garaz, C Cruz, J Litofsky, I Freytes, C Tsai, T Anderson, J Alsina, M Holle, L TI Active smoking increases morbidity associated with autologous marrow and peripheral blood progenitor cell transplantation. SO BLOOD LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1137 BP 277A EP 277A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301130 ER PT J AU Colby, C McAfee, SL Sackstein, R Finkelstein, D Fishman, JA Spitzer, TR AF Colby, C McAfee, SL Sackstein, R Finkelstein, D Fishman, JA Spitzer, TR TI A prospective randomized trial comparing the toxicity and safety of atovaquone versus trimethoprim/sulfarieteioxazole as Pneumocystis carinii pneumonia prophylaxis following autologous peripheral blood stem cell transplantation. SO BLOOD LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1138 BP 278A EP 278A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301131 ER PT J AU Spitzer, TR Friedman, C Bushnell, W Raschko, J Frankel, SR AF Spitzer, TR Friedman, C Bushnell, W Raschko, J Frankel, SR TI Oral granisetron (Kytril((R))) and ondansetron (Zofran((R))) in the prevention of hyperfractionated total body irradiation induced emesis: The results of a double-blind, randomized parallel group study SO BLOOD LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. SmithKline Beecham Pharmaceut, Collegeville, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1140 BP 278A EP 278A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301133 ER PT J AU Vasconcelles, MJ Bernardo, MVP King, C Weller, EA Antin, JH AF Vasconcelles, MJ Bernardo, MVP King, C Weller, EA Antin, JH TI Aerosolized pentamidine (AP) as Pneumocystis prophylaxis following bone marrow transplantation (BMT) is inferior to other regimens and is associated with decreased survival and an increased risk of other infections SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Partners Canc Care, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1163 BP 284A EP 284A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301156 ER PT J AU Sykes, M Pearson, DA Swenson, K Zhao, G Yang, YG Pelot, MR AF Sykes, M Pearson, DA Swenson, K Zhao, G Yang, YG Pelot, MR TI Lymphohematopoietic graft-vs-host reactions without graft-vs-host disease induced in murine mixed chimeras established with a cyclophosphamide-based non-myeloablative conditioning regimen. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Surg Serv,Transplantat Biol Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 4246.5 BP 289B EP 289B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121401270 ER PT J AU Soiffer, R Alyea, E Weller, E Mauch, P Freedman, A Fisher, D Schlossman, R Gribben, J Stone, R Webb, I Kuhlman, C Nazir, F Antin, J Ritz, J AF Soiffer, R Alyea, E Weller, E Mauch, P Freedman, A Fisher, D Schlossman, R Gribben, J Stone, R Webb, I Kuhlman, C Nazir, F Antin, J Ritz, J TI Impact of CD6(+) T-cell depletion on GVHD, engraftment, and outcome in patients undergoing allogeneic BMT from unrelated donors SO BLOOD LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1187 BP 290A EP 290A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301180 ER PT J AU Chang, Q Sciortino, T Colby, C Fuchimoto, Y Nash, K Cooper, DKC Sachs, DH White-Scharf, ME AF Chang, Q Sciortino, T Colby, C Fuchimoto, Y Nash, K Cooper, DKC Sachs, DH White-Scharf, ME TI Porcine recombinant cytokines are effective in mobilizing peripheral blood progenitor cells (PBPC) in the miniature swine. SO BLOOD LA English DT Meeting Abstract C1 BioTransplant Inc, Charlestown, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 4287 BP 298B EP 299B PN 2 PG 2 WC Hematology SC Hematology GA 141AX UT WOS:000077121401312 ER PT J AU Nichols, KE Harkin, DP Levitz, S Krainer, M Kolquist, A Gresko, C Bernard, A Ferguson, M Zuo, L Snyder, E Buckler, AJ Wise, C Ashley, J Lovett, M Valentine, M Look, AT Gerald, W Housman, DE Haber, DA AF Nichols, KE Harkin, DP Levitz, S Krainer, M Kolquist, A Gresko, C Bernard, A Ferguson, M Zuo, L Snyder, E Buckler, AJ Wise, C Ashley, J Lovett, M Valentine, M Look, AT Gerald, W Housman, DE Haber, DA TI Inactivating mutations in an SH2 domain-encoding gene in X-linked lymphoproliferative syndrome. SO BLOOD LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Axys Pharmaceut, San Diego, CA USA. Univ Texas, SW Med Ctr, Dallas, TX USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1233 BP 301A EP 301A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301225 ER PT J AU Schiffer, CR Miller, K Larson, RA Stone, R Amrein, P Antin, JH Zani, VJ AF Schiffer, CR Miller, K Larson, RA Stone, R Amrein, P Antin, JH Zani, VJ TI A double blind, placebo controlled trial evaluating pegylated recombinant human megakaryocyte growth and development factor (MGDF) as an adjunct to induction and consolidation therapy inpatients with acute myeloid leukemia (AML). SO BLOOD LA English DT Meeting Abstract C1 Univ Chicago, Chicago, IL 60637 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. NR 0 TC 3 Z9 3 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1283 BP 313A EP 313A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301275 ER PT J AU Ilaria, RL Harley, B Rumjantsev, S Grusby, MJ Van Etten, RA AF Ilaria, RL Harley, B Rumjantsev, S Grusby, MJ Van Etten, RA TI STAT6 is required for efficient transformation of B-lymphoid cells by Bcr/Abl and v-Abl. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1304 BP 318A EP 318A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301296 ER PT J AU Gribben, JG Neuberg, D Soiffer, RJ Fisher, DC Schlossman, R Alyea, EP Kuhlman, C Ritz, J Nadler, LM AF Gribben, JG Neuberg, D Soiffer, RJ Fisher, DC Schlossman, R Alyea, EP Kuhlman, C Ritz, J Nadler, LM TI Autologous versus allogeneic bone marrow transplantation for patients with poor prognosis CLL. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 14 Z9 14 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1320 BP 322A EP 322A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301312 ER PT J AU Lavoie, J Belanger, R Robertson, MJ Stone, R Perreault, C Kassis, J Busque, L Soiffer, RJ Ritz, J Roy, DC AF Lavoie, J Belanger, R Robertson, MJ Stone, R Perreault, C Kassis, J Busque, L Soiffer, RJ Ritz, J Roy, DC TI Autologous bone marrow transplant (BMT) purged with anti-CD33 immunotoxin for patients with acute myeloid leukemia (AML). SO BLOOD LA English DT Meeting Abstract C1 Hop Maison Neuve Rosemont, Div Hematol Immunol, Montreal, PQ H1T 2M4, Canada. Dana Farber Canc Inst, Ctr Hematol Oncol, Boston, MA 02115 USA. RI Perreault, Claude/A-7220-2008 OI Perreault, Claude/0000-0001-9453-7383 NR 0 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1325 BP 323A EP 323A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301317 ER PT J AU Stuhler, G Zobywalski, A Grunebach, F Brossart, P Reichardt, VL Stevanovic, S Brugger, W Kanz, L Schlossman, SF AF Stuhler, G Zobywalski, A Grunebach, F Brossart, P Reichardt, VL Stevanovic, S Brugger, W Kanz, L Schlossman, SF TI CD70 molecules, expressed by activated cytolytic T lymphocytes, determine helper T cells to upregulate CD40L for subsequent dendritic cell stimulation. SO BLOOD LA English DT Meeting Abstract C1 Univ Tubingen, Dept Med 2, Tubingen, Germany. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1396 BP 340A EP 340A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301388 ER PT J AU Berger, G Hartwell, DW Wagner, DD AF Berger, G Hartwell, DW Wagner, DD TI Platelet death. An apoptotic-like process? SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1429 BP 347A EP 347A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301421 ER PT J AU Frenette, PS Denis, C Subbarao, S Vestweber, D Wagner, DD AF Frenette, PS Denis, C Subbarao, S Vestweber, D Wagner, DD TI P-selectin glycoprotein ligand-1 is expressed on platelets and mediates platelet-endothelial interactions in vivo. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Univ Muenster, Munster, Germany. RI Frenette, Paul/J-8272-2012 NR 0 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1433 BP 348A EP 348A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301425 ER PT J AU Peng, JP deSauvage, FJ Shivdasani, RA Burstein, SA AF Peng, JP deSauvage, FJ Shivdasani, RA Burstein, SA TI Thrombocytopenia modestly decreases the extent of atherosclerosis in female hyperlipidemic mice. SO BLOOD LA English DT Meeting Abstract C1 Univ Oklahoma, Hlth Sci Ctr, WK Warren Med Res Inst, Oklahoma City, OK USA. Genentech Inc, S San Francisco, CA 94080 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1444 BP 351A EP 351A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301436 ER PT J AU Carlesso, N Aster, J Sklar, J Scadden, DT AF Carlesso, N Aster, J Sklar, J Scadden, DT TI Notch-induced delay of human hematopoietic progenitor cell differentiation is associated with altered cell cycle kinetics SO BLOOD LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1494 BP 363A EP 363A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301486 ER PT J AU Shen, H Garcia-Zepeda, EG Luster, AD Scadden, DT AF Shen, H Garcia-Zepeda, EG Luster, AD Scadden, DT TI Disparate chemokine receptor expression and function on human CD34+ cells from different tissue types. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1506 BP 366A EP 366A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301498 ER PT J AU Robinson, SN Freedman, AS Neuberg, D Mauch, PM AF Robinson, SN Freedman, AS Neuberg, D Mauch, PM TI In vitro determination of hematopoietic stem cell content correlates with poor engraftment in lymphoma patients receiving autologous bone marrow transplantation. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Radiat Oncol, Joint Ctr Radiat Therapy, Boston, MA USA. Dana Farber Canc Inst, Div Hematol Malignancies & Biostat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 4600 BP 372B EP 372B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121401626 ER PT J AU Italiano, JE Lecine, P Shivdasani, RA Hartwig, JH AF Italiano, JE Lecine, P Shivdasani, RA Hartwig, JH TI Ultrastructure and dynamics of proplatelet formation by mouse megakaryocytes. SO BLOOD LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. 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 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 15505 BP 376A EP 376A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301543 ER PT J AU Parsons, S Mayer, D Neuberg, D Land, V Laver, J AF Parsons, S Mayer, D Neuberg, D Land, V Laver, J TI Growth factor practice patterns in pediatric oncology: Results of the 1998 POG survey. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. POG Operat Off, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1568 BP 380A EP 380A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301561 ER PT J AU Lu, FM John, KM Peters, LL Lux, SE AF Lu, FM John, KM Peters, LL Lux, SE TI Ban1, a ubiquitous 16 kDa protein, binds to the ankyrin repeats of Notch1 and inhibits Notch1 signaling. SO BLOOD LA English DT Meeting Abstract C1 Jackson Lab, Bar Harbor, ME 04609 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1586 BP 384A EP 384A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301579 ER PT J AU Loh, ML Silverman, LB Young, ML Neuberg, D Golub, TR Sallan, SE Gilliland, DG AF Loh, ML Silverman, LB Young, ML Neuberg, D Golub, TR Sallan, SE Gilliland, DG TI Low incidence of TEL/AML1 fusion in children with relapsed acute lymphoblastic leukemia. SO BLOOD LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Howard Hughes Med Inst, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1617 BP 391A EP 391A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301609 ER PT J AU Wang, S Rosenwald, IB Hutzler, MJ Pihan, GA Schmidt, EV Savas, L Woda, BA AF Wang, S Rosenwald, IB Hutzler, MJ Pihan, GA Schmidt, EV Savas, L Woda, BA TI Expression of the eukaryotic translation initiation factors 4E and 2 alpha in non-Hodgkins lymphomas. SO BLOOD LA English DT Meeting Abstract C1 Univ Massachusetts, Med Ctr, Dept Pathol, Worcester, MA USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1686 BP 408A EP 408A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301678 ER PT J AU Liou, JR Zaleskas, JM Kaneki, M Stone, RM AF Liou, JR Zaleskas, JM Kaneki, M Stone, RM TI Activation of the extracellular signal-regulated kinase (ERK) pathway is involved in granulocytic and monocytic differentiation of human leukemia cells. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1728 BP 418A EP 418A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301720 ER PT J AU Pan, L Teshima, T Hill, G Burgard, D Brinson, Y Reddy, V Ferrara, JLM AF Pan, L Teshima, T Hill, G Burgard, D Brinson, Y Reddy, V Ferrara, JLM TI G-CSF mobilized allogeneic peripheral blood stem cell transplant (PBSCT) maintains the GVL effect through a perforin dependent pathway. SO BLOOD LA English DT Meeting Abstract C1 Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RI teshima, takanori/G-1671-2012 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 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1803 BP 436A EP 436A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301795 ER PT J AU Teoh, G Chen, L Urashima, M Tai, YT Celi, LA Chen, D Chauhan, D Ogata, A Finberg, RW Webb, IJ Kufe, DW Anderson, KC AF Teoh, G Chen, L Urashima, M Tai, YT Celi, LA Chen, D Chauhan, D Ogata, A Finberg, RW Webb, IJ Kufe, DW Anderson, KC TI Adenovirus vector-based purging of multiple myeloma cells. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1840 BP 445A EP 445A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301831 ER PT J AU Webb, IJ Weller, E Daley, HL Schott, DM Alyea, EP Ritz, J Soiffer, RJ AF Webb, IJ Weller, E Daley, HL Schott, DM Alyea, EP Ritz, J Soiffer, RJ TI Determination of cell thresholds for acute graft-versus-host disease (GVHD) in recipients of T cell depleted bone marrow infused without GVHD prophylaxis. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1869 BP 452A EP 452A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301860 ER PT J AU Friedberg, J Neuberg, D Stone, R Alyea, E Jallow, H Ritz, J Soiffer, R Freedman, A AF Friedberg, J Neuberg, D Stone, R Alyea, E Jallow, H Ritz, J Soiffer, R Freedman, A TI Outcome of allogeneic bone marrow transplantation in patients with myelodysplasia following autologous bone marrow transplantation for non-Hodgkin's lymphoma. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1880 BP 455A EP 455A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301871 ER PT J AU Pang, Q Fagerlie, S Christianson, TA Keeble, W Bagby, GC AF Pang, Q Fagerlie, S Christianson, TA Keeble, W Bagby, GC TI The Fanconi anemia (FA) protein FAC is required for recruitment of Stat1 to the IFN gamma receptor complex. SO BLOOD LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Oregon Canc Ctr, Dept Med, Div Hematol & Med Oncol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. 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 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1967 BP 476A EP 477A PN 1 PG 2 WC Hematology SC Hematology GA 141AW UT WOS:000077121301957 ER PT J AU Uemura, N Griffin, JD AF Uemura, N Griffin, JD TI Overexpression of the adaptor protein CRKL in hematopoietic cells increases spontaneous migration across a transwell membrane. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1975 BP 479A EP 479A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301965 ER PT J AU Donovan, JW Poor, C Bowers, D Waters, S Sallan, S Gribben, JG AF Donovan, JW Poor, C Bowers, D Waters, S Sallan, S Gribben, JG TI Prospective analysis of residual disease in childhood acute lymphoblastic leukemia: Detection, quantitation and the utility of bone marrow versus peripheral blood samples. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1983 BP 481A EP 481A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301973 ER PT J AU Silverman, LB Gelber, RD Kimball-Dalton, V Young, ML Sallan, SE AF Silverman, LB Gelber, RD Kimball-Dalton, V Young, ML Sallan, SE TI Results of the Dana-Farber Cancer Institute (DFCI) Consortium Protocol 91-01 for children with acute lymphoblastic leukemia (ALL). SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, DFCI ALL Consortium, Boston, MA 02115 USA. NR 0 TC 4 Z9 4 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1990 BP 483A EP 483A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301980 ER PT J AU Johnson, PWM Gribben, JG Nadler, LM Schultze, JL AF Johnson, PWM Gribben, JG Nadler, LM Schultze, JL TI Soluble CD40 ligand induces proliferation rather than apoptosis in primary human low-grade lymphoma: Implications for immunotherapy. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 0 TC 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1995 BP 484A EP 484A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301985 ER PT J AU Li, S Ilaria, RL Million, RP Daley, GQ Van Etten, RA AF Li, S Ilaria, RL Million, RP Daley, GQ Van Etten, RA TI The P190, P210, and P230 forms of the BCR/ABL oncogene induce a similar chronic myeloid leukemia-like syndrome in mice but have different lymphoid leukemogenic activity. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2007 BP 486A EP 487A PN 1 PG 2 WC Hematology SC Hematology GA 141AW UT WOS:000077121301997 ER PT J AU Salgia, R Lin, J Narsimhan, RP Chen, WC Mach, N Dranoff, G Sattler, M Griffin, JD AF Salgia, R Lin, J Narsimhan, RP Chen, WC Mach, N Dranoff, G Sattler, M Griffin, JD TI Role of small GTPases and PI3-kinase in controlling cell motility of untransformed and BCR/ABL-transformed hematopoietic cells. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. 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 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2010 BP 487A EP 487A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302000 ER PT J AU Sattler, M Saigia, R Weisberg, E Shrikhande, G Verma, S Byrne, C Winkler, T Algate, P Rohrschneider, LR Griffin, JD AF Sattler, M Saigia, R Weisberg, E Shrikhande, G Verma, S Byrne, C Winkler, T Algate, P Rohrschneider, LR Griffin, JD TI BCR/ABL directly inhibits expression of SHIP, the SH2- containing polyinositol-5-phosphatase involved in the regulation of hematopoiesis. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. 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 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2009 BP 487A EP 487A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301999 ER PT J AU Schmittling, R Lu, T Ritz, J Monroy, R AF Schmittling, R Lu, T Ritz, J Monroy, R TI Rapid and effective depletion of B cells using CD19 and CD20 monclonal antibodies coupled to high density microparticles (HDM). SO BLOOD LA English DT Meeting Abstract C1 Coulter Cellular Therapies Inc, Roxbury, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. 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 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2026 BP 492A EP 492A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302016 ER PT J AU Vonderheide, RH Hahn, WC Schultze, JL Nadler, LM AF Vonderheide, RH Hahn, WC Schultze, JL Nadler, LM TI Search for universal tumor antigens: Potential of the catalytic telomerase subunit. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2058 BP 500A EP 500A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302048 ER PT J AU Adler, HT Chinery, R Wu, DY Kussick, SJ Tkachuk, DC AF Adler, HT Chinery, R Wu, DY Kussick, SJ Tkachuk, DC TI Leukemic HRX fusion proteins abrogate DNA damage-induced apoptosis. SO BLOOD LA English DT Meeting Abstract C1 Va Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA USA. Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Lab Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Vanderbilt Univ, Dept Cell Biol, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2094 BP 509A EP 509A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302084 ER PT J AU Ghia, P Schaniel, C Sallusto, F Rolink, AG Nadler, L Cardoso, AA AF Ghia, P Schaniel, C Sallusto, F Rolink, AG Nadler, L Cardoso, AA TI Activated pre-B ALL cells secrete the novel chemokine, MDC, inducing transendothelial migration of anti-leukemia-specific T cells. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Basel Inst Immunol, Basel, Switzerland. RI Schaniel, Chrisoph/C-9655-2012 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 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2104 BP 511A EP 511A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302094 ER PT J AU Veiga, JP Afonso, H Sallan, SE Nadler, LM Cardoso, AA AF Veiga, JP Afonso, H Sallan, SE Nadler, LM Cardoso, AA TI Acute lymphoblastic leukemia cells and their bone marrow stroma collaborate to induce endothelial cell proliferation thereby promoting leukemia cell survival. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2102 BP 511A EP 511A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302092 ER PT J AU Aguiar, RCT Kharbanda, S Yakushijin, Y Salgia, R Freeman, GJ Morgan, T Fletcher, J Shipp, MA AF Aguiar, RCT Kharbanda, S Yakushijin, Y Salgia, R Freeman, GJ Morgan, T Fletcher, J Shipp, MA TI Molecular and functional analyses of a novel risk-related gene, bal, in diffuse large B-cell lymphomas. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2110 BP 513A EP 513A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302100 ER PT J AU Chauhan, D Barati, A Raje, N Pinkus, GS Pinkus, JL Hideshima, T Teoh, G Ogata, A Fingeroth, JD Gustafson, EA Treon, SP Anderson, KC AF Chauhan, D Barati, A Raje, N Pinkus, GS Pinkus, JL Hideshima, T Teoh, G Ogata, A Fingeroth, JD Gustafson, EA Treon, SP Anderson, KC TI Detection of human herpes virus-8 (HHV-8) sequence in multiple myeloma (MM) bone marrow stomal cells (BMSCs). SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2116 BP 514A EP 515A PN 1 PG 2 WC Hematology SC Hematology GA 141AW UT WOS:000077121302106 ER PT J AU Trojan, AH Schultze, JL Vonderheide, RH Ladetto, M Donovan, JW Gribben, JG AF Trojan, AH Schultze, JL Vonderheide, RH Ladetto, M Donovan, JW Gribben, JG TI Low likelihood of CD8(+) T cell responses against peptides derived from Ig heavy chain rearrangements in B-cell malignancies. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2113 BP 514A EP 514A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302103 ER PT J AU Wu, CJ Neuberg, D Alyea, EP Chillemi, A Orsini, E Soiffer, R Ritz, J AF Wu, CJ Neuberg, D Alyea, EP Chillemi, A Orsini, E Soiffer, R Ritz, J TI Reconstitution of T cell receptor repertoire diversity following allogeneic bone marrow transplantation is related to hematopoietic chimerism. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2126 BP 517A EP 517A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302116 ER PT J AU Spitzer, TR McAfee, SL Sackstein, R Toh, HC Saidman, S Weymouth, D Preffer, F Colby, C Sachs, DH Sykes, M AF Spitzer, TR McAfee, SL Sackstein, R Toh, HC Saidman, S Weymouth, D Preffer, F Colby, C Sachs, DH Sykes, M TI Induction of mixed chimerism and potent anti-tumor responses following non-myeloablative conditioning therapy and HLA-matched and mismatched donor bone marrow transplantation (BMT) for refractory hematologic malignancies (HM). SO BLOOD LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Bone Marrow Transplant Program, Boston, MA 02114 USA. NR 0 TC 4 Z9 4 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2134 BP 519A EP 519A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302124 ER PT J AU Sykes, M Saidman, SL Preffer, F McAfee, S Weymouth, D Dombkowski, D Andrews, D Colby, C Sackstein, R Sachs, DH Spitzer, TR AF Sykes, M Saidman, SL Preffer, F McAfee, S Weymouth, D Dombkowski, D Andrews, D Colby, C Sackstein, R Sachs, DH Spitzer, TR TI Mixed lymphohematopoietic chimerism in adult recipients following non-myeloablative therapy and HLA-matched or mismatched donor bone marrow transplantation, and the effect of donor leukocyte infusions. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02129 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2136 BP 520A EP 520A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302126 ER PT J AU Pozzi, N Gaetaniello, L Matrecano, E Cavalcanti, MR Duke-Cohan, JS Pignata, C AF Pozzi, N Gaetaniello, L Matrecano, E Cavalcanti, MR Duke-Cohan, JS Pignata, C TI Defective costimulation mediated by the gp175 kDa attractin in common variable immunodeficiency. SO BLOOD LA English DT Meeting Abstract C1 Univ Naples Federico II, Dept Pediat, Naples, Italy. Dana Farber Canc Inst, Boston, MA 02115 USA. RI Pignata, Claudio/O-2466-2013 OI Pignata, Claudio/0000-0003-1568-9843 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2212 BP 539A EP 539A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302201 ER PT J AU Golub, TR Tamayo, P Zhu, Q Coller, H Park, J Theilhaber, J Nowillo, K Kitarewan, S Slonim, D Mesiroy, J Dmitrovsky, E Lander, ES AF Golub, TR Tamayo, P Zhu, Q Coller, H Park, J Theilhaber, J Nowillo, K Kitarewan, S Slonim, D Mesiroy, J Dmitrovsky, E Lander, ES TI A genome-wide approach to hematopoietic differentiation. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2342 BP 569A EP 569A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302329 ER PT J AU Lecine, P Italiano, JE Aksoy, E Shivdasani, RA AF Lecine, P Italiano, JE Aksoy, E Shivdasani, RA TI Molecular analysis of genetically thrombocytopenic mice reveals a potential biochemical pathway for terminal megakaryocyte differentiation and platelet release. SO BLOOD LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RI Lecine, Patrick/H-9338-2016 NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2340 BP 569A EP 569A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302327 ER PT J AU Kwiatkowski, BA Hickstein, DD AF Kwiatkowski, BA Hickstein, DD TI Expression of the ETS family member Tel reverses the phenotype in cells expressing Fli-1. SO BLOOD LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Sch Med, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2348 BP 571A EP 571A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302335 ER PT J AU Fagerlie, SR Christianson, TA Keeble, W Diaz, J Bagby, GC AF Fagerlie, SR Christianson, TA Keeble, W Diaz, J Bagby, GC TI The fanconi anemia (FA) protein FAC modulates expression of IFN gamma inducible genes (IRF-1, p21(waf1), and ISGF3 gamma). SO BLOOD LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Ctr Canc, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Med, Div Hematol & Med Oncol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2371 BP 576A EP 576A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302358 ER PT J AU Jaster, R Baek, KH D'Andrea, AD AF Jaster, R Baek, KH D'Andrea, AD TI Identification of a conserved interleukin-3 inducible, JAK-dependent, STAT-independent enhancer element regulating DUB gene expression. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Rostock, Inst Med Biochem, Rostock, Germany. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2370 BP 576A EP 576A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302357 ER PT J AU Sackstein, R Antoniu, B AF Sackstein, R Antoniu, B TI Structural biology of a novel L-selectin ligand expressed on hematopoietic progenitor cells. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2402 BP 583A EP 583A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302389 ER PT J AU Feng, S Christodoulides, N Kroll, MH AF Feng, S Christodoulides, N Kroll, MH TI Expression of the Gp Ib/IX complex regulates cell growth. SO BLOOD LA English DT Meeting Abstract C1 Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA. Rice Univ, Houston, TX 77251 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2405 BP 584A EP 584A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302392 ER PT J AU Frenette, PS Subbarao, S Mazo, IB von Andrian, UH Wagner, DD AF Frenette, PS Subbarao, S Mazo, IB von Andrian, UH Wagner, DD TI Endothelial selectins and VCAM-1 promote hematopoietic progenitor homing to bone marrow. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol & Med, Boston, MA 02115 USA. 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 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2411 BP 585A EP 585A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302398 ER PT J AU Cripe, L Neuberg, D Tallman, M Saba, H Wiernik, P Jones, D Ghalie, R Gordon, M AF Cripe, L Neuberg, D Tallman, M Saba, H Wiernik, P Jones, D Ghalie, R Gordon, M TI A pilot study of recombinant human thrombopoietin (rh-TPO) and GM-CSF following induction therapy in patients older than 55 years with acute myeloid leukemia (AML). SO BLOOD LA English DT Meeting Abstract C1 Indiana Univ, Med Ctr, Bloomington, IN 47405 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Sch Med, Evanston, IL 60208 USA. Genentech Inc, S San Francisco, CA 94080 USA. Immunex Corp, Seattle, WA USA. Montefiore Med Ctr, Bronx, NY 10467 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2539 BP 616A EP 616A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302526 ER PT J AU Cardoso, AA Veiga, JP Ghia, P Afonso, HM Nadler, LM AF Cardoso, AA Veiga, JP Ghia, P Afonso, HM Nadler, LM TI Lymphoblastic leukemia cells express CXCR-4 and migrate through endothelium in response to SDF-1: Implications for leukemia cell vaccination. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2548 BP 618A EP 618A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302535 ER PT J AU Lehmann, LE Tarbell, NJ Renella, R Sallan, SE Weinstein, HJ Billett, AL AF Lehmann, LE Tarbell, NJ Renella, R Sallan, SE Weinstein, HJ Billett, AL TI Excellent outcome for pediatric patients with mediastinal lymphoblastic lymphoma when treated with intensive acute lymphoblastic leukemia therapy. SO BLOOD LA English DT Meeting Abstract C1 Childrens Hosp, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2556 BP 620A EP 620A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302543 ER PT J AU Stone, RM Galinsky, I Berg, D Daftary, F Kinchla, N Zaleskas, JM Xu, G Liou, JR AF Stone, RM Galinsky, I Berg, D Daftary, F Kinchla, N Zaleskas, JM Xu, G Liou, JR TI Protein kinase C (PKC)-based anti-leukemic therapy: A randomized phase II trial of all-trans retinoic acid (ATRA) and bryostatin 1 (BRYO) in patients (PTS) with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2602 BP 631A EP 631A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302589 ER PT J AU Shu, J Cheng, G Lichtenstein, A AF Shu, J Cheng, G Lichtenstein, A TI Interleukin-6 (IL-6)-induced prevention against apoptosis in multiple myeloma (MM) cells: Possible involvement of an induced jun kinase (JNK) phosphatase. SO BLOOD LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2615 BP 634A EP 634A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302602 ER PT J AU Treon, SP Chauhan, D Raje, N Teoh, G Webb, I Anderson, KC AF Treon, SP Chauhan, D Raje, N Teoh, G Webb, I Anderson, KC TI Recombinant human tnf-related apoptosis inducing ligand (hu TRAIL) induces apoptosis of human multiple myeloma (MM) cells. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2614 BP 634A EP 634A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302601 ER PT J AU Treon, SP Macduff, BM Chauhan, D Raje, N Teoh, G Anderson, KC AF Treon, SP Macduff, BM Chauhan, D Raje, N Teoh, G Anderson, KC TI Soluble CD40 ligand (sCD40L) induces multiple myeloma (MM) cell proliferation but is not elevated in patient plasma. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Immunex Corp, Seattle, WA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2613 BP 634A EP 634A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302600 ER PT J AU Chauhan, D Hideshima, T Pandey, P Treon, SP Teoh, G Raje, N Kufe, DW Okada, H Kharbanda, S Anderson, KC AF Chauhan, D Hideshima, T Pandey, P Treon, SP Teoh, G Raje, N Kufe, DW Okada, H Kharbanda, S Anderson, KC TI Role of proline-rich tyrosine kinase 2 (PYK2) in dexamethasone (DEX)-induced apoptosis in multiple myeloma (MM) cells. SO BLOOD LA English DT Meeting Abstract C1 Nagoya City Univ, Sch Med, Dept Mol Biol, Nagoya, Aichi, Japan. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2624 BP 636A EP 636A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302611 ER PT J AU Chauhan, D Hideshima, T Treon, SP Teoh, G Raje, N Anderson, KC AF Chauhan, D Hideshima, T Treon, SP Teoh, G Raje, N Anderson, KC TI Role of retinoblastoma (RB) protein in irradiation (IR)-induced apoptosis in multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2623 BP 636A EP 636A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302610 ER PT J AU Reddy, V Hill, GR Pan, L Gerbitz, A Brinson, Y Ferrara, JLM AF Reddy, V Hill, GR Pan, L Gerbitz, A Brinson, Y Ferrara, JLM TI G-CSF modulates acute GVHD through effects on the donor but not the recipient after allogeneic stem cell transplantation. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2644 BP 640A EP 640A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302631 ER PT J AU Dey, BR Yang, YG Pearson, DA Swenson, K Sykes, M AF Dey, BR Yang, YG Pearson, DA Swenson, K Sykes, M TI Natural killer cells of both donor and host origin play a role in IL-12-mediated protection against acute GVHD in mice. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2646 BP 641A EP 641A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302633 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 Quantitation of bcr-abl transcript copy number after allogeneic bone marrow transplantation in patients with CML using "real-time" PCR detection. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2689 BP 652A EP 652A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302676 ER PT J AU Donovan, JW Andersen, NS Poor, C Bowers, D Gribben, JG AF Donovan, JW Andersen, NS Poor, C Bowers, D Gribben, JG TI Prospective analysis of minimal residual disease detection in patients with CLL undergoing autologous and allogeneic BMT. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2688 BP 652A EP 652A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302675 ER PT J AU Harris, KW Hu, XJ Schultz, S Arcasoy, M AF Harris, KW Hu, XJ Schultz, S Arcasoy, M TI Normal and truncated erythropoietin receptors are able to transfer distinct cellular phenotypes to the IL-3 receptor SO BLOOD LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, Div Hematol, San Antonio, TX USA. Yale Univ, Div Hematol, New Haven, CT 06520 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2783 BP 675A EP 675A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302769 ER PT J AU Okuda, K Foster, R Griffin, JD AF Okuda, K Foster, R Griffin, JD TI Identification of a 24 amino acid domain within the PC chain of the GM-CSF receptor required for viability signaling. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2782 BP 675A EP 675A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302768 ER PT J AU Frank, DA Mahajan, S Ritz, J AF Frank, DA Mahajan, S Ritz, J TI Fludarabine inhibits STAT1 signaling in normal T cells and CLL cells. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2789 BP 677A EP 677A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302775 ER PT J AU Teoh, G Urashima, M Ogata, A Daley, JF Shirahama, S Matsuzaki, M Chauhan, D Tai, YT Treon, SP Raje, N Hideshima, T Greenfield, EA Nguyen, KA Anderson, KC AF Teoh, G Urashima, M Ogata, A Daley, JF Shirahama, S Matsuzaki, M Chauhan, D Tai, YT Treon, SP Raje, N Hideshima, T Greenfield, EA Nguyen, KA Anderson, KC TI p53-dependent cell cycle regulation mediated by DNA-dependent protein kinase-Ku holoenzyme on the cell membrane of human multiple myeloma cell lines. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2804 BP 680A EP 680A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302790 ER PT J AU DiNubile, MJ Antin, JH Bressler, S Stossel, T Ferrara, JLM AF DiNubile, MJ Antin, JH Bressler, S Stossel, T Ferrara, JLM TI Decreased gelsolin levels are associated with interstitial pneumonia after allogeneic BMT. SO BLOOD LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden, NJ 08103 USA. 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 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2814 BP 683A EP 683A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302800 ER PT J AU Toh, HC Preffer, F Spitzer, TR Dombkowski, D Clark, JS McAffee, SL Colby, C Saidman, S Sachs, DH Sackstein, R Sykes, M AF Toh, HC Preffer, F Spitzer, TR Dombkowski, D Clark, JS McAffee, SL Colby, C Saidman, S Sachs, DH Sackstein, R Sykes, M TI Characterisation of phenotypic and functional lymphocyte reconstitution in adult patients with chemoradiorefractory hematolocical malignancies (HM) receiving a novel non-myeloablative conditioning therapy and HLA-matched and mismatched donor bone marrow transplantation (BMT). SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplant Program, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2818 BP 684A EP 684A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302804 ER PT J AU Guinan, EC Boussiotis, VA Hirano, N Brennan, LL Nadler, LM Gribben, JG AF Guinan, EC Boussiotis, VA Hirano, N Brennan, LL Nadler, LM Gribben, JG TI Successful haploidentical BMT post ex vivo anergization of donor BM alloreactive T cells. SO BLOOD LA English DT Meeting Abstract C1 Childrens & Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA USA. 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 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2829 BP 687A EP 687A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302814 ER PT J AU Lambert, MW Walsh, CE D'Andrea, A McMahon, LW AF Lambert, MW Walsh, CE D'Andrea, A McMahon, LW TI A 230 kDa DNA repair protein which is deficient in Fanconi anemia complementation group A and C cells forms a complex with the FAA and FAC proteins in the nucleus. SO BLOOD LA English DT Meeting Abstract C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pathol, Newark, NJ 07103 USA. Univ N Carolina, Gene Therapy Ctr, Chapel Hill, NC 27515 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2850 BP 693A EP 693A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302838 ER PT J AU Schultze, JL Michalak, S Gribben, JG Nadler, LM AF Schultze, JL Michalak, S Gribben, JG Nadler, LM TI B cells maintain Th1 cell polarization: The production of IL-12 by naive and memory B cells is regulated by T cell signals CD40L, IFN-gamma and IL-10. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2876 BP 699A EP 699A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302860 ER PT J AU Aguiar, RCT Kharbanda, S Yakushijin, Y Gribben, JG Freeman, GJ Harris, NL Shipp, MA AF Aguiar, RCT Kharbanda, S Yakushijin, Y Gribben, JG Freeman, GJ Harris, NL Shipp, MA TI PTPROt, an alternatively spliced B-lymphoid protein tyrosine phosphatase: Regulation and functional analyses. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dana Farber Canc Inst, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2877 BP 700A EP 700A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302866 ER PT J AU Boussiotis, VA Berezovskaya, A Appleman, LJ Freeman, GJ Nadler, LM AF Boussiotis, VA Berezovskaya, A Appleman, LJ Freeman, GJ Nadler, LM TI Increased expression of p27(kip1) cyclin dependent kinase inhibitor is responsible for G1 arrest in alloantigen-specific helper T cell clonal anergy. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2880 BP 700A EP 700A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302864 ER PT J AU Manis, JP van der Stoep, N Tian, M Ferrini, R Davidson, L Bottaro, A Alt, FW AF Manis, JP van der Stoep, N Tian, M Ferrini, R Davidson, L Bottaro, A Alt, FW TI Immunoglobulin heavy chain class-switching in B cells lacking 3' IgH enhancers. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2879 BP 700A EP 700A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302863 ER PT J AU Appleman, LJ Berezovskaya, A Nadler, LM Boussiotis, VA AF Appleman, LJ Berezovskaya, A Nadler, LM Boussiotis, VA TI CD28 signal mediates cell cycle progression via degradation of cyclin dependent kinase inhibitor in the ubiquitin-proteasome pathway. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2881 BP 701A EP 701A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302870 ER PT J AU Frank, DA Mahajan, S Ritz, J AF Frank, DA Mahajan, S Ritz, J TI Activation of T cells through CD2 leads to the delayed and prolonged activation of STAT1. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2883 BP 701A EP 701A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302867 ER EF