FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Henson, JW Louis, DN AF Henson, JW Louis, DN TI Edward Peirson Richardson Jr (1918-1998) and the discovery of PML - Obituary SO JOURNAL OF NEUROVIROLOGY LA English DT Biographical-Item C1 Massachusetts Gen Hosp, Div Neuropathol, MGH Brain Tumor Ctr, Mol Neurooncol Lab, Boston, MA 02114 USA. RP Henson, JW (reprint author), Massachusetts Gen Hosp, Div Neuropathol, MGH Brain Tumor Ctr, Mol Neurooncol Lab, Boston, MA 02114 USA. NR 1 TC 2 Z9 2 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 AUG PY 1999 VL 5 IS 4 BP 325 EP 326 PG 2 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 224MN UT WOS:000081903000001 PM 10463854 ER PT J AU Leaf, A Kang, JX Xiao, YF Billman, GE Voskuyl, RA AF Leaf, A Kang, JX Xiao, YF Billman, GE Voskuyl, RA TI Experimental studies on antiarrhythmic and antiseizure effects of polyunsaturated fatty acids in excitable tissues SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Review DE omega-3; n-3; omega-6; n-6; eicosapentaenoic acid; docosahexaenoic acid; arrhythmias; seizures ID RAT CARDIAC MYOCYTES; VENTRICULAR MYOCYTES; PURKINJE-FIBERS; LONG-CHAIN; ARRHYTHMIAS; ISCHEMIA; LYSOPHOSPHATIDYLCHOLINE; PREVENTION; LYSOPHOSPHOGLYCERIDES; DYSFUNCTION AB It has been shown that in animals, and probably in humans, n-3 polyunsaturated fatty acids (PUFAs) are antiarrhythmic. We discuss our recent studies on the antiarrhythmic actions of PUFAs. PUFAs stabilize the electrical activity of isolated cardiac myocytes by requiring a stronger electrical stimulus to elicit an action potential and by markedly prolonging the refractory period. These electrophysiologic effects are the result of specific modulation of ion currents, particularly of the voltage-dependent sodium current and of the L-type calcium currents across sarcolemmal phospholipid membranes. This appears to be the probable major, antiarrhythmic mechanism of PUFAs. However, they also similarly affect neuronal ion channels with potentially important functional effects oil the nervous system. (C) Elsevier Science Inc. 1999. All rights reserved. C1 Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Ohio State Univ, Dept Physiol, Columbus, OH 43210 USA. Leiden Univ, Med Ctr, Dept Physiol, Leiden, Netherlands. Stichting Epilepsie Instellingen Nederland, Heemstede, Netherlands. RP Leaf, A (reprint author), Massachusetts Gen Hosp, Dept Med, E Bldg 149,13th St, Charlestown, MA 02129 USA. RI Billman, George/E-2758-2011 NR 41 TC 18 Z9 20 U1 0 U2 0 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 AUG PY 1999 VL 10 IS 8 BP 440 EP 448 DI 10.1016/S0955-2863(99)00034-0 PG 9 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 230EW UT WOS:000082239700001 PM 15539321 ER PT J AU Seldin, EB AF Seldin, EB TI Biomechanics of mandibular distracter orientation: An animal model analysis SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Editorial Material C1 Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Seldin, EB (reprint author), Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, 188 Longwood Ave, Boston, MA 02115 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD AUG PY 1999 VL 57 IS 8 BP 963 EP 964 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 229ZP UT WOS:000082226400019 ER PT J AU Martinez, V Rivier, J Tache, Y AF Martinez, V Rivier, J Tache, Y TI Peripheral injection of a new corticotropin-releasing factor (CRF) antagonist, astressin, blocks peripheral CRF- and abdominal surgery-induced delayed gastric emptying in rats SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID STRESS-RELATED ALTERATIONS; COLONIC MOTOR FUNCTION; NERVOUS-SYSTEM ACTION; COMPETITIVE ANTAGONISTS; INDUCED INHIBITION; ACTH-SECRETION; PITUITARY; RECEPTORS; HORMONE; BRAIN AB The effect of the corticotropin-releasing factor (CRF) receptor antagonists astressin and D-Phe CRF12-41 injected i.v. on CRF-induced delayed gastric emptying (GE) was investigated in conscious rats. Gastric transit was assessed by the recovery of methyl cellulose/phenol red solution 20 min after its intragastric administration. The 55% inhibition of GE induced by CRF (0.6 mu g i.v.) was antagonized by 87 and 100% by i.v. astressin at 3 and 10 mu g, respectively, and by 68 and 64% by i.v. D-Phe CRF12-41 at 10 and 20 mu g, respectively. CRF (0.6 mu g)-injected intracisternally (i.c.) induced 68% reduction of GE was not modified by i.v. astressin (10 mu g) whereas i.c. astressin (3 or 10 mu g) blocked by 58 and 100%, respectively, i.v. CRF inhibitory action. Abdominal surgery with cecal manipulation reduced GE to 7.1 +/- 3.1 and 27.5 +/- 3.3% at 30 and 180 min postsurgery, respectively, compared with 40.3 +/- 4.3 and 59.5 +/- 2.9% at similar times after anesthesia alone. Astressin (3 mu g i.v.) completely and D-Phe CRF12-41 (20 mu g i.v.) partially (60%) blocked surgery-induced gastric stasis observed at 30 or 180 min. The CRF antagonists alone (i.v. or i.c.) had no effect on basal GE. These data indicate that CRF acts in the brain and periphery to inhibit GE through receptor-mediated interaction and that peripheral CRF is involved in acute postoperative gastric ileus; astressin is a potent peripheral antagonist of CRF when injected i.v. whereas i.c. doses greater than or equal to 3 mu g exert dual central and peripheral blockade of CRF action on gastric transit. C1 W Los Angeles Vet Adm Med Ctr, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, Los Angeles, CA USA. Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, La Jolla, CA 92037 USA. RP Tache, Y (reprint author), W Los Angeles Vet Adm Med Ctr, CURE Digest Dis Res Ctr, Bldg 115,Room 203,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [DK-33061, DK-26741, DK-41301] NR 47 TC 48 Z9 50 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD AUG PY 1999 VL 290 IS 2 BP 629 EP 634 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 219AB UT WOS:000081583900020 PM 10411571 ER PT J AU Schorge, JO Goldhaber, SZ Duska, LR Goodman, A Feldman, S AF Schorge, JO Goldhaber, SZ Duska, LR Goodman, A Feldman, S TI Clinically significant venous thromboembolism after gynecologic surgery SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE thromboembolism; gynecologic surgical procedures; anticoagulants ID LOW-DOSE HEPARIN; PNEUMATIC CALF COMPRESSION; DEEP-VEIN THROMBOSIS; CONTROLLED TRIAL; PROPHYLAXIS; PREVENTION; MALIGNANCY; ONCOLOGY AB OBJECTIVE: To review the incidence and outcome of clinically significant venous thromboembolism (VTE) following gynecologic surgery in a population receiving provider-specified prophylaxis. STUDY DESIGN: A computerized patient database was used to identify all patients diagnosed with VTE following gynecologic surgery from 1992 to 1997. Medical records were retrospectively reviewed. Clinically significant postoperative VTE was defined as pulmonary Embolism or deep venous thrombosis, suggested by symptoms and physical findings, with subsequent confirmation by appropriate imaging study. Patients having VTE at the time of preoperative hospital admission and patients diagnosed with VTE after postoperative day 30 were excluded. RESULTS: Fifty-three patients developed postoperative VTE after >30,000 gynecologic surgical procedures (incidence, <1 event per 500 procedures). Forty-eight (91%) patients received some form of prophylaxis. Patients with benign disease, surgical anesthesia less than three hours and no history of prior VTE or factor V Leiden deficiency rarely developed postoperative VTE (incidence, <1 event in 4,000 procedures). Thirteen (25%) patients had complications from anticoagulation therapy requiring prolonged hospital stay or readmission. CONCLUSION: Clinically significant VTE following gynecologic surgery is rave in the absence of malignancy, prolonged surgical anesthesia or hypercoagulation factors. Complications from anticoagulation therapy are common among gynecologic patients undergoing treatment for VTE. C1 Brigham & Womens Hosp, Div Gynecol Oncol, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gynecol Oncol, Dept Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. Massachusetts Gen Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Schorge, JO (reprint author), Brigham & Womens Hosp, Div Gynecol Oncol, Dept Obstet Gynecol & Reprod Biol, 75 Francis St, Boston, MA 02115 USA. NR 15 TC 7 Z9 7 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD AUG PY 1999 VL 44 IS 8 BP 669 EP 673 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 230FZ UT WOS:000082242300002 PM 10483535 ER PT J AU Cober, SR Randolph, MA Lee, WPA AF Cober, SR Randolph, MA Lee, WPA TI Skin allograft survival following intrathymic injection of donor bone marrow SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE skin; allograft; thymus; intrathymic; bone marrow; rat; tolerance ID MAJOR HISTOCOMPATIBILITY COMPLEX; RAT CARDIAC ALLOGRAFTS; SERUM-TREATED MICE; ANTILYMPHOCYTE-SERUM; RENAL-ALLOGRAFTS; CLASS-I; ISLET TRANSPLANTATION; THYMIC RECOGNITION; INDUCTION; UNRESPONSIVENESS AB Background. Success has been reported using intrathymic injection in the preconditioning regimen to induce allograft tolerance. Although long-term stable tolerance has been achieved in numerous rodent vas cularized solid organ allograft models, tolerance to skin transplants has only been achieved across minor antigenic or concordant species disparities. This study sought to induce tolerance across an allogeneic barrier in a rat model with a major genetic disparity. Materials and methods. Lewis rats were injected intrathymically with 1 x 10(8) Brown-Norway (BN) bone marrow cells and intraperitoneally with 1.0 cc of rabbit anti-rat anti-lymphocyte serum (ALS). Twenty-one days later, BN skin grafts were placed on the injected animals. Control groups were included to isolate the effect of technique, thymic manipulation, strain specificity, and ALS. Results. Animals receiving both intrathymic bone marrow cells and ALS had a skin graft median survival time of 24 days versus 8 days for the control group (P = 0.003). Groups receiving anti-lymphocyte serum alone or intrathymic bone marrow cell injection alone exhibited no skin graft survival prolongation. Mixed lymphocyte reactions revealed normal responsiveness of tolerant animal lymphocytes to donor strain lymphocytes. Conclusions. This protocol utilizing the intrathymic injection of donor bone marrow cells along with shortterm immunosuppression with anti-lymphocyte serum produced markedly prolonged survival of skin allografts transplanted across a major histocompatibility barrier. Although tolerance was incomplete, significant prolongation has not previously been reported in genetic disparities of this degree. These results suggest that the application of this technique for central immune modulation may be beneficial for allograft tolerance induction and deserves further study in large animals models. a lees Academic Press. C1 Harvard Univ, Div Plast Surg, WACC 453, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. RP Lee, WPA (reprint author), Harvard Univ, Div Plast Surg, WACC 453, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. NR 22 TC 21 Z9 22 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD AUG PY 1999 VL 85 IS 2 BP 204 EP 208 DI 10.1006/jsre.1999.5688 PG 5 WC Surgery SC Surgery GA 226EW UT WOS:000082008200003 PM 10423320 ER PT J AU Stankovic, JM Guinan, JJ AF Stankovic, JM Guinan, JJ TI Medial efferent effects on auditory-nerve responses to tail-frequency tones. I. Rate reduction SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID CROSSED-OLIVOCOCHLEAR-BUNDLE; COCHLEAR HAIR-CELLS; BASILAR-MEMBRANE; GUINEA-PIG; ELECTRICAL-STIMULATION; CAT COCHLEA; FIBER RESPONSES; SERIAL SECTIONS; TUNING CURVES; NEURONS AB One way medial efferents are thought to inhibit responses of auditory-nerve fibers (ANFs) is by reducing the gain of the cochlear amplifier thereby reducing motion of the basilar membrane. If this is the only mechanism of medial efferent inhibition, then medial efferents would not be expected to inhibit responses where the cochlear amplifier has little effect, i.e., at sound frequencies in the tails of tuning curves. Inhibition at tail frequencies was tested for by obtaining randomized rate-level functions from cat ANFs with high characteristic frequencies (CF greater than or equal to 5 kHz), stimulated with tones two or more octaves below CF. It was found that electrical stimulation of medial efferents can indeed inhibit ANF responses to tail-frequency tones. The amplitude of efferent inhibition depended on both sound level (largest near to threshold) and frequency (largest two to three octaves below CF). On average, inhibition of high-CF ANFs responding to 1 kHz tones was around 5 dB. Although an efferent reduction of basilar-membrane motion cannot be ruled out as the mechanism producing the inhibition of ANF responses to tail frequency tones, it seems more likely that efferents produce this effect by changing the micromechanics of the cochlear partition. (C) 1999 Acoustical Society of America. [S0001-4966(99)00908-X]. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Lab Autitory Physiol, Boston, MA 02114 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Stankovic, JM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Lab Autitory Physiol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [5 RO1 DC 00235, T32 DC00038]; NIGMS NIH HHS [T32 GM007753, T32 MGM07753] NR 50 TC 26 Z9 27 U1 0 U2 1 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 AUG PY 1999 VL 106 IS 2 BP 857 EP 869 DI 10.1121/1.427102 PG 13 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 225YN UT WOS:000081993700036 PM 10462791 ER PT J AU Frazier, JA Meyer, MC Biederman, J Wozniak, J Wilens, TE Spencer, TJ Kim, GS Shapiro, S AF Frazier, JA Meyer, MC Biederman, J Wozniak, J Wilens, TE Spencer, TJ Kim, GS Shapiro, S TI Risperidone treatment for juvenile bipolar disorder: A retrospective chart review SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE juvenile; bipolar disorder; risperidone ID DEFICIT HYPERACTIVITY DISORDER; MANIA; CHILDREN; ADOLESCENTS; SCHIZOPHRENIA; COMORBIDITY; DYSKINESIA; TARDIVE; AUTISM AB Objective: To investigate the effectiveness and tolerability of the atypical neuroleptic risperidone in the treatment of juvenile mania. Method: This is a retrospective chart review of outpatients with the diagnosis of bipolar disorder (DSM-IV) treated with risperidone at a university center. Response to treatment was evaluated using the Clinical Global Impression Scale (CGI) with separate assessments of mania, psychosis, aggression, and attention-deficit/hyperactivity disorder (ADHD). Results: Twenty-eight youths (mean +/- SD age, 10.4 +/- 3.8 years) with bipolar disorder (25 mixed and 3 hypomanic) who had been treated with risperidone were identified. These children received a mean dose of 1.7 +/- 1.3 mg over an average period of 6.1 +/- 8.5 months. Using a CGI Improvement score of less than or equal to 2 (very much/much improved) to define robust improvement, 82% showed improvement in both their manic and aggressive symptoms, 69% in psychotic symptoms, but only 8% in ADHD symptoms. Conclusions: Although limited by its retrospective nature, this study suggests that risperidone may be effective in the treatment of manic young people and indicates the need for controlled clinical trials of risperidone and other atypical neuroleptics in juvenile mania. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Child Psychiat Dept, Boston, MA 02114 USA. RP Frazier, JA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Child Psychiat Dept, ACC 725,15 Parkman St, Boston, MA 02114 USA. NR 28 TC 146 Z9 153 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD AUG PY 1999 VL 38 IS 8 BP 960 EP 965 DI 10.1097/00004583-199908000-00011 PG 6 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 220KT UT WOS:000081664700011 PM 10434487 ER PT J AU Biederman, J Faraone, SV Mick, E Williamson, S Wilens, TE Spencer, TJ Weber, W Jetton, J Kraus, I Pert, J Zallen, B AF Biederman, J Faraone, SV Mick, E Williamson, S Wilens, TE Spencer, TJ Weber, W Jetton, J Kraus, I Pert, J Zallen, B TI Clinical correlates of ADHD in females: Findings from a large group of girls ascertained from pediatric and psychiatric referral sources SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit hyperactivity disorder; females; childhood psychopathology ID ATTENTION-DEFICIT HYPERACTIVITY; SUBSTANCE USE DISORDERS; FOLLOW-UP; LEARNING-DISABILITIES; GENDER DIFFERENCES; CIGARETTE-SMOKING; SEX-DIFFERENCES; RISK FACTOR; CHILDREN; FAMILY AB Objective: The scientific literature about attention-deficit hyperactivity disorder (ADHD) is based almost exclusively on male subjects, and girls with ADHD may be underidentified and undertreated. The aim of this study was to examine clinical correlates of ADHD in females using comprehensive assessments in multiple domains of functioning. Method: Subjects were 140 girls with ADHD and 122 comparison girls without ADHD ascertained from pediatric and psychiatric referral sources of the same age and social class. Subjects, were assessed with structured diagnostic interviews, psychometric tests assessing intellectual functioning and academic achievement, as well as standardized assessments of interpersonal, school, and family functioning by raters who were blind to clinical diagnosis. Results: Compared with female controls. girls with ADHD were more likely to have conduct, mood, and anxiety disorders; lower IQ and achievement scores; and more impairment on measures of social, school, and family functioning. Conclusions: These results extend to girls previous findings in boys indicating that ADHD is characterized by prototypical core symptoms of the disorder, high levels of comorbid psychopathology, and dysfunction in multiple domains. These results not only support findings documenting phenotypic similarities between the genders but also stress the severity of the disorder in females. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Pilgrim Hlth Care, Boston, MA USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, ACC 725,Fruit St, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH-50657-04] NR 34 TC 211 Z9 214 U1 6 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD AUG PY 1999 VL 38 IS 8 BP 966 EP 975 DI 10.1097/00004583-199908000-00012 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 220KT UT WOS:000081664700012 PM 10434488 ER PT J AU Schwartz, CE Snidman, N Kagan, J AF Schwartz, CE Snidman, N Kagan, J TI Adolescent social anxiety as an outcome of inhibited temperament in childhood SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE social anxiety; social phobia; temperament; adolescence; developmental psychopathology ID BEHAVIORAL-INHIBITION; PSYCHIATRIC-DISORDERS; LONGITUDINAL EVIDENCE; YOUNG-CHILDREN; BIRTH COHORT; PHOBIA; RELIABILITY; STABILITY AB Objective: Chess and Thomas suggested that temperament might make a contribution to social phobia and other forms of extreme social anxiety. This study provides the first investigation of the outcomes in adolescents who had been inhibited (subdued to and avoidant of novelty) or uninhibited (approaching novelty) in the second year of life, utilizing both direct interview and direct observation. Method: Seventy-nine subjects, aged 13 years, who had been classified as inhibited or uninhibited in the second year were assessed with both standardized interview and direct observation. Results: There was a significant association between earlier classification of a child as inhibited and generalized social anxiety at adolescence, but no association with specific fears, separation anxiety, or performance anxiety. The adolescents who were classified as socially anxious made fewer spontaneous comments than those without social anxiety; no relation was seen between any other type of fear and the number of spontaneous comments. Adolescent girls who had been inhibited as toddlers were more likely to be impaired by generalized social anxiety than boys. Conclusions: The interview and observational data indicate that important aspects of an inhibited temperament are preserved from the second year of life to early adolescence, which predispose an adolescent to social anxiety. C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Dev Psychopathol Res Grp, Boston, MA 02114 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Schwartz, CE (reprint author), Massachusetts Gen Hosp E, Dept Psychiat, Bldg 149,9th Floor,13th St, Charlestown, MA 02129 USA. FU NIMH NIH HHS [MH00891] NR 29 TC 404 Z9 410 U1 12 U2 58 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD AUG PY 1999 VL 38 IS 8 BP 1008 EP 1015 DI 10.1097/00004583-199908000-00017 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 220KT UT WOS:000081664700017 PM 10434493 ER PT J AU Asarnow, J Glynn, S Pynoos, RS Nahum, J Guthrie, D Cantwell, DP Franklin, B AF Asarnow, J Glynn, S Pynoos, RS Nahum, J Guthrie, D Cantwell, DP Franklin, B TI When the earth stops shaking: Earthquake sequelae among children diagnosed for pre-earthquake psychopathology SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE disaster; posttraumatic stress disorder; depression; anxiety; stress; youth ID POSTTRAUMATIC-STRESS-DISORDER; DISASTER; DEPRESSION; SYMPTOMS AB Objective: To examine risk and protective processes for posttraumatic stress reactions and negative sequelae following the Northridge earthquake (EQ) among youths diagnosed for pre-EQ psychopathology. Method: Symptoms of posttraumatic stress disorder (PTSD), depression, general anxiety, and social impairment were evaluated using telephone interviews among 66 children participating in a family-genetic study of childhood-onset depression at the time of the EQ. Results: Significant predictors of PTSD symptoms 1 year after the EQ included perceived stress and resource loss associated with the EQ, a pre-EQ anxiety disorder. and more frequent use of cognitive and avoidance coping strategies. PTSD symptoms were associated with high rates of concurrent general anxiety symptoms, depressive symptoms, and social adjustment problems with friends. The only significant correlation between sibling scores was on measures of sibling reports of objective exposure. Conclusions: Preexisting anxiety disorders represent a risk factor for postdisaster PTSD reactions. Postdisaster services need to attend to the needs of these youths as well as those of youths experiencing high levels of subjective stress, resource loss, and/or high exposure. That children within families show significant variation in postdisaster reactions underscores the need for attention to individual child characteristics and unshared environmental attributes. C1 Univ Calif Los Angeles, NPI, Los Angeles, CA 90024 USA. W Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. RP Asarnow, J (reprint author), Univ Calif Los Angeles, NPI, 760 Westwood Plaza, Los Angeles, CA 90024 USA. FU NIMH NIH HHS [MH46981] NR 35 TC 105 Z9 108 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD AUG PY 1999 VL 38 IS 8 BP 1016 EP 1023 DI 10.1097/00004583-199908000-00018 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 220KT UT WOS:000081664700018 PM 10434494 ER PT J AU Manuskiatti, W Dierickx, CC Gonzalez, S Lin, TYD Campos, VB Gonzalez, E Anderson, RR AF Manuskiatti, W Dierickx, CC Gonzalez, S Lin, TYD Campos, VB Gonzalez, E Anderson, RR TI Laser hair removal affects sebaceous glands and sebum excretion: A pilot study SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID MODE RUBY-LASER; SELECTIVE PHOTOTHERMOLYSIS; FOLLICLES; OUTPUT AB Background: During laser-assisted hair removal, sebaceous glands closely associated with hair Follicles might also be affected. Objective: We investigated the effect of the long-pulsed ruby laser on sebaceous glands. Methods: Sebum excretion rates (SERs) of 16 subjects were measured quantitatively by means of sebum-absorbent tape and analyzed by means of image analysis techniques on laser-treated sites, compared with adjacent untreated areas. Evaluation was done at an average of 9 months (range, 4.5 to 12 months) after the last treatment. Histologic examinations were performed on 3 representative subjects before treatment, immediately after treatment, and 9 months after the last treatment. Results: Significant increases in SERs were observed in 11 of 16 subjects (68.75%). Three subjects (18.75%) showed lower SERs, whereas 2 subjects (12.5%) demonstrated no difference in SERs between treated and untreated areas. Biopsy specimens showed an apparent reduction in sebaceous gland size. Specimens taken immediately after laser irradiation revealed sporadic damage to sebaceous glands. Conclusion: In some patients a variable but statistically significant increase in sebum excretion occurs ii to 12 months after ruby-laser hair removal treatment at high fluences. A reduction in sebaceous gland sizes on laser-treated areas was observed. We hypothesize that decreased resistance to sebum outflow may explain this result, following miniaturization or absence of hair shaft after ruby laser treatment. Further study is needed to assess mechanisms for this interesting response. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Dermatol Laser Ctr,Dept Dermatol, Boston, MA 02114 USA. RP Anderson, RR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, 50 Blossom St,BHX-630, Boston, MA 02114 USA. NR 15 TC 10 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 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD AUG PY 1999 VL 41 IS 2 BP 176 EP 180 DI 10.1016/S0190-9622(99)70045-9 PN 1 PG 5 WC Dermatology SC Dermatology GA 224WA UT WOS:000081921900004 PM 10426885 ER PT J AU Drake, LA Patrick, DL Fleckman, P Andre, J Baran, R Haneke, E Sapede, C Tosti, A AF Drake, LA Patrick, DL Fleckman, P Andre, J Baran, R Haneke, E Sapede, C Tosti, A TI The impact of onychomycosis on quality of life: Development of an international onychomycosis-specific questionnaire to measure patient quality of life SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID OF-LIFE AB Background: Onychomycosis is a widespread refractory disease deleteriously affecting quality of life via social stigma and disrupting daily activities. Many physicians perceive onychomycosis as a cosmetic rather than a medical problem. Objective: Our purpose was to develop a questionnaire-based instrument to quantify the impact of onychomycosis on patients' quality of life. Methods: The questionnaire was developed and validated in a multinational cross-sectional study. Completed questionnaires from 532 patients were analyzed: 284 toenail, 248 fingernail (onychomycosis or paronychia). Results:The degree of quality of life impairment from onychomycosis varied by country studied, possibly reflecting cross-national health perception differences. Longer duration of disease, greater involvement of individual nails, and greater number of nails involved were associated with more serious adverse effects. Many physicians underestimated the associated degree of pain. Conclusion: The study confirms that onychomycosis physically and psychologically affects patients' lives. The questionnaire may be a valuable tool in evaluating the effect of therapeutic agents on quality of life of patients with onychomycosis. C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Univ Washington, Seattle, WA 98195 USA. Hop Univ St Pierre, Dept Dermatol, B-1000 Brussels, Belgium. Nail Dis Ctr, Cannes, France. Klinikum Stadt Wuppertal, Wuppertal, Germany. MAPI, Lyon, France. Univ Bologna, Inst Clin Dermatol, I-40126 Bologna, Italy. RP Drake, LA (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 40 Blossom St,BAR 604, Boston, MA 02114 USA. NR 19 TC 78 Z9 79 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD AUG PY 1999 VL 41 IS 2 BP 189 EP 196 DI 10.1016/S0190-9622(99)70047-2 PN 1 PG 8 WC Dermatology SC Dermatology GA 224WA UT WOS:000081921900006 PM 10426887 ER PT J AU Stratigos, AJ Stern, R Gonzalez, E Johnson, RA O'Connell, J Dover, JS AF Stratigos, AJ Stern, R Gonzalez, E Johnson, RA O'Connell, J Dover, JS TI Prevalence of skin disease in a cohort of shelter-based homeless men SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID DRUG-RESISTANT TUBERCULOSIS; NEW-YORK-CITY; MEDICAL PROBLEMS; PHYSICAL HEALTH; RISK-FACTORS; ADULTS; INDIVIDUALS; KERATOLYSIS; INFECTION AB Background: Cutaneous disease is a frequent cause of morbidity in homeless people. A variety of infectious and noninfectious conditions have been described in this population that are exacerbated by malnutrition, exposure to hazardous environment, psychiatric disease, physical injuries, and limited access to health care. Objective: Our purpose was to study the prevalence of skin disease in a selected group of the homeless population. Methods: We evaluated skin diseases in a cohort of 142 homeless men who were staying overnight in a major Boston homeless shelter for men over a period of 3 months (March-June 1992). The subjects participated in the study by volunteering for a free skin examination. Completion of a detailed questionnaire on age, race, duration of homelessness, and general medical status was followed by a thorough skin examination performed by dermatologists. Results: The most prevalent skin diseases in the examined population were tinea pedis (38%), pitted keratolysis of the feet (20.4%), traumatic injuries (19.7%), toenail onychomycosis (15.4%), acne vulgaris (18.3%), and seborrheic dermatitis (13.3%). Conclusion: To our surprise the majority of patients had relatively normal findings from skin examinations with only a few pathologic findings, most often related to poor foot hygiene and long-term exposure to moisture. We attribute the relatively good condition of our cohort to the excellent care provided by the shelter with regard to clothing, cleaning facilities, and medical care. Our findings may represent the prevalence of skin diseases in shelter-based homeless but not in street homeless persons who are likely to have much poorer hygiene and perhaps more skin disease. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Dermatol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02215 USA. Boston City Hosp, Boston Hlth Care Homeless Program, Dept Dermatol, Boston, MA 02118 USA. RP Dover, JS (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Dermatol, 110 Francis St,Suite 7H, Boston, MA 02215 USA. NR 30 TC 25 Z9 25 U1 1 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD AUG PY 1999 VL 41 IS 2 BP 197 EP 202 DI 10.1016/S0190-9622(99)70048-4 PN 1 PG 6 WC Dermatology SC Dermatology GA 224WA UT WOS:000081921900008 PM 10426888 ER PT J AU Drake, LA Cohen, L Gillies, R Flood, JG Riordan, AT Phillips, SB Stiller, MJ AF Drake, LA Cohen, L Gillies, R Flood, JG Riordan, AT Phillips, SB Stiller, MJ TI Pharmacokinetics of doxepin in subjects with pruritic atopic dermatitis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article AB Background: Doxepin applied topically by itself or in combination with triamcinolone acetonide is a safe and effective treatment for atopic dermatitis, Objective: We evaluated the pharmacokinetic profile of doxepin and desmethyldoxepin after topical application of doxepin hydrochloride 5% cream alone or in combination with 0.025% triamcinolone acetonide (doxepin/TAC). Methods: Twenty-four subjects with atopic dermatitis received either doxepin or doxepin/TAC cream 4 times daily for 7 days in a randomized, double-blind, controlled trial. Serum samples were obtained and pharmacokinetic parameters estimated from the dose-normalized serum concentrations of doxepin and desmethyldoxepin, Efficacy and adverse experiences were determined by physician and subject evaluations. Results: Pharmacokinetic parameters (K-e, t(1/2) and AUG) calculated in 9 subjects (doxepin/TAC = 4 subjects, doxepin = 5 subjects) with detectable serum concentrations were similar for both groups. Pruritus relief and lessening of pruritus severity were significantly greater with doxepin/TAC than doxepin alone. Conclusion: Topically applied doxepin is safe and effective therapy for pruritus. C1 Massachusetts Gen Hosp, Dermatol Clin Investigat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Chem, Boston, MA 02114 USA. RP Drake, LA (reprint author), Massachusetts Gen Hosp, Dermatol Clin Investigat Unit, 40 Blossom St, Boston, MA 02114 USA. NR 15 TC 12 Z9 14 U1 1 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD AUG PY 1999 VL 41 IS 2 BP 209 EP 214 DI 10.1016/S0190-9622(99)70051-4 PN 1 PG 6 WC Dermatology SC Dermatology GA 224WA UT WOS:000081921900011 PM 10426891 ER PT J AU Tannous, Z Baldassano, MF Li, VW Kvedar, J Duncan, LM AF Tannous, Z Baldassano, MF Li, VW Kvedar, J Duncan, LM TI Syringolymphoid hyperplasia and follicular mucinosis in a patient with cutaneous T-cell lymphoma SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID ALOPECIA AB Springolymphoid hyperplasia with alopecia is an uncommon chronic dermatosis of which 9 cases have been reported, with or without follicular mucinosis or cutaneous T-cell lymphoma. We report a patient with cutaneous T-cell lymphoma and syringolymphoid hyperplasia and follicular mucinosis and review the previously reported cases. All reported cases with syringolymphoid hyperplasia were men (10 of 10), with the clinical findings of alopecia (9 of 10) and anhidrosis (3 of 10). Only 3 of 10 cases had associated follicular mucinosis, Of the 7 cases investigated, 6 were found to hve cutaneous T-cell lymphoma. Three patients were not investigated for cutaneous T-cell lymphoma. Although syringolymphoid hyperplasia can be idiopathic, it can also reflect a syringotropic cutaneous T-cell lymphoma. Careful follow-up with a biopsy of persistent lesions is recommended to evaluate for the presence of lymphoma. C1 Massachusetts Gen Hosp, Dermatopathol Unit WRN 827, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Amer Univ Beirut, Med Ctr, Dept Dermatol, Beirut, Lebanon. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dermatopathol Unit, Boston, MA 02115 USA. RP Duncan, LM (reprint author), Massachusetts Gen Hosp, Dermatopathol Unit WRN 827, Boston, MA 02114 USA. RI Duncan, Lyn/E-9878-2013 NR 8 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 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD AUG PY 1999 VL 41 IS 2 SU S BP 303 EP 308 DI 10.1016/S0190-9622(99)70370-1 PN 2 PG 6 WC Dermatology SC Dermatology GA 225JK UT WOS:000081954400007 PM 10426915 ER PT J AU Sheridan, R Nackel, A Lydon, M Petras, L Basha, G AF Sheridan, R Nackel, A Lydon, M Petras, L Basha, G TI Infradiaphragmatic central venous pressures reflect supradiaphragmatic pressures in stable burn patients SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the American-Burn-Association CY MAR 18-21, 1998 CL CHICAGO, ILLINOIS SP Amer Burn Assoc ID INFERIOR VENA-CAVA; CHILDREN; CATHETERS; ACCURACY AB Objective: Because the skin of the groin is often spared, femoral central venous catheters are sometimes used in patients with extensive burns. The accuracy of central venous pressures obtained from the infradiaphragmatic location relative to the traditional supradiaphragmatic value is not known in this population. Methods: Seventeen seriously injured but hemodynamically stable burn patients were enrolled in a protocol approved by the human studies committee in which, during scheduled central venous line rotations, supradiaphragmatic and infradiaphragmatic central venous pressures were determined simultaneously, Results: These 17 patients were an average of 21.8 +/- 20.1 years old (range, 6 months to 61 years), and the average burn size was 60.8 +/- 22.6% (range, 20 to 90%). Supradiaphragmatic and infradiaphragmatic pressures correlated well, with an r value of 0.903, p less than 0.01, Conclusion: In the absence of clinically significant abdominal distention, infradiaphragmatic central venous pressure is an accurate reflection of supradiaphragmatic pressure, and indirectly, circulating blood volume. C1 Shriners Burns Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Burns & Trauma, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Sheridan, R (reprint author), Shriners Burns Hosp, 51 Blossom St, Boston, MA 02114 USA. NR 12 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD AUG PY 1999 VL 47 IS 2 BP 300 EP 302 DI 10.1097/00005373-199908000-00013 PG 3 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 226LK UT WOS:000082021300015 PM 10452465 ER PT J AU Carter, EA Yu, YM Alpert, NM Bonab, AA Tompkins, RG Fischman, AJ AF Carter, EA Yu, YM Alpert, NM Bonab, AA Tompkins, RG Fischman, AJ TI Measurement of muscle protein synthesis by positron emission tomography with L-[methyl-(11)C]methionine: Effects of transamination and transmethylation SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE rat; methionine; positron emission tomography; skeletal muscle; cycloheximide; protein synthesis rate ID SYNTHESIS RATES; PET; HUMANS; BRAIN AB Background: Positron emission tomography with L-[methyl-(11)C]methionine provides a measure of regional protein synthesis rate (PSR) in skeletal muscle. However, the validity of the method depends on incorporation of methionine into protein with minimal transamination, transmethylation, or both. To test directly these assumptions, uptake of L-[methyl-(14)C]methionine in skeletal muscle was measured in control and cycloheximide-treated rats. Methods: Normal and cycloheximide-treated rats (n = 8/group) were injected with 50 mu Ci of L-[methyl-(14)C]methionine and arterial blood sampled over 90 minutes. After killing, thigh muscle was homogenized, centrifuged, and treated with trichloroacetic acid. PSR from circulating methionine was estimated from trichloroacetic acid-precipitable radioactivity, arterial time-activity curves, and plasma methionine concentrations. Results: In normal rats, similar to 70% of the tissue radioactivity was precipitated with trichloroacetic acid. In normal animals, PSR was 0.22 nmoles.min(-1).g(-1), in excellent agreement with previous results. In the cyclohexamide-treated group, PSR was 0.0032 nmoles.min(-1).g(-1); similar to 98% reduction compared with controls. Conclusion: These studies support the hypothesis that L-[methyl-(11(14))C]methionine accumulates in skeletal muscle as (11(14))C-labeled protein. C1 Harvard Univ, Div Nucl Med, Massachusetts Gen Hosp, Sch Med,Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Trauma Serv, Boston, MA 02114 USA. Shriners Burns Inst, Boston, MA USA. RP Fischman, AJ (reprint author), Harvard Univ, Div Nucl Med, Massachusetts Gen Hosp, Sch Med,Dept Radiol, Boston, MA 02114 USA. EM fischman@petw6.mgh.harvard.edu FU NCI NIH HHS [T32-CA09362]; NIGMS NIH HHS [T32-GM07035, P50-GM21700] NR 22 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD AUG PY 1999 VL 47 IS 2 BP 341 EP 345 DI 10.1097/00005373-199908000-00021 PG 5 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 226LK UT WOS:000082021300022 PM 10452471 ER PT J AU Sheridan, RL Shank, ES AF Sheridan, RL Shank, ES TI Hyperbaric oxygen treatment: A brief overview of a controversial topic SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Review ID CARBON-MONOXIDE INTOXICATION; AIR-EMBOLISM; SKIN FLAPS; DECOMPRESSION-SICKNESS; NEUROLOGIC SEQUELAE; REPERFUSION INJURY; PATHO-PHYSIOLOGY; CLINICAL-TRIAL; INFARCT SIZE; THERAPY C1 Harvard Univ, Sch Med, Shriners Burns Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Massachusetts Eye & Ear Infirm, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Massachusetts Eye & Ear Infirm, Dept Anesthesia, Boston, MA 02114 USA. RP Sheridan, RL (reprint author), Harvard Univ, Sch Med, Shriners Burns Hosp, 51 Blossom St, Boston, MA 02114 USA. NR 125 TC 25 Z9 28 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD AUG PY 1999 VL 47 IS 2 BP 426 EP 435 DI 10.1097/00005373-199908000-00045 PG 10 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 226LK UT WOS:000082021300043 PM 10452491 ER PT J AU Bromley, B Shipp, T Benacerraf, BR AF Bromley, B Shipp, T Benacerraf, BR TI Genetic sonogram scoring index: Accuracy and clinical utility SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE genetic sonogram scoring index; sonogram, genetic; Down syndrome ID DOWNS-SYNDROME; MATERNAL AGE; 2ND-TRIMESTER FETUSES; AUTOSOMAL TRISOMY; RISK; ANOMALIES AB We sought to evaluate the accuracy of the genetic sonogram scoring index in detecting Down syndrome fetuses in a high-risk population. Women referred for genetic sonogram scoring index based on increased risk for aneuploidy were prospectively evaluated. Each fetus was assigned a score based on our previously published genetic sonogram scoring index. A score of 1 or greater was an indication for karyotype determination. Of 1076 patients (1118 fetuses) in the study group, follow-up data were available for 1030 (92%), eight of whom had Down syndrome (prevalence 0.8%). Three fetuses with Down syndrome had a genetic sonogram scoring index of 0, and for one or these the mother was 42 years old. One affected fetus had a score of 1 and the other four had scores of 2 or greater. Using a genetic sonogram scoring index of 1 or greater (age not considered), five of eight fetuses with Down syndrome (62.5%) were identified, as well as 150 of 1030 (14.6%) of normals. Down syndrome was undetected in three fetuses of 1030 (1 in 343) or 0.29%. In addition, when all women 40 years old or older underwent karyotype testing regardless of their sonographic findings, six of eight Down syndrome fetuses were identified (75%), as well as 271 of 1030 (26.3%) of normals. The number of cases of Down syndrome not detected was two in 1030 (1 in 515) or 0.19%. In conclusion, the genetic sonogram scoring index was used to identify approximately 75% of fetuses with Down syndrome, with amniocentesis being recommended in 26.7% of a high-risk population. C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA USA. RP Bromley, B (reprint author), Diagnost Ultrasound Associates, 333 Longwood Ave, Boston, MA 02115 USA. NR 18 TC 28 Z9 32 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 AUG PY 1999 VL 18 IS 8 BP 523 EP 528 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 220DQ UT WOS:000081649600001 PM 10447076 ER PT J AU Litwin, MS McNaughton-Collins, M Fowler, FJ Nickel, JC Calhoun, EA Pontari, MA Alexander, RB Farrar, JT O'Leary, MP AF Litwin, MS McNaughton-Collins, M Fowler, FJ Nickel, JC Calhoun, EA Pontari, MA Alexander, RB Farrar, JT O'Leary, MP CA Chronic Prostatitis Collaborative Res Network TI The National Institutes of Health chronic prostatitis symptom index: Development and validation of a new outcome measure SO JOURNAL OF UROLOGY LA English DT Article DE prostatitis; pain; pelvis; quality of life; health status ID NONBACTERIAL PROSTATITIS; PROSTATODYNIA; QUESTIONNAIRE; DIAGNOSIS; QUALITY; VISITS; LIFE AB Purpose: Chronic abacterial prostatitis is a syndrome characterized by pelvic pain and voiding symptoms, which is poorly defined, poorly understood, poorly treated and bothersome. Research and clinical efforts to help men with this syndrome have been hampered by the absence of a widely accepted, reliable and valid instrument to measure symptoms and quality of life impact. We developed a psychometrically valid index of symptoms and quality of life impact for men with chronic prostatitis. Materials and Methods: We conducted a structured literature review of previous work to provide a foundation for the new instrument. We then conducted a series of focus groups comprising chronic prostatitis patients at 4 centers in North America, in which we identified the most important symptoms and effects of the condition. The results were used to create an initial draft of 55 questions that were used for formal cognitive testing on chronic prostatitis patients at the same centers. After expert panel review formal validation testing of a revised 21-item draft was performed in a diverse group of chronic prostatitis patients and 2 control groups of benign prostatic hyperplasia patients and healthy men. Based on this validation study, the index was finalized. Results: Analysis yielded an index of 9 items that address 3 different aspects of the chronic prostatitis experience. The primary component was pain, which we captured in 4 items focused on location, severity and frequency. Urinary function, another important component of symptoms, was captured in 2 items (1 irritative and 1 obstructive). Quality of life impact was captured with 3 items about the effect of symptoms on daily activities. The 9 items had high test-retest reliability (r = 0.83 to 0.93) and internal consistency (alpha = 0.86 to 0.91). All but the urinary items discriminated well between men with and without chronic prostatitis. Conclusions: The National Institutes of Health chronic prostatitis symptom index provides a valid outcome measure for men with chronic prostatitis. The index is psychometrically robust, easily self-administered and highly discriminative. It was formally developed and psychometrically validated, and may be useful in clinical practice as well as research protocols. C1 Univ Calif Los Angeles, Dept Urol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA USA. Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Urol Surg, Boston, MA USA. Queens Univ, Dept Urol, Kingston, ON, Canada. Northwestern Univ, Sch Med, Inst Hlth Serv Res & Hlth Policy Studies, Chicago, IL USA. Northwestern Univ, Sch Med, Dept Urol, Chicago, IL 60611 USA. Temple Univ, Sch Med, Dept Urol, Philadelphia, PA 19122 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Maryland, Sch Med, Dept Surg, Baltimore, MD 21201 USA. RP Litwin, MS (reprint author), Univ Calif Los Angeles, Dept Urol, Los Angeles, CA 90095 USA. RI Farrar, John/A-1037-2007 OI Farrar, John/0000-0001-8656-5157 FU NIDDK NIH HHS [R01DK53736, R01DK53738, R01DK53746] NR 27 TC 448 Z9 555 U1 3 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD AUG PY 1999 VL 162 IS 2 BP 369 EP 375 DI 10.1016/S0022-5347(05)68562-X PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 214UA UT WOS:000081344900021 PM 10411041 ER PT J AU Meigs, JB Barry, MJ Giovannucci, E Rimm, EB Stampfer, MJ Kawachi, I AF Meigs, JB Barry, MJ Giovannucci, E Rimm, EB Stampfer, MJ Kawachi, I TI Incidence rates and risk factors for acute urinary retention: The health professionals followup study SO JOURNAL OF UROLOGY LA English DT Article; Proceedings Paper CT 93rd Annual Meeting of the American-Urological-Association CY MAY 30-JUN 04, 1998 CL SAN DIEGO, CALIFORNIA SP Amer Urol Assoc DE urinary retention; prostatic hyperplasia; epidemiology; cohort studies; risk factors ID BENIGN PROSTATIC HYPERPLASIA; NATURAL-HISTORY; SYMPTOMS; PROSTATECTOMY; SURGERY; QUALITY; LIFE; MEN AB Purpose: We define incidence rates and risk factors for acute urinary retention. Materials and Methods: In 1992, 41,276 United States male health professionals 45 to 83 years old self-reported baseline health data and American Urological Association symptom index scores. In 1995 a subset reported the year of any episode of acute urinary retention requiring catheterization. Of 8,418 respondents 6,100 without a history of prostate cancer, prostatectomy or acute urinary retention before 1992 provided data. Incidence rates from 1992 to 1995 were calculated and risk factors were assessed using logistic regression, Results: During 15,851 person-years of followup 82 men reported an episode of acute urinary retention (sampling weighted incidence 4.5/1,000 person-years, 95% confidence intervals 3.1 to 6.2). Rates increased with age and baseline symptom severity, In men with symptom score 0 to 7 (none or mild lower urinary tract symptoms) the incidence of acute urinary retention increased from 0.4/1.000 person-years for those 45 to 49 years old to 7.9/1.000 person-years for those 70 to 83 years old. In men with symptom score 8 to 35 (moderate or severe lower urinary tract symptoms) rates increased from 3.3/1,000 person-years for those 45 to 49 years old to 11.3/1,000 person-years for those 70 to 83 years old. Men with a clinical diagnosis of benign prostatic hyperplasia and a symptom score 8 or greater had the highest rates (age adjusted incidence 13.7/1,000 person-years). All 7 lower urinary tract symptoms comprising the American Urological Association symptom index individually predicted acute urinary retention (age adjusted odds ratio 1.8 to 2.9 for symptoms occurring more than 25% of the time during the last month). The sensation of incomplete bladder emptying, having to void again after less than 2 hours and a weak urinary stream were the best independent symptom predictors. Use of medications with adrenergic or anticholinergic side effects also predicted acute urinary retention. Conclusions: Acute urinary retention occurred relatively infrequently but older age, moderate or severe lower urinary tract symptoms, a diagnosis of benign prostatic hyperplasia and specific drug therapies significantly increased the risk of occurrence. C1 Massachusetts Gen Hosp, Med Serv, Div Gen Med, Gen Internal Med Unit S50 9, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Channing Lab, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Social Behav, Boston, MA 02115 USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Med Serv, Div Gen Med, Gen Internal Med Unit S50 9, Boston, MA 02114 USA. FU NCI NIH HHS [CA55075]; NHLBI NIH HHS [HL35464]; NIDDK NIH HHS [DK45779] NR 29 TC 101 Z9 109 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD AUG PY 1999 VL 162 IS 2 BP 376 EP 382 DI 10.1016/S0022-5347(05)68563-1 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 214UA UT WOS:000081344900022 PM 10411042 ER PT J AU Barry, MJ AF Barry, MJ TI Editorial: Quality of life and prostate cancer treatment SO JOURNAL OF UROLOGY LA English DT Editorial Material DE prostatic neoplasms; therapeutics; quality of life C1 Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. NR 4 TC 15 Z9 16 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD AUG PY 1999 VL 162 IS 2 BP 407 EP 407 DI 10.1016/S0022-5347(05)68571-0 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 214UA UT WOS:000081344900030 PM 10411048 ER PT J AU Shipley, WU Kaufman, DS Heney, NM Althausen, AF Zietman, AL AF Shipley, WU Kaufman, DS Heney, NM Althausen, AF Zietman, AL TI An update of combined modality therapy for patients with muscle invading bladder cancer using selective bladder preservation or cystectomy SO JOURNAL OF UROLOGY LA English DT Article; Proceedings Paper CT 93rd Annual Meeting of the American-Urological-Association CY MAY 30-JUN 04, 1998 CL SAN DIEGO, CALIFORNIA SP Amer Urol Assoc DE neoplasm invasiveness; bladder; cystectomy ID TRANSITIONAL-CELL-CARCINOMA; 5-YEAR FOLLOW-UP; ORGAN-SPARING TREATMENT; NEOADJUVANT CHEMOTHERAPY; CISPLATIN CHEMOTHERAPY; ADJUVANT CHEMOTHERAPY; RADICAL RADIOTHERAPY; INTERSTITIAL IR-192; RADIATION-THERAPY; TRANSURETHRAL RESECTION AB Purpose: We update the results of tri-modality treatment for patients with muscle invading bladder tumors with selection for bladder preservation based on tumor response to induction therapy. Material and Methods: We reviewed the literature on modern tri-modality bladder preserving approaches using transurethral resection, radiation and concurrent chemotherapy followed by either bladder conservation with careful surveillance for complete responding patients or prompt cystectomy in those whose tumors persist after induction therapy. Results: The published experiences from 3 centers and 2 prospective trials done by the Radiation Therapy Oncology Group were evaluated for 5-year overall survival of patients selected for bladder preservation or prompt cystectomy (49 to 63%) and for those with a conserved bladder (38 to 43%). The overall 5-year survival rates were comparable to other series of immediate cystectomy based approaches in patients of similar age and presenting with tumors of similar clinical stage. Of patients treated with the bladder preserving approach 20 to 30% cured of muscle invading cancer will subsequently have a new superficial tumor. The superficial tumors have responded well to intravesical drug therapy. Modern bladder preserving treatments usually result in a well functioning bladder without incontinence or significant hematuria. However, concurrent systemic chemotherapy and radiation have the potential for acute morbidity. Presently the ideal candidate for bladder preservation has primary clinical stage T2 tumor, no associated ureteral obstruction, visibly complete transurethral resection and complete response after induction chemoradiation based on endoscopic evaluation including re-biopsy and cytology. Conclusions: It is recommended that tri-modality treatment be administered by dedicated multimodality teams. In this country this approach to treatment is available at many of the institutions participating in the Radiation Therapy Oncology Group study. This treatment may be considered a reasonable alternative in patients who are deemed medically unfit for cystectomy and for those who are seeking an alternative to radical cystectomy. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc,Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc,Dept Med Oncol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc,Dept Urol, Boston, MA USA. RP Shipley, WU (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc,Dept Radiat Oncol, Boston, MA 02115 USA. NR 52 TC 50 Z9 53 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD AUG PY 1999 VL 162 IS 2 BP 445 EP 450 DI 10.1016/S0022-5347(05)68582-5 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 214UA UT WOS:000081344900041 PM 10411054 ER PT J AU Ropiquet, F Giri, D Lamb, DJ Ittmann, M AF Ropiquet, F Giri, D Lamb, DJ Ittmann, M TI FGF7 and FGF2 are increased in benign prostatic hyperplasia and are associated with increased proliferation SO JOURNAL OF UROLOGY LA English DT Article DE prostatic hyperplasia; fibroblast growth factor; cell proliferation ID FIBROBLAST GROWTH-FACTOR; FAMILY; EXPRESSION; RECEPTORS AB Purpose: To determine if overexpression of FGF7 and FGF2 occurs in benign prostatic hyperplasia (BPH) and if so, whether such overexpression is correlated with increased proliferation of epithelial and/or stromal cells. Materials and Methods: The FGF7 and FGF2 content of protein extracts of normal peripheral zone, normal transition zone and hyperplastic prostatic tissues were determined by enzyme-linked immunoabsorption assay. Proliferation of epithelial and stromal cells was assessed by immunohistochemistry with anti-Ki67 antibodies on frozen sections of the same tissues used for protein extraction. The in vitro effects of FGF7 and FGF2 on proliferation were assessed by addition of recombinant growth factor to primary cultures of prostatic epithelial and stromal cells. Results: We have found that both FGF7 and FGF2 are overexpressed in hyperplastic prostate in comparison to normal peripheral and transition zone tissue. FGF7 is a potent mitogen for epithelial cells in culture. Consistent with these in vitro effects, quantitative analysis of cellular proliferation by Ki67 immunohistochemistry revealed a strong correlation of epithelial proliferation with FGF7 content in BPH tissue, consistent with a key role for this growth factor in driving the abnormal epithelial proliferation in BPH, FGF2 is mitogenic for stromal cells in culture and there was a weaker correlation of FGF2 content with increased stromal proliferation. Conclusion: Overexpression of FGF7 and FGF2 may play an important role in the abnormal cellular proliferation seen in benign prostatic hyperplasia. C1 Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Urol, Houston, TX 77030 USA. Houston Dept Vet Affairs Med Ctr, Houston, TX USA. RP Ittmann, M (reprint author), Vet Affairs Med Ctr, Res Serv 151, 2002 Holcombe Blvd, Houston, TX 77030 USA. FU NIDDK NIH HHS [R01 DK54170] NR 17 TC 66 Z9 69 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD AUG PY 1999 VL 162 IS 2 BP 595 EP 599 DI 10.1016/S0022-5347(05)68632-6 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 214UA UT WOS:000081344900093 PM 10411093 ER PT J AU Kalams, SA Buchbinder, SP Rosenberg, ES Billingsley, JM Colbert, DS Jones, NG Shea, AK Trocha, AK Walker, BD AF Kalams, SA Buchbinder, SP Rosenberg, ES Billingsley, JM Colbert, DS Jones, NG Shea, AK Trocha, AK Walker, BD TI Association between virus-specific cytotoxic T-lymphocyte and helper responses in human immunodeficiency virus type 1 infection SO JOURNAL OF VIROLOGY LA English DT Article ID LOW VIRAL LOAD; LONGITUDINAL ANALYSIS; HIV-1 INFECTION; ANTIBODY-RESPONSES; CELL RESPONSES; IN-VIVO; DISEASE; GAG; VIREMIA; QUANTITATION AB Cellular immune responses are thought to be an important antiviral host defense, but the relationship between virus-specific T-helper and cytotoxic-T-lymphocyte (CTL) responses has not been defined. To investigate a potential link between these responses, we examined functional human immunodeficiency virus type 1 (HIV-l)-specific memory CTL precursor frequencies and p24-specific proliferative responses in a cohort of infected untreated persons with a wide range of viral loads and CD4 cell counts. Levels of p24-specific proliferative responses positively correlated with levels of Gag-specific CTL precursors and negatively correlated with levels of plasma HIV-1 RNA. These data linking the levels of HIV-specific CTL with virus-specific helper cell function during chronic viral infection provide cellular immunologic parameters to guide therapeutic and prophylactic vaccine development. C1 Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Dept Publ Hlth, AIDS Off, San Francisco, CA 94140 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. RP Kalams, SA (reprint author), Massachusetts Gen Hosp, Ctr AIDS Res, 149th 13th St,Rm 5217, Charlestown, MA 02129 USA. FU NIAID NIH HHS [R01 AI039966, R01 AI028568, AI40873, R01-AI39966, AI28568, R01 AI040873, R21 AI040873, R37 AI028568] NR 32 TC 304 Z9 306 U1 2 U2 5 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 AUG PY 1999 VL 73 IS 8 BP 6715 EP 6720 PG 6 WC Virology SC Virology GA 215HZ UT WOS:000081377400060 PM 10400769 ER PT J AU Kalams, SA Goulder, PJ Shea, AK Jones, NG Trocha, AK Ogg, GS Walker, BD AF Kalams, SA Goulder, PJ Shea, AK Jones, NG Trocha, AK Ogg, GS Walker, BD TI Levels of human immunodeficiency virus type 1-specific cytotoxic T-lymphocyte effector and memory responses decline after suppression of viremia with highly active antiretroviral therapy SO JOURNAL OF VIROLOGY LA English DT Article ID LOW VIRAL LOAD; HIV-1 INFECTION; IN-VIVO; LONGITUDINAL ANALYSIS; FINE SPECIFICITY; VACCINIA VIRUS; IMMUNE MICE; CELL; QUANTITATION; RECOGNITION AB Therapeutic suppression of human immunodeficiency virus type 1 (HIV-1) replication may help elucidate interactions between the host cellular immune responses and HIV-1 infection. We performed a detailed longitudinal evaluation of two subjects before and after the start of highly active antiretroviral therapy (HAART). Both subjects had evidence of in vivo-activated and memory cytotoxic T-lymphocyte precursor (CTLp) activity against multiple HIV-1 gene products. After the start of therapy, both subjects had declines in the levels of in vivo-activated HIV-1-specific CTLs and had immediate increases in circulating HIV-1-specific CTL memory cells. With continued therapy, and continued suppression of viral load, levels of memory CTLps declined. HLA A*0201 peptide tetramer staining demonstrated that declining levels of in vivo-activated CTL activity were associated with a decrease in the expression of the CD38(+) activation marker. Transient increases in viral load during continued therapy were associated with increases in the levels of virus-specific CTLps in both individuals. The results were confirmed by measuring CTL responses to discrete optimal epitopes. These studies illustrate the dynamic equilibrium between the host immune response and levels of viral antigen burden and suggest that efforts to augment HIV-1-specific immune responses in subjects on HAART may decrease the incidence of virologic relapse. C1 Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Inst Mol Med, Nuffield Dept Med, Oxford OX3 9DS, England. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. RP Kalams, SA (reprint author), Massachusetts Gen Hosp, AIDS Res Ctr, 149 13th St,Room 5217, Charlestown, MA 02129 USA. FU NIAID NIH HHS [R01 AI028568, R01 AI039966, R01 AI28568, R01 AI39966, R01 AI040873, R01 AI40873] NR 31 TC 253 Z9 256 U1 0 U2 0 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 AUG PY 1999 VL 73 IS 8 BP 6721 EP 6728 PG 8 WC Virology SC Virology GA 215HZ UT WOS:000081377400061 PM 10400770 ER PT J AU Braaten, KM Van Cott, EM Laposata, M AF Braaten, KM Van Cott, EM Laposata, M TI Point-of-care activated cloning time test SO LABORATORY MEDICINE LA English DT Editorial Material ID CLOTTING TIME; HEPARIN C1 Massachusetts Gen Hosp, Dept Pathol, Special Coagulat Lab, Clin Labs, Boston, MA 02114 USA. RP Braaten, KM (reprint author), Massachusetts Gen Hosp, Dept Pathol, Special Coagulat Lab, Clin Labs, Boston, MA 02114 USA. NR 7 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0007-5027 J9 LAB MED JI Lab. Med. PD AUG PY 1999 VL 30 IS 8 BP 507 EP 509 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 222QB UT WOS:000081795300008 ER PT J AU Wackym, PA King, WA Poe, DS Meyer, GA Ojemann, RG Barker, FG Walsh, PR Staecker, H AF Wackym, PA King, WA Poe, DS Meyer, GA Ojemann, RG Barker, FG Walsh, PR Staecker, H TI Adjunctive use of endoscopy during acoustic neuroma surgery SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the Middle Section of the American-Laryngological-Rhinological-and-Otological-Society CY JAN 23-24, 1999 CL MILWAUKEE, WISCONSIN SP Amer Laryngol Rhinol & Otol Soc Inc, Middle Sect ID CEREBROSPINAL-FLUID OTORHINORRHEA; CEREBELLOPONTINE ANGLE; RETROSIGMOID APPROACH; MANAGEMENT; REMOVAL; TUMORS; LEAK AB Objective/Hypothesis: In specific clinical situations, endoscopes offer better visualization than the microscope during acoustic neuroma (vestibular schwannoma) surgery and can therefore decrease the incidence of the postoperative complications of cerebrospinal fluid (CSF) leakage and recurrence of tumor. This study was undertaken to determine if the use of adjunctive endoscopy provides complementary information to the operating surgeon during surgery for acoustic neuromas. Method Seventy-eight patients with acoustic neuromas underwent tumor excision by two neurotologists (P.A.W., D.S.P.), together with their respective neurosurgical partners, via a retrosigmoid (suboccipital) approach (n=68), translabyrinthine approach (n=7), or middle cranial fossa approach (n=3), Endoscopy with a rigid glass lens endoscope was used during tumor removal to examine posterior fossa neurovascular structures, and after tumor excision to inspect the internal auditory canal (IAC), inner ear, and middle ear, depending on the approach used, One of the authors (D.S.P.) has not used adjunctive endoscopy during resections via the translabyrinthine and middle cranial fossa approaches, and therefore, these cases were excluded from the data collection and analysis. Results: Complete tumor excision was achieved in 73 patients. Endoscopy allowed improved identification of tumor and adjacent neurovascular relationships in all cases, In addition, residual tumor at the fundus of the LAC (n=11) and exposed air cells (n=24) not seen with the microscope during retrosigmoid approaches were identified endoscopically. In one of the translabyrinthine cases, the endoscope allowed identification of open air cells not visualized with the microscope, None of the 78 patients developed CSF rhinorrhea. Incorporating the endoscope did not significantly increase operative time, Conclusions: Endoscopy can be performed safely during surgery to remove acoustic neuromas. The adjunctive use of endoscopy may offer some advantages including improved visualization, more complete tumor removal, and a lowered risk of CSF leakage. C1 Med Coll Wisconsin, Dept Otolaryngol & Commun Sci, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Dept Neurosurg, Milwaukee, WI 53226 USA. Mt Sinai Sch Med, Dept Neurosurg, New York, NY USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Wackym, PA (reprint author), Froedtert Mem Lutheran Hosp, Med Coll Wisconsin, Dept Otolaryngol & Commun Sci, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. NR 20 TC 32 Z9 43 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD AUG PY 1999 VL 109 IS 8 BP 1193 EP 1201 DI 10.1097/00005537-199908000-00003 PG 9 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 224BY UT WOS:000081877300003 PM 10443819 ER PT J AU Ghaffari, S Daley, GQ Lodish, HF AF Ghaffari, S Daley, GQ Lodish, HF TI Growth factor independence and BCR/ABL transformation: promise and pitfalls of murine model systems and assays SO LEUKEMIA LA English DT Review DE BCR-ABL; signal transduction; chronic myeloid leukemia (CML); growth factor independence ID CHRONIC MYELOGENOUS LEUKEMIA; BCR-ABL ONCOGENE; CHRONIC MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; POSITIVE HUMAN LEUKEMIAS; FACTOR-DEPENDENT CELLS; ERYTHROPOIETIN RECEPTOR; TYROSINE KINASE; C-ABL; PHILADELPHIA-CHROMOSOME AB The expression of the BCR-ABL fusion oncoprotein in primitive hematopoietic cells results in chronic myeloid leukemia. Over the past decade studies of several in vitro and in vivo cell systems revealed multiple signal transduction pathways activated by BCR-ABL. However, the precise function of BCR-ABL in the pathogenesis of CML is still unclear. The goal of this review is to synthesize data on intracellular signaling in the context of the diverse murine assay systems employed. We emphasize the importance of in vivo assays and assays using primary cells in understanding the biology of CML and the molecular mechanisms by which BCR-ABL exerts its effects. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Ghaffari, S (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. FU NCI NIH HHS [CA76418-01]; NHLBI NIH HHS [HL 32262] NR 65 TC 40 Z9 41 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD AUG PY 1999 VL 13 IS 8 BP 1200 EP 1206 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 225YP UT WOS:000081993800005 PM 10450747 ER PT J AU Stone, M AF Stone, M TI The Harvard Medical School family health guide. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. RP Stone, M (reprint author), Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD AUG PY 1999 VL 124 IS 13 BP 78 EP 78 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 225NZ UT WOS:000081968800064 ER PT J AU Tseng, WI Reese, TG Weisskoff, RM Wedeen, VJ AF Tseng, WI Reese, TG Weisskoff, RM Wedeen, VJ TI Cardiac diffusion tensor MRI in vivo without strain correction SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; diffusion; myocardium; strain; motion effects; fiber architecture ID MAGNETIC-RESONANCE; WATER DIFFUSION; HYPERTROPHIC CARDIOMYOPATHY; IN-VIVO; HEART; MYOCARDIUM; MOTION; RATES AB Cardiac diffusion MRI with diffusion encoding that spans a cardiac cycle is complicated by myocardial strains. This paper presents a method to obtain accurate diffusion data without strain correction. Owing to the synchrony of normal cardiac motion, there are time points in the cardiac cycle, "sweet spots," when the cardiac configuration approximates its temporal mean. If the diffusion is encoded then, the net effect of strain on the observed diffusion approximates zero. To test this, MRI diffusion and strain-rate movies are performed on cyclically deformed gel phantoms and in five normal subjects. In phantoms, the sweet spots predicted from the strain time curves agree with the times when the observed diffusion equals the true diffusion. In humans, the strain prediction of the sweet spots and the locations determined by the diffusion trace show a high correlation, r = 0.99. In all subjects, diffusion MRI presents a fiber orientation pattern comparable to that obtained from a stationary specimen. Magn Reson Med 42:393-403, 1999. (C) 1999 Wiley-Liss. Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr,Dept Radiol, Charlestown, MA 02129 USA. RP Wedeen, VJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr,Dept Radiol, Bldg 149,13th St, Charlestown, MA 02129 USA. OI Tseng, Wen-Yih Isaac/0000-0002-2314-6868 FU NHLBI NIH HHS [1RO1-HL56737] NR 29 TC 76 Z9 77 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD AUG PY 1999 VL 42 IS 2 BP 393 EP 403 DI 10.1002/(SICI)1522-2594(199908)42:2<393::AID-MRM22>3.0.CO;2-F PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 221ZQ UT WOS:000081758100022 PM 10440965 ER PT J AU Chernof, BA Sherman, SE Lanto, AB Lee, ML Yano, EM Rubenstein, LV AF Chernof, BA Sherman, SE Lanto, AB Lee, ML Yano, EM Rubenstein, LV TI Health habit counseling amidst competing demands - Effects of patient health habits and visit characteristics SO MEDICAL CARE LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the National-Society-of-General-Internal-Medicine CY MAY 04-06, 1995 CL SAN DIEGO, CALIFORNIA SP Natl Soc Gen Internal Med DE health promotion; counseling; doctor-patient communication; health surveys; primary care ID PRIMARY-CARE; PREVENTIVE SERVICES; AMBULATORY CARE; MEDICAL-CARE; SMOKING; MODEL; TRIAL; QUESTIONNAIRE; VALIDITY; OUTCOMES AB OBJECTIVE. This study assesses the effects of competing demands, such as poor health habits or new medical problems, on health-habit counseling during a primary care visit. METHODS. We sun eyed a consecutive sample of 1,259 patients visiting primary care clinicians at an academic VA medical center. Before the visit, patients reported their health status, health habits, and sociodemographics; immediately after the visit, patients reported reasons for the visit and whether they had been counseled about specific health habits. We scored visit acuity ranging from visits for unscheduled walk-in care or new medical problems to scheduled visits for check-ups or old problems. We defined counseling "triggers" as clinical indications for counseling about particular health habits (eg, smoking). We developed a logistic model predicting primary care provider counseling during a visit. RESULTS. Over two-thirds of patients (68.9%) received some health habit counseling. Controlling for other independent variables, patients with more triggers were more likely to report being counseled. Counseling rates went up as visit acuity went down; patients with the lowest visit acuity having 67% greater odds of being counseled than patients with the highest visit acuity. CONCLUSIONS. Physicians set priorities for health-habit counseling during a visit based on patients' health habit problems or triggers; whether the visit is scheduled or walk-in; and whether the patient has new or acute problems. Future research about primary care performance of health habit counseling should account for these patient and visit characteristics, and prevention-oriented health care organizations should ensure access to scheduled "check-up" visits. C1 Hlth Net, Woodland Hills, CA 91367 USA. Dept Vet Affairs, VA Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr & Nursing Home, VA Hlth Serv Res & Dev,VA Ctr Study Healthcare Pr, Los Angeles, CA USA. Olive View UCLA Med Ctr, Dept Ambulatory Care, Sylmar, CA 91342 USA. Olive View UCLA Med Ctr, Dept Med, Sylmar, CA 91342 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Chernof, BA (reprint author), Hlth Net, 21600 Oxnard St, Woodland Hills, CA 91367 USA. NR 30 TC 33 Z9 33 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD AUG PY 1999 VL 37 IS 8 BP 738 EP 747 DI 10.1097/00005650-199908000-00004 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 224EM UT WOS:000081884500004 PM 10448717 ER PT J AU Rabeneck, L Menke, J Wray, NP AF Rabeneck, L Menke, J Wray, NP TI How good are US studies of HIV costs of care? SO MEDICAL CARE LA English DT Article DE HIV infection; AIDS; cost of illness; costs and cost analysis; health care costs ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; MEDICAL-CARE; INFECTED PATIENTS; HOSPITAL-CARE; NEW-YORK; DRUG-USE; AIDS; HEALTH; PATTERNS; EXPENDITURES AB BACKGROUND. Valid, timely estimates of the costs of HIV care are needed by health planners and policy makers. OBJECTIVE. To perform a methodologic critique of published estimates of resource utilization and costs of HIV care. DATA SOURCES. MEDLINE database for 1990-1998. DATA SELECTION. Included articles focused on adults with a spectrum of HIV disease in which the authors developed their own resource use and cost data. Thirty one articles met these criteria. DATA EXTRACTION. Studies were compared based on: (1) utilization and cost estimates, in 1995 dollars; (2) study period; (3) research design; (4) sampling frame; (5) sample size and patient characteristics; (6) data sources and scope of services; and (7) methods used in the analysis. DATA SYNTHESIS. The most recent estimates pertain to the first half of 1995, before the use of protease inhibitor therapy. We found wide variations in the estimates and identified three major sources for this: (1) patient samples that were restricted to subgroups of the national HIV-infected population; (2) utilization data that were limited in scope leg, inpatient (are only); and (3) invalid methods for estimating annual or lifetime costs, particularly in dealing with decedents. CONCLUSIONS. TO accurately estimate resource use and costs for HIV care nationwide, a nationally representative probability sample of HIV-infected patients is required. Even in research that is not intended to provide national estimates, the scope of utilization data should be broadened and greater attention to methodologic issues in the analysis of annual and lifetime costs is needed. C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Vet Affairs Hlth Serv Res & Dev, Field Program, Hlth Serv Res Sect, Houston, TX 77030 USA. RP Rabeneck, L (reprint author), VA Med Ctr, 111D,2002 Holcombe Blvd, Houston, TX 77030 USA. NR 35 TC 12 Z9 12 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD AUG PY 1999 VL 37 IS 8 BP 748 EP 759 DI 10.1097/00005650-199908000-00005 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 224EM UT WOS:000081884500005 PM 10448718 ER PT J AU Ashton, CM Kuykendall, DH Johnson, ML Wray, NP AF Ashton, CM Kuykendall, DH Johnson, ML Wray, NP TI An empirical assessment of the validity of explicit and implicit process-of-care criteria for quality assessment SO MEDICAL CARE LA English DT Article DE quality of health care; process assessment ID EARLY READMISSION; AMBULATORY CARE; INPATIENT CARE; ASSOCIATION; RELIABILITY AB OBJECTIVE. TO evaluate the validity of three criteria-based methods of quality assessment: unit weighted explicit process-of-tare criteria; differentially weighted explicit process-of-care criteria; and structured implicit process-of-care criteria. METHODS. The three methods were applied to records of index hospitalizations in a study of unplanned readmission involving roughly 2,500 patients with one of three diagnoses treated at 12 Veterans Affairs hospitals. Convergent validity among the three methods was estimated using Spearman rank correlation. Predictive validity was evaluated by comparing process-of-care scores between patients who were or were not subsequently readmitted within 14 days. RESULTS. The three methods displayed high convergent validity and substantial predictive validity. Index-stay mean scores, using explicit criteria, were generally lower in patients subsequently readmitted, and differences between readmitted and nonreadmitted patients achieved statistical significance as follows: mean readiness-for-discharge scores were significantly lower in patients with heart failure or with diabetes who were readmitted; and mean admission work-up scores were significantly lower in patients with lung disease who were readmitted. Scores derived from the structured implicit review were lower in patients eventually readmitted but significantly so only in diabetics. CONCLUSIONS. These three criteria-based methods of assessing process of fare appear to be measuring the same construct, presumably "quality of care." Both the explicit and implicit methods had substantial validity, but the explicit method is preferable. In this study, as in others, it had greater inter-rater reliability. C1 Baylor Coll Med, Houston, TX 77030 USA. Vet Affairs Hlth Serv Res & Dev Field Program, Ctr Qual Care & Utilizat Studies, Houston, TX USA. RP Ashton, CM (reprint author), VA Med Ctr, 152,2002 Holcombe Blvd, Houston, TX 77030 USA. NR 20 TC 44 Z9 45 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD AUG PY 1999 VL 37 IS 8 BP 798 EP 808 DI 10.1097/00005650-199908000-00009 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 224EM UT WOS:000081884500009 PM 10448722 ER PT J AU Fisher, CM AF Fisher, CM TI Hysteria: a delusional state SO MEDICAL HYPOTHESES LA English DT Article AB This paper explores the hypothesis that hysterical symptoms may best be regarded as the product of delusional thinking. Hysteria has generally been interpreted as a process quite distinct from other psychiatric disorders. An attempt is made to bring it within more conventional bounds. C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Fisher, CM (reprint author), Massachusetts Gen Hosp, Neurol Serv, Fruit St, Boston, MA 02114 USA. NR 22 TC 2 Z9 3 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD AUG PY 1999 VL 53 IS 2 BP 152 EP 156 DI 10.1054/mehy.1998.0735 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 236CQ UT WOS:000082581000014 PM 10532711 ER PT J AU Fajas, L Schoonjans, K Gelman, L Kim, JB Najib, J Martin, G Fruchart, JC Briggs, M Spiegelman, BM Auwerx, J AF Fajas, L Schoonjans, K Gelman, L Kim, JB Najib, J Martin, G Fruchart, JC Briggs, M Spiegelman, BM Auwerx, J TI Regulation of peroxisome proliferator-activated receptor gamma expression by adipocyte differentiation and determination factor 1/sterol regulatory element binding protein 1. Implications for adipocyte differentiation and metabolism SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ADIPOSE-CELL-DIFFERENTIATION; LEUCINE ZIPPER PROTEIN; PPAR-GAMMA; GENE-EXPRESSION; FATTY-ACIDS; TRANSCRIPTION FACTOR; TRANSGENIC MICE; 3T3-L1 PREADIPOCYTES; ECTOPIC EXPRESSION; STEROL REGULATION AB Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear receptor implicated in adipocyte differentiation and insulin sensitivity. We investigated whether PPAR gamma expression is dependent on the activity of adipocyte differentiation and determination factor 1/sterol regulatory element binding protein 1 (ADD-1/SREBP1), another transcription factor associated with both adipocyte differentiation and cholesterol homeostasis. Ectopic expression of ADD-1/SREBP-1 in 3T3-L1 and HepG2 cells induced endogenous PPAR gamma mRNA levels. The related transcription factor SREBP-2 likewise induced PPAR gamma expression. In addition, cholesterol depletion, a condition known to result in proteolytic activation of transcription factors of the SREBP family, induced PPAR gamma expression and improved PPRE-driven transcription. The effect of the SREBPs on PPAR gamma expression was mediated through the PPAR gamma 1 and -3 promoters. Both promoters contain a consensus E-box motif that mediates the regulation of the PPAR gamma gene by ADD-1/SREBP-1 and SREBP-2. These results suggest that PPAR gamma expression can be controlled by the SREBP family of transcription factors and demonstrate new interactions between transcription factors that can regulate different pathways of lipid metabolism. C1 Inst Pasteur, LBRE, Dept Atherosclerose, INSERM,U325, F-59019 Lille, France. Ligand Pharmaceut Inc, San Diego, CA 92121 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Auwerx, J (reprint author), Inst Pasteur, LBRE, Dept Atherosclerose, INSERM,U325, 1 Rue Calmette, F-59019 Lille, France. NR 58 TC 257 Z9 267 U1 0 U2 8 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 AUG PY 1999 VL 19 IS 8 BP 5495 EP 5503 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 217RY UT WOS:000081513800025 PM 10409739 ER PT J AU Parker, D Rivera, M Zor, T Henrion-Caude, A Radhakrishnan, I Kumar, A Shapiro, LH Wright, PE Montminy, M Brindle, PK AF Parker, D Rivera, M Zor, T Henrion-Caude, A Radhakrishnan, I Kumar, A Shapiro, LH Wright, PE Montminy, M Brindle, PK TI Role of secondary structure in discrimination between constitutive and inducible activators SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CREB-BINDING-PROTEIN; TRANSCRIPTION FACTOR CREB; COACTIVATOR INTERACTIONS; CBP; RECEPTOR; TRANSACTIVATION; CAMP; MYB; PHOSPHORYLATION; SPECIFICITY AB We have examined structural differences between the proto-oncogene c-Myb and the cyclic AMP-responsive factor CREB that underlie their constitutive or signal-dependent activation properties. Both proteins stimulate gene expression via activating regions that articulate with a shallow hydrophobic groove in the KIX domain of the coactivator CRFEB-binding protein (CBP). Three hydrophobic residues in c-Myb that are conserved in CREB function importantly in cellular gene activation and in complex formation with KM. These hydrophobic residues are assembled on one face of an amphipathic helix in both proteins, and mutations that disrupt c-Myb or CREB helicity in this region block interaction of either factor with KM. Binding of the helical c-Myb domain to KIX is accompanied by a substantial increase in entropy that compensates for the comparatively low enthalpy of complex formation. By contrast, binding of CREB to KIX entails a large entropy cost due to a random coil-to-helix transition in CREB that accompanies complex formation. These results indicate that the constitutive and inducible activation properties of c-Myb and CREB reflect secondary structural characteristics of their corresponding activating regions that influence the thermodynamics of formation of a complex with CBP. C1 Harvard Univ, Sch Med, Dept Cell Biol, Joslin Diabet Ctr,Res Div, Cambridge, MA 02138 USA. Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. St Jude Childrens Res Hosp, Dept Expt Oncol, Memphis, TN 38105 USA. St Jude Childrens Res Hosp, Dept Biochem, Memphis, TN 38105 USA. RP Montminy, M (reprint author), Salk Inst Biol Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. RI Zor, Tsaffrir/H-1802-2013; Henrion Caude, Alexandra/I-2778-2016; OI Wright, Peter/0000-0002-1368-0223 FU NCI NIH HHS [CA70909, P30 CA021765, R01 CA076385, R01 CA76385]; NIGMS NIH HHS [R37 GM037828, R01GM37828] NR 24 TC 95 Z9 95 U1 0 U2 7 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 AUG PY 1999 VL 19 IS 8 BP 5601 EP 5607 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 217RY UT WOS:000081513800035 PM 10409749 ER PT J AU Izumi, KM McFarland, EC Ting, AT Riley, EA Seed, B Kieff, ED AF Izumi, KM McFarland, EC Ting, AT Riley, EA Seed, B Kieff, ED TI The Epstein-Barr virus oncoprotein latent membrane protein 1 engages the tumor necrosis factor receptor-associated proteins TRADD and receptor-interacting protein (RIP) but does not induce apoptosis or require RIP for NF-kappa B activation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID LYMPHOCYTE GROWTH TRANSFORMATION; TERMINAL CYTOPLASMIC DOMAIN; SIGNALS CELL-DEATH; INFECTION MEMBRANE-PROTEIN-1; BINDING-SITE; KINASE RIP; IKK-ALPHA; LMP1; TNF; CD40 AB A site in the Epstein-Barr virus (EBV) transforming protein LMP1 that constitutively associates with the tumor necrosis factor receptor 1 (TNFR1)-associated death domain protein TRADD to mediate NF-kappa B and c-Jun N-terminal kinase activation is critical for long-term lymphoblastoid cell proliferation. We now find that LMP1 signaling through TRADD differs from TNFR1 signaling through TRADD. LMP1 needs only 11 amino acids to activate NF-kappa B or synergize with TRADD in NF-kappa B activation, while TNFR1 requires similar to 70 residues. Further, LMP1 does not require TRADD residues 294 to 312 for NF-kappa B activation, while TNFR1 requires TRADD residues 296 to 302. LMP1 is partially blocked for NF-kappa B activation by a TRADD mutant consisting of residues 122 to 293. Unlike TNFR1, LMP1 can interact directly with receptor-interacting protein (RIP) and stably associates with RIP in EBV-transformed lymphoblastoid cell lines. Surprisingly, LMP1 does not require RIP for NF-kappa B activation. Despite constitutive association with TRADD or RIP, LMP1 does not induce apoptosis in EBV-negative Burkitt lymphoma or human embryonic kidney 293 cells. These results add a different perspective to the molecular interactions through which LMP1, TRADD, and RTP participate in B-lymphocyte activation and growth. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Labs, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Kieff, ED (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA047006, R35 CA047006, CA47006] NR 59 TC 113 Z9 121 U1 0 U2 0 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 AUG PY 1999 VL 19 IS 8 BP 5759 EP 5767 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 217RY UT WOS:000081513800049 PM 10409763 ER PT J AU Lukas, ER Bartley, SM Graveel, CR Diaz, ZM Dyson, N Harlow, E Yamasaki, L Farnham, PJ AF Lukas, ER Bartley, SM Graveel, CR Diaz, ZM Dyson, N Harlow, E Yamasaki, L Farnham, PJ TI No effect of loss of E2F1 on liver regeneration or hepatocarcinogenesis in C57BL/6J or C3H/HeJ mice SO MOLECULAR CARCINOGENESIS LA English DT Article DE cell cycle; liver; nullizygous mice; diethylnitrosamine ID CELL-CYCLE REGULATION; DIHYDROFOLATE-REDUCTASE PROMOTER; TRANSCRIPTION FACTOR E2F1; B-MYB TRANSCRIPTION; RETINOBLASTOMA PROTEIN; IN-VIVO; GROWTH-REGULATION; DNA-SYNTHESIS; MOUSE E2F1; S-PHASE AB The E2F family of transcription factors regulates the expression of genes needed for DNA synthesis and cell-cycle control. However, the individual contributions of the different E2F family members in regulating proliferation in various tissues have not been well characterized. Mouse liver is an excellent system for investigating proliferation because its growth state can be experimentally manipulated. As observed in cell culture systems, E2F1 protein is present at low levels in the quiescent liver, with an increase in expression during proliferation. Therefore, we expected that E2F1 may play an important role in cell-growth control during periods of robust proliferation. Using E2F1-nullizygous mice, we performed partial hepatectomies to investigate the role of E2F1 in the synchronous proliferation of adult hepatocytes. We found that E2F1 deficiency resulted in only minor changes in gene expression and that the timing of liver regeneration was not altered in E2F1 nullizygous mice. E2F1 has displayed properties of both a tumor suppressor and an oncogene in different model systems. Therefore, we investigated the role of E2F1 in rapidly growing liver tumor cells in strains of mice that have high (C3H/HeJ) and low (C57BL/6J) rates of hepatocarcinogenesis. We observed no significant differences in the number of liver tumors that developed after diethylnitrosamine treatment of wild type versus E2F1-nullizygous mice. We suggest that abundant levels of E2F4 in the mouse liver compensate for loss of E2F1. (C) 1999 Wiley-Liss, Inc. C1 Univ Wisconsin, Mcardle Lab Canc Res, Madison, WI 53706 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. Columbia Univ, Dept Biol Sci, New York, NY 10027 USA. RP Farnham, PJ (reprint author), Univ Wisconsin, Mcardle Lab Canc Res, 1400 Univ Ave, Madison, WI 53706 USA. FU NCI NIH HHS [CA 09135]; NIGMS NIH HHS [T32GM08349] NR 54 TC 18 Z9 18 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 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD AUG PY 1999 VL 25 IS 4 BP 295 EP 303 DI 10.1002/(SICI)1098-2744(199908)25:4<295::AID-MC8>3.0.CO;2-9 PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 223BF UT WOS:000081819300008 PM 10449036 ER PT J AU Anisowicz, A Sotiropoulou, G Sager, R AF Anisowicz, A Sotiropoulou, G Sager, R TI Re-expression of SPR1 in breast cancer cells by phorbol 12-myristate 13-acetate (PMA) or UV irradiation is mediated by the AP-1 binding site in the SPR1 promoter SO MOLECULAR MEDICINE LA English DT Article ID MAMMARY EPITHELIAL-CELLS; MOUSE EPIDERMAL-CELLS; C-FOS GENE; DIFFERENTIATION MARKER; ACTIVATION DOMAIN; DNA-BINDING; TRANSFORMATION; TRANSCRIPTION; JUN; INDUCTION AB Background: Invasive tumor cells are characterized by multiple phenotypic changes as a result of the large number of cDNAs being differentially expressed in tumor cells compared to normal progenitors. Expression genetics focuses on changes at the RNA level with the aim of identifying functionally important genes whose aberrant expression in cancer cells is regulated at the level of transcription. These genes were named class II genes and are distinguished from class I genes, which are characterized by genomic mutations, deletions, or other alterations. Reversal of the tumor cell phenotype accompanying normalization of the expression of such genes may be exploited therapeutically if gene expression can be specifically modulated by drugs or other treatments. Considering that genes are coordinately regulated in complex networks, it is Likely that the expression of multiple genes can be simultaneously modulated in tumor cells by drugs acting on the signal transduction pathway that regulates their expression. The SPR1 gene is associated with differentiation and its expression is down-regulated or inactivated in malignant cells. Analysis of the SPR1 promoter showed that down-regulation of SPR1 expression in breast tumor cells occurs at the level of transcription. SPR1 presents an example of class II genes, since its expression was up-regulated in tumor cells by phorbol 12-myristate 13-acetate (PMA) or by ultraviolet (UV) irradiation. Materials and Methods: The SPR1 gene was identified by differential display on the basis of its reduced or absent expression in human breast tumor cell lines compared to normal mammary epithelial cell strains. Differential expression was confirmed by Northern blot analysis employing multiple normal and tumor cell lines. The promoter region -619 to +15 of the SPR1 gene was sequenced and analyzed by CAT assays, deletion analysis, and mutagenesis. Up-regulation of SPR1 expression by PMA and UV irradiation was monitored by Northern analysis and analyzed by CAT assays. Results: The mechanism of down-regulation of SPR1 expression in breast tumor cells was investigated. It was found that the -619 to +15 upstream promoter region is sufficient for SPR1 expression in normal breast cells, but it is transcriptionally silent in most breast tumor cell lines. By deletion analysis and mutagenesis, two upstream cis-acting promoter elements were identified. Our data indicate that the AP-1 element located between -139 and -133 acts as a major enhancer of SPR1 transcription only in normal mammary epithelial cells but not in corresponding tumor cells, whereas the sequences flanking the AP-1 site do not affect its promoter enhancing activity. In addition, a transcriptional repressor was identified that binds unknown factor(s) and is active in both normal and tumor breast cells. Inhibitor function was mapped to a 35-bp element located from -178 to -139 upstream of the human SPR1 mRNA start site. The expression of SPR1 could be induced in the 21MT-2 metastatic breast tumor cell line by PMA treatment or by short UV irradiation via a transcriptional mechanism. AP-1 is the cis element mediating the transcriptional activation of SPR1 by PMA, which induces the expression of AP-1 factors in 21MT-2 cells. Mutation of the AP-1 site abolishes the induction of SPR1 expression by PMA. Conclusions: Our results demonstrate that loss of SPR1 expression in breast tumor cells results from impaired transactivation through the AP-1 site in the SPR1 promoter, as well as from the presence of a negative regulatory element active in both normal and tumor cells. Furthermore, our results provide a basis for therapeutic manipulation of down-regulated genes, such as SPR1, in human cancers. C1 Univ Patras, Sch Hlth Sci, Dept Pharm, Patras 26500, Greece. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Canc Genet, Boston, MA 02115 USA. RP Sotiropoulou, G (reprint author), Univ Patras, Sch Hlth Sci, Dept Pharm, Patras 26500, Greece. NR 44 TC 4 Z9 4 U1 1 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD AUG PY 1999 VL 5 IS 8 BP 526 EP 541 PG 16 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 244LX UT WOS:000083054000004 PM 10501656 ER PT J AU Ikeda, K Ichikawa, T Wakimoto, H Silver, JS Deisboeck, TS Finkelstein, D Harsh, GR Louis, DN Bartus, RT Hochberg, FH Chiocca, EA AF Ikeda, K Ichikawa, T Wakimoto, H Silver, JS Deisboeck, TS Finkelstein, D Harsh, GR Louis, DN Bartus, RT Hochberg, FH Chiocca, EA TI Oncolytic virus therapy of multiple tumors in the brain requires suppression of innate and elicited antiviral responses SO NATURE MEDICINE LA English DT Article ID HERPES-SIMPLEX VIRUS-1; THYMIDINE KINASE GENE; IN-VIVO; RIBONUCLEOTIDE REDUCTASE; BRADYKININ ANALOG; DNA-SYNTHESIS; HUMAN GLIOMA; HUMAN SERUM; MUTANT; VECTOR AB The occurrence of multiple tumors in an organ heralds a rapidly fatal course. Although intravascular administration may deliver oncolytic viruses/vectors to each of these tumors, its efficiency is impeded by an antiviral activity present in complement-depleted plasma of rodents and humans. Here, this activity was shown to interact with complement in a calcium-dependent fashion, and antibody neutralization studies indicated preimmune IgM has a contributing role. Short-term exposure to cyclophosphamide (CPA) partially suppressed this activity in rodents and humans. At longer time points, cyclophosphamide also abrogated neutralizing antibody responses. Cyclophosphamide treatment of rats with large single or multiple intracerebral tumors substantially increased viral survival and propagation, leading to neoplastic regression. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurooncol Labs, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosurg Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Alkermes, Cambridge, MA 02111 USA. RP Chiocca, EA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurooncol Labs, Charlestown, MA 02129 USA. FU NCI NIH HHS [P01 CA 69246] NR 38 TC 208 Z9 213 U1 3 U2 7 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 AUG PY 1999 VL 5 IS 8 BP 881 EP 887 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 220TR UT WOS:000081684000030 PM 10426310 ER PT J AU Craft, S Asthana, S Schellenberg, G Cherrier, M Baker, LD Newcomer, J Plymate, S Latendresse, S Petrova, A Raskind, M Peskind, E Lofgreen, C Grimwood, K AF Craft, S Asthana, S Schellenberg, G Cherrier, M Baker, LD Newcomer, J Plymate, S Latendresse, S Petrova, A Raskind, M Peskind, E Lofgreen, C Grimwood, K TI Insulin metabolism in Alzheimer's disease differs according to apolipoprotein E genotype and gender SO NEUROENDOCRINOLOGY LA English DT Article DE insulin; Alzheimer's disease; apolipoprotein E; clinical neuroendocrinology ID CEREBRAL ENERGY-METABOLISM; RECEPTOR-RELATED PROTEIN; DEGRADING ENZYME; MEMORY; DEGRADATION; RATS; HYPERINSULINEMIA; STREPTOZOTOCIN; ASSOCIATION; DEMENTIA AB Higher fasting plasma insulin levels and reduced CSF-to-plasma insulin ratios, suggestive of insulin resistance, have been observed in patients with Alzheimer's disease (AD) who do not possess an apolipoprotein E (APOE)epsilon E4 allele. We examined the relationship of APOE and gender to peripheral insulin action and hyperinsulinemic memory facilitation in patients with AD using a sensitive measure of insulin-mediated glucose disposal. Participants were 32 patients with AD (9 without an epsilon 4 allele, 23 with an epsilon 4 allele) and 25 healthy age-matched adults (16 without an epsilon 4 allele, 9 with an epsilon 4 allele). AD subjects without an epsilon 4 allele had significantly lower insulin-mediated glucose disposal rates than AD patients with an epsilon 4 allele (p < 0.03), or than normal adults without an epsilon 4 allele (p < 0.02). Female AD subjects showed lower insulin-mediated glucose disposal rates than did male AD subjects (p < 0.02). No significant interaction was observed between APOE group and gender, suggesting that these effects are independent. AD subjects without an epsilon 4 allele also showed significant memory facilitation in the hyperinsulinemic condition (p < 0.04), whereas the AD-epsilon 4 group did not. Also in the hyperinsulinemic condition, AD patients without an epsilon 4 allele had lower insulin levels than patients with an epsilon 4 allele (p < 0.02), and women with AD had lower insulin levels than did men with AD despite similar insulin infusion rates and body mass (p < 0.004). No gender or genotype effects were observed in either condition for normal subjects. These results provide in vivo evidence of differences in insulin-mediated energy metabolism between epsilon 4 and non-epsilon 4 AD, and suggest that defective insulin action may be of particular pathophysiologic significance for patients without an epsilon-4 allele. C1 Vet Affairs Puget Sound Hlth Care Syst, GRECC 182B, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. Washington Univ, Dept Psychiat, St Louis, MO USA. RP Craft, S (reprint author), Vet Affairs Puget Sound Hlth Care Syst, GRECC 182B, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIA NIH HHS [R01-AG-10880] NR 29 TC 109 Z9 119 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD AUG PY 1999 VL 70 IS 2 BP 146 EP 152 DI 10.1159/000054469 PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 229QQ UT WOS:000082206400009 PM 10461029 ER PT J AU Yoshiura, T Wu, O Sorensen, AG AF Yoshiura, T Wu, O Sorensen, AG TI Advanced MR techniques - Diffusion MR imaging, perfusion MR imaging, and spectroscopy SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID CEREBRAL BLOOD-FLOW; MAGNETIC-RESONANCE SPECTROSCOPY; HIGH-RESOLUTION MEASUREMENT; TRACER BOLUS PASSAGES; ACUTE HUMAN STROKE; CONTRAST AGENTS; ISCHEMIC PENUMBRA; T2-WEIGHTED MRI; WATER DIFFUSION; BRAIN AB Recent technical advances in MR imaging have enabled the authors to investigate early physiological changes in acute ischemic stroke lesion. Diffusion and perfusion MR imaging can provide clinically useful information not only for early detection of ischemia, but also for prediction of tissue outcome. MR spectroscopy is a potentially powerful tool to study acute stroke, but its clinical value has been limited due to long examination time and low spatial resolution. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. NR 50 TC 18 Z9 18 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD AUG PY 1999 VL 9 IS 3 BP 439 EP + PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 232XK UT WOS:000082395100005 PM 10433637 ER PT J AU Reid, V Cros, D AF Reid, V Cros, D TI Proximal sensory neuropathies of the leg SO NEUROLOGIC CLINICS LA English DT Article ID FEMORAL CUTANEOUS NERVE; MERALGIA-PARESTHETICA; DIAGNOSIS; NEURALGIA; ENTRAPMENT; PARAESTHETICA; MANAGEMENT; SURGERY; INJURY AB This article addresses the proximal sensory neuropathies of the leg, concentrating on those nerves that are purely sensory or have a predominately sensory onset. These include the lateral femoral cutaneous nerve the ilioinguinal nerve, the genitofemoral, nerve, and the posterior femoral cutaneous nerve. The obturator and femoral nerves are also summarily mentioned with respect to their sensory symptoms. C1 Massachusetts Gen Hosp, Dept Neurol, Clin Neurophysiol Lab, Boston, MA 02114 USA. RP Reid, V (reprint author), Massachusetts Gen Hosp, Dept Neurol, Clin Neurophysiol Lab, Fruit St, Boston, MA 02114 USA. NR 45 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 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD AUG PY 1999 VL 17 IS 3 BP 655 EP + DI 10.1016/S0733-8619(05)70157-2 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 220FD UT WOS:000081653100014 PM 10393758 ER PT J AU Wojciulik, E Kanwisher, N AF Wojciulik, E Kanwisher, N TI The generality of parietal involvement in visual attention SO NEURON LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; HUMAN EXTRASTRIATE CORTEX; WORKING-MEMORY; SUSTAINED ATTENTION; SELECTIVE ATTENTION; UNILATERAL NEGLECT; FUNCTIONAL-ANATOMY; DIRECTED ATTENTION; NEURAL SYSTEMS; BRAIN ACTIVITY AB Functional magnetic resonance imaging (fMRI) was used to determine whether different kinds of visual attention rely on a common neural substrate. Within one session, subjects performed three different attention experiments (each comparing an attentionally demanding task with an easier task using identical stimuli): (1) peripheral shifting, (2) object matching, and (3) a nonspatial conjunction task. Two areas were activated in all three experiments: one at the junction of intraparietal and transverse occipital sulci (IPTO), and another in the anterior intraparietal sulcus (AIPS). These regions are not simply involved in any effortful task, because they were not activated in a fourth experiment comparing a difficult language task with an easier control task. Thus, activity in IPTO and AIPS generalizes across a wide variety of attention-requiring tasks, supporting the existence of a common neural substrate underlying multiple modes of visual selection. C1 Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. UCL, Inst Cognit Neurosci, London WC1N 3AR, England. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. RP Wojciulik, E (reprint author), Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. EM e.wojciulik@ucl.ac.uk FU NIMH NIH HHS [MH56037] NR 54 TC 401 Z9 413 U1 4 U2 15 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD AUG PY 1999 VL 23 IS 4 BP 747 EP 764 DI 10.1016/S0896-6273(01)80033-7 PG 18 WC Neurosciences SC Neurosciences & Neurology GA 230ZE UT WOS:000082280900018 PM 10482241 ER PT J AU Zhu, JJG Maruyama, T Jacoby, LB Herman, JG Gusella, JF Black, PM Wu, JK AF Zhu, JJG Maruyama, T Jacoby, LB Herman, JG Gusella, JF Black, PM Wu, JK TI Clonal analysis of a case of multiple meningiomas using multiple molecular genetic approaches: Pathology case report SO NEUROSURGERY LA English DT Article DE clonality assay; methylation-specific polymerase chain reaction; multiple meningiomas; NF2 mutations; X chromosome inactivation ID NF2 GENE; DINUCLEOTIDE REPEAT; TUMOR-SUPPRESSOR; DNA METHYLATION; HUMAN CANCERS; LINKAGE MAP; SCHWANNOMAS; LOCUS; NEUROFIBROMATOSIS-2; HETEROZYGOSITY AB OBJECTIVE: Multiple meningiomas are uncommon brain tumors occurring concurrently in several intracranial locations in the same patient. In the present study, we determined the clonality, methylation status of deoxyribonucleic acid, and relationship of genetic alterations in eight meningiomas from one female patient. METHODS: Six molecular genetic techniques, including two methylation-based clonality assays and one transcription-based clonality assay, methylation analysis of CpG islands by methylation-specific polymerase chain reaction, loss of heterozygosity, microsatellite instability, and mutational analysis of the NF2 gene on chromosome 22, were used in comparative investigations on clonality and genetic alterations. RESULTS: The presence of clonal tumor cells was demonstrated by 1) loss of the same copy of chromosome 22 in all eight tumors; 2) transcription of the human AR gene from the same allele in six of eight tumors; 3) a common unmethylated allele at the AR locus in all eight tumors; and 4) the identical single-basepair insertion mutation in exon 9 of the NF2 gene in six of eight tumors. In addition, loss of a copy of the X chromosome in one tumor nodule and microsatellite instability in another nodule were observed. CONCLUSION: Taken together, this case of multiple meningiomas was most likely monoclonal in origin. Loss of chromosome 22 was an early event during the development of multiple meningiomas and was followed by mutations at the NF2 locus. Later events, including loss of the X chromosome, variation of AR gene expression, or microsatellite instability, may also have played a role in the development of multiple meningiomas in this patient. C1 Beth Israel Deaconess Med Ctr, Div Neurosurg, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Brain Tumor Ctr, Boston, MA 02215 USA. Johns Hopkins Med Inst, Ctr Oncol, Baltimore, MD 21205 USA. Brigham & Womens Hosp, Neurosurg Labs, Boston, MA 02115 USA. Brigham & Womens Hosp, Brain Tumor Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Tufts Univ New England Med Ctr, Dept Neurosurg, Boston, MA 02111 USA. RP Wu, JK (reprint author), Beth Israel Deaconess Med Ctr, Div Neurosurg, 110 Francis St,Suite 3B, Boston, MA 02215 USA. FU NCI NIH HHS [CA51410]; NINDS NIH HHS [NS24279] NR 45 TC 21 Z9 22 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD AUG PY 1999 VL 45 IS 2 BP 409 EP 416 DI 10.1097/00006123-199908000-00049 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 224NY UT WOS:000081906200054 PM 10449091 ER PT J AU Gragoudas, ES Li, WJ Lane, AM Munzenrider, J Egan, KM AF Gragoudas, ES Li, WJ Lane, AM Munzenrider, J Egan, KM TI Risk factors for radiation maculopathy and papillopathy after intraocular irradiation SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Ophthalmology CY NOV 08-09, 1998 CL NEW ORLEANS, LOUISIANA SP Amer Acad Ophthalmol ID PROTON-BEAM IRRADIATION; UVEAL MELANOMAS; UTERINE CERVIX; THERAPY; RETINOPATHY; COMPLICATIONS; REGRESSION; CANCER AB Purpose: To evaluate rates of occurrence and risk factors for radiation maculopathy and radiation papillopathy in patients with choroidal melanoma at high risk for these complications, Design: Cohort study, Participants: A total of 558 patients treated with proton irradiation for choroidal melanoma between 1986 and 1996 with small to moderate sized tumors (less than 5 mm in height and 15 mm in diameter) located within 4 disc diameters of the macula or optic nerve and with a median ocular follow-up of 4 years. Methods: Annual and cumulative rates of each endpoint were estimated using life table approaches. Prognostic factors were evaluated using the Cox proportional hazards regression. Main Outcome Measures: Radiation maculopathy, radiation papillopathy, and vision loss to worse than 20/100. Results: Cumulative 5-year rates for radiation maculopathy, radiation papillopathy, and vision loss were 64%, 35%, and 68%, respectively. Complication rates rose as a function of radiation exposure to the macula (P for trend = 0.04) or optic disc (P for trend < 0.001), although dose-response patterns were nonlinear. History of diabetes was a significant risk factor for maculopathy (P < 0.001) and optic neuropathy (P = 0.009). Conclusions: The onset of radiation vasculopathy is determined primarily by the degree of irradiation exposure to the macula and optic disc. Risk may be enhanced among those with underlying vascular disorders. C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Gragoudas, ES (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. RI Li, Wenjun/F-5634-2015 OI Li, Wenjun/0000-0001-5335-7386 NR 34 TC 74 Z9 76 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD AUG PY 1999 VL 106 IS 8 BP 1571 EP 1577 DI 10.1016/S0161-6420(99)90455-4 PG 7 WC Ophthalmology SC Ophthalmology GA 221NC UT WOS:000081732300034 PM 10442906 ER PT J AU Ximenez-Fyvie, LA Haffajee, AD Martin, L Tanner, A Macuch, P Socransky, SS AF Ximenez-Fyvie, LA Haffajee, AD Martin, L Tanner, A Macuch, P Socransky, SS TI Identification of oral Actinomyces species using DNA probes SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE Actinomyces; DNA probes; subtraction hybridization; periodontal microorganism ID POLYACRYLAMIDE-GEL-ELECTROPHORESIS; RESTRICTION ENDONUCLEASE ANALYSIS; HUMAN EXPERIMENTAL GINGIVITIS; HUMAN CLINICAL SPECIMENS; SP-NOV; DENTAL PLAQUE; NAESLUNDII; MICROBIOTA; HYBRIDIZATION; VISCOSUS AB Oral Actinomyces comprise a major segment of both the supra- and subgingival microbiota; however, little is known about the distribution of individual species in different sites or clinical conditions. The purpose of the present investigation was to develop DNA probes for suggested species and genotypes of oral Actinomyces. Whole genomic DNA probes to 12 human oral species and/or serotypes were labeled with digoxigenin and used to seek cross-reactions among the taxa using the checkerboard DNA-DNA hybridization assay. The Actinomyces formed three distinct groups: 1) Actinomyces georgiae, Actinomyces meyeri and Actinomyces odontolyticus serotypes I and II; 2) Actinomyces viscosus and Actinomyces naeslundii serotypes I, II, III and WVA 963; and 3) Actinomyces gerencseriae and Actinomyces israelii. Cross-reactions among taxa were detected and minimized by increasing the temperature of the post-hybridization high-stringency wash to 80 degrees C. Despite the elevation in high stringency wash temperature, cross-reactions among strains of the A. naeslundii/A. viscosus group persisted. Probes for two of the three currently recognized genospecies in this group were prepared by removing the DNA in common between cross-reacting species using subtraction hybridization and polymerase chain reaction. Nine species and genospecies could be clearly separated by a combination of whole genomic and subtraction hybridization probes and by increasing the high-stringency wash temperature. A total of 195 fresh isolates of Actinomyces were grouped in a blind study using DNA probes and separately by SDS-PAGE protein profiles. Concordance between the two methods was 97.3%. The probes and hybridization conditions were tested for their ability to detect the Actinomyces species and genospecies in samples of supragingival and subgingival plaque from periodontitis subjects using checkerboard DNA-DNA hybridization. The probes detected the species in samples of supragingival and subgingival plaque, We concluded that whole genomic and subtraction hybridization DNA probes facilitate the detection and enumeration of species and genospecies of Actinomyces in plaque samples. C1 Forsyth Dent Ctr, Dept Periodontol, Boston, MA 02115 USA. Forsyth Dent Ctr, Dept Bioadhes, Boston, MA 02115 USA. RP Ximenez-Fyvie, LA (reprint author), Forsyth Dent Ctr, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-09513, DE-04881, DE-10977] NR 52 TC 12 Z9 12 U1 0 U2 6 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 AUG PY 1999 VL 14 IS 4 BP 257 EP 265 DI 10.1034/j.1399-302X.1999.140410.x PG 9 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA 220ZX UT WOS:000081700700010 PM 10551171 ER PT J AU Woolf, CJ Decosterd, I AF Woolf, CJ Decosterd, I TI Implications of recent advances in the understanding of pain pathophysiology for the assessment of pain in patients SO PAIN LA English DT Article DE pain pathophysiology; assessment of pain; pathogenesis of pain ID PROGRESSIVE TACTILE HYPERSENSITIVITY; PERIPHERAL-NERVE INJURY; PRIMARY SENSORY NEURONS; DORSAL HORN; SPINAL-CORD; MECHANICAL HYPERALGESIA; CENTRAL SENSITIZATION; PRIMARY AFFERENTS; RAT; INFLAMMATION AB As we approach the new millennium, it is clear that we are on the brink of a major change in clinical pain management. We are poised to move from a treatment paradigm that has been almost entirely empirical to one that will be derived from an understanding of the actual mechanisms involved in the pathogenesis of pain. When this is achieved, pain treatment will at last be rationally based. The implications of this are immense and will necessitate major changes in the way we classify pain, which until now has been based on disease, duration and anatomy, to a mechanism-based classification. In addition, the assessment, diagnosis and treatment of pain will change. The aim in the future will be to identify in individual patients what mechanisms are responsible for their pain and to target treatment specifically at those mechanisms. We present for discussion, a new approach for classifying pain, based on an analysis of mechanisms, and show how this could be used to assess pain clinically. Such kinds of pain assessment, which need to be designed to reveal as much as possible about mechanisms, are necessary for more sophisticated epidemiology and clinical research as well as for providing the outcome measures necessary for the evaluation of the efficacy of new treatments targeted at particular pain mechanisms. (C) 1999 International Association for the Study of Pain. Published by Elsevier Science B.V. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plastic Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp E, Charlestown, MA 02129 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plastic Res Grp, Charlestown, MA 02129 USA. EM woolf@etherdome.mgh.harvard.edu NR 37 TC 1 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD AUG PY 1999 SU 6 BP S141 EP S147 PG 7 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 233EH UT WOS:000082412200019 ER PT J AU Biederman, J Wilens, T Mick, E Spencer, T Faraone, SV AF Biederman, J Wilens, T Mick, E Spencer, T Faraone, SV TI Pharmacotherapy of attention-deficit/hyperactivity disorder reduces risk for substance use disorder SO PEDIATRICS LA English DT Article DE ADHD; pharmacotherapy substance use disorders ID DEFICIT HYPERACTIVITY DISORDER; 4-YEAR FOLLOW-UP; PSYCHIATRIC COMORBIDITY; CHILDREN; ADULTS; ADHD; BOYS AB Objective. To assess the risk for substance use disorders (SUD) associated with previous exposure to psychotropic medication in a longitudinal study of boys with attention-deficit/hyperactivity disorder (ADHD). Methods. The cumulative incidence of SUD throughout adolescence was compared in 56 medicated subjects with ADHD, 19 nonmedicated subjects with ADHD, and 137 non-ADHD control subjects. Results. Unmedicated subjects with ADHD were at a significantly increased risk for any SUD at follow-up compared with non-ADHD control subjects (adjusted OR: 6.3 [1.8-21.6]). Subjects with ADHD medicated at baseline were ata significantly reduced risk for a SUD at follow-up relative to untreated subjects with ADHD (adjusted OR: 0.15 [0.04-0.6]). For each SUD subtype studied, the direction of the effect of exposure to pharmacotherapy was similar to that seen for the any SUD category. Conclusions. Consistent with findings in untreated ADHD in adults, untreated ADHD was a significant risk factor for SUD in adolescence. In contrast, pharmacotherapy was associated with an 85% reduction in risk for SUD in ADHD youth. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, 15 Parkman St,WACC 725, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145 FU NICHD NIH HHS [R01-HD36317]; NIDA NIH HHS [DA-R2911315] NR 27 TC 168 Z9 173 U1 2 U2 11 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 AUG PY 1999 VL 104 IS 2 BP art. no. EP e20 DI 10.1542/peds.104.2.e20 PG 5 WC Pediatrics SC Pediatrics GA 222EP UT WOS:000081770700024 PM 10429138 ER PT J AU Kubin, CJ Sherman, O Hussain, KB Feinman, L AF Kubin, CJ Sherman, O Hussain, KB Feinman, L TI Delayed-onset ticlopidine-induced cholestatic jaundice SO PHARMACOTHERAPY LA English DT Article ID INDUCED PROLONGED CHOLESTASIS; HEPATITIS; HEPATOTOXICITY; THERAPY AB An 86-year-old man experienced a rash approximately 2 weeks after starting ticlopidine therapy, necessitating discontinuation of the drug. About 1 month later, despite discontinuation, he developed jaundice and liver test abnormalities. These resolved gradually over the next few months. Based on case reports and the drug's pharmacokinetic profile, a high index of suspicion for ticlopidine-induced jaundice is prudent in patients with recent exposure to the agent who have evidence of liver damage. C1 Vet Adm Med Ctr, Pharm Program 119, Med Surg Patient Care Ctr, Bronx, NY 10468 USA. Vet Adm Med Ctr, Dept Pharm, Bronx, NY 10468 USA. Vet Adm Med Ctr, Dept Gastroenterol, Bronx, NY 10468 USA. Mt Sinai Hosp, Bronx Vet Adm Med Ctr, Dept Med, Gastroenterol Sect, New York, NY 10029 USA. RP Sherman, O (reprint author), Vet Adm Med Ctr, Pharm Program 119, Med Surg Patient Care Ctr, W Kingsbridge Rd, Bronx, NY 10468 USA. NR 23 TC 6 Z9 7 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD AUG PY 1999 VL 19 IS 8 BP 1006 EP 1010 DI 10.1592/phco.19.11.1006.31567 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 224AG UT WOS:000081873300014 PM 10453975 ER PT J AU Gonzalez, S Moran, M Kochevar, IE AF Gonzalez, S Moran, M Kochevar, IE TI Chronic photodamage in skin of mast cell-deficient mice SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID IRRADIATED HAIRLESS MOUSE; ULTRAVIOLET-B IRRADIATION; NECROSIS-FACTOR-ALPHA; GENE-EXPRESSION; AGED SKIN; ELASTOSIS; NUMBERS; DAMAGE; MODEL; LIGHT AB Solar elastosis is a hallmark of photoaged human skin and a prominent feature in experimentally produced photoaging in murine skin. The products of mast cells have been implicated in the development of photoaged skin. We evaluated whether products from mast cells mediate chronic UVB-induced changes in murine skin by employing a strain of mast cell-deficient mice, WWv, The responses in these mice were compared to those in BALB/c, another albino mouse strain. Mice were exposed three times per week to UVB radiation for 11 weeks; the total dose was 18.8 J/cm(2), Irradiated WWv mice showed greater epidermal alterations than the irradiated BALB/c mice. In the dermis, a 3.6-fold increase in elastin content, as measured by desmosine, was produced in the WE-treated BALB/c mice; in contrast, no difference was observed in elastin between UVB-treated and untreated WWv mice. Collagen content was not increased by UVB treatment in either strain, and the glycosaminoglycan content increased a similar amount in UVB-treated mice in both strains. The number of mast cells increased twofold and the number of neutrophils increased six-fold in UVB-treated BALB/c mice compared to age-matched unirradiated controls. Neutrophils, as well as mast cells, were absent in untreated and UVB-treated WWv mouse skin. These results suggest that products of mast cells are important in the development of solar elastosis in murine skin either by directly inducing elastin production by fibroblasts or indirectly by mediating the presence of other cell types that produce products that increase fibroblast elastin production. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. RP Kochevar, IE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, WEL 224,37 Fruit St, Boston, MA 02114 USA. FU NIAMS NIH HHS [R01 AR43895] NR 30 TC 34 Z9 35 U1 0 U2 4 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 AUG PY 1999 VL 70 IS 2 BP 248 EP 253 DI 10.1111/j.1751-1097.1999.tb07996.x PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 226MG UT WOS:000082023300019 PM 10461464 ER PT J AU Urbanc, B Cruz, L Buldyrev, SV Havlin, S Hyman, BT Stanley, HE AF Urbanc, B Cruz, L Buldyrev, SV Havlin, S Hyman, BT Stanley, HE TI Dynamic feedback in an aggregation-disaggregation model SO PHYSICAL REVIEW E LA English DT Article ID DIFFUSION-LIMITED AGGREGATION; AMYLOID BETA-PROTEIN; SENILE PLAQUES; ALZHEIMERS-DISEASE; EDEN MODELS; KINETICS; GROWTH; FRAGMENTATION; LATTICE AB We study an aggregation-disaggregation model which is relevant to biological processes such as the growth of senile plaques in Alzheimer disease. In this model, during the aggregation each deposited particle has a probability of producing a new particle in its vicinity, while during disaggregation the particles are anihilated randomly. The model is held in a dynamic equilibrium by a feedback mechanism which changes the disaggregation probability in proportion to the change in the total number of particles. We also include surface diffusion which influences the morphology of growing aggregates and colonies. A colony includes the descendents of a single particle. We investigate the statistical properties of the model in two dimensions. We find that unlike the colonies, individual aggregates are fractals with a fractal dimension of D-f=1.92+/-0.06 in the absence of surface diffusion. We show that the surface diffusion changes the fractal dimension of aggregates: at a small aggregation-disaggregation rate, D-f is independent of the strength of the surface diffusion, D-f=1.73+/-0.03. At larger aggregation-disaggregation rates and different strengths of surface diffusion, aggregates with fractal dimensions between D-f=1.73 and 1.92 form, The steady-state distribution of aggregate sizes is shown to be power law if the aggregation-disaggregation process dominates over We surface diffusion. In the limit of weak aggregation-disaggregation and strong surface diffusion the size distribution is log-normal. [S1063-651X(99)01008-9]. C1 Boston Univ, Ctr Polymer Studies, Boston, MA 02215 USA. Boston Univ, Dept Phys, Boston, MA 02215 USA. Bar Ilan Univ, Gonda Goldschmited Ctr, IL-52900 Ramat Gan, Israel. Bar Ilan Univ, Dept Phys, IL-52900 Ramat Gan, Israel. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Urbanc, B (reprint author), Boston Univ, Ctr Polymer Studies, Boston, MA 02215 USA. RI Urbanc, Brigita/G-5839-2011; Cruz Cruz, Luis/B-2685-2013; Buldyrev, Sergey/I-3933-2015 OI Urbanc, Brigita/0000-0001-9159-7698; NR 35 TC 18 Z9 18 U1 1 U2 3 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1063-651X J9 PHYS REV E JI Phys. Rev. E PD AUG PY 1999 VL 60 IS 2 BP 2120 EP 2126 DI 10.1103/PhysRevE.60.2120 PN B PG 7 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 230CW UT WOS:000082235100057 PM 11970004 ER PT J AU Ring, D Jupiter, JB Toh, S AF Ring, D Jupiter, JB Toh, S TI Transarticular bony defects after trauma and sepsis: Arthrodesis using vascularized fibular transfer SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID SKELETAL DEFECTS; GRAFT; RECONSTRUCTION; TIBIA; EXTREMITY; SURGERY; TISSUE; TUMOR; FEMUR; KNEE AB Ten male patients with previously infected bony defects involving both sides of an articulation underwent arthrodesis using a vascularized fibular transfer. The average age of these patients was 38 years (range, 20 to 60 years). The size of the bony defect averaged 9 cm (range, 3 to 21 cm). The ankle was involved in five patients, the knee in two patients, the wrist in two patients, and the elbow in one patient. Nine cases represented septic pseudarthroses (eight after trauma and one after attempted ankle arthrodesis). One patient had a defect across the wrist after debridement of a chronic infection. The patients were followed for an average of 71 months (range, 26 to 144 months). Nine patients healed after the index vascularized fibular transfer, and one patient (ankle arthrodesis) required a second cancellous bone-grafting procedure for delayed union at the junction of the fibula with the talus. Four of seven patients with lower limb involvement had residual leg length discrepancies averaging 5 cm (range, 3 to 8 cm), and one had a persistent 20-degree internal rotation deformity. Two of the patients with upper limb involvement had stiff digits. Five of the nine previously employed patients returned to their former occupation (including heavy labor in four cases). Complications included two wound separations, one case of instability of the donor ankle after removal of a large fibular graft (related in part to a prier injury), and one fracture at the junction of the fibular graft with the local bone 10 months after the index procedure, which united after plate fixation and application of autogenous cancellous bone graft. Arthrodesis using a transfer of vascularized fibular bone represents a viable option for limb salvage in the face of an infected transarticular bony defect. C1 Massachusetts Gen Hosp, Dept Orthopaed, Hand Surg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed, Harvard Combined Orthopaed Residency, Boston, MA 02114 USA. Hirosaki Univ, Sch Med, Dept Orthopaed Surg, Hirosaki, Aomori, Japan. RP Jupiter, JB (reprint author), ACL 527,15 Parkinson St, Boston, MA 02114 USA. RI Toh, Satoshi/K-5737-2013 NR 73 TC 21 Z9 22 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD AUG PY 1999 VL 104 IS 2 BP 426 EP 434 DI 10.1097/00006534-199908000-00016 PG 9 WC Surgery SC Surgery GA 219LJ UT WOS:000081608500016 PM 10654686 ER PT J AU Asthana, S Craft, S Baker, LD Raskind, MA Birnbaum, RS Lofgreen, CP Veith, RC Plymate, SR AF Asthana, S Craft, S Baker, LD Raskind, MA Birnbaum, RS Lofgreen, CP Veith, RC Plymate, SR TI Cognitive and neuroendocrine response to transdermal estrogen in postmenopausal women with Alzheimer's disease: results of a placebo-controlled, double-blind, pilot study SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Alzheimer's disease; estrogen; cognition; neuroendocrine; memory; dementia ID GROWTH-FACTOR-I; REPLACEMENT THERAPY; CONTROLLED TRIAL; FEMALE-PATIENTS; MEMORY FUNCTION; PLASMA-LEVELS; DEMENTIA; INSULIN; ESTRADIOL; HORMONE AB Preliminary evidence from clinical studies indicates that treatment with estrogen augments cognitive function for women with Alzheimer's disease (AD). The neurobiology of estrogen, particularly its neuromodulatory and neuroprotective actions, provide a viable basis to support such cognition-enhancing effects, We conducted a placebo-controlled, double-blind, parallel-group design pilot clinical study to evaluate the cognitive and neuroendocrine response to estrogen administration for postmenopausal women with AD. Twelve women with probable AD of mild-moderate severity completed the study. During an eight week treatment period, six women received 0.05 mg/day dosage of 17 beta-estradiol via a skin patch and the remaining six wore a placebo skin patch. Subjects were randomized to equal distribution, and evaluated at baseline, at weeks 1, 3, 5, and 8 on treatment, and at weeks 9, 10, 11, and 13 off treatment. On each day of evaluation, cognition was assessed using a battery of neuropsychological tests, and blood samples were collected to measure plasma concentrations of estradiol and estrone. In addition, several neuroendocrine markers were measured in plasma to evaluate the relationship between estrogen-induced cognitive effects and fluctuations in the catecholaminergic and insulin-like growth factor systems. Significant effects of estrogen treatment were observed on attention (i.e. Stroop: number of self-corrections in the Interference condition, F[1,8] = 8.22, P < 0.03) and verbal memory (i.e., Buschke: delayed cued recall, F[3,30] = 4.31, P < 0.02). The salutary effects of estrogen on cognition were observed after the first week of treatment, and started to diminish when treatment was terminated. For women treated with estrogen, enhancement in verbal memory was positively correlated with plasma levels of estradiol (r = 0.96, P < 0.02) and negatively correlated with concentrations of insulin-like growth factor binding protein-3 (IGFBP-3) in plasma (r = -0.92, P < 0.03). Furthermore, a trend in the data was evident to suggest a negative relationship between plasma levels of insulin-like growth factor-1 (IGF-1) and verbal memory (r = -0.86, P = 0.06). Estrogen administration suppressed peripheral markers of the IGF system, as evidenced by a negative correlation between plasma concentration of estradiol and IGF-1 (r = -0.93, P < 0.03), and a trend for a similar relationship between plasma levels of estradiol and IGFBP-3 (r = - 0.86, P = 0.06). With respect to the catecholamines assayed, norepinephrine was positively correlated with verbal memory (r = 0.95, P < 0.02) for women who were treated with estrogen. Furthermore, there was a trend to suggest a negative relationship between plasma epinephrine levels and the number of errors committed on a test of attention (r = -0.84, P = 0.07). In the placebo group, no significant effects of estrogen replacement were evident either on measures of cognition or on any of the neuroendocrine markers. The results of this study suggest that estrogen replacement may enhance cognition for postmenopausal women with AD. Furthermore, several markers of neuroendocrine activity may serve to index the magnitude of estrogen-induced facilitation on cognition. In addition, research findings from the present study will provide important information for the design of larger prospective clinical studies that are essential to definitively establish the therapeutic role of estrogen replacement for postmenopausal women with AD. Published by Elsevier Science Ltd. C1 VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Amer Lake Div, Tacoma, WA 98493 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98115 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98115 USA. RP Asthana, S (reprint author), VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Amer Lake Div, Tacoma, WA 98493 USA. NR 54 TC 166 Z9 170 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD AUG PY 1999 VL 24 IS 6 BP 657 EP 677 DI 10.1016/S0306-4530(99)00020-7 PG 21 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 204MB UT WOS:000080767100005 PM 10399774 ER PT J AU Michaelson, JS Halpern, E Kopans, DB AF Michaelson, JS Halpern, E Kopans, DB TI Breast cancer: Computer simulation method for estimating optimal intervals for screening SO RADIOLOGY LA English DT Article DE breast neoplasms; breast neoplasms, metastases; breast radiography, utilization; cancer screening; computers, simulation ID TERM FOLLOW-UP; NATURAL-HISTORY; GROWTH-RATE; NUDE-MICE; CLINICAL IMPLICATIONS; AGE; MAMMOGRAPHY; TUMORS; TRANSPLANTATION; ANGIOGENESIS AB PURPOSE: To develop and evaluate a mathematic method that can be used to determine the optimal screening interval for detection of breast cancer prior to distant metastic spread. MATERIALS AND METHODS: A computer simulation was developed with the use of biologically based data from the literature on the rates of tumor growth and spread, which can be used to calculate the course of breast cancer growth and metastasis. RESULTS: On the basis of the data available at this time, the results of the simulations suggested that a screening interval of 2 years would result in a 22% reduction in the rate of distant metastatic disease, an interval of 1 year would result in a 51% reduction, and an interval of 6 months would result in an 80% reduction. CONCLUSION: These findings suggest that more frequent screening could dramatically reduce the death rate from breast cancer. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. RP Michaelson, JS (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NR 50 TC 72 Z9 74 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 1999 VL 212 IS 2 BP 551 EP 560 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 218RM UT WOS:000081565500037 PM 10429717 ER PT J AU Birkmeyer, JD Warshaw, AL Finlayson, SRG Grove, MR Tosteson, ANA AF Birkmeyer, JD Warshaw, AL Finlayson, SRG Grove, MR Tosteson, ANA TI Relationship between hospital volume and late survival after pancreaticoduodenectomy SO SURGERY LA English DT Article; Proceedings Paper CT 60th Annual Meeting of the Society-of-University-Surgeons CY FEB 11-13, 1999 CL NEW ORLEANS, LOUISIANA SP Soc Univ Surgeons ID BREAST-CANCER AB Background. Several studies have reported lower perioperative mortality rates with pancreaticoduodenectomy at high-volume hospitals than at low-volume hospitals. We sought to determine whether volume is also related to survival after hospital discharge. Methods, Using information from the Medicare claims database, we performed a retrospective cohort study of all 7229 patients over age 65 undergoing pancreaticoduodenectomy in the United States between 1992 and 1995. We divided the study population into approximate quartiles according to their hospital's average annual volume of pancreaticoduodenectomy in Medicine patients: very low (<1/y), low (1-2/y), medium (2-5/y), and high (5+/y). To adjust for potentially confounding variables, we used a Cox proportional hazards model to examine relationships between hospital volume and mortality, our primary outcome measure. Results. Overall, 3-year survival was higher at high-volume centers (37%) than at medium- (29%), low- (26%), and very low volume hospitals (25%) (log-rank P < .0001). After excluding perioperative deaths and adjusting for case-mis patients undergoing surgery at high-volume hospitals remained less likely to experience late mortality than patients at very low volume centers (adjusted hazard ratio 0.69, 95% CI 0.62-0.76). Relationships between hospital volume and survival after discharge were not ? restricted to patients with cancer diagnoses, patients with benign disease had similar improvements in late survival after surgery at high-volume centers. Conclusions. Hospital volume strongly influences both perioperative risk and long-tnm survival after pancreaticoduodenectomy. Our data suggest that both patient selection and differences in quality of care may underlie better outcomes at high-volume referral centers. C1 Dept Vet Affairs Med Ctr, VA Outcomes Grp 111B, White River Junction, VT 05009 USA. Dartmouth Med Sch, Dept Med, Ctr Evaluat Clin Sci, Hanover, NH USA. Dartmouth Med Sch, Dept Surg, Hanover, NH USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Birkmeyer, JD (reprint author), Dept Vet Affairs Med Ctr, VA Outcomes Grp 111B, White River Junction, VT 05009 USA. NR 11 TC 246 Z9 246 U1 0 U2 1 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 AUG PY 1999 VL 126 IS 2 BP 178 EP 183 DI 10.1067/msy.1999.98741 PG 6 WC Surgery SC Surgery GA 226NJ UT WOS:000082025800011 PM 10455881 ER PT J AU Hartwell, DW Wagner, DD AF Hartwell, DW Wagner, DD TI New discoveries with mice mutant in endothelial and platelet selectins SO THROMBOSIS AND HAEMOSTASIS LA English DT Article ID CELL-ADHESION MOLECULE-1; P-SELECTIN; DEFICIENT MICE; IN-VIVO; BONE-MARROW; HEMATOPOIETIC PROGENITORS; CYTOPLASMIC DOMAIN; HUMAN NEUTROPHILS; CONTACT HYPERSENSITIVITY; ACTIVATED PLATELETS C1 Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, Boston, MA 02115 USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [P01 HL56949, R01 HL53756] NR 69 TC 30 Z9 33 U1 0 U2 1 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 43, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD AUG PY 1999 VL 82 IS 2 BP 850 EP 857 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 246QN UT WOS:000083176200094 PM 10605793 ER PT J AU Grabowski, EF Petteruti, P Tsukarov, O Conroy, N Orkin, RW AF Grabowski, EF Petteruti, P Tsukarov, O Conroy, N Orkin, RW TI Shear stress diminishes the expression of tissue factor (TF) by cultured vascular endothelial cells while augmenting the production of tissue factor pathway inhibitor (TFPI) SO THROMBOSIS AND HAEMOSTASIS 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 F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 43, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD AUG PY 1999 SU S MA 236 BP 78 EP 78 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 290FP UT WOS:000085665900237 ER PT J AU George, M Hoppensteadt, DA Lietz, H Richardson, P Cella, G Fareed, J AF George, M Hoppensteadt, DA Lietz, H Richardson, P Cella, G Fareed, J TI Selective markers of pathogenesis in endothelial oxidative stress in various groups of patients SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Padua, Padua, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 43, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD AUG PY 1999 SU S MA 463 BP 149 EP 149 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 290FP UT WOS:000085665900463 ER PT J AU Messmore, HL Fabbrini, N Eichorst, M Nawrocki, J Godwin, J Wood, W Molnar, Z AF Messmore, HL Fabbrini, N Eichorst, M Nawrocki, J Godwin, J Wood, W Molnar, Z TI Pseudothrombocytopenia due to cryoglobulinemia SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Lab Serv, Hines, IL USA. Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 43, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD AUG PY 1999 SU S MA 515 BP 165 EP 165 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 290FP UT WOS:000085665900515 ER PT J AU Feng, SJ Christodoulides, N Berndt, MC Kroll, MH AF Feng, SJ Christodoulides, N Berndt, MC Kroll, MH TI The cytoplasmic domains of GpIb alpha and GpIb beta regulate 14-3-3 zeta binding to the GPIB/IX complex SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 VA Med Ctr, Houston, TX 77211 USA. Baylor Coll Med, Houston, TX 77030 USA. Rice Univ, Houston, TX 77251 USA. Baker Med Res Inst, Prahran, Vic 3181, Australia. RI Berndt, Michael/D-5580-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 43, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD AUG PY 1999 SU S MA 654 BP 207 EP 208 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 290FP UT WOS:000085665900653 ER PT J AU Christodoulides, N Feng, SJ Resendiz, JC Kroll, MH AF Christodoulides, N Feng, SJ Resendiz, JC Kroll, MH TI Shear stress induces the dynamic association of GPIb alpha with ABP and actin in human platelets SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 VA Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Rice Univ, Houston, TX 77251 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 43, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD AUG PY 1999 SU S MA 660 BP 209 EP 209 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 290FP UT WOS:000085665900659 ER PT J AU Ni, H Subbarao, S Denis, C Degen, JL Hynes, RO Wagner, DD AF Ni, H Subbarao, S Denis, C Degen, JL Hynes, RO Wagner, DD TI Distinct roles of von Willebrand factor and fibrinogen in thrombus growth in arterioles SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, Boston, MA 02115 USA. MIT, Ctr Canc Res, Howard Hughes Med Inst, Cambridge, MA 02139 USA. Childrens Hosp, Res Fdn, Cincinnati, OH 45229 USA. Univ Cincinnati, Cincinnati, OH 45221 USA. NR 0 TC 2 Z9 2 U1 1 U2 1 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 43, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD AUG PY 1999 SU S MA 1303 BP 411 EP 411 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 290FP UT WOS:000085665901305 ER PT J AU Schade, A Dong, JF Romo, EM Andrews, RK Gao, S Lopez, JA McIntire, LV AF Schade, A Dong, JF Romo, EM Andrews, RK Gao, S Lopez, JA McIntire, LV TI Naturally occurring and synthetic gain-of-function mutations of platelet glycoprotein (GP) Iba decrease the rolling velocity of GP Ib-IX-V-expressing cells on immobilized von Willebrand factor SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 Rice Univ, Baylor Coll Med, Houston, TX 77251 USA. VA Med Ctr, Houston, TX USA. Baker Inst, Melbourne, Vic, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 43, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD AUG PY 1999 SU S MA 1579 BP 501 EP 502 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 290FP UT WOS:000085665901581 ER PT J AU Afshar-Kharghan, V Aleksic, N Ahn, C Boerwinkle, E Wu, KK Lopez, JA AF Afshar-Kharghan, V Aleksic, N Ahn, C Boerwinkle, E Wu, KK Lopez, JA TI Prospective study of the association of the variable number of tandem repeats (VNTR) polymorphism in platelet glycoprotein (GP) Ib alpha and incidence of coronary heart disease SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. RI Wu, Kenneth Kun-Yu/B-1070-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 43, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD AUG PY 1999 SU S MA 1693 BP 537 EP 538 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 290FP UT WOS:000085665901695 ER PT J AU Richardson, PG Hoppensteadt, DA Elias, AD Kinchla, N Warren, D Iacobelli, M Guinan, EC Fareed, J AF Richardson, PG Hoppensteadt, DA Elias, AD Kinchla, N Warren, D Iacobelli, M Guinan, EC Fareed, J TI Elevation of endothelial stress products and trends seen in patients with severe veno-occlusive disease treated with defibrotide SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Crinos SpA, Como, Italy. NR 0 TC 1 Z9 1 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 43, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD AUG PY 1999 SU S MA 1982 BP 628 EP 629 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 290FP UT WOS:000085665901988 ER PT J AU Reed, GL Houng, AK Liu, L Parhami-Seren, B Matsueda, LH Hedstrom, L AF Reed, GL Houng, AK Liu, L Parhami-Seren, B Matsueda, LH Hedstrom, L TI A catalytic switch and the conversion of streptokinase to a fibrin-targeted plasminogen activator SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 Harvard Univ, Sch Publ Hlth, Massachusetts Gen Hosp, Boston, MA 02115 USA. Brandeis Univ, Waltham, MA 02254 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 43, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD AUG PY 1999 SU S MA 2238 BP 709 EP 709 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 290FP UT WOS:000085665902247 ER PT J AU Baker, R Lofthouse, E Staples, N Shen, Y Berndt, MC Lopez, JA Sadler, S Hankey, G AF Baker, R Lofthouse, E Staples, N Shen, Y Berndt, MC Lopez, JA Sadler, S Hankey, G TI Platelet glycoprotein (GP) IB alpha polymorphisms and risk of stroke SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 Univ Western Australia, Baker Med Res Inst, Royal Perth Hosp, Dept Haematol,Clin Thrombosis Unit, Nedlands, WA 6009, Australia. Univ Western Australia, Baker Med Res Inst, Royal Perth Hosp, Stroke Unit, Nedlands, WA 6009, Australia. VA Med Ctr, Houston, TX USA. RI Berndt, Michael/D-5580-2012; Hankey, Graeme /H-4968-2014 OI Hankey, Graeme /0000-0002-6044-7328 NR 0 TC 1 Z9 1 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 43, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD AUG PY 1999 SU S MA 2680 BP 845 EP 845 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 290FP UT WOS:000085665902691 ER PT J AU Lewandrowski, KU Cattaneo, MV Gresser, JD Wise, DL White, RL Bonassar, L Trantolo, DJ AF Lewandrowski, KU Cattaneo, MV Gresser, JD Wise, DL White, RL Bonassar, L Trantolo, DJ TI Effect of a poly(propylene fumarate) foaming cement on the healing of bone defects SO TISSUE ENGINEERING LA English DT Article ID IN-VITRO DEGRADATION; MORPHOGENETIC PROTEINS; HYDROXYAPATITE CEMENT; TISSUE; REGENERATION; TRANSPLANTATION; PROSTHESES; OSTEOLYSIS; SCAFFOLD AB Regeneration of skeletal tissues has been recognized as a new means for reconstruction of skeletal defects. We investigated the feasibility of an injectable and expandable porous implant system for in situ regeneration of bone. Therefore, a composite biodegradable foaming cement based on poly(propylene fumarate) was injected into a critical size defect made in the rat tibia. Animals were divided into two groups comparing the foam in the experimental group against sham-operated animals having a drill hole but no implant in the control group. Eight animals were included in each group. Animals were sacrificed at 1, 3, and 7 weeks postoperatively. Implantation sites were then evaluated with histologic and histomorphometric methods. Results of this study showed that defects did not heal in sham-operated animals. In the experimental group, metaphyseal and cortical defects healed within the first postoperative week by formation of immature woven bone. At the site of the cortical drill hole defect, healing was noted to progress to complete closure by formation of mature bone. Histomorphometry corroborated these findings and showed that metaphyseal bone remodeling peaked at 1 week postoperatively and then decreased as healing of the cortical defect progressed. This suggests that near-complete restoration of the original state of the tibial bone occurred in this animal model supporting the concept of in situ bone regeneration by application of engineered biodegradable porous scaffolds. C1 Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. Cambridge Sci Inc, Cambridge, MA 02138 USA. Univ Massachusetts, Med Ctr, Lab Tissue Engn, Worcester, MA USA. RI Bonassar, Lawrence/C-2103-2016 OI Bonassar, Lawrence/0000-0003-1094-6433 FU NIAMS NIH HHS [AR45062]; NIDCR NIH HHS [1R43DE12290-01A1] NR 45 TC 32 Z9 32 U1 0 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD AUG PY 1999 VL 5 IS 4 BP 305 EP 316 DI 10.1089/ten.1999.5.305 PG 12 WC Cell & Tissue Engineering SC Cell Biology GA 227FY UT WOS:000082069400002 PM 10477853 ER PT J AU Peretti, GM Bonassar, LJ Caruso, EM Randolph, MA Trahan, CA Zaleske, DJ AF Peretti, GM Bonassar, LJ Caruso, EM Randolph, MA Trahan, CA Zaleske, DJ TI Biomechanical analysis of a chondrocyte-based repair model of articular cartilage SO TISSUE ENGINEERING LA English DT Article ID PERIOSTEAL GRAFTS; OSTEOCHONDRAL DEFECTS; CULTURED CHONDROCYTES; MECHANICAL-PROPERTIES; IN-VITRO; MATRIX; TRANSPLANTATION; RECONSTRUCTION; LESIONS; RABBIT AB The objective of this study was to evaluate the biomechanical properties of newly formed cartilaginous tissue synthesized from isolated chondrocytes, Cartilage from articular joints of lambs was either digested in collagenase to isolated chondrocytes or cut into discs that were devitalized by multiple freeze-thaw cycles, Isolated cells were incubated in suspension culture in the presence of devitalized cartilage matrix for 3 weeks, Multiple chondrocyte/matrix constructs were assembled with fibrin glue and implanted subcutaneously in nude mice for up to 6 weeks. Testing methods were devised to quantify integration of cartilage pieces and mechanical properties of constructs. These studies showed monotonic increase with time in tensile strength, fracture strain, fracture energy, and tensile modulus to values 5-10% of normal articular cartilage by 6 weeks in vivo. Histological analysis indicated that chondrocytes grown on dead cartilage matrix produced new matrix that integrated individual cartilage pieces with mechanically functional tissue. C1 Hosp San Raffaele, Dept Orthopaed, I-20132 Milan, Italy. Univ Massachusetts, Med Ctr, Ctr Tissue Engn, Worcester, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Lab,Pediat Orthopaed Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Plast Surg Res Lab, Boston, MA 02114 USA. RI Bonassar, Lawrence/C-2103-2016; Peretti, Giuseppe/K-6358-2016 OI Bonassar, Lawrence/0000-0003-1094-6433; Peretti, Giuseppe/0000-0001-9341-7187 FU NIAMS NIH HHS [AR31068] NR 33 TC 54 Z9 56 U1 0 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD AUG PY 1999 VL 5 IS 4 BP 317 EP 326 DI 10.1089/ten.1999.5.317 PG 10 WC Cell & Tissue Engineering SC Cell Biology GA 227FY UT WOS:000082069400003 PM 10477854 ER PT J AU Kaihara, S Kim, S Benvenuto, M Kim, BS Mooney, DJ Tanaka, K Vacanti, JP AF Kaihara, S Kim, S Benvenuto, M Kim, BS Mooney, DJ Tanaka, K Vacanti, JP TI End-to-end anastomosis between tissue-engineered intestine and native small bowel SO TISSUE ENGINEERING LA English DT Article ID TRANSPLANTATION; TUBES AB The purpose of this study was to demonstrate the feasibility of end-to-end anastomosis between tissue-engineered intestine and native small bowel and to investigate the effect of this anastomosis on their growth. Microporous biodegradable polymer tubes were created from a fiber mesh of polyglycolic acid sprayed with 5% polylactic acid. Intestinal epithelial organoid units were harvested from neonatal Lewis rats and seeded onto polymers, These constructs were implanted into the omentum of adult Lewis rats, Three weeks after the implantation, the constructs (n = 7) were anastomosed to the native jejunum in an end-to-end fashion. Ten weeks after implantation, the tissue-engineered intestine was harvested. Four of 7 rats survived for 10 weeks and the overall patency rate of the anastomosis was 78% (11 of 14 anastomosis). The maximal length of the tissue-engineered intestine at week 3 and 10 was 1.80 +/- 0.32 and 1.93 +/- 0.39 cm (mean +/- SD). Histologically, the tissue-engineered intestine was lined with a well-developed neomucosal layer that was continuous with the native intestine. We conclude that anastomosis between tissue-engineered intestine and native small bowel had a moderately high patency rate and had a positive effect on maintenance of the size of the neointestine and development of the neomucosa. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Grad Sch Med, Dept Transplantat Immunol, Kyoto, Japan. Univ Chicago, Dept Surg, Chicago, IL 60637 USA. Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA. RI Kim, Byung-Soo/O-2352-2013 NR 15 TC 24 Z9 29 U1 0 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD AUG PY 1999 VL 5 IS 4 BP 339 EP 346 DI 10.1089/ten.1999.5.339 PG 8 WC Cell & Tissue Engineering SC Cell Biology GA 227FY UT WOS:000082069400005 PM 10477856 ER PT J AU Lee, K Berthiaume, F Stephanopoulos, GN Yarmush, ML AF Lee, K Berthiaume, F Stephanopoulos, GN Yarmush, ML TI Metabolic flux analysis: A powerful tool for monitoring tissue function SO TISSUE ENGINEERING LA English DT Review ID CITRIC-ACID CYCLE; MASS ISOTOPOMER ANALYSIS; NUCLEAR-MAGNETIC-RESONANCE; C-13 NMR-SPECTROSCOPY; PERFUSED RAT HEARTS; EUBACTERIUM CHLOROFLEXUS-AURANTIACUS; BIDIRECTIONAL REACTION STEPS; HYBRIDOMA CELL-METABOLISM; HUMAN HEPATOMA-CELLS; IN-VIVO AB In recent years, metabolic flux analysis has been widely used in bioprocess engineering to monitor cell viability and improve strain activity. Metabolic flux analysis refers to a methodology for investigating cellular metabolism whereby intracellular fluxes are calculated using a stoichiometric model for the major intracellular reactions and applying mass balances around intracellular metabolites. A powerful feature of this methodology is its ability to consider cellular biochemistry in terms of reaction networks. By considering the stoichiometry of biochemical reactions, it is possible to estimate the degree of engagement of each pathway participating in overall cellular activity, and hence obtain a comprehensive view of a cell's metabolic state. Given the potential impact of cellular energy metabolism on the function of engineered tissues, such comprehensive analysis of metabolic activity can be an extremely useful tool for tissue engineers. Estimates of intracellular fluxes under various environmental conditions could be used to optimize function in vivo as well as culture conditions in vitro. In this review, we provide a brief theoretical background of metabolic flux analysis and summarize the most widely used experimental approaches to obtain flux data. This review is intended as an overview of the field and as a starting point for tissue engineers wishing to learn about and eventually employ this methodology. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RI Lee, Kyongbum/D-9230-2013 NR 147 TC 33 Z9 39 U1 0 U2 7 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD AUG PY 1999 VL 5 IS 4 BP 347 EP 368 DI 10.1089/ten.1999.5.347 PG 22 WC Cell & Tissue Engineering SC Cell Biology GA 227FY UT WOS:000082069400006 PM 10477857 ER PT J AU Weller, E Long, N Smith, A Williams, P Ravi, S Gill, J Henessey, R Skornik, W Brain, J Kimmel, C Kimmel, G Holmes, L Ryan, L AF Weller, E Long, N Smith, A Williams, P Ravi, S Gill, J Henessey, R Skornik, W Brain, J Kimmel, C Kimmel, G Holmes, L Ryan, L TI Dose-rate effects of ethylene oxide exposure on developmental toxicity SO TOXICOLOGICAL SCIENCES LA English DT Article DE ethylene oxide (EtO); inhalation exposure; developmental toxicity; Haber's Law; mouse ID MOUSE FETUSES; LONG-TERM; DURATION; OZONE; TRICHLOROETHYLENE; NEUROTOXICITY; INHALATION; CANCER; DESIGN; BEANS AB In risk assessment, evaluating a health effect at a duration of exposure that is untested involves assuming that equivalent multiples of concentration (C) and duration (T) of exposure have: the same effect. The limitations of this approach (attributed to F. Haber, Zur Geschichte des Gaskrieges [On the history of gas warfare], in Funf Vortrage aus den Jahren 1920-1923 [Five lectures from the years 1920-1923], 1924, Springer, Berlin, pp. 76-92), have been noted in several studies. The study presented in this paper was designed to specifically look at dose-rate (C x T) effects, and it forms an ideal case study to implement statistical models and to examine the statistical issues in risk assessment. Pregnant female C57BL/6J mice were exposed, on gestational day 7, to ethylene oxide (EtO) via inhalation for 1.5, 3;, or 6 h at exposures that result in C x T multiples of 2100 or 2700 ppm-hi EtO was selected because of its short half-life, documented developmental toxicity, and relevance to exposures that occur in occupational settings. Concurrent experiments were run with animals exposed to air for similar periods. Statistical analysis using models developed to assess dose-rate effects revealed significant effects with respect to fetal death and resorptions, malformations, crown-to-rump length, and fetal weight. Animals exposed to short, high exposures of EtO on day 7 of gestation were found to have more adverse effects than animals exposed to the same C x T multiple but at longer, lower exposures. The implication for risk assessment is that applying Haber's Law could potentially lead to an underestimation of risk at a shorter duration of exposure and an overestimation of risk at a longer duration of exposure. Further research, toxicological and statistical, are required to understand the mechanism of the dose-rate effects, and how to incorporate the mechanistic information into the risk assessment decision process. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. US EPA, Washington, DC 20460 USA. Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. RP Weller, E (reprint author), Dana Farber Canc Inst, Dept Biostat Sci, 44 Binney St,Mayer 2nd Floor, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 37 TC 25 Z9 26 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD AUG PY 1999 VL 50 IS 2 BP 259 EP 270 DI 10.1093/toxsci/50.2.259 PG 12 WC Toxicology SC Toxicology GA 251QA UT WOS:000083455300013 PM 10478863 ER PT J AU Wang, SJ Lantz, RC Vermeulen, MW Chen, GJ Breceda, V Robledo, RF Hays, AM Young, S Witten, ML AF Wang, SJ Lantz, RC Vermeulen, MW Chen, GJ Breceda, V Robledo, RF Hays, AM Young, S Witten, ML TI Functional alterations of alveolar macrophages subjected to smoke exposure and antioxidant lazaroids SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE alveolar macrophages; lazaroids; lung injury; smoke inhalation; superoxide; tumor necrosis factor ID INDUCED LUNG INJURY; TUMOR-NECROSIS-FACTOR; CYTOKINE EXPRESSION; LIPID-PEROXIDATION; RABBIT MODEL; PRETREATMENT; ATTENUATION; INHALATION; INCREASE; RELEASE AB Acute inhalation of diesel fuel-polycarbonate plastic (DFPP) smoke causes severe lung injury, leading to acute respiratory distress syndrome (ARDS) and death. It has been reported that the initiation of acute lung injury is associated with the activation of pulmonary alveolar macrophages (PAM). To further explore the pathogenesis, alveolar macrophages (AM) of New Zealand rabbits ventilated and exposed to a 60 tidal volume of DFPP smoke in vivo were recovered at 1 h post-smoke. Smoke exposure induced significant increases in both mRNA and protein levels for PAM tumor necrosis factor-alpha (TNF-alpha), when compared to smoke control. Smoke also induced a biphasic response (inhibited at 2 h, enhanced at 24 h after cell isolation) in the production of superoxide (O-2(-)) by PAM. However, aerosolized lazaroid, U75412E (1.6 mg/kg body weight), significantly attenuated smoke-induced expression in AM TNF-alpha at the protein level but not at the mRNA level, and smoke-induced changes in AM production of O-2(-) This study suggests that highly expressing AM TNF-alpha following smoke may be a key contributor to the cascade that establishes an acute injury process and exacerbates oxidant-derived cell injury. Whereas, the lazaroid may ameliorate smoke-induced lung injury by attenuating AM TNF-alpha release, in addition to its primary antioxidative mechanism. C1 Univ Arizona, Dept Pediat, Hlth Sci Ctr, Joan B & Donald R Diamond Lung Injury Lab, Tucson, AZ 85724 USA. Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Witten, ML (reprint author), Univ Arizona, Dept Pediat, Hlth Sci Ctr, Joan B & Donald R Diamond Lung Injury Lab, POB 245073,1501 N Campbell Ave, Tucson, AZ 85724 USA. FU NIEHS NIH HHS [ES06694] NR 28 TC 10 Z9 10 U1 0 U2 0 PU STOCKTON PRESS PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD AUG PY 1999 VL 15 IS 5 BP 464 EP 469 DI 10.1177/074823379901500501 PG 6 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 295BL UT WOS:000085946000003 PM 10487357 ER PT J AU Dzik, WHS Okayama, A AF Dzik, WHS Okayama, A TI Can blood transfusion transmit disease-producing genes? SO TRANSFUSION LA English DT Editorial Material ID VIRUS TYPE-I; T-CELL LEUKEMIA; ANTI-TAX ANTIBODY; HTLV-I; INDIVIDUALS; PREVALENCE; INFECTION; PROVIRUS; DONORS; JAPAN C1 Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. Miyazaki Med Coll, Dept Med 2, Miyazaki 88916, Japan. RP Dzik, WHS (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, J-224, Boston, MA 02114 USA. NR 24 TC 3 Z9 3 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 AUG PY 1999 VL 39 IS 8 BP 795 EP 800 DI 10.1046/j.1537-2995.1999.39080795.x PG 6 WC Hematology SC Hematology GA 226ZH UT WOS:000082052700001 PM 10504112 ER PT J AU Dzik, W Sniecinski, I Fischer, J AF Dzik, W Sniecinski, I Fischer, J CA Biomed Excellence Safer Transfusion Working Par TI Toward standardization of CD34+ cell enumeration: an international study SO TRANSFUSION LA English DT Article ID PERIPHERAL-BLOOD; PROGENITOR CELLS; LEUKAPHERESIS PRODUCTS; WORLDWIDE STANDARD; QUALITY ASSURANCE; FLOW-CYTOMETRY; STEM-CELLS; YIELD; THERAPY; HARVEST AB BACKGROUND: An international multicenter study, involving six sites in North America and six sites in Europe, was undertaken to assess the performance of standardized methods for the enumeration of CD34+ cells in peripheral blood over the dynamic range from 200 cells per mu L to zero. Two commercially available techniques were studied, a flow cytometry method and a microvolume fluorimetry method. STUDY DESIGN AND METHODS: Coded samples were centrally prepared and sent to test sites by overnight mail. Samples included internal replicates, linear dilutions, and specimens at the lower limit of detection. In addition, commercially available reagent positive control cells were sent to a subset of laboratories. RESULTS: Over the sample range studied, the intersite precision among different laboratories was good with coefficients of variation ranging from 14 percent to 24 percent for microvolume fluorimetry and from 20 percent to 31 percent for flow cytometry. Intrasite precision ranged from 7 percent to 21 percent. Test linearity was excellent with sites demonstrating a mean r(2) = 0.992 for microvolume fluorimetry and r(2) = 0.984 for flow cytometry. The lower limit of detection was 5 CD34+ cells per mu L for both commercial assays. Over the range of 5 to 50 CD34+ cells per mu L, the microvolume fluorimetry assay reported slightly higher values than the flow cytometry assay. Preliminary analysis of reagent positive control cells showed very good precision and accuracy. CONCLUSIONS: Standardization of CD34+ cells enumeration is improving and commercially available assays provide accurate and precise methods. More investigation of reagent positive control cells is warranted. C1 Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. RP Dzik, W (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, J-224,55 Fruit St, Boston, MA 02114 USA. RI Selogie, Eileen/L-3628-2016 NR 24 TC 17 Z9 17 U1 0 U2 1 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD AUG PY 1999 VL 39 IS 8 BP 856 EP 863 DI 10.1046/j.1537-2995.1999.39080856.x PG 8 WC Hematology SC Hematology GA 226ZH UT WOS:000082052700011 PM 10504122 ER PT J AU Benjamin, RJ Rojas, P Christmas, S Neal, J Broughton, S Burgio, C Barrett, B Churchill, WH AF Benjamin, RJ Rojas, P Christmas, S Neal, J Broughton, S Burgio, C Barrett, B Churchill, WH TI Plateletpheresis efficiency: a comparison of the Spectra LRS and AMICUS separators SO TRANSFUSION LA English DT Article ID TRANSFUSION; COLLECTION; PLATELETS; APHERESIS; BLOOD; RISK AB BACKGROUND: Optimizing the yields of plateletpheresis by increasing collection efficiencies may provide several benefits: to patients, by increasing the dose in single-donor platelet (SDP) units; to the collection center, by increasing the percentage of components that may be split into double units; and/or to the donor, by reducing the duration of donation. STUDY DESIGN AND METHODS: A prospective, randomized study was undertaken to compare the efficiency of platelet collection in paired donations by 21 donors on two cell separators (Spectra LRS, version [v] 5.1; and AMICUS, v2.37). The order of donation was randomly assigned; donations were performed at least 2 weeks apart. A fixed blood volume (4000 mL) was processed by utilizing standard protocols. Findings were confirmed in a retrospective, matched study that compared the two separators by using fixed collection times (90 min). RESULTS: The AMICUS and Spectra LRS separators consistently produced white cell-reduced (<1 x 10(6) white cells) components. The AMICUS harvested 32 percent more platelets on average (median, 4.9 x 10(11); range, 1.5-8.7 x 10(11)) than the Spectra LRS (median, 3.7 x 10(11); range, 2.1-7.7 x 10(11)) (p = 0.03), with mean times of 71.5 and 66.0 minutes (p = 0.03), respectively, to process 4000 mt. Mild donor reactions tended to be more common on the AMICUS separator, which used significantly more ACD (median 482 mt vs. 389 mL; p<0.0001) than on the Spectra LRS. CONCLUSIONS: The AMICUS separator harvested more platelets per unit of blood volume processed than the Spectra LRS. Possible benefits include increased dose in each single-donor unit, increased double-unit harvests, and/or shorter donation time. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Partners CancerCare, Boston, MA USA. Baxter Healthcare Corp, Deerfield, IL 60015 USA. RP Benjamin, RJ (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 12 TC 25 Z9 25 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 AUG PY 1999 VL 39 IS 8 BP 895 EP 899 DI 10.1046/j.1537-2995.1999.39080895.x PG 5 WC Hematology SC Hematology GA 226ZH UT WOS:000082052700016 PM 10504127 ER PT J AU Jasper, JD Nickerson, CAE Hershey, JC Asch, DA AF Jasper, JD Nickerson, CAE Hershey, JC Asch, DA TI The public's attitudes toward incentives for organ donation SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT Conference on Ischemia-Reperfusion Injury and Organ Preservation for Transplantation CY MAR 20-21, 1998 CL WARSAW, POLAND ID FINANCIAL INCENTIVES; TRANSPLANT ORGANS; FUTURES MARKET; COMPENSATION; CONSENT; DONORS C1 Univ Toronto, Fac Pharm, Toronto, ON M5S 2S2, Canada. Univ Illinois, Dept Psychol, Urbana, IL 61801 USA. Univ Penn, Wharton Sch, Dept Operat & Informat Management, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Dept Hlth Care Syst, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Bioeth, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Jasper, JD (reprint author), Univ Toronto, Fac Pharm, 19 Russell St, Toronto, ON M5S 2S2, Canada. NR 25 TC 19 Z9 19 U1 0 U2 3 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 AUG PY 1999 VL 31 IS 5 BP 2181 EP 2184 DI 10.1016/S0041-1345(99)00301-2 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 226FD UT WOS:000082008900088 PM 10456008 ER PT J AU D'Amico, AV AF D'Amico, AV TI Analysis of the clinical utility of the use of salvage brachytherapy in patients who have a rising PSA after definitive external beam radiation therapy SO UROLOGY LA English DT Editorial Material ID LOCALIZED PROSTATE-CANCER; RADICAL PROSTATECTOMY; RADIOTHERAPY; RECURRENCE C1 Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst,Sch Med, Joint Ctr Radiat Therapy,Dept Radiat Oncol, Boston, MA 02115 USA. RP D'Amico, AV (reprint author), Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Dept Radiat Oncol, 330 Brookline Ave,5th Floor, Boston, MA 02215 USA. NR 13 TC 9 Z9 9 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 AUG PY 1999 VL 54 IS 2 BP 201 EP 203 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 221RL UT WOS:000081740000001 PM 10443710 ER PT J AU Grocela, JA McDougal, WS AF Grocela, JA McDougal, WS TI Ammonium transport in the intestine chronically exposed to urine: Is it reduced over time? SO UROLOGY LA English DT Article ID ABSORPTION; VESICLES; CONDUITS AB Objectives. To determine whether chronic exposure of urine to intestinal segments alters ammonium transport and thereby would be expected to reduce the metabolic acidosis of intestinal diversion. Methods. Ileal patch cystoplasty specimens and control-matched ileum segments were harvested from mongrel dogs after 6 months. Acridine orange fluorescence quenching was used to determine the Km, Vmax, and Hill coefficient of ileal patch cystoplasty membrane vesicles and of control-matched ileum membrane vesicles. Enzyme activities for glucose uptake and sodium transport were also determined. Results. A shift of the Km and Vmax for ammonium occurred with chronic exposure of the intestine to urine. However, some specific enzyme activities remained unchanged, particularly those of intracellular and basolateral membrane locations. Conclusions. Chronic exposure of the intestine to urine alters transport at the brush border by reducing the number of ports available for ammonium transport. It is less detrimental to intracellular and basolateral membrane enzyme activities. (C) 1999, Elsevier Science Inc. C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP McDougal, WS (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St,GRB 1102, Boston, MA 02114 USA. FU PHS HHS [5-RO1-DIC-Y6825-02] NR 20 TC 2 Z9 2 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 AUG PY 1999 VL 54 IS 2 BP 373 EP 376 DI 10.1016/S0090-4295(99)00095-3 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 221RL UT WOS:000081740000040 PM 10443743 ER PT J AU Biederman, I Bar, M AF Biederman, I Bar, M TI One-shot viewpoint invariance in matching novel objects SO VISION RESEARCH LA English DT Article DE shape recognition; shape representation; object perception; geons; nonaccidental properties; viewpoint invariance ID 3-DIMENSIONAL OBJECTS; MENTAL ROTATION; RECOGNITION; REPRESENTATION; VIEWS; NETWORK; IMAGES; SHAPE AB Humans often evidence little difficulty at recognizing objects from arbitrary orientations in depth. According to one class of theories, this competence is based on generalization from templates specified by metric properties (MPs), that were learned for the various orientations. An alternative class of theories assumes that non-accidental properties (NAPs) might be exploited so that even novel objects can be recognized under depth rotation. After scaling MP and NAP differences so that they were equally detectable when the objects were at the same orientation in depth, the present investigation assessed the effects of rotation on same-different judgments for matching novel objects. Judgments of a sequential pair of images of novel objects, when rendered from different viewpoints, revealed relatively low costs when the objects differed in a NAP of a single part, i.e. a geon. However, rotation dramatically reduced the detectability of MP differences to a level well below that expected by chance. NAPs offer a striking advantage over MPs for object classification and are therefore more likely to play a central role in the representation of objects. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Univ So Calif, Dept Psychol, Neurosci Program, Los Angeles, CA 90089 USA. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. RP Biederman, I (reprint author), Univ So Calif, Dept Psychol, Neurosci Program, Hedco Neurosci Bldg,MC 2520, Los Angeles, CA 90089 USA. NR 33 TC 112 Z9 115 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0042-6989 J9 VISION RES JI Vision Res. PD AUG PY 1999 VL 39 IS 17 BP 2885 EP 2899 DI 10.1016/S0042-6989(98)00309-5 PG 15 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 205MB UT WOS:000080824200008 PM 10492817 ER PT J AU Anand, BS AF Anand, BS TI Cirrhosis of liver SO WESTERN JOURNAL OF MEDICINE LA English DT Article ID CHRONIC HEPATITIS-B; INTRAHEPATIC PORTOSYSTEMIC SHUNT; INTERFERON-ALPHA-2B; METAANALYSIS; COMBINATION; LAMIVUDINE; RIBAVIRIN; ASCITES C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. VA Med Ctr, Digest Dis Sect 111D, Houston, TX 77030 USA. RP Anand, BS (reprint author), Baylor Coll Med, Dept Med, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 28 TC 13 Z9 13 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD AUG PY 1999 VL 171 IS 2 BP 110 EP 115 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 238CE UT WOS:000082692700021 PM 10510657 ER PT J AU Alwayn, IPJ Basker, M Buhler, L Cooper, DKC AF Alwayn, IPJ Basker, M Buhler, L Cooper, DKC TI The problem of anti-pig antibodies in pig-to-primate xenografting: current and novel methods of depletion and/or suppression of production of anti-pig antibodies SO XENOTRANSPLANTATION LA English DT Review DE anti-alpha-Gal antibodies; anti-CD40 ligand monoclonal antibody; B-cells; pig-to-primate; tolerance; xenotransplantation ID ANTI-CD20 MONOCLONAL-ANTIBODY; ALPHA-GALACTOSYL EPITOPES; B-CELL LYMPHOMA; HYPERACUTE REJECTION; NATURAL ANTIBODIES; IN-VIVO; ORGAN XENOTRANSPLANTATION; ANTI-GAL-ALPHA-1-3GAL ANTIBODY; XENOREACTIVE ANTIBODIES; CARBOHYDRATE ANTIGENS AB The role of antibodies directed against Gal alpha l-3Gal (alpha-Gal) epitopes in porcine-to-primate xenotransplantation has been widely studied during the past few years. These antibodies (anti-alpha-Gal) have been associated with both hyperacute rejection and acute vascular rejection of vascularized organs. Depletion and (temporary or permanent) suppression of production of anti-alpha-Gal seem to be essential to the long-term survival of these organs, even when the ultimate aim is accommodation or tolerance. Although more than 95% depletion of anti-alpha-Gal can be achieved by the use of immunoaffinity column technology, to date no regimen has been successful in preventing the return of anti-alpha-Gal (from continuing production). In this review, we discuss current and novel methods for achieving depletion or inhibition (i.e. extracorporeal immunoadsorption, anti-idiotypic antibodies, the intravenous infusion of immunoglobulin or oligosaccharides) and suppression of production (i.e. irradiation, pharmacologic agents, specific monoclonal antibodies, immunotoxins) of anti-alpha-Gal antibodies. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,MGH E, Boston, MA 02129 USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,MGH E, Bldg 149,13th St, Boston, MA 02129 USA. NR 92 TC 66 Z9 68 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD AUG PY 1999 VL 6 IS 3 BP 157 EP 168 DI 10.1034/j.1399-3089.1999.00030.x PG 12 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 237QB UT WOS:000082666600001 PM 10503781 ER PT J AU Buhler, L Pidwell, D Dowling, RD Newman, D Awwad, M Cooper, DKC AF Buhler, L Pidwell, D Dowling, RD Newman, D Awwad, M Cooper, DKC TI Different responses of human anti-HLA and anti-alpha gal antibody to long-term intravenous immunoglobulin therapy SO XENOTRANSPLANTATION LA English DT Article DE anti-alpha Gal antibodies; anti-HLA antibodies; cardiac assist device; intravenous immunoglobulin therapy ID HYPERACUTE REJECTION; IMMUNE GLOBULIN; GAMMA-GLOBULIN; DRUG-THERAPY; XENOTRANSPLANTATION; TRANSPLANTATION; ALLOANTIBODIES; SUPPRESSION; RECIPIENTS; DISEASES AB Concentrated human immunoglobulin (IVIG) has been administered intravenously in the treatment of autoimmune disorders and to reduce anti-HLA antibodies in highly sensitized patients awaiting organ transplantation. It has also been shown, in experimental animals, to prevent the hyperacute rejection of discordant xenografts, possibly by anticomplement activity. The aim of the present study was to assess the effect of IVIG therapy on both acquired anti-HLA antibodies and natural antigalactose alpha 1-3 galactose (alpha Gal) antibodies in five patients awaiting heart transplantation. Five patients placed on mechanical circulatory support who had developed high HLA panel-reactive antibodies (PRA) or in whom the percentage of PRA was increasing rapidly were treated weekly with 500 mg/kg IVIG, which contained 1% of anti-alpha Gal IgG. Levels of PRA, anti-alpha Gal IgG and IgM, and serum cytotoxicity to pig cells were measured before, during, and after therapy. PRA percentages in the five patients were initially 85%, 53%, 23%, 19% and 19% (mean 39%). Mean PRA fell by 66% after 3 months of therapy (to a mean PRA of 14%), and by 96% after 6 months therapy (to a mean PRA of 2%), Anti-alpha Gal antibody levels and serum cytotoxicity to pig aortic endothelial cells did not change significantly. These results confirm the effectiveness of IVIG therapy in reducing PRA in HLA highly sensitized patients. It is likely that IVIG does not contain the relevant anti-HLA antibody, resulting in an accelerated catabolism of native alloantibodies. However, as IVIG contains a normal level of anti-alpha Gal IgG, catabolism of anti-alpha Gal IgG is not modified, as it is being continuously replaced. To achieve a decrease in the anti-alpha Gal IgG level it would be necessary to use IVIG depleted of this antibody. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,MGH E, Boston, MA 02129 USA. Univ Louisville, Dept Surg, Div Cardiothorac Surg, Louisville, KY 40292 USA. BioTransplant, Charlestown, MA USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,MGH E, Bldg 149-9019,13th St, Boston, MA 02129 USA. NR 25 TC 6 Z9 8 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD AUG PY 1999 VL 6 IS 3 BP 181 EP 186 DI 10.1034/j.1399-3089.1999.00026.x PG 6 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 237QB UT WOS:000082666600004 PM 10503784 ER PT J AU Huang, CA Lorf, T Arn, JS Koo, GC Blake, T Sachs, DH AF Huang, CA Lorf, T Arn, JS Koo, GC Blake, T Sachs, DH TI Characterization of a monoclonal anti-porcine CD3 antibody SO XENOTRANSPLANTATION LA English DT Article DE calcium; monoclonal antibody; swine CD3; T cells; xenotransplantation ID MAJOR HISTOCOMPATIBILITY COMPLEX; LYMPHOCYTES-T; MINIATURE SWINE; INTRAEPITHELIAL LYMPHOCYTES; SIGNAL-TRANSDUCTION; WORKSHOP FINDINGS; ACTIVATION; CELLS; RECEPTORS; TRANSPLANTATION AB Partially inbred miniature swine have been developed in this laboratory as a large animal model for studies related to transplantation tolerance and as a source of hematopoietic cells and organs for xenotransplantation. The identification of swine CD3 specific mAbs capable of activating or depleting T cells in vitro and inducing an immunosuppressive state in vivo greatly facilitates studies of the swine immune system, transplantation tolerance and xenotransplantation research. Flow cytometry was used to determine the phenotypic profile of the swine specific mAb 898H2-6-15 (2-6-15). The specificity of 2-6-15 was further defined biochemically by surface labeling and immunoprecipitation. The ability of this mAb to activate pig T cells in vitro was examined by several criteria including proliferation assays, calcium flux analysis and detection of surface CD25 upregulation by fluorescence activated cell sorter (FACS) analysis. Monoclonal antibody 898H2-6-15 is specific for swine CD3 and is capable of inducing proliferation and CD25 upregulation in cultured swine peripheral blood lymphocytes. In addition, it induces calcium flux in purified pig T cells. Surprisingly, in contrast to described antibodies to CD3 in swine and other species, the binding of this antibody to porcine CD3 is dependent on the presence of extracellular calcium. Thus calcium was required in order to immunoprecipitate labeled surface molecules for biochemical analysis and to stain cell surfaces for FAGS analysis of swine lymphocytes. In this paper, we describe a new swine CD3 specific mAb, 898H2-6-15 (2-6-15) the characteristics of which make it an extremely useful tool for in vitro and in vivo studies of the swine immune system and xenotransplantation. The availability of swine T cell specific reagents should facilitate the monitoring of swine T cell engraftment and/or release amongst xenogeneic mixed chimeras and thymic transplant recipients as well as provide a means to treat potential GVHD across xenogeneic barriers. We are currently evaluating the in vivo effects of 2-6-15 in the pig. C1 Harvard Univ, Massachusetts Gen Hosp, MGH E, Sch Med,Transplantat Biol Res Ctr, Boston, MA 02129 USA. Univ Gottingen, Klin Transplantat Chirurg, D-3400 Gottingen, Germany. Merck & Co Inc, Merck Res Labs, Rahway, NJ 07065 USA. RP Sachs, DH (reprint author), Harvard Univ, Massachusetts Gen Hosp, MGH E, Sch Med,Transplantat Biol Res Ctr, Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [5RO1 AI39755-03, 2O1 AI31046B08] NR 30 TC 16 Z9 16 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD AUG PY 1999 VL 6 IS 3 BP 201 EP 212 DI 10.1034/j.1399-3089.1999.00022.x PG 12 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 237QB UT WOS:000082666600007 PM 10503787 ER PT J AU Auchincloss, H AF Auchincloss, H TI Literature update 1999, part 1 SO XENOTRANSPLANTATION LA English DT Review C1 Massachusetts Gen Hosp, Transplantat Unit, Surg Serv, Boston, MA 02114 USA. RP Auchincloss, H (reprint author), Massachusetts Gen Hosp, Transplantat Unit, Surg Serv, GRB 504, Boston, MA 02114 USA. NR 57 TC 1 Z9 1 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD AUG PY 1999 VL 6 IS 3 BP 220 EP 223 DI 10.1034/j.1399-3089.1999.00028.x PG 4 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 237QB UT WOS:000082666600009 PM 10503789 ER PT J AU Lee, SK Kim, JR Bai, SJ Shin, YS Nam, YT Cohen, SP AF Lee, SK Kim, JR Bai, SJ Shin, YS Nam, YT Cohen, SP TI Effects of priming with pancuronium or rocuronium on intubation with rocuronium in children SO YONSEI MEDICAL JOURNAL LA English DT Article DE neuromuscular relaxants; rocuronium; pancuronium; onset time; priming principle ID NEUROMUSCULAR BLOCKING ACTION; RAPID TRACHEAL INTUBATION; ACCELERATED ONSET; DELAYED RECOVERY; D-TUBOCURARINE; SUCCINYLCHOLINE; SUXAMETHONIUM; COMBINATIONS; MIVACURIUM; ANESTHESIA AB Rocuronium is a non-depolarizing neuromuscular blocking agent which has a rapid onset and intermediate duration of action. The goal of this study was to compare the neuromuscular blocking actions of rocuronium with and without a priming dose of pancuronium or rocuronium in children. Thirty patients were randomly allocated into 3 groups. Ten patients received a single dose of 0.6 mg/kg rocuronium (Group I). The others received either 0.015 mg/kg pancuronium (Group II) or 0.06 mg/kg rocuronium (Group III) 3 minutes before an intubating dose of 0.54 mg/kg rocuronium was given. Neuromuscular blockade was measured via accelerographic response to single stimulations (1 Hz) of the ulnar nerve until maximal twitch depression was reached followed by train-of-four (TOF) stimuli (2 Hz) at 15 second intervals for the remainder of recovery. Groups were compared with regard to onset time, duration and recovery indices. The onset time and duration of block did not differ significantly between groups. However, the time to recovery in group II (24.5+/-9.9 min) was significantly prolonged compared to that in group I (12.7+/-3.1 min) or group III (12.7+/-3.9 min). We concluded that the use of rocuronium with a preceding dose of either pancuronium or rocuronium provided no advantage for intubation in children. C1 Yonsei Univ, Coll Med, Dept Anesthesiol, Seoul 135270, South Korea. Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. RP Shin, YS (reprint author), Yonsei Univ, Coll Med, Yongdong Severance Hosp, Dept Anesthesiol, POB 1217, Seoul 135270, South Korea. NR 17 TC 3 Z9 4 U1 0 U2 0 PU YONSEI UNIV COLLEGE MEDICINE PI SEOUL PA C/O KYUN0-IL IM, M.D., PH.D, SHINCHON DONG 134, SEODAEMOON KU, SEOUL 120-752, SOUTH KOREA SN 0513-5796 J9 YONSEI MED J JI Yonsei Med. J. PD AUG PY 1999 VL 40 IS 4 BP 327 EP 330 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 233ZP UT WOS:000082457300005 PM 10487134 ER PT J AU Andersson, J Behbahani, H Lieberman, J Connick, E Landay, A Patterson, B Sonnerborg, A Lore, K Uccini, S Fehniger, TE AF Andersson, J Behbahani, H Lieberman, J Connick, E Landay, A Patterson, B Sonnerborg, A Lore, K Uccini, S Fehniger, TE TI Perforin is not co-expressed with granzyme A within cytotoxic granules in CD8 T lymphocytes present in lymphoid tissue during chronic HIV infection SO AIDS LA English DT Article DE HIV; cytotoxicity; CTL; perforin; granzyme A; lymphoid tissue ID IMMUNODEFICIENCY-VIRUS TYPE-1; MEDIATED CYTOTOXICITY; CTL RESPONSES; IN-VIVO; CELLS; ACTIVATION; LOAD; RNA; PROGRESSION; THERAPY AB Background: Residual HIV-l-infected cells are poorly eliminated from lymphoid tissue (LT) reservoirs by effector cytotoxic T lymphocytes (eCTL) despite antiretroviral therapy. Perforin and granzyme A (grA) constitute major effector molecules within eCTL granules that induce apoptosis and lysis of virally infected cells. Objective: Expression of perforin and grA was studied at the single cell level in LT and blood from 16 patients infected with HIV-1 (stage A1-C) who were not taking antiretroviral therapy. Method: Immunohistochemical analysis by in situ imaging of cells from blood and LT. Results: Quantitative in situ imaging showed that perforin-expressing CD8 T cells comprised 0.3-1.5% of total cells within the LT from recent HIV-1 seroconverters, while grA was found in 2.1-7.2% of total cells. However, despite high-level grA upregulation (1.5-4.5% of total cells) compared with that in non-infected individuals (0.4-0.9%), perforin expression remained low (< 0.1% of total cells) (P < 0.02) in LT from patients with chronic HIV-1 infection (stage A2-C). This contrasted with findings in peripheral blood mononuclear cells (PBMC) from the same HIV-1 infected cohort where perforin was detected in 13-31% of all PBMC, which was 10- to 100-fold higher than in lymphoid tissue (P < 0.001); grA was found in 14-32% of total PBMC. Two-colour staining showed that granular expression of perforin and grA was restricted to CD8 T cells in over 90% of total cells in both LT and blood. Conclusions: These findings indicate that cytotoxic perforin expression is impaired at local sites of HIV replication within lymphoid tissue. Since perforin is required together with grA for granule-mediated cytolysis, the low perforin expression in the LT may limit the ability of eCTL to eliminate HIV-1 infected cells in lymphoid tissue. (C) 1999 Lippincott Williams & Wilkins. C1 Huddinge Univ Hosp, Dept Infect Dis, Karolinska Inst, Stockholm, Sweden. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Univ Colorado, Hlth Sci Ctr, Div Infect Dis, Denver, CO USA. Rush Presbyterian St Lukes Med Ctr, Dept Immunol Microbiol, Chicago, IL 60612 USA. Northwestern Univ, Sch Med, Div Obstet Gynecol & Med, Chicago, IL USA. Univ Rome La Sapienza, Dept Expt Med & Pathol, Rome, Italy. RP Andersson, J (reprint author), Huddinge Univ Hosp, Div Infect Dis, I-63, S-14186 Huddinge, Sweden. RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [AI41536-01]; PHS HHS [2490] NR 36 TC 85 Z9 87 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUL 30 PY 1999 VL 13 IS 11 BP 1295 EP 1303 DI 10.1097/00002030-199907300-00005 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 221JD UT WOS:000081723200005 PM 10449281 ER PT J AU Hirsch, MS Wilfert, C Ammann, A Coovadia, HM Cu-Uvin, S Dabis, F Ekpini, RAE Kallings, LO Mofenson, L Tess, B Bryson, Y Cao, Y Chotpitayasunondh, T Nduati, R Solomon, S AF Hirsch, MS Wilfert, C Ammann, A Coovadia, HM Cu-Uvin, S Dabis, F Ekpini, RAE Kallings, LO Mofenson, L Tess, B Bryson, Y Cao, Y Chotpitayasunondh, T Nduati, R Solomon, S TI IAS position paper on prevention of HIV1 mother-to-child transmission SO AIDS LA English DT Article ID ZIDOVUDINE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Infect Dis Unit, Boston, MA 02114 USA. Glaser Pediat AIDS Fdn, Durham, NC USA. Duke Univ, Med Ctr, Durham, NC USA. Global Strategies HIV Prevent, San Rafael, CA USA. Univ Natal, Dept Pediat & Child Hlth, ZA-4001 Durban, South Africa. Brown Univ, Miriam Hosp, Providence, RI USA. Univ Victor Segalen, Bordeaux, France. Project RETEO CI, Abidjan, Cote Ivoire. Int AIDS Soc, Stockholm, Sweden. NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD USA. Minist Publ Hlth, Brasilia, DF, Brazil. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Natl Ctr AIDS Prevent & Control, Dept Clin Virol, Beijing, Peoples R China. Queen Sirikit Natl Inst Child Hlth, Childrens Hosp, Bangkok, Thailand. Univ Nairobi, Dept Pediat, Nairobi, Kenya. Ctr AIDS Res & Educ, Chennai, India. RP Hirsch, MS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Infect Dis Unit, Boston, MA 02114 USA. NR 22 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUL 30 PY 1999 VL 13 IS 11 BP A5 EP A9 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 221JD UT WOS:000081723200035 ER PT J AU Sinilnikova, OM Egan, KM Quinn, JL Boutrand, L Lenoir, GM Stoppa-Lyonnet, D Desjardins, L Levy, C Goldgar, D Gragcoudas, ES AF Sinilnikova, OM Egan, KM Quinn, JL Boutrand, L Lenoir, GM Stoppa-Lyonnet, D Desjardins, L Levy, C Goldgar, D Gragcoudas, ES TI Germline brca2 sequence variants in patients with ocular melanoma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID BREAST-CANCER FAMILIES; UVEAL MELANOMA; SUSCEPTIBILITY GENE; CHROMOSOME 13Q12-13; FREQUENCY; MUTATIONS AB On the basis, chiefly, of anecdotal reports of cases of ocular melanoma (OM) occurring in families with inherited susceptibility to breast cancer due to brca2 germline mutations, we examined the frequency of brca2 alterations in a series of 62 ocular melanoma cases. These cases were preferentially selected on the basis of reported family history of breast or ovarian cancer, or OM, although the series also included a randomly selected set of cases without family history of cancer. A total of 7 germline alterations were found, of which 3 were likely to be associated with disease. While all 3 deleterious mutations were found in patients who also had a personal history of breast cancer, only 1 of the 3 families had a family history of breast/ovarian cancer or OM. Although germline brca2 mutations may account for a small proportion of all OM cases, there may be additional loci that contribute to familial aggregation of OM and to the familial association between OM and breast cancer. Int. J. Cancer 82:325-328, 1999. (C) 1999 Wiley-Liss, Inc. C1 Int Agcy Res Canc, Unit Viral & Hereditary Factors Carcinogenesis, F-69372 Lyon, France. Univ Lyon 1, CNRS, UMR 5641, F-69365 Lyon, France. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Retina Serv, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Inst Curie, Unite Oncol Genet, Paris, France. Inst Curie, Unite Ophtalmol, Paris, France. Int Agcy Res Canc, Unit Genet Epidemiol, F-69372 Lyon, France. RP Egan, KM (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Retina Serv, 243 Charles St, Boston, MA 02114 USA. NR 21 TC 40 Z9 41 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 30 PY 1999 VL 82 IS 3 BP 325 EP 328 PG 4 WC Oncology SC Oncology GA 211YJ UT WOS:000081189200003 PM 10399947 ER PT J AU Schendel, SL Azimov, R Pawlowski, K Godzik, A Kagan, BL Reed, JC AF Schendel, SL Azimov, R Pawlowski, K Godzik, A Kagan, BL Reed, JC TI Ion channel activity of the BH3 only Bcl-2 family member, BID SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYTOCHROME-C; APOPTOSIS; MITOCHONDRIA; PROTEIN; BAX; DEATH; BCL-X(L); PEPTIDE; RELEASE; PATHWAY AB BID is a member of the BH3-only subgroup of Bcl-2 family proteins that displays pro-apoptotic activity. The NH2-terminal region of BID contains a caspase-8 (Casp-8) cleavage site and the cleaved form of BID translocates to mitochondrial membranes where it is a potent inducer of cytochrome c release. Secondary structure and fold predictions suggest that BID has a high degree of ct-helical content and structural similarity to Bcl-X-L, which itself is highly similar to bacterial pore-forming toxins. Moreover, circular dichroism analysis confirmed a high alpha-helical content of BID. Amino-terminal truncated BID Delta 1-55, mimicking the Casp-8-cleaved molecule, formed channels in planar bilayers at neutral pH and in liposomes at acidic pH. In contrast, full-length BID displayed channel activity only at nonphysiological pH 4.0 (but not at neutral pH) in planar bilayers and failed to form channels in liposomes even under acidic conditions. On a single channel level, BID Delta 1-55 channels were voltage-gated and exhibited multiconductance behavior at neutral pH. When full-length BID was cleaved by Casp-8, it too demonstrated channel activity similar to that seen with BID Delta 1-55. Thus, BID appears to share structural and functional similarity with other Bcl-2 family proteins known to have channel-forming activity, but its activity exhibits a novel form of activation: proteolytic cleavage. C1 Burnham Inst, La Jolla, CA 92307 USA. Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. RP Reed, JC (reprint author), Burnham Inst, La Jolla, CA 92307 USA. RI Pawlowski, Krzysztof/E-3262-2012; Pawlowski, Krzysztof/C-2949-2013; Godzik, Adam/A-7279-2009 OI Pawlowski, Krzysztof/0000-0002-5367-0935; Godzik, Adam/0000-0002-2425-852X FU NIGMS NIH HHS [GM-60049]; NIMH NIH HHS [MH 01174] NR 29 TC 148 Z9 153 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 JUL 30 PY 1999 VL 274 IS 31 BP 21932 EP 21936 DI 10.1074/jbc.274.31.21932 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 221HF UT WOS:000081721100068 PM 10419515 ER PT J AU Kawakubo, K Coy, DH Walsh, JH Tache, Y AF Kawakubo, K Coy, DH Walsh, JH Tache, Y TI Urethane-induced somatostatin mediated inhibition of gastric acid: Reversal by the somatostatin 2 receptor antagonist PRL-2903 SO LIFE SCIENCES LA English DT Article DE somatostatin receptor antagonist; acid secretion; PRL-2903; somatostatin antibody ID ENTEROCHROMAFFIN-LIKE CELLS; MONOCLONAL-ANTIBODY; ANESTHETIZED RATS; SECRETION; RELEASE; IMMUNONEUTRALIZATION; BIOLOGY; SUBTYPES AB Urethane increases the release of somatostatin (SRIF) which inhibits gastric acid secretion. The SRIF monoclonal antibody, CURE.S6 and the novel sst(2) antagonist, PRL-2903 injected intravenously at maximal effective doses increased gastric acid secretion by 2 and 10 fold respectively from basal values within 30 min in urethane-anesthetized rats. Plasma gastrin levels were elevated 2.5 fold within 15 min by PRL-2903 (1.3 mu mol/kg, iv). These data indicate that the low gastrin and acid secretion levels induced by urethane result from endogenous SRIF acting on sst(2) and that PRL-2903 is a valuable SRIF antagonist to assess sst(2) mediated events. (C) 1999 Elsevier Science Inc. C1 W Los Angeles Vet Affairs Med Ctr, CURE Digest Dis Res Ctr, Dept Med, Div Digest Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. Tulane Univ, Med Ctr, Dept Med, New Orleans, LA 70112 USA. RP Tache, Y (reprint author), W Los Angeles Vet Affairs Med Ctr, CURE Digest Dis Res Ctr, Dept Med, Div Digest Dis, Bldg 115,Room 203,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK 17294, DK-41301, DK 33061] NR 20 TC 5 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JUL 30 PY 1999 VL 65 IS 10 BP PL115 EP PL120 DI 10.1016/S0024-3205(99)00340-9 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 224BK UT WOS:000081876100014 PM 10499878 ER PT J AU Rauch, SL Shin, LM Dougherty, DD Alpert, NM Orr, SP Lasko, M Macklin, ML Fischman, AJ Pitman, RK AF Rauch, SL Shin, LM Dougherty, DD Alpert, NM Orr, SP Lasko, M Macklin, ML Fischman, AJ Pitman, RK TI Neural activation during sexual and competitive arousal in healthy men SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE limbic system; globus pallidus; cingulate cortex; emotion; positron emission tomography ID POSTTRAUMATIC-STRESS-DISORDER; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL BLOOD-FLOW; FUNCTIONAL NEUROANATOMY; SUBSTANTIA INNOMINATA; SYMPTOM PROVOCATION; FACIAL EXPRESSIONS; COMBAT VETERANS; IMAGERY; HAPPINESS AB To investigate the mediating neuroanatomy of positively valenced arousal, we used script-driven imagery in conjunction with positron emission tomography to measure relative regional cerebral blood flow (rCBF) during sexual and competitive arousal, as well as neutral comparison states. Subjects were eight healthy right-handed men. Psychophysiologic responses and subjective ratings confirmed that the desired state manipulations were achieved. Statistical parametric mapping revealed similar patterns of rCBF changes for both positively valenced arousal conditions: increases were found within anterior cingulate and anterior temporal cortex as well as the ventral globus pallidus; decreases were found within widespread heteromodal association areas. These results complement findings from studies of other normal and pathological emotional states, and provide new insights regarding the neural substrates of pleasurable arousal in healthy men. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Vet Affairs Res Serv, Manchester, NH USA. RP Rauch, SL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bldg 149,13th St,9th Floor, Charlestown, MA 02129 USA. EM rauch@psych.mgh.harvard.edu FU NIMH NIH HHS [MH01215] NR 37 TC 73 Z9 76 U1 4 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD JUL 30 PY 1999 VL 91 IS 1 BP 1 EP 10 DI 10.1016/S0925-4927(99)00020-7 PG 10 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 233ZX UT WOS:000082458000001 PM 10496688 ER PT J AU Hahn, WC Counter, CM Lundberg, AS Beijersbergen, RL Brooks, MW Weinberg, RA AF Hahn, WC Counter, CM Lundberg, AS Beijersbergen, RL Brooks, MW Weinberg, RA TI Creation of human tumour cells with defined genetic elements SO NATURE LA English DT Article ID LARGE T-ANTIGEN; TELOMERASE ACTIVITY; EPITHELIAL-CELLS; HUMAN-FIBROBLASTS; TRANSFORMATION; EXPRESSION; SENESCENCE; ONCOGENE; SARCOMA; CANCER AB During malignant transformation, cancer cells acquire genetic mutations that override the normal mechanisms controlling: cellular proliferation. Primary rodent cells are efficiently converted into tumorigenic cells by the coexpression of cooperating oncogenes(1,2). However, similar experiments with human cells have consistently failed to yield tumorigenic transformants(3-5), indicating a fundamental difference in the biology of human and rodent cells. The few reported successes in the creation of human tumour cells have depended on the use of chemical or physical agents to achieve immortalization(6), the selection of rare, spontaneously arising immortalized cells(7-10), or the use of an entire viral genome(11). We show here that the ectopic expression of the telomerase catalytic subunit (hTERT)(12) in combination with two oncogenes (the simian virus 40 large-T oncoprotein and an oncogenic allele of H-ras) results in direct tumorigenic conversion of normal human epithelial and fibroblast cells. These results demonstrate that disruption of the intracellular pathways regulated by large-T, oncogenic ras and telomerase suffices to create a human tumor cell. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA 02142 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Duke Univ, Med Ctr, Dept Radiat Oncol, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. RP Weinberg, RA (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. NR 30 TC 1631 Z9 1678 U1 9 U2 75 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 29 PY 1999 VL 400 IS 6743 BP 464 EP 468 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 221FZ UT WOS:000081715000054 PM 10440377 ER PT J AU Chin, L Tam, A Pomerantz, J Wong, M Holash, J Bardeesy, N Shen, Q O'Hagan, R Pantginis, J Zhou, H Horner, JW Cordon-Cardo, C Yancopoulos, GD DePinho, RA AF Chin, L Tam, A Pomerantz, J Wong, M Holash, J Bardeesy, N Shen, Q O'Hagan, R Pantginis, J Zhou, H Horner, JW Cordon-Cardo, C Yancopoulos, GD DePinho, RA TI Essential role for oncogenic Ras in tumour maintenance SO NATURE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; TRANSGENIC MICE; FACTOR EXPRESSION; UP-REGULATION; ANGIOGENESIS; MELANOMA; CELLS; INDUCTION; HYPOXIA AB Advanced malignancy in tumours represents the phenotypic endpoint of successive genetic lesions that affect the function and regulation of oncogenes and tumour-suppressor genes(1). The established tumour is maintained through complex and poorly understood host-tumour interactions that guide processes such as angiogenesis and immune sequestration. The many different genetic alterations that accompany tumour genesis raise questions as to whether experimental cancer-promoting mutations remain relevant during tumour maintenance. Here we show thar melanoma genesis and maintenance are strictly dependent upon expression of H-Ras(V12G) in a doxycycline-inducible H-Ras mouse melanoma model null for the tumour suppressor INK4a. Withdrawal of doxycycline and H-Ras(V12G) down-regulation resulted in clinical and histological regression of primary and explanted tumours. The initial stages of regression involved marked apoptosis in the tumour cells and host-derived endothelial cells. Although the regulation of vascular endothelial growth factor (VEGF) was found td be Ras-dependent in vitro, the failure of persistent endogenous and enforced VEGF expression to sustain tumour viability indicates that the tumour-maintaining actions of activated Ras extend beyond the regulation of VEGF expression in vivo. Our results provide genetic evidence that H-Ras(V12G) is important in both the genesis and maintenance of solid tumours. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA. Albert Einstein Coll Med, Bronx, NY 10461 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 25 TC 623 Z9 638 U1 1 U2 13 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 29 PY 1999 VL 400 IS 6743 BP 468 EP 472 DI 10.1038/22788 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 221FZ UT WOS:000081715000055 PM 10440378 ER PT J AU Berger, AK Schulman, KA Gersh, BJ Pirzada, S Breall, JA Johnson, AE Every, NR AF Berger, AK Schulman, KA Gersh, BJ Pirzada, S Breall, JA Johnson, AE Every, NR TI Primary coronary angioplasty vs thrombolysis for the management of acute myocardial infarction in elderly patients SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID COOPERATIVE CARDIOVASCULAR PROJECT; THERAPY; EXPERIENCE; HOSPITALS; MEDICARE; VOLUME AB Context Despite evidence from randomized trials that, compared with early thrombolysis, primary percutaneous transluminal coronary angioplasty (PTCA) after acute myocardial infarction (AMI) reduces mortality in middle-aged adults, whether elderly patients with AMI are more likely to benefit from PTCA or early thrombolysis is not known. Objective To determine survival after primary PTCA vs thrombolysis in elderly patients, Design The Cooperative Cardiovascular Project, a retrospective cohort study using data from medical charts and administrative files. Setting Acute care hospitals in the United States. Patients A total of 20 683 Medicare beneficiaries, who arrived within 12 hours of the onset of symptoms, were admitted between January 1994 and February 1996 with a principal discharge diagnosis of AMI, and were eligible for reperfusion therapy. Main Outcome Measures Thirty-day and 1-year survival. Results A total of 80 356 eligible patients had an AMI at hospital arrival and met the inclusion criteria, of whom 23.2% received thrombolysis and 2.5% underwent primary PTCA within 6 hours of hospital arrival, Patients undergoing primary PTCA had lower 30-day (8.7% vs 11.9%, P=.001) and 1-year mortality (14.4% vs 17.6%, P=.001). After adjusting for baseline cardiac risk factors and admission and hospital characteristics, primary PTCA was associated with improved 30-day (hazard ratio [HR] of death, 0.74; 95% confidence interval [CI], 0.63-0.88) and 1-year (HR, 0.88; 95% CI, 0.73-0.94) survival. The benefits of primary coronary angioplasty persisted when stratified by hospitals' AMI volume and the presence of on-site angiography. In patients classified as ideal for reperfusion therapy, the mortality benefit of primary PTCA was not significant at 1-year follow-up (HR, 0.92; 95% CI, 0.78-1.08). Conclusion In elderly patients who present with AMI, primary PTCA is associated with modestly lower short- and long-term mortality rates, In the subgroup of patients who were classified as ideal for reperfusion therapy, the observed benefit of primary PTCA was no longer significant. C1 Georgetown Univ, Med Ctr, Clin Econ Res Unit, Washington, DC 20007 USA. Georgetown Univ, Sch Med, Inst Cardiovasc Sci, Div Cardiol, Washington, DC 20007 USA. Delmarva Fdn Med Care Inc, Easton, MD USA. Univ Washington, NW Hlth Serv Res & Dev Field Program, Vet Affairs Puget Sound Healthcare Syst, Seattle, WA 98195 USA. Univ Washington, Div Cardiol, Seattle, WA 98195 USA. Univ Washington, Cardiovasc Outcomes Res Ctr, Seattle, WA 98195 USA. RP Schulman, KA (reprint author), Georgetown Univ, Med Ctr, Clin Econ Res Unit, 2233 Wisconsin Ave NW,Suite 440, Washington, DC 20007 USA. NR 23 TC 119 Z9 126 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 28 PY 1999 VL 282 IS 4 BP 341 EP 348 DI 10.1001/jama.282.4.341 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 219FG UT WOS:000081596800029 PM 10432031 ER PT J AU VanderLugt, JT Mattioni, T Denker, S Torchiana, D Ahern, T Wakefield, LK Perry, KT Kowey, PR AF VanderLugt, JT Mattioni, T Denker, S Torchiana, D Ahern, T Wakefield, LK Perry, KT Kowey, PR CA Ibutilide Investigators TI Efficacy and safety of ibutilide fumarate for the conversion of atrial arrhythmias after cardiac surgery SO CIRCULATION LA English DT Article; Proceedings Paper CT North American-Society-of-Pacing-and-Electrophysiology CY MAY 07-10, 1997 CL NEW ORLEANS, LOUISIANA SP Amer Soc Pac & Electrophysiol DE fibrillation; atrial flutter; surgery; ibutilide; antiarrhythmia agents ID ARTERY BYPASS-SURGERY; OPEN-HEART-SURGERY; SUPRAVENTRICULAR ARRHYTHMIAS; CARDIOPULMONARY BYPASS; GRAFT-SURGERY; FIBRILLATION; FLUTTER; DIGOXIN; METAANALYSIS; DISOPYRAMIDE AB Background-Atrial arrhythmias occur commonly after cardiac surgery and are a cause of significant morbidity and increased hospital costs, yet there is no well-studied treatment strategy to deal with them expeditiously. The purpose of this study was to determine the efficacy and safety of ibutilide fumarate, an approved drug for the rapid conversion of atrial fibrillation and flutter, in patients after cardiac surgery. Methods and Results-Patients with atrial fibrillation or flutter occurring 1 to 7 days after surgery and lasting 1 hour to 3 days were randomized to receive two 10-minute blinded infusions of placebo or 0.25, 0.5, or 1.0 mg of ibutilide fumarate, Treatment was considered successful if sinus rhythm was restored for any period of time by hour 1.5. A total of 302 patients were randomized, 201 with fibrillation and 101 with flutter, Treatment with ibutilide resulted in significantly higher conversion rates than placebo, and efficacy was dose related (placebo 15%; ibutilide 0.25 mg 40%, 0.5 mg 47%, and 1.0 mg 57%), Conversion rates at all doses were higher for atrial flutter than for atrial fibrillation, Mean time to conversion decreased as the dose was increased. Polymorphic ventricular tachycardia was the most serious adverse effect and occurred in 1.8% of the ibutilide-treated patients compared with 1.2% of patients who received placebo. Conclusions-Ibutilide is a useful and safe treatment alternative for the atrial arrhythmias that occur after cardiac surgery. C1 Lankenau Hosp & Med Res Ctr, Wynnewood, PA 19096 USA. Pharmacia & Upjohn Inc, Kalamazoo, MI 49001 USA. Healthwest Reg Med Ctr, Arizona Heart Inst, Phoenix, AZ USA. St Lukes Med Ctr, Milwaukee, WI 53215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Humana Hosp Sunrise Desert Springs, Las Vegas, NV USA. RP Kowey, PR (reprint author), Lankenau Hosp & Med Res Ctr, 100 Lancaster Ave,Suite 558,Med Off Bldg E, Wynnewood, PA 19096 USA. NR 34 TC 86 Z9 88 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 27 PY 1999 VL 100 IS 4 BP 369 EP 375 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 220UV UT WOS:000081686600010 PM 10421596 ER PT J AU Zeng, XM Kahana, JA Silver, PA Morphew, MK McIntosh, JR Fitch, IT Carbon, J Saunders, WS AF Zeng, XM Kahana, JA Silver, PA Morphew, MK McIntosh, JR Fitch, IT Carbon, J Saunders, WS TI Slk19p is a centromere protein that functions to stabilize mitotic spindles SO JOURNAL OF CELL BIOLOGY LA English DT Article DE spindle; Saccharomyces cerevisiae; kinetochore; motor; yeast ID KINESIN-RELATED PROTEINS; SACCHAROMYCES-CEREVISIAE; BUDDING YEAST; MICROTUBULES; CELLS; KINETOCHORE; ANAPHASE; MOTOR; METAPHASE; POLYMERIZATION AB We have identified a novel centromere-associated gene product from Saccharomyces cerevisiae that plays a role in spindle assembly and stability. Strains with a deletion of SLK19 (synthetic lethal Kar3p gene) exhibit abnormally short mitotic spindles, increased numbers of astral microtubules, and require the presence of the kinesin motor Kar3p for viability. When cells are deprived of both Slk19p and Kar3p, rapid spindle breakdown and mitotic arrest is observed. A functional fusion of Slk19p to green fluorescent protein (GFP) localizes to kinetochores and, during anaphase, to the spindle midzone, whereas Kar3p-GFP was found at the nuclear side of the spindle pole body. Thus, these proteins seem to play overlapping roles in stabilizing spindle structure while acting from opposite ends of the microtubules. C1 Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Colorado, Dept Mol Cell & Dev Biol, Boulder, CO 80309 USA. Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA. RP Univ Pittsburgh, Dept Biol Sci, 258 Cranford Hall, Pittsburgh, PA 15260 USA. EM wsaund+@pitt.edu FU NCRR NIH HHS [P41 RR000592, RR0592] NR 49 TC 109 Z9 111 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 JUL 26 PY 1999 VL 146 IS 2 BP 415 EP 425 DI 10.1083/jcb.146.2.415 PG 11 WC Cell Biology SC Cell Biology GA 221KF UT WOS:000081725700013 PM 10427094 ER PT J AU Soriano, SG Wang, YMF Wagner, DD Frenette, PS AF Soriano, SG Wang, YMF Wagner, DD Frenette, PS TI P- and E-selectin-deficient mice are susceptible to cerebral ischemia-reperfusion injury SO BRAIN RESEARCH LA English DT Article DE selectin; cerebral ischemia ID ADHESION MOLECULES; ARTERY OCCLUSION; INFARCT VOLUME; RATS; RECRUITMENT AB We examined brain sections from P- and E-selectin-deficient mice (-/-)and their nontransgenic littermates (+/+) after focal cerebral ischemia and reperfusion (I/R) tissue injury. There was no difference in the subsequent infarct volume after 3 h of ischemia and 21 h of reperfusion. These data indicate that selectin-independent mechanisms mediate tissue injury after a prolonged period of transient focal ischemia. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Childrens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Soriano, SG (reprint author), Childrens Hosp, Dept Anesthesia, 300 Longwood Ave, Boston, MA 02115 USA. RI Frenette, Paul/J-8272-2012 NR 25 TC 18 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 24 PY 1999 VL 835 IS 2 BP 360 EP 364 DI 10.1016/S0006-8993(99)01637-6 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 221MG UT WOS:000081730400033 PM 10415396 ER PT J AU Lev, MH Rhea, JT Bramson, RT AF Lev, MH Rhea, JT Bramson, RT TI Avoidance of variability and error in radiology SO LANCET LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Lev, MH (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 8 TC 18 Z9 18 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUL 24 PY 1999 VL 354 IS 9175 BP 272 EP 272 DI 10.1016/S0140-6736(99)00145-2 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 220CB UT WOS:000081646000007 PM 10440301 ER PT J AU Kume, K Zylka, MJ Sriram, S Shearman, LP Weaver, DR Jin, XW Maywood, ES Hastings, MH Reppert, SM AF Kume, K Zylka, MJ Sriram, S Shearman, LP Weaver, DR Jin, XW Maywood, ES Hastings, MH Reppert, SM TI mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop SO CELL LA English DT Article ID DROSOPHILA PERIOD GENE; SUPRACHIASMATIC NUCLEUS; MESSENGER-RNA; LIGHT; PROTEIN; MOUSE; EXPRESSION; TRANSCRIPTION; CRYPTOCHROME; TIMELESS AB We determined that two mouse cryptochrome genes, mCry1 and mCry2, act in the negative limb of the clock feedback loop. In cell lines, mPER proteins (alone or in combination) have modest effects on their cellular location and ability to inhibit CLOCK:BMAL1-mediated transcription. This suggested cryptochrome involvement in the negative limb of the feedback loop. Indeed, mCry1 and mCry2 RNA levels are reduced in the central and peripheral clocks of Clock/Clock mutant mice. mCRY1 and mCRY2 are nuclear proteins that interact with each of the mPER proteins, translocate each mPER protein from cytoplasm to nucleus, and are rhythmically expressed in the suprachiasmatic circadian clock. Luciferase reporter gene assays show that mCRY1 or mCRY2 alone abrogates CLOCK:BMAL1-E box-mediated transcription. The mPER and mCRY proteins appear to inhibit the transcriptional complex differentially. C1 Massachusetts Gen Hosp, Lab Dev Chronobiol, Serv Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Univ Cambridge, Dept Anat, Cambridge CB2 3DY, England. RP Kume, K (reprint author), Massachusetts Gen Hosp, Lab Dev Chronobiol, Serv Pediat, Boston, MA 02114 USA. OI Weaver, David/0000-0001-7941-6719 FU NICHD NIH HHS [R37 HD14427]; NIMH NIH HHS [MH11547, MH12067] NR 44 TC 917 Z9 942 U1 8 U2 52 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUL 23 PY 1999 VL 98 IS 2 BP 193 EP 205 DI 10.1016/S0092-8674(00)81014-4 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 219XA UT WOS:000081632300009 PM 10428031 ER PT J AU Gu, JJ Dong, RP Zhang, CH McLaughlin, DF Wu, MX Schlossman, SF AF Gu, JJ Dong, RP Zhang, CH McLaughlin, DF Wu, MX Schlossman, SF TI Functional interaction of DFF35 and DFF45 with caspase-activated DNA fragmentation nuclease DFF40 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-DEATH; APOPTOSIS; INHIBITOR; ONCOSIS; DEGRADATION; NECROSIS AB DNA fragmentation factor (DFF) functions downstream of caspase-3 and directly triggers DNA fragmentation during apoptosis, Here we described the identification and characterization of DFF35, an isoform of DFF45 comprised of 268 amino acids. Functional assays have shown that only DFF45, not DFF35, can assist in the synthesis of highly active DFF40, Using the deletion mutants, we mapped the function domains of DFF35/45 and demonstrated that the intact structure/conformation of DFF45 is essential for it to function as a chaperone and assist in the synthesis of active DFF40, Whereas the amino acid residues 101-180 of DFF35/45 mediate its binding to DFF40, the amino acid residues 23-100, which is homologous between DFF35/45 and DFF40, may function to inhibit the activity of DFF40. In contrast to DFF45, DFF35 cannot work as a chaperone, but it can bind to DFF40 more strongly than DFF45 and can inhibit its nuclease activity. These findings suggest that DFF35 may function in vivo as an important alternative mechanism to inhibit the activity of DFF40 and further, that the inhibitory effects of both DFF35 and DFF45 on DFF40 can put the death machinery under strict control. C1 Dana Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Schlossman, SF (reprint author), Dana Farber Canc Inst, Div Tumor Immunol, 44 Binney St, Boston, MA 02115 USA. NR 20 TC 67 Z9 71 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 23 PY 1999 VL 274 IS 30 BP 20759 EP 20762 DI 10.1074/jbc.274.30.20759 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 219NJ UT WOS:000081613100005 PM 10409614 ER PT J AU Higaki, Y Wojtaszewski, JFP Hirshman, MF Withers, DJ Towery, H White, MF Goodyear, LJ AF Higaki, Y Wojtaszewski, JFP Hirshman, MF Withers, DJ Towery, H White, MF Goodyear, LJ TI Insulin receptor substrate-2 is not necessary for insulin- and exercise-stimulated glucose transport in skeletal muscle SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; PHOSPHOTYROSINE PROTEIN; INDUCED TRANSLOCATION; CONTRACTION; MICE; WORTMANNIN; RESISTANCE; NIDDM; GLUT4; PHOSPHORYLATION AB Insulin receptor substrate-2-deficient (IRS2(-/-)) mice develop type 2 diabetes. The purpose of this study was to determine whether there is a defect in basal, insulin-, and exercise-stimulated glucose transport in the skeletal muscle of these animals. IRS2(-/-) and wild-type (WT) mice (male, 8-10 weeks) exercised on a treadmill for 1 h or remained sedentary. 2-Deoxyglucose (2DG) uptake was measured in isolated soleus muscles incubated in vitro in the presence or absence of insulin. Resting blood glucose concentration in IRS2(-/-) mice (10.3 mM) was higher than WT animals (4.1 mM), but there was a wide range among the IRS2(-/-) mice (3-25 mM), Therefore, IRS2(-/-) mice were divided into two subgroups based on blood glucose concentrations (IRS2(-/-)L < 7.2 mM, IRS2(-/-)H > 7.2 mM), Only IRS2(-/-)H had lower basal, exercise-, and submaximally insulin-stimulated 2DG uptake, while maximal insulin-stimulated 2DG uptake was similar among the three groups. The ED50 for insulin to stimulate 2DG uptake above basal in IRS2(-/-)H was higher than WT and IRS2(-/-)L mice, suggesting insulin resistance in the skeletal muscle from the IRS2(-/-) mice with high blood glucose concentrations. Furthermore, resting blood glucose concentrations from all groups were negatively correlated to submaximally insulin-stimulated 2DG uptake (r(2) = 0.33, p < 0.01). Muscle GLUT4 content was significantly lower in IRS2(-/-)H mice compared with WT and IRS2(-/-)L mice. These results demonstrate that the IRS2 protein in muscle is not necessary for insulin- or exercise-stimulated glucose transport, suggesting that the onset of diabetes in the IRS2(-/-) mice is not due to a defect in skeletal muscle glucose transport; hyperglycemia may cause insulin resistance in the muscle of IRS2(-/-) mice. C1 Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Howard Hughes Med Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Goodyear, LJ (reprint author), Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. RI Withers, Dominic/D-7671-2014; Wojtaszewski, Jorgen /P-6583-2014 OI Withers, Dominic/0000-0002-8009-7521; Wojtaszewski, Jorgen /0000-0001-9785-6830 FU NIAMS NIH HHS [AR-45670, AR-42238]; NIDDK NIH HHS [DK-43808] NR 31 TC 76 Z9 76 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 23 PY 1999 VL 274 IS 30 BP 20791 EP 20795 DI 10.1074/jbc.274.30.20791 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 219NJ UT WOS:000081613100009 PM 10409618 ER PT J AU Raychowdhury, R Zhang, ZS Hocker, M Wang, TC AF Raychowdhury, R Zhang, ZS Hocker, M Wang, TC TI Activation of human histidine decarboxylase gene promoter activity by gastrin is mediated by two distinct nuclear factors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHORBOL 12-MYRISTATE 13-ACETATE; MESSENGER-RNA; CANCER CELLS; EXPRESSION; PROTEIN; RAT; PROLIFERATION; RECEPTORS; STOMACH; ELEMENT AB The human histidine decarboxylase gene is regulated by gastrin through a cis-acting element known as the gastrin response element (GAS-RE) that was initially localized to a site (+2 to +24) downstream of the transcriptional start site. Electrophoretic mobility shift assays using sequentially deleted DNA probes and nuclear extracts from AGS-B gastric cancer cells showed that the GAS-RE is actually composed of two overlapping binding sites (GAS-RE1, +1 +10; and GAS-REB, +11 to +27) that bind distinct nuclear factors. Reporter gene assays demonstrated that each element alone could confer gastrin responsiveness, but the presence of both elements was required for complete gastrin response. Stimulation of AGS-B cells with gastrin for 10-20 min resulted in a >2-fold increase in factor binding. The binding was inhibited by pretreatment of AGS-B cells with cycloheximide and the MEK1 inhibitor PD98059, indicating a requirement for protein synthesis and also indicating that activation occurs through the MEK/mitogen-activated protein kinase pathway. UV cross-linking and Southwestern blot analysis showed that GAS-RE1 bound a 52-kDa protein, whereas GAS-RE2 bound a 35-kDa protein. Hence, activation of histidine decarboxylase gene promoter activity by gastrin is most likely mediated by two separate nuclear factors. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Humboldt Univ, Univ Klinikum Charite, Campus Virchow Klinikum, Med Klin Schwerpunkt Hepatol & Gastroenterol, D-13353 Berlin, Germany. RP Wang, TC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 724,32 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK48077] NR 21 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 23 PY 1999 VL 274 IS 30 BP 20961 EP 20969 DI 10.1074/jbc.274.30.20961 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 219NJ UT WOS:000081613100034 PM 10409643 ER PT J AU Steveson, TC Keutmann, HT Mains, RE Eipper, BA AF Steveson, TC Keutmann, HT Mains, RE Eipper, BA TI Phosphorylation of cytosolic domain Ser(937) affects both biosynthetic and endocytic trafficking of peptidylglycine alpha-amidating monooxygenase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MANNOSE 6-PHOSPHATE RECEPTOR; TRANS-GOLGI NETWORK; CASEIN KINASE-II; PEPTIDE-PROCESSING ENZYME; GRANULE-ASSOCIATED PROTEINS; CYTOPLASMIC DOMAIN; SECRETORY GRANULES; INTRACELLULAR TRAFFICKING; ROUTING DETERMINANTS; NEUROENDOCRINE CELLS AB Peptidylglycine alpha-amidating monooxygenase (PARI), a bifunctional enzyme, catalyzes the COOH-terminal amidation of bioactive peptides. In test tube assays, PAM is phosphorylated by protein kinase C at Ser(937). The roles of phosphorylation and dephosphorylation of Ser(937) in the biosynthetic and endocytic trafficking of integral membrane PAM were examined using an antiserum specific for the phosphorylation of Ser(937) and using AtT-20 cells expressing membrane PAM in which Ser(937) was mutated to Ala or Asp. Although phosphorylation at Ser(937) can occur while PAM is in the endoplasmic reticulum,, early steps in the biosynthetic trafficking of membrane PAM were not affected by Ser(937) phosphorylation. The inability to phosphorylate PAM/S937A increased its intracellular degradation and decreased secretion of the soluble monooxygenase portion of PAM. In contrast, the biosynthetic trafficking of PAM/S937A was indistinguishable from wild-type PAM. Despite the fact that Ser(937) is adjacent to the only Tyr-based internalization motif in PARZ internalization and trafficking through early endosomes were unaffected by phosphorylation, However, PAM antibody internalized by wild-type PAM acquired a perinuclear localization, while antibody internalized by PAM/S937A was routed to lysosomes, and antibody bound to PAM/S937D maintained a dispersed, punctate pattern. In cells stimulated with phorbol ester, phosphorylation of Ser(937) increased and phosphorylated PAM accumulated in large vesicular structures. Therefore, phosphorylation of PAM-1 at Ser(937) directs newly synthesized and internalized protein away from lysosomes, while dephosphorylation is needed for a different step in the late endocytic pathway. C1 Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Eipper, BA (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurosci, WSB 907,725 N Wolfe St, Baltimore, MD 21205 USA. FU NIDDK NIH HHS [DK-32949, DK-09520] NR 62 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 23 PY 1999 VL 274 IS 30 BP 21128 EP 21138 DI 10.1074/jbc.274.30.21128 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 219NJ UT WOS:000081613100057 PM 10409666 ER PT J AU Raab, M Kang, H da Silva, A Zhu, XC Rudd, CE AF Raab, M Kang, H da Silva, A Zhu, XC Rudd, CE TI FYN-T-FYB-SLP-76 interactions define a T-cell receptor zeta/CD3-mediated tyrosine phosphorylation pathway that up-regulates interleukin 2 transcription in T-cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADAPTER PROTEIN SLP-76; C-CBL PROTOONCOGENE; ANTIGEN-RECEPTOR; SIGNAL-TRANSDUCTION; MOLECULAR-CLONING; MICE LACKING; INTRACELLULAR-LOCALIZATION; GENETIC-EVIDENCE; ZAP-70 KINASE; ZETA-CHAIN AB Protein-tyrosine kinases p56(Lck), SYK, and ZAP-70 and downstream adaptors LAT and SLP-76 have been implicated as essential components in T-cell activation. Another lymphoid-specific adaptor FYB/SLAP has also been identified as a predominant binding partner of SLP-76 and the Src kinase FYN-T, although its role in the activation process has been unclear. Inthis study, we demonstrate that FYN-T selectively phosphorylates FYB providing a template for the recruitment of FYN-T and SLP-76 SH2 domain binding. This interaction is unusual in its distinct cytoplasmic localization and its long term stable kinetics of phosphorylation. Furthermore, we demonstrate for the first time that the co-expression of all three components of the FYN-T-FYB-SLP-76 matrix can synergistically up-regulate T-cell receptor-driven interleukin 2 transcription activity. These findings document the existence of a T-cell receptor-regulated FYN-T-FYB pathway that interfaces with the adaptor SLP-76 and cap-regulates lymphokine production in T-cells. C1 Harvard Med Sch, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Div Tumor Immunol, Boston, MA 02115 USA. Harvard Med Sch, Dept Med, Boston, MA 02115 USA. Harvard Med Sch, Dept Pathol, Boston, MA 02115 USA. RP Rudd, CE (reprint author), Harvard Med Sch, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Div Tumor Immunol, Boston, MA 02115 USA. NR 60 TC 82 Z9 84 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 23 PY 1999 VL 274 IS 30 BP 21170 EP 21179 DI 10.1074/jbc.274.30.21170 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 219NJ UT WOS:000081613100062 PM 10409671 ER PT J AU Christmas, P Ursino, SR Fox, JW Soberman, RJ AF Christmas, P Ursino, SR Fox, JW Soberman, RJ TI Expression of the CYP4F3 gene - Tissue-specific splicing and alternative promoters generate high and low K-m forms of leukotriene B-4 omega-hydroxylase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; TRACT BINDING-PROTEIN; FUNCTIONAL-CHARACTERIZATION; MESSENGER-RNA; CDNA CLONING; EXON; IDENTIFICATION; 20-HYDROXYLASE; INFLAMMATION; LIVER AB Cytochrome P450 4F3 (CYP4F3) catalyzes the inactivation of leukotriene Bq by omega-oxidation in human neutrophils, To understand the regulation of CYP4F3 expression, we analyzed the CYP4F3 gene and cloned a novel isoform (CYP4F3B) that is expressed in fetal and adult liver, but not in neutrophils, The CYP4F3 gene contains 14 exons and 13 introns, The cDNAs for CYP4F3A (the neutrophil isoform) and CYP4F3B have identical coding regions, except that they contain exons 4 and 3, respectively. Both exons code for amino acids 66-114 but share only 27% identity. When expressed in COS-7 cells, the K-m of CYP4F3B was determined to be 26-fold higher than the K-m of CYP4F3A using leukotriene B-4 as a substrate. 5'-Rapid amplification of cDNA end studies reveal that the CYP4F3A and CYP4F3B transcripts have 5'-termini derived from different parts of the gene and are initiated from distinct transcription start sites located 519 and 71 base pairs (bp), respectively, from the ATG initiation codon, A consensus TATA box is located 27 bp upstream of the CYP4F3B transcription start site, and a TATA box-like sequence is located 23 bp upstream of the CYP4F3A transcription start site. The data indicate that the tissue-specific expression of functionally distinct CYP4F3 isoforms is regulated by alternative promoter usage and mutually exclusive exon splicing. C1 Massachusetts Gen Hosp, Dept Med, Arthrit Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Soberman, RJ (reprint author), Massachusetts Gen Hosp E, Dept Med, Arthritis Unit, 149 Navy Yard,13th St, Charlestown, MA 02129 USA. FU NIEHS NIH HHS [ES50859] NR 39 TC 54 Z9 59 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 23 PY 1999 VL 274 IS 30 BP 21191 EP 21199 DI 10.1074/jbc.274.30.21191 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 219NJ UT WOS:000081613100065 PM 10409674 ER PT J AU Lai, F Kammann, E Rebeck, GW Anderson, A Chen, Y Nixon, RA AF Lai, F Kammann, E Rebeck, GW Anderson, A Chen, Y Nixon, RA TI APOE genotype and gender effects on Alzheimer disease in 100 adults with Down syndrome SO NEUROLOGY LA English DT Article ID APOLIPOPROTEIN-E GENOTYPES; MISSENSE MUTATIONS; REDUCED SURVIVAL; TYPE-4 ALLELE; DEMENTIA; ONSET; GENE; HOMOZYGOTES; EPSILON-2 AB Background: Alzheimer disease (AD) neuropathology is present in Down syndrome (DS) after age 35, but dementia onset varies from ages 40 to 70 years. Because of small sample sizes and nonuniform determination of dementia, previous studies produced differing results on the influence of APOE subtypes on AD in DS. Objective: To determine the influence of the APOE genotype and gender on development of AD in adults with DS to ascertain similarities with AD in the general population. Methods: A total of 100 adults with DS (ages 35 to 79 years), almost all of whom were longitudinally assessed by neurologists, underwent APOE genotyping. Dementia onset was determined using criteria applied from the Tenth International Classification of Mental and Behavioral Disorders. This cohort contains the largest number of DS subjects with dementia (n = 57) in a single study, thus increasing reliability of the results. Results, The epsilon 2 allele frequency was 4% in those with dementia versus 13% in those without dementia (p = 0.03); epsilon 4 allele frequency was 18% in those with dementia versus 13% in those without dementia (p = 0.45), Using APOE-epsilon 3/3 as the reference group, the risk ratio for the development of AD at any given time was 0.34 for the APOE-epsilon 2/3 group (p = 0.04) and 1.44 for the APOE-epsilon(3/4,4/4) group (p = 0.25). Women were 1.77 times as likely to dement as men at any given point in time (p = 0.04). Conclusions: The epsilon 2 allele confers a protective effect, and women with DS have an increased risk for AD, as in the general population. In this sample, epsilon 4 does not confer a significantly increased risk for AD in DS. C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. McLean Hosp, Labs Mol Neurosci, Belmont, MA USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Eunice Kennedy Shriver Ctr Mental Retardat Inc, Waltham, MA USA. RP Lai, F (reprint author), Massachusetts Gen Hosp, Neurol Serv, E002E,55 Fruit St, Boston, MA 02114 USA. FU NIA NIH HHS [AG10916] NR 37 TC 57 Z9 58 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL 22 PY 1999 VL 53 IS 2 BP 331 EP 336 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 219BE UT WOS:000081587300015 PM 10430422 ER PT J AU Vaccarino, V Parsons, L Every, NR Barron, HV Krumholz, HM AF Vaccarino, V Parsons, L Every, NR Barron, HV Krumholz, HM CA Natl Registry Myocardial Infarction 2 Participa TI Sex-based differences in early mortality after myocardial infarction SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; THROMBOLYTIC THERAPY; UNITED-STATES; CASE-FATALITY; SHORT-TERM; INTERVENTION REGISTRY; NATIONAL REGISTRY; DIABETES-MELLITUS; CLINICAL OUTCOMES; BYPASS-SURGERY AB Background There is conflicting information about whether short-term mortality after myocardial infarction is higher among women than among men after adjustment for age and other prognostic factors. We hypothesized that younger, but not older, women have higher mortality rates during hospitalization than their male peers. Methods We analyzed data on 384,878 patients (155,565 women and 229,313 men) who were 30 to 89 years of age and who had been enrolled in the National Registry of Myocardial Infarction 2 between June 1994 and January 1998. Patients who had been transferred from or to other hospitals were excluded. Results The overall mortality rate during hospitalization was 16.7 percent among the women and 11.5 percent among the men. Sex-based differences in the rates varied according to age. Among patients less than 50 years of age, the mortality rate for the women was more than twice that for the men. The difference in the rates decreased with increasing age and was no longer significant after the age of 74 (P < 0.001 for the interaction between sex and age). Logistic-regression analysis showed that the odds of death were 11.1 percent greater for women than for men with every five-year decrease in age (95 percent confidence interval, 10.1 to 12.1 percent). Differences in medical history, the clinical severity of the infarction, and early management accounted for only about one third of the difference in the risk. After adjustment for these factors, women still had a higher risk of death for every five years of decreasing age (increase in the odds of death, 7.0 percent; 95 percent confidence interval, 5.9 to 8.1 percent). Conclusions After myocardial infarction, younger women, but not older women, have higher rates of death during hospitalization than men of the same age. The younger the age of the patients, the higher the risk of death among women relative to men. Younger women with myocardial infarction represent a high-risk group deserving of special study. (N Engl J Med 1999;341:217-25.) (C) 1999, Massachusetts Medical Society. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Med Cardiol, New Haven, CT 06520 USA. Univ Washington, Sch Med, Vet Affairs Puget Sound Healthcare Syst, Hlth Serv Res & Dev Field Program, Seattle, WA USA. Univ Washington, Sch Med, Div Cardiol, Cardiovasc Outcomes Res Ctr, Seattle, WA USA. Univ Calif San Francisco, Div Cardiol, San Francisco, CA 94143 USA. Genentech Inc, Div Med Affairs, San Francisco, CA 94080 USA. Yale New Haven Hosp, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. RP Vaccarino, V (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, 60 Coll St,POB 208034, New Haven, CT 06520 USA. NR 63 TC 694 Z9 722 U1 1 U2 8 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 JUL 22 PY 1999 VL 341 IS 4 BP 217 EP 225 DI 10.1056/NEJM199907223410401 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 217ZL UT WOS:000081528800001 PM 10413733 ER PT J AU Syngal, S Fox, EA Li, C Dovidio, M Eng, C Kolodner, RD Garber, JE AF Syngal, S Fox, EA Li, C Dovidio, M Eng, C Kolodner, RD Garber, JE TI Interpretation of genetic test results for hereditary nonpolyposis colorectal cancer - Implications for clinical predisposition testing SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MISMATCH REPAIR GENES; COLON-CANCER; MICROSATELLITE INSTABILITY; MLH1 MUTATIONS; HMSH2 MUTATIONS; HNPCC FAMILIES; HMLH1 GENES; HOMOLOG; MSH2; CARCINOMA AB Context Genetic testing for cancer predisposition is evolving from purely research applications to affecting clinical management. Objective To determine how often genetic lest results for hereditary nonpolyposis colorectal cancer (HNPCC) can be definitively interpreted and used to guide clinical management. Design Case-series study conducted in 1996 to 1998 in which a complete sequence analysis of hMSH2 and hMLH1 coding sequence and flanking intronic regions was performed. Mutations were categorized as protein truncating and missense. In the case of missense alterations, additional analyses were performed in an effort to assess pathogenicity. Setting and Participants Families were identified by self-referral or health care provider referral to a cancer genetics program. Participants and kindreds were classified into 1 of 4 categories: (1) Amsterdam criteria for HNPCC, (2) modified Amsterdam criteria for HNPCC, (3) young age at onset, or (4) HNPCC-variant. In addition, each proband was classified according to the Bethesda guidelines for identification of individuals with HNPCC. Main Outcome Measure Alterations of hMSH2 and hMLH1 genes. Results Twenty-seven alterations of hMSH2 and hMLH1 were found in 24 of 70 families (34.3 %), Of these, deleterious mutations that could be used with confidence in clinical management were identified in 25.7% (18/70) of families. The rates of definitive results for families fulfilling Amsterdam criteria, modified Amsterdam criteria, young age at onset, HNPCC-variant, and Bethesda guidelines were 27 (39.3%), 13 (18.2%), 12 (16.7%), 11 (15.8%), and 21 (30.4%), respectively. The prevalence of missense mutations, genetic heterogeneity of the syndrome, and limited availability of validated functional assays present a challenge in the interpretation of genetic test results of HNPCC families. Conclusions The identification of pathogenic mutations in a significant subset of families for whom the results may have marked clinical importance makes genetic testing an important option for HNPCC and HNPCC-like kindreds. However, for the majority of individuals in whom sequence analysis of hMSH2 and hMLH1 does not give a definitive result, intensive follow-up is still warranted. C1 Dana Farber Canc Inst, Dept Populat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Dana Farber Canc Inst, Charles A Dana Human Canc Genet Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Ludwig Inst Canc Res, La Jolla, CA USA. RP Garber, JE (reprint author), Dana Farber Canc Inst, Dept Populat Sci, 44 Binney St,Smith 208, Boston, MA 02115 USA. OI Eng, Charis/0000-0002-3693-5145 NR 53 TC 92 Z9 97 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 21 PY 1999 VL 282 IS 3 BP 247 EP 253 DI 10.1001/jama.282.3.247 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 217MW UT WOS:000081504400030 PM 10422993 ER PT J AU Leape, LL Cullen, DJ Clapp, MD Burdick, E Demonaco, HJ Erickson, JI Bates, DW AF Leape, LL Cullen, DJ Clapp, MD Burdick, E Demonaco, HJ Erickson, JI Bates, DW TI Pharmacist participation on physician rounds and adverse drug events in the intensive care unit SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HOSPITALIZED-PATIENTS; PREVENTION; COSTS AB Context Pharmacist review of medication orders in the intensive care unit (ICU) has been shown to prevent errors, and pharmacist consultation has reduced drug costs. However, whether pharmacist participation in the ICU at the time of drug prescribing reduces adverse events has not been studied. Objective To measure the effect bf pharmacist participation on medical rounds in the ICU on the rate of preventable adverse drug events (ADEs) caused by ordering errors. Design Before-after comparison between phase 1 (baseline) and phase 2 (after intervention implemented) and phase 2 comparison with a control unit that did not receive the intervention. Setting A medical ICU (study unit) and a coronary care unit (control unit) in a large urban teaching hospital. Patients Seventy-five patients randomly selected from each of 3 groups: all admissions to the study unit from February 1, 1993, through July 31, 1993 (baseline) and all admissions to the study unit (postintervention) and control unit from October 1, 1994, through July 7, 1995. In addition, 50 patients were selected at random from the control unit during the baseline period. Intervention A senior pharmacist made rounds with the ICU team and remained in the ICU for consultation in the morning, and was available on call throughout the day. Main Outcome Measures Preventable ADEs due to ordering (prescribing) errors and the number, type, and acceptance of interventions made by the pharmacist. Preventable ADEs were identified by review of medical records of the randomly selected patients during both preintervention and postintervention phases. Pharmacists recorded all recommendations, which were then analyzed by type and acceptance. Results The rate of preventable ordering ADEs decreased by 66% from 10.4 per 1000 patient-days (95% confidence interval [CI], 7-14) before the intervention to 3.5 (95% CI, 1-5, P<.001) after the Intervention. In the control unit, the rate was essentially unchanged during the same time periods: 10.9 (95% CI, 6-16) and 12.4 (95% CI, 8-17) per 1000 patient-days. The pharmacist made 366 recommendations related to drug ordering, of which 362 (99%) were accepted by physicians. Conclusions The presence of a. pharmacist on rounds as a full member of the patient care team in a medical ICU was associated with a substantially lower rate of ADEs caused by prescribing errors. Nearly all the changes were readily accepted by physicians. C1 Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Nursing, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. RP Leape, LL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. NR 13 TC 673 Z9 705 U1 1 U2 29 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 21 PY 1999 VL 282 IS 3 BP 267 EP 270 DI 10.1001/jama.282.3.267 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 217MW UT WOS:000081504400033 PM 10422996 ER PT J AU Ripple, MO Henry, WF Schwarze, SR Wilding, G Weindruch, R AF Ripple, MO Henry, WF Schwarze, SR Wilding, G Weindruch, R TI Effect of antioxidants on androgen-induced AP-1 and NF-kappa B DNA-binding activity in prostate carcinoma cells SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PROTEIN-PROTEIN-INTERACTION; REDOX REGULATION; GLUCOCORTICOID RECEPTOR; TRANSCRIPTION FACTOR; OXIDATION-REDUCTION; C-JUN; CANCER; FOS; ACTIVATION; TESTOSTERONE AB Background: Previous studies have suggested that male hormones (androgens) and certain forms of oxygen (reactive oxygen species) are linked to the development of prostate cancer. We hypothesized that androgens contribute to prostate carcinogenesis by increasing oxidative stress. We further hypothesized that antioxidants reduce prostate cancer risk by modulating androgen effects on cellular processes. Methods: To test these hypotheses, we looked for 1) a change in the level of reactive oxygen species in the presence of androgens, 2) androgen-induced binding activity of transcriptional activators AP-1 and NF-kappa B, whose activities are known to be altered during cell proliferation, and 3) the effect of antioxidants on androgen-induced transcription factor binding. Results: Physiologic concentrations (1 nM) of 5 alpha-dihydrotestosterone or 1-10 nM R1881, a synthetic androgen, produced sustained elevation of AP-1 and NF-kappa B DNA-binding activity in LNCaP cells, an androgen-responsive human prostate carcinoma cell line. Androgen-independent DU145 cells (another human prostate carcinoma cell line) were unaffected by R1881 treatment, AP-1-binding activity increased 5 hours after 1 nM R1881 treatment; NF-kappa B DNA-binding activity increased after 36 hours, Both activities remained elevated for at least 120 hours. Nuclear AP-1 and NF-kappa B protein levels were not elevated. Antioxidant vitamins C plus E blocked both androgen-induced DNA-binding activity and production of reactive oxygen species. Conclusion: Physiologic concentrations of androgens induce production of reactive oxygen species and cause prolonged AP-1 and NF-kappa B DNA-binding activities, which are diminished by vitamins C and E. C1 Univ Wisconsin, Dept Med, Inst Aging, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. Univ Wisconsin, Dept Med, Ctr Comprehens Canc, Madison, WI USA. Univ Wisconsin, Inst Aging, Ctr Geriatr Res Educ & Clin, William S Middleton Mem Vet Hosp, Madison, WI USA. RP Wilding, G (reprint author), Univ Wisconsin, Dept Med, Inst Aging, K6-550 CSC,600 Highland Ave, Madison, WI 53792 USA. FU NIA NIH HHS [T32AG00213] NR 49 TC 78 Z9 79 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 21 PY 1999 VL 91 IS 14 BP 1227 EP 1232 DI 10.1093/jnci/91.14.1227 PG 6 WC Oncology SC Oncology GA 225FA UT WOS:000081946700013 PM 10413424 ER PT J AU Aghi, M Kramm, CM Breakefield, XO AF Aghi, M Kramm, CM Breakefield, XO TI Folylpolyglutamyl synthetase gene transfer and glioma antifolate sensitivity in culture and in vivo SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SIMPLEX VIRUS TYPE-1; HUMAN-LEUKEMIC CELLS; ANTITUMOR-ACTIVITY; DEAMINASE GENE; FOLATE ANALOGS; MESSENGER-RNA; BRAIN-TUMORS; L1210 CELL; METHOTREXATE; DRUG AB Background: Although antifolates are popular agents for use in chemotherapy, they display minimal toxicity against slow-growing tumors and are toxic to actively replicating cells in normal tissues. These drugs are converted intracellularly into polyglutamate derivatives by the enzyme folylpolyglutamyl synthetase (FPGS). Because tumors with high expression of FPGS often respond to nontoxic antifolate doses, we investigated whether augmenting tumoral FPGS activity by gene delivery would enhance tumoral antifolate sensitivity. Methods: 9L rat gliosarcoma cells were stably transfected with a human FPGS complementary DNA (cDNA), producing 9L/FPGS cells. The sensitivity of these cells to the antifolates methotrexate and edatrexate was measured in culture and in subcutaneous tumors, as was their ability to increase the chemosensitivity of nearby nontransfected cells, i.e., a bystander effect. The antifolate sensitivity of nonselected cells transduced with a hybrid amplicon vector that expressed FPGS was also ascertained. Results: In comparison with 9L cells, 9L/FPGS cells displayed enhanced sensitivity to 4-hour pulses of antifolate, Subcutaneous 9L/FPGS tumors responded as well to methotrexate given every third day as 9L tumors did to daily treatment. A modest bystander effect was observed with edatrexate treatment in culture and in vivo. The observed bystander effect appeared to result from the release of antifolates by transfected cells after the removal of extracellular drug. In culture, enhanced antifolate sensitivity was also seen in other stably transfected rodent and human glioma cell lines, including one with high preexisting FPGS activity, and in canine and human glioblastoma cell lines transduced with a vector bearing FPGS cDNA, Conclusions: FPGS gene delivery enhances the antifolate sensitivity of several glioma cell lines and merits further evaluation as a therapeutic strategy. C1 Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, East Bldg,Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [P30CA69246] NR 46 TC 23 Z9 23 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 21 PY 1999 VL 91 IS 14 BP 1233 EP 1241 DI 10.1093/jnci/91.14.1233 PG 9 WC Oncology SC Oncology GA 225FA UT WOS:000081946700014 PM 10413425 ER PT J AU Suh-Burgmann, EJ Goodman, A AF Suh-Burgmann, EJ Goodman, A TI Surveillance for endometrial cancer in women receiving tamoxifen SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID NONPOLYPOSIS COLORECTAL-CANCER; SURGICAL-ADJUVANT-BREAST; POSTMENOPAUSAL WOMEN; ULTRASONOGRAPHIC EVALUATION; VAGINAL EPITHELIUM; CERVICAL CYTOLOGY; TREATED PATIENTS; CARCINOMA; THERAPY; TRIAL AB Recent studies showing a protective effect of tamoxifen in women at high risk for breast cancer have expanded the indications of the drug. While acting as an estrogen antagonist in the breast, tamoxifen can have estrogenic effects on the endometrium; consensus opinion is that tamoxifen increases the risk for endometrial cancer. Because an increasing number of women are taking tamoxifen, a strategy for gynecologic surveillance is needed. Studies examining the relation between risk for endometrial cancer and tamoxifen use have conflicting results. However, because of an overall interpretation that tamoxifen use slightly increases risk for endometrial cancer, some researchers advocate routine ultrasonography and endometrial biopsy for screening asymptomatic women receiving tamoxifen. This paper reviews the literature on endometrial cancer in women taking tamoxifen and the usefulness of various screening methods in this setting. Risk factors and screening criteria for endometrial cancer in the general population are discussed, and a strategy for surveillance of women taking tamoxifen is proposed. Patients should be screened for signs or symptoms of endometrial abnormality before taking tamoxifen. This evaluation, which should include a careful history, pelvic examination, and Papanicolaou smear, should be repeated annually while the patient is receiving tamoxifen. Although transvaginal ultrasonography is not recommended for routine screening, it is indicated if an adequate pelvic examination cannot be performed or if additional risk factors are present. The likelihood of abnormality is greater for patients who have abnormal bleeding, discharge, abnormal glandular cells on Papanicolaou smear, or an endometrial measurement on ultrasonography of more than 8 mm; these findings should prompt an aggressive evaluation of the endometrium. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Goodman, A (reprint author), Massachusetts Gen Hosp, Wang ACC 2, Boston, MA 02114 USA. NR 87 TC 42 Z9 43 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 JUL 20 PY 1999 VL 131 IS 2 BP 127 EP 135 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 217QD UT WOS:000081509700008 PM 10419429 ER PT J AU Zhang, WT Canziani, G Plugariu, C Wyatt, R Sodroski, J Sweet, R Kwong, P Hendrickson, W Chaiken, L AF Zhang, WT Canziani, G Plugariu, C Wyatt, R Sodroski, J Sweet, R Kwong, P Hendrickson, W Chaiken, L TI Conformational changes of gp120 in epitopes near the CCR5 binding site are induced by CD4 and a CD4 miniprotein mimetic SO BIOCHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ENVELOPE GLYCOPROTEIN GP120; HUMAN MONOCLONAL-ANTIBODY; RECEPTOR-MEDIATED ACTIVATION; SOLUBLE CD4; HTLV-III; DISULFIDE BONDS; AIDS PATIENTS; HIV-1 ENTRY; NEUTRALIZATION AB Binding of the T-cell antigen CD4 to human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 has been reported to induce conformational rearrangements in the envelope complex that facilitate recognition of the CCR5 coreceptor and consequent viral entry into cells. To better understand the mechanism of virus docking and cell fusion, we developed a three-component gp120-CD4-17b optical biosensor assay to visualize the CD4-induced conformational change of gp120 as seen through envelope binding to a neutralizing human antibody, 17b, which binds to epitopes overlapping the CCR5 binding site. The 17b Fab fragment was immobilized on a dextran sensor surface, and kinetics of gp120 binding were evaluated by both global and linear transformation analyses. Adding soluble CD4 (sCD4) increased the association rate of full-length JR-FL gp120 by 25-fold. This change is consistent with greater exposure of the 17b binding epitope on gp120 when CD4 is bound and correlates with CD4-induced conformational changes in gp120 leading to higher affinity binding to coreceptor. A smaller enhancement of 17b binding by sCD4 was observed with a mutant of gp120, Delta JR-FL protein, which lacks V1 and V2 variable loops and N- and C-termini. Biosensor results for JR-FL and Delta JR-FL argue that CD4-induced conformational changes in the equilibrium state of gp120 lead both to movement of V1/V2 loops and to conformational rearrangement in the gp120 core structure and that both of these lead to greater exposure of the coreceptor-binding epitope in gp120. A 17b binding enhancement effect on JR-R, also was observed with a 32-amino acid charybdotoxin miniprotein construct that contains an epitope predicted to mimic the Phe 43/Arg 59 region of CD4 and that competes with CD4 for gp120 binding. Results with this construct argue that CD4-mimicking molecules with surrogate structural elements for the Phe 43/Arg 59 components of CD4 are sufficient to elicit a similar gp120 conformational isomerization as expressed by CD4 itself. C1 Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. SmithKline Beecham Pharmaceut, Dept Mol Immunol, King Of Prussia, PA 19406 USA. Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA. RP Chaiken, L (reprint author), Stellar Chance Labs 913, 422 Curie Blvd, Philadelphia, PA 19104 USA. FU NIAID NIH HHS [AI28691]; NIGMS NIH HHS [1PO1 GM 56550-01] NR 51 TC 84 Z9 85 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 20 PY 1999 VL 38 IS 29 BP 9405 EP 9416 DI 10.1021/bi990654o PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 219PQ UT WOS:000081616000025 PM 10413516 ER PT J AU Dhe-Paganon, S Ottinger, EA Nolte, RT Eck, MJ Shoelson, SE AF Dhe-Paganon, S Ottinger, EA Nolte, RT Eck, MJ Shoelson, SE TI Crystal structure of the pleckstrin homology-phosphotyrosine binding (PH-PTB) targeting region of insulin receptor substrate 1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE; GLUCOSE-UPTAKE; DOMAIN; PROTEIN; IRS-1; SPECIFICITY; RECOGNITION; ADIPOCYTES; ACTIVATION; MEMBRANE AB We have determined the crystal structure at 2.3-Angstrom resolution of an amino-terminal segment of human insulin receptor substrate 1 that encompasses its pleckstrin homolog (PH) and phosphotyrosine binding (PTB) domains. Both domains adopt the canonical selen-stranded beta-sandwich PR domain fold. The domains are closely associated, with a 720-Angstrom(2) contact surface buried between them that appears to he stabilized by ionic, hydrophobic, and hydrogen bonding interactions. The nonconserved 46-residue linker between the domains is disordered. The PTB domain peptide binding site is fully exposed on the molecular surface, as is a large cationic patch at the base of the PH domain that is a likely binding site for the head groups of phosphatidylinositol phosphates, Binding assays confirm that phosphatidylinositol phosphates bind the PH domain, but not the PTB domain. Ligand binding to the PH domain does not alter PTB domain interactions, and vice versa. The structural and accompanying functional data illustrate how the two binding domains might act cooperatively to effectively increase local insulin receptor substrate 1 concentration at the membrane and transiently fix the receptor and substrate, to allow multiple phosphorylation reactions to occur during each union. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Mol Med Lab, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. 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 Shoelson, SE (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02115 USA. FU NIDDK NIH HHS [F32 DK009517, DK43123, F32 DK009146, R01 DK051729, R01 DK043123, DK51729, R37 DK051729, DK09517] NR 37 TC 60 Z9 61 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 JUL 20 PY 1999 VL 96 IS 15 BP 8378 EP 8383 DI 10.1073/pnas.96.15.8378 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 219CB UT WOS:000081589400020 PM 10411883 ER PT J AU Rattner, DW AF Rattner, DW TI Inguinal herniorrhaphy: for surgical specialists only? SO LANCET LA English DT Editorial Material ID HERNIA REPAIR C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 7 TC 5 Z9 5 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUL 17 PY 1999 VL 354 IS 9174 BP 175 EP 176 DI 10.1016/S0140-6736(99)90103-4 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 217MU UT WOS:000081504200003 PM 10421293 ER PT J AU Tabor, DE Kim, JB Spiegelman, BN Edwards, PA AF Tabor, DE Kim, JB Spiegelman, BN Edwards, PA TI Identification of conserved cis-elements and transcription factors required for sterol-regulated transcription of stearoyl-CoA desaturase 1 and 2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FARNESYL DIPHOSPHATE SYNTHASE; POLYUNSATURATED FATTY-ACIDS; LIPOPROTEIN RECEPTOR GENE; BINDING PROTEIN; DIFFERENTIATION FACTOR-1; 3T3-L1 PREADIPOCYTES; NF-Y; EXPRESSION; PROMOTER; LIVER AB We previously identified stearoyl-CoA desaturase 2 (SCD2) as a new member of the family of genes that are transcriptionally regulated in response to changing levels of nuclear sterol regulatory element binding proteins (SREBPs) or adipocyte determination and differentiation factor 1 (ADD1). A novel sterol regulatory element (SRE) (5'-AGCAGATTGTG-3') identified in the proximal promoter of the mouse SCD2 gene is required for induction of SCD2 promoter-reporter genes in response to cellular sterol depletion (Tabor, D. E,, Kim, J. B., Spiegelman, B. M., and Edwards, P. A. (1998) J, Biol, Chem. 273, 22052-22058). In this report, we demonstrate that this novel SRE is both present in the promoter of the SCD1 gene and is critical for the sterol-dependent transcription of SCD1 promoter-reporter genes. Two conserved cis elements (5'-CCAAT-3') lie 5 and 48 base pairs 3' of the novel SREs in the promoters of both the SCD1 and SCDB murine genes. Mutation of either of these putative NF-Y binding sites attenuates the transcriptional activation of SCD1 or SCD2 promoter-reporter genes in response to cellular sterol deprivation, Induction of both reporter genes is also attenuated when cells are cotransfected with dominant-negative forms of either NF-Y or SREBP. In addition, we demonstrate that the induction of SCD1 and SCD2 mRNAs that occurs during the differentiation of 3T3-L1 preadipocytes to adipocytes is paralleled by an increase in the levels of ADD1/SREBP-1c and that the SCD1 and SCD2 mRNAs are induced to even higher levels in response to ectopic expression of ADD 1/SREBP-1c. We conclude that transcription of both SCD1 and SCD2 genes is responsive to cellular sterol levels and to the levels of nuclear SREBP/ADD1 and that transcriptional induction requires three spatially conserved cis elements, that bind SREBP and NF-Y. Additional studies demonstrate that maximal transcriptional repression of SCD2 reporter genes in response to an exogenous polyunsaturated fatty acid is dependent upon the SRE and the adjacent CCAAT motif. C1 Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Edwards, PA (reprint author), Univ Calif Los Angeles, Dept Biol Chem, CHS 33-257, Los Angeles, CA 90095 USA. FU NHLBI NIH HHS [HL 30568] NR 44 TC 161 Z9 166 U1 0 U2 5 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 JUL 16 PY 1999 VL 274 IS 29 BP 20603 EP 20610 DI 10.1074/jbc.274.29.20603 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 216JE UT WOS:000081438300084 PM 10400691 ER PT J AU Itoh, H Inoue, N Podolsky, DK AF Itoh, H Inoue, N Podolsky, DK TI Goblet-cell-specific transcription of mouse intestinal trefoil factor gene results from collaboration of complex series of positive and negative regulatory elements SO BIOCHEMICAL JOURNAL LA English DT Article DE colon; enhancer; epithelium; promoter; silencer ID EPIDERMAL GROWTH-FACTOR; SPASMOLYTIC POLYPEPTIDE; P-DOMAIN; MOLECULAR-CLONING; MESSENGER-RNAS; C-FOS; EXPRESSION; PS2; PROTEIN; PEPTIDE AB Intestinal trefoil factor (ITF) is expressed selectively in intestinal goblet cells. Previous studies of the rat ITF gene identified one cis-regulatory element, designated the goblet-cell-response element (GCRE), present in the proximal region of the promoter. To identify additional cis-regulatory elements responsible for goblet-cell-specific expression, a DNA fragment containing 6353 bp of the 5'-flanking region of the mouse ITF gene was cloned and its promoter activity was examined extensively. In human and murine intestinal-derived cell lines (LS174T and CMT-93), the luciferase activities of a 6.3-kb construct were 5- and 2-fold greater than the smaller 1.8-kb construct, respectively. In contrast, the activity in non-intestinal cell lines (HepG2 and HeLa) was 2-4-fold lower than the smaller construct. In the region downstream from the 1.8-kb position, strong luciferase activities in LS174T and HepG2 cells were observed using a 201-bp construct. Interestingly, increased activity was almost completely suppressed in cells transfected with a 391-bp construct. Detailed analyses of this region revealed the existence of a 11-bp positive regulatory element(-181 to -170; ACCTCTTCCTG) and a 9-bp negative regulatory element (-208 to -200; ATTGACAGA) in addition to the GCRE. All three elements were well conserved among human, rat and mouse ITF gene promoters. In addition, a mutant 1.8-kb construct in which the negative regulatory region was deleted yielded the same approximate luciferase activity as a 6.3-kb construct, suggesting binding of a goblet-cell-specific silencer inhibitor (SI) between -6.3 and -1.8 kb. The SI present in goblet cells may block the silencers' binding to the pre-initiation complex and allow increased transcriptional activity driven by specific and non-specific enhancers. High-level expression of the mouse ITF gene specifically in intestinal goblet cells may be achieved through the combined effects of these regulatory elements. C1 Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, 32 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK46906, DK43351] NR 47 TC 20 Z9 21 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUL 15 PY 1999 VL 341 BP 461 EP 472 DI 10.1042/0264-6021:3410461 PN 2 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 219FQ UT WOS:000081597600029 PM 10393106 ER PT J AU Dukoff, R Wilkinson, CW Lasser, P Friz, J Conway, A Bahro, M Peskind, ER Sunderland, T AF Dukoff, R Wilkinson, CW Lasser, P Friz, J Conway, A Bahro, M Peskind, ER Sunderland, T TI Physostigmine challenge before and after chronic cholinergic blockade in elderly volunteers SO BIOLOGICAL PSYCHIATRY LA English DT Article DE aging; Alzheimer's; neuroendocrine; cortisol; physostigmine; scopolamine; plasticity ID ADRENOCORTICAL AXIS RESPONSES; ALZHEIMERS-DISEASE; RECEPTOR PLASTICITY; NEUROENDOCRINE RESPONSES; ANTERIOR-PITUITARY; FRONTAL-CORTEX; SCOPOLAMINE; BRAIN; RATS; AGE AB Background: As a test of possible muscarinic up-regulation, the cortisol response to intravenous (IV) physostigmine (an anticholinesterase) was measured in 9 elderly volunteers before and after chronic cholinergic blockade with the muscarinic cholinergic antagonist scopolamine, Methods: Each of the 9 elderly control subjects was given two physostigmine (0.5 mg IV) infusions separated by 21 doses of nightly scopolamine (1.2 mg p.o,). No scopolamine tr as administered the night before infusions, and glycopyrrolate (0.2 mg IV) was administered prior to physostigmine to block its peripheral effects, Vital signs were monitored and blood samples were collected at six time points surrounding the physostigmine infusion (-10, +10, +20 +30, +50, and +70 min). Behavioral measures and cognitive tests were administered prior to and 30 min after the physostigmine. Results: The cortisol response to physostigmine was greater after the second (post-chronic scopolamine) infusion study compared to the first (p < .05) as measured by an area under the curve analysis of all time points. When individual time points were compared, the mean cortisol response was significantly increased after the second physostigmine infusion at the +50- and +70-min rime points (p < .05). There were no significant changes in behavioral rating scales, cognitive tests, or vital signs between the Mlo physostigmine infusion study days. Conclusions: This study demonstrates increased hypothalamic-pituitary-adrenocortical axis responsivity to a central nervous system cholinergic stimulus after chronic muscarinic blockade in 9 elderly control subjects. it also gives further evidence to support previous suggestions of muscarinic plasticity, specifically postsynaptic up-regulation, in the aging brain following exposure to chronic anticholinergic treatment. (C) 1999 Society of Biological Psychiatry. C1 NIMH, Geriatr Psychiat Branch, NIH, Ctr Clin, Bethesda, MD 20892 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Mental Res Educ & Clin Ctr, Seattle, WA USA. RP Sunderland, T (reprint author), NIMH, Geriatr Psychiat Branch, NIH, Ctr Clin, Bldg 10,Rm 3N228,10 Ctr Dr,MSC 1264, Bethesda, MD 20892 USA. NR 53 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 15 PY 1999 VL 46 IS 2 BP 189 EP 195 DI 10.1016/S0006-3223(98)00286-8 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 217BL UT WOS:000081479400005 PM 10418693 ER PT J AU Alpert, JE Fava, M Uebelacker, LA Nierenberg, AA Pava, JA Worthington, JJ Rosenbaum, JF AF Alpert, JE Fava, M Uebelacker, LA Nierenberg, AA Pava, JA Worthington, JJ Rosenbaum, JF TI Patterns of axis I comorbidity in early-onset versus late-onset major depressive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 148th Annual Meeting of the American-Psychiatric-Association CY MAY 20-26, 1995 CL MIAMI BEACH, FLORIDA SP Amer Psychiat Assoc DE major depression; comorbidity; age of onset; Axis I disorders ID CONTROLLED FAMILY HISTORY; ANXIETY DISORDERS; SOCIAL PHOBIA; PSYCHIATRIC-DISORDERS; ADOLESCENT DEPRESSION; DYSTHYMIC DISORDER; COMMUNITY SAMPLE; ADULT OUTCOMES; UNITED-STATES; CO-MORBIDITY C1 Massachusetts Gen Hosp, Clin Psychopharmacol Unit WAC 812, Depress Clin & Res Program, Boston, MA 02114 USA. RP Alpert, JE (reprint author), Massachusetts Gen Hosp, Clin Psychopharmacol Unit WAC 812, Depress Clin & Res Program, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [R01MH 48483-01] NR 54 TC 46 Z9 47 U1 2 U2 4 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 JUL 15 PY 1999 VL 46 IS 2 BP 202 EP 211 DI 10.1016/S0006-3223(99)00017-7 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 217BL UT WOS:000081479400007 PM 10418695 ER PT J AU Taniguchi, Y London, R Schinkmann, K Jiang, SX Avraham, H AF Taniguchi, Y London, R Schinkmann, K Jiang, SX Avraham, H TI The receptor protein tyrosine phosphatase, PTP-RO, is upregulated during megakaryocyte differentiation and is associated with the c-Kit receptor SO BLOOD LA English DT Article ID STEM-CELL FACTOR; SH3-SH2-SH3 ADAPTER PROTEIN; HOMOLOGOUS KINASE CHK; SIGNAL-TRANSDUCTION; BINDING-SITE; PHOSPHOTYROSINE PHOSPHATASE; CHROMOSOMAL LOCALIZATION; HOMOPHILIC BINDING; MOLECULAR-CLONING; GENE-EXPRESSION AB We have recently isolated a cDNA encoding a novel human receptor-type tyrosine phosphatase, termed PTP-RO (for a protein tyrosine phosphatase receptor omicron), from Ei-fluorouracil-treated murine bone marrow cells. PTP-RO is a human homologue of murine PTP lambda and is related to the homotypically adhering kappa and mu receptor-type tyrosine phosphatases. PTP-RO is expressed in human megakaryocytic cell lines, primary bone marrow megakaryocytes, and stem cells. PTP-RO mRNA and protein expression are upregulated upon phorbol 12-myristate 13-acetate (PMA) treatment of the megakaryocytic cell lines CMS, CMK, and Dami. To elucidate the function of PTP-RO in megakaryocytic cells and its potential involvement in the stem cell factor (SCF)/c-Kit receptor pathway, COS-7 and 293 cells were cotransfected with the cDNAs of both the c-Kit tyrosine kinase receptor and PTP-RO. PTP-RO was found to be associated with the c-Kit receptor in these transfected cells and the SCF/Kit ligand induced a rapid tyrosine phosphorylation of PTP-RO. Interestingly, these transfected cells demonstrated a decrease in their proliferative response to the SCF/Kit ligand. In addition, we assessed the association of PTP-RO with c-Kit in vivo. The results demonstrated that PTP-RO associates with c-Kit but not with the tyrosine kinase receptor FGF-R and that PTP-RO is tyrosine-phosphorylated after SCF stimulation of Mo7e and CMK cells. Antisense oligonucleotides directed against PTP-RO mRNA sequences significantly inhibited megakaryocyte progenitor proliferation. Therefore, these data show that the novel tyrosine kinase phosphatase PTP-RO is involved in megakaryocytopoiesis and that its function is mediated by the SCF/c-Kit pathway. (C) 1999 by The American Society of Hematology. C1 Harvard Univ, Inst Med, Div Expt Med, BIDMC, Boston, MA 02115 USA. RP Avraham, H (reprint author), Harvard Univ, Inst Med, Div Expt Med, BIDMC, 4 Blackfan Circle, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL 51456] NR 59 TC 16 Z9 18 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 1999 VL 94 IS 2 BP 539 EP 549 PG 11 WC Hematology SC Hematology GA 214RX UT WOS:000081342300019 PM 10397721 ER PT J AU Krijanovski, OI Hill, GR Cooke, KR Teshima, T Crawford, JM Brinson, YS Ferrara, JLM AF Krijanovski, OI Hill, GR Cooke, KR Teshima, T Crawford, JM Brinson, YS Ferrara, JLM TI Keratinocyte growth factor separates graft-versus-leukemia effects from graft-versus-host disease SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; NECROSIS-FACTOR-ALPHA; IN-VIVO; EXPERIMENTAL-MODEL; CELLS; MICE; PROLIFERATION; STIMULATION; IRRADIATION; EXPRESSION AB The major obstacles to successful outcome after allogeneic bone marrow transplantation (BMT) for leukemia remain graft-versus-host disease (GVHD) and leukemic relapse. Improved survival after BMT therefore requires more effective GVHD prophylaxis that does not impair graft-versus-leukemia (GVL) effects, We studied the administration of human recombinant keratinocyte growth factor (KGF) in a well-characterized murine BMT model for its effects on GVHD. KGF administration from day -3 to +7 significantly reduced GVHD mortality and the severity of GVHD in the gastrointestinal(GI) tract, reducing serum lipopolysaccharide (LPS) and tumor necrosis factor (TNF)alpha levels, but preserving donor T-cell responses (cytotoxic T lymphocyte [CTL] activity, proliferation, and interleukin [IL]-2 production) to host antigens. When mice received lethal doses of P815 leukemia cells at the time of BMT, KGF treatment significantly decreased acute GVHD compared with control-treated allogeneic mice and resulted in a significantly improved leukemia-free survival (42% v 4%, P < .001). KGF administration thus offers a novel approach to the separation of GVL effects from GVHD. (C) 1999 by The American Society of Hematology. C1 Univ Michigan, Ctr Canc, Div Hematol & Oncol, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Canc, Div Hematol & Oncol, Dept Pediat, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. RP Ferrara, JLM (reprint author), Univ Michigan, Ctr Canc, Div Hematol & Oncol, Dept Internal Med, Ann Arbor, MI 48109 USA. RI teshima, takanori/G-1671-2012; Hill, Geoffrey/O-2630-2016 OI Hill, Geoffrey/0000-0003-2994-0429 FU NCI NIH HHS [CA39542]; NHLBI NIH HHS [HL55162] NR 34 TC 123 Z9 126 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 1999 VL 94 IS 2 BP 825 EP 831 PG 7 WC Hematology SC Hematology GA 214RX UT WOS:000081342300049 PM 10397751 ER PT J AU Gorski, DH Beckett, MA Jaskowiak, NT Calvin, DP Mauceri, HJ Salloum, RM Seetharam, S Koons, A Hari, DM Kufe, DW Weichselbaum, RR AF Gorski, DH Beckett, MA Jaskowiak, NT Calvin, DP Mauceri, HJ Salloum, RM Seetharam, S Koons, A Hari, DM Kufe, DW Weichselbaum, RR TI Blockade of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation SO CANCER RESEARCH LA English DT Article ID FACTOR-NEUTRALIZING ANTIBODY; TUMOR-GROWTH; INHIBITION; ANGIOGENESIS; ANGIOSTATIN; METASTASIS; THERAPY AB The family of vascular endothelial growth factor (VEGF) proteins include potent and specific mitogens for vascular endothelial cells that function in the regulation of angiogenesis. Inhibition of VEGF-induced angiogenesis, either by neutralizing antibodies or a dominant-negative soluble receptor, blocks the growth of primary and metastatic experimental tumors. Here me report that VEGF expression is induced in Lewis lung carcinomas (LLCs) both in vitro and in vivo after exposure to ionizing radiation (IR) and in human tumor cell lines (Seg-1 esophageal adenocarcinoma, SQ20E squamous cell carcinoma, T98 and U87 glioblastomas, and U1 melanoma) in vitro, The biological significance of IR-induced VEGF production is supported by our finding that treatment of tumor-bearing mice (LLC, Seg-1, SQ20B, and U87) with a neutralizing antibody to VEGF-165 before irradiation is associated dth a greater than additive antitumor effect. In vitro, the addition of VEGF decreases IR-induced killing of human umbilical vein endothelial cells, and the anti-VEGF treatment potentiates IR-induced lethality of human umbilical vein endothelial cells. Neither recombinant VEGF protein nor neutralizing antibody to VEGF affects the radiosensitivity of tumor cells. These findings support a model in which induction of VEGF by IR contributes to the protection of tumor blood vessels from radiation-mediated cytotoxicity and thereby to tumor radioresistance. C1 Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. Univ Chicago, Dept Surg, Chicago, IL 60637 USA. Harvard Med Sch, Dana Farber Canc Inst, 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 [CA41068, CA42596]; NIDCR NIH HHS [DE/CA11921] NR 19 TC 667 Z9 705 U1 2 U2 23 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1999 VL 59 IS 14 BP 3374 EP 3378 PG 5 WC Oncology SC Oncology GA 218EH UT WOS:000081539900018 PM 10416597 ER PT J AU Sagasti, A Hobert, O Troemel, ER Ruvkun, G Bargmann, CI AF Sagasti, A Hobert, O Troemel, ER Ruvkun, G Bargmann, CI TI Alternative olfactory neuron fates are specified by the LIM homeobox gene lim-4 SO GENES & DEVELOPMENT LA English DT Article DE olfactory neuron; cell fate specification; LIM homeobox gene; C. elegans ID NUCLEOTIDE-GATED CHANNEL; CAENORHABDITIS-ELEGANS; C-ELEGANS; CHEMOSENSORY RECEPTORS; ODORANT RECEPTOR; SENSORY NEURONS; NERVOUS-SYSTEM; MOTOR-NEURONS; HOMEODOMAIN; EXPRESSION AB The Caenorhabditis elegans AWA, AWB, and AWC olfactory neurons are each required for the recognition of a specific subset of volatile odorants. lim-4 mutants express an AWC reporter gene inappropriately in the AWE olfactory neurons and fail to express an AWE reporter gene. The AWE cells are morphologically transformed toward an AWC fate in lim-4 mutants, adopting cilia and axon morphologies characteristic of AWC. AWE function is also transformed in these mutants: Rather than mediating the repulsive behavioral responses appropriate for AWE, the AWE neurons mediate attractive responses, like AWC. LIM-4 is a predicted LIM homeobox gene that is expressed in AWE and a few other head neurons. Ectopic expression of LIM-4 in the AWC neuron pair is sufficient to force those cells to adopt an AWE fate. The AWA nuclear hormone receptor ODR-7 described previously also represses AWC genes, as well as inducing AWA genes. We propose that the LIM-4 and ODR-7 transcription factors function to diversify C. elegans olfactory neuron identities, driving them from an AWC-like state into alternative fates. C1 Univ Calif San Francisco, Howard Hughes Med Inst, Dept Anat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Bargmann, CI (reprint author), Univ Calif San Francisco, Howard Hughes Med Inst, Dept Anat, San Francisco, CA 94143 USA. RI Marion-Poll, Frederic/D-8882-2011; OI Marion-Poll, Frederic/0000-0001-6824-0180; Bargmann, Cornelia/0000-0002-8484-0618; Hobert, Oliver/0000-0002-7634-2854 NR 38 TC 88 Z9 101 U1 1 U2 2 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 JUL 15 PY 1999 VL 13 IS 14 BP 1794 EP 1806 DI 10.1101/gad.13.14.1794 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 221EM UT WOS:000081711100005 PM 10421632 ER PT J AU Pold, M Zhou, J Chen, GL Hall, JM Vescio, RA Berenson, JR AF Pold, M Zhou, J Chen, GL Hall, JM Vescio, RA Berenson, JR TI Identification of a new, unorthodox member of the MAGE gene family SO GENOMICS LA English DT Article ID REPRESENTATIONAL DIFFERENCE ANALYSIS; CYTOLYTIC T-LYMPHOCYTES; EXPRESSION; CELLS; MELANOMA AB Several tumor-associated antigen families, such as MAGE, GAGE/PAGE, PRAME, BAGE, and LAGE/NY-ESO-1, exist. These antigens are of particular interest in tumor immunology, because their expression, with exception of testis and fetal tissues, seems to be restricted to tumor cells only. We have identified a novel member of the MAGE gene family, MAGED1. Northern hybridization and RT-PCR demonstrated that the expression level of MAGED1 in different normal adult tissues is comparable to that in testis and fetal liver. Thus, MAGED1 does not possess an expression pattern characteristic of previously identified MAGE family genes, suggesting that the biology of the MAGE-family genes is more complex than previously thought. Chromosome mapping linked MAGED1 tot marker AFM119xd6 (DXS1039) on chromosome Xp11.23. (C) 1999 Academic Press. C1 W Los Angeles Vet Affairs Med Ctr, Brentwood Biomed Res Inst, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Div Hematol & Oncol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. Axys Pharmaceut, La Jolla, CA 92037 USA. RP Pold, M (reprint author), W Los Angeles Vet Affairs Med Ctr, Brentwood Biomed Res Inst, Bldg 304,E1-106,11301 Wilshire Blvd,111-H, Los Angeles, CA 90073 USA. NR 17 TC 63 Z9 69 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JUL 15 PY 1999 VL 59 IS 2 BP 161 EP 167 DI 10.1006/geno.1999.5870 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 221YZ UT WOS:000081756600006 PM 10409427 ER PT J AU Kamiguchi, K Tachibana, K Iwata, S Ohashi, Y Morimoto, C AF Kamiguchi, K Tachibana, K Iwata, S Ohashi, Y Morimoto, C TI Cas-L is required for beta(1) integrin-mediated costimulation in human T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FOCAL ADHESION KINASE; SUBSTRATE-RELATED PROTEIN; TYROSINE PHOSPHORYLATION; TRANSCRIPTION FACTOR; ADAPTER PROTEINS; CD4 CELLS; C-SRC; V-CRK; ACTIVATION; P130(CAS) AB beta(1) integrins provide a costimulus for TCR/CD3-driven T cell activation and IL-2 production in human peripheral T cells. However, this beta(1) integrin-mediated costimulation is impaired in a human T lymphoblastic line, Jurkat, We studied the molecular basis of this impaired costimulation and found that Cas-L, a 105-kDa docking protein, is marginally expressed in Jurkat T cells, whereas Cas-L is well expressed in peripheral T cells. Cas-L is a binding protein and a substrate for focal adhesion kinase and is tyrosine phosphorylated by beta(1) integrin stimulation, We here show that the transfection of wild-type Cas-L in Jurkat T cells restores beta(1) integrin-mediated costimulation, However, Cas-L transfection had no effect on CD28-mediated costimulation, indicating that Cas-L is specifically involved in the beta(L) integrin-mediated signaling pathway. Furthermore, transfection of the Cas-L Delta SH3 mutant failed to restore beta(1) integrin-mediated costimulation in Jurkat cells, Cas-L Delta SH3 mutant lacks the binding site for focal adhesion kinase and is not tyrosine phosphorylated after beta(1) integrin stimulation, These findings strongly suggest that the tyrosine phosphorylation of Cas-L plays a key role in the signal transduction in the beta(1) integrin-mediated T cell costimulation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Tokyo, Inst Med Sci, Dept Clin Immunol, Tokyo, Japan. Univ Tokyo, Inst Med Sci, Ctr AIDS Res, Tokyo, Japan. RP Morimoto, C (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Tumor Immunol, 44 Binney St, Boston, MA 02115 USA. RI Iwata, Satoshi/A-8819-2011 FU NIAID NIH HHS [AI29530]; NIAMS NIH HHS [AR33713] NR 40 TC 32 Z9 32 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 JUL 15 PY 1999 VL 163 IS 2 BP 563 EP 568 PG 6 WC Immunology SC Immunology GA 215AY UT WOS:000081360800003 PM 10395641 ER PT J AU Chuntharapai, A Gibbs, V Lu, J Ow, A Marsters, S Ashkenazi, A De Vos, A Kim, KJ AF Chuntharapai, A Gibbs, V Lu, J Ow, A Marsters, S Ashkenazi, A De Vos, A Kim, KJ TI Determination of residues involved in ligand binding and signal transmission in the human IFN-alpha receptor 2 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID I INTERFERON RECEPTOR; EXTRACELLULAR DOMAIN; MONOCLONAL-ANTIBODY; CRYSTAL-STRUCTURE; BETA; CLONING; COMPONENTS; EXPRESSION; SUBUNITS; COMPLEX AB The human IFN-alpha receptor (hIFNAR) is a complex composed of at least two chains, hIFNAR1 and hIFNAR2. We have performed a structure-function analysis of hIFNAR2 extracellular domain regions using anti-hIFNAR2 mAbs (1D3, 1F3, and 3B7) and several type I human IFNs. These mAbs block receptor activation, as determined by IFN-stimulated gene factor 3 formation, and block the antiviral cytopathic effects induced by type I IFNs. We generated alanine substitution mutants of hIFNAR2-IgG and determined that regions of hIFNAR2 are important for the binding of these blocking mAbs and hIFN-alpha 2/alpha 1. We further demonstrated that residues E78, W101, I104, and D105 are crucial for the binding of hIFN-alpha 2/alpha 1 and form a defined protrusion when these residues are mapped upon a structural model of hIFNAR2. To confirm that residues important for ligand binding are indeed important for IPN signal transduction, we determined the ability of mouse L929 cells expressing hIFNAR2 extracellular domain mutants to mediate hIFN signal. hIFN-alpha 8, previously shown to signal a response in L929 cells expressing hIFNAR1, was unable to signal in L929 cells expressing hIFNAR2, Transfected cells expressing hIFNAR2 containing mutations at residues E78, W101, I104, or D105 were unresponsive to hIFN-alpha 2, but remained responsive to hIFN-beta. In summary, we have identified specific residues of hIFNAR2 important for the binding to hIFN-alpha 2/1 and demonstrate that specific regions of the IFNAR interact with the subspecies of type I IFN in different manners. C1 Genentech Inc, Dept Antibody Technol, S San Francisco, CA 94080 USA. Genentech Inc, Dept Mol Oncol, S San Francisco, CA 94080 USA. Genentech Inc, Dept Prot Engn, S San Francisco, CA 94080 USA. San Francisco Vet Affairs Med Ctr, Dept Surg, San Francisco, CA 94121 USA. RP Kim, KJ (reprint author), Genentech Inc, Dept Antibody Technol, S San Francisco, CA 94080 USA. NR 35 TC 30 Z9 31 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 JUL 15 PY 1999 VL 163 IS 2 BP 766 EP 773 PG 8 WC Immunology SC Immunology GA 215AY UT WOS:000081360800031 PM 10395669 ER PT J AU Tzianabos, AO Russell, PR Onderdonk, AB Gibson, FC Cywes, C Chan, M Finberg, RW Kasper, DL AF Tzianabos, AO Russell, PR Onderdonk, AB Gibson, FC Cywes, C Chan, M Finberg, RW Kasper, DL TI IL-2 mediates protection against abscess formation in an experimental model of sepsis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL INTRAABDOMINAL ABSCESSES; INTRA-ABDOMINAL ABSCESS; T-CELL ACTIVATION; BACTEROIDES-FRAGILIS; IN-VITRO; POLYSACCHARIDES; TOLERANCE; GAMMA AB Little is known regarding the mechanism by which T cells control intraabdominal abscess formation. Treating animals with polysaccharide A (PS A) from Bacteroides fragilis shortly before or after challenge protects against abscess formation subsequent to challenge with different abscess-inducing bacteria, Although bacterial polysaccharides are considered to be T cell-independent Ags, T cells from PS A-treated animals mediate this protective activity. In the present study, we demonstrate that CD4(+) T cells transfer PS A-mediated protection against abscess formation, and that a soluble mediator produced by these cells confers this activity. Cytokine mRNA analysis showed that T cells from PS A-treated animals produced transcript for IL-2, IFN-gamma, and IL-10, but not for IL-4, The addition of IL-2-specific Ab to T cell lysates taken from PS A-treated animals abrogated the ability to transfer protection, whereas the addition of Abs specific for IFN-gamma and IL-10 did not affect protection. Finally, administration of rIL-2 to animals at the time of bacterial challenge prevented abscess formation in a dose-dependent manner. These data demonstrate that PS A-mediated protection against abscess formation is dependent upon a CD4(+) T cell-dependent response, and that IL-2 is essential to this immune mechanism. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Boston Univ, Sch Med, Maxwell Finland Lab, Boston, MA 02118 USA. RP Tzianabos, AO (reprint author), Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. RI Finberg, Robert/E-3323-2010 FU NIAID NIH HHS [AI 34073, AI 39576] NR 29 TC 33 Z9 34 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1999 VL 163 IS 2 BP 893 EP 897 PG 5 WC Immunology SC Immunology GA 215AY UT WOS:000081360800046 PM 10395684 ER PT J AU Eliasson, MJL Huang, ZH Ferrante, RJ Sasamata, M Molliver, ME Snyder, SH Moskowitz, MA AF Eliasson, MJL Huang, ZH Ferrante, RJ Sasamata, M Molliver, ME Snyder, SH Moskowitz, MA TI Neuronal nitric oxide synthase activation and peroxynitrite formation in ischemic stroke linked to neural damage SO JOURNAL OF NEUROSCIENCE LA English DT Article DE citrulline; ischemial; peroxynitrite; 3-nitrotyrosine; nitric oxide; nitric oxide synthase; peroxynitrite ID CEREBRAL-ARTERY OCCLUSION; RAT-BRAIN; INCREASED 3-NITROTYROSINE; MEDIATED NEUROTOXICITY; SYNAPTIC PLASTICITY; MICE; MESSENGER; NMDA; IMMUNOCYTOCHEMISTRY; DIAPHORASE AB Nitric oxide (NO) is a new intercellular messenger that occurs naturally in the brain without causing overt toxicity. Yet, NO has been implicated as a mediator of cell death in cell death. One explanation is that ischemia causes overproduction of NO, allowing it to react with superoxide to form the potent oxidant peroxynitrite. To address this question, we used immunohistochemistry for citrulline, a marker for NO synthase activity, and 3-nitrotyrosine, a marker for peroxynitrite formation, in mice subjected to reversible middle cerebral artery occlusion. We show that ischemia triggers a marked augmentation in citrulline immunoreactivity but more so in the peri-infarct than the infarcted tissue. This increase is attributable to the activation of a large population (similar to 80%) of the neuronal isoform of NO synthase (nNOS)that is catalytically inactive during basal conditions, indicating a tight regulation of physiological NO production in the brain. In contrast, 3-nitrotyrosine immunoreactivity is restricted to the infarcted tissue and is not present in the peri-infarct tissue. In nNOS(Delta/Delta) mice, known to be protected against ischemia, no 3-nitrotyrosine immunoreactivity is detected. Our findings provide a cellular localization for nNOS activation in association with ischemic stroke and establish that NO is not likely a direct neurotoxin, whereas its conversion to peroxynitrite is associated with cell death. C1 Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. Massachusetts Gen Hosp, Serv Neurol, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neurosurg Serv, Charlestown, MA 02129 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Vet Adm Med Ctr, GRECC Unit 182B, Bedford, MA 01730 USA. RP Snyder, SH (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurosci, 725 N Wolfe St 813 Wood Basic Sci Bldg, Baltimore, MD 21205 USA. RI Moskowitz, Michael/D-9916-2011 FU NIA NIH HHS [AG12992]; NINDS NIH HHS [NS35255, NS37102] NR 50 TC 252 Z9 263 U1 1 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 15 PY 1999 VL 19 IS 14 BP 5910 EP 5918 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 215JB UT WOS:000081377600021 PM 10407030 ER PT J AU Ghosh, PM Ghosh-Choudhury, N Moyer, ML Mott, GE Thomas, CA Foster, BA Greenberg, NM Kreisberg, JI AF Ghosh, PM Ghosh-Choudhury, N Moyer, ML Mott, GE Thomas, CA Foster, BA Greenberg, NM Kreisberg, JI TI Role of RhoA activation in the growth and morphology of a murine prostate tumor cell line SO ONCOGENE LA English DT Article DE RhoA; actin stress fibers; H-Ras; lovastatin; geranylgeraniol; farnesol ID ACTIN STRESS FIBERS; CULTURED MESANGIAL CELLS; RAS TRANSFORMATION; FOCAL ADHESIONS; SIGNALING PATHWAY; PROTEIN-KINASES; TRAMP MODEL; GTPASES; PROGRESSION; RAC1 AB Prostate cancer cells derived from transgenic mice with adenocarcinoma of the prostate (TRAMP cells) were treated with the HMG-CoA reductase inhibitor, lovastatin, This caused inactivation of the small GTPase RhoA, actin stress fiber disassembly, cell rounding, growth arrest in the GZ phase of the cell cycle, cell detachment and apoptosis, Addition of geranylgeraniol (GGOL) in the presence of lovastatin, to stimulate protein geranylgeranylation, prevented lovastatin's effects. That is, RhoA was activated, actin stress fibers were assembled, the cells assumed a flat morphology and cell growth resumed. The following observations support an essential role for RhoA in TRAMP cell growth: (1) TRAMP cells expressing dominant-negative RhoA (T19N) mutant protein displayed few actin stress fibers and grew at a slower rate than controls (35 h doubling time for cells expressing RhoA (T19N) vs 20 h for untransfected cells); (2) TRAMP cells expressing constitutively active RhoA. (Q63L) mutant protein displayed a contractile phenotype and grew faster than controls (13 h doubling time), Interestingly, addition of farnesol (FOL) with lovastatin, to stimulate protein farnesylation, prevented lovastatin-induced cell rounding, cell detachment and apoptosis, and stimulated cell spreading to a spindle shaped morphology. However, RhoA remained inactive and growth arrest persisted. The morphological effects of FOL addition were prevented in TRAMP cells expressing dominant-negative H-Ras (T17N) mutant protein. Thus, it appears that H-Ras is capable of inducing cell spreading, but incapable of supporting cell proliferation, in the absence of geranylgeranylated proteins like RhoA. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Microbiol, San Antonio, TX 78284 USA. Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. Audie L Murphy Mem Vet Hosp, Res & Dev Serv, San Antonio, TX 78284 USA. RP Kreisberg, JI (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 56 TC 78 Z9 80 U1 1 U2 7 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 15 PY 1999 VL 18 IS 28 BP 4120 EP 4130 DI 10.1038/sj.onc.1202792 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 216FP UT WOS:000081431000009 PM 10435593 ER PT J AU Dey, B Yang, YG Preffer, F Shimizu, A Swenson, K Dombkowski, D Sykes, M AF Dey, B Yang, YG Preffer, F Shimizu, A Swenson, K Dombkowski, D Sykes, M TI The fate of donor T-cell receptor transgenic T cells with known host antigen specificity in a graft-versus-host disease model SO TRANSPLANTATION LA English DT Article ID II H-2 DIFFERENCES; ACTIVATION-INDUCED DEATH; APOPTOSIS IN-VIVO; CLONAL ANERGY; DOWN-REGULATION; EXTRATHYMIC TOLERANCE; MONOCLONAL-ANTIBODY; LYMPHOCYTES-T; FAS RECEPTOR; L3T4+ CELLS AB Background. The expansion of transgenic donor CD8(+) T-cells with known allospecificity against a host MHC class I alloantigen was examined in a murine graft-versus-host disease (GVHD) model. Methods. Lethally irradiated, Ld+ BALB/c mice received bone marrow cells and spleen cells from anti-L-d 2C T-cell receptor (TCR)-transgenic B6 mice, alone or with normal Be spleen cells. Transgenic TCR-bearing T-cell expansion, apoptosis, and function were monitored at various time points and were correlated with clinical outcome. Results. Fifteen-fold clonal expansion of 2C CD8 cells occurred by day 4 after bone marrow transplantation. Between days 4 and 7, increasing proportions of 2C CD8 cells underwent apoptotic cell death, coincident with a 7-15-fold decline in their numbers. CD8 and TCR expression were down-regulated on 2C CD8 cells by day +4 after bone marrow transplantation, and they were anergic to TCR-mediated stimulation. Clinically, the BALB/c recipients of 2C spleen cells exhibited only minimal chronic GVHD, In contrast, lethally irradiated BALB/c mice receiving similar numbers of non-transgenic B6 bone marrow cells and spleen cells exhibited severe GVHD (median survival time: 28 days). The addition of a small number of 2C spleen cells to the inoculum accelerated GVHD mortality, and 2C CD8 cells showed a similar time course of expansion and decline to that observed in recipients of larger numbers of 2C cells alone. Conclusions. Initial clonal expansion, down-regulation of CD8 and TCR, anergy, and later deletion of graft versus-host-reactive CD8 cells via apoptosis occurs in lethally irradiated recipients. Expansion of a single CD8 clone produces much less severe GVHD than that induced by a polyclonal, mixed CD4 plus CD8 response. These results have implications for GVHD pathogenesis and its sometimes self-limited nature. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr,Surg Serv, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr,Surg Serv, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. FU NCI NIH HHS [R01CA64912] NR 56 TC 27 Z9 27 U1 1 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 JUL 15 PY 1999 VL 68 IS 1 BP 141 EP 149 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 220AZ UT WOS:000081643100026 PM 10428282 ER PT J AU Schacter, DL Badgaiyan, RD Alpert, NM AF Schacter, DL Badgaiyan, RD Alpert, NM TI Visual word stem completion priming within and across modalities: a PET study SO NEUROREPORT LA English DT Article DE angular gyrus; cross modal priming; explicit memory; extrastriate cortex; implicit memory; lexical processes; prefrontal cortex; priming; word stem completion task ID POSITRON EMISSION TOMOGRAPHY; EPISODIC MEMORY; WORKING-MEMORY; RETRIEVAL; RECOLLECTION; CORTEX; BRAIN AB USING positron emission tomography, we studied changes in the regional cerebral blood flow (rCBF) associated with cross modality (auditory to visual) and within modality visual priming in a word stem completion task. Compared to baseline completion performance and to within modality visual priming, cross modality priming was associated with increased rCBF in prefrontal cortex and decreased rCBF in the left angular gyrus. The results confirm and complement trends observed in a previous study concerning visual to auditory cross modality priming, and suggest that distinct cortical mechanisms may mediate within- and cross modality priming on the stem completion task. The findings are consistent with the neuropsychological data concerning auditory to visual cross modality priming, and indicate involvement of aspects of explicit retrieval and lexical processes in cross modality priming. NeuroReport 10:2061-2065 (C) 1999 Lippincott Williams & Wilkins. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, PET Imaging Lab, Boston, MA 02114 USA. RP Schacter, DL (reprint author), Harvard Univ, Dept Psychol, William James hall,33 Kirkland St, Cambridge, MA 02138 USA. OI Schacter, Daniel/0000-0002-2460-6061 FU NIMH NIH HHS [MH57915-02] NR 24 TC 46 Z9 46 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUL 13 PY 1999 VL 10 IS 10 BP 2061 EP 2065 DI 10.1097/00001756-199907130-00013 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 214YB UT WOS:000081354200013 PM 10424675 ER PT J AU Tritos, NA Hartzband, P AF Tritos, NA Hartzband, P TI Rapid improvement of osteoporosis following parathyroidectomy in a premenopausal woman with acute primary hyperparathyroidism SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CALCIUM-RECEPTOR; HYPERCALCEMIA; HORMONE; MANAGEMENT; CARCINOMA; SECRETION AB We describe a premenopausal white woman with symptomatic acute primary hyperparathyroidism and marked osteoporosis. After undergoing a parathyroidectomy, the patient experienced not only rapid symptomatic relief, but also marked improvement in bone mineral density, which increased by 25% in the hip and by 22% in the lumbar spine 1 year after the surgery. Acute primary hyperparathyroidism should be considered in any patient with severe symptomatic hypercalcemia. Appropriate treatment with early parathyroidectomy can result in significant and rapid improvement in bone mineral density. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Hartzband, P (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol, W Campus,110 Francis St,Suite 9D, Boston, MA 02215 USA. NR 22 TC 9 Z9 9 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 12 PY 1999 VL 159 IS 13 BP 1495 EP 1498 DI 10.1001/archinte.159.13.1495 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 212PA UT WOS:000081224400013 PM 10399902 ER PT J AU Shiraha, H Glading, A Gupta, K Wells, A AF Shiraha, H Glading, A Gupta, K Wells, A TI IP-10 inhibits epidermal growth factor-induced motility by decreasing epidermal growth factor receptor-mediated calpain activity SO JOURNAL OF CELL BIOLOGY LA English DT Article DE EGF receptor; cell motility; calpain; chemokine; fibroblasts ID CELL-MIGRATION; INDUCIBLE PROTEIN-10; EXTRACELLULAR-MATRIX; KINASE-ACTIVITY; T-LYMPHOCYTES; EGF RECEPTOR; FIBROBLAST; PROTEASE; ADHESION; MOVEMENT AB During wound healing, fibroblasts are recruited from the surrounding tissue to accomplish repair. The requisite migration and proliferation of the fibroblasts is promoted by growth factors including those that activate the epidermal growth factor receptor (EGFR), Counterstimulatory factors in wound fluid are postulated to limit this response; among these factors is the ELR-negative CXC chemokine, interferon inducible protein-10 (IP-10),We report here that IP-10 inhibited EGF- and heparin-binding EGF-like growth factor-induced Hs68 human dermal fibroblast motility in a dose-dependent manner (to 52% and 44%, respectively, at 50 ng/ml IP-10), whereas IP-10 had no effect on either basal or EGFR-mediated mitogenesis (96 +/- 15% at 50 ng/ml). These data demonstrate for the first time a counterstimulatory effect of IP-10 on a specific induced fibroblast response, EGFR-mediated motility. To define the molecular basis of this negative transmodulation of EGFR signaling, we found that IP-10 did not adversely impact receptor or immediate postreceptor signaling as determined by tyrosyl phosphorylation of EGFR and two major downstream effecters phospholipase C-gamma and erk mitogen-activated protein kinases, Morphological studies suggested which biophysical steps may be affected by demonstrating that IP-10 treatment resulted in an elongated cell morphology reminisce:nt of failure to detach the uropod; in support of this, IP-10 pretreatment inhibited EGF-induced cell detachment. These data suggested that calpain activity may be involved. The cell permeant agent, calpain inhibitor I, limited EGF-induced motility and de-adhesion similarly to IP-10, IP-10 also prevented EGF induced calpain activation (reduced by 71 +/- 7%).That this inhibition of EGF-induced calpain activity was secondary to IP-10 initiating a cAMP-protein kinase A-calpain cascade is supported by the following evidence: (a:) the cell permeant analogue 8-(4-chlorophenylthio)-cAMP (CPT-cAMP) prevented EGF-induced calpain activity and motility; (b) other ELR-negative CXC chemokines, monokine induced by IFN-gamma and platelet factor 4 that also generate cAMP, inhibited EGF-induced cell migration and calpain activation; and (c) the protein kinase A inhibitor Rp-8-Br-cANIPS abrogated IP-10 inhibition of cell migration, cell detachment, and calpain activation. Our findings provide a model by which IP-10 suppresses EGF-induced cell motility by inhibiting EGF-induced detachment of the trailing edges of motile cells. C1 Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. RP Wells, A (reprint author), Univ Pittsburgh, Dept Pathol, Scaife 713, Pittsburgh, PA 15261 USA. OI Wells, Alan/0000-0002-1637-8150; Glading, Angela/0000-0002-1830-6601 FU NIGMS NIH HHS [R01 GM054739, GM54739] NR 43 TC 99 Z9 102 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUL 12 PY 1999 VL 146 IS 1 BP 243 EP 253 PG 11 WC Cell Biology SC Cell Biology GA 217QB UT WOS:000081509500019 PM 10402474 ER PT J AU Shao, ZH Raible, F Mollaaghababa, R Guyon, JR Wu, CT Bender, W Kingston, RE AF Shao, ZH Raible, F Mollaaghababa, R Guyon, JR Wu, CT Bender, W Kingston, RE TI Stabilization of chromatin structure by PRC1, a polycomb complex SO CELL LA English DT Article ID POLYMERASE-II TRANSCRIPTION; DROSOPHILA BITHORAX COMPLEX; CHROMOSOME-BINDING-SITES; HOMEOTIC GENE-EXPRESSION; GROUP PROTEINS; CAENORHABDITIS-ELEGANS; MEDIATED REPRESSION; GROUP PRODUCTS; MELANOGASTER; DOMAIN AB The Polycomb group (PcG) genes are required for maintenance of homeotic gene repression during development. Mutations in these genes can be suppressed by mutations in genes of the SWI/SNF family. We have purified a complex, termed PRC1 (Polycomb repressive complex 1), that contains the products of the PcG genes Polycomb, Posterior sex combs, polyhomeotic, Sex combs on midleg, and several other proteins. Preincubation of PRC1 with nucleosomal arrays blocked the ability of these arrays to be remodeled by SWI/SNF. Addition of PRC1 to arrays at the same time as SWI/SNF did not block remodeling. Thus, PRC1 and SWI/SNF might compete with each other for the nucleosomal template. Several different types of repressive complexes, including deacetylases, interact with histone tails. In contrast, PRC1 was active on nucleosomal arrays formed with tailless histones. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RI Raible, Florian/G-6019-2011 NR 53 TC 526 Z9 540 U1 3 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUL 9 PY 1999 VL 98 IS 1 BP 37 EP 46 DI 10.1016/S0092-8674(00)80604-2 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 216PL UT WOS:000081451000006 PM 10412979 ER PT J AU Wu, ZD Puigserver, P Andersson, U Zhang, CY Adelmant, G Mootha, V Troy, A Cinti, S Lowell, B Scarpulla, RC Spiegelman, BM AF Wu, ZD Puigserver, P Andersson, U Zhang, CY Adelmant, G Mootha, V Troy, A Cinti, S Lowell, B Scarpulla, RC Spiegelman, BM TI Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1 SO CELL LA English DT Article ID BROWN ADIPOSE-TISSUE; UNCOUPLING PROTEIN HOMOLOG; DIET-INDUCED THERMOGENESIS; ACTIVATED RECEPTOR-GAMMA; SKELETAL-MUSCLE; TRANSCRIPTION FACTOR; DNA-BINDING; GENE-EXPRESSION; NUCLEAR; OBESITY AB Mitochondrial number and function are altered in response to external stimuli in eukaryotes. While several transcription/replication factors directly regulate mitochondrial genes, the coordination of these factors into a program responsive to the environment is not understood. We show here that PGC-1, a cold-inducible coactivator of nuclear receptors, stimulates mitochondrial biogenesis and respiration in muscle cells through an induction of uncoupling protein 2 (UCP-2) and through regulation of the nuclear respiratory factors (NRFs). PGC-1 stimulates a powerful induction of NRF-1 and NRF-5 gene expression; in addition, PGC-1 binds to and coactivates the transcriptional function of NRF-1 on the promoter for mitochondrial transcription factor A (mtTFA), a direct regulator of mitochondrial DNA replication/transcription. These data elucidate a pathway that directly links external physiological stimuli to the regulation of mitochondrial biogenesis and function. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Northwestern Univ, Sch Med, Dept Cell & Mol Biol, Chicago, IL 60611 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol & Metab, Boston, MA 02115 USA. Univ Ancona, Fac Med & Chirurg, Ist Morfol Umana Normale Anat, I-60020 Ancona, Italy. RP Spiegelman, BM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK54477]; NIGMS NIH HHS [GM32525] NR 44 TC 1956 Z9 2041 U1 17 U2 157 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUL 9 PY 1999 VL 98 IS 1 BP 115 EP 124 DI 10.1016/S0092-8674(00)80611-X PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 216PL UT WOS:000081451000013 PM 10412986 ER PT J AU Stanislaus, R Pahan, K Singh, AK Singh, I AF Stanislaus, R Pahan, K Singh, AK Singh, I TI Amelioration of experimental allergic encephalomyelitis in Lewis rats by lovastatin SO NEUROSCIENCE LETTERS LA English DT Article DE experimental allergic encephalomyelitis; tumor necrosis factor-alpha; interferon-gamma; inducible nitric oxide synthase; lovastatin; Lewis rats ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; NITRIC-OXIDE SYNTHASE; CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; INDUCTION; CYTOKINES; MICE; DEMYELINATION; EXPRESSION; ALPHA AB Proinflammatory cytokines and inducible nitric oxide synthase (iNOS) are involved in the pathogenesis of experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). We have previously reported that lovastatin (Pahan, K., Sheikh., F.G., Namboodiri, A. and Singh, I., Lovastatin and Phenylacetate inhibit the induction of nitric oxide synthase and cytokines in rat primary astrocytes, microglia and macrophages. J. Clin. Invest., 100 (1997) 2671-2679.), an inhibitor of the mevalonate pathway, inhibits the expression of iNOS and proinflammatory cytokines in rat primary glial cells (astroglia and microglia) and macrophages. The present study underlines the therapeutic importance of lovastatin in ameliorating the neuroinflammatory disease process in the central nervous system of EAE rats. Immunohistochemical results show a higher degree of expression of iNOS, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in brains of rats with acute monophasic EAE relative to the control animals. Administration of lovastatin inhibited the expression of iNOS, TNF-alpha and IFN-gamma in the CNS of EAE rats and improved the clinical signs of EAE suggesting that this compound may have therapeutic potential in the treatment of neuroinflammatory diseases like MS. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Ralph H Johnson VA Med Ctr, Dept Pathol & Lab Med, Charleston, SC 29425 USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, 171 Ashley Ave, Charleston, SC 29425 USA. FU NINDS NIH HHS [NS-22576, NS-34741, NS-37766] NR 15 TC 123 Z9 128 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUL 9 PY 1999 VL 269 IS 2 BP 71 EP 74 DI 10.1016/S0304-3940(99)00414-0 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 211VE UT WOS:000081181900004 PM 10430507 ER PT J AU Tao, T Gong, BJ Grabarek, Z Gergely, J AF Tao, T Gong, BJ Grabarek, Z Gergely, J TI Conformational changes induced in troponin I by interaction with troponin T and actin/tropomyosin SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE striated muscle; Ca2+; troponin subunit; conformation; actin; chymotryptic digestion ID RABBIT SKELETAL-MUSCLE; THIN FILAMENT; TROPOMYOSIN-TROPONIN; ANGSTROM RESOLUTION; BIOLOGICAL-ACTIVITY; CRYSTAL-STRUCTURE; CA2+ REGULATION; COMPLEX; CALCIUM; CONTRACTION AB Troponin I (TnI) is the inhibitory component of the striated muscle Ca2+ regulatory protein troponin (Tn). The other two components of Tn are troponin C (TnC), the Ca2+-binding component, and troponin T (TnT), the tropomyosin-binding component. We have used limited chymotryptic digestion to probe the local conformation of TnI in the free state, the binary TnC TnI complex, the ternary TnC TnI TnT (Tn) complex, and in the reconstituted Tn tropomyosin F-actin filament. The digestion of TnI alone or in the TnC TnI complex produced initially two major fragments via a cleavage of the peptide bond between Phe100 and Asp101 in the so-called inhibitory region. In the ternary Tn complex cleavage occurred at a new site between Leu140 and Lys141. In the absence of Ca2+ this was followed by digestion of the 1-140 fragment at Leu122 and Met116. In the reconstituted thin filament the same fragments as in the case of the ternary complex were produced, but the rate of digestion was slower in the absence than in the presence of Ca2+. These results indicate firstly that in both free TnI and TnI complexed with TnC there is an exposed and flexible site in the inhibitory region. Secondly, TnT affects the conformation of TnI in the inhibitory region and also in the region that contains the 140-141 bond. Thirdly, the 140-141 region of TnI is likely to interact with actin in the reconstituted thin filament when Ca2+ is absent. These findings are discussed in terms of the role of TnI in the mechanism of thin filament regulation, and in light of our previous results [Y. Luo, J.-L. Wu, J. Gergely, T. Tao, Biochemistry 36 (1997) 13449-13454] on the global conformation of TnI. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Boston Biomed Res Inst, Muscle Res Grp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Gergely, J (reprint author), Boston Biomed Res Inst, Muscle Res Grp, 20 Staniford St, Boston, MA 02114 USA. OI Grabarek, Zenon/0000-0002-3636-5701 FU NCRR NIH HHS [RR11301]; NIAMS NIH HHS [AR21673] NR 54 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD JUL 8 PY 1999 VL 1450 IS 3 BP 423 EP 433 DI 10.1016/S0167-4889(99)00050-6 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 218LV UT WOS:000081554800021 PM 10395953 ER PT J AU Catlin, EA Roberts, JD Erana, R Preffer, FI Ferry, JA Kelliher, AS Atkins, L Weinstein, HJ AF Catlin, EA Roberts, JD Erana, R Preffer, FI Ferry, JA Kelliher, AS Atkins, L Weinstein, HJ TI Transplacental transmission of natural-killer-cell lymphoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HLA C1 Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Neonatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Weinstein, HJ (reprint author), Massachusetts Gen Hosp, Div Hematol & Oncol, Blake 2,55 Fruit St, Boston, MA 02114 USA. NR 19 TC 47 Z9 50 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 JUL 8 PY 1999 VL 341 IS 2 BP 85 EP 91 DI 10.1056/NEJM199907083410204 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 214ET UT WOS:000081316200004 PM 10395632 ER PT J AU Quesnel, S Verselis, S Portwine, C Garber, J White, M Feunteun, J Malkin, D Li, FP AF Quesnel, S Verselis, S Portwine, C Garber, J White, M Feunteun, J Malkin, D Li, FP TI p53 compound heterozygosity in a severely affected child with Li-Fraumeni Syndrome SO ONCOGENE LA English DT Article DE Li-Fraumeni Syndrome; p53; germline mutations; functional assays ID WILD-TYPE P53; TUMOR-SUPPRESSOR P53; CYCLIN-DEPENDENT KINASES; CANCER FAMILY SYNDROME; SOFT-TISSUE SARCOMA; GENE-MUTATIONS; CELL-LINES; GROWTH SUPPRESSION; ANTICANCER AGENTS; BREAST-CANCER AB The Li-Fraumeni Syndrome (LFS) is a rare, dominantly inherited syndrome that features high risk of cancers in childhood and early adulthood. Affected families tend to develop bone and soft tissue sarcomas, breast cancers, brain tumors, leukemias, and adrenocortical carcinomas. In some kindreds, the genetic abnormality associated with this cancer phenotype is a heterozygous germline mutation in the p53 tumor suppressor gene. Recently, we identified one patient who presented in early childhood with multiple primary cancers and who harbored three germline p53 alterations (R156H and R267Q on the maternal allele and R290H on the paternal allele), To classify the biologic effects of these alterations, functional properties of each of the p53 mutants were examined using in vitro assays of cellular growth suppression and transcriptional activation. Each amino acid substitution conferred partial or complete loss of wild-type p53 function, but the child completed normal embryonic development. This observation has not been previously reported in a human, but is consistent with observations of normal embryogenesis in p53-deficient mice. C1 Hosp Sick Children, Div Oncol, Toronto, ON M5G 1X8, Canada. Dana Farber Canc Inst, Div Human Canc Genet, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. OncorMed Inc, Gaithersburg, MD 20877 USA. Inst Gustave Roussy, Mol Oncol Lab, F-75016 Villejuif, France. RP Malkin, D (reprint author), Hosp Sick Children, Div Oncol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. NR 68 TC 20 Z9 21 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 8 PY 1999 VL 18 IS 27 BP 3970 EP 3978 DI 10.1038/sj.onc.1202783 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 214KU UT WOS:000081327800007 PM 10435620 ER PT J AU Burman, ML Taplin, SH Herta, DF Elmore, JG AF Burman, ML Taplin, SH Herta, DF Elmore, JG TI Effect of false-positive mammograms on interval breast cancer screening in a health maintenance organization SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE mammography; false-positive reactions; patient compliance; age factors; mass screening ID WOMEN; PROGRAM; RISK AB Background: Despite the mortality benefits of breast cancer screening, not all women receive regular mammography. Such factors as age, socioeconomic status, and physician recommendation have been associated with greater use of screening. However, we do not know whether having an abnormal mammogram affects future screening. Objective: To examine the effect of a false-positive mammogram on adherence to the next recommended screening mammogram. Design: Prospective cohort study. Setting: The breast cancer screening program at Group Health Cooperative, a health maintenance organization in Washington state. Patients: 5059 women 40 years of age or older with no history of breast cancer or breast surgery who had false-positive (n = 813) or true-negative (n = 4246) index screening mammograms between 1 August 1990 and 31 July 1992. Measurements: Screening rates and odds ratios for recommended interval screening up to 42 months after the index mammogram. Results: After adjustment for differences in age; previous use of mammography; family history of breast cancer; exogenous hormone use; and age at menarche, first childbirth, and menopause, women with false-positive index mammograms were more likely than those with true-negative index mammograms to obtain their next recommended screening mammogram (odds ratio, 1.21 [95% CI, 1.01 to 1.45]). The relation between a false-positive mammogram and the likelihood of adherence to screening in the next recommended interval was strongest among women who had not previously undergone mammography (odds ratio, 1.66 [CI, 1.26 to 2.17]). Conclusions: Having a false-positive mammogram did not adversely affect screening behavior in the next recommended interval. Women with false-positive mammograms, especially those without previous mammography, were more likely to return for the next scheduled screening. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98108 USA. Grp Hlth Cooperat Puget Sound, Dept Prevent Care, Seattle, WA 98101 USA. Univ Washington, Sch Med, Div Gen Internal Med, Dept Med, Seattle, WA 98195 USA. RP Burman, ML (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, 1660 S Columbian Way,Mailstop 152, Seattle, WA 98108 USA. FU NCI NIH HHS [CA6371] NR 26 TC 64 Z9 64 U1 1 U2 4 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 6 PY 1999 VL 131 IS 1 BP 1 EP + PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 214UD UT WOS:000081345200001 PM 10391809 ER PT J AU Woolf, CJ Costigan, M AF Woolf, CJ Costigan, M TI Transcriptional and posttranslational plasticity and the generation of inflammatory pain SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT National-Academy-of-Sciences Colloguium on the Neurobiology of Pain CY DEC 11-13, 1998 CL IRVINE, CALIFORNIA ID PRIMARY SENSORY NEURONS; DORSAL-ROOT GANGLION; NERVE GROWTH-FACTOR; RAT SPINAL-CORD; PROGRESSIVE TACTILE HYPERSENSITIVITY; PROTEIN-KINASE-C; PERIPHERAL INFLAMMATION; CENTRAL SENSITIZATION; HORN NEURONS; MECHANICAL HYPERALGESIA AB Inflammatory pain manifests as spontaneous pain and pain hypersensitivity. Spontaneous pain reflects direct activation of specific receptors on nociceptor terminals by inflammatory mediators. Pain hypersensitivity is the consequence of early posttranslational changes, both in the peripheral terminals of the nociceptor and in dorsal horn neurons, as well as later transcription-dependent changes in effector genes, again in primary sensory and dorsal horn neurons. This inflammatory neuroplasticity is the consequence of a combination of activity-dependent changes in the neurons and specific signal molecules initiating particular signal-transduction pathways. These pathways phosphorylate membrane proteins, changing their function, and activate transcription factors, altering gene expression. Two distinct aspects of sensory neuron function are changed as a result of these processes, basal sensitivity, or the capacity of peripheral stimuli to evoke pain, and stimulus-evoked hypersensitivity, the capacity of certain inputs to generate prolonged alterations in the sensitivity of the system. Posttranslational changes largely alter basal sensitivity. Transcriptional changes bath potentiate the system and alter neuronal phenotype, Potentiation occurs as a result of the up-regulation in the dorsal root ganglion of centrally acting neuromodulators and simultaneously in the dorsal horn of their receptors. This means that the response to subsequent inputs is augmented, particularly those that induce stimulus-induced hypersensitivity, Alterations in phenotype includes the acquisition by A fibers of neurochemical features typical of C fibers, enabling these fibers to induce stimulus-evoked hypersensitivity, something only C fiber inputs normally can do. Elucidation of the molecular mechanisms responsible provides new opportunities for therapeutic approaches to managing inflammatory pain. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp E, Charlestown, MA 02129 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, 149 13th St,Room 4310, Charlestown, MA 02129 USA. FU NINDS NIH HHS [R01 NS38253-01, R01 NS038253] NR 82 TC 352 Z9 365 U1 0 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 6 PY 1999 VL 96 IS 14 BP 7723 EP 7730 DI 10.1073/pnas.96.14.7723 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 214RV UT WOS:000081342100025 PM 10393888 ER PT J AU She, JX Ellis, TM Wilson, SB Wasserfall, CH Marron, M Reimsneider, S Kent, SC Hafler, DA Neuberg, DS Muir, A Strominger, JL Atkinson, MA AF She, JX Ellis, TM Wilson, SB Wasserfall, CH Marron, M Reimsneider, S Kent, SC Hafler, DA Neuberg, DS Muir, A Strominger, JL Atkinson, MA TI Heterophile antibodies segregate in families and are associated with protection from type 1 diabetes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FIRST-DEGREE RELATIVES; SUSCEPTIBILITY GENES; INSULIN; MELLITUS; IDDM; INTERFERENCE; IMMUNOASSAYS; SEARCH AB Markedly elevated levels of serum IL-4 were reported previously in 50% of a small group of type 1 diabetes nonprogessors, To determine the patterns of expression for this phenotype, a larger cohort of 58 families containing type 1 diabetic patients was examined. Analysis of the two-site ELISA assay used to measure serum IL-4 revealed evidence for heterophile antibodies, i.e., nonanalyte substances in serum capable of binding antibodies mutivalently and providing erroneous analyte (e.g,, IL-4) quantification, Interestingly, relatives without type 1 diabetes were significantly more likely to have this phenotype than were patients with the disease (P = 0.003), In addition, the trait appears to have clustered within certain families and was associated with the protective MBC allele DQB1*0602 (P = 0.008), These results suggest that heterophile antibodies represent an in vivo trait associated with self-tolerance and nonprogression to diabetes. C1 Univ Florida, Dept Pathol, Gainesville, FL 32610 USA. Univ Florida, Dept Immunol, Gainesville, FL 32610 USA. Univ Florida, Dept Lab Med, Gainesville, FL 32610 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Atkinson, MA (reprint author), Univ Florida, Dept Pathol, 100275 JHMHC, Gainesville, FL 32610 USA. RI wasserfall, clive/J-9078-2012 OI wasserfall, clive/0000-0002-3522-8932 FU NIAID NIH HHS [P01 AI042288, R01 AI/DK39250]; NICHD NIH HHS [R01 HD052127]; NIDDK NIH HHS [R01 DK 50220, R01 DK 53103] NR 20 TC 21 Z9 21 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 JUL 6 PY 1999 VL 96 IS 14 BP 8116 EP 8119 DI 10.1073/pnas.96.14.8116 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 214RV UT WOS:000081342100094 PM 10393957 ER PT J AU Yagi, M Ritchie, KA Sitnicka, E Storey, C Roth, GJ Bartelmez, S AF Yagi, M Ritchie, KA Sitnicka, E Storey, C Roth, GJ Bartelmez, S TI Sustained ex vivo expansion of hematopoietic stem cells mediated by thrombopoietin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TERM REPOPULATING ABILITY; MESSENGER-RNA EXPRESSION; EARLY ACTING CYTOKINES; MARROW STROMAL CELLS; BONE-MARROW; PROGENITOR CELLS; GROWTH-FACTOR; C-MPL; MICE; LIGAND AB The hematopoietic stem cell (HSC) is defined as a cell that can either self-replicate or generate daughter cells that are destined to commit to mature cells of different specific Lineages. Self-replication of the most primitive HSC produces daughter cells that possess a long (possibly unlimited) clonal lifespan, whereas differentiation of HSC produces daughter cells that demonstrate a progressive reduction of their clonal lifespan, a loss of multilineage potential, and lineage commitment. Previous studies indicated that the proliferation of HSC ex vivo favors differentiation at the expense of self-replication, eventually resulting in a complete Lass of HSC. In contrast, transplantation studies have shown that a single HSC can repopulate the marrow of lethally irradiated mouse, demonstrating that self-renewal of HSC occurs in vivo. Thrombopoietin (TPO) has been shown to function both as a proliferative and differentiative factor for megakaryocytes and as a survival and weakly proliferative factor for HSC. Our studies focused on the effects of exogenous TPO on HSC in mouse long-term bone marrow cultures (LTBMC). Previous results indicate that HSC decline in LTBMC in the absence of TPO. In contrast, the continuous presence of TPO resulted in the generation of both long- and short-term repopulating HSC: as detected by an in vivo competitive repopulation assay. HSC were generated over a 4-month period at concentrations similar to normal bone marrow. Our results demonstrate that TPD can mediate the self-replication of HSC in LTBMC, and provide proof that HSC can self-replicate ex vivo. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Dept Res, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Dept Pathol, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Dept Hematol, Seattle, WA 98108 USA. Univ Washington, Dept Med, Div Hematol, Seattle, WA 98195 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA. Seattle Biomed Res Inst, Seattle, WA 98109 USA. RP Roth, GJ (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Dept Res, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NHLBI NIH HHS [HL02959, HL39947]; NIDDK NIH HHS [DK48708] NR 46 TC 85 Z9 87 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 JUL 6 PY 1999 VL 96 IS 14 BP 8126 EP 8131 DI 10.1073/pnas.96.14.8126 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 214RV UT WOS:000081342100096 PM 10393959 ER PT J AU Narula, J Pandey, P Arbustini, E Haider, N Narula, N Kolodgie, FD Dal Bello, B Semigran, MJ Bielsa-Masdeu, A Dec, GW Israels, S Ballester, M Virmani, R Saxena, S Kharbanda, S AF Narula, J Pandey, P Arbustini, E Haider, N Narula, N Kolodgie, FD Dal Bello, B Semigran, MJ Bielsa-Masdeu, A Dec, GW Israels, S Ballester, M Virmani, R Saxena, S Kharbanda, S TI Apoptosis in heart failure: Release of cytochrome c from mitochondria and activation of caspase-3 in human cardiomyopathy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TUMOR-NECROSIS-FACTOR; CELL-DEATH; DILATED CARDIOMYOPATHY; PROLONGED ACTIVATION; CARDIAC MYOCYTES; FACTOR-ALPHA; HYPERTROPHY; PROTEASE; INHIBITION; KINASE AB Apoptosis has been shown to contribute to loss of cardiomyocytes in cardiomyopathy, progressive decline in left ventricular function,, and congestive heart failure, Because the molecular mechanisms involved in apoptosis of cardiocytes are not, completely understood, we studied the biochemical and ultrastructural characteristics of upstream regulators of apoptosis in hearts explanted from patients undergoing transplantation. Sixteen explanted hearts from patients undergoing heart transplantation were studied by electron microscopy or immunoblotting to detect release of mitochondrial cytochrome c and activation of caspase-3, The hearts explanted from five victims of motor vehicle accidents;or myocardial ventricular tissues from three donor hearts were used as controls, Evidence of apoptosis was observed only in endstage cardiomyopathy, There was significant accumulation of cytochrome c in the cytosol, over myofibrils, and near intercalated discs of cardiomyocytes in failing hearts. The release of mitochondrial cytochrome c was associated with activation of caspase-3 and cleavage of its substrate protein kinase C delta but not poly(ADP-ribose) polymerase. By contrast there was no apparent accumulation of cytosolic cytochrome c or caspase-3 activation in the hearts used as controls, The present study provides irt vivo evidence of cytochrome c-dependent activation of cysteine proteases in human cardiomyopathy. Activation of proteases supports the phenomenon of apoptosis in myopathic process. Because loss of myocytes contributes to myocardial dysfunction and is a predictor of adverse outcomes in the patients with congestive heart failure, the present demonstration of an activated apoptotic cascade in cardiomyopathy could-provide the basis for novel interventional strategies. C1 Med Coll Penn & Hahnemann Univ, Sch Med, Philadelphia, PA 19102 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Inst Pathol Anat, I-27100 Pavia, Italy. Armed Forces Inst Pathol, Washington, DC 20306 USA. Hosp St Pau, Barcelona 08025, Spain. Univ Manitoba, Winnipeg, MB R3E 0V9, Canada. RP Narula, J (reprint author), Hahnemann Univ Hosp, Heart Failure Transplant Ctr, Broad & Vine St,Mail Stop 115, Philadelphia, PA 19102 USA. OI Israels, Sara/0000-0002-1849-4825 FU NCI NIH HHS [CA 75216] NR 43 TC 426 Z9 434 U1 0 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 6 PY 1999 VL 96 IS 14 BP 8144 EP 8149 DI 10.1073/pnas.96.14.8144 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 214RV UT WOS:000081342100099 PM 10393962 ER PT J AU Schust, DJ Tortorella, D Seebach, J Phan, C Bacik, I Bennink, JR Yewdell, JW Ploegh, HL AF Schust, DJ Tortorella, D Seebach, J Phan, C Bacik, I Bennink, JR Yewdell, JW Ploegh, HL TI Trophoblast class I major histocompatibility complex (MHC) products are resistant to rapid degradation imposed by the human cytomegalovirus (HCMV) gene products US2 and US11 (vol 188, pg 497, 1998) SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Correction C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02119 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Schust, DJ (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012; OI Tortorella, Domenico/0000-0003-0961-3535 NR 1 TC 0 Z9 0 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 5 PY 1999 VL 190 IS 1 BP 151 EP 151 PG 1 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 215RW UT WOS:000081397500016 ER PT J AU Grundhoff, AT Kremmer, E Turecin, O Glieden, A Gindorf, C Atz, J Mueller-Lantzsch, N Schubach, WH Grasser, FA AF Grundhoff, AT Kremmer, E Turecin, O Glieden, A Gindorf, C Atz, J Mueller-Lantzsch, N Schubach, WH Grasser, FA TI Characterization of DP103, a novel DEAD box protein that binds to the Epstein-Barr virus nuclear proteins EBNA2 and EBNA3C SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LATENT MEMBRANE-PROTEIN; RBP-J-KAPPA; RNA-DEPENDENT ATPASE; BIOCHEMICAL-CHARACTERIZATION; HODGKINS-DISEASE; HELICASE GENE; POLYMERASE-II; EXPRESSION; PROMOTER; TRANSCRIPTION AB The Epstein-Barr virus-encoded nuclear antigens EBNA2 and EBNA3C both interact with the cellular transcription factor RBP-JK and modulate the expression of several shared target genes, suggesting a tight cooperation in latently infected cells. In a survey for additional cellular factors that bind to EBNA2 as well as EBNA3C, we have isolated and characterized DP1031 a novel human member of the DEAD box family of putative ATP-dependent RNA helicases, The interaction with DP103 is mediated by amino acids (aa) 121-213 of EBNA2 and aa 534-778 of EBNA3C, regions that are not involved in binding of the viral proteins to RBP-JK, The DP103-cDNA encodes a protein of 824 aa that harbors all of the common DEAD box motifs, Monoclonal antibodies raised against DP103 detect a protein of 103 kDa in mammalian cells that resides in high molecular weight complexes in vivo. We have detected an ATPase activity intrinsic to or closely associated with DP103, By subcellular fractionation, we find DP103 in both a soluble nuclear fraction as well as in the insoluble skeletal fraction. Whereas the protein and its mRNA are uniformly expressed in all tested cell lines, we observed differential expression of the mRNA. in normal human tissues. C1 Univ Kliniken Saarlandes, Abt Virol, Inst Med Mikrobiol & Hyg, D-66421 Homburg, Germany. GSF, Inst Mol Immunol, D-81377 Munich, Germany. Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Oncol, Seattle, WA 98108 USA. RP Grasser, FA (reprint author), Univ Kliniken Saarlandes, Abt Virol, Inst Med Mikrobiol & Hyg, D-66421 Homburg, Germany. NR 62 TC 81 Z9 88 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 JUL 2 PY 1999 VL 274 IS 27 BP 19136 EP 19144 DI 10.1074/jbc.274.27.19136 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 212BK UT WOS:000081196300041 PM 10383418 ER PT J AU Westphal, RS Tavalin, SJ Lin, JW Alto, NM Fraser, IDC Langeberg, LK Sheng, M Scott, JD AF Westphal, RS Tavalin, SJ Lin, JW Alto, NM Fraser, IDC Langeberg, LK Sheng, M Scott, JD TI Regulation of NMDA receptors by an associated phosphatase-kinase signaling complex SO SCIENCE LA English DT Article ID DEPENDENT PROTEIN-KINASE; D-ASPARTATE RECEPTORS; POSTSYNAPTIC DENSITY; ANCHORING PROTEIN; SUBUNIT NR1; PDZ-DOMAIN; BINDING; SCAFFOLD; CHANNEL; IDENTIFICATION AB Regulation of N-methyl-D-aspartate (NMDA) receptor activity by kinases and phosphatases contributes to the modulation of synaptic transmission. Targeting of these enzymes near the substrate is proposed to enhance phosphorylation-dependent modulation. Yotiao, an NMDA receptor-associated protein, bound the type I protein phosphatase (PP1) and the adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase (PKA) holoenzyme. Anchored PP1 was active, limiting channel activity, whereas PKA activation overcame constitutive PP1 activity and conferred rapid enhancement of NMDA receptor currents. Hence, yotiao is a scaffold protein that physically attaches PP1 and PKA to NMDA receptors to regulate channel activity. C1 Oregon Hlth Sci Univ, Vollum Inst, Howard Hughes Med Inst, Portland, OR 97201 USA. Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Scott, JD (reprint author), Oregon Hlth Sci Univ, Vollum Inst, Howard Hughes Med Inst, 3181 SW Sam Jackson Rd, Portland, OR 97201 USA. FU NIGMS NIH HHS [GM 48231]; NINDS NIH HHS [F32 NS010202, NS10202, NS10543] NR 50 TC 379 Z9 390 U1 0 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUL 2 PY 1999 VL 285 IS 5424 BP 93 EP 96 DI 10.1126/science.285.5424.93 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 212CY UT WOS:000081199800037 PM 10390370 ER PT J AU Rutherford, GW Gerrity, TR Kizer, KW Feussner, JR AF Rutherford, GW Gerrity, TR Kizer, KW Feussner, JR TI Research in the veterans health administration: The report of the Research Realignment Advisory Committee SO ACADEMIC MEDICINE LA English DT Article ID CARE SYSTEM; VA; AFFAIRS; FUTURE AB In 1995 the Under Secretary for Health of the Department of Veterans Affairs constituted the Research Realignment Advisory Committee and-charged it with reviewing the VA's research program. After meeting in 1995 and 1996, the committee identified 12 findings, which fall into four broad categories: allocation,of research resources among VA research programs, acquisition and protection of resources, stability and maintenance of infrastructure, and outreach and communications. The most far-reaching recommendation was to establish designated research areas so that VA research could be focused more sharply on the specific needs of veterans while maintaining a research base for relatively less common conditions and needs: integral to the VA's mission. The second major issue was that research funding should be increased (because it had-fallen in inflation-adjusted dollars while the cost of doing research continued to rise). The third major area dealt with operational issues about how research was administered in the newly created system of geographically defined "veterans integrated service networks" and at the medical centers and how research monies flowed to medical centers. The final major area had to do with career development, for the committee considered the recruitment and retention of outstanding junior investigators to be a core function of VA research. The committee's recommendations, some of which have already been implemented, form the basis for strengthening the VA's research enterprise and for fully integrating it within the new structure of health care delivery in the VA. C1 Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. Vet Hlth Adm, Med Res Serv, Off Res & Dev, US Dept Vet Affairs, Washington, DC USA. RP Rutherford, GW (reprint author), Prevent Sci Grp, 74 New Montgomery St,Suite 600, San Francisco, CA 94105 USA. NR 24 TC 3 Z9 3 U1 1 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUL PY 1999 VL 74 IS 7 BP 773 EP 781 DI 10.1097/00001888-199907000-00010 PG 9 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 218CC UT WOS:000081534800011 PM 10429585 ER PT J AU Pahlavani, MA Vargas, DM AF Pahlavani, MA Vargas, DM TI Age-related decline in activation of calcium/calmodulin-dependent phosphatase calcineurin and kinase CAMK-IV in rat T cells. SO AGE LA English DT Meeting Abstract C1 Audie L Murphy Mem Vet Hosp, S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER AGING ASSOC PI MEDIA PA SALLY BALIN MEDICAL CENTER, 110 CHESLEY DR, MEDIA, PA 19063 USA SN 0161-9152 J9 AGE JI Age PD JUL PY 1999 VL 22 IS 3 MA 40 BP 126 EP 127 PG 2 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 289RD UT WOS:000085635000043 ER PT J AU Petrie, EC Pascualy, M Brodkin, K Peskind, ER Raskind, MA AF Petrie, EC Pascualy, M Brodkin, K Peskind, ER Raskind, MA TI Effects of advanced aging on plasma catecholamine responses to thermal stress SO AGE LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98195 USA. Univ Washington, Geriatr Res Educ & Clin Ctr, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER AGING ASSOC PI MEDIA PA SALLY BALIN MEDICAL CENTER, 110 CHESLEY DR, MEDIA, PA 19063 USA SN 0161-9152 J9 AGE JI Age PD JUL PY 1999 VL 22 IS 3 MA 57 BP 130 EP 131 PG 2 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 289RD UT WOS:000085635000058 ER PT J AU Harris, GJ Oscar-Berman, M Gansler, A Streeter, C Lewis, RF Ahmed, I Achong, D AF Harris, GJ Oscar-Berman, M Gansler, A Streeter, C Lewis, RF Ahmed, I Achong, D TI Hypoperfusion of the cerebellum and aging effects on cerebral cortex blood flow is abstinent alcoholics: A SPECT study SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcoholism; abstinence; SPECT; regional cerebral blood flow; cerebellum ID WHITE-MATTER; HUMAN BRAIN; ATROPHY; TOMOGRAPHY; GRAY; AGE; ASYMMETRIES; METABOLISM; DEFICITS; DISEASE AB Background: This study evaluated hypotheses concerning alcoholism, aging, and the relationship between cerebral hypoperfusion and residual deficits in the functioning of cerebellar and neocortical brain systems. Methods: The participants were 10 healthy abstinent alcoholics (9 men, 1 woman) and 12 nonalcoholic controls (10 men, 2 women) ranging in age from 35 to 67 years. Cerebral blood flow was observed through the use of regionally specific computer-derived quantitative analysis of single photon emission computed tomography (SPECT) perfusion images. Cerebellar perfusion was measured and compared with cerebral cortex perfusion in age-equivalent subgroups of alcoholics and controls (under 55 years; 55 years and over). Results: In abstinent alcoholics under age 55, cerebellar perfusion ratios were significantly reduced compared with the controls. In alcoholics asd nonalcoholic controls 55 years old and older, this relationship was reversed, probably as a result of diminished cortical perfusion with aging in the alcoholics and of cerebellar decline in the controls. Conclusions: The findings support hypotheses that the residual effects of alcoholism include cerebellar brain abnormalities and that aging combined with long-term alcoholism leads to cerebral cortical decline. C1 Massachusetts Gen Hosp, Radiol Comp Aided Diagnost Lab, Boston, MA 02114 USA. Tufts Univ, Sch Med, Dept Psychiat, New England Med Ctr, Boston, MA 02111 USA. Dept Vet Affairs Med Ctr, Psychol Serv, Boston, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. NIDA, Boston Vet Adm, Med Dev Res Unit, Boston, MA USA. Dept Vet Affairs Med Ctr, Boston, MA USA. Tufts Univ, Sch Med, Dept Radiol, New England Med Ctr, Boston, MA 02111 USA. Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. RP Harris, GJ (reprint author), Massachusetts Gen Hosp, Radiol Comp Aided Diagnost Lab, Zero Emerson Pl,3C, Boston, MA 02114 USA. FU NIAAA NIH HHS [R37-AA07112, R37 AA007112, K05 AA000219]; NIDA NIH HHS [R03-DA09480]; NINDS NIH HHS [R29-NS31338] NR 61 TC 11 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUL PY 1999 VL 23 IS 7 BP 1219 EP 1227 PG 9 WC Substance Abuse SC Substance Abuse GA 219RB UT WOS:000081619600013 PM 10443989 ER PT J AU Kovacs, TOG Campbell, D Richter, J Haber, M Jennings, DE Rose, P AF Kovacs, TOG Campbell, D Richter, J Haber, M Jennings, DE Rose, P TI Double-blind comparison of lansoprazole 15 mg, lansoprazole 30 mg and placebo as maintenance therapy in patients with healed duodenal ulcers resistant to H-2-receptor antagonists SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID SYMPTOM RELIEF; OMEPRAZOLE; RANITIDINE; PREVENTION; TRIAL AB Background: Maintenance antisecretory therapy is often used to prevent duodenal ulcer recurrence and control symptoms. This study compared the efficacy and safety of lansoprazole 15 mg and 30 mg daily with placebo in preventing ulcer recurrence in patients with a recent history of duodenal ulcer disease. Methods: Fifty-six patients were treated with either lansoprazole 15 mg, 30 mg or placebo o.m. Results: Within 1 month of study initiation. 27% (four out of 15) of placebo-treated patients experienced ulcer recurrence as compared to 13% (two out of 15) and 6% (one out of 18) of lansoprazole 15 mg and 30 mg treated patients, respectively. Median time to first ulcer recurrence was > 12 months in lansoprazole patients. At Month 12, significantly (P < 0.001) more lansoprazole 15 mg patients (70%) and lansoprazole 30 mg patients (85%) remained healed. Eighty-two per cent of lansoprazole 15 mg and 76% of lansoprazole 30 mg patients remained asymptomatic during the entire study period. All placebo patients became symptomatic, experienced ulcer recurrence, or withdrew from the study by month six. The incidence of adverse events was comparable among the three treatment groups. Conclusions: Lansoprazole safely and effectively reduces duodenal ulcer recurrence and ulcer-related symptoms. C1 W Los Angeles Vet Affairs Med Ctr, Ctr Ulcer Res & Educ, Los Angeles, CA 90073 USA. Kansas City Vet Adm Med Ctr, Kansas City, MO 64128 USA. Cleveland Clin, Dept Gastroenterol, Cleveland, OH 44106 USA. Allegheny Univ Hlth Sci, Dept Pathol, Philadelphia, PA 19102 USA. TAP Holdings, Deerfield, IL USA. RP Kovacs, TOG (reprint author), W Los Angeles Vet Affairs Med Ctr, Ctr Ulcer Res & Educ, 11301 Wilshire Blvd,Bldg 115,Room 212, Los Angeles, CA 90073 USA. NR 28 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 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD JUL PY 1999 VL 13 IS 7 BP 959 EP 967 PG 9 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 220QH UT WOS:000081677800017 PM 10383532 ER PT J AU Solomon, PR Adams, FA Groccia, ME DeVeaux, R Growdon, JH Pendlebury, WW AF Solomon, PR Adams, FA Groccia, ME DeVeaux, R Growdon, JH Pendlebury, WW TI Correlational analysis of five commonly used measures of mental status/functional abilities in patients with Alzheimer disease SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE Alzheimer disease; mental status testing ID STATE; SCALE AB There are multiple assessment techniques to help clinicians diagnose, stage, and measure the rate of progression in Alzheimer disease (AD). We analyzed retrospectively the relationship between scores on commonly used scales and tests (Mini-Mental State, the Blessed Information-Memory-Concentration Test, the Alzheimer's Dis ease Assessment Scale-cognitive portion, the Activities of Daily Living Scale, and the Global Deterioration Scale) of 100 successive admissions to a memory clinic. Patients were included in the study if they were diagnosed subsequently with probable AD and if all five measures were administered in the same day. Regression analysis yielded 20 linear equations that allowed for conversion between test scores on any two instruments. With the exception of the Activities of Daily Living Scale (intercorrelation range with the other four instruments, r = 0.56-0.66), intercorrelations were generally high (r = 0.81-0.87). The results of this study should provide a clinically useful tool for converting test scores on five commonly used dementia screening/rating instruments. C1 Williams Coll, Bronfman Sci Ctr, Dept Psychol, Williamstown, MA 01267 USA. Williams Coll, Program Neurosci, Williamstown, MA 01267 USA. Williams Coll, Dept Math, Williamstown, MA 01267 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. Univ Vermont, Coll Med, Dept Neurol, Burlington, VT USA. SW Vermont Med Ctr, Memory Clin, Bennington, VT USA. RP Solomon, PR (reprint author), Williams Coll, Bronfman Sci Ctr, Dept Psychol, Williamstown, MA 01267 USA. FU NIA NIH HHS [AG-01534-0852] NR 9 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD JUL-SEP PY 1999 VL 13 IS 3 BP 147 EP 150 DI 10.1097/00002093-199907000-00006 PG 4 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 268NT UT WOS:000084423000006 PM 10485573 ER PT J AU Rao, PM Rhea, JT Rao, JA Conn, AKT AF Rao, PM Rhea, JT Rao, JA Conn, AKT TI Plain abdominal radiography in clinically suspected appendicitis: Diagnostic yield, resource use, and comparison with CT SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE appendix; appendicitis; plain abdominal radiography; CT ID EMERGENCY AB This study determined the diagnostic utility and hospital resource impact of plain abdominal radiography in emergency department patients with suspected appendicitis, The authors reviewed medical records of 821 consecutive patients hospitalized for suspected appendicitis; 78% had plain abdominal radiography. Sixty-four percent had appendicitis. Radiographic findings were noted in 51% of patients with, and 47% of patients without appendicitis; no individual radiographic finding was sensitive or specific. Specific conditions were suggested in 10% of impressions; these failed to correlate with final clinical diagnoses 57% of the time, Hospital cost per abdominal radiograph was $67; cost per specific, correct radiographic diagnosis was $1,593, This is compared with $270 per appendiceal computed tomography scan (based on recent literature data). The authors conclude that plain abdominal radiographs in patients with suspected appendicitis are neither sensitive nor specific, are frequently misleading, are costly per specific and correct diagnosis, and should not be routinely obtained on patients with suspected appendicitis. Copyright (C) 1999 by W.B. Saunders Company. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Rao, PM (reprint author), Sparrow Hosp, Dept Radiol, Lansing, MI 48909 USA. NR 15 TC 29 Z9 31 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD JUL PY 1999 VL 17 IS 4 BP 325 EP 328 DI 10.1016/S0735-6757(99)90077-3 PG 4 WC Emergency Medicine SC Emergency Medicine GA 223JC UT WOS:000081837100001 PM 10452424 ER PT J AU Brugge, WR AF Brugge, WR TI Endoscopic ultrasound staging of esophageal cancer: Assuming responsibility SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Editorial Material ID FINE-NEEDLE ASPIRATION; LYMPH-NODE; CARCINOMA; ENDOSONOGRAPHY; SURGERY; ULTRASONOGRAPHY; CLASSIFICATION C1 Massachusetts Gen Hosp, Gastrointestinal Endoscopy Unit, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, Gastrointestinal Endoscopy Unit, 55 Fruit St,Blake 452C, Boston, MA 02114 USA. NR 27 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JUL PY 1999 VL 94 IS 7 BP 1724 EP 1727 DI 10.1111/j.1572-0241.1999.01724.x PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 212NW UT WOS:000081224000003 PM 10406227 ER PT J AU Stewart, JE Strack, S Graves, P AF Stewart, JE Strack, S Graves, P TI Self-efficacy, outcome expectancy, dental health value, and dental plaque SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Article AB Objective: This study measured the independent contributions of self-efficacy, outcome expectations, and dental health value in predicting an objective measure of preventive oral hygiene behavior, dental plaque, Methods: One hundred forty-eight subjects completed study measures and then had their dental plaque levels measured, Results: Structural equation modeling revealed that self-efficacy for flossing significantly predicted plaque levels but self-efficacy for brushing, outcome expectations, and dental value did not. Conclusion: Results supported Bandura's belief that self-efficacy for specific behavior can predict outcomes of that behavior, and outcome expectations and value beliefs do not play an independent role in explaining behavior. C1 US Dept Vet Affairs, Outpatient Clin, Dent Serv, Los Angeles, CA 90012 USA. US Dept Vet Affairs, Outpatient Clin, Psychol Serv, Los Angeles, CA 90012 USA. RP Stewart, JE (reprint author), US Dept Vet Affairs, Outpatient Clin, Dent Serv, 351 E Temple St, Los Angeles, CA 90012 USA. NR 29 TC 5 Z9 5 U1 2 U2 6 PU PNG PUBLICATIONS PI STAR CITY PA PO BOX 4593, STAR CITY, WV 26504-4593 USA SN 1087-3244 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PD JUL-AUG PY 1999 VL 23 IS 4 BP 303 EP 310 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 209PN UT WOS:000081057100008 ER PT J AU Boon, LM Brouillard, P Irrthum, A Karttunen, L Warman, ML Rudolph, R Mulliken, JB Olsen, BR Vikkula, M AF Boon, LM Brouillard, P Irrthum, A Karttunen, L Warman, ML Rudolph, R Mulliken, JB Olsen, BR Vikkula, M TI A gene for inherited cutaneous venous anomalies ("glomangiomas") localizes to chromosome 1p21-22 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID RECEPTOR TYROSINE KINASE; MULTIPLE GLOMANGIOMAS; BINDING-PROTEIN; TIE2 RECEPTOR; TISSUE FACTOR; ANGIOPOIETIN-1; ANGIOGENESIS; MALFORMATIONS; EXPRESSION; MUTATION AB Venous malformations (VMs) are localized defects of vascular morphogenesis. They can occur in every organ system, most commonly in skin and muscle. They can cause pain and bleeding, and in some critical locations they can be life threatening. Usually venous anomalies occur sporadically, but families with dominant inheritance have been identified. Using linkage analysis, we have established in earlier reports that some families with inherited VMs show linkage to chromosome 9p21; the mutation causes ligand-independent activation of an endothelial cell-specific receptor tyrosine kinase, TIE-2. Here we show that VMs with glomus cells (known as "glomangiomas"), inherited as an autosomal dominant trait in five families, are not linked to 9p21 but, instead, link to a new locus, on 1p21-p22, called "VMGLOM" (LOD score 12.70 at recombination fraction .00). We exclude three known positional candidate genes, DR1 (depressor of transcription 1), TGFBR3 (transforming growth factor-beta receptor, type 3), and TFA (tissue factor). We hypothesize that cutaneous venous anomalies (i.e., glomangiomas) are caused by mutations in a novel gene that may act to regulate angiogenesis, in concert with the TIE-2 signaling pathway. C1 Catholic Univ Louvain, B-3000 Louvain, Belgium. Catholic Univ Louvain, Clin Univ St Luc, Div Plast Surg, Ctr Vasc Anomalies, B-1348 Louvain, Belgium. Harvard Univ, Sch Med, Dept Cell Biol, Cambridge, MA 02138 USA. Harvard Univ, Sch Dent Med, Forsyth Dept Oral Biol, Cambridge, MA 02138 USA. Childrens Hosp, Div Plast Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Case Western Reserve Univ, Sch Med, Dept Genet, Cleveland, OH 44106 USA. Scripps Res Inst, Div Plast & Reconstruct Surg, La Jolla, CA 92037 USA. Univ California, La Jolla, CA USA. EM vikkula@bchm.ucl.ac.be OI Vikkula, Miikka/0000-0002-6236-338X; Brouillard, Pascal/0000-0001-9548-8229 FU NHLBI NIH HHS [HL33014]; NIAMS NIH HHS [AR36820] NR 32 TC 78 Z9 80 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUL PY 1999 VL 65 IS 1 BP 125 EP 133 DI 10.1086/302450 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 212NZ UT WOS:000081224300016 PM 10364524 ER PT J AU Chen, L Keane, AT Every, NR AF Chen, L Keane, AT Every, NR TI The food and drug administration and atrial defibrillation devices SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID QUALITY-OF-LIFE; SUPRAVENTRICULAR TACHYCARDIA; RADIOFREQUENCY ABLATION; CORRIDOR OPERATION; CATHETER ABLATION; EXERCISE CAPACITY; RANDOMIZED TRIAL; SINUS RHYTHM; FIBRILLATION; STROKE AB Context: Atrial fibrillation is a common arrhythmia. It leads to significant morbidity and mortality, primarily from the increased incidence of stroke. The implantable atrial defibrillator, a new therapeutic option for the management of atrial fibrillation, is currently undergoing Food and Drug Administration (FDA) scrutiny for approval to market in the United States. Data Sources: A review of the basic epidemiology of atrial fibrillation, as well as the current status of accepted treatment options in light of the development of the implantable atrial defibrillator, was conducted. A literature search using the terms atrial fibrillation, implantable defibrillator, Food and Drug Administration, medical devices, and medical device regulatory law was conducted using the MEDLINE and Current Contents databases. Results: Currently, there is no consensus on the optimal treatment of atrial fibrillation. Despite the lack of definitive studies showing overall benefit associated with maintaining sinus rhythm in patients in atrial fibrillation, the implantable atrial defibrillator may soon reach the general market. We examine the FDA process for the evaluation of this new medical device and discuss implications for the patient, physician, industry, and health insurers. Conclusions: Current FDA approval processes for new devices are a compromise between (a) the needs for expediency and encouraging innovation by the medical device industry and (b) the need to ensure that new devices will contribute to improved patient outcomes. We suggest alternative FDA- approval processes that address these issues. C1 Univ Washington, COR Ctr, Dept Med, Div Cardiol, Seattle, WA 98102 USA. VA Puget Sound Hlth Care Syst, NW Hlrh Serv Res & Dev Field Program, Seattle, WA USA. RP Every, NR (reprint author), Univ Washington, COR Ctr, Dept Med, Div Cardiol, 1910 Fairview Ave E,Suite 205, Seattle, WA 98102 USA. NR 77 TC 2 Z9 2 U1 0 U2 1 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD JUL PY 1999 VL 5 IS 7 BP 899 EP 909 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 219FV UT WOS:000081598000005 PM 10557410 ER PT J AU McCormick, D Fine, MJ Coley, CM Marrie, TJ Lave, JR Obrosky, DS Kapoor, WN Singer, DE AF McCormick, D Fine, MJ Coley, CM Marrie, TJ Lave, JR Obrosky, DS Kapoor, WN Singer, DE TI Variation in length of hospital stay in patients with community-acquired pneumonia: Are shorter stays associated with worse medical outcomes? SO AMERICAN JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 19th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 02-04, 1996 CL WASHINGTON, D.C. SP Soc Gen Internal Med ID ACUTE MYOCARDIAL-INFARCTION; SEVERITY; DECISION; THERAPY; ILLNESS; QUALITY; COHORT AB PURPOSE: To assess the variation in length of stay for patients hospitalized with community-acquired pneumonia and to determine whether patients who are treated in hospitals with shorter mean stays have worse medical outcomes. SUBJECTS AND METHODS: We prospectively studied a cohort of 1,188 adult patients with community-acquired pneumonia who had been admitted to one community and three university teaching hospitals. We compared patients' mean length of stay, mortality, hospital readmission, return to usual activities, return to work, and pneumonia-related symptoms among the four study hospitals. All outcomes were adjusted for baseline differences in severity of illness and comorbidity. RESULTS: Adjusted interhospital differences in mean length of stay ranged from 0.9 to 2.3 days (P <0.001). When the risk of each medical outcome was compared between patients admitted to the hospital with the shortest length of stay and those admitted to longer stay hospitals, there were no differences in mortality [relative risk (RR) = 0.7; 95% CI, 0.3 to 1.7], hospital readmission (RR = 0.8; 95% CI, 0.5 to 1.2), return to usual activities (RR = 1.1; 95% CI, 0.9 to 1.3), or return to work (RR = 1.2; 95% CI, 0.8 to 2.0) during the first 14 days after discharge, or in the mean number of pneumonia-related symptoms 30 days after admission (P = 0.54). CONCLUSIONS: We observed substantial interhospital variation in the lengths of stay for patients hospitalized with community-acquired pneumonia. The finding that medical outcomes were similar in patients admitted to the hospital with the shortest length of stay and those admitted to hospitals with longer mean lengths of stay suggests that hospitals with longer stays may be able to reduce the mean duration of hospitalization for this disease without adversely affecting patient outcomes. (C) 1999 by Excerpta Medica, Inc. C1 Massachusetts Gen Hosp, Dept Med, Div Gen Med, Clin Epidemiol Unit, Boston, MA 02114 USA. Dalhousie Univ, Victoria Gen Hosp, Halifax, NS, Canada. Univ Pittsburgh, Grad Sch Publ Hlth, Div Gen Internal Med, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Ctr Res Hlth Care, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Serv Adm, Pittsburgh, PA USA. RP McCormick, D (reprint author), Cambridge Hosp, Dept Med, 1493 Cambridge St, Cambridge, MA 02139 USA. FU AHRQ HHS [R01 HS06468]; BHP HRSA HHS [5 T32 PE11001] NR 27 TC 94 Z9 94 U1 1 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUL PY 1999 VL 107 IS 1 BP 5 EP 12 DI 10.1016/S0002-9343(99)00158-8 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 215RJ UT WOS:000081396100002 PM 10403346 ER PT J AU Cohen, RA Hennekens, CH Christen, WG Krolewski, A Nathan, DM Peterson, MJ LaMotte, F Manson, JE AF Cohen, RA Hennekens, CH Christen, WG Krolewski, A Nathan, DM Peterson, MJ LaMotte, F Manson, JE TI Determinants of retinopathy progression in type 1 diabetes mellitus SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID LOW-DENSITY LIPOPROTEIN; BLOOD-PRESSURE; GLUCOSE CONTROL; CHOLESTEROL; ASSOCIATION; DISEASE; SERUM; HYPERCHOLESTEROLEMIA; ATHEROSCLEROSIS; COMPLICATIONS AB PURPOSE: To determine the risk factors for retinopathy progression in type 1 (insulin-dependent) diabetes mellitus in a prospective cohort study. SUBJECTS AND METHODS: Subjects were 485 participants in the Sorbinil Retinopathy Trial, a randomized trial of aldose reductase inhibition among patients aged 18 to 56 years with type 1 diabetes mellitus (duration of 1 to 15 years) and no or only mild retinopathy. Retinopathy progression, assessed by seven-field stereoscopic fundus photography, was defined as worsening by two or more levels on a standardized grading scale at the end of follow-up (median, 41 months). RESULTS: The relative risks for retinopathy progression according to successively greater quintiles of total glycosylated hemoglobin level at baseline, after adjusting for age, diabetes duration, sorbinil assignment, and other variables, were 1.0, 2.0, 1.6, 3.7, and 4.4 (P trend <0.0001). Risk increased with greater baseline diastolic blood pressure: 1.0 for <70 mm Hg, 1.2 for 70 to 79 mm Hg, and 1.8 for greater than or equal to 80 mm Hg (P for trend = 0.04). Diastolic blood pressure was a significant risk factor for progression in participants with mild baseline retinopathy (P for trend <0.02) but not in those without retinopathy at entry. Systolic blood pressure, by comparison, was not associated with progression. Baseline total cholesterol level was a marginally significant predictor of retinopathy progression when examined as a categorical variable (relative risks for increasing quartiles; 1.0, 1.6, 1.8, 1.9; P for trend = 0.03) but not when it was examined as a continuous variable or when hypercholesterolemic patients were compared with those with normal levels. Furthermore, when cholesterol levels were updated in subsequent visits, it was not a significant predictor of progression, and low density lipoprotein (LDL) cholesterol levels did not predict progression no matter how analyzed. Smoking was not associated with progression of retinopathy. CONCLUSIONS: Levels of hyperglycemia and diastolic blood pressure predicted progression of retinopathy in type 1 diabetes mellitus. We found only a suggestion of an association between total cholesterol level (but not of LDL cholesterol level) and progression of retinopathy; resolution of this issue will require additional studies with larger sample sizes and longer follow-up. (C) 1999 by Excerpta Medica, Inc. C1 Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Epidemiol & Genet, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Diabet Unit, Boston, MA USA. Pfizer Pharmaceut, Res Dept, Groton, CT USA. RP Manson, JE (reprint author), Brigham & Womens Hosp, Div Prevent Med, Dept Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. FU NEI NIH HHS [EY10624] NR 50 TC 31 Z9 33 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUL PY 1999 VL 107 IS 1 BP 45 EP 51 DI 10.1016/S0002-9343(99)00165-5 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 215RJ UT WOS:000081396100008 PM 10403352 ER PT J AU Foster, CS Stavrou, P Zafirakis, P Rojas, B Tesavibul, N Baltatzis, S AF Foster, CS Stavrou, P Zafirakis, P Rojas, B Tesavibul, N Baltatzis, S TI Intraocular lens removal patients with uveitis SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID EXTRACAPSULAR CATARACT-EXTRACTION; JUVENILE RHEUMATOID-ARTHRITIS; PARS PLANITIS; IMPLANTATION; SURGERY; EXPLANTATION; IOL AB PURPOSE: To report a series of patients with uveitis and cataract who had undergone cataract extraction with posterior chamber intraocular lens implantation and who subsequently had the intraocular lens removed because of progressive intraocular damage from inflammation. METHODS: Review of the records of 19 patients after removal of a posterior chamber intraocular lens. The decision to perform surgery was based on standard criteria after evaluation at a single uveitis referral center. RESULTS: The complications leading to intraocular lens removal were perilental membrane (eight eyes), chronic low-grade inflammation not responding to antiinflammatory treatment (eight eyes), and cyclitic membrane resulting in hypotony and maculopathy (three eyes). After intraocular lens removal the inflammation subsided and the visual acuity improved or stabilized in 14 of the 19 eyes. The causes of further reduction in the visual acuity of the other five patients were macular edema (two patients), maculopathy resulting from hypotony (one patient), retinal detachment (one patient), and vitreous hemorrhage (one patient). CONCLUSIONS: Intraocular lens implantation can form part of a reasonable plan for visual rehabilitation of patients with uveitic cataract, but inclusion of an intraocular lens in the plan is not always in the overall long-term best interest of the patient, Intraocular lens removal may salvage useful vision for patients who continue to exhibit complications secondary to uveitis after cataract extraction and intraocular lens implantation, provided the intraocular lens is removed before irreparable damage has been done to macula or optic nerve. (Am J Ophthalmol 1999;128:31-37. (C) 1999 by Elsevier Science Inc. All rights reserved.) C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Uveitis & Immunol Serv, Boston, MA 02114 USA. Univ Athens, Gen Hosp Athens, Eye Clin, Athens, Greece. Univ Madrid, Madrid 3, Spain. Pramongkutklao Hosp, Bangkok, Thailand. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Uveitis & Immunol Serv, 243 Charles St, Boston, MA 02114 USA. OI ROJAS LOPEZ, MARIA BLANCA/0000-0002-8980-4659 NR 23 TC 18 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUL PY 1999 VL 128 IS 1 BP 31 EP 37 DI 10.1016/S0002-9394(99)00139-7 PG 7 WC Ophthalmology SC Ophthalmology GA 212FW UT WOS:000081207500005 PM 10482091 ER PT J AU Mangione, CM Gutierrez, PR Lowe, G Orav, EJ Seddon, JM AF Mangione, CM Gutierrez, PR Lowe, G Orav, EJ Seddon, JM TI Influence of age-related maculopathy on visual functioning and health-related quality of life SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID OF-LIFE; CATARACT-SURGERY; SURVEY SF-36; PHYSICAL FUNCTION; ELDERLY PATIENTS; RISK-FACTORS; VISION; IMPAIRMENT; OUTCOMES; ACUITY AB PURPOSE: To describe the influence of age-related maculopathy on visual functioning and health-related quality of life. METHODS: A prospective, cross-sectional, observational cohort sample of 201 persons with various stages of age-related maculopathy was recruited from the Massachusetts Eye and Ear Infirmary as part of a longitudinal study of age-related macular degeneration, Persons were considered to have age-related maculopathy if one or more of the following clinical characteristics were present: drusen, retinal pigment epithelial changes, geographic atrophy, or evidence of exudative disease. Median corrected visual acuity for this sample was 20/25 in the better eye, with all subjects having 20/200 or better visual acuity in at least one eye at baseline. All participants underwent a comprehensive ophthalmologic examination with a dilated pupil. In addition to the usual clinical data collection, severity of age-related maculopathy was graded by an ophthalmologist who used standard clinical criteria and was masked to the participants' descriptions of visual functioning and health-related quality of life. All participants completed an interview that included the Activities of Daily Vision Scale, a survey designed to assess difficulties with routine daily activities that require vision, and the Short Form-36 Health Survey, a generic measure of multidimensional health-related quality of life, RESULTS: Severity of age-related maculopathy was associated with poorer scores of the Activities of Daily Vision Scale. This association was most significant for near vision and driving activities. In this sample, the SF-36 Health Survey scales were not significantly correlated with severity of age-related maculopathy. CONCLUSIONS: Reported visual functioning is significantly associated with the clinical severity of age-related maculopathy. However, once visual acuity is taken into consideration, clinical grading of age-related maculopathy did not explain a significant portion of the variation in visual functioning. The lack of significant correlation between severity of age-related maculopathy and the SF-36 Health Survey may have resulted from the small number of participants in our sample with severe bilateral age-related maculopathy. (Am J Ophthalmol 1999; 128:4-5-53. (C) 1999 by Elsevier Science Inc. All rights reserved.) C1 Univ Calif Los Angeles, Sch Med, Dept Med, Div Gen Med & Hlth Serv Res, Los Angeles, CA 90024 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Epidemiol Unit, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Gen Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Mangione, CM (reprint author), Univ Calif Los Angeles, Sch Med, Dept Med, Div Gen Med & Hlth Serv Res, 911 Broxton Plaza, Los Angeles, CA 90024 USA. FU NIA NIH HHS [1K08-AG00605] NR 58 TC 135 Z9 139 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUL PY 1999 VL 128 IS 1 BP 45 EP 53 DI 10.1016/S0002-9394(99)00169-5 PG 9 WC Ophthalmology SC Ophthalmology GA 212FW UT WOS:000081207500007 PM 10482093 ER PT J AU Setsuda, J Teruya-Feldstein, J Harris, NL Ferry, JA Sorbara, L Gupta, G Jaffe, ES Tosato, G AF Setsuda, J Teruya-Feldstein, J Harris, NL Ferry, JA Sorbara, L Gupta, G Jaffe, ES Tosato, G TI Interleukin-18, interferon-gamma, IP-10, and Mig expression in Epstein-Barr virus-induced infectious mononucleosis and posttransplant lymphoproliferative disease SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; NECROSIS IN-VIVO; LIVER-TRANSPLANTATION; INDUCIBLE PROTEIN-10; VIRAL INTERLEUKIN-10; T-CELLS; KAPPA-B; DISORDERS; RECIPIENTS; CYTOKINE AB T cell immunodeficiency plays an important role in the pathogenesis of posttransplant lymphoproliferative disease (PTLD) by permitting the unbridled expansion of Epstein-Barr virus (EBV)-infected B lymphocytes. However, factors other than T cell function may contribute to PTLD pathogenesis because PTLD infrequently develops even in the context of severe T cell immunodeficiency, and athymic mice that are T-cell-immunodeficient can reject EBV-immortalized cells. Here we report that PTLD tissues express significantly lower levels of IL-18, interferon-gamma (IFN-gamma), Mig, and RANTES compared to lymphoid tissues diagnosed with acute EBV-induced infectious mononucleosis, as assessed by semiquantitative RT-PCR analysis. Other cytokines and chemokines are expressed at similar levels. Immunohistochemistry confirmed that PTLD tissues contain less IL-18 and Mig protein than tissues with infectious mononucleosis. IL-18, primarily a monocyte product, promotes the secretion of IFN-gamma, which stimulates Mig and RANTES expression. Both IL-18 and Mig display antitumor activity in mice involving inhibition of angiogenesis, These results document greater expression of IL-18, IFN-gamma, Mig, and RANTES in lymphoid tissues with acute EBV-induced infectious mononucleosis compared to tissues with PTLD and raise the possibility that these mediators participate in critical host responses to EBV infection. C1 NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, NIH, Bldg 10,Room 2A33,10 Ctr Dr MSC 1500, Bethesda, MD 20892 USA. NR 49 TC 43 Z9 46 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 1999 VL 155 IS 1 BP 257 EP 265 DI 10.1016/S0002-9440(10)65119-X PG 9 WC Pathology SC Pathology GA 212HE UT WOS:000081210600030 PM 10393857 ER PT J AU McCabe, CP Bergman, SB AF McCabe, CP Bergman, SB TI Vision rehabilitation for physiatry residents: A model curriculum SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Editorial Material ID VISUAL IMPAIRMENT C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Vis Rehabil Ctr, Boston, MA 02114 USA. Boston Univ, Dept Phys Med & Rehabil, Boston, MA 02215 USA. RP McCabe, CP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Vis Rehabil Ctr, 243 Charles St, Boston, MA 02114 USA. NR 8 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD JUL-AUG PY 1999 VL 78 IS 4 BP 389 EP 391 DI 10.1097/00002060-199907000-00021 PG 3 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 216AP UT WOS:000081418600016 PM 10418848 ER PT J AU Wang, TC Dockray, GJ AF Wang, TC Dockray, GJ TI Lessons From Genetically Engineered Animal Models I. Physiological studies with gastrin in transgenic mice SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE acid secretion; gastrointestinal growth ID DIFFERENTIATION; GENE; EXPRESSION; PROGASTRIN; RECEPTORS; GROWTH; MUCOSA AB The role of gastrin in the regulation of gastrointestinal growth and acid secretion has been addressed through recent studies involving transgenic and knockout mice. The role of gastrin as key modulator of parietal cell function and gastric acid secretion has been confirmed through studies in mice deficient in either gastrin or the gastrin/CCK-B receptor. However, although gastrin-deficient mice show no changes in gastric proliferation, they do show reduced colonic proliferation, and rates of colonic proliferation are increased in transgenic mice overexpressing glycine-extended gastrin or progastrin. This themes article highlights recent progress in our understanding of the biology of gastrin through studies in genetically modified mice. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Univ Liverpool, Physiol Lab, Liverpool L69 3BX, Merseyside, England. RP Wang, TC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 724,32 Fruit St, Boston, MA 02114 USA. EM wang@helix.mgh.harvard.edu FU NCI NIH HHS [CA-67463]; NIDDK NIH HHS [DK-52778]; Wellcome Trust NR 20 TC 50 Z9 50 U1 0 U2 0 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 JUL PY 1999 VL 277 IS 1 BP G6 EP G11 PG 6 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 216UZ UT WOS:000081464000002 PM 10409145 ER PT J AU Tu, SP Taplin, SH Barlow, WE Boyko, EJ AF Tu, SP Taplin, SH Barlow, WE Boyko, EJ TI Breast cancer screening by Asian-American women in a managed care environment SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE screening; mammography; Asians (Asian Americans); utilization ID UNITED-STATES; MAMMOGRAPHY; PROGRAM; TRENDS; RISK AB Context: Cross-sectional surveys show that Asian-American women are less likely to have had screening mammograms. Objective: To prospectively assess mammography screening by Asian-American women in a program with mailed recommendations and no out-of-pocket costs. Design: Two prospective cohort studies. Setting: A nonprofit health care system where women members greater than or equal to 40 years old are surveyed for breast cancer risk factors and enrolled into a screening program on survey completion. Participants: Program enrollment-All Asian-American women identified through a compilation of Asian surnames (Chinese, Japanese, Vietnamese, and Korean) and a random sample of 2000 women with non-Asian surnames, who were mailed a survey from May 1988 to April 1995. Mammogram participation-All Asian-American women and a random sample of 3000 women with non-Asian surnames, enrolled in the screening program and were mailed a first recommendation for screening from May 1988 to April 1994. Main Outcome Measures: Odds of program enrollment and mammogram use within one year (participation) by Asian-American women compared to non-Asian controls. Results: Compared to controls, Asian-American women were less likely to enroll in Breast Cancer Screening Program (BCSP) (odds ratio 0.53; 95% CI 0.43, 0.64). In aggregate, Asian American women had similar mammogram participation rates. Among older Chinese-American women participation was lower compared to controls (odds ratio 0.66; 95% CI 0.44, 0.97). Conclusion: Participation in mammography screening (program enrollment and participation) by Asian-American women was not necessarily enhanced by the removal of financial barriers. Variations of screening behavior among Asian-American women may be obscured when analyzed in aggregate. C1 Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Family Med, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. RP Tu, SP (reprint author), Univ Washington, Harborview Med Ctr, Div Gen Internal Med, Box 359780,325 9th Ave, Seattle, WA 98104 USA. FU NCI NIH HHS [UOICA 63731] NR 33 TC 24 Z9 24 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL PY 1999 VL 17 IS 1 BP 55 EP 61 DI 10.1016/S0749-3797(99)00043-4 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 216VQ UT WOS:000081465500009 PM 10429754 ER PT J AU Cohen, AJ Miller, YE AF Cohen, AJ Miller, YE TI Neuroendocrine differentiation, neuropeptides, and neprilysin SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Editorial Material ID IDIOPATHIC DIFFUSE HYPERPLASIA; NEUTRAL ENDOPEPTIDASE; LUNG-CANCER; EXPRESSION; CELLS C1 Univ Colorado, Hlth Sci Ctr,Denver Vet Affairs Med Ctr, Specialized Program Res Excellence Lung Canc, Div Pulm Sci & Crit Care Med,Dept Med, Denver, CO 80220 USA. RP Miller, YE (reprint author), Univ Colorado, Hlth Sci Ctr,Denver Vet Affairs Med Ctr, Specialized Program Res Excellence Lung Canc, Div Pulm Sci & Crit Care Med,Dept Med, 4200 E 9th Ave, Denver, CO 80220 USA. NR 20 TC 15 Z9 15 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JUL PY 1999 VL 21 IS 1 BP 1 EP 3 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 215RZ UT WOS:000081397800002 PM 10447344 ER PT J AU Willett, CG Shahsafei, A Graham, SA Sunday, ME AF Willett, CG Shahsafei, A Graham, SA Sunday, ME TI CD10/neutral endopeptidase inhibition augments pulmonary neuroendocrine cell hyperplasia in hamsters treated with diethylnitrosamine and hyperoxia SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID GASTRIN-RELEASING PEPTIDE; BOMBESIN-LIKE PEPTIDES; FETAL LUNG GROWTH; MATURATION INUTERO; GENE-EXPRESSION; APOPTOSIS; PROLIFERATION; CHROMOGRANIN; CARCINOMAS; MODULATION AB In previous studies, we demonstrated that pulmonary neuroendocrine cell (PNEC) hyperplasia in hamsters treated with diethylnitrosamine (DEN) plus 65% hyperoxia (DEN/O-2) reflects predominantly neuroendocrine cell differentiation. Several peptides implicated in non-neoplastic PNEC hyperplasia are hydrolyzed by CD10/neutral endopeptidase 24.11 (CD10/NEP), an enzyme known to downregulate neurogenic inflammation of the lung by modulating locally effective concentrations of multiple bioactive peptides. In fetal mice, we observed that CD10/NEP inhibition by SCH32615 potentiates cell proliferation and type II cell differentiation in the lung in utero. Further, CD10/NEP messenger RNA levels parallelled relative PNEC numbers in DEN/O-2-treated hamster lung, suggesting that the enzyme might mediate spontaneous regression of PNEC hyperplasia. The goals of the present study were: (I) to determine whether CD10/NEP inhibition would alter the extent of PNEC hyperplasia occurring in these hamsters. and (2) to analyze cellular mechanisms potentially involved in altering numbers of PNECs in this model. We administered SCH32615 chronically to a subset of DEN/O-2-treated hamsters, Immunostaining of lungs from the CD10/ NEP-inhibited subset demonstrated significant acceleration of the development of PNEC hyperplasia, increased PNEC proliferation, and diminished PNEC apoptosis as compared with animals receiving no SCH32615, These observations indicate that PNEC hyperplasia can occur as a result of multiple cellular processes, including increased neuroendocrine cell differentiation, proliferation, and survival. CD10/NEP modulates PNEC numbers primarily by promoting cell differentiation and proliferation during lung injury, probably via increasing the half-life of bioactive peptides in the lung. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Sunday, ME (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL44984] NR 23 TC 12 Z9 13 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JUL PY 1999 VL 21 IS 1 BP 13 EP 20 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 215RZ UT WOS:000081397800006 PM 10385588 ER PT J AU Holzmann, A Manktelow, C Taut, FJH Bloch, KD Zapol, WM AF Holzmann, A Manktelow, C Taut, FJH Bloch, KD Zapol, WM TI Inhibition of nitric oxide synthase prevents hyporesponsiveness to inhaled nitric oxide in lungs from endotoxin-challenged rats SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT Experimental Biology 97 Conference CY APR 06-10, 1997 CL NEW ORLEANS, LOUISIANA DE aminoguanidine; dexamethasone; pulmonary circulation ID RESPIRATORY-DISTRESS-SYNDROME; SMOOTH-MUSCLE; RODENT MODELS; INHALATION; AMINOGUANIDINE; PEROXYNITRITE; EXPRESSION; SHOCK; SUPEROXIDE; CYTOKINES AB Background Inhalation of nitric oxide (NO) selectively dilates the pulmonary circulation and improves arterial oxygenation in patients with adult respiratory distress syndrome (ARDS). In approximately 60% of patients with septic ARDS, minimal or no response to inhaled NO is observed. Because sepsis is associated with increased NO production by inducible NO synthase (NOS2), the authors investigated whether NOS inhibition alters NO responsiveness in rats exposed to gramnegative lipopolysaccharide (LPS). Methods: Sprague-Dawley rats were treated with 0.4 mg/kg Escherichia coli 0111:B4 LPS with or without dexamethasone (inhibits NOS2 gene expression; 5 mg/kg), L-NAME (a nonselective NOS inhibitor; 7 mg/kg), or aminoguanidine (selective NOS2 inhibitor; 30 mg/kg). Sixteen hours after LPS treatment, lungs were isolated-perfused; a thromboxane-analog U46619 was added to increase pulmonary artery pressure (PAP) by 5 mmHg, and the pulmonary vasodilator response to inhaled NO was measured. Results: Ventilation with 0.4, 4, and 40 ppm NO decreased the PAP less than in lungs of LPS-treated rats (0.75 +/- 0.25, 1.25 +/- 0.25, 1.75 +/- 0.25 mmHg) than in lungs of control rats (3 +/- 0.5, 4.25 +/- 0.25, 4.5 +/- 0.25 mmHg; P < 0.01). Dexamethasone treatment preserved pulmonary vascular responsiveness to NO in LPS-treated rats (3.75 +/- 0.25, 4.5 +/- 0.25, 4.5 +/- 0.5 mmHg, respectively; P < 0.01 vs. LPS, alone). Responsiveness to NO in LPS-challenged rats was also preserved by treatment with L-NAME (3.0 +/- 1.0, 4.0 +/- 1.0, 4.0 +/- 0.75 mmHg, respectively; P < 0.05 vs. LPS, alone) or aminoguanidine (1.75 +/- 0.25, 2.25 +/- 0.5, 2.75 +/- 0.5 mmHg, respectively; P < 0.05 vs. LPS, alone). In control rats, treatment with dexamethasone, L-NAME, and aminoguanidine had no effect on inhaled NO responsiveness. Conclusion: These observations demonstrate that LPS-mediated increases in pulmonary NOS2 are involved in decreasing responsiveness to inhaled NO. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Zapol, WM (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-55377, HL-42397] NR 30 TC 18 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUL PY 1999 VL 91 IS 1 BP 215 EP 221 DI 10.1097/00000542-199907000-00030 PG 7 WC Anesthesiology SC Anesthesiology GA 211YA UT WOS:000081188400029 PM 10422947 ER PT J AU Raines, DE Zachariah, VT AF Raines, DE Zachariah, VT TI The alkyl chain dependence of the effect of normal alcohols on agonist-induced nicotinic acetylcholine receptor desensitization kinetics SO ANESTHESIOLOGY LA English DT Article DE activation; anesthetic mechanism; cutoff; ion channel; Torpedo ID ANESTHETIC TARGET SITES; GATED ION CHANNELS; GENERAL-ANESTHETICS; POSTSYNAPTIC MEMBRANES; MOLECULAR DIMENSIONS; XENOPUS-LAEVIS; TORPEDO; ACTIVATION; ALKANOLS; BINDING AB Background: The nAcChoR is the prototypical member of a superfamily of ligand-gated ion channels that are all relevant targets of anesthetics and undergo desensitization upon prolonged exposure to agonist, This study was designed to investigate the effects of representative normal alcohols on the apparent rate of acetylcholine-induced nAcChoR desensitization, Methods: Nicotinic acetylcholine receptors were obtained from the electroplax organ of Torpedo nobiliana. The apparent rate of acetylcholine-induced desensitization in the presence and absence of normal alcohols was measured using stopped-flow fluorescence. Results: Normal alcohols as long as octanol (the longest studied) increased the apparent rate of desensitization induced by low concentrations of acetylcholine, shifting the agonist concentration-response curve for desensitization to the left. Ethanol, butanol, and, to a lesser extent, hexanol increased the maximal rate of desensitization induced by high, saturating concentrations of agonist, Beyond hexanol, heptanol and octanol had no effect on this maximal apparent rate of desensitization, even at concentrations that approach those that directly induce desensitization in the absence of agonist, Conclusion: Normal alcohols ranging from ethanol to octanol increase the apparent affinity of nAcChoR for agonist with potencies that are proportional to their hydrophobicities, However, normal alcohol effects on the rate constant for desensitization show a cutoff beyond hexanol. This suggests that the effects of normal alcohols on the apparent agonist affinity and rate constant for desensitization of nAcChoR may be modulated by distinct sites that have different steric constraints; the site(s) responsible for increasing the maximal rate of desensitization are predicted to be smaller than those that increase the apparent agonist affinity. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Raines, DE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, 32 Fruit St, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM53481] NR 37 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUL PY 1999 VL 91 IS 1 BP 222 EP 230 DI 10.1097/00000542-199907000-00031 PG 9 WC Anesthesiology SC Anesthesiology GA 211YA UT WOS:000081188400030 PM 10422948 ER PT J AU Hall, JE AF Hall, JE TI Physiologic and genetic insights into the pathophysiology and management of hypogonadotropic hypogonadism SO ANNALES D ENDOCRINOLOGIE LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; FOLLICLE-STIMULATING-HORMONE; FREE ALPHA-SUBUNIT; LUTEINIZING-HORMONE; BETA-SUBUNIT; ADRENAL HYPOPLASIA; MENSTRUAL-CYCLE; POINT MUTATIONS; NORMAL WOMEN; DEFICIENCY AB Initiation and maintenance of reproductive capacity is contingent upon the pulsatile secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus. While GnRH deficiency manifests itself clinically as hypogonadism. the time of onset of the defect in GnRH secretion (i.e. before or after the onset of puberty) determines the clinical presentation that is further modified by the severity of the defect. GnRH deficiency can be associated with structural lesions that interfere with the normal pattern of GnRH secretion through compression or destruction of critical areas of the median eminence of the hypothalamus. Idiopathic hypogonadotropic hypogonadism (IHH) has been described and is characterized by isolated GnRH deficiency in the absence of a hypothalamic or pituitary lesion. Typically, patients with hypogonadotropic hypogonadism and anosmia have been given the diagnosis of Kallmann's syndrome and those with normal olfaction, IHH. However. both entities can be present in the same family. demonstrating variability in phenotypic expression and raising questions about the usefulness of this distinction. GnRH deficiency may be inherited via autosomal dominant, autosomal recessive and X-linked modes of inheritance. Specific defects in a number of genes have now been found in association with GnRH deficiency in the human and including the KAL gene, the DAX gene and the GnRH receptor gene, but not the gene encoding GnRH itself. While these mutations account for only a small fraction of cases, genetic studies not only provide promise for future treatment, but also insights into the complexity of the GnRH neuronal system. The treatment of GnRH deficiency is highly successful whether designed for steroid hormone replacement or for fertility. The challenge in the treatment of these abnormalities is in the early and accurate diagnosis and the use of replacement therapies that are as close to physiologic as possible. C1 Massachusetts Gen Hosp, Reprod Endocrine Sci Ctr, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. RP Massachusetts Gen Hosp, Reprod Endocrine Sci Ctr, Reprod Endocrine Unit, Boston, MA 02114 USA. NR 45 TC 8 Z9 8 U1 0 U2 0 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0003-4266 EI 2213-3941 J9 ANN ENDOCRINOL-PARIS JI Ann Endocrinol. PD JUL PY 1999 VL 60 IS 2 BP 93 EP 101 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 224TM UT WOS:000081915300005 PM 10456179 ER PT J AU Crawford, WW Yusin, JS Klaustermeyer, WB AF Crawford, WW Yusin, JS Klaustermeyer, WB TI Nonsurgical regression of thymoma following corticosteroid/azathioprine therapy SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID COMMON VARIED IMMUNODEFICIENCY; HYPOGAMMAGLOBULINEMIA; APLASIA C1 W Los Angeles Vet Affairs Med Ctr, Allergy & Immunol Sect, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Klaustermeyer, WB (reprint author), Vet Adm Wadsworth Med Ctr, Allergy & Immunol Sect 111R, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 20 TC 5 Z9 6 U1 0 U2 3 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD JUL PY 1999 VL 83 IS 1 BP 13 EP 16 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 220CU UT WOS:000081647600002 PM 10437809 ER PT J AU Klein, C Vieregge, P Hagenah, J Sieberer, M Doyle, E Jacobs, H Gasser, T Breakefield, XO Risch, NJ Ozelius, LJ AF Klein, C Vieregge, P Hagenah, J Sieberer, M Doyle, E Jacobs, H Gasser, T Breakefield, XO Risch, NJ Ozelius, LJ TI Search for the PARK3 founder haplotype in a large cohort of patients with Parkinson's disease from Northern Germany SO ANNALS OF HUMAN GENETICS LA English DT Article ID RECESSIVE JUVENILE PARKINSONISM; ALPHA-SYNUCLEIN GENE; MUTATIONS; FAMILIES; REGION; COMPLEXITY; ABSENCE; LINKAGE; MAPS AB A founder haplotype on chromosome 2p for autosomal dominant Parkinson's disease (PD) has been postulated for two families of Northern European descent, and a new mutation in the alpha-synuclein gene (Ala30Pro) has been found in a German PD family. We evaluated 85 German PD patients and 85 ethnically matched controls for shared markers on chromosome 2p and for the new a-synuclein mutation. We found no evidence for linkage disequilibrium suggesting that the putative founder mutation on chromosome 2p is not a common cause of PD in the local population. Furthermore, no patient carried the Ala30Pro change, supporting earlier findings that mutations in the a-synuclein gene are extremely rare. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. Univ Munich, Klinikum Grosshadern, Dept Neurol, Munich, Germany. Stanford Univ, Dept Genet, Stanford, CA 94305 USA. RP Ozelius, LJ (reprint author), AECOM, 1300 Morris Pk Ave, Bronx, NY 10461 USA. FU NHGRI NIH HHS [HG00348]; NINDS NIH HHS [NS28384] NR 33 TC 20 Z9 20 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD JUL PY 1999 VL 63 BP 285 EP 291 DI 10.1046/j.1469-1809.1999.6340285.x PN 4 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 274LJ UT WOS:000084767100002 PM 10738540 ER PT J AU Bartfay, E Donner, A Klar, N AF Bartfay, E Donner, A Klar, N TI Testing the equality of twin correlations with multinomial outcomes SO ANNALS OF HUMAN GENETICS LA English DT Article ID LOGISTIC-REGRESSION; BINARY TRAIT; CONCORDANCE; RELIABILITY; MODEL AB Twin studies are widely used to study genetic and environmental influences on human measurements. Correlations are often used in such studies to compare the levels of similarity between monozygotic and dizygotic twins with respect to a specified trait. In this paper, we compare three procedures for testing the equality of twin correlations when the outcome variable of interest is multinominal. One method is a likelihood ratio test based on an underlying Dirichlet-multinomial distribution. The second method is based on the estimated large sample variance of the estimated correlation, and the third method is based on a chi(2) goodness-of-fit test. The results of a Monte Carlo simulation show that the three methods have similar properties if the number of twin pairs is large (> 100), and the prevalence of the underlying trait is not extreme. Otherwise, the goodness-of-fit approach is to be preferred. We illustrate the methods by analyzing data from a previously published smoking study. C1 Univ Western Ontario, Dept Epidemiol & Biostat, London, ON N6A 5C1, Canada. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Donner, A (reprint author), Univ Western Ontario, Dept Epidemiol & Biostat, London, ON N6A 5C1, Canada. NR 20 TC 6 Z9 6 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD JUL PY 1999 VL 63 BP 341 EP 349 DI 10.1046/j.1469-1809.1999.6340341.x PN 4 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 274LJ UT WOS:000084767100007 PM 10738545 ER PT J AU Echevarria, KL Hardin, TC Smith, JA AF Echevarria, KL Hardin, TC Smith, JA TI Hyperlipidemia associated with protease inhibitor therapy SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE hyperlipidemia; protease inhibitors; human immunodeficiency virus ID IMMUNODEFICIENCY-VIRUS INFECTION; HIV-1 PROTEASE; RITONAVIR; HYPERTRIGLYCERIDEMIA; INTERFERON; LESIONS; LIPIDS AB OBJECTIVE: To report a case of extreme hyperlipidemia associated with protease inhibitor-based antiretroviral therapy and review the relevant literature concerning lipid abnormalities with HIV infection and antiretroviral therapy. CASE SUMMARY: A 35-year-old HIV-infected man developed a serum cholesterol of 1472 mg/dL and fasting serum triglycerides of 8660 mg/dL after initiation of antiretroviral therapy consisting of ritonavir, saquinavir, nevirapine, and didanosine. AU other medications had been stable during this time period and the abnormality resolved after discontinuation of antiretroviral therapy and initiation of lipid-lowering therapy. The elevated cholesterol and triglyceride concentrations did not recur when therapy was reinstituted with nelfinavir, saquinavir, nevirapine, and didanosine. The hyperlipidemia then was attributed to ritonavir. DISCUSSION: Lipid abnormalities are common in patients with HIV infection and usually consist of hypocholesterolemia and moderate hypertriglyceridemia. Hypercholesterolemia and hypertriglyceridemia have been reported with ritonavir and, less commonly, with other currently available protease inhibitors. Some cases of ritonavir-associated hyperlipidemia have been extreme. Although an association between hyperlipidemia and clinical consequences such as pancreatitis and atherosclerotic disease has not been well described with protease inhibitor therapy, pancreatitis is common in HIV-infected patients, it is possible that in some cases, protease inhibitor-induced hypertriglyceridemia may contribute to the development of pancreatitis. CONCLUSIONS: Optimal management of lipid abnormalities in HIV-infected patients is controversial, The potential benefit of reducing the incidence of pancreatitis and atherosclerotic events must be weighed against the risk of intolerance, toxicity, and drug interactions. C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. RP Echevarria, KL (reprint author), 406 E Whitener, Euless, TX 76040 USA. NR 23 TC 56 Z9 56 U1 0 U2 0 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD JUL-AUG PY 1999 VL 33 IS 7-8 BP 859 EP 863 DI 10.1345/aph.18174 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 227VE UT WOS:000082100000016 PM 10466916 ER PT J AU Chakravarti, A Compton, CC Shellito, PC Wood, WC Landry, J Machuta, SR Kaufman, D Ancukiewicz, M Willett, CG AF Chakravarti, A Compton, CC Shellito, PC Wood, WC Landry, J Machuta, SR Kaufman, D Ancukiewicz, M Willett, CG TI Long-term follow-up of patients with rectal cancer managed by local excision with and without adjuvant irradiation SO ANNALS OF SURGERY LA English DT Article ID POSTOPERATIVE RADIATION-THERAPY; CARCINOMAS; RESECTION AB Objective The long-term outcomes of patients undergoing local excision with or without pelvic irradiation were examined to define the role of adjuvant irradiation after local excision of T1 and T2 rectal cancers. Methods Ninety-nine patients with T1 or T2 rectal cancers underwent local excision with or without adjuvant irradiation at Massachusetts General Hospital and Emery University Hospital between January 1966 and January 1997. Of these, 52 patients were treated by local excision alone and 47 patients by local excision plus adjuvant irradiation. Twenty-six of these 47 patients were treated by irradiation in combination with 5-fluorouracil chemotherapy. The outcomes of these groups were compared. Results The 5-year actuarial local control and recurrence-free survival rates were 72% and 66%, respectively, for the local excision alone group and 90% and 74%, respectively, for the adjuvant irradiation group. This improvement in outcome was evident despite the presence of a higher-risk patient population in the adjuvant irradiation group. Adverse pathologic features such as poorly differentiated histology and lymphatic or blood vessel invasion decreased local control and recurrence-free survival rates in the local excision only group. Adjuvant: irradiation significantly improved 5-year outcomes in patients with highrisk pathologic features. Four cases of late local recurrence were seen at 64, 72, 86, and 91 months in the adjuvant irradiation group. Conclusions The authors recommend adjuvant chemoradiation for ail patients undergoing local excision for T2 tumors, and for T1 tumors with high-risk pathologic features. The four cases of late local failures beyond 5 years in the adjuvant irradiation group underscores the need for careful long-term follow-up in these patients. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Radiat Oncol, Atlanta, GA 30322 USA. RP Willett, CG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. NR 11 TC 156 Z9 160 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JUL PY 1999 VL 230 IS 1 BP 49 EP 54 DI 10.1097/00000658-199907000-00008 PG 6 WC Surgery SC Surgery GA 211XV UT WOS:000081187900008 PM 10400036 ER PT J AU Baldini, EH Demetri, GD Fletcher, CDM Foran, J Marcus, KC Singer, S AF Baldini, EH Demetri, GD Fletcher, CDM Foran, J Marcus, KC Singer, S TI Adults with Ewing's sarcoma primitive neuroectodermal tumor - Adverse effect of older age and primary extraosseous disease on outcome SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT American-Society-of-Clinical-Oncology Annual Meeting CY MAY 17-24, 1996 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Clin Oncol ID ROUND-CELL TUMORS; TERM FOLLOW-UP; PERIPHERAL NEUROEPITHELIOMA; MULTIMODAL THERAPY; PROGNOSTIC FACTOR; RADIATION-THERAPY; CHILDREN; BONE; EXPERIENCE; CHEMOTHERAPY AB Objective To assess outcome and prognostic factors for survival of adults with Ewing's sarcoma/primitive neuroectodermal tumor (PNET). Background Ewing's sarcoma/PNET is a disease of childhood rarely seen in adults. Accordingly, there is a relative paucity of published literature pertaining to outcome for adults with this disease. Methods Between 1979 and 1996, 37 patients with newly diagnosed Ewing's sarcoma/PNET were evaluated and treated at the Adult Sarcoma Program at Dana-Farber Cancer Institute and Brigham & Women's Hospital. Twenty-six patients had localized disease at presentation and II had metastatic disease. All but two patients received multiagent chemotherapy. Local treatment consisted of surgery (7 patients), surgery and radiation therapy (19), radiation therapy (6), or no local treatment (5). Median follow-up for living patients was 100 months (range 8 to 199). Results The 5-year survival rate for the group overall was 37% +/- 9%. The 5-year local control rate was 85% +/- 7%. Significant favorable predictors for survival on univariate analysis included localized disease at presentation. primary origin in bone, primary size <8 cm, and a favorable objective response to chemotherapy. Patients with localized disease had a 5-year survival rate of 49% +/- 11% compared with 0% for those with metastatic disease at presentation. Multivariate analysis showed three significant independent predictors for death: metastatic disease at presentation, primary origin in extraosseous tissue versus bone, and age 26 years or older. Conclusion Adult patients with Ewing's sarcoma/PNET at highest risk for death are those who are older than 26 years and have metastatic disease or an extraosseous primary tumor. The development of novel therapies should target these highrisk groups. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Adult Sarcoma Program, Div Surg Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Div Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Div Med Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Div Pathol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Div Surg Oncol, Boston, MA 02115 USA. RP Singer, S (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Adult Sarcoma Program, Div Surg Oncol, 75 Francis St, Boston, MA 02115 USA. NR 45 TC 57 Z9 61 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JUL PY 1999 VL 230 IS 1 BP 79 EP 86 DI 10.1097/00000658-199907000-00012 PG 8 WC Surgery SC Surgery GA 211XV UT WOS:000081187900012 PM 10400040 ER PT J AU Steele, GD Herndon, JE Bleday, R Russell, A Benson, A Hussain, M Burgess, A Tepper, JE Mayer, RJ AF Steele, GD Herndon, JE Bleday, R Russell, A Benson, A Hussain, M Burgess, A Tepper, JE Mayer, RJ TI Sphincter-sparing treatment for distal rectal adenocarcinoma SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 52nd Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 04-07, 1999 CL ORLANDO, FLORIDA SP Soc Surg Oncol DE rectal cancer; sphincter prevervation ID CANCER; ELECTROCOAGULATION; MANAGEMENT; EXCISION; SURVIVAL AB Background: Studies suggest that the anal sphincter can be preserved in some patients with distal rectal adenocarcinoma (DRA), but this has not been validated in any prospective multi-institutional trial. Methods: To test the hypothesis that the anal sphincter can be preserved in some patients with DRA, the Cancer and Leukemia Group B and collaborators reviewed 177 patients who had T1/T2 adenocarcinomas less than or equal to 4 cm in diameter, which encompassed less than or equal to 10% of bowel wall circumference, and were less than or equal to 10 cm from the dentate line. Of the 177 patients, 59 patients who were eligible for the study had T1 adenocarcinomas and received no further treatment; 51 eligible T2 patients received external beam irradiation (5400 cGY/30 fractions 5 days/week) and 5-fluorouracil (500 mg/m2 IV d1-3, d29-31) after local excision. Results: At 48 months median follow-up, B-year survival and failure-free survival rates of the eligible patients are 85% and 78% respectively. Three patients died of unrelated disease. Two patients were treated for second primary colorectal tumors; both remain disease free (NED). Another eight patients died of disease, four with distant recurrence only. One T1 patient is alive with distant disease. Two T1 and seven T2 patients experienced isolated local recurrences; all underwent salvage abdominoperineal resection (APR). After APR, one T1 and four of seven T2 patients were NED at the time of last visit (2-7 years). One T1 patient died of local and distant disease. Three of seven T2 patients died with distant disease. Conclusions: We conclude that sphincter preservation can be achieved with excellent cancer control without initial sacrifice of anal function in most patients. After local recurrence, salvage resection appears effective, but longer follow-up time of local and distant disease-free survival is advised before extrapolation to patients with T3 primaries. C1 Univ Chicago, Chicago, IL 60637 USA. CALGB Stat Ctr, Durham, NC USA. Univ Washington, Med Ctr, Seattle, WA 98195 USA. Beth Israel Deaconess Hosp, Boston, MA USA. Northwestern Univ, Med Ctr, Evanston, IL 60208 USA. Wayne State Univ, Barbara Ann Karmanos Canc Inst, Detroit, MI USA. Wayne State Univ, Detroit, MI USA. Univ N Carolina, Chapel Hill, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Steele, GD (reprint author), Univ Chicago, 5841 S Maryland, Chicago, IL 60637 USA. FU NCI NIH HHS [CA722955, CA723286, CA724701] NR 24 TC 160 Z9 161 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JUL-AUG PY 1999 VL 6 IS 5 BP 433 EP 441 DI 10.1007/s10434-999-0433-5 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA 224AT UT WOS:000081874300007 PM 10458680 ER PT J AU Lopez-Ribot, JL McAtee, RK Perea, S Kirkpatrick, WR Rinaldi, MG Patterson, TF AF Lopez-Ribot, JL McAtee, RK Perea, S Kirkpatrick, WR Rinaldi, MG Patterson, TF TI Multiple resistant phenotypes of Candida albicans coexist during episodes of oropharyngeal candidiasis in human immunodeficiency virus-infected patients SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID AZOLE ANTIFUNGAL AGENTS; FLUCONAZOLE RESISTANCE; MOLECULAR MECHANISMS; ORAL CANDIDIASIS; CHROMOGENIC AGAR; DRUG-RESISTANCE; SUSCEPTIBILITY; CONTRIBUTE; AIDS; CORRELATE AB Mechanisms of resistance to azoles in Candida albicans, the main etiologic agent of oropharyngeal candidiasis (OPC), include alterations in the target enzyme (lanosterol demethylase) and increased efflux of drug. Previous studies on mechanisms of resistance have been limited by the fact that only a single isolate from each OPC episode was available for study. Multiple isolates from each OPC episode were evaluated with oral samples plated in CHROMagar Candida with and without fluconazole to maximize detection of resistant yeasts. A total of 101 isolates from each of three serial episodes of OPC from four different patients were evaluated. Decreasing geometric means of fluconazole MICs with serial episodes of infection were detected in the four patients. However, 8-fold or larger (up to 32-fold) differences in fluconazole MICs were detected within isolates recovered at the same time point in 7 of 12 episodes. Strain identity was analyzed by DNA typing techniques and indicated that isolates from each patient represented mainly isogenic strains, but differed among patients. A Northern blot technique was used to monitor expression of ERG11 (encoding lanosterol demethylase) and genes coding for efflux pumps. This analysis revealed that clinical isolates obtained from the same patient and episode were phenotypically heterogeneous in their patterns of expression of these genes involved in fluconazole resistance. These results demonstrate the complexity of the distribution of the molecular mechanisms of antifungal drug resistance and indicate that different subpopulations of yeasts may coexist at a given time in the same patient and may develop resistance through different mechanisms. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78284 USA. RP Lopez-Ribot, JL (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM ribot@uthscsa.edu RI Lopez-Ribot, Jose/D-2048-2010 FU NCRR NIH HHS [M01 RR001346, M01-RR-01346]; NIAID NIH HHS [1 R29 AI42401]; NIDCR NIH HHS [R01 DE011381, 1 R01 DE11381] NR 38 TC 66 Z9 71 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 1999 VL 43 IS 7 BP 1621 EP 1630 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 212HG UT WOS:000081210800015 PM 10390213 ER PT J AU Dore, MP Graham, DY Sepulveda, AR Realdi, G Osato, MS AF Dore, MP Graham, DY Sepulveda, AR Realdi, G Osato, MS TI Sensitivity of amoxicillin-resistant Helicobacter pylori to other penicillins SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article AB The sensitivities to penicillins and to a penicillin and beta-lactamase inhibitor combination agent were determined for Helicobacter pylori strains that were sensitive, moderately resistant, or highly resistant to amoxicillin. All strains were resistant to nafcillin and oxacillin. Moderately resistant strains showed an intermediate zone of inhibition to ticarcillin, mezlocillin, piperacillin, and amoxicillin-clavulanic acid. High-level resistance was associated with the smallest zone size for all penicillins tested. C1 VA Med Ctr, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Sassari, Dept Internal Med, I-07100 Sassari, Italy. RP Dore, MP (reprint author), VA Med Ctr, Dept Med, 111D,2002 Holcombe Blvd, Houston, TX 77030 USA. EM mariap@bcm.tmc.edu NR 10 TC 15 Z9 17 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 1999 VL 43 IS 7 BP 1803 EP 1804 PG 2 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 212HG UT WOS:000081210800051 PM 10390249 ER PT J AU Yablon, AD Nishioka, NS Mikic, BB Venugopalan, V AF Yablon, AD Nishioka, NS Mikic, BB Venugopalan, V TI Measurement of tissue absorption coefficients by use of interferometric photothermal spectroscopy (vol 38, pg 1259, 1999) SO APPLIED OPTICS LA English DT Correction C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. Univ Calif Irvine, Beckman Laser Inst & Med Clin, Laser Microbeam & Med Program, Irvine, CA 92612 USA. RP Yablon, AD (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. EM vasan@bli.uci.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD JUL 1 PY 1999 VL 38 IS 19 BP 4266 EP 4266 DI 10.1364/AO.38.004266 PG 1 WC Optics SC Optics GA 212GF UT WOS:000081208400038 ER PT J AU Egan, KM Quinn, JL Gragoudas, ES AF Egan, KM Quinn, JL Gragoudas, ES TI Childbearing history associated with improved survival in choroidal melanoma SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 10-15, 1998 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol ID PROTON-BEAM IRRADIATION; MALIGNANT-MELANOMA; UVEAL MELANOMA; BREAST-CANCER; PROGNOSIS; PREGNANCY; RISK; SEX; AGE AB Background: Research in cutaneous melanoma suggests that women may experience better tumor-dependent survival than men, and some studies have shown that the advantage is specific to childbearing. Objective: To examine whether childbearing may be a favorable prognostic factor in melanoma of the uveal tract. Design: Prospective follow-up study. Setting: Hospital. Main Outcome Measure: Death from metastatic choroidal melanoma. Methods: We evaluated a consecutive series of 1818 patients with choroidal melanoma, 748 parous and 165 nulliparous women and 905 men, after treatment with proton irradiation. Three hundred fifty-two deaths from metastasis were documented in follow-up. Results: Overall multivariate-adjusted death rates from metastasis were approximately 25% higher in nulliparous women (relative risk [RR], 1.23; 95% confidence interval [CI], 0.83-1.82) and men (RR, 1.25; 95% CI, 1.00-1.56) than in women who had given birth. The protective influence of parity was strongest in the early period following diagnosis and treatment (RR, 1.58; 95% CI, 0.88-2.86, and RR, 1.51; 95% CI, 1.04-2.19, in nulliparous women and men, respectively, during the first 16 months of follow-up). The level of protection increased with the number of live births (P for trend, .04). Conclusion: These data provide support for the hypothesis that a history of childbearing confers protection from death in choroidal melanoma. C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Egan, KM (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. NR 22 TC 18 Z9 18 U1 0 U2 2 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 JUL PY 1999 VL 117 IS 7 BP 939 EP 942 PG 4 WC Ophthalmology SC Ophthalmology GA 215RA UT WOS:000081395300012 PM 10408460 ER PT J AU Ansley, JF Shapiro, NL Cunningham, MJ AF Ansley, JF Shapiro, NL Cunningham, MJ TI Rigid tracheobronchoscopy-induced bacteremia in the pediatric population SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT 13th Annual Meeting of the American-Society-of-Pediatric-Otolaryngology CY MAY 12-14, 1998 CL PALM BEACH, FLORIDA SP Amer Soc Pediatr Otolaryngol ID FIBEROPTIC BRONCHOSCOPY; ENDOCARDITIS; FEVER AB Objective: To assess the incidence of bacteremia following rigid tracheobronchoscopy in children to determine whether use of prophylactic antibiotics is warranted in pediatric patients at risk for perioperative endocarditis. Design: Prospective nonrandomized clinical study. Setting: specialty care referral center. Patients: Patients younger than 18 years undergoing diagnostic rigid tracheobronchoscopy for airway assessment. Twenty-five patients (14 boys and 11 girls) were enrolled. The mean age was 5.2 years (range, 10 months to 13 years). Interventions: Blood samples for culture were obtained intraoperatively at 2 time intervals. The first culture was obtained after the induction of mask anesthesia prior to airway instrumentation; the second, within 5 minutes following the completion of tracheobronchoscopy. Blood cultures were performed under sterile technique and were placed into 20 mL of brain heart infusion broth. All cultures were incubated at 35 degrees C and observed for growth over a 14-day period. Results: There were no documented cases of bacterial growth in blood cultures. All blood cultures, obtained before and after tracheobronchoscopy, were negative for bacterial growth after incubation for 14 days. Two culture bottles yielded contaminant organisms. Conclusions: Rigid tracheobronchoscopy in the pediatric population is a low-risk procedure for the development of bacteremia. This may bear on present guidelines regarding perioperative antibiotic prophylaxis for endocarditis in the high-risk population. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Cunningham, MJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 10 TC 7 Z9 7 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JUL PY 1999 VL 125 IS 7 BP 774 EP 776 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 215ZX UT WOS:000081416800009 PM 10406315 ER PT J AU Harada, ND Chiu, V Stewart, AL AF Harada, ND Chiu, V Stewart, AL TI Mobility-related function in older adults: Assessment with a 6-minute walk test SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT 50th Annual Scientific Meeting of the Gerontological-Society-of-America CY NOV 07-18, 1997 CL CINCINNATI, OHIO SP Gerontol Soc Amer ID CHRONIC HEART-FAILURE; EXERCISE CAPACITY; MUSCLE STRENGTH; DISEASE; AGE; PERFORMANCE; QUALITY; PEOPLE AB Objective: To determine the usefulness of the 6-minute walk test as an integrated measure of mobility in older adults. Design: Observational study. Setting: Community centers and retirement homes in the Los Angeles area. Patients: Eighty-six older adults without significant disease. Interventions: None Main Outcome Measures: Assessments included the 6-minute walk, chair stands, standing balance, gait speed, body mass index, and self-reported physical functioning and general health perceptions. Results: One-week test-retest reliability of the 6-minute walk was .95. As hypothesized, the 6-minute walk distance was significantly greater for active than for inactive older adults (p < .0001), moderately correlated with chair stands (r = .67), standing balance (r = .52), and gait speed (r = -.73). It had a low correlation with body mass index (r = -.07), The correlation of the 6-minute walk with self-reported physical functioning was .55, and its correlation with general health perceptions was .39. Self-report and performance measures explained 69% of the variance in 6-minute walk scores. Conclusions: The 6-minute walk test is reliable and is valid in relation to the performance and self-reported indicators of physical functioning tested in this study. It could serve as a useful integrated measure of mobility. (C) 1999 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 W Los Angeles Vet Affairs Med Ctr, PT, GRECC 11G, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, MEDTEP, RAND, VA,Ctr Asians & Pacific Islanders, Los Angeles, CA USA. Univ Calif San Francisco, Inst Hlth & Aging, San Francisco, CA 94143 USA. RP Harada, ND (reprint author), W Los Angeles Vet Affairs Med Ctr, PT, GRECC 11G, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU AHRQ HHS [HS07370]; NIA NIH HHS [AG09931] NR 30 TC 187 Z9 192 U1 1 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUL PY 1999 VL 80 IS 7 BP 837 EP 841 DI 10.1016/S0003-9993(99)90236-8 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 214EY UT WOS:000081316700018 PM 10414771 ER PT J AU Huang, Y Jaffa, A Koskinen, S Takei, A Lopes-Virella, MF AF Huang, Y Jaffa, A Koskinen, S Takei, A Lopes-Virella, MF TI Oxidized LDL-containing immune complexes induce Fc gamma receptor I-mediated mitogen-activated protein kinase activation in THP-1 macrophages SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE oxidized LDL; immune complex; mitogen-activated protein kinase; Fc gamma receptor ID LOW-DENSITY-LIPOPROTEIN; MONOCYTE-DERIVED MACROPHAGES; SMOOTH-MUSCLE CELLS; CAROTID ATHEROSCLEROSIS; GENE-EXPRESSION; UP-REGULATION; COLLAGEN; BIOSYNTHESIS; AUTOANTIBODIES; HYPERTROPHY AB Our previous studies have shown that Fc gamma receptor (Fc gamma R)-mediated uptake of LDL-containing immune complexes (oxLDL-ICs) by human monocyte-derived macrophages leads to not only transformation of macrophages into foam cells but also macrophage activation and release of cytokines. It has been shown that cross-linking of Fc gamma R triggers activation of signal transduction pathways that alter gene expression in macrophages. In this study, we determined whether engagement of Fc gamma R by oxLDL-ICs leads to activation of mitogen-activated protein (MAP) kinase pathway, a signaling cascade serving many important functions, including the regulation of gene expression, in THP-1 macrophage-like cells. Our results from immunoblotting, using specific anti-phosphorylated MAP kinase antibodies, showed that oxLDL-ICs induced extracellular signal regulated kinase 2 (ERK2) MAP kinase phosphorylation in THP-1 macrophage-like cells in time- and dose-dependent manners. Cholesterol loading before stimulation led to a longer phosphorylation of ERK2. Nuclear translocation of phosphorylated ERK was markedly increased after the stimulation. Moreover, our data showed that oxLDL-IC induction of MAP kinase was prevented by human monomeric IgG1, suggesting that the specific engagement of type I Fc gamma R by oxLDL-IC is responsible for the MAP kinase activation. Finally, we showed that human anti-oxLDL autoantibody-containing immune complexes immobilized on type I collagen induced MAP kinase activation in THP-1 cells. These results strongly suggest that oxLDL-IC, which has been detected in atherosclerotic plaques, may play an important role in macrophage activation and atherogenesis. C1 Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29403 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Lopes-Virella, MF (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, 114 Doughty St, Charleston, SC 29403 USA. FU NHLBI NIH HHS [HL-55782] NR 44 TC 45 Z9 53 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUL PY 1999 VL 19 IS 7 BP 1600 EP 1607 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 216BG UT WOS:000081420200003 PM 10397676 ER PT J AU Helfgott, SM AF Helfgott, SM TI Stiff-man syndrome - From the bedside to the bench SO ARTHRITIS AND RHEUMATISM LA English DT Review ID GLUTAMIC-ACID DECARBOXYLASE; DEPENDENT DIABETES-MELLITUS; INTRATHECAL BACLOFEN THERAPY; PERSON-SYNDROME; MYASTHENIA-GRAVIS; GABAERGIC NEURONS; BREAST-CANCER; SUDDEN-DEATH; AUTOANTIBODIES; ANTIBODIES C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, PBBH, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Helfgott, SM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, PBBH, B-3,45 Francis St, Boston, MA 02115 USA. NR 90 TC 12 Z9 12 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUL PY 1999 VL 42 IS 7 BP 1312 EP 1320 DI 10.1002/1529-0131(199907)42:7<1312::AID-ANR2>3.0.CO;2-W PG 9 WC Rheumatology SC Rheumatology GA 213EK UT WOS:000081259400002 PM 10403257 ER PT J AU Reite, M Teale, P Rojas, DC Sheeder, J Arciniegas, D AF Reite, M Teale, P Rojas, DC Sheeder, J Arciniegas, D TI Schizoaffective disorder: Evidence for reversed cerebral asymmetry SO BIOLOGICAL PSYCHIATRY LA English DT Article DE somatosensory evoked fields; cerebral laterality; magnetoencephalography; psychoses; M20 ID EVOKED MAGNETIC-FIELDS; SOMATOSENSORY CORTEX; EXTENSIVE REORGANIZATION; SEX-DIFFERENCES; ADULT HUMANS; SCHIZOPHRENIA; PSYCHOSIS; LATERALIZATION; MAGNETOENCEPHALOGRAPHY; ABNORMALITIES AB Background: Schizoaffective disorder is one of the most severe of the affective psychoses, but its pathophysiology is poorly understood, Because cerebral lateralization may be disturbed in psychotic disorders generally, studies examining cerebral asymmetry may improve understanding of the neurobiology specific to schizoaffective disorder. This study examines cerebral lateralization in this patient population using magnetic source localization. Methods: We studied 16 subjects with schizoaffective disorder and 16 controls. Magnetic source localization was used to identify the location of the 20 msec latency somatosensory evoked field component (M20), Results: In control subjects, the source location was further anterior in the right hemisphere, The subjects with schizoaffective disorder were reverse lateralized, Conclusions: The findings of a reversed asymmetry of the M20 in patients with schizoaffective disorder suggest an anatomical shift in the placement of the post central gyrus in this disorder, compatible with a disorder of cerebral lateralization. Whether this finding converges or diverges with measurement of the M20 in other psychotic disorders will require further investigation (C) 1999 Society of Biological Psychiatry. C1 Univ Colorado, Hlth Sci Ctr, Biomagnet Imaging Lab, Dept Psychiat, Denver, CO 80262 USA. Denver VAMC, Mental Hlth Serv, Denver, CO USA. RP Reite, M (reprint author), Univ Colorado, Hlth Sci Ctr, Biomagnet Imaging Lab, Dept Psychiat, Box C268-68,4200 E 9th Ave, Denver, CO 80262 USA. RI Arciniegas, David/A-3792-2009; Rojas, Don/F-4296-2012; OI Rojas, Don/0000-0001-6560-9616; Sheeder, Jeanelle/0000-0002-4463-3569 FU NIMH NIH HHS [MH47476] NR 30 TC 8 Z9 8 U1 1 U2 2 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 JUL 1 PY 1999 VL 46 IS 1 BP 133 EP 136 DI 10.1016/S0006-3223(99)00053-0 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 210KE UT WOS:000081103400018 PM 10394484 ER PT J AU Pluen, A Netti, PA Jain, RK Berk, DA AF Pluen, A Netti, PA Jain, RK Berk, DA TI Diffusion of macromolecules in agarose gels: Comparison of linear and globular configurations SO BIOPHYSICAL JOURNAL LA English DT Article ID ATOMIC-FORCE MICROSCOPY; SINGLE-STRANDED-DNA; IONIC-STRENGTH; FLUORESCENCE MICROSCOPY; CONCENTRATED PROTEIN; POLYACRYLAMIDE GELS; PERSISTENCE LENGTH; HINDERED TRANSPORT; FIBROUS MEMBRANES; PORE-SIZE AB The diffusion coefficients (D) of different types of macromolecules (proteins, dextrans, polymer beads, and DNA) were measured by fluorescence recovery after photobleaching (FRAP) both in solution and in 2% agarose gels to compare transport properties of these macromolecules. Diffusion measurements were conducted with concentrations low enough to avoid macromolecular interactions. For gel measurements, diffusion data were fitted according to different theories: polymer chains and spherical macromolecules were analyzed separately. As chain length increases, diffusion coefficients of DNA show a clear shift from a Rouse-like behavior (D(G) congruent to N(0)(-0.5)) to a reptational behavior (D(G) similar or equal to N(0)(-2.0)). Th, pore size, a, of a 2% agarose gel cast in a 0.1 M PBS solution was estimated. Diffusion coefficients of the proteins and the polymer beads were analyzed with the Ogston model and the effective medium model permitting the estimation of an agarose gel fiber radius and hydraulic permeability of the gels. Not only did flexible macromolecules exhibit greater mobility in the gel than did comparable-size rigid spherical particles, they also proved to be a more useful probe of available space between fibers. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA. RP Jain, RK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab, 100 Blossom St,Cox 7, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu RI Berk, David/A-4863-2012; Pluen, Alain/F-5300-2015; OI Berk, David/0000-0002-3855-6886; Pluen, Alain/0000-0002-5953-8011; NETTI, PAOLO/0000-0002-2435-7181 NR 69 TC 290 Z9 293 U1 10 U2 90 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 1999 VL 77 IS 1 BP 542 EP 552 DI 10.1016/S0006-3495(99)76911-0 PG 11 WC Biophysics SC Biophysics GA 214RQ UT WOS:000081341700045 PM 10388779 ER PT J AU Kling, DE Madoff, LC Michel, JL AF Kling, DE Madoff, LC Michel, JL TI Subcellular fractionation of group B Streptococcus SO BIOTECHNIQUES LA English DT Article ID ALPHA-C-PROTEIN; CELL-WALL; CONJUGATE VACCINE; SURFACE-PROTEINS; POLYSACCHARIDE; CLEAVAGE C1 Univ Massachusetts, Amherst, MA 01003 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kling, DE (reprint author), Massachusetts Gen Hosp, Dept Pediat Surg, WRN-1024,32 Fruit St, Boston, MA 02114 USA. FU NIAID NIH HHS [AI25152, AI38424, AI33963] NR 14 TC 20 Z9 20 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JUL PY 1999 VL 27 IS 1 BP 24 EP + PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 214RJ UT WOS:000081341100003 PM 10407656 ER PT J AU Corman, JM Moody, JA Aronson, WJ AF Corman, JM Moody, JA Aronson, WJ TI Fournier's gangrene in a modern surgical setting: improved survival with aggressive management SO BJU INTERNATIONAL LA English DT Article DE Fournier's gangrene; management; morbidity; mortality; debridement; surgery ID ETIOLOGY AB Objective. To examine the outcome of 23 consecutive patients with Fournier's gangrene. Patients and methods. Patients' charts were reviewed retrospectively from all those treated for Fournier's gangrene between July 1994 and July 1997 at the UCLA affiliated hospitals. Results. Twenty-three patients were identified (mean age 51.7 years, range 13-71). The aetiologies included perirectal abscess (43%), urethral stricture (30%), scrotal abscess (21%) and unknown (4%). Predisposing factors included diabetes mellitus (43%), steroids or chemotherapy (21%), alcohol abuse (43%), malignancy (26%) and radiation therapy (9%). All 23 patients initially received wide debridement and placement of a percutaneous suprapubic tube. At the time of the first surgery, total scrotectomy was required in all, colostomy in 17% and penectomy in 4%. An additional 35% required eventual colostomy and an additional 9% required a penectomy. Patients underwent repeat debridement a mean of 2.5 times; the overall survival was 96%. Conclusion. Survival can be improved in patients with Fournier's gangrene by combining aggressive surgical and medical management. The keys to successful outcome included a high index of suspicion, prompt fluid resuscitation, rapid initiation of broad-spectrum antibiotics, a multidisciplinary approach, early surgical intervention with radical debridement, haemodynamic support in an intensive care setting, and frequent repeat operative debridement. C1 Univ Calif Los Angeles, Vet Adm Med Ctr, Sch Med, Dept Urol, W Los Angeles, CA USA. RP Corman, JM (reprint author), VA Puget Sound Hlth Care Syst, Sect Urol 112 UR, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 13 TC 35 Z9 37 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD JUL PY 1999 VL 84 IS 1 BP 85 EP 88 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 216GP UT WOS:000081433300017 PM 10444130 ER PT J AU Gregory, T Yu, CN Ma, A Orkin, SH Blobel, GA Weiss, MJ AF Gregory, T Yu, CN Ma, A Orkin, SH Blobel, GA Weiss, MJ TI GATA-1 and erythropoietin cooperate to promote erythroid cell survival by regulating bcl-x(L) expression SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; RECEPTOR-DEFICIENT MICE; MOUSE BCL-X; ESTROGEN-RECEPTOR; ERYTHROLEUKEMIA-CELLS; HEMATOPOIETIC-CELLS; PROGENITOR CELLS; BINDING DOMAINS; HUMAN LEUKEMIA; STEM-CELLS AB The transcription factor GATA-1 is essential for normal erythropoiesis, By examining in vitro-differentiated embryonic stem cells, we showed previously that in the absence of GATA-1, committed erythroid precursors fail to complete maturation and instead undergo apoptosis. The mechanisms by which GATA-1 controls cell survival are unknown. Here we report that in erythroid cells, GATA-1 strongly induces the expression of the anti-apoptotic protein bcl-x(L), but not the related proteins bcl-2 and mcl-1. Consistent with a role for bcl-x(L) in mediating GATA-1-induced erythroid cell survival, in vitro-differentiated bcl-x(L)(-/-) embryonic stem cells fail to generate viable mature definitive erythroid cells, a phenotype resembling that of GATA-1 gene disruption, In addition, we show that erythropoietin, which is also required for erythroid cell survival, cooperates with GATA-1 to stimulate bcl-x(L) gene expression and to maintain erythroid cell viability during terminal maturation. Together, our data show that bcl-x(L) is essential for normal erythroid development and suggest a regulatory hierarchy in which bcl-x(L) is a critical downstream effector of GATA-1 and erythropoietin-mediated signals. (C) 1999 by The American Society of Hematology. C1 Ontogeny Inc, Cambridge, MA 02138 USA. Childrens Hosp, Div Hematol Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Univ Chicago, Comm Immunol, Dept Med, Chicago, IL 60637 USA. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Hematol, Philadelphia, PA 19104 USA. Howard Hughes Med Inst, Boston, MA USA. RP Weiss, MJ (reprint author), Ontogeny Inc, 45 Moulton St, Cambridge, MA 02138 USA. RI Weiss, Mitchell/A-1245-2013; Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 FU NHLBI NIH HHS [K08 HL03364] NR 57 TC 240 Z9 248 U1 1 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 1999 VL 94 IS 1 BP 87 EP 96 PG 10 WC Hematology SC Hematology GA 212CF UT WOS:000081198200011 PM 10381501 ER PT J AU Juppner, H AF Juppner, H TI Receptors for parathyroid hormone and parathyroid hormone-related peptide: Exploration of their biological importance SO BONE LA English DT Article; Proceedings Paper CT 2nd Joint Meeting of the American-Society-for-Bone-and-Mineral-Research/International-Bone-and-Mi neral-Society CY DEC 01-06, 1998 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Bone & Mineral Res, Int Bone & Mineral Soc ID PTH-RELATED PEPTIDE; JANSENS METAPHYSEAL CHONDRODYSPLASIA; ADVANCED SKELETAL MATURATION; MESSENGER RIBONUCLEIC-ACIDS; PTH/PTHRP RECEPTOR; PROTEIN-RECEPTOR; BLOMSTRAND CHONDRODYSPLASIA; SUPRAOPTIC NUCLEUS; INDIAN HEDGEHOG; AMINO-TERMINUS C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Wellman 50, Boston, MA 02114 USA. NR 61 TC 35 Z9 36 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 8756-3282 J9 BONE JI Bone PD JUL PY 1999 VL 25 IS 1 BP 87 EP 90 DI 10.1016/S8756-3282(99)00110-6 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 213FU UT WOS:000081262700014 PM 10423028 ER PT J AU St-Arnaud, R Arabian, A Travers, R Demay, MB Glorieux, FH AF St-Arnaud, R Arabian, A Travers, R Demay, MB Glorieux, FH TI Genetic analysis of vitamin D metabolism during development through targeted inactivation of the vitamin D 24-hydroxylase gene (CYP24) SO BONE LA English DT Meeting Abstract C1 Shriners Hosp Crippled Children, Genet Unit, Montreal, PQ H3G 1A6, Canada. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 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 8756-3282 J9 BONE JI Bone PD JUL PY 1999 VL 25 IS 1 MA 24 BP 161 EP 161 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 213FU UT WOS:000081262700053 ER PT J AU Schipani, E AF Schipani, E TI Receptors for parathyroid hormone and parathyroid hormone related peptide: from molecular cloning to definition of diseases SO BONE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 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 8756-3282 J9 BONE JI Bone PD JUL PY 1999 VL 25 IS 1 MA 27 BP 162 EP 162 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 213FU UT WOS:000081262700056 ER PT J AU Caviness, VS Lange, NT Makris, N Herbert, MR Kennedy, DN AF Caviness, VS Lange, NT Makris, N Herbert, MR Kennedy, DN TI MRI-based brain volumetrics: emergence of a developmental brain science SO BRAIN & DEVELOPMENT LA English DT Review DE volumetrics; MRI; cerebral cortex; human brain ID OBSESSIVE-COMPULSIVE DISORDER; CEREBRAL-CORTEX; STRUCTURAL ABNORMALITIES; SCHIZOPHRENIC-PATIENTS; MORPHOMETRIC ANALYSIS; HUNTINGTONS-DISEASE; INFANTILE-AUTISM; HUMAN NEOCORTEX; SIZE; PARCELLATION AB MRI-based brain volumetrics is an established methodology of great versatility and reliability with a broad range of potential applications in medicine and basic human brain science. We consider here, more theoretical implications of brain tissue volumes. Specifically, we suggest that volume is an evolutionarily and developmentally regulated fundamental property of tissue, in this instance the brain and its component structures. Within this framework (1), regularities in relative variation of volumes with respect to mean volume of a structure are viewed as systematic manifestations of the rules of histogenetic process (2), regularities in the relative strength of correlation of volumes of structures are suggested to reflect constraints which serve systematically the requirements of neural systems operation. These hypotheses, if supported by extensive observation, may guide the design of applications of MRI based volumetric analysis of the human brain. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, McLean Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Caviness, VS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. EM caviness@helix.mgh.harvard.edu RI Kennedy, David/H-3627-2012 FU NIDA NIH HHS [DA09467]; NINDS NIH HHS [NS27950, NS37483] NR 69 TC 62 Z9 66 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0387-7604 J9 BRAIN DEV-JPN JI Brain Dev. PD JUL PY 1999 VL 21 IS 5 BP 289 EP 295 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 210KA UT WOS:000081102900001 PM 10413014 ER PT J AU Louis, DN AF Louis, DN TI Glioma genetics: Widening the light under the lamppost SO BRAIN PATHOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Louis, DN (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT SOC NEUROPATHOLOGY PI PITTSBURGH PA 200 LOTHROP ST A506, PITTSBURGH, PA 15213 USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JUL PY 1999 VL 9 IS 3 BP 442 EP 443 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 214YE UT WOS:000081354500003 ER PT J AU Isacson, O AF Isacson, O TI The neurobiology and neurogenetics of stem cells SO BRAIN PATHOLOGY LA English DT Editorial Material ID LONG-TERM SURVIVAL; PARKINSONS-DISEASE; NEURAL PROGENITOR; NERVOUS-SYSTEM; TRANSPLANTATION; ENGRAFTMENT; NEURONS; BRAIN C1 Harvard Univ, McLean Hosp, Sch Med, Neuroregenerat Labs, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Cambridge, MA 02138 USA. RP Isacson, O (reprint author), Harvard Univ, McLean Hosp, Sch Med, Neuroregenerat Labs, 115 Mill St, Belmont, MA 02478 USA. NR 15 TC 8 Z9 8 U1 0 U2 1 PU INT SOC NEUROPATHOLOGY PI PITTSBURGH PA 200 LOTHROP ST A506, PITTSBURGH, PA 15213 USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JUL PY 1999 VL 9 IS 3 BP 495 EP 498 PG 4 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 214YE UT WOS:000081354500008 PM 10416989 ER PT J AU Zavosh, A Schaefer, J Ferrel, A Figlewicz, DP AF Zavosh, A Schaefer, J Ferrel, A Figlewicz, DP TI Desipramine treatment decreases H-3-nisoxetine binding and norepinephrine transporter mRNA in SK-N-SHSY5Y cells SO BRAIN RESEARCH BULLETIN LA English DT Article DE norepinephrine transporter; quantitative RTPCR; desipramine; neuroblastoma ID MESSENGER-RNA LEVELS; DOWN-REGULATION; NORADRENALINE; EXPRESSION AB The antidepressant desipramine has been shown to decrease synaptic membrane concentrations of the norepinephrine re-uptake transporter (NET) in vivo and in vitro, on both an acute and a chronic basis. The possible contribution of decreased NET synthesis to the chronic downregulation of the NETs has not been definitively established. In this study, we treated SK-N-SHSY5Y cells with 100 nM desipramine for 24 or 72 h, and measured H-3-nisoxetine binding (as an estimate of NETs) and NET mRNA by quantitative reverse transcription polymerase chain reaction. Similar to what has been reported previously, membrane 3H-nisoxetine binding was significantly decreased at both 24 and 72 h (approximately 50% at both time points). However, a significant decrease (64 +/- 8% of paired control) of NET mRNA was observed only at the 72-h time point. We conclude that decreased NET synthesis may contribute to the chronic, but not acute, effect of desipramine to downregulate the NET. (C) 1999 Elsevier Science Inc. C1 VA Puget Sound Hlth Care Syst, Div Endocrinol & Metab 151, Seattle, WA USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA USA. RP Figlewicz, DP (reprint author), VA Puget Sound Hlth Care Syst, Div Metab Endocrinol 151, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [DK17047, R01 DK40963] NR 18 TC 16 Z9 16 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD JUL 1 PY 1999 VL 49 IS 4 BP 291 EP 295 DI 10.1016/S0361-9230(99)00063-5 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 215TT UT WOS:000081399800008 PM 10424850 ER PT J AU Leyton, J Gozes, Y Pisegna, J Coy, D Purdom, S Casibang, M Zia, F Moody, TW AF Leyton, J Gozes, Y Pisegna, J Coy, D Purdom, S Casibang, M Zia, F Moody, TW TI PACAP(6-38) is a PACAP receptor antagonist for breast cancer cells SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE PACAP; VIP; breast cancer; proliferation ID CYCLASE-ACTIVATING POLYPEPTIDE; INTESTINAL-PEPTIDE VIP; ADENYLATE-CYCLASE; FUNCTIONAL EXPRESSION; SIGNAL-TRANSDUCTION; SPLICE VARIANTS; I RECEPTOR; RAT-BRAIN; LUNG; GROWTH AB The effects of pituitary adenylate cyclase activating polypeptide (PACAP) analogs were investigated using breast cancer cells. I-125-PACAP-27 bound with high affinity (Kd = 5 nM) to T47D cells (Bmax = 29,000 per cell). Specific I-125-PACAP-27 binding was inhibited half maximally by PACAP-27, PACAP-38, PACAP(6-38) and PACAP(28-38) with IC50 values of 8, 17, 750 and > 3000 nM, respectively. By RT-PCR, PACAP receptor mRNA was present in MCF-7 and T47D cell lines. Polyclonal antibodies to a PACAP receptor fragment (A-8-C) were elicited. The antibodies were affinity purified, recognized a 60-kDa protein by western blot, and stained malignant cells in breast cancer biopsy specimens by immunohistochemistry. PACAP-27 elevated the cAMP in T47D cells and the increase in cAMP caused by PACAP was inhibited by PACAP(6-38). PACAP-27 stimulated c-fos mRNA in T47D cells and the increase in c-fos gene expression caused by PACAP was reversed by PACAP(6-38). PACAP(6-38) inhibited colony formation using a soft agar assay and inhibited breast cancer xenograft growth in nude mice. These data suggest that PACAP(6-38) functions as a breast cancer PACAP receptor antagonist. C1 NCI, Dept Cell & Canc Biol, Med Branch, Rockville, MD 20850 USA. Israel Inst Biol Res, IL-70450 Ness Ziona, Israel. W Los Angeles Vet Affairs Med Ctr, CURE VA UCLA, Ctr Digest Dis, Los Angeles, CA 90073 USA. Tulane Univ, Sch Med, Med Branch, New Orleans, LA 70112 USA. George Washington Univ, Med Ctr, Dept Microbiol, Washington, DC 20037 USA. RP Leyton, J (reprint author), NCI, Dept Cell & Canc Biol, Med Branch, MCI 9610 Med Ctr, Rockville, MD 20850 USA. FU NIDDK NIH HHS [DK-36107] NR 41 TC 24 Z9 24 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUL PY 1999 VL 56 IS 2 BP 177 EP 186 PG 10 WC Oncology SC Oncology GA 239NW UT WOS:000082776400008 PM 10573110 ER PT J AU Menon, U Talaat, A Jeyarajah, AR Rosenthal, AN MacDonald, ND Skates, SJ Sibley, K Oram, DH Jacobs, IJ AF Menon, U Talaat, A Jeyarajah, AR Rosenthal, AN MacDonald, ND Skates, SJ Sibley, K Oram, DH Jacobs, IJ TI Ultrasound assessment of ovarian cancer risk in postmenopausal women with CA125 elevation SO BRITISH JOURNAL OF CANCER LA English DT Article DE ovarian cancer; risk; ultrasound; CA125; screening ID PREOPERATIVE DIAGNOSIS; MENOPAUSAL STATUS; SERUM CA-125; CHEMOTHERAPY; CARCINOMA AB We have previously shown that, in asymptomatic post-menopausal women, serum CA125 elevation is associated with a 36-fold increase in risk of ovarian cancer. This study was undertaken to assess the value of pelvic ultrasound for further stratification of ovarian cancer risk. Of 22 000 post-menopausal women, aged greater than or equal to 45 participating in an Ovarian Cancer Screening Trial, 741 with a CA125 greater than or equal to 30 U ml(-1) underwent pelvic ultrasonography. Twenty index cancers (primary invasive epithelial carcinomas of the ovary and fallopian tube) were diagnosed amongst these 741 women during a median follow-up of 6.8 years; Ultrasound results separated the women with CA125 elevation into two groups. Those with normal ovarian morphology had a cumulative risk (CR) of index cancer of 0.15% (95% confidence interval (CI) 0.02-1.12) which is similar to that of the entire population of 22 000 women (0.22%, 95% Cr 0.18-0.30). In contrast, women with abnormal ovarian morphology had a CR of 24% (15-37) and a significantly increased relative risk (RR) of 327 (156-683). Ultrasound can effectively separate post-menopausal women with raised CA125 levels into those with normal Scan findings who are not at increased risk of index cancer and those with abnormal findings who are at substantially increased risk of index cancer. C1 St Bartholomews & Royal London Sch Med & Dent, Gynaecol Canc Res Unit, London EC1A 7BE, England. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jacobs, IJ (reprint author), St Bartholomews & Royal London Sch Med & Dent, Gynaecol Canc Res Unit, London EC1A 7BE, England. RI Menon, Usha/C-4716-2008; Jacobs, Ian/F-1743-2013 OI Jacobs, Ian/0000-0002-8112-4624 NR 11 TC 41 Z9 46 U1 0 U2 1 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 JUL PY 1999 VL 80 IS 10 BP 1644 EP 1647 DI 10.1038/sj.bjc.6690575 PG 4 WC Oncology SC Oncology GA 213UE UT WOS:000081291000027 PM 10408412 ER PT J AU Shcherbina, A Bretscher, A Rosen, FS Kenney, DM Remold-O'Donnell, E AF Shcherbina, A Bretscher, A Rosen, FS Kenney, DM Remold-O'Donnell, E TI The cytoskeletal linker protein moesin: decreased levels in Wiskott-Aldrich syndrome platelets and identification of a cleavage pathway in normal platelets SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 1996 CL ORLANDO, FLORIDA SP Amer Soc Hematol, US Dept Vet Affairs Merit Res Funds, NIH DE Wiskott-Aldrich syndrome; platelets; lymphocytes; moesin; ERM proteins ID PROCOAGULANT ACTIVITY; PLASMA-MEMBRANE; F-ACTIN; CALPAIN; EZRIN; ACTIVATION; BINDING; CELLS; DOMAIN; PHOSPHORYLATION AB The Wiskott-Aldrich syndrome (WAS) is a severe disease of platelets (small size, thrombocytopenia) and lymphocytes (immunodeficiency) arising from mutations of the X-chromosome gene WASP. Because of the prominent role of cytoskeletal abnormalities, particularly the paucity of surface microvilli, in the cellular pathology of this disease, blood cells from WAS patients were examined for moesin, a cytoskeletal linker protein that stabilizes cell surface microvilli, filopodia and lamellipodia. Comparison of patient and normal lymphocytes by immunofluorescence microscopy and immunoblotting showed normal levels and distribution of moesin in lymphocytes of WAS patients. In contrast, platelets from WAS patients stained only dimly for moesin relative to normal platelets. Quantitation by immunoblot revealed significantly decreased moesin levels in WAS patient platelets relative to normal platelets (63.5 +/- 4.9% of normal levels, n=8, P < 0.0001). A novel reaction of normal platelets was discovered that may play a role in the depletion of moesin in patient platelets, namely the cleavage of moesin as a late event in platelet activation in response to certain platelet agonists. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Moscow Med Univ, Moscow, Russia. Cornell Univ, Biochem Mol & Cell Biol Sect, Ithaca, NY USA. RP Remold-O'Donnell, E (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL59561, P01 HL059561]; NIAID NIH HHS [AI39574, R01 AI039574]; NIGMS NIH HHS [GM36652] NR 36 TC 7 Z9 8 U1 0 U2 3 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 JUL PY 1999 VL 106 IS 1 BP 216 EP 223 DI 10.1046/j.1365-2141.1999.01508.x PG 8 WC Hematology SC Hematology GA 219QP UT WOS:000081618500036 PM 10444190 ER PT J AU Safa, AA Tran, LM Rege, S Brown, CV Mandelkern, MA Wang, MB Sadeghi, A Juillard, G AF Safa, AA Tran, LM Rege, S Brown, CV Mandelkern, MA Wang, MB Sadeghi, A Juillard, G TI The role of positron emission tomography in occult primary head and neck cancers SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Article; Proceedings Paper CT 80th Annual Meeting of the American-Radium-Society CY MAY 02-06, 1998 CL MONTE CARLO, MONACO SP Amer Radium Soc DE emission CT; tomography; fluorine radioisotope; head and neck neoplasms; diagnosis ID UNKNOWN PRIMARY; CERVICAL METASTASES; FDG-PET; TUMORS; IRRADIATION; CARCINOMA AB PURPOSE To evaluate the utility of positron emission tomography (PET) fluorodeoxyglucose (FDG) imaging in the workup of unknown primary head and neck tumors. METHODS Fourteen patients with squamous cell carcinoma of cervical lymph node metastasis of unknown primary origin (clinical stage N2-N3) were studied prospectively. The patients underwent conventional workup, including physical examination, computed tomography, and random biopsies of the potentially suspected sites. If no primary site was found, 8 to 13 mCi of FDG was given intravenously, and whole-body scans with standardized uptake values were obtained. The results of FDG-PET imaging were compared with clinical, CT, and histopathologic findings. To eliminate bias, PET scans were reviewed by nuclear medicine physicians who had no previous knowledge of the other findings. RESULTS PET identified the location of primary tumor in three patients: lung hilum, base of tongue, and pyriform sinus. These lesions were pathologically confirmed, AU these primary sites were not visualized on CT or physical examination, except for a pyriform sinus lesion, which was seen on CT, but initial biopsy result was negative. In one patient, the initial PET did not identify a primary tumor, but a nasopharyngeal carcinoma was identified in post-radiation therapy follow-up PET. In the remaining nine patients, a primary lesion was never found. All cervical lymph nodes detected by CT were identified by PET. DISCUSSION A previously unknown primary tumor can be identified with FDG-PET in about 21% of the patients in our prospective series. PET can be of value in guiding endoscopic biopsies for histologic diagnosis and treatment options. C1 Univ Calif Los Angeles, Dept Radiat Oncol, Los Angeles, CA 90024 USA. W Los Angeles Vet Adm Hosp, Dept Radiat Oncol, Los Angeles, CA USA. W Los Angeles Vet Adm Hosp, Dept Nucl Med & Biophys, Los Angeles, CA USA. W Los Angeles Vet Adm Hosp, Dept Head & Neck Surg, Los Angeles, CA USA. RP Safa, AA (reprint author), Univ Calif Los Angeles, Dept Radiat Oncol, 200 UCLA Mee Plaza,Suite B265, Los Angeles, CA 90024 USA. NR 17 TC 46 Z9 48 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 USA SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD JUL-AUG PY 1999 VL 5 IS 4 BP 214 EP 218 PG 5 WC Oncology SC Oncology GA 221VR UT WOS:000081748100005 PM 10439166 ER PT J AU Willett, CG Goldberg, S Shellito, PC Grossbard, M Clark, J Fung, C Proulx, G Daly, M Kaufman, DS AF Willett, CG Goldberg, S Shellito, PC Grossbard, M Clark, J Fung, C Proulx, G Daly, M Kaufman, DS TI Does postoperative irradiation play a role in the adjuvant therapy of stage T4 colon cancer? SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Article DE colon cancer; adjuvant radiation therapy; adjuvant chemotherapy ID WHOLE-ABDOMINAL RADIATION; CARCINOMA; PATTERNS; FLUOROURACIL; ADENOCARCINOMA; RECURRENCE; LEVAMISOLE; RESECTION; SURGERY; FAILURE AB PURPOSE This study analyzes the long-term outcome of patients with stage T4 colon cancer who receive postoperative irradiation. The purpose of the study is to define the potential role of this modality with current systemic therapies. PATIENTS AND METHODS A retrospective analysis was performed of 152 patients undergoing resection of T4 colon cancer followed by moderate- to high-dose postoperative tumor bed irradiation with and without 5-fluorouracil-based chemotherapy. Of the 152 patients, 110 patients (T4N0 or T4N+) were treated adjuvantly, whereas 42 patients received irradiation for the control of gross or microscopic residual local tumor. RESULTS For 79 adjuvantly treated patients with stage T4N0 or T4N+ cancer with one lymph node metastasis, the 10-year actuarial rates of local control and recurrence-free survival were 88% and 58%, respectively. Results were less satisfactory for patients with more extensive nodal involvement. The 10-year actuarial rates of local control and recurrence-free survival of 39 patients with T4 tumors complicated by perforation or fistulas were 81% and 53%, respectively. For 42 patients with incompletely resected tumors, the 10-year actuarial recurrence-free survival was 19%. CONCLUSIONS In comparison with historical controls, postoperative tumor bed irradiation improves local control for some subsets of patients. In addition to standard 5-fluorouracil-based chemotherapy, adjuvant tumor Led irradiation should be considered when colon cancers invade adjoining structures, when they are complicated by perforation or fistulas, or when they are incompletely excised at the primary site. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. RP Willett, CG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. NR 16 TC 17 Z9 17 U1 0 U2 2 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 USA SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD JUL-AUG PY 1999 VL 5 IS 4 BP 242 EP 247 PG 6 WC Oncology SC Oncology GA 221VR UT WOS:000081748100010 PM 10439171 ER PT J AU Iwamoto, R Fitzgibbons, K Langer, CJ Sarna, L Eisenberg, P AF Iwamoto, R Fitzgibbons, K Langer, CJ Sarna, L Eisenberg, P TI Woman with lung cancer who continues to smoke SO CANCER PRACTICE LA English DT Article C1 Virginia Mason Med Ctr, Dept Radiat Oncol, Seattle, WA 98101 USA. Vet Affairs Puget Sound Hlth Care Syst, Addict Treatment Ctr, Seattle, WA USA. Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. Community Hosp Indianapolis, Indianapolis, IN USA. RP Iwamoto, R (reprint author), Virginia Mason Med Ctr, Dept Radiat Oncol, Seattle, WA 98101 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1065-4704 J9 CANCER PRACT JI Cancer Pract. PD JUL-AUG PY 1999 VL 7 IS 4 BP 165 EP 169 PG 5 WC Oncology; Health Care Sciences & Services; Nursing SC Oncology; Health Care Sciences & Services; Nursing GA 217VQ UT WOS:000081520000002 ER PT J AU Chuang, YYE Chen, Q Liber, HL AF Chuang, YYE Chen, Q Liber, HL TI Radiation-induced mutations at the autosomal thymidine kinase locus are not elevated in p53-null cells SO CANCER RESEARCH LA English DT Article ID HOMOLOGOUS RECOMBINATION; X-IRRADIATION; P53 STATUS; LINES; SENSITIVITY; APOPTOSIS; GENE; GAIN; RADIOSENSITIVITY; RESPONSES AB To explore further the possibility that some forms of mutated p53 may increase mutagenesis in a positive manner, a double p53 knockout cell line was created, using a promoterless gene targeting approach. The identity of these p53-null cells was confirmed by Southern blot and Western blot analyses. Radiation-induced toxicity and mutagenicity was then compared among p53-null cells, TK6 cells with wild-type p53, and WTK1 cells with a p53 point mutation in codon 237, At the autosomal, heterozygous thymidine kinase locus, p53-null cells had equivalent background mutation frequencies and sere approximately equally mutable as TK6, whereas WTK1 was much more sensitive to spontaneously arising and X-ray-induced mutation. Thus, these results indicate! that the lack of wild-type p53 did not lead to increased mutagenesis. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Liber, HL (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 302, Boston, MA 02114 USA. FU NCI NIH HHS [CA09078, CA49696] NR 20 TC 69 Z9 70 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1999 VL 59 IS 13 BP 3073 EP 3076 PG 4 WC Oncology SC Oncology GA 212BL UT WOS:000081196400012 PM 10397247 ER PT J AU Brandstetter, H Whittington, DA Lippard, SJ Frederick, CA AF Brandstetter, H Whittington, DA Lippard, SJ Frederick, CA TI Mutational and structural analyses of the regulatory protein B of soluble methane monooxygenase from Methylococcus capsulatus (Bath) SO CHEMISTRY & BIOLOGY LA English DT Article DE circular dichroism spectroscopy; glycine hinge; hydroxylase; secondary structure prediction; size exclusion chromatography ID METHYLOSINUS-TRICHOSPORIUM OB3B; HYDROXYLASE COMPONENT; LIMITED PROTEOLYSIS; SECONDARY STRUCTURE; PHENOL HYDROXYLASE; SUBSTRATE; SEQUENCE; IDENTIFICATION; BACTERIA AB Background: The soluble methane monooxygenase (sMMO) system in methanotrophic bacteria uses three protein components to catalyze the selective oxidation of methane to methanol. The coupling protein B (MMOB) both activates the carboxylate-bridged diiron center in the hydroxylase (MMOH) for substrate oxidation and couples the reaction to electron transfer from NADH through the sMMO reductase. Although the X-ray structure of the hydroxylase is known, little structural information is available regarding protein B. Results: Wild-type protein B from Methylococcus capsulatus (Bath) is very susceptible to degradation. The triple mutant protein B, Gly10-->Ala, Gly13-->Gln, Gly16-->Ala is resistant to degradation. Analyzing wild-type and mutant forms of protein B using size exclusion chromatography and circular dichroism spectroscopy suggests that the amino terminus of MMOB (Ser1-Ala25) is responsible for the proteolytic sensitivity and unusual mobility of the protein. We used the stable triple glycine protein B mutant to generate an affinity column for the hydroxylase and investigated the interaction between MMOH and MMOB. These results suggest the interaction is dominated by hydrophobic contacts. Conclusions: A structural model is presented for protein B that explains both its proclivity for degradation and its anomalous behavior during size exclusion chromatography, The model is consistent with previously published biophysical data, including the NMR structure of the phenol hydroxylase regulatory protein P2. Furthermore, this model allows for detailed and testable predictions about the structure of protein B and the role of proposed recognition sites for the hydroxylase. C1 MIT, Dept Chem, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lippard, SJ (reprint author), MIT, Dept Chem, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RI Brandstetter, Hans/E-6754-2011 OI Brandstetter, Hans/0000-0002-6089-3045 FU NIGMS NIH HHS [GM48388, GM32134] NR 41 TC 29 Z9 30 U1 0 U2 10 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD JUL PY 1999 VL 6 IS 7 BP 441 EP 449 DI 10.1016/S1074-5521(99)80062-3 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 218UH UT WOS:000081569700006 PM 10381404 ER PT J AU Levine, SM AF Levine, SM TI Can bronchiolitis obliterans syndrome be diagnosed by phone from the comfort of home? SO CHEST LA English DT Editorial Material ID LUNG-TRANSPLANTATION; HEART-LUNG; REJECTION; SPIROMETRY C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. RP Levine, SM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 11 TC 8 Z9 8 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 JUL PY 1999 VL 116 IS 1 BP 5 EP 6 DI 10.1378/chest.116.1.5 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 217RR UT WOS:000081513200003 PM 10424495 ER PT J AU Quinn, D Tager, A Joseph, PM Bonventre, JV Force, T Hales, CA AF Quinn, D Tager, A Joseph, PM Bonventre, JV Force, T Hales, CA TI Stretch-induced mitogen-activated protein kinase activation and interleukin-8 production in type II alveolar cells SO CHEST LA English DT Article; Proceedings Paper CT 41st Annual Thomal L Petty Aspen Lung Conference on Acute Lung Injury CY JUN 03-06, 1998 CL ASPEN, COLORADO SP 3M Pharmaceut, Alliance Pharmaceut Corp, Astra USA, Bayer Pharmaceut Div, Boehringer Ingelheim Pharmaceut Inc, Bristol-Myers Squibb Oncol, Dura Pharmaceut, Eli Lilly & Co Inc, Genetech Inc, Glaxo Wellcome, Hoechst Marion Roussel Inc, Human Genome Sci Inc, Invitrogen Corp, Key Pharmaceut, Merck Res Labs & Merck Frosst Canada, NEXSTAR Pharmaceut Inc, Novartis Pharmaceut Corp, Ohmeda Inc, Ortho-McNeil Pharmaceut Inc, PathoGenesis Corp, Pfizer Inc, Pharmacia & Upjohn, Rhone-Poulenc Rorer Pharmaceut, Roche Labs, Sanofi Winthrop Inc, Schering Corp, Teijin Ltd, Wallace Labs, Zeneca Pharmaceut, Francis Families Fdn, Respiratory Distress Syndrome Fdn, Aspen Lung Conf Endowment Fund C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Unit, Boston, MA 02114 USA. RP Quinn, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm Crit Care Unit, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL39150, HL09572]; NIDDK NIH HHS [DK50282] NR 0 TC 32 Z9 34 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 JUL PY 1999 VL 116 IS 1 SU S BP 89S EP 90S DI 10.1378/chest.116.suppl_1.89S PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 220CC UT WOS:000081646100053 PM 10424608 ER PT J AU Tager, A Luster, A Kradin, R AF Tager, A Luster, A Kradin, R TI T-cell chemokines interferon-inducible protein-10 and monokine induced by interferon-gamma are upregulated in bleomycin-induced lung injury SO CHEST LA English DT Article; Proceedings Paper CT 41st Annual Thomal L Petty Aspen Lung Conference on Acute Lung Injury CY JUN 03-06, 1998 CL ASPEN, COLORADO SP 3M Pharmaceut, Alliance Pharmaceut Corp, Astra USA, Bayer Pharmaceut Div, Boehringer Ingelheim Pharmaceut Inc, Bristol-Myers Squibb Oncol, Dura Pharmaceut, Eli Lilly & Co Inc, Genetech Inc, Glaxo Wellcome, Hoechst Marion Roussel Inc, Human Genome Sci Inc, Invitrogen Corp, Key Pharmaceut, Merck Res Labs & Merck Frosst Canada, NEXSTAR Pharmaceut Inc, Novartis Pharmaceut Corp, Ohmeda Inc, Ortho-McNeil Pharmaceut Inc, PathoGenesis Corp, Pfizer Inc, Pharmacia & Upjohn, Rhone-Poulenc Rorer Pharmaceut, Roche Labs, Sanofi Winthrop Inc, Schering Corp, Teijin Ltd, Wallace Labs, Zeneca Pharmaceut, Francis Families Fdn, Respiratory Distress Syndrome Fdn, Aspen Lung Conf Endowment Fund C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kradin, R (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. FU NCI NIH HHS [R01 CA69212]; NIAID NIH HHS [R01 AI39054-01] NR 0 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 JUL PY 1999 VL 116 IS 1 SU S BP 90S EP 90S DI 10.1378/chest.116.suppl_1.90S PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 220CC UT WOS:000081646100054 PM 10424609 ER PT J AU Steinberg, B Padwa, BL Boyne, P Kaban, L AF Steinberg, B Padwa, BL Boyne, P Kaban, L TI State of the art in oral and maxillofacial surgery: Treatment of maxillary hypoplasia and anterior palatal and alveolar clefts SO CLEFT PALATE-CRANIOFACIAL JOURNAL LA English DT Article DE alveolar cleft; bone grafting; maxillary hypoplasia; maxillary osteotomy; orthognathic surgery; palatal cleft ID ORTHOGNATHIC SURGERY; DISTRACTION OSTEOGENESIS; MIDFACE DISTRACTION; ENDOSSEOUS IMPLANTS; RESIDUAL ALVEOLAR; LIP; MANAGEMENT; OSTEOTOMIES; RECONSTRUCTION; ADVANCEMENT AB As the new millennium approaches, it seems appropriate to look back at where we have been and where we are going with the care of patients with facial deformities. None of us can deny that although changes have been made, many current treatment modalities are no more than modifications of old techniques. We are, however, poised to make dramatic improvements in the management of facial abnormalities as we enter the new century and millennium, Biotechnology, genetic manipulation, and new surgical technology will become pervasive, and perhaps we will move from "modification" of the old into a completely new era of therapeutic approaches to the care of dentofacial deformities. "Opportunities multiply as they are seized" (from Sun Tzu), and the time of opportunity is approaching. This review will attempt to look at the state of the art in cleft care and in oral and maxillofacial surgery: where we have been and where we are going. It will be clear that there is overlap between specialties and that these overlaps will become greater as new regimens in the care of facial deformities come to the forefront. C1 Univ Florida, Hlth Sci Ctr Jacksonville, Dept Maxillofacial Surg, Jacksonville, FL 32209 USA. Univ Med Ctr, Jacksonville, FL USA. Harvard Univ, Sch Dent Med, Childrens Hosp, Div Oral & Maxillofacial Surg, Cambridge, MA 02138 USA. Loma Linda Univ, Med Ctr, Dept Surg, Loma Linda, CA USA. Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Steinberg, B (reprint author), 653-1 W 8th St, Jacksonville, FL 32209 USA. NR 44 TC 18 Z9 20 U1 0 U2 2 PU AMER CLEFT PALATE-CRANIOFACIAL ASSOC PI CHAPEL HILL PA 1829 EAST FRANKLIN ST, STE 1022, CHAPEL HILL, NC 27514 USA SN 1055-6656 J9 CLEFT PALATE-CRAN J JI Cleft Palate-Craniofac. J. PD JUL PY 1999 VL 36 IS 4 BP 283 EP 291 DI 10.1597/1545-1569(1999)036<0284:SOTAIO>2.3.CO;2 PG 9 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA 216DM UT WOS:000081426000001 PM 10426593 ER PT J AU Bruss, JB Siber, GR AF Bruss, JB Siber, GR TI Protective effects of pertussis immunoglobulin (P-IGIV) in the aerosol challenge model SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID CELL-MEDIATED-IMMUNITY; BORDETELLA-PERTUSSIS; WHOLE-CELL; RESPIRATORY-INFECTION; FILAMENTOUS HEMAGGLUTININ; CONTROLLED TRIAL; PROMOTING FACTOR; TH1 CELLS; VACCINE; MICE AB Pertussis in infants is often severe, resulting in prolonged hospitalization. Treatment is limited to supportive care. Antibiotics do not significantly alter the course of the disease unless administered during the catarrhal phase. Therapies directed at pertussis toxin, a major virulence factor of Bordetella pertussis, may be beneficial. This study uses the aerosol challenge model to further examine the protective effects of P-IGIV, a new intravenous immunoglobulin product, which has high levels of pertussis toxin antibodies. P-IGIV was prepared as a 4% immunoglobulin G (IgG) solution from the pooled donor plasma from donors immunized with inactivated pertussis toroid. The IgG pertussis toxin antibody concentration in P-IGIV is >7 fold higher than conventional intravenous immunoglobulin products. In the aerosol challenge model, P-IGIV-treated mice exhibited a dose-dependent decrease in mortality when monitored for 28 days postchallenge. P-IGIV in doses of 2,800, 1,400, and 350 mg/kg significantly reduced mortality compared to saline (P < 0.01)- and human IGIV (P < 0.01)-treated controls. The 50% protective dose of pertussis toxin antibodies in P-IGIV was 147 mu g/ml. Recovery of weight gain and normalization of leukocyte counts occurred in all P-IGIV-treated groups but did not exhibit dose-dependent characteristics. Even after 7 days of infection, P-IGIV reversed the effects of pertussis in mice. This study provides further evidence that pertussis toxin antibodies not only play a role in passive protection but can also reverse symptoms of established disease in mice. We feel that P-IGIV deserves further evaluation in children hospitalized with severe pertussis. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Bruss, JB (reprint author), Pharmacia & Upjohn Inc, 7000 Portage Rd, Kalamazoo, MI 49001 USA. NR 63 TC 16 Z9 18 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD JUL PY 1999 VL 6 IS 4 BP 464 EP 470 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 215LA UT WOS:000081382100004 PM 10391844 ER PT J AU Jain, RK AF Jain, RK TI Understanding barriers to drug delivery: High resolution in vivo imaging is key SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID ENDOTHELIAL GROWTH-FACTOR; IN-VIVO; NEOPLASTIC TISSUES; SOLID TUMORS; ANGIOGENESIS; CELL; PERMEABILITY; DOXORUBICIN; ADRIAMYCIN; TRANSPORT C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. NR 29 TC 63 Z9 64 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL PY 1999 VL 5 IS 7 BP 1605 EP 1606 PG 2 WC Oncology SC Oncology GA 217TG UT WOS:000081514600001 PM 10430057 ER PT J AU Barnett, ED Pelton, SI Cabral, HJ Eavey, RD Allen, C Cunningham, MJ McNamara, ER Klein, JO AF Barnett, ED Pelton, SI Cabral, HJ Eavey, RD Allen, C Cunningham, MJ McNamara, ER Klein, JO TI Immune response to pneumococcal conjugate and polysaccharide vaccines in otitis-prone and otitis-free children SO CLINICAL INFECTIOUS DISEASES LA English DT Article AB We compared responses to pneumococcal conjugate and polysaccharide vaccines in 48 otitis-free and 64 otitis-prone children. Pre- and postimmunization concentrations of antibodies to pneumococcal serotypes 6B, 14, 19F, and 23F were measured by enzyme-linked immunosorbent assay. Postimmunization mean concentrations of antibodies to all four serotypes were significantly higher for children receiving conjugate vaccine than for those receiving polysaccharide vaccine; the difference in responses was primarily due to a better response to conjugate vaccine in the otitis-prone group, Significantly higher postimmunization concentrations of antibodies to all four serotypes and to one of the four serotypes were found in otitis-prone children and otitis-free children who received conjugate vaccine, respectively, Pneumococcal conjugate vaccine has the potential to reduce the incidence of disease due to vaccine serotypes, even among children with recurrent otitis media. C1 Boston Med Ctr, Maxwell Finland Lab Infect Dis, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA USA. Childrens Hlth Care, Arlington, MA USA. RP Barnett, ED (reprint author), Boston Med Ctr, Maxwell Finland Lab Infect Dis, Room 503,774 Albany St, Boston, MA 02118 USA. NR 3 TC 37 Z9 38 U1 0 U2 1 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 JUL PY 1999 VL 29 IS 1 BP 191 EP 192 DI 10.1086/520151 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 220UF UT WOS:000081685300031 PM 10433584 ER PT J AU Swartz, BE Goldensohn, ES AF Swartz, BE Goldensohn, ES TI Timeline of the history of EEG and associated fields (vol 106, pg 173, 1998) SO CLINICAL NEUROPHYSIOLOGY LA English DT Correction C1 W Los Angeles Vet Affairs Med Ctr, Epilepsy Ctr, Los Angeles, CA 90073 USA. Montefiore Med Ctr, Albert Einstein Sch Med, Bronx, NY 10467 USA. RP Swartz, BE (reprint author), W Los Angeles Vet Affairs Med Ctr, Epilepsy Ctr, W127B,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 1 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD JUL PY 1999 VL 110 IS 7 BP 1323 EP 1323 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 212LX UT WOS:000081219100020 ER PT J AU Rosenthal, RK Folkman, J Glowacki, J AF Rosenthal, RK Folkman, J Glowacki, J TI Demineralized bone implants for nonunion fractures, bone cysts, and fibrous lesions SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID INDUCED OSTEOGENESIS; AUTOLOGOUS BONE; DEFECTS AB Demineralized bone implants were used to treat eight patients with fracture nonunion, five patients with bone cysts, and eight patients with fibrous lesions. Five of the eight patients with nonunions had had previous unsuccessful attempts at reconstruction. After fixation and implantation with either human or bovine demineralized bone, all eight fractures healed. For those patients with nonunion fractures, mean followup time was 8 years, 5 months, and longest followup was 15 years, 3 months. The cystic lesions in five patients included three typical aneurysmal bone cysts and two recurrent unicameral bone cysts. The aneurysmal bone cysts had excellent healing and bone remodeling. The two unicameral bone cysts were repacked more densely after 1 year and healed. For these patients with bone cysts, the mean followup time was 12 years, 5 months, and longest followup was 15 years, 1 month. The various fibrous lesions in seven of the eight patients were healed within 6 months, with only one requiring repacking. For these patients with fibrous bone lesions, the mean followup time was 9 years, 8 months, and longest followup was 14 years. A biopsy of the lesions in five patients was performed and in two cases showed osteoblasts and new bone around small particles of the implants, These results with long term followup show that allogeneic or xenogeneic demineralized bone implants offer a reasonable alternative for the treatment of typical nonunion fractures, bone cysts, and fibrous lesions of bone. C1 Childrens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Skeletal Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Rosenthal, RK (reprint author), Childrens Hosp, Dept Orthoped Surg, 300 Longwood Ave, Boston, MA 02115 USA. NR 31 TC 29 Z9 35 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 JUL PY 1999 IS 364 BP 61 EP 69 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 216CZ UT WOS:000081424800010 PM 10416393 ER PT J AU Podolsky, DK AF Podolsky, DK TI Inflammatory bowel disease 1999: present and future prom ises SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St GRJ-719, 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 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD JUL PY 1999 VL 15 IS 4 BP 283 EP 284 DI 10.1097/00001574-199907000-00001 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 209BH UT WOS:000081027000001 PM 17023958 ER PT J AU Bhan, AK Mizoguchi, E Smith, N Mizoguchi, A AF Bhan, AK Mizoguchi, E Smith, N Mizoguchi, A TI Lessons for human inflammatory bowel disease from experimental models SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article ID ALPHA-MUTANT MICE; CD4(+) T-CELLS; TUMOR-NECROSIS-FACTOR; ENTERIC BACTERIAL-ANTIGENS; ULCERATIVE-COLITIS; CROHNS-DISEASE; DEFICIENT MICE; B-CELLS; HELICOBACTER-HEPATICUS; TRANSGENIC MICE AB Experiments carried out in new rodent models of chronic intestinal inflammation provide important clues about the pathogenesis of human inflammatory bowel disease (IBD). Genetic factors and enteric microflora are driving forces regulating mucosal immune responses, some of which are pathogenic and lead to colitis, CD4+ T cells are the major pathogenic cells in colitis, and the type of injury depends on the nature of the cytokine imbalance, The cytokine network controlled by CD4+ T cells dictates the outcome of the mucosal immune responses. Certain cytokines, such as transforming growth factor-p and interleukin-10, have a suppressive role, and immunoregulatory T cells capable of secreting these cytokines may be induced at intestinal mucosal sites, Lessons learned from these experimental models are leading to new strategies for the treatment of IBD. (C) 1999 Lippincott Williams & Wilkins, Inc. C1 Massachusetts Gen Hosp, Immunopathol Unit, Dept Pathol, Boston, MA 02114 USA. RP Bhan, AK (reprint author), Massachusetts Gen Hosp, Immunopathol Unit, Dept Pathol, 100 Blossom St,Cox 502, Boston, MA 02114 USA. NR 66 TC 10 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD JUL PY 1999 VL 15 IS 4 BP 285 EP 290 DI 10.1097/00001574-199907000-00002 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 209BH UT WOS:000081027000002 PM 17023959 ER PT J AU Ooi, CJ Sands, BE AF Ooi, CJ Sands, BE TI Treatment of ulcerative colitis SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article ID PLATELET-ACTIVATING-FACTOR; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; CYCLOSPORINE; MESALAZINE; MESALAMINE; PREDNISOLONE; ANTAGONIST; PREGNANCY; PROCTITIS AB Advances in the treatment of ulcerative colitis have continued to focus on improved local delivery of existing agents, such as 5-aminosalicylate and corticosteroids, and on novel immunosuppressive agents. Although newer preparations of 5-aminosalicylate continue to provide incremental benefits in safety, tolerance, and efficacy, there is a growing understanding of the limits of benefit from increasing doses. Knowledge of the safety of these agents, particularly in regard to their use in pregnancy, continues to expand. Novel corticosteroids are used in much of the world for the treatment of ulcerative colitis, with the exception of the United States, with anticipated benefits in safety but little additional therapeutic benefit. Innovative use of oral emulsion preparations of cyclosporine has been reported in the treatment of ulcerative colitis and adds to the growing body of literature on the efficacy of cyclosporine in severe disease. Relatively limited experience with other immunosuppressive agents, such as tacrolimus, has been reported. The role of antibiotics in the treatment of ulcerative colitis has continued to present controversy. (C) 1999 Lippincott Williams & Wilkins, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Gastrointestinal Unit, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. RP Sands, BE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Gastrointestinal Unit, Ctr Study Inflammatory Bowel Dis, 55 Fruit St, Boston, MA 02114 USA. NR 17 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD JUL PY 1999 VL 15 IS 4 BP 298 EP 301 DI 10.1097/00001574-199907000-00004 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 209BH UT WOS:000081027000004 PM 17023961 ER PT J AU Duncan, LM AF Duncan, LM TI Cutaneous lymphoma - Understanding the new classification schemes SO DERMATOLOGIC CLINICS LA English DT Review ID T-CELL LYMPHOMA; NATURAL-KILLER-CELL; POLYMERASE CHAIN-REACTION; RECEPTOR GENE REARRANGEMENT; FUNGOIDES SEZARY-SYNDROME; BCL-2 PROTEIN EXPRESSION; VIRUS TYPE-I; MYCOSIS-FUNGOIDES; LYMPHOPROLIFERATIVE DISORDERS; HTLV-I AB Both the REAL and EORTC classification schemes classify lymphomas according to their cell of origin. These schemata also incorporate clinical features that allow for the distinction of some of these disorders. The EORTC classification scheme for primary cutaneous tumors uses similar terminology to that of the REAL classification and should allow for the recognition of teleologically similar tumors in cutaneous and extracutaneous sites. An understanding of the new lymphoma classification schemata will enable dermatologists to present the appropriate information regarding prognosis, staging procedures, and therapeutic options to their patients with cutaneous lymphoma. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatopathol Unit, Boston, MA 02114 USA. RP Duncan, LM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatopathol Unit, Boston, MA 02114 USA. NR 126 TC 13 Z9 14 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0733-8635 J9 DERMATOL CLIN JI Dermatol. Clin. PD JUL PY 1999 VL 17 IS 3 BP 569 EP + DI 10.1016/S0733-8635(05)70108-X PG 25 WC Dermatology SC Dermatology GA 214FV UT WOS:000081318700009 PM 10410859 ER PT J AU Kinsley, BT Weinger, K Bajaj, M Levy, CJ Simonson, DC Quigley, M Cox, DJ Jacobson, AM AF Kinsley, BT Weinger, K Bajaj, M Levy, CJ Simonson, DC Quigley, M Cox, DJ Jacobson, AM TI Blood glucose awareness training and epinephrine responses to hypoglycemia during intensive treatment in type 1 diabetes SO DIABETES CARE LA English DT Article ID MELLITUS; IDDM; SYMPTOMS; THERAPY; COUNTERREGULATION; PLASMA AB OBJECTIVE - To determine the effect of blood glucose awareness training (BGAT) on epinephrine and symptom responses to hypoglycemia in patients with type 1 diabetes enrolled in an intensive diabetes treatment (IDT) program. RESEARCH DESIGN AND METHODS - A total of 47 subjects with uncomplicated diabetes (duration 9 +/- 3 years, HbA(1c) 9.0 +/- 1.2%; reference range 4-6%) enrolled in a 4-month outpatient IDT program were randomized to classes in BGAT (n = 25) (BGAT group) or cholesterol awareness (n = 22) (control group). Subjects underwent stepped hypoglycemic clamp studies before and at completion of IDT. Plasma glucose was lowered from 6.7 mmol/l (baseline) to 4.4, 3,9, 3.3, 2.8, and 2.2 mmol/l over 190 min. Symptoms, counterregulatory hormones, and ability of the subject to estimate their glucose level were assessed at each plateau, At home, subjects used a handheld computer to first estimate and then measure and record blood glucose levels for 70 trials over a 4-week period immediately before IDT and again immediately following the educational intervention. RESULTS - HbA(1c) decreased in both BGAT group (9.1 +/- 1.4 to 7.9 +/- 1.1%; P < 0.001) and control group (9.0 +/- 1.1 to 7.8 +/- 0.8%; P < 0.001) (NS between groups). Frequency of hypoglycemia (<3.9 mmol/l) increased in both groups, from 0.45 +/- 0.06 to 0.69 +/- 0.07 episodes per day (P < 0.001) in the BGAT group and horn 0.50 +/- 0.08 to 0.68 +/- 0.06 episodes per day (P < 0.05) in the control group (NS between groups). Epinephrine responses after IDT were greater in the BGAT group (repeated measure analysis of variance [ANOVA], F = 3.5, P < 0.05). a separate analysis of subjects (n = 26) most at risk for hypoglycemia (HbA(1c), after IDT <7.8% or an HbA(1c) improvement of >2 percentage points) showed that frequency of hypoglycemia increased in both the groups: from 0.50 +/- 0.09 to 0.80 +/- 0.11 episodes per day (P < 0.01) in the BGAT soup (n = 14) and from 0.43 +/- 0.11 to 0.75 +/- 0.07 episodes per day (P < 0.05) in the control group (n = 12) (NS between groups). However, the epinephrine response in control subjects decreased with IDT while the response in the BGAT subjects was preserved (repeated measure ANOVA, F = 4.4, P < 0.02). CONCLUSIONS - BGAT is a useful intervention to decrease blunting of counterregulatory responses associated with improved glycemic control and may modify the severity of hypoglycemia associated with improved glycemic control in type 1 diabetes. C1 Joslin Diabet Ctr, Behav & Mental Hlth Unit, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Sect Diabet & Metab, Boston, MA 02115 USA. Univ Virginia, Dept Psychiat Med, Charlottesville, VA 22903 USA. RP Jacobson, AM (reprint author), Joslin Diabet Ctr, Behav & Mental Hlth Unit, 1 Joslin Pl, Boston, MA 02215 USA. RI Bajaj, Mandeep/B-6060-2009 FU NIDDK NIH HHS [DK-42315]; NINR NIH HHS [NINR/NRSA-5157] NR 27 TC 29 Z9 29 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 1999 VL 22 IS 7 BP 1022 EP 1028 DI 10.2337/diacare.22.7.1022 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 208XZ UT WOS:000081018900002 PM 10388961 ER PT J AU Adler, AI Boyko, EJ Ahroni, JH Smith, DG AF Adler, AI Boyko, EJ Ahroni, JH Smith, DG TI Lower-extremity amputation in diabetes - The independent effects of peripheral vascular disease, sensory neuropathy, and foot ulcers SO DIABETES CARE LA English DT Article ID LOWER-LIMB AMPUTATIONS; RISK-FACTORS; PHYSICAL-EXAMINATION; ULCERATION; MELLITUS; NIDDM; ABNORMALITIES; COMPLICATIONS; EPIDEMIOLOGY; MORTALITY AB OBJECTIVE - To identify risk factors for lower-extremity amputation (LEA) in individuals with diabetes and to estimate the incidence of LEA. RESEARCH DESIGN AND METHODS - This is a prospective study of 776 U.S. veterans in a general medicine clinic in Seattle, Washington. The outcome was first LEA during follow-up. Potential risk factors evaluated in proportional hazards models included, among others, peripheral vascular disease (PVD), sensory neuropathy, former LEA, foot deformities and ulcers, diabetes duration and treatment, and hyperglycemia. RESULTS - Associated with an increased risk for LEA were PVD defined as transcutaneous oxygen less than or equal to 50 mmHg (relative risk [RR] = 3.0, 95% CI 1.3-7.2), insensitivity to monofilament testing (RR = 2.9, odds ratio = 1.1-7.8), lower-extremity ulcers (RR = 2.5, CI 1.1-5.4), former LEA, and treatment with insulin when controlling for duration of diabetes and other factors in the model. PVD defined as absent or diminished lower-extremity pulses or an ankle arm index less than or equal to 0.8 was also associated with a significantly higher risk of LU in separate models. Foot ulcers were associated with an increased ipsilateral risk of amputation. The age-adjusted incidence among men only for LEA standardized to the 1991 U.S. male diabetic population was 11.3/1,000 patient-years. CONCLUSIONS- This prospective study shows that peripheral sensory neuropathy PVD, foot ulcers (particularly if they appear on the same side as the eventual LEA), former amputation, and treatment with insulin are independent risk factors for LEX in patients with diabetes. C1 Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Program, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Med Serv, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Orthoped Surg, Seattle, WA 98195 USA. RP Adler, AI (reprint author), Univ Oxford, Radcliffe Infirm, Dept Clin Med, Diabet Res Labs, Woodstock Rd, Oxford OX2 6HE, England. NR 45 TC 216 Z9 224 U1 1 U2 15 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 1999 VL 22 IS 7 BP 1029 EP 1035 DI 10.2337/diacare.22.7.1029 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 208XZ UT WOS:000081018900003 PM 10388962 ER PT J AU Boyko, EJ Ahroni, JH Stensel, V Forsberg, RC Davignon, DR Smith, DG AF Boyko, EJ Ahroni, JH Stensel, V Forsberg, RC Davignon, DR Smith, DG TI A prospective study of risk factors for diabetic foot ulcer - The Seattle diabetic foot study SO DIABETES CARE LA English DT Article ID PERIPHERAL VASCULAR-DISEASE; AUTONOMIC NEUROPATHY; BLOOD-FLOW; OXYGEN-TENSION; PRESSURE; AMPUTATION; PERCEPTION; DIAGNOSIS; LIMBS; GREAT AB OBJECTIVE - Little prospective research exists on risk factors for diabetic foot ulcer that considers the independent effects of multiple potential etiologic agents. We prospectively studied the effects of diabetes characteristics, foot deformity, behavioral factors, and neurovascular function on foot ulcer risk among 749 diabetic veterans with 1,483 lower limbs. RESEARCH DESIGN AND METHODS - Eligible subjects included all diabetic enrollees of a general internal medicine clinic without fool ulcer, of whom 83% agreed to participate. Baseline assessment included history and lower-limb physical examination, tests for sensory and autonomic neuropathy, and measurements of macro- and microvascular perfusion in the foot. Subjects were followed for the occurrence of a full thickness skin defect on the foot that took >14 days to heal, with a mean follow-up of 3.7 years. RESULTS - Using stepwise Cox regression analysis, the following factors were independently related to foot ulcer risk: foot insensitivity to the 5.07 monofilament (relative risk [95% CI]) 2.2 (1.5-3.1), past history of amputation 2.8 (1.8-4.3) or foot ulcer 1.6 (1.2-2.3), insulin use 1.6 (1.1-2.2), Charcot deformity 3.5 (1.2-9.9), 15 mmHg higher dorsal foot transcutaneous Po-2 0.8 (0.7-0.9), 20 kg higher body weight 1.2 (1.1-1.4), 0.3 higher ankle-arm index 0.8 (0.7-1.0), poor vision 1.9 (1.4-2.6), and 13 mmHg orthostatic blood pressure fall 1.2 (1.1-1.5). Higher ulcer risk was associated with hammer/claw toe deformity and history of laser photocoagulation in certain subgroups. Unrelated to fool ulcer risk in multivariate models were diabetes duration and type, race, smoking status, diabetes education,joint mobility hallux blood pressure, and other foot deformities. CONCLUSIONS - Certain foot deformities, reduced skin oxygenation and foot perfusion, poor vision, greater body mass, and both sensory and autonomic neuropathy independently influence foot ulcer risk, thereby providing support For a multifactorial etiology For diabetic foot ulceration. C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Orthoped Surg, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Res & Dev Serv, Seattle, WA USA. RP Boyko, EJ (reprint author), VA Med Ctr, S-111-GIMC,1660 S Columbian Way, Seattle, WA 98108 USA. NR 39 TC 262 Z9 269 U1 2 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 1999 VL 22 IS 7 BP 1036 EP 1042 DI 10.2337/diacare.22.7.1036 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 208XZ UT WOS:000081018900004 PM 10388963 ER PT J AU Castillo, G Brun, RP Rosenfield, JK Hauser, S Park, CW Troy, AE Wright, ME Spiegelman, BM AF Castillo, G Brun, RP Rosenfield, JK Hauser, S Park, CW Troy, AE Wright, ME Spiegelman, BM TI An adipogenic cofactor bound by the differentiation domain of PPAR gamma SO EMBO JOURNAL LA English DT Article DE adipogenesis; coactivator; differentiation; PGC-2; PPAR gamma ID ACTIVATED RECEPTOR-GAMMA; HUMAN BREAST-CANCER; TRANSCRIPTION FACTOR; TERMINAL DIFFERENTIATION; COACTIVATOR COMPLEX; NUCLEAR RECEPTORS; FATTY-ACIDS; LIGAND; PROTEIN; GENE AB Ligand activation of the nuclear receptor PPAR gamma induces adipogenesis and increases insulin sensitivity, while activation of other PPAR isoforms (-alpha and -delta) induces little or no fat cell differentiation. Expression and activation of chimeras formed between PPAR gamma and PPAR delta in fibroblasts has allowed us to localize a major domain of PPAR gamma responsible for adipogenesis to the N-terminal 138 amino acids, a region with AF-1 transcriptional activity. Using this region of PPAR gamma as bait, we have used a yeast two-hybrid screen to clone a novel protein, termed PGC-2, containing a partial SCAN domain. PGC-2 binds to and increases the transcriptional activity of PPAR gamma but does not interact with other PPARs or most other nuclear receptors. Ectopic expression of PGC-2 in preadipocytes containing endogenous PPAR gamma causes a dramatic increase in fat cell differentiation at both the morphological and molecular levels. These results suggest that interactions between PGC-2, a receptor isoform-selective cofactor and PPAR gamma contribute to the adipogenic action of this receptor. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. RP Spiegelman, BM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK-09090, R01 5R37DK31405] NR 48 TC 99 Z9 101 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD JUL 1 PY 1999 VL 18 IS 13 BP 3676 EP 3687 DI 10.1093/emboj/18.13.3676 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 218CP UT WOS:000081535900015 PM 10393183 ER PT J AU Wirfel, KL Bruder, JM Vardag, A Roodman, GD AF Wirfel, KL Bruder, JM Vardag, A Roodman, GD TI Osteoclast function in healthy subjects and in patients with Paget's disease SO ENDOCRINOLOGIST LA English DT Review ID HUMAN MARROW CULTURES; MULTINUCLEATED CELLS; MOLECULAR-CLONING; CHROMOSOME 18Q; BONE; EXPRESSION; MICE; OSTEOPETROSIS; LOCALIZATION; PRECURSORS AB Osteoclasts, the bone resorbing cells, are important in normal bone remodeling. Resorption of bone by osteoclasts is coupled to osteoblastic bone formation. An increase in osteoclastic bone resorption relative to bone formation is found in many conditions, which lead to a net loss of bone resulting in osteoporosis. Like osteoporosis, Paget's disease of the bone is also characterized by an increase in osteoclastic resorption. It is an important clinical entity in our aging population, and the osteoclasts are the primary cells responsible for the characteristic bone lesions. Unlike osteoporosis, the profound increase in bone resorption is followed by excessive new bone formation. The study of the factors responsible for normal osteo elastic differentiation, maturation and activation has been invaluable in understanding the patho physiology of osteoporosis and Paget's disease. This review will focus on normal osteoclastic mor phology, the factors that affect osteoclast function and formation, and then contrast these with ab normalities of osteoclasts in Paget's disease. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Endocrinol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Hematol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Wirfel, KL (reprint author), 107 Charles Rd, San Antonio, TX 78209 USA. NR 32 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD JUL-AUG PY 1999 VL 9 IS 4 BP 263 EP 269 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 219LR UT WOS:000081609200005 ER PT J AU Hentunen, TA Jackson, SH Chung, H Reddy, SV Lorenzo, J Choi, SJ Roodman, GD AF Hentunen, TA Jackson, SH Chung, H Reddy, SV Lorenzo, J Choi, SJ Roodman, GD TI Characterization of immortalized osteoclast precursors developed from mice transgenic for both bcl-X-L and simian virus 40 large T antigen SO ENDOCRINOLOGY LA English DT Article ID CELL-LINES; IN-VITRO; MOUSE; BONE; MARROW; DIFFERENTIATION; ACTIVATION; EXPRESSION; GENERATION; RESORPTION AB We recently developed an immortalized osteoclast (OCL) precursor cell line that forms large numbers of OCLs. This cell line was derived from mice doubly transgenic for bcl-X-L, and large T antigen that was targeted to cells in the OCL lineage (bcl-X-L/Tag cells). We have now characterized these cells in terms of their surface and enzymatic phenotype, responsiveness to osteotropic factors, and differentiation potential. The bcl-X-L/Tag cells expressed interleukin-l receptors 1 and 2, gelatinase B (MMP9), as well as Mac-1, CD16/CD32 (Fc gamma receptors), CD45.2 (common leukocyte marker), CD86 (costimulatory molecule expressed on B cells, follicular dendritic cells, and thymic epithelium), major histocompatibility complex I, and nonspecific esterase when cocultured with MC3T3E1 cells. However, they did not express the antigens for F4/80 (mature macrophage/dendritic cell marker) by immunostaining. Treatment of bcl;X-L/Tag cells, cocultured with MC3T3E1 cells, with the combination of 1,25-dihydroxyvitamin D-3, and dexamethasone induced high levels of OCL formation. The bcl-X-L/Tag cells formed large numbers of OCLs when cultured with RANK ligand and macrophage colony-stimulating factor in the absence of feeder cells. In the absence of RANK ligand and a feeder cell layer, 100% of the cells differentiated into F4/80-positive cells. However, neither PTH nor PTH-related protein enhanced OCL formation by bcl-X-L/Tag cells even when they were cocultured with primary osteoblasts, suggesting that they differ from primary mouse bone mat-row cells in their responsiveness to PTWPTK-related protein. Thus, bcl-X-L/Tag cells have many of the properties of primary mouse OCL precursors and should be very useful for studies of OCL differentiation and divergence of OCL precursors from the macrophage lineage. C1 Audie L Murphy Mem Vet Adm Med Ctr, Res Serv 151, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Hematol, San Antonio, TX 78284 USA. NIH, Bethesda, MD 20892 USA. Vet Adm Med Ctr, Dept Res, Newington, CT 06111 USA. RP Roodman, GD (reprint author), Audie L Murphy Mem Vet Adm Med Ctr, Res Serv 151, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. EM roodman@uthscsa.edu NR 19 TC 21 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 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1999 VL 140 IS 7 BP 2954 EP 2961 DI 10.1210/en.140.7.2954 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 208JL UT WOS:000080987200004 PM 10385386 ER PT J AU Benbassat, C Shoba, LNN Newman, M Adamo, ML Frank, SJ Lowe, WL AF Benbassat, C Shoba, LNN Newman, M Adamo, ML Frank, SJ Lowe, WL TI Growth hormone-mediated regulation of insulin-like growth factor I promoter activity in C6 glioma cells SO ENDOCRINOLOGY LA English DT Article ID ACID PROTEIN INTERACTIONS; SERUM RESPONSE ELEMENT; TRANSCRIPTION START SITES; JAK2 TYROSINE KINASE; IGF-I; GENE-EXPRESSION; TARGETED DISRUPTION; LEADER EXONS; DIFFERENTIAL REGULATION; STAT5 ACTIVATION AB The molecular mechanisms by which GH regulates insulin-like growth factor (IGF-I) gene expression remain obscure. One difficulty has been the lack of established GH-responsive cell lines that express the IGF-I gene. To develop such a cell line, we used rat C6 glioma cells which, as determined by RNase protection assay, express the IGF-I gene but not the GH receptor gene. To confer GH responsiveness, C6 cells were cotransfected with vectors that express the GH receptor (pRc/CMV WTrGHR) and Jak2 (pRc/CMV Jak2). GH responsiveness was demonstrated using luciferase reporter genes containing either the Sis-inducible element from the c-fos gene (pTK81-SIE-Luc) or 6 copies of the GH-responsive GAS-like element (GLE) from the rat spt2. I gene (pSpi-GLE-Luc). The SIE is activated by binding of STAT1 and 3, whereas the GLE binds STAT5. In cells cotransfected with pRc/CMV WTrGHR, pRc/CMV Jak2, and either pTK81-SIE-Luc or pSpi GLE-Luc, treatment with 500 ng/ml GH for 24 h stimulated a 3.1- and 1.7-fold increase in luciferase activity, respectively. These data suggest that in C6 cells cotransfected with pRc/CMV WTrGHR and pRc/CMV Jak2, GH activates STAT1, 3, and 5. To determine whether GH-responsive IGF-I promoter activity could be demonstrated, C6 cells were cotransfected with pRc/CMV WTrGHR, pRc/CMV Jak2, and an IGF-I-luciferase fusion gene that contained a fragment of the rat IGF-I gene that extended from -412 in the 5'-flanking region of exon Ito the Met-22 in exon 3. GH stimulated a modest, but reproducible, 1.7-fold increase in luciferase activity in these cells, suggesting that a GH-responsive element is present in this region of the IGF-I gene. To better localize the GH-responsive element, cells were cotransfected with pRc/CMV WTrGHR, pRc/CMV Jak2 plus one of several IGF-I-Iuciferase fusion genes containing either fragments of one of the two promoters in the IGF-I gene or a fragment of intron 2 that includes a GH-responsive DNase I hypersensitivity site. For all constructs, treatment with GH for 24 h did not stimulate a significant increase in luciferase activity, suggesting that GH-responsive sequences are not located in these specific regions of the IGF-I gene or that GH-directed transcription of the IGF-I gene is mediated via several different regions of the IGF-I gene and the effect of any one of these regions in isolation was not sufficiently robust to be detected in this model system. In summary, transient expression of the GH receptor and Jak2 in C6 cells creates a GH-responsive system that activates STAT1, 3, and 5. Moreover, a fragment of the IGF-I gene that contains exons 1 and 2, a fragment of exon 3, and introns 1 and 2 is GH responsive using this model system. C1 Vet Affairs Chicago Healthcare Syst, Lakeside Div, Dept Med, Chicago, IL USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA. Univ Alabama Birmingham, Dept Med, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. RP Lowe, WL (reprint author), Northwestern Univ, Sch Med, Ctr Endocrinol Metab & Mol Med, Tarry 15-703,303 E Chicago Ave, Chicago, IL 60611 USA. EM wlowe@nwu.edu FU NIDDK NIH HHS [DK-47357, DK-46935] NR 61 TC 32 Z9 32 U1 1 U2 1 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 JUL PY 1999 VL 140 IS 7 BP 3073 EP 3081 DI 10.1210/en.140.7.3073 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 208JL UT WOS:000080987200017 PM 10385399 ER PT J AU Usdin, TB Hilton, J Vertesi, T Harta, G Segre, G Mezey, E AF Usdin, TB Hilton, J Vertesi, T Harta, G Segre, G Mezey, E TI Distribution of the parathyroid hormone 2 receptor in rat: Immunolocalization reveals expression by several endocrine cells SO ENDOCRINOLOGY LA English DT Article ID MESSENGER RIBONUCLEIC-ACIDS; IN-SITU LOCALIZATION; PTH/PTHRP RECEPTOR; INSULIN-SECRETION; CYTOSOLIC CALCIUM; PANCREATIC-ISLETS; MEDIAL CISTERNAE; GOLGI-APPARATUS; PEPTIDE PTHRP; SOMATOSTATIN AB The PTH2 receptor is a G protein-coupled receptor selectively activated by PTH. We are studying the receptors distribution to guide the investigation of its physiological function. We have now generated an antibody from a C-terminal peptide sequence of the PTH2 receptor and used this to study its cellular distribution. Labeling with the antibody identified a number of endocrine cells expressing the PTH2 receptor, including thyroid parafollicular cells, pancreatic islet D cells, and some gastrointestinal peptide synthesizing cells. There was complete overlap of PTH2 receptor labeling with somatostatin in pancreatic islets, and partial overlap with somatostatin in thyroid parafollicular cells and in the gastrointestinal tract. Furthermore, observations made previously by in situ hybridization histochemistry, including expression throughout the cardiovascular system, as well as by discrete populations of cells within the gastrointestinal tract and reproductive system were confirmed. These data suggest a broad role for the PTH2 receptor, especially within the endocrine system, and provide a basis for experimental exploration of its physiology. C1 Natl Inst Mental Hlth, Genet Lab, Bethesda, MD 20892 USA. Natl Inst Neurol Dis & Stroke, BAsic Neurosci Program, Bethesda, MD 20892 USA. Natl Inst Hlth, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Usdin, TB (reprint author), Natl Inst Mental Hlth, Genet Lab, Bldg 36,Room 3D06,36 Convent Dr MSC4094, Bethesda, MD 20892 USA. EM usdin@codon.nih.gov NR 44 TC 46 Z9 46 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 JUL PY 1999 VL 140 IS 7 BP 3363 EP 3371 DI 10.1210/en.140.7.3363 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 208JL UT WOS:000080987200052 PM 10385434 ER PT J AU Hill, RA Chiappa, KH Huang-Hellinger, F Jenkins, BG AF Hill, RA Chiappa, KH Huang-Hellinger, F Jenkins, BG TI Hemodynamic and metabolic aspects of photosensitive epilepsy revealed by functional magnetic resonance imaging and magnetic resonance spectroscopy SO EPILEPSIA LA English DT Article; Proceedings Paper CT 10th International Congress on Electromyography and Clinical Neurophysiology CY OCT 19, 1995 CL KYOTO, JAPAN DE functional MRI; MR spectroscopy; generalized epilepsy; photosensitive; EEG ID CEREBRAL BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; HUMAN VISUAL-CORTEX; GLUCOSE-METABOLISM; ELECTRICAL-STIMULATION; PHOTIC-STIMULATION; ICTAL ACTIVITY; HUMAN BRAIN; SEIZURES; EEG AB Purpose: To study in humans the hemodynamic and metabolic consequences of both photic stimulation-triggered and spontaneous generalized epileptiform discharges. Methods: Simultaneous EEG, functional magnetic resonance imaging (fMRI) and MR spectroscopy were performed in a 1.5-T scanner in 16 patients with generalized epilepsy, including nine with photosensitive epilepsy, and 12 normal subjects. Results: With a flash stimulation duration of 2 s, prominent visual cortex activation was seen in all normals and patients. There were no fMRI-registered hemodynamic abnormalities found in relation to the brief photoparoxysmal spike-wave activity evoked in the photosensitive patients. However, irrespective of the presence of a spike-wave response to the photic stimulation, the photosensitive patients showed four unique findings compared with normals: (a) slightly, but significantly, increased lactate levels in the occipital cortex in the resting state, Co) an increased area of visual cortical activation with photic stimulation, (c) simultaneous with the occipital cortex stimulus-induced increased fMRI signal there were noncontiguous areas of signal attenuation most prominent in perirolandic regions, and (d) a marked decrement (undershoot) of fMRI signal intensity immediately after the photic stimulation in the occipital cortex and in the region of the posterior cingulate gyrus. Conclusions: These findings suggest abnormal interictal metabolism and increased vascular reactivity in the photosensitive patients. C1 Massachusetts Gen Hosp, EEG Lab, Dept Neurol, Clin Neurophysiol Lab, Boston, MA 02214 USA. Massachusetts Gen Hosp, Dept Radiol, NMR Ctr, Boston, MA 02214 USA. RP Chiappa, KH (reprint author), Massachusetts Gen Hosp, EEG Lab, Dept Neurol, Clin Neurophysiol Lab, 55 Fruit St, Boston, MA 02214 USA. NR 36 TC 31 Z9 33 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUL PY 1999 VL 40 IS 7 BP 912 EP 920 DI 10.1111/j.1528-1157.1999.tb00798.x PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 212ZH UT WOS:000081247200013 PM 10403215 ER PT J AU Earle, CC Maroun, JA AF Earle, CC Maroun, JA TI Adjuvant chemotherapy after curative resection for gastric cancer in non-Asian patients: Revisiting a meta-analysis of randomised trials SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE stomach cancer; adjuvant chemotherapy; meta-analysis ID ONCOLOGY-GROUP; MITOMYCIN-C; FOLLOW-UP; CLINICAL-TRIAL; INTERIM-REPORT; THERAPY; 5-FLUOROURACIL; FLUOROURACIL; DOXORUBICIN; CARCINOMA AB The aim of this study was to assess whether adjuvant chemotherapy after curative resection of gastric cancer increases survival rates. Data sources: MEDLINE (1966-1999), CancerLit (1983-1999), bibliographies, personal reprint files, and review articles were searched for relevant articles. Studies had to be randomised controlled trials of adjuvant chemotherapy versus observation following curative resection of stomach cancer that took place in non-Asian countries. Two reviewers independently evaluated the trials for eligibility, quality assessment and data abstraction. 13 trials met the eligibility criteria. The odds ratio for death in the treated group was 0.80 (95% confidence interval (CI) 0.66-0.97), corresponding to a relative risk of 0.94 (95% CI 0.89-1.00), Subgroup analyses showed a trend towards a larger magnitude of the effect when analysis was restricted to trials in which at least 2/3 of patients had node-positive disease. Our results suggest that adjuvant chemotherapy may produce a small survival benefit of borderline statistical significance in patients with curatively resected gastric carcinoma. Continued trials to find and confirm an effective adjuvant strategy are warranted. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Ottawa Reg Canc Ctr, Ottawa, ON K1Y 4K7, Canada. RP Earle, CC (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 44 Binney St, Boston, MA 02115 USA. NR 51 TC 304 Z9 321 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JUL PY 1999 VL 35 IS 7 BP 1059 EP 1064 DI 10.1016/S0959-8049(99)00076-3 PG 6 WC Oncology SC Oncology GA 221RD UT WOS:000081739300012 PM 10533448 ER PT J AU Francis, SA Kelly, JM McCormack, J Rogers, RA Lai, J Schneeberger, EE Lynch, RD AF Francis, SA Kelly, JM McCormack, J Rogers, RA Lai, J Schneeberger, EE Lynch, RD TI Rapid reduction of MDCK cell cholesterol by methyl-beta-cyclodextrin alters steady state transepithelial electrical resistance SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Article DE cholesterol; methyl-beta-cyclodextrin; tight junction; MDCK cells ID TIGHT JUNCTION STRANDS; PLASMA-MEMBRANES; OCCLUDIN; TRANSPORT; PROTEIN; EFFLUX; DISSOCIATION; PERMEABILITY; EXPRESSION; CALCIUM AB The role of plasma membrane lipids in regulating the passage of ions and other solutes through the paracellular pathway remains controversial. In this study we explore the contribution of cholesterol (CH) in maintaining the barrier function of an epithelial cell line using the CH-solubilizing agent methyl beta-cyclodextrin (MBCD) to stimulate CH efflux, Inclusion of 20 mM MBCD in both epical and basolateral media reduced CH levels by 70-80 % with no significant effect on cell viability. Most of that decrease occurred during the first 30 min of incubation, Recovery of CH content to initial values was nearly complete 22 h after removal of MBCD. Within 30 min of adding MBCD to the culture medium, transepithelial electrical resistance (TER) increased, reaching maximum values 30-40 % above controls. This early rise in TER occurred when MBCD was added to either side of the monolayer. The later rapid decline in TER was observed only when MBCD bathed the basolateral surface from which, coincidentally, CH efflux was most rapid, Freeze fracture replicas and transmission electron microscopy of monolayers exposed to MBCD for only 30 min revealed no increase in either the average tight junction (TJ) strand number or the dimensions of the lateral intercellular space. There was a statistically significant increase in the number of TJ particles associated with the E fracture face at this time. This raises the interesting possibility that during CH efflux there is a change in the interaction between TJ particles and underlying cytoskeletal elements. There was no change in staining for occludin and ZO-1. After exposing the basolateral surface to MBCD for 2 h, TER fell below control levels. The accompanying increase in mannitol flux suggests strongly that the decrease in TER resulted from an increase in the permeability of the paracellular and not the transcellular pathway A decrease in immune-staining for occludin and ZO-1 at TJs, a striking accumulation of actin at tri-cellular areas as well as a decline in the number of parallel strands, as seen in freeze fracture replicas, suggest that changes in cytoskeletal organization during long incubations with MBCD had physically disrupted the TJ network. Data are presented which suggest that the observed changes in paracellular permeability during CH efflux may be related to increased levels of lipid-derived second messengers, some of which may trigger changes in the phosphorylation status of TJ proteins. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Massachusetts, Dept Biol Sci, Lowell, MA USA. Harvard Univ, Sch Publ Hlth, Physiol Program, Boston, MA 02115 USA. RP Schneeberger, EE (reprint author), Massachusetts Gen Hosp, Dept Pathol, Cox Bldg 5,Room 554,100 Blossom St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL25822, HL33009, HL43510] NR 40 TC 79 Z9 79 U1 0 U2 4 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX NO.100 537, D-07705 JENA, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD JUL PY 1999 VL 78 IS 7 BP 473 EP 484 PG 12 WC Cell Biology SC Cell Biology GA 225RM UT WOS:000081975200005 PM 10472800 ER PT J AU Tsubota, K Kwong, KK Lee, TY Nakamura, J Cheng, HM AF Tsubota, K Kwong, KK Lee, TY Nakamura, J Cheng, HM TI Functional MRI of brain activation by eye blinking SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE fMRI; eye blinking; dry eye; orbitofrontal cortex; visual cortex ID VISUAL-CORTEX; REFLEX AB Functional magnetic resonance imaging (fMRI) was used to map cortical areas that control eye blinking. T2*-weighted asymmetric spin-echo MRI (or BOLD-blood oxygen level dependent-MRI) was used to detect changes caused by focal variations in blood oxygenation. Six normal volunteers and two cases of dry eye (less than 5-mm Schirmer's test) entered the study. The experimental scheme consisted of three cycles of a two-step sequence: (eyes closed)-(blink or blink inhibition). And to minimize contamination from photic activation, the experiments were carried out in a dark environment and the volunteers reported no light perception during the MR scans. In all eight cases, normal blinking (about one blink every 4 sec) activated areas in the orbitofrontal cortex and in some cases, the visual cortex including the anterior portion of the visual cortex and the primary visual cortex. In severe dry eye, blink-inhibition strongly activated the visual cortex even after irritation due to corneal desiccation was removed by topical anesthesia. The blinking process, especially the rate, appears to be controlled in the orbitofrontal cortex. The significance of visual cortex activation in the dark and in the case of severe dry eye still remains unclear; although it may be associated with attention and arousal. (C) 1999 Academic Press. C1 Tokyo Dent Coll, Dept Ophthalmol, Chiba 272, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Howe Lab Ophthalmol, NMR Res, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Cheng, HM (reprint author), Schepens Retina Associates, 100 Charles River Plaza, Boston, MA 02114 USA. FU NEI NIH HHS [EY07620] NR 14 TC 30 Z9 31 U1 1 U2 4 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD JUL PY 1999 VL 69 IS 1 BP 1 EP 7 DI 10.1006/exer.1999.0660 PG 7 WC Ophthalmology SC Ophthalmology GA 211ZU UT WOS:000081192400001 PM 10375444 ER PT J AU Kwiatkowski, BA Zielinska-Kwiatkowska, AG Hickstein, DD AF Kwiatkowski, BA Zielinska-Kwiatkowska, AG Hickstein, DD TI Expression of the ETS family member Tel reverses the phenotype in cells expressing Fli-1. SO EXPERIMENTAL HEMATOLOGY 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 ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 1999 VL 27 IS 7 SU 1 MA 63 BP 52 EP 52 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 209CM UT WOS:000081030100064 ER PT J AU Yang, L Embree, LJ Hickstein, DD AF Yang, L Embree, LJ Hickstein, DD TI TLS ERG leukemia fusion protein disrupts RNA splicing mediated by serine-arginine proteins. SO EXPERIMENTAL HEMATOLOGY 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 ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 1999 VL 27 IS 7 SU 1 MA 86 BP 58 EP 58 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 209CM UT WOS:000081030100087 ER PT J AU Guo, D Wang, T Liu, F Savinov, S Kufe, D Won, JH Lerma, E Austin, D Deisseroth, A AF Guo, D Wang, T Liu, F Savinov, S Kufe, D Won, JH Lerma, E Austin, D Deisseroth, A TI Development of chemical inhibitors of P210bcrabl SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 Yale Univ, Sch Med, New Haven, CT USA. Yale Univ, Dept Chem, New Haven, CT USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 1999 VL 27 IS 7 SU 1 MA 161 BP 78 EP 78 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 209CM UT WOS:000081030100162 ER PT J AU Dallalio, G North, M Worden, BD Means, RT AF Dallalio, G North, M Worden, BD Means, RT TI Inhibition of human erythroid colony formation by ceramide SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE erythropoiesis; ceramide; interferon; anemia; apoptosis ID FAS-INDUCED APOPTOSIS; NECROSIS-FACTOR-ALPHA; FORMING-UNITS; GAMMA-INTERFERON; SIGNALING PATHWAY; PROGENITOR CELLS; ERYTHROPOIETIN; QUANTITATION; SUPPRESSION; EXPRESSION AB In previous studies, we have demonstrated that the inhibitory effects of tumor necrosis factor (TNF) and interleukin (IL)-1 on human erythroid colony formation are indirect and mediated by beta and gamma interferon (IFN), respectively, which act directly upon erythroid colony forming units (CFU-E). The in vitro inhibitory effect of gamma IFN but not beta IFN is reversed by exposure to high concentrations of recombinant human (rh) erythropoietin (EPO), Ceramide, a product of sphingomyelin hydrolysis, is a known mediator of apoptotic effects of TNF, IL-1, and gamma IFN, In this report, the effects of ceramide on CFU-E colony formation and its implication in the model described above are evaluated. Endogenous ceramide produced by exposure to bacterial sphingomyelinase (0.2-2.0 U/mL) and exogenous cell-permeable ceramide (C-2-ceramide; 5 and 10 mM) significantly inhibited bone marrow CFU-E colony formation, This effect was reversed by the ceramide antagonist sphingosine-1l-phosphate (S-1-P), Inhibition of CFU-E by rh gamma IFN, but not rh beta IFN, was significantly reversed by S-1-P, rhEPO 10 U/mL reversed CFU-E inhibition by Cz-ceramide 10 mM, Exposure of marrow cells to rh gamma IFN led to a 57% increase in ceramide content, The present study demonstrates that colony formation by human CFU-E is inhibited by endogenous and exogenous ceramide, and that inhibition by rh gamma IFN can be reversed by the ceramide antagonist S-I-P, Inhibition of CFU-E colony formation by ceramide and by are both reversed by high concentrations of rhEPO, These findings strongly suggest that ceramide mediates inhibition of human CFU-E colony formation hv gamma IFN. (C) 1999 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 Dept Vet Affairs Med Ctr, Dept Internal Med, Div Hematol Oncol, Cincinnati, OH USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Ralph H Johnson Vet Affairs Med Ctr, Med Serv 111, Hematol Oncol Sect, Charleston, SC 29401 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Ohio State Univ, Dept Ecol Evolut & Organismal Biol, Columbus, OH 43210 USA. RP Means, RT (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Med Serv 111, Hematol Oncol Sect, 109 Bee St, Charleston, SC 29401 USA. RI Means, Robert/A-4454-2008 FU NHLBI NIH HHS [HL53703] NR 29 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 1999 VL 27 IS 7 BP 1133 EP 1138 DI 10.1016/S0301-472X(99)00054-5 PG 6 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 207ZT UT WOS:000080966200003 PM 10390188 ER PT J AU Kawamata, T Ren, JM Cha, JH Finklestein, SP AF Kawamata, T Ren, JM Cha, JH Finklestein, SP TI Intracisternal antisense oligonucleotide to growth associated protein-43 blocks the recovery-promoting effects of basic fibroblast growth factor after focal stroke SO EXPERIMENTAL NEUROLOGY LA English DT Article DE stroke; behavioral recovery; basic fibroblast growth factor; GAP-43; antisense oligonucleotide ID ENHANCES FUNCTIONAL RECOVERY; ADULT-RAT BRAIN; NEOCORTICAL DAMAGE; GAP-43; INFARCTION; NEURONS; SYNAPTOGENESIS AB Focal infarction (stroke) of the lateral cerebral cortex of rats (including the sensorimotor cortex) produces deficits in sensorimotor function of the contralateral limbs that recover partially over time. In previous studies, we found that the intracisternal injection of basic fibroblast growth factor (bFGF), a potent neurotrophic growth factor, starting at 1 day after stroke, significantly enhanced recovery of sensorimotor function of the contralateral forelimb and hindlimb. Moreover, immunoreactivity (IR) for growth-associated protein-43 (GAP-43), a molecular marker of new axonal growth, was increased in the intact contralateral sensorimotor cortex following bFGF treatment. In the current study, we found that the intracisternal administration of antisense, but not missense, oligonucleotide to GAP-43 blocked the recovery-enhancing effects of bFGF and blocked the increase in GAP-43 IR in the contralateral cortex. These results suggest that upregulation of GAP-43 expression and consequent enhanced axonal sprouting in intact uninjured parts of the brain are likely mechanisms for the recovery-promoting effects of bFGF. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, CNS Growth Factor Res Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kawamata, T (reprint author), Massachusetts Gen Hosp, CNS Growth Factor Res Lab, Boston, MA 02114 USA. FU NINDS NIH HHS [NS-P0110828] NR 25 TC 27 Z9 28 U1 1 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 JUL PY 1999 VL 158 IS 1 BP 89 EP 96 DI 10.1006/exnr.1999.7101 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 218PW UT WOS:000081561800008 PM 10448420 ER PT J AU Iverson, RE Chelmow, D Strohbehn, K Waldman, L Evantash, EG Aronson, MP AF Iverson, RE Chelmow, D Strohbehn, K Waldman, L Evantash, EG Aronson, MP TI Myomectomy fever: testing the dogma SO FERTILITY AND STERILITY LA English DT Article DE abdominal myomectomy; postoperative fever; postoperative complications ID PELVIC FLUID COLLECTIONS; ABDOMINAL MYOMECTOMY; FEBRILE MORBIDITY; HYSTERECTOMY AB Objective: To test the hypothesis that elevated temperature is more common after abdominal myomectomy than after hysterectomy. Design: Retrospective cohort study. Setting: Academic medical center. Patient(s): One hundred one women who underwent abdominal myomectomy and 160 women who underwent total abdominal hysterectomy for benign disease from 1988-1993. Intervention(s): Abdominal myomectomy. Main Outcome Measure(s): Temperature of greater than or equal to 38.5 degrees C within 48 hours after operation. Result(s): Although univariate analysis showed that the incidence of elevated temperature was slightly greater among patients who underwent myomectomy (33% versus 26%, relative risk 1.29, 95% confidence interval 0.88-1.90), multivariate logistic regression analysis showed a 3.29 relative risk of elevated temperature (95% confidence interval 1.56-6.96) with myomectomy after controlling for age, parity, estimated blood loss, and treatment by the general gynecology service. Conclusion(s): After controlling for confounders, myomectomy was found to be an independent predictor for fever in the first 48 hours after operation. (Fertil Steril(R) 1999;72:104-8. (C)1999 by American Society for Reproductive Medicine.). C1 Tufts Univ, Sch Med, Dept Obstet & Gynecol, Div Gen Obstet & Gynecol, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Obstet & Gynecol, Div Urogynecol Pelv Reconstruct Surg, Boston, MA 02111 USA. New England Med Ctr, Boston, MA 02111 USA. Massachusetts Gen Hosp, Div Gen Obstet & Gynecol, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Chelmow, D (reprint author), Tufts Univ, Sch Med, Dept Obstet & Gynecol, Div Gen Obstet & Gynecol, Box 022,750 Washington St, Boston, MA 02111 USA. NR 10 TC 24 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JUL PY 1999 VL 72 IS 1 BP 104 EP 108 DI 10.1016/S0015-0282(99)00156-9 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 212PL UT WOS:000081225400018 PM 10428156 ER PT J AU Ray, PS Maulik, G Cordis, GA Bertelli, AAE Bertelli, A Das, DK AF Ray, PS Maulik, G Cordis, GA Bertelli, AAE Bertelli, A Das, DK TI The red wine antioxidant resveratrol protects isolated rat hearts from ischemia reperfusion injury SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE resveratrol; ischemia; reperfusion; free radicals; antioxidant; red wine; peroxyl radical ID MODERATE ALCOHOL-CONSUMPTION; HIGH-DENSITY-LIPOPROTEIN; TRANS-RESVERATROL; CIS-RESVERATROL; CARDIOVASCULAR MORTALITY; PLASMINOGEN-ACTIVATOR; VASORELAXING ACTIVITY; PLATELET-AGGREGATION; LIPID-PEROXIDATION; FRENCH PARADOX AB The consumption of red wine has been reported to impart a greater benefit in the prevention of coronary heart disease than the consumption of other alcoholic beverages. This beneficial effect is increasingly being attributed to certain antioxidants comprising the polyphenol fraction of red wine such as transresveratrol. In the present study, we investigated the potential cardioprotective effects of resveratrol in the face of ischemia reperfusion (I/R) injury. Isolated perfused working rat hearts after stabilization were perfused with Krebs-Henseleit Bicarbonate buffer (KHB) either in the presence or absence of transresveratrol (RVT) at a concentration of 10 mu M for 15 min prior to subjecting them to 30 min of global ischemia followed by 2 h of reperfusion. Left ventricular functions were monitored at various timepoints throughout the reperfusion period to assess the extent of postischemic recovery in comparison with baseline values. Coronary perfusate samples were also collected to determine malonaldehyde (MDA) levels. The results demonstrated that RVT exhibited significant myocardial protection. This was evidenced by improved recovery of post-ischemic ventricular function including developed pressure and aortic flow as compared to the control group (KHB). Values for developed pressure in the RVT-treated group were significantly higher than those in the control group throughout the reperfusion period (71.09 +/- 4.88 mmHg vs. 58.47 +/- 3.88 mmHg, 68.87 +/- 5.07 mmHg vs. 49.74 +/- 2.65 mmHg and 51.67 +/- 3.95 mmHg vs. 30.50 +/- 4.80 mmHg at reperfusion timepoints R-15, R-60, and R-120, respectively). From R-30 onwards, aortic flow was markedly higher in the RVT treated group as compared with the control group, the differences being most significant at R-90 (32.45 +/- 2.19 ml/min vs. 19.83 +/- 1.62 ml/min) and R-120 (27.15 +/- 2.27 ml/min vs. 14.10 +/- 1.69 ml/min). In contrast to the KHB treated group, the RVT-treated group displayed significant reduction in MDA formation especially in the immediate early reperfusion period (63.71 +/- 8.19 pM/ml vs. 130.86 +/- 4.76 pM/ml, 63.84 +/- 15.62 pM/ml vs. 156.99 +/- 18.93 pM/ml, 71.29 +/- 2.80 pM/ml vs. 129.5 +/- 10.30 pM/ml and 56.25 +/- 5.79 pM/ml vs. 127.99 +/- 3.50 pM/ml at timepoints R-1, R-3, R-5, and R-7, respectively) indicating a reduction in I/R injury related oxidative stress. Infarct size was markedly reduced in the RVT group when compared with the control group (10.57 +/- 0.35% vs. 36.27 +/- 5.28%). In vitro studies revealed RVT to be a potent scavenger of peroxyl radicals suggestive of a probable mechanism involved in the protective ability of RVT. The results of this study indicate that resveratrol possesses cardioprotective effects which may be attributed to its peroxyl radical scavenging activity. (C) 1999 Elsevier Science Inc. C1 Univ Connecticut, Sch Med, Dept Surg, Div Cardiovasc, Farmington, CT 06030 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Milan, Inst Anat, Milan, Italy. Univ Milan, Dept Pharmacol, Milan, Italy. RP Das, DK (reprint author), Univ Connecticut, Sch Med, Dept Surg, Div Cardiovasc, Farmington, CT 06030 USA. FU NHLBI NIH HHS [HL 22559, HL 33889, HL 34360] NR 64 TC 280 Z9 294 U1 0 U2 21 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JUL PY 1999 VL 27 IS 1-2 BP 160 EP 169 DI 10.1016/S0891-5849(99)00063-5 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 220FW UT WOS:000081654800020 PM 10443932 ER PT J AU Sands, BE Bank, S Sninsky, CA Robinson, M Katz, S Singleton, JW Miner, PB Safdi, MA Galandiuk, S Hanauer, SB Varilek, GW Buchman, AL Rodgers, VD Salzberg, B Cai, B Loewy, J DeBruin, MF Rogge, H Shapiro, M Schwertschlag, US AF Sands, BE Bank, S Sninsky, CA Robinson, M Katz, S Singleton, JW Miner, PB Safdi, MA Galandiuk, S Hanauer, SB Varilek, GW Buchman, AL Rodgers, VD Salzberg, B Cai, B Loewy, J DeBruin, MF Rogge, H Shapiro, M Schwertschlag, US TI Preliminary evaluation of safety and activity of recombinant human interleukin 11 in patients with active Crohn's disease SO GASTROENTEROLOGY LA English DT Article ID INFLAMMATORY BOWEL-DISEASE; INDUCED COLONIC INJURY; RHIL-11 GROWTH-FACTOR; FACTOR-KAPPA-B; CHEMOTHERAPY; IL-11; RATS; RECOVERY; CYTOKINE; BIOLOGY AB Background & Aims: Recombinant human interleukin 11 (rhIL-11) is a cytokine with thrombocytopoietic activity and anti-inflammatory and mucosal protective effects, The objectives of this study were to investigate the safety and tolerability of rhIL-11 in patients with Crohn's disease and to explore the effects of dose and schedule on platelet count and Crohn's disease activity. Methods: A multicenter, double-masked, placebo-controlled, dose-escalation study of 76 patients with active Crohn's disease was performed. Patients were randomized to receive subcutaneous placebo or rhIL-11 at doses of 5, 16, or 40 mu g . kg(-1) . wk(-1) given 2 or 5 times weekly for 3 weeks. Clinical and laboratory safety data were recorded, and disease activity was measured at each visit, Results: Subcutaneous injection of rhIL-11 generally was well tolerated. Significantly greater increases in platelet counts were found among patients receiving rhIL-11 40 mu g . kg(-1) . wk(-1) as 2 or 5 weekly doses and 16 mu g . kg(-1) . week(-1) as 5 weekly doses compared with patients receiving placebo (P < 0.05), Patients receiving 16 mu g . kg(-1). wk(-1) had the highest clinical response rates, with a response seen in 42% of patients (5/12) receiving 5 weekly doses and 33% of patients (4/12) receiving 2 weekly doses, compared with 7% of patients (1/15) receiving placebo. Conclusions: Short-term treatment with rhIL-11 is well tolerated in patients with active Crohn's disease. The thrombocytopoietic effect of rhIL-11 seems to be both dose and schedule dependent and may be minimized with retained clinical benefit in Crohn's disease at 16 mu g . kg(-1) . wk(-1) given in 2 equal doses. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Long Isl Jewish Med Ctr, Hyde Pk, NY USA. Univ Florida, Div Gastroenterol, Gainesville, FL USA. Oklahoma Fdn Digest Res, Oklahoma City, OK USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Nassau Gastroenterol Associates PC, Great Neck, NY USA. Univ Colorado, Denver, CO 80202 USA. Consultants Clin Res, Cincinnati, OH USA. Univ Louisville, Dept Surg, Louisville, KY 40292 USA. Univ Chicago, Med Ctr, Div Gastroenterol, Chicago, IL 60637 USA. Univ Kentucky, Dept Med, Div Gastroenterol, Lexington, KY 40506 USA. Baylor Coll Med, Dept Med, Gastroenterol Sect, Houston, TX 77030 USA. Scripps Clin & Res Fdn, La Jolla, CA USA. Atlanta Specialists Gastroenterol PC, Atlanta, GA USA. Genet Inst, Cambridge, MA 02140 USA. RP Sands, BE (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ 825A, Boston, MA 02114 USA. NR 35 TC 153 Z9 157 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 JUL PY 1999 VL 117 IS 1 BP 58 EP 64 DI 10.1016/S0016-5085(99)70550-0 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 212GJ UT WOS:000081208700015 PM 10381910 ER PT J AU Barrett, JE Williams, JW Oxman, TE Katon, W Frank, E Hegel, MT Sullivan, M Schulberg, HC AF Barrett, JE Williams, JW Oxman, TE Katon, W Frank, E Hegel, MT Sullivan, M Schulberg, HC TI The treatment effectiveness project. A comparison of the effectiveness of paroxetine, problem-solving therapy, and placebo in the treatment of minor depression and dysthymia in primary care patients: Background and research plan SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article ID DIAGNOSTIC INTERVIEW SCHEDULE; MENTAL-DISORDERS; GENERAL-PRACTICE; PSYCHIATRIC-DISORDERS; EMOTIONAL DISORDERS; SOCIAL SUPPORT; PHYSICIANS; PREVALENCE; PSYCHOTHERAPY; EPIDEMIOLOGY AB This report describes the background, rationale, and research plan for a comparative treatment trial of the effectiveness of paroxetine, problem-solving therapy (PST-PC), and placebo in the treatment of minor depression and dysthymia in primary care patients. Patients were recruited from a variety of primary care practice settings in Jour separate geographic locations (Hanover, New Hampshire; Pittsburgh, Pennsylvania; San Antonio, Texas; and Seattle, Washington). Patients were randomly assigned to each of the three intervention conditions the medication/placebo conditions were double-blinded. The treatment trial was II weeks, with independent assessments of patient clinical status at baseline, 6 weeks, and II weeks. There was a follow-up at 25 weeks. Since there are relatively few placebo-controlled trials in primary care settings on patients with these disorders, the background of this project and a description of it are presented at ellis time, prior to the avaliability of outcome data, to proving methodological detail and to increase awareness in Nle research community of this treatment trial, with results to appear subsequently. (C) 1999 Elsevier Science Inc. C1 Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH 03755 USA. Dartmouth Med Sch, Dept Psychiat, Hanover, NH 03755 USA. Univ Texas, Hlth Sci Ctr, Audie Murphy Mem Vet Hosp, San Antonio, TX USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. RP Barrett, JE (reprint author), Dartmouth Med Sch, Dept Community & Family Med, 7250 Strasenburgh, Hanover, NH 03755 USA. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 59 TC 35 Z9 35 U1 3 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JUL-AUG PY 1999 VL 21 IS 4 BP 260 EP 273 DI 10.1016/S0163-8343(99)00023-7 PG 14 WC Psychiatry SC Psychiatry GA 239KQ UT WOS:000082767600006 PM 10514950 ER PT J AU Haddow, JE Bradley, LA Palomaki, GE Doherty, RA Bernhardt, BA Brock, DJH Cheuvront, B Cunningham, GC Donnenfeld, AE Erickson, JL Erlick, HA Ferrie, RM FitzSimmons, SC Greene, MF Grody, WW Haddow, PK Harris, H Holmes, LB Howell, RR Katz, M Klinger, KW Kloza, EM LeFevre, ML Little, S Loeben, G McGovern, M Pyeritz, RE Rowley, PT Saiki, RK Short, MP Tabone, J Wald, NJ Wilker, NL Witt, DR AF Haddow, JE Bradley, LA Palomaki, GE Doherty, RA Bernhardt, BA Brock, DJH Cheuvront, B Cunningham, GC Donnenfeld, AE Erickson, JL Erlick, HA Ferrie, RM FitzSimmons, SC Greene, MF Grody, WW Haddow, PK Harris, H Holmes, LB Howell, RR Katz, M Klinger, KW Kloza, EM LeFevre, ML Little, S Loeben, G McGovern, M Pyeritz, RE Rowley, PT Saiki, RK Short, MP Tabone, J Wald, NJ Wilker, NL Witt, DR TI Issues in implementing prenatal screening for cystic fibrosis: Results of a working conference (vol 1, pg 129, 1999) SO GENETICS IN MEDICINE LA English DT Correction C1 Fdn Blood Res, Scarborough, ME 04074 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland. Univ N Carolina, Chapel Hill, NC 27515 USA. Calif Dept Hlth, Berkeley, CA USA. Penn Hosp, Philadelphia, PA 19107 USA. Roche Mol Syst, Alameda, CA 94501 USA. Cyst Fibrosis Fdn, Bethesda, MD USA. Vincent Mem Obstet Assoc, Boston, MA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Cent Manchester Hlth Care Trust, Manchester, Lancs, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Miami, Sch Med, Miami, FL 33152 USA. March Dimes Birth Defects Fdn, White Plains, NY USA. Genzyme, Framingham, MA USA. Univ Missouri, Columbia, MO 65211 USA. Univ Penn, Philadelphia, PA 19104 USA. Mt Sinai Sch Med, New York, NY 10029 USA. Allegheny Univ Hlth Sci, Pittsburgh, PA USA. Univ Rochester, Sch Med, Rochester, NY 14642 USA. Univ Chicago, Chicago, IL 60637 USA. Rapigene Inc, Bothell, WA USA. Wolfson Inst Prevent Med, London, England. Alliance Genet Support Grp, Washington, DC USA. Kaiser Permanente, San Jose, CA USA. RP Haddow, JE (reprint author), Fdn Blood Res, Scarborough, ME 04074 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD JUL-AUG PY 1999 VL 1 IS 5 BP 193 EP 193 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 248HX UT WOS:000083270000006 ER PT J AU Smith, VV Eng, C Milla, PJ AF Smith, VV Eng, C Milla, PJ TI Intestinal ganglioneuromatosis and multiple endocrine neoplasia type 2B: implications for treatment SO GUT LA English DT Article DE intestinal ganglioneuromatosis; RET; MEN 2B; thyroidectomy ID RET PROTOONCOGENE; MUTATION; SPECIFICITY; FAMILIES; DISEASE; KINASE; CELLS; 2A AB Three infants, who presented with intestinal obstruction due to diffuse transmural intestinal ganglioneuromatosis, are described. Mutation analysis of exon 16 of the RET proto-oncogene revealed germline M918T and thus, a molecular diagnosis of multiple endocrine neoplasia type 2B (MEN 2B). Two infants developed medullary carcinoma of the thyroid. The third had a prophylactic thyroidectomy despite no obvious thyroid masses and normal calcitonin concentrations, but microscopic multifocal medullary carcinoma was found on histological examination. Early recognition of intestinal ganglioneuromatosis with germline RET M918T mutation in pseudo-Hirschsprung's disease is an indication for prophylactic thyroidectomy. C1 Great Ormond St Hosp, Camelia Botnar Labs, Dept Histopathol, London WC1N 3JH, England. Inst Child Hlth, London, England. Great Ormond St Hosp, Dept Gastroenterol, London WC1N 3JH, England. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Smith, VV (reprint author), Great Ormond St Hosp, Camelia Botnar Labs, Dept Histopathol, Great Ormond St, London WC1N 3JH, England. RI Smith, Virpi/C-2159-2008 NR 18 TC 57 Z9 60 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD JUL PY 1999 VL 45 IS 1 BP 143 EP 146 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 209ZE UT WOS:000081079400027 PM 10369718 ER PT J AU Solhkhah, R Olds, J Englund, DW AF Solhkhah, R Olds, J Englund, DW TI To change the patient or the patient's world: The suicide attempt of a teased 12-year-old girl SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID CHILDHOOD C1 Massachusetts Gen Hosp, Div Child & Adolescent Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. McLean Hosp, Belmont, MA 02178 USA. Ctr Trauma, Brookline, MA USA. RP Solhkhah, R (reprint author), Massachusetts Gen Hosp, Div Child & Adolescent Psychiat, WACC 725,15 Parkman St, Boston, MA 02114 USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JUL-AUG PY 1999 VL 7 IS 2 BP 102 EP 108 PG 7 WC Psychiatry SC Psychiatry GA 214ZJ UT WOS:000081357200004 PM 10471248 ER PT J AU Smoller, JW Nierenberg, AA AF Smoller, JW Nierenberg, AA TI Small numbers, big impact SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID THERAPEUTIC DECISION-MAKING; PRESCRIBING BEHAVIOR; PHYSICIANS; PROBABILITY; FLUOXETINE; EXPRESSIONS; RISK; UNCERTAINTY; HEURISTICS; SUICIDE C1 Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. RP Smoller, JW (reprint author), Massachusetts Gen Hosp, Clin Psychopharmacol Unit, 15 Parkman St,Suite ACC-815, Boston, MA 02114 USA. FU NIMH NIH HHS [T32MH17119] NR 44 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JUL-AUG PY 1999 VL 7 IS 2 BP 109 EP 113 PG 5 WC Psychiatry SC Psychiatry GA 214ZJ UT WOS:000081357200005 PM 10471249 ER PT J AU Wiener-Vacher, SR Guinan, JJ Kobler, JB Norris, BE AF Wiener-Vacher, SR Guinan, JJ Kobler, JB Norris, BE TI Motoneuron axon distribution in the cat stapedius muscle SO HEARING RESEARCH LA English DT Article DE acoustic reflex; middle-ear muscle; motor control; motor unit size ID RESPONSES; NUCLEUS AB Stapedius-motoneuron cell bodies in the brainstem are spatially organized according to their acoustic response laterality, as demonstrated by intracellular labeling of physiologically identified motoneurons [Vacher et al., 1989. J. Comp. Neurol, 289, 401-415]. To determine whether a similar functional spatial segregation is present in the muscle, we traced physiologically identified, labeled axons into the stapedius muscle. Ten labeled axons were visible in the facial nerve and five could be traced to endplates within the muscle. These five axons had 39 observed branches (others may have been missed). This indicates an average innervation ratio (greater than or equal to 7.8) which is much higher than that obtained from previous estimates of the numbers of stapedius motoneurons and muscle fibers in the cat. One well-labeled stapedius motor axon innervated only a single muscle fiber. In contrast, two labeled axons had over 10 endings and innervated muscle fibers spread over wide areas in the muscle. Two of the axons branched and coursed through two primary stapedius fascicles, indicating that the muscle zones innervated by different primary fascicles are not functionally segregated. In another series of experiments, retrograde tracers were deposited in individual primary nerve fascicles. In every case, labeled stapedius-motoneuron cell bodies were found in each of the physiologically identified stapedius-motoneuron regions in the brainstem. These observations suggest there is little, if any, functional spatial segregation based on separate muscle compartments in the stapedius muscle, despite there being functional spatial segregation in the stapedius-motoneuron pool centrally. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, HP Mosher Laryngol Res Lab, Boston, MA 02114 USA. RP Guinan, JJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. FU FIC NIH HHS [3 FO5 TWO 3605-01S1]; NIDCD NIH HHS [P01 DC00119]; NINDS NIH HHS [P01 NS13162A] NR 33 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD JUL PY 1999 VL 133 IS 1-2 BP 139 EP 148 DI 10.1016/S0378-5955(99)00064-7 PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 212PN UT WOS:000081225600014 PM 10416872 ER PT J AU Carroll, DL Hamilton, GA McGovern, BA AF Carroll, DL Hamilton, GA McGovern, BA TI Changes in health status and quality of life and the impact of uncertainty in patients who survive life-threatening arrhythmias SO HEART & LUNG LA English DT Article ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; HOSPITAL CARDIAC-ARREST; VENTRICULAR-TACHYCARDIA; OF-LIFE; DEATH; RESPONSES; ILLNESS AB OBJECTIVE: The purpose of this study was to describe the changes in perception of health status and quality of life from before treatment to 6 months after and the impact of uncertainty on these variables I : in survivors of life-threatening arrhythmia. DESIGN AND SETTING: A descriptive correlational design at a large urban teaching hospital. MEASURES: We measured health status, quality of life; and uncertainty before treatment and 6 months after a life-threatening arrhythmia. RESULTS: Survivors included 66 men and 15 women, 41 of whom received pharmacologic therapy and 36 of whom received an implantable cardioverter defibrillator (ICD), completed the Medical Outcomes F Survey (SF-36), Ferrans and Powers Quality of Life Index: (QLI), and the Mishel Uncertainty in Illness Scale (MUIS-C) before treatment and 6 months after. There were significant improvements in the men tal and physical health composite summaries as measured by the SF36 (P < .01). Conversely, there were significant reductions in the overall score and specifically in socioeconomic and psychological/spiritual quality of life domains as measured by the QLI (P < .05).:An increased perception of uncertainty was related to decreased perception of health status and quality of life at both measurement times, with higher correlations 6 months later. CONCLUSIONS: Survivors demonstrated improvements in perceived health status, although this did not appear to translate into improvements in the subjective domains of quality of life. The overall quality of life and the domains of psychological/spiritual state and socioeconomic status were lower 6 months after a life-threatening arrhythmia. Uncertainty had a significant impact on these perceptions, identifying an area for nursing interventions. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Carroll, DL (reprint author), Massachusetts Gen Hosp, GRB 1034, Boston, MA 02114 USA. NR 61 TC 37 Z9 38 U1 1 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0147-9563 J9 HEART LUNG JI Heart Lung PD JUL-AUG PY 1999 VL 28 IS 4 BP 251 EP 260 DI 10.1016/S0147-9563(99)70071-3 PG 10 WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System SC Cardiovascular System & Cardiology; Nursing; Respiratory System GA 218BR UT WOS:000081533800003 PM 10409311 ER PT J AU Johnson, RJ Gordon, KL Suga, S Duijvestijn, AM Griffin, K Bidani, A AF Johnson, RJ Gordon, KL Suga, S Duijvestijn, AM Griffin, K Bidani, A TI Renal injury and salt-sensitive hypertension after exposure to catecholamines SO HYPERTENSION LA English DT Article DE phenylephrine; renal circulation; hypertension, episodic; sympathetic nervous system ID SYMPATHETIC NERVOUS-SYSTEM; TUBULOINTERSTITIAL DISEASE; BLOOD-PRESSURE; ANGIOTENSIN-II; POTENTIAL ROLE; NOREPINEPHRINE; OSTEOPONTIN; KIDNEY; CELLS; DAMAGE AB We investigated whether chronic infusion of phenylephrine could induce structural and functional changes in the kidney of rats with the subsequent development of salt-sensitive hypertension. Rats were infused with phenylephrine (0.15 mmol/kg per day) by minipump, resulting in a moderate increase in systolic blood pressure (BP) (17 to 25 mm Hg) and a marked increase in BP variability as measured by an internal telemetry device. After 8 weeks, the phenylephrine infusion was stopped with the return of BP to normal, and a nephrectomy was performed for histological studies. Glomeruli were largely spared, but focal tubulointerstitial fibrosis was present, with the de novo expression of osteopontin by injured tubules, macrophage and "myofibroblast" accumulation, and focal increases in mRNA for transforming growth factor beta by in situ hybridization, Peritubular capillaries at sites of injury had distorted morphology with shrinkage, rounding, and focal rarefaction, and endothelial cell proliferation was also identified. Rats were randomized to a high (8% NaCl or 1.36 mol/kg) or low (0.1% NaCl or 17 mmol/kg) salt diet. After 4 to 8 weeks, phenylephrine-treated rats on a high salt diet developed marked hypertension, which was in contrast with phenylephrine-treated rats placed on a low salt diet or vehicle-treated rats given a high salt diet, Hypertension after phenylephrine exposure correlated with the initial mean systolic BP (r(2)=0.99) and the degree of BP lability (r(2)=0.99) during the phenylephrine infusion, the amount of osteopontin expressed in the initial biopsy/nephrectomy (r(2)=0.74), and the final glomerular filtration rate (r(2)=0.58). These studies provide a mechanism by which a markedly elevated sympathetic nervous system can induce salt-dependent hypertension even when the hyperactive sympathetic state is no longer engaged. C1 Univ Washington, Med Ctr, Div Nephrol, Seattle, WA 98195 USA. Univ Maastricht, Dept Internal Med, Immunol Sect, Maastricht, Netherlands. Loyola Univ, Med Ctr, Div Nephrol, Maywood, IL 60153 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. RP Johnson, RJ (reprint author), Univ Washington, Med Ctr, Div Nephrol, Box 356521, Seattle, WA 98195 USA. FU NIDDK NIH HHS [DK-47659, DK-43422, DK-52121] NR 44 TC 70 Z9 74 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUL PY 1999 VL 34 IS 1 BP 151 EP 159 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 217XW UT WOS:000081525100027 PM 10406839 ER PT J AU Lin, CP Kelly, NW Sibayan, SAB Latina, MA Anderson, RR AF Lin, CP Kelly, NW Sibayan, SAB Latina, MA Anderson, RR TI Selective cell killing by microparticle absorption of pulsed laser radiation SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Article DE cavitation; cell targeting; microparticle; pulse laser ID ND-YAG LASER; OPTICAL-BREAKDOWN; REDUCTION; ABLATION; DAMAGE AB The mechanism of interaction between subcellular pigment microparticles and short pulse laser radiation was investigated with nanosecond time-resolved microscopy and fluorescence microscopy, Stroboscopic illumination was used to capture images of transient events induced in cells by laser pulses. Fluorescence microscopy enabled assessment of cell damage using fluorescent probes, Short-lived intracellular cavitation bubbles were directly visualized within nanoseconds after laser irradiation. Microbubble expansion and implosion took place on the timescale of 0.1-1 mu s and were confined entirely within pigmented cells with remarkable selectivity. Cells containing particles underwent cavitation and rapidly lost viability, while adjacent cells without particles remained viable. Nonpigmented cells can be targeted by labeling them with absorbing particles. Laser-pumped microparticles provide an efficient means of selective cell targeting. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Lin, CP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. NR 12 TC 82 Z9 82 U1 0 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD JUL-AUG PY 1999 VL 5 IS 4 BP 963 EP 968 DI 10.1109/2944.796318 PG 6 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 248CM UT WOS:000083257800014 ER PT J AU Lee, S Doukas, AG AF Lee, S Doukas, AG TI Laser-generated stress waves and their effects on the cell membrane SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Article DE ablation; cell loading; cell viability; drug delivery; membrane permeability; photoacoustics; photomechanical effects; shock waves; stress waves ID INDUCED SHOCK-WAVES; EXCIMER-LASER; IN-VITRO; PHOTOACOUSTIC INJURY; PLASMA-MEMBRANE; ULTRASOUND; PERMEABILIZATION; IRRADIATION; DELIVERY; TISSUE AB High-power lasers can generate well characterized stress (pressure) waves. The characteristics of the stress waves can be controlled by the appropriate choice of the laser parameters and the properties of the target material. Laser-generated stress waves can alter the structure and function of cells in vitro. Furthermore, they render the cell membrane permeable. Molecules present in the extracellular medium diffuse into the cytoplasm under the concentration gradient, Subsequently, the plasma membrane reseals, keeping the exogenous molecules inside the cell, Laser-generated stress waves can provide a potentially powerful tool for drug delivery. C1 Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp,Wellman Labs Photomed, Boston, MA 02114 USA. RP Lee, S (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp,Wellman Labs Photomed, Boston, MA 02114 USA. NR 41 TC 35 Z9 35 U1 1 U2 7 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD JUL-AUG PY 1999 VL 5 IS 4 BP 997 EP 1003 DI 10.1109/2944.796322 PG 7 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 248CM UT WOS:000083257800018 ER PT J AU Paithankar, DY Schomacker, KT Nishioka, NS AF Paithankar, DY Schomacker, KT Nishioka, NS TI Frequency-domain optical detection of subsurface blood vessels: Experimental and computational studies using a scattering phantom SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Article DE blood vessel detection; frequency-domain photon migration; light transport in tissue ID PHOTON MIGRATION; TOMOGRAPHY; MEDIA; ABSORBERS; FLOW AB A simple method to localize blood vessels beneath the surface of tissue could be very useful during laparoscopic and endoscopic procedures. However, the detection of blood vessels deep within tissue using light is limited by tissue scattering. In this study, frequency-domain photon migration methods were used to detect blood vessels within a scattering medium. The depth at which blood vessels could be detected was greater than 10 mm. The experimental measurements agree well with predictions obtained from the diffusion approximation to the radiative transport equation. These studies demonstrate the potential of frequency-domain optical methods to detect subsurface blood vessels. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Paithankar, DY (reprint author), Candela Corp, Wayland, MA 01778 USA. NR 16 TC 3 Z9 3 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD JUL-AUG PY 1999 VL 5 IS 4 BP 1032 EP 1039 DI 10.1109/2944.796327 PG 8 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 248CM UT WOS:000083257800023 ER PT J AU Brezinski, ME Fujimoto, JG AF Brezinski, ME Fujimoto, JG TI Optical coherence tomography: High-resolution imaging in nontransparent tissue SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Article DE dysplasia; imaging; intravascular ultrasound; light; optical coherence tomography; plaque rupture ID BIOPSY; FEASIBILITY AB Optical coherence tomography (OCT) is a method of high-resolution imaging originally developed for the transparent tissue of the eye. Recently, the technology has been advanced toward the difficult challenge of imaging in nontransparent tissue. In this paper, three topics are addressed. First, the principles behind OCT imaging are discussed. Second, the difficulties associated with OCT imaging in nontransparent tissue are outlined. Finally, the feasibility of OCT for medical imaging will be discussed. Specifically, OCT demonstrates its greatest potential in situations where conventional biopsy is either dangerous or ineffective. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. MIT, Elect Res Lab, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. RP Brezinski, ME (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 39 TC 148 Z9 150 U1 10 U2 18 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD JUL-AUG PY 1999 VL 5 IS 4 BP 1185 EP 1192 DI 10.1109/2944.796345 PG 8 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 248CM UT WOS:000083257800041 ER PT J AU Simon, AR Warrens, AN Sykes, M AF Simon, AR Warrens, AN Sykes, M TI Efficacy of adhesive interactions in pig-to-human xenotransplantation SO IMMUNOLOGY TODAY LA English DT Article ID PORCINE E-SELECTIN; CELL-ADHESION; BONE-MARROW; MONOCLONAL-ANTIBODIES; CARDIAC ALLOGRAFT; TRANSPLANTATION TOLERANCE; EXTRACELLULAR-MATRIX; XENOGRAFT REJECTION; DEFICIENT MICE; STEM-CELLS AB Successful xenotransplantation depends on many factors, one being the interactions of cross-species adhesion molecule-ligand pairs. Depending on the approach used to facilitate xenotransplantation, these interactions can play differing roles. Here, Andre Simon, Anthony Warrens and Megan Sykes review the existing information on pig-to-human adhesive interactions and its implication for different approaches to pig-to-human xenotransplantation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Surg Serv,Bone Marrow Transplantat Sect, Boston, MA 02129 USA. Hammersmith Hosp, Imperial Coll, Sch Med, Dept Immunol,Renal Unit, London W12 0NN, England. RP Simon, AR (reprint author), Med Hsch Hannover, Klin Thorax Herz & Gefasschirurg, Carl Neuberg Str 1, D-30623 Hannover, Germany. NR 59 TC 32 Z9 34 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD JUL PY 1999 VL 20 IS 7 BP 323 EP 330 DI 10.1016/S0167-5699(99)01485-1 PG 8 WC Immunology SC Immunology GA 216RG UT WOS:000081455200005 PM 10379051 ER PT J AU Dong, H Chen, TT Dewhirst, FE Fleischmann, RD Fraser, CM Duncan, MJ AF Dong, H Chen, TT Dewhirst, FE Fleischmann, RD Fraser, CM Duncan, MJ TI Genomic loci of the Porphyromonas gingivalis insertion element IS1126 SO INFECTION AND IMMUNITY LA English DT Article ID DEFICIENT MUTANT; ARG-GINGIPAIN; IS4 FAMILY; SEQUENCE; TRANSPOSASE; PROTEINASE; HOMOLOG; CLONING; PRPRI; GENES AB The Porphyromonas gingivalis genome contains multiple copies of insertion element IS1126. When chromosomal DNA digests of different strains were probed with IS1126, between 25 and 35 hybridizing fragments per genome were detected, depending on the strain, Unrelated strains had very different restriction fragment length polymorphism (RFLP) patterns. When different laboratory copies of a specific strain were examined, the IS1126 RFLP patterns were very similar but small differences were observed, indicating that element associated changes had occurred during laboratory passage. Within the nest year, genome sequencing, assembly, and annotation for P. gingivalis W83 will be completed. Because repetitive elements complicate the assembly of randomly sequenced DNA fragments, we isolated and sequenced the flanking regions of IS1126 copies in strain W83, We also isolated and sequenced the flanking regions of IS1126 copies in strain ATCC 33277 in order to compare insertion sites in phylogenetically divergent strains, We identified 37 new sequences flanking IS1126 from strain ATCC 33277 and 30 from strain W83, The insertion element was found between genes except where it transposed into another insertion element. Examination of identifiable flanking genes or open reading frames indicated that the insertion sites were different in the two strains, except that both strains possess an insertion adjacent to the Lys-gingipain gene (J. P. Lewis and F. L. Macrina, Infect, Immun, 66:3035-3042, 1998). Most of the genes or sequences flanking IS1126 in ATCC 33277 were present in W83 but were contiguous and not insertion element associated. Thus, where genes were identified in both strains, their order was maintained, indicating that the two genomes are organized similarly, but the loci of IS1126 are different, In both strains, insertion element-associated duplicated target sites were lost from several copies of IS1126, providing evidence of homologous recombination between elements. Larger organizational differences between the genomes, such as deletions and inversions, may result from insertion element-mediated recombination events. C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Inst Genom Res, Rockville, MD 20850 USA. RP Duncan, MJ (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. OI Fraser, Claire/0000-0003-1462-2428 FU NIDCR NIH HHS [DE 10510, DE 12082, R01 DE010510] NR 23 TC 13 Z9 14 U1 0 U2 0 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 JUL PY 1999 VL 67 IS 7 BP 3416 EP 3423 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 209RZ UT WOS:000081063800034 PM 10377121 ER PT J AU Kacmarek, RM AF Kacmarek, RM TI NIPPV: patient-ventilator synchrony, the difference between success and failure? SO INTENSIVE CARE MEDICINE LA English DT Editorial Material ID POSITIVE-PRESSURE VENTILATION; ACUTE RESPIRATORY-FAILURE; OBSTRUCTIVE PULMONARY-DISEASE; MECHANICAL VENTILATION; SUPPORT VENTILATION; CONTROLLED TRIAL C1 Massachusetts Gen Hosp, Resp Care Dept, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Resp Care Dept, 55 Fruit St, Boston, MA 02114 USA. NR 18 TC 9 Z9 12 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD JUL PY 1999 VL 25 IS 7 BP 645 EP 647 DI 10.1007/s001340050924 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 223TL UT WOS:000081856900001 PM 10470565 ER PT J AU Baker, PM Clement, PB Bell, DA Young, RH AF Baker, PM Clement, PB Bell, DA Young, RH TI Superficial endometriosis of the uterine cervix: A report of 20 cases of a process that may be confused with endocervical glandular dysplasia or adenocarcinoma in situ SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE cervix; endometriosis; atypical glandular cells; adenocarcinoma in situ ID METAPLASIA; DIAGNOSIS AB Twenty cases of superficial endometriosis of the uterine cervix that occurred in patients from 20 to 51 (mean 37.1) years of age are described. The majority of the cases were seen in consultation and were usually referred because of diagnostic problems; endocervical glandular dysplasia, adenocarcinoma in situ, or rarely invasive adenocarcinoma were a frequent consideration of the contributor, The endometriosis was almost always an incidental microscopic finding. The endometriotic foci were usually confined to the superficial third of the cervical wall, but in one case there was also involvement of the middle third of the cervical wall. Deep cervical endometriosis was not present in any case. The endometriotic glands were typically evenly spaced and were surrounded at least Focally by endometriotic stroma in all cases. The endometriotic stromal cells, however, were significantly obscured by inflammatory cells (two cases), inflammatory cells and hemorrhage (two cases), hemorrhage (four cases), and in one case by smooth muscle metaplasia causing initial failure to recognize the stromal component of the process. The presence of mitotic figures in the glandular epithelium contributed to an initial diagnosis of a premalignant or malignant glandular lesion being made or seriously entertained in 10 cases. Awareness that mitotic figures may be conspicuous in endometriosis from women of reproductive age, the usually bland cytologic features of the endometriotic epithelium, and the presence of associated endometrial stromal cells all facilitate establishing the correct diagnosis. C1 Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Vancouver Hosp & Hlth Sci Ctr, Dept Pathol, Vancouver, BC, Canada. Univ British Columbia, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. RP Young, RH (reprint author), Massachusetts Gen Hosp, Dept Pathol, 32 Fruit St, Boston, MA 02114 USA. NR 17 TC 33 Z9 34 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JUL PY 1999 VL 18 IS 3 BP 198 EP 205 DI 10.1097/00004347-199907000-00002 PG 8 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 210ML UT WOS:000081109200002 PM 12090586 ER PT J AU Means, RT AF Means, RT TI Advances in the anemia of chronic disease SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Review DE anemia; erythropoiesis; ferrokinetics; cytokines; tumor necrosis factor; interferon-beta; interferon-gamma; interleukin-1 ID TUMOR-NECROSIS-FACTOR; RECOMBINANT-HUMAN-ERYTHROPOIETIN; COLONY-FORMING-UNITS; RHEUMATOID-ARTHRITIS; INTERFERON-GAMMA; FACTOR-ALPHA; TRANSFERRIN RECEPTORS; ERYTHROID PROGENITORS; AUTOLOGOUS BLOOD; CELLS-INVITRO AB The anemia found in patients with chronic infectious, inflammatory, and neoplastic disorders, known as the anemia of chronic disease (ACD), is one of the most common syndromes in medicine. A characteristic finding of the disorders associated with ACD is increased production of the cytokines that mediate the immune or inflammatory response, such as tumor necrosis factor, interleukin-1, and the interferons. All the processes involved in the development of ACD can be attributed to these cytokines, including shortened red cell survival, blunted erythropoietin response to anemia, impaired erythroid colony formation in response to erythropoietin, and abnormal mobilization of reticuloendothelial iron stores. In this review advances in the understanding of the diagnostic, pathophysiologic, and therapeutic aspects of this syndrome are summarized. (C) 1999 The Japanese Society of Hematology. C1 Med Univ S Carolina, Div Hematol Oncol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Div Hematol Oncol, Charleston, SC USA. RP Means, RT (reprint author), Med Univ S Carolina, Div Hematol Oncol, 903 CSB,96 Jonathan Lucas St, Charleston, SC 29425 USA. RI Means, Robert/A-4454-2008 FU NHLBI NIH HHS [HL53703] NR 61 TC 117 Z9 124 U1 2 U2 5 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD JUL PY 1999 VL 70 IS 1 BP 7 EP 12 PG 6 WC Hematology SC Hematology GA 284RW UT WOS:000085347100002 PM 10446488 ER PT J AU Belliveau, JW AF Belliveau, JW TI Spatiotemporal brain imaging of human visual system processing SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, NMR Ctr, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD JUL PY 1999 VL 33 IS 1 MA 2 BP 35 EP 35 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 223AF UT WOS:000081817000009 ER PT J AU Dale, AM AF Dale, AM TI Spatiotemporal imaging of human brain function SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, MGH NMR Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD JUL PY 1999 VL 33 IS 1 MA 19 BP 40 EP 41 PG 2 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 223AF UT WOS:000081817000026 ER PT J AU Chiappa, KH AF Chiappa, KH TI Clinical validation of EEG dipole source analysis SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, EEG Lab, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD JUL PY 1999 VL 33 IS 1 MA 35 BP 45 EP 45 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 223AF UT WOS:000081817000042 ER PT J AU Freedman, R Adler, LE Olincy, A Leonard, S AF Freedman, R Adler, LE Olincy, A Leonard, S TI Inhibition of P50 auditory evoked potentials in schizophrenia SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Univ Colorado, Denver, CO 80262 USA. Denver VAMC, Denver, CO 80262 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD JUL PY 1999 VL 33 IS 1 MA 62 BP 53 EP 54 PG 2 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 223AF UT WOS:000081817000069 ER PT J AU Moore, A Sergeyev, N Bredow, S Weissleder, R AF Moore, A Sergeyev, N Bredow, S Weissleder, R TI A model system to quantitate tumor burden in locoregional lymph nodes during cancer spread SO INVASION & METASTASIS LA English DT Article DE cancer; metastasis; lymph nodes; lymphotropic drugs ID METASTASIS; CARCINOMA; CELLS; AGENT AB In order to quantitate the metastatic burden of secondary tumor deposits in locoregional lymph nodes, we produced a green fluorescent protein (GFP)-expressing murine cell line (B16F1) metastatic to lymph nodes in immunocompetent mice, When implanted into the hindleg of mice, all animals developed paraaortic lymph node metastases, Fluorescence microscopy, immunohistochemistry, and RT-PCR confirmed the presence of metastatic cells in lymph nodes, Tumoral deposits occurred preferentially in marginal sinuses and spread superficially to the subcortical area, Western blot analysis showed that the local tumor burden could be quantitated in individual lymph nodes, This model system should be useful for quantitating metastatic invasion particularly of micrometastases and aid in the development of lymphotropic drugs to detect and/or treat lymph node metastases in advanced cancers, Copyright (C) 2000 S. Karger AG, Basel. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,5403, Charlestown, MA 02129 USA. NR 17 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-1789 J9 INVAS METAST JI Invasion Metastasis PD JUL-AUG PY 1999 VL 18 IS 4 BP 192 EP 197 PG 6 WC Oncology SC Oncology GA 279EE UT WOS:000085030800004 ER PT J AU Lu, M Perez, VL Ma, NL Miyamoto, K Peng, HB Liao, JK Adamis, AP AF Lu, M Perez, VL Ma, NL Miyamoto, K Peng, HB Liao, JK Adamis, AP TI VEGF increases retinal vascular ICAM-1 expression in vivo SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 10-15, 1998 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol ID ENDOTHELIAL GROWTH-FACTOR; DIABETIC-RETINOPATHY; ADHESION MOLECULES; IN-VIVO; NEOVASCULARIZATION; PRIMATE; ANGIOGENESIS; INHIBITION; CYTOKINES; ISCHEMIA AB PURPOSE. Intraocular injections of vascular endothelial growth factor (VEGF), a peptide implicated in the pathogenesis of diabetic retinopathy, can induce retinal ischemia. Diabetic retinal ischemia may be caused, in part, by the adhesion of leukocytes to the retinal vasculature. In this study, the ability of VEGF to increase the expression of intercellular adhesion molecule-1 (ICAM-1) and other adhesion molecules in capillary endothelium and the retinal vasculature was examined. METHODS. The expression of ICAM-1, vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and P-selectin on human brain capillary endothelial cell monolayers exposed to VEGF was quantitated by immunoassay. The effect of VEGF on retinal vascular ICAM-1 expression was determined in ICAM-1 immunofluorescence studies of retinal flat-mounts and in RNase protection assays. RESULTS. VEGF increased capillary endothelial cell ICAM-1 levels in a dose- and time-dependent manner (6-24 hours, plateau after 6 hours; EC50, 25 ng/ml). VEGF failed to alter E-selectin, P-selectin, or VCAM-1 levels under the conditions tested. Intravitreal injections of pathophysiologically relevant concentrations of VEGF increased ICAM-1 protein and mRNA levels in the retinal vasculature. CONCLUSIONS. VEGF increases retinal vascular ICAM-1 expression. VEGF-induced increases in ICAM-1 may promote retinal leukostasis in diabetic eyes. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Childrens Hosp, Surg Res Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Schepens Eye Res Inst, Boston, MA USA. RP Adamis, AP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 18 TC 140 Z9 155 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 1999 VL 40 IS 8 BP 1808 EP 1812 PG 5 WC Ophthalmology SC Ophthalmology GA 210DR UT WOS:000081090300026 PM 10393052 ER PT J AU Dryja, TP Rucinski, DE Chen, SH Berson, EL AF Dryja, TP Rucinski, DE Chen, SH Berson, EL TI Frequency of mutations in the gene encoding the alpha subunit of rod cGMP-phosphodiesterase in autosomal recessive retinitis pigmentosa SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID CYCLIC GUANOSINE MONOPHOSPHATE; AMINO-ACID-SEQUENCE; BETA-SUBUNIT; NONSENSE MUTATION; MOLECULAR CHARACTERIZATION; CHROMOSOMAL LOCALIZATION; GMP PHOSPHODIESTERASE; CONE DYSPLASIA; RD MOUSE; IDENTIFICATION AB PURPOSE. To determine the mutation spectrum of the PDE6A gene encoding the cu subunit of rod cyclic guanosine monophosphate (cGMP)-phosphodiesterase and the proportion of patients with recessive retinitis pigmentosa (RP) due to mutations in this gene. METHODS. The single-strand conformation polymorphism (SSCP) technique and a direct genomic sequencing technique were used to screen all 22 exons of this gene for mutations in 164 unrelated patients with recessive or isolate RP. Variant DNA fragments revealed by SSCP analysis were subsequently sequenced. Selected alleles that altered the coding region or intron splice sites were evaluated further through segregation analysis in the families of the index cases. RESULTS. Four new families were identified with five novel mutations in this gene that cosegregated with disease. Combining the data presented here with those published earlier by the authors, eight different mutations in six families have been discovered to be pathogenic. Two of the mutations are nonsense, five are missense, and one affects a canonical splice-donor site. CONCLUSIONS. The PDE6A gene appears to account for roughly 3% to 4% of families with recessive RP in North America. A compilation of the pathogenic mutations in PDE6A and those reported in the homologous gene PDE6B encoding the beta subunit of rod cGMP-phosphodiesterase shows that the cGMP-binding and catalytic domains are frequently affected. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. RP Dryja, TP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY00169, EY08683] NR 47 TC 68 Z9 70 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 1999 VL 40 IS 8 BP 1859 EP 1865 PG 7 WC Ophthalmology SC Ophthalmology GA 210DR UT WOS:000081090300036 PM 10393062 ER PT J AU Schima, W Saini, S Petersein, J Weissleder, R Harisinghani, M Mayo-Smith, W Hahn, PF AF Schima, W Saini, S Petersein, J Weissleder, R Harisinghani, M Mayo-Smith, W Hahn, PF TI MR imaging of the liver with Gd-BOPTA: Quantitative analysis of T1-weighted images at two different doses SO JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article ID GADOBENATE DIMEGLUMINE; LESIONS; CT AB This study evaluates the efficacy of gadobentate-dimeglumine (Gd-BOPTA) for enhancement of liver signal-to-noise ratio (SNR) and lesion-liver contrast-to-noise ratio (CNR) on T1-weighted spin-echo (SE) and gradient-recalled-echo (GRE) images at two different doses. Fifty patients with known or suspected liver lesions were examined at 1.5 T. T1-weighted SE (TR/TE 300/12 msec) and GRE images (TR/TE80/4.2 msec/flip angle80 degrees) were obtained before and at 40-80 minutes and 90-120 minutes after administration of 0.05 or 0.1 mmol/kg Gd-BOPTA. Quantitative measurements of tissue signal intensity were performed at each dose. Liver showed significant enhancement after Gd-BOPTA on T1-weighted SE and GRE images (0.05 mmol: P < 0.05; 0.1 mmol: P < 0.001). The dose of 0.1 mmol/kg provided higher liver SNR than 0.05 mmol/kg. Mean liver SNR was higher on GRE than SE images (p < 0.0001). Lesion-Iiver CNR significantly increased on GRE images after 0.1 mmol (P < 0.05). There was a trend toward superiority of 0.1 mmol over 0.05 mmol/kg, GRE images were superior to SE images for pre- and post Gd-BOPTA lesion-liver CNR (P < 0.05). Our study suggests that Gd-BOPTA provides prolonged enhancement of liver SNR and CNR, that a dose of 0.1 mmol/Kg appears to be superior than 0.05 mmol/Kg, and that GRE techniques should be used in preference over SE techniques. J. Magn. Reson. Imaging 1999:10:80-83. (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Saini, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 13 TC 13 Z9 15 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1053-1807 J9 JMRI-J MAGN RESON IM JI JMRI-J. Magn. Reson. Imaging PD JUL PY 1999 VL 10 IS 1 BP 80 EP 83 DI 10.1002/(SICI)1522-2586(199907)10:1<80::AID-JMRI11>3.0.CO;2-S PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 212CW UT WOS:000081199600011 PM 10398981 ER PT J AU McNally, RJ Otto, MW Yap, L Pollack, MH Hornig, CD AF McNally, RJ Otto, MW Yap, L Pollack, MH Hornig, CD TI Is panic disorder linked to cognitive avoidance of threatening information? SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE panic disorder; directed forgetting; memory bias; hemispheric laterality ID MEMORY BIAS; EXPLICIT MEMORY; ANXIETY; WORDS; IMPLICIT AB We used a directed-forgetting paradigm to investigate whether panic disorder patients cognitively avoid threatening information. To determine if hemispheric laterality predicts processing biases in this paradigm, we used dichotic listening methods to ascertain participants' auditory perceptual asymmetry (PA). Panic disorder patients and healthy control participants viewed a series of intermixed threat, positive, and neutral words, each followed by an instruction to either remember the word or forget it. They then performed free recall and recognition tests for all words, irrespective of initial instructions, )iDirected-forgetting effects occurred equally for ail word types: both groups recalled remember-words better than forget-words. Because this task is strongly affected by encoding style, panic patients as a group do not seem to avoid encoding threat cues. However, PA analyses revealed that cognitive avoidance of threat forget-words was significantly associated with greater left hemisphere bias in the control group and nonsignificantly associated with lesser left hemisphere bias in the panic disorder group. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP McNally, RJ (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. FU NIMH NIH HHS [MH51927] NR 25 TC 12 Z9 12 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD JUL-AUG PY 1999 VL 13 IS 4 BP 335 EP 348 DI 10.1016/S0887-6185(99)00008-0 PG 14 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 228XZ UT WOS:000082164000001 PM 10504105 ER PT J AU Deem, S Hedges, RG McKinney, S Polissar, NL Alberts, MK Swenson, ER AF Deem, S Hedges, RG McKinney, S Polissar, NL Alberts, MK Swenson, ER TI Mechanisms of improvement in pulmonary gas exchange during isovolemic hemodilution SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE anemia; oxygen; carbon dioxide; rabbits ID BLOOD-FLOW DISTRIBUTION; NORMOVOLEMIC HEMODILUTION; OXYGEN-TRANSPORT; SEA-LEVEL; MICROVASCULAR HEMODYNAMICS; HEMOGLOBIN CONCENTRATION; EXTREME HEMODILUTION; SIMULATED ALTITUDE; CARDIAC-OUTPUT; O-2 TRANSPORT AB Severe anemia is associated with remarkable stability of pulmonary gas exchange (S. Deem, M. K. Alberts, M. J. Bishop, A. Bidani, and E. R. Swenson. J. Appl. Physiol. 83: 240-246, 1997), although the factors that contribute to this stability have not been studied in detail. In the present study, 10 Flemish Giant rabbits were anesthetized, paralyzed, and mechanically ventilated at a fixed minute ventilation. Serial hemodilution was performed in five rabbits by simultaneous withdrawal of blood and infusion of an equal volume of 6% hetastarch; five rabbits were followed over a comparable time. Ventilation-perfusion (VA/Q) relationships were studied by using the multiple inert-gas-elimination technique, and pulmonary blood flow distribution was assessed by using fluorescent microspheres. Expired nitric oxide (NO) was measured by chemiluminescence. Hemodilution resulted in a linear fall in hematocrit over time, from 30 +/- 1.6 to 11 +/- 1%. Anemia was associated with an increase in arterial Po-2 in comparison with controls (P < 0.01 between groups). The improvement in O-2 exchange was associated with reduced VA/Q heterogeneity, a reduction in the fractal dimension of pulmonary blood flow (P = 0.04), and a relative increase in the spatial correlation of pulmonary blood flow (P = 0.04). Expired NO increased with anemia, whereas it remained stable in control animals (P < 0.0001 between groups). Anemia results in improved gas exchange in the normal lung as a result of an improvement in overall VA/Q matching. In turn, this may be a result of favorable changes in pulmonary blood flow distribution, as assessed by the fractal dimension and spatial correlation of blood flow and as a result of increased NO availability. C1 Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Mt Whisper Light Stat Cousulting, Seattle, WA 98112 USA. RP Deem, S (reprint author), Univ Washington, Harborview Med Ctr, Dept Anesthesiol, 325 9th Ave,Box 359724, Seattle, WA 98104 USA. FU NHLBI NIH HHS [HL-03796-01, HL-45571] NR 62 TC 36 Z9 38 U1 2 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JUL PY 1999 VL 87 IS 1 BP 132 EP 141 PG 10 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 215HN UT WOS:000081376200018 PM 10409567 ER PT J AU Vrahas, MS Widding, KK Thomas, KA AF Vrahas, MS Widding, KK Thomas, KA TI The effects of simulated transverse, anterior column, and posterior column fractures of the acetabulum on the stability of the hip joint SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID BIOCHEMICAL CHANGES; OSTEOARTHRITIS AB Background: Knowledge of the location of the weight-bearing portion of the acetabulum would assist orthopaedic surgeons in the treatment of acetabular fractures. With use of controlled experimental transverse, anterior column, and posterior column osteotomies, we investigated the weight-bearing region of the acetabulum. Methods: Twenty-four fresh-frozen cadaveric hip joints were tested. Simulated transverse fractures were evaluated in twelve specimens, and simulated anterior column and posterior column fractures were tested in six specimens each. Each femur and acetabulum was potted and mounted in an aluminum fixture, with the acetabulum positioned in 25 degrees of flexion and 20 degrees of abduction. Each specimen was tested intact and after successive osteotomies. The transverse osteotomies had roof-are angles of 60, 50, 40, and 30 degrees. The anterior column and posterior column osteotomies were classified as very low low intermediate, or high. Compressive loading to 800, 1200, and 1600 newtons was performed four times for each intact specimen and after each osteotomy, A specimen was considered to be stable if no gross dislocation occurred during any of the four loading cycles. Translation of the femur within the acetabulum also was measured during each trial. Results: The number of stable specimens decreased both with higher applied loads and with more superior osteotomies. The stability of the hip was significantly affected by both the location of the fracture and the magnitude of the applied load (p < 0.00005), Translation of the femur within the acetabulum increased,vith higher applied loads and with more superior osteotomies. Conclusions: Fractures that have a medial roof-are angle of 45 degrees or less, an anterior roof-are angle of 25 degrees or less, or a posterior roof-are angle of 70 degrees or less cross the weight-bearing portion of the acetabulum and necessitate operative treatment. Clinical Relevance: Fractures exiting the posterior column just superior to the ischial spine and those exiting the anterior column through the iliac wing lead to instability, When a patient has a displaced fracture crossing this area, every effort should be made to achieve anatomical reduction in order to prevent posttraumatic arthritis. C1 Louisiana State Univ, Med Ctr, Dept Orthopaed Surg, Bioengn Lab, New Orleans, LA 70112 USA. RP Vrahas, MS (reprint author), Massachusetts Gen Hosp, 55 Fruit St,WAC 517K, Boston, MA 02114 USA. NR 24 TC 15 Z9 19 U1 1 U2 2 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 JUL PY 1999 VL 81A IS 7 BP 966 EP 974 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 218LY UT WOS:000081555100009 PM 10428128 ER PT J AU Yarmush, DM MacDonald, AD Foy, BD Berthiaume, F Tompkins, RG Yarmush, ML AF Yarmush, DM MacDonald, AD Foy, BD Berthiaume, F Tompkins, RG Yarmush, ML TI Cutaneous burn injury alters relative tricarboxylic acid cycle fluxes in rat liver SO JOURNAL OF BURN CARE & REHABILITATION LA English DT Article ID SYNERGISTIC INTERACTIONS; HEPATIC GLUCONEOGENESIS; PYRUVATE-KINASE; KREBS CYCLE; IN-VITRO; METABOLISM; C-13; GLUCOSE; ISOTOPOMER; GLUCAGON AB Severe injury induces a hypermetabolic state in the liver; however, the pathways that are responsible for the increase in hepatic energy demand have not been identified. Relative fluxes in the tricarboxylic acid (TCA) cycle mere determined in perfused livers from rats 4 days after administration of a cutaneous burn injury. The perfusate was supplemented with 5 mM uniformly labeled C-13-laaate to efficiently label intracellular metabolites. Flux ratios mere calculated on the basis of (1) the C-13-labeling pattern of the glutamate and lactate isotopomers within the liver as determined by nuclear magnetic resonance spectroscopy and (2) an isotopomer mass balance model of the TCA cycle. Calculated flux ratios suggest that burn injury results in an increase in the contribution of pyruvate to the oxaloacetate pool at the expense of non-TCA cycle sources. Furthermore, a dramatic increase in C-13-labeling of glucose was observed in burned rat livers. These data taken together suggest that burn injury induces intrinsic changes in intrahepatic metabolism, including an alteration of the relative fluxes consistent with increased gluconeogenesis from lactate. C1 Massachusetts Gen Hosp, Surg Res Labs, Ctr Engn Med & Surg Serv, Boston, MA 02129 USA. Harvard Univ, Sch Med, Shriners Burns Inst, Boston, MA USA. Wright State Univ, Dept Phys, Dayton, OH 45435 USA. RP Yarmush, ML (reprint author), Massachusetts Gen Hosp, Surg Res Labs, Ctr Engn Med & Surg Serv, 149 13th St, Boston, MA 02129 USA. FU NIGMS NIH HHS [P50-GM-21700] NR 31 TC 20 Z9 20 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0273-8481 J9 J BURN CARE REHABIL JI J. Burn Care Rehabil. PD JUL-AUG PY 1999 VL 20 IS 4 BP 292 EP 302 DI 10.1097/00004630-199907000-00004 PG 11 WC Emergency Medicine; Rehabilitation; Surgery SC Emergency Medicine; Rehabilitation; Surgery GA 218LK UT WOS:000081553900003 PM 10425591 ER PT J AU Miller, SP McDonald-Smith, GP AF Miller, SP McDonald-Smith, GP TI BurnWare (c): National TRACS (R)/ABA computer use in the burn center SO JOURNAL OF BURN CARE & REHABILITATION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Trauma & Burn Serv, Boston, MA 02114 USA. RP Miller, SP (reprint author), 1 Wyoming St,Ste 7000 CHE, Dayton, OH 45409 USA. NR 0 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 0273-8481 J9 J BURN CARE REHABIL JI J. Burn Care Rehabil. PD JUL-AUG PY 1999 VL 20 IS 4 BP 325 EP 325 DI 10.1097/00004630-199907000-00010 PG 1 WC Emergency Medicine; Rehabilitation; Surgery SC Emergency Medicine; Rehabilitation; Surgery GA 218LK UT WOS:000081553900010 ER PT J AU McDonald-Smith, GP AF McDonald-Smith, GP TI Report of the NATIONAL TRACS (R)/ABA Burn Registry training and the TRACS (R) Sunrise Symposium SO JOURNAL OF BURN CARE & REHABILITATION LA English DT Article C1 Massachusetts Gen Hosp, Trauma & Burn Serv, Boston, MA 02114 USA. RP McDonald-Smith, GP (reprint author), Massachusetts Gen Hosp, Trauma & Burn Serv, GRB 1302, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0273-8481 J9 J BURN CARE REHABIL JI J. Burn Care Rehabil. PD JUL-AUG PY 1999 VL 20 IS 4 BP 326 EP 327 PG 2 WC Emergency Medicine; Rehabilitation; Surgery SC Emergency Medicine; Rehabilitation; Surgery GA 218LK UT WOS:000081553900011 PM 10425597 ER PT J AU Giri, D Ropiquet, F Ittmann, M AF Giri, D Ropiquet, F Ittmann, M TI FGF9 is an autocrine and paracrine prostatic growth factor expressed by prostatic stromal cells SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID FACTOR FAMILY; FIBROBLAST; RECEPTOR; PROTEIN AB Polypeptide growth factors, including members of the fibroblast growth factor (FGF) family, play an important role in the growth and maintenance of the normal prostate. We have found that FGF9 is expressed at high levels in the normal peripheral and transition zone of the human prostate. Analysis of FGF9 production by primary cultures of prostatic epithelial and stromal cells has shown that FGF9 is produced and secreted by the prostatic stromal cells. Neither of these processes appears to be modulated by androgens. Production of FGF9 by stromal cells in vivo was confirmed by immunohistochemistry. FGF9 is a potent mitogen for both prostatic epithelial and stromal cells in culture and is a more potent mitogen for these cells than either FGF2 or FGF7, two other FGFs expressed in the human prostate. FGF9 is an abundant secreted growth factor that can act as both a paracrine mitogen for epithelial cells and an autocrine mitogen for stromal cells. Western blot analysis of tissue extracts from the normal and hyperplastic transition zone shows that FGF9 is present at two to threefold higher levels in the hyperplastic transition zone. Overexpression of this paracrine and autocrine growth factor may play an important tote in the epithelial and stromal proliferation in benign prostatic hyperplasia. (C)1999 Wiley-Liss, Inc. C1 Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Dept Vet Affairs Med Ctr, Houston, TX USA. RP Ittmann, M (reprint author), VAMC, Res Serv 151, 2002 Holcombe Blvd, Houston, TX 77030 USA. FU NIDDK NIH HHS [R01 DK54170-02] NR 17 TC 57 Z9 58 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 JUL PY 1999 VL 180 IS 1 BP 53 EP 60 DI 10.1002/(SICI)1097-4652(199907)180:1<53::AID-JCP6>3.0.CO;2-P PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 200ZX UT WOS:000080571100006 PM 10362017 ER PT J AU Stagliano, NE Perez-Pinzon, MA Moskowitz, MA Huang, PL AF Stagliano, NE Perez-Pinzon, MA Moskowitz, MA Huang, PL TI Focal ischemic preconditioning induces rapid tolerance to middle cerebral artery occlusion in mice SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE ischemic preconditioning; cerebral ischemia; focal ischemia; middle cerebral artery occlusion ID C-FOS; RAT-BRAIN; SPREADING DEPRESSION; POTASSIUM-CHLORIDE; FOREBRAIN ISCHEMIA; HIPPOCAMPAL SLICES; EXPRESSION; ADENOSINE; PROTECTS; CHANNELS AB In a process called ischemic preconditioning, a brief, sublethal ischemic insult protects tissue from subsequent, more severe injury. There have been no reports of rapidly induced ischemic preconditioning. The authors sought to develop a model of cerebral ischemic preconditioning in the mouse that can be applied to transgenic and knockout animals. They found that brief middle cerebral artery (MCA) occlusion only minutes before a severe ischemic insult can induce protection from that insult. Here the investigators describe a mouse model of preconditioning using intraluminal MCA occlusion as both the conditioning and the test stimulus. One or three 5-minute episodes of ischemia given 30 minutes before MCA occlusion for 1 or 24 hours (permanent occlusion) confer significant protection as assessed by infarct volume measurements 24 hours later. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiovasc Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA USA. Univ Miami, Sch Med, Dept Neurol, Miami, FL 33152 USA. RP Huang, PL (reprint author), Massachusetts Gen Hosp East, CVRC, 4th Floor,149 13th St, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS33335, NS 34773, NS10828] NR 36 TC 99 Z9 107 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUL PY 1999 VL 19 IS 7 BP 757 EP 761 PG 5 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 277TC UT WOS:000084948800005 PM 10413030 ER PT J AU Marino, M Chiovato, L Friedlander, JA Latrofa, F Pinchera, A McCluskey, RT AF Marino, M Chiovato, L Friedlander, JA Latrofa, F Pinchera, A McCluskey, RT TI Serum antibodies against megalin (GP330) in patients with autoimmune thyroiditis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RECEPTOR GENE FAMILY; HEYMANN NEPHRITIS; MEDIATES ENDOCYTOSIS; LDL RECEPTOR; PROTEIN RAP; THYROGLOBULIN; ANTIGEN; CELLS; AUTOANTIBODY; CLONING AB Megalin (gp330) is a multiligand receptor found on the apical surface of selected epithelial cells, including thyroid cells. We recently showed that megalin is a high-affinity receptor for thyroglobulin. Megalin is capable of inducing autoantibodies, as shown in the rat model, Heymann nephritis. Based on this consideration and on the knowledge that autoantibodies against several thyroid antigens develop in patients with autoimmune thyroid diseases, we searched for antimegalin antibodies in 78 patients with autoimmune and nonautoimmune thyroid diseases. We developed an assay, based on flow cytometry, to measure binding of serum IgGs to L2 cells, a rat carcinoma cell line that expresses abundant megalin. After incubation of L2 cells with serum samples and then with fluorescein isothiocynate-conjugated antihuman IgG Fc-specide antibody, the mean fluorescence intensity (MFI) was determined. Using results obtained in sera from 32 normal subjects, we established a cutoff value for MFI (50.62), above which, tests were considered positive. Significantly elevated values were found in 18 patients, including 13 of 26 patients with autoimmune thyroiditis (50.0%) and in 2 of 19 patients with Graves' disease (10.5%). Furthermore, 2 of 19 patients with nontoxic goiter (10.5%) and 1 of 14 patients with differentiated thyroid cancer (7.14%) had MFI values greater than 50.62, associated with the presence of circulating anti-thyroid autoantibodies. As a control cell line, we used Chinese hamster ovary cells, which do not express megalin. We found that, among the 18 patients with positive tests for binding to L2 cells, only 1 patient with nontoxic goiter had significant binding of serum IgGs to Chinese hamster ovary cells. Binding of serum IgGs to L2 cells was significantly reduced by coincubation with purified megalin in 15 of 18 positive patients (83.33%) and by a rabbit antimegalin antibody in II patients (61.11%). Further and more conclusive evidence that positive tests (MFI > 50.62) for binding to L2 cells were attributable to serum antimegalin antibodies was demonstrated by immunoprecipitation experiments. After incubation of serum samples with L2 cell extracts, incubation with antihuman IgG Fc-specific agarose beads resulted in immunoprecipitation of megalin in all the 18 positive patients, but not in normal subjects, as assessed by Western blotting using a monoclonal antibody against megalin. Furthermore, the intensity of the band corresponding to megalin precipitated by serum IgGs in the above 18 patients was significantly correlated with the L2 binding MFI. This is the first clear-cut demonstration of antibodies against megalin in humans. Further studies are needed to determine whether antimegalin antibodies have pathogenic significance or diagnostic value in autoimmune thyroid diseases. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pathol Res Lab, Charlestown, MA 02129 USA. Univ Pisa, Dept Endocrinol, I-56124 Pisa, Italy. RP McCluskey, RT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pathol Res Lab, 149 13th St, Charlestown, MA 02129 USA. EM mccluskey.robert@mgh.harvard.edu OI Latrofa, Francesco/0000-0003-0297-5904 FU PHS HHS [46301] NR 45 TC 18 Z9 19 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1999 VL 84 IS 7 BP 2468 EP 2474 DI 10.1210/jc.84.7.2468 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 213EH UT WOS:000081259200037 PM 10404822 ER PT J AU Parsons, SK Gelber, S Cole, BF Ravindranath, Y Ogden, A Yeager, AM Chang, M Shuster, J Weinstein, HJ Gelber, RD AF Parsons, SK Gelber, S Cole, BF Ravindranath, Y Ogden, A Yeager, AM Chang, M Shuster, J Weinstein, HJ Gelber, RD TI Quality-adjusted survival after treatment for acute myeloid leukemia in childhood: A Q-TWiST analysis of the Pediatric Oncology Group study 8821 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 2nd Joint Meeting of the Society-for-Clinical-Trials/International-Society-for-Clinical-Biostatis tics (ISCB) CY JUL 06-10, 1997 CL BOSTON, MASSACHUSETTS SP Soc Clin Trials, Int Soc Clin Biostatist ID BONE-MARROW TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; ACUTE NONLYMPHOCYTIC LEUKEMIA; CHILDRENS CANCER GROUP; 1ST REMISSION; INTENSIVE CHEMOTHERAPY; CLINICAL-SIGNIFICANCE; INDUCTION THERAPY; FOLLOW-UP; OF-LIFE AB purpose: Ta describe quality-of-life considerations in postremission therapies for children with acute myelogenous leukemia. Patients and Methods: A quality-adjusted survival analysis, using the quality-adjusted time without symptoms or toxicity (Q-TWiST) method, was applied to Pediatric Oncology Group Trial 8821,which compared randomized assignment with intensive consolidation chemotherapy (CC) or autologous bone marrow trans plantation (ABMT), Nonrandomized assignment to allogeneic bone marrow transplantation (allo BMT) on the basis of availability of a matched related donor wets also evaluated. A 25 patient cohort provided data for modeling chronic graft-versus-host disease. The TWiST analysis war performed based on the intent-to-treat principle. Results: As previously reported, the 3 year event-free survival was not significantly different between the randomized arms (CC v ABMT), At a median follow-up of 5 years (of the censoring distribution), the CC group had less time in toxicity (TOX) and more time without symptoms ar toxicity (TWiST), relapse-free time, and alive time than patients assigned to ABMT (none of these were statistically significant). Compared with the CC group alla BMT patients spent more time in TOX (P <.001), more time in TWiST (P =.06), and had more relapse-free time (P =.03) and time alive (P = .07), Allo BMT was superior to ABMT with greater time in TWiST (P =.03), relapse-free time (P =.01), and time alive P = .002). Conclusion: The Q-TWiST analysis is a powerful decision aid in choosing among alternative therapies. prospective information on patient preferences will facilitate future trials evaluating treatment outcomes. Refinements in the Q-TWiST method could be included to further enhance the power of this patient care decisionmaking tool. C1 Harvard Univ, Dept Pediat Oncol,Med Sch, Dana Farber Canc Inst, Massachusetts Gen Hosp, Boston, MA 02115 USA. Dartmouth Med Sch, Lebanon, NH USA. Childrens Hosp Michigan, Barbara Ann Karmanos Canc Inst, Detroit, MI USA. Wayne State Univ, Detroit, MI USA. Texas Children Canc Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX USA. Emory Univ, Sch Med, Atlanta, GA USA. Pediat Oncol Grp Stat Off, Dept Stat, Gainesville, FL USA. RP Parsons, SK (reprint author), Harvard Univ, Dept Pediat Oncol,Med Sch, Dana Farber Canc Inst, Massachusetts Gen Hosp, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA29139, CA23108, CA37379] NR 44 TC 25 Z9 26 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL PY 1999 VL 17 IS 7 BP 2144 EP 2152 PG 9 WC Oncology SC Oncology GA 213GL UT WOS:000081264300027 PM 10561270 ER PT J AU Thomas, CR Wright, CD Loehrer, PJ AF Thomas, CR Wright, CD Loehrer, PJ TI Thymoma: State of the art SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID POSTOPERATIVE RADIATION-THERAPY; GERM-CELL TUMORS; PHASE-II TRIAL; INVASIVE THYMOMA; MALIGNANT THYMOMA; PROGNOSTIC FACTORS; SURGICAL-TREATMENT; MYASTHENIA-GRAVIS; EPITHELIAL-CELLS; METASTATIC THYMOMA AB Thymoma is the most common tumor of the anterior mediastinum, This tumor is associated with unique paraneoplastic syndromes, such as myasthenia gravis, hypogammaglobulinemia, and pure red cell aplasia. The rarity of this tumor, however, has somewhat obscured the optimal treatment for this disease. For the majority of patients who present with localised tumor, surgical extirpation remains the standard of choice. Adjuvant radiotherapy seems to improve local control and survival. In more advanced disease, systemic therapy has been demonstrated to produce a 50% to 80% objective response rate. These observations have led to the development of multimodality therapy for the treatment of patients with advanced thymoma. In this article, we will review the current perspectives on the management of early stage and advanced thymoma, (C) 1999 by American Society of Clinical Oncology. C1 Med Univ S Carolina, Dept Radiat Oncol, Hollings Canc Ctr, Charleston, SC 29425 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA USA. Indiana Univ, Sch Med, Dept Med, Div Hematol Oncol, Indianapolis, IN USA. Walther Canc Inst, Indianapolis, IN USA. RP Thomas, CR (reprint author), Med Univ S Carolina, Dept Radiat Oncol, Hollings Canc Ctr, 171 Ashley Ave, Charleston, SC 29425 USA. FU NCI NIH HHS [U10 CA21115, CA23318, R35 CA39844-08] NR 86 TC 145 Z9 151 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL PY 1999 VL 17 IS 7 BP 2280 EP 2289 PG 10 WC Oncology SC Oncology GA 213GL UT WOS:000081264300042 PM 10561285 ER PT J AU Wilhelm, S Keuthen, NJ Deckersbach, T Engelhard, IM Forker, AE Baer, L O'Sullivan, RL Jenike, MA AF Wilhelm, S Keuthen, NJ Deckersbach, T Engelhard, IM Forker, AE Baer, L O'Sullivan, RL Jenike, MA TI Self-injurious skin picking: Clinical characteristics and comorbidity SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID STEREOTYPIC MOVEMENT DISORDER; BODY DYSMORPHIC DISORDER; NEUROTIC EXCORIATIONS AB Background: Repetitive skin picking, a self injurious behavior that may cause severe tissue damage, has received scant empirical attention. The authors examined the demographics, phenomenology, and associated psychopathology in a series of 31 subjects with this problem. Method: Subjects were administered the Structured Clinical Interview for DSM-IV for Axis I and Axis II disorders. They also completed several mood questionnaires and a new self-report inventory designed to assess phenomenology, triggers, cognitions, emotions, and consequences associated with skin picking. Results: The mean age at onset on self-injurious skin picking was 15 years, and the mean duration of illness was 21 years. All subjects picked at more than one body area, and the most frequent sites of skin picking were pimples and scabs (87%). The most common comorbid Axis I diagnoses were obsessive-compulsive disorder (OCD; 52%), alcohol abuse/dependence (39%), and body dysmorphic disorder (32%). Forty-eight percent (N = 15) of the subjects met criteria for at least one mood disorder, and 65% (N = 20) for at least one anxiety disorder. The most common Axis II disorders were obsessive-compulsive personality disorder (48%) and borderline personality disorder (26%). Conclusion: Self-injurious skin picking is a severe and chronic psychiatric and dermatologic problem associated with high rates of psychiatric comorbidity. It may be conceptualized as a variant of OCD or impulse-control disorder with self-injurious features and may, in some cases, represent an attempt to regulate intense emotions. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Wilhelm, S (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 26 TC 121 Z9 122 U1 2 U2 13 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 JUL PY 1999 VL 60 IS 7 BP 454 EP 459 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 225EJ UT WOS:000081945200007 PM 10453800 ER PT J AU Lorr, M Strack, S AF Lorr, M Strack, S TI A study of Benjamin's eight-facet Structural Analysis of Social Behavior (SASB) model (vol 55, pg 207, 1999) SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Correction C1 Catholic Univ Amer, Washington, DC 20064 USA. US Dept Vet Affairs, Outpatient Clin, Los Angeles, CA USA. RP Lorr, M (reprint author), Catholic Univ Amer, Washington, DC 20064 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD JUL PY 1999 VL 55 IS 7 BP 924 EP 924 DI 10.1002/(SICI)1097-4679(199907)55:7<924::AID-JCLP14>3.0.CO;2-1 PG 1 WC Psychology, Clinical SC Psychology GA 213FC UT WOS:000081261200014 ER PT J AU Badgaiyan, RD Schacter, DL Alpert, NM AF Badgaiyan, RD Schacter, DL Alpert, NM TI Auditory priming within and across modalities: Evidence from positron emission tomography SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID EXTRASTRIATE VISUAL-CORTEX; EVENT-RELATED FMRI; IMPLICIT MEMORY; STEM COMPLETION; EXPLICIT MEMORY; FUNCTIONAL MRI; PREFRONTAL CORTEX; CEREBRAL-CORTEX; WORKING-MEMORY; ACTIVATION AB Previous neuroimaging studies of perceptual priming have reported priming-related decreases in the extrastriate cortex. However, because these experiments have used visual stimuli, it is unclear whether the observed decreases are associated specifically with some aspect of visual perceptual processing or with more general aspects of priming. We studied within- and cross-modality priming using an auditor word stem completion paradigm. Positron emission tomography (PET) images were obtained during stem completion and a fixation task. Within-modality auditor priming was associated with blood flow decreases in the extrastriate cortex (bilateral), medial/right anterior prefrontal cortex, right angular gyrus, and precuneus. In cross-modality priming, the stud list was presented visually, and subjects completed auditor word stems. Cross-modality priming was associated with trends for blood flow decreases in the left angular gyrus and increases in the medial/right anterior prefrontal cortex. Results thus indicate that reduced activity in the extrastriate cortex accompanies within-modality priming in both visual and auditor modalities. C1 Harvard Univ, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Badgaiyan, RD (reprint author), Harvard Univ, William James Hall,Rm 875,Kirkland St, Cambridge, MA 02138 USA. EM rajendra@wjh.harvard.edu OI Schacter, Daniel/0000-0002-2460-6061 FU NIMH NIH HHS [MH57915-02] NR 73 TC 75 Z9 76 U1 4 U2 6 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD JUL PY 1999 VL 11 IS 4 BP 337 EP 348 DI 10.1162/089892999563463 PG 12 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 227DW UT WOS:000082063900001 PM 10471844 ER PT J AU Margolis, HC Zhang, YP Lee, CY Kent, RL Moreno, EC AF Margolis, HC Zhang, YP Lee, CY Kent, RL Moreno, EC TI Kinetics of enamel demineralization in vitro SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE enamel; demineralization; caries mechanism ID HUMAN TOOTH ENAMEL; POOLED PLAQUE FLUID; CARIES-POSITIVE INDIVIDUALS; CARIOUS LESION FORMATION; DENTAL ENAMEL; BUFFER SOLUTIONS; IN-VITRO; SUBSURFACE DEMINERALIZATION; CONSTANT-COMPOSITION; MOLECULAR-WEIGHT AB Previously, we reported that the rate (R) of hydroxyapatite dissolution in acetic, lactic, and phosphoric acid solutions is a function of the degree of saturation with respect to the dissolving mineral, DS (defined as the ratio of the mean ionic activity product for hydroxyapatite [Ca5OH(PO4)(3)] in solution to its solubility product constant), and the sum of the acid activities (Sigma BiH) in solution: R = K(1-DS)(m)(Sigma BiH)(n). The present study was undertaken to explore the general validity of this model in describing the kinetics of enamel demineralization. Thin sections of human enamel were exposed to partially saturated 0.1 mol/L lactic acid solutions, at two different DS levels, and at pH values of 4.3 to 6.0. Thin sections of human enamel were also exposed to solutions with four different concentrations of acetic and lactic acids (pH 4.3) with three different DS values and, at one DS value, to solutions of propionic acid. Mineral loss was monitored by quantitative microradiography. In solutions with pH values of 4.3 and 5.0, "lesions" were formed with well-defined surface layers, whereas, in solutions with pH 6.0, "lesions" were produced with no apparent surface layers. The formation of relatively intact surface layers was consistent with predicted phase transformations. Rates of mineral loss were found to be inversely proportional to both the degree of saturation with respect to enamel mineral, DSEn, and the pH of the solution and increased with increased activities of each organic acid, consistent with the proposed model. However, at the same DSEn and acid activity, rates of demineralization were the same in the acetic and propionic acid solutions, whereas rates of demineralization in lactic acid were greater. It is suggested that specific interactions of acid species with enamel mineral may modify the rate of enamel demineralization. These in vitro findings suggest that relatively small differences in DSEn values found in plaque fluid may result in very significant differences in the rate of enamel demineralization in vivo. C1 Forsyth Dent Ctr, Dept Biomineralizat, Boston, MA 02115 USA. Colgate Palmol Co, Piscataway, NJ 08855 USA. Yonsei Univ, Coll Dent, Seoul 120749, South Korea. Forsyth Dent Ctr, Dept Biostat & Epidemiol, Boston, MA USA. RP Margolis, HC (reprint author), Forsyth Dent Ctr, Dept Biomineralizat, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-07009, DE-07493, DE-03187] NR 28 TC 57 Z9 63 U1 1 U2 11 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 JUL PY 1999 VL 78 IS 7 BP 1326 EP 1335 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 212GD UT WOS:000081208200007 PM 10403460 ER PT J AU Adler, JN Brown, DFM Nadel, ES Juang, P Davis, M Silvers, S Legome, E Horak, M Castro, E Walls, R Wolfe, R Conn, A Rosen, C AF Adler, JN Brown, DFM Nadel, ES Juang, P Davis, M Silvers, S Legome, E Horak, M Castro, E Walls, R Wolfe, R Conn, A Rosen, C TI Acute gastrointestinal hemorrhage SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID AORTOENTERIC FISTULA; ENTERIC FISTULAS; MANAGEMENT; DIAGNOSIS C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Emergency Med, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Adler, JN (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Founders House 150,55 Fruit St, Boston, MA 02114 USA. NR 14 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 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD JUL-AUG PY 1999 VL 17 IS 4 BP 731 EP 733 PG 3 WC Emergency Medicine SC Emergency Medicine GA 229HX UT WOS:000082189300021 PM 10431967 ER PT J AU Krithivas, K Yurgalevitch, SM Mohr, BA Wilcox, CJ Batter, SJ Brown, M Longcope, C McKinlay, JB Kantoff, PW AF Krithivas, K Yurgalevitch, SM Mohr, BA Wilcox, CJ Batter, SJ Brown, M Longcope, C McKinlay, JB Kantoff, PW TI Evidence that the CAG repeat in the androgen receptor gene is associated with the age-related decline in serum androgen levels in men SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID BULBAR MUSCULAR-ATROPHY; PROSTATE-CANCER; ESTROGENS; HORMONES; TRACT; WOMEN AB In men over 30 years old, serum levels of testosterone (T) decrease with age. A shorter polymorphic CAG repeat length in exon 1 of the androgen receptor (AR) gene is associated with higher transcription activation by the AR. We determined the number of CAG repeats for 882 men aged between 40 and 70 years from the Massachusetts Male Aging Study (MMAS). MMA.S is a population-based random sample survey of men for whom baseline (1987-1989, mean age 53 +/- 8 years) and follow-up (1995-1997, mean age 61 +/- 8 years) serum hormone levels were available. Multiple linear regression was used to determine ii CAG repeat length would be predictive of hormone levels at follow-up. Hormone levels measured included T, free T, albumin-bound T, dihydrotestosterone (DHT), sex hormone-binding globulin (SHBG) and luteinizing hormone (LH). The CAG repeat length was significantly associated with T (P=0.041), albumin-bound T (P=0.025) and free T (P=0.003) when controlled for age, baseline hormone levels and anthropometrics. Follow-up levels of T decreased by 0.74% +/- 0.36 per CAG repeat decrement. Likewise, the percentages of free and albumin-bound T decreased by 0.93% +/- 0.31 and 0.71% +/- 0.32 per CAG repeat decrement respectively. These results suggest that androgen levels may be modulated by AR genotype. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. New England Res Inst, Watertown, MA 02172 USA. Univ Massachusetts, Med Ctr, Dept Obstet & Gynecol, Worcester, MA 01655 USA. RP Kantoff, PW (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. RI Myles, Brown/B-6906-2008; Perez , Claudio Alejandro/F-8310-2010; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Brown, Myles/0000-0002-8213-1658 FU NIDDK NIH HHS [DK 44995-03, DK 51345-03] NR 23 TC 125 Z9 133 U1 0 U2 6 PU SOC ENDOCRINOLOGY PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4NQ, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD JUL PY 1999 VL 162 IS 1 BP 137 EP 142 DI 10.1677/joe.0.1620137 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 215GA UT WOS:000081372500016 PM 10396030 ER PT J AU Willett, CG AF Willett, CG TI Irradiation for unresectable pancreatic cancer SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article ID INTRAOPERATIVE RADIATION-THERAPY; EXTERNAL BEAM IRRADIATION; CARCINOMA C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Willett, CG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU QUALITY MEDICAL PUBLISHING INC PI ST LOUIS PA 11970 BORMAN DR, STE 222, ST LOUIS, MO 63146 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD JUL-AUG PY 1999 VL 3 IS 4 BP 351 EP 353 DI 10.1016/S1091-255X(99)80049-3 PG 3 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 247LW UT WOS:000083223100008 ER PT J AU Handran, SD MacDonald, ME Young, AB AF Handran, SD MacDonald, ME Young, AB TI Cellular distribution, protein interactions, and aggregate formation of Huntingtin's amino terminus using GFP variants and fluorescence resonance energy transfer (FRET) analysis SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 JUL PY 1999 VL 114 IS 1 MA 29 BP 8A EP 8A PG 1 WC Physiology SC Physiology GA 215HU UT WOS:000081376900036 ER PT J AU Emmons, KM Koch-Weser, S Atwood, K Conboy, L Rudd, R Colditz, G AF Emmons, KM Koch-Weser, S Atwood, K Conboy, L Rudd, R Colditz, G TI A qualitative evaluation of the Harvard Cancer Risk Index SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID HEALTH; APPRAISAL AB There is an extensive amount of information in the popular press about cancer risk factors. The volume and sometimes contradictory nature of this information makes it difficult for individuals to understand their own level of risk or how one risk factor compares with another. The Harvard Cancer Risk Index (HCRI) was developed by an interdisciplinary working group of epidemiologists and behavioral scientists to educate the public about the major risk factors associated with the 11 most common forms of cancer in the United States. Following the development and validation of the HCRI, we initiated a qualitative research study to obtain initial feedback on the wording and presentation of the index and to elicit information regarding the meaning of risks, perception of cancer, and interpretation of the HCRI results. The results indicated that the HCRI was well received by participants and that they highly regarded the inclusion of information related to the latest risks for cancer and the description of the mechanisms by which these factors impact on risk. Personalization of the risk score helped participants to focus on behaviors that they could change. However, dissatisfaction with the HCRI was noted By some participants because exposures they believed to be important were not included (e.g., poverty, toxic waste, air pollution). Evaluation of the impact of the index on intention to change provided preliminary evidence that this may be an effective toll for helping mobilize individuals toward change across a number of risk factors. Further quantitative evaluation of the HCRI is planned. C1 Dana Farber Canc Inst, Div Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. RP Emmons, KM (reprint author), Dana Farber Canc Inst, Div Community Based Res, 44 Binney St, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 NR 19 TC 15 Z9 15 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PD JUL-SEP PY 1999 VL 4 IS 3 BP 181 EP 193 PG 13 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 241FK UT WOS:000082871900002 PM 10977287 ER PT J AU Fiscus, SA Adimora, AA Schoenbach, VJ McKinney, R Lim, W Rupar, D Kenny, J Woods, C Wilfert, C Johnson, VA AF Fiscus, SA Adimora, AA Schoenbach, VJ McKinney, R Lim, W Rupar, D Kenny, J Woods, C Wilfert, C Johnson, VA TI Trends in human immunodeficiency virus (HIV) counseling, testing, and antiretroviral treatment of HIV-infected women and perinatal transmission in North Carolina SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 12th World AIDS Conference CY JUN 28-JUL 03, 1998 CL GENEVA, SWITZERLAND ID MOTHER-TO-INFANT; VERTICAL TRANSMISSION; ZIDOVUDINE THERAPY; VIRAL LOAD; TYPE-1; PREGNANCY; REDUCTION; RESISTANCE; RISK AB Since 1993, trends in perinatal human immunodeficiency virus (HIV) transmission have been monitored by use of chart review of patients identified at a central diagnostic laboratory. In the population studied, either pre- or postnatal antiretroviral therapy to the infant increased from 21% in 1993 to 95% in 1997, Concurrently, the number of HIV-infected infants declined from 25 in 1993 to 4 in 1997, The complete Pediatric AIDS Clinical Trials Group Protocol 076 regimen was the most effective in reducing transmission (3.1%). Twenty-two of 35 infants who became infected in 1995-1997 had mothers who did not receive antiretroviral therapy, although counseling practices improved with time. In 1995, 87% of the mothers of HIV-seropositive infants were counseled, whereas in 1997, 96% were counseled (P<.005), None of 59 infants tested had high-level phenotypic zidovudine resistance, although 5 (8.8%) of 57 infants had virus isolates with at least one mutation in the reverse transcriptase gene associated with reduced phenotypic susceptibility to zidovudine. C1 Univ N Carolina, Sch Med, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Dept Epidemiol, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Dept Pediat, Chapel Hill, NC 27599 USA. Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27706 USA. Duke Univ, Med Ctr, Dept Microbiol & Immunol, Durham, NC 27706 USA. Carolinas Med Ctr, Dept Pediat, Charlotte, NC 28203 USA. E Carolina Univ, Dept Pediat, Greenville, NC 27858 USA. Wake Forest Univ, Sch Med, Dept Pediat, Winston Salem, NC 27109 USA. Univ Alabama, Sch Med, Dept Med, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Fiscus, SA (reprint author), Univ N Carolina, Sch Med, Dept Microbiol & Immunol, CB 7140, Chapel Hill, NC 27599 USA. FU NIAID NIH HHS [AI-40876, AI-127535, AI-41530] NR 30 TC 54 Z9 55 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL PY 1999 VL 180 IS 1 BP 99 EP 105 DI 10.1086/314840 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 210YA UT WOS:000081132100014 PM 10353867 ER PT J AU Lee, JS Kahlon, SS Culbreth, R Cooper, JAD AF Lee, JS Kahlon, SS Culbreth, R Cooper, JAD TI Modulation of monocyte chemokine production and nuclear factor kappa B activity by oxidants SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID CHEMOATTRACTANT PROTEIN-1 GENE; ISCHEMIA-REPERFUSION INJURY; LOW-DENSITY-LIPOPROTEIN; CHEMOTACTIC PROTEIN-1; INTERLEUKIN-8 IL-8; SYNOVIAL-FLUID; EXPRESSION; CELLS; CYTOKINES; TRANSCRIPTION AB Reactive oxygen species can directly damage tissue. In this setting, amplification of tissue damage also occurs through infiltration of inflammatory cells either acutely or chronically. Several recent studies suggest that reactive oxygen species stimulate production of certain chemokines, which are potent chemoattractants for inflammatory cells. In the present study, we examined whether oxidants, generated by the combination of xanthine and xanthine oxidase (X/XO), alter chemokine production by monocytes and U937 cells. Our findings demonstrate that X/XO stimulates monocytes, but not U937 cells, to produce increased amounts of interleukin-8 (IL-8) and monocyte chemoattractant protein. This effect is attenuated by pretreatment with dimethylsulfoxide (DMSO), a scavenger of hydroxyl radicals, but is not affected by superoxide dismutase or catalase, In contrast, X/XO-induced cytotoxicity, evidenced by lactate dehydrogenase release, is mediated primarily by hydrogen peroxide, as catalase reverses this effect. Finally, exposure to X/XO causes an increase in nuclear factor kappa B (NF-kappa B), and this effect is attenuated by DMSO, These studies suggest that reactive oxygen species can induce production of molecules that amplify inflammation through attraction of inflammatory cells, It appears the hydroxyl radical is the principal oxidant species involved in stimulation of chemokine production. C1 Univ Alabama, Div Pulm & Crit Care Med, Pulm Sect, Birmingham, AL 35294 USA. Birmingham VAMC, Pulm Sect, Birmingham, AL 35233 USA. RP Cooper, JAD (reprint author), Univ Alabama, Div Pulm & Crit Care Med, Pulm Sect, 215 Tinsley Harrison Tower,1900 Univ Blvd, Birmingham, AL 35294 USA. NR 41 TC 15 Z9 15 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD JUL PY 1999 VL 19 IS 7 BP 761 EP 767 DI 10.1089/107999099313613 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 224LA UT WOS:000081899500009 PM 10454347 ER PT J AU Asch, DA AF Asch, DA TI From boardroom to bedside: Bioethical implications of policy research for clinical practice SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article C1 Univ Penn, Leonard Davis Inst Hlth Econ, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. RP Asch, DA (reprint author), Univ Penn, Leonard Davis Inst Hlth Econ, Vet Affairs Med Ctr, 3641 Locust Walk, Philadelphia, PA 19104 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JUL PY 1999 VL 47 IS 6 BP 273 EP 277 PG 5 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 215HP UT WOS:000081376300005 PM 10431481 ER PT J AU Mazo, IB von Andrian, UH AF Mazo, IB von Andrian, UH TI Adhesion and homing of blood-borne cells in bone marrow microvessels SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE hematopoiesis; lymphocytes; mouse ID HEMATOPOIETIC STEM-CELLS; CHEMOKINE RECEPTOR CXCR4; L-SELECTIN; STROMAL CELLS; P-SELECTIN; ENDOTHELIAL-CELLS; PROGENITOR CELLS; MOUSE EMBRYO; IN-VIVO; MOLECULE-1 AB After birth, the bone marrow (BM) is the principal site of hematopoiesis in mammals. Thus, a large number of newly formed blood cells must penetrate the wall of BM microvessels to enter the circulation. In addition, the BM appears to function as a lymphoid organ and is also part of the macrophagal system, Subsets of circulating lymphocytes and other cells of the immune system continuously home to the BM. However, neither the mechanisms of blood cell migration to and front the BM nor its precise role in the immune system are well understood, One reason for the relative paucity of data on BM physiology is the fact that normal BM is surrounded by thick cortical bone that impedes direct observation and experimental manipulation. One notable exception is the calvaria of the murine skull where hematopoietically active BM is only covered by a thin lamella of bone that is sufficiently translucent to allow a detailed in situ analysis of the BM microcirculation by epi-fluorescence microscopy, Here, we review our current knowledge of the anatomic, hemodynamic, and endothelial properties of the specialized microvascular bed within murine skull. BM, In addition, we summarize recent studies on the molecular mechanisms that mediate the homing of circulating hematopoietic progenitor cells to the BM, an event that is critical for the success of BM transplantations. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [HL 56949] NR 58 TC 67 Z9 69 U1 1 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 JUL PY 1999 VL 66 IS 1 BP 25 EP 32 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 215YW UT WOS:000081413900003 PM 10410986 ER PT J AU Medh, JD Bowen, SL Fry, GL Ruben, S Hill, J Wong, H Chappell, DA AF Medh, JD Bowen, SL Fry, GL Ruben, S Hill, J Wong, H Chappell, DA TI Hepatic triglyceride lipase promotes low density lipoprotein receptor-mediated catabolism of very low density lipoproteins in vitro SO JOURNAL OF LIPID RESEARCH LA English DT Article DE hepatic lipase; lipoprotein lipase; LDL receptor; LDL receptor-related protein; heparan sulfate proteoglycans ID PROTEIN ALPHA(2)-MACROGLOBULIN RECEPTOR; CHYLOMICRON REMNANT-REMOVAL; ISOLATED RAT HEPATOCYTES; CELLULAR CATABOLISM; TERMINAL DOMAIN; LDL RECEPTOR; IN-VITRO; FAMILIAL HYPERCHOLESTEROLEMIA; III HYPERLIPOPROTEINEMIA; APOLIPOPROTEIN-E AB We demonstrate here that hepatic triglyceride lipase (HTGL) enhances VLDL degradation in cultured cells by a LDL receptor-mediated mechanism, VLDL binding at 4 degrees C and degradation at 37 degrees C by normal fibroblasts was stimulated by HTGL in a dose-dependent manner. A maximum increase of up to 7-fold was seen at 10 mu g/ml HTGL, Both VLDL binding and degradation were significantly increased (4-fold) when LDL receptors were up-regulated by treatment with lovastatin, HTGL also stimulated VLDL degradation by LDL receptor-deficient FH fibroblasts but the level of maximal degradation was 40-fold lower than in lovastatin-treated normal fibroblasts, A prominent role for LDL receptors was confirmed by demonstration of similar HTGL-promoted VLDL degradation by normal and LRP-deficient murine embryonic fibroblasts, HTGL enhanced binding and internalization of apoprotein-free triglyceride emulsions, however, this was LDL receptor-independent. HTGL-stimulated binding and internalization of apoprotein-free emulsions was totally abolished by heparinase indicating that it was mediated by HSPG, In a cell-free assay HTGL competitively inhibited the binding of VLDL to immobilized LDL receptors at 4 degrees C suggesting that it may directly bind to LDL receptors but may not bind VLDL particles at the same time. We conclude that the ability of HTGL to enhance VLDL degradation is due to its ability to concentrate lipoprotein particles on HSPG sites on the cell surface leading to LDL receptor-mediated endocytosis and degradation. C1 Univ Iowa, Coll Med, Dept Internal Med, Iowa City, IA 52242 USA. W Los Angeles Vet Affairs Med Ctr, Lipid Res Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. RP Medh, JD (reprint author), Univ Iowa, Coll Med, Dept Internal Med, Iowa City, IA 52242 USA. FU NHLBI NIH HHS [HL49264] NR 68 TC 11 Z9 13 U1 0 U2 0 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JUL PY 1999 VL 40 IS 7 BP 1263 EP 1275 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 212CN UT WOS:000081198900010 PM 10393211 ER PT J AU Seaton, BE Allen, DN Goldstein, G Kelley, ME van Kammen, DP AF Seaton, BE Allen, DN Goldstein, G Kelley, ME van Kammen, DP TI Relations between cognitive and symptom profile heterogeneity in schizophrenia SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID NEUROPSYCHOLOGICAL DIFFERENCES; NEGATIVE SYMPTOMS; SUBTYPES; DEFINITION; DICHOTOMY AB Although numerous studies have consistently revealed cognitive heterogeneity in schizophrenia, the relationships between such heterogeneity and clinical phenomenology are not clear. Clusters derived from cognitive heterogeneity studies may or may not be associated with symptom profile or severity of illness. The purpose of this study was to examine the relationship between cognitive heterogeneity and demographic and clinical phenomenological measures. We examined cognitive heterogeneity in schizophrenia by empirically deriving clusters of patients based upon WAIS-R subtest scores and then analyzed the way in which these clusters related to demographic and symptom variables and to DSM-III-R, diagnostic subtypes. Four cognitive clusters were identified that were consistent with previous research. These clusters were differentiated on the basis of educational level and occupational status but not on the basis of symptom profile, severity, or DSM-III-R subtypes. Results suggest that cognitive measures are independent of severity of the disorder and phenomenological symptom presentation in these subgroups of schizophrenic patients. C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. Univ Rochester, Sch Med & Dent, Dept Psychiat, Rochester, NY 14642 USA. VA Pittsburgh Healthcare Syst, Highland Dr Div, Pittsburgh, PA 15206 USA. Robert Wood Johnson Pharmaceut Res Inst, Global Clin Res, Raritan, NJ 08864 USA. RP Goldstein, G (reprint author), Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. FU NIMH NIH HHS [R01MH44-841] NR 34 TC 27 Z9 27 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JUL PY 1999 VL 187 IS 7 BP 414 EP 419 DI 10.1097/00005053-199907000-00004 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 217BU UT WOS:000081480200004 PM 10426461 ER PT J AU Candilis, PJ McLean, RYS Otto, MW Manfro, GG Worthington, JJ Penava, SJ Marzol, PC Pollack, MH AF Candilis, PJ McLean, RYS Otto, MW Manfro, GG Worthington, JJ Penava, SJ Marzol, PC Pollack, MH TI Quality of life in patients with panic disorder SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID OF-LIFE; MEDICAL OUTCOMES; HEALTH-CARE; MENTAL-DISORDERS; ANXIETY DISORDER; RECOGNITION; DEPRESSION; MANAGEMENT; COMMUNITY; PROVIDERS AB In this study we assessed the quality of life of patients with panic disorder, with particular attention to the influence of anxiety and depression comorbidity on quality of life. Findings were compared with established general population norms as well as norms for patients with chronic medical conditions and major depression. The Medical Outcomes Study Short-Form Health Survey (SF-36) was administered to panic disorder patients entering clinical trials or treatment in an outpatient anxiety disorders program. Subjects were 73 consecutive patients with a primary diagnosis of panic disorder without current substance abuse or contributory medical illness. Their quality of life scores were compared with population mean estimates using single-sample t-tests, and the influence of comorbidity was examined with between-group comparisons. All SF-36 mental and physical health subscale scores were worse in patients with panic disorder than in the general population. This was true regardless of the presence of comorbid anxiety or mood disorders, although the presence of the comorbid conditions worsened select areas of functioning according to subscale analyses. SF-36 scores in panic patients were at approximately the same level as patients with major depression and tended to be worse in specific areas than patients with select medical conditions. This study provides evidence of the pervasive negative effects of panic disorder on both mental and physical health. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. RP Pollack, MH (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA. RI Manfro, Gisele/B-7020-2009 NR 31 TC 79 Z9 83 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JUL PY 1999 VL 187 IS 7 BP 429 EP 434 DI 10.1097/00005053-199907000-00006 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 217BU UT WOS:000081480200006 PM 10426463 ER PT J AU Herrlinger, U AF Herrlinger, U TI Primary CNS lymphoma: Findings outside the brain SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article; Proceedings Paper CT UICC International Symposium on Primary CNS Lymphoma CY OCT 18, 1997 CL TUBINGEN, GERMANY DE non-Hodgkin's lymphoma; primary central nervous system lymphoma; ocular lymphoma; systemic dissemination; diagnostics; staging ID CENTRAL-NERVOUS-SYSTEM; NON-HODGKINS-LYMPHOMA; RETICULUM-CELL SARCOMA; INTRAOCULAR LYMPHOMA; RADIATION-THERAPY; CHEMOTHERAPY; SURVIVAL; METHOTREXATE; MANAGEMENT; DIAGNOSIS AB In addition to the brain parenchyma and the leptomeninges, primary central nervous system lymphoma (PCNSL) can involve the posterior parts of the eye with ocular lymphoma in up to 20% of patients and lead to systemic dissemination of lymphoma in 7-8% of patients. Ocular lymphoma is diagnosed by slit lamp examination and requires treatment by ocular irradiation. However, the clinical significance of systemic dissemination, which occurs mainly in the end stage of the disease, appears to be disputable. Extensive systemic staging at the time of initial presentation proved to be unrewarding in the vast majority of studies. So far, only 10 patients have been reported with occult systemic lymphoma at time of initial presentation, and systemic lymphoma determined the course of the disease in none of them. Thus, initial staging procedures for patients with biopsy-confirmed PCNSL can be restricted to regular blood tests, including HIV testing, and slit lamp examination of the eye. C1 Univ Tubingen, Dept Neurol, D-72076 Tubingen, Germany. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Herrlinger, U (reprint author), Univ Tubingen, Dept Neurol, Hoppe Seyler Str 3, D-72076 Tubingen, Germany. NR 31 TC 17 Z9 19 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JUL PY 1999 VL 43 IS 3 BP 227 EP 230 DI 10.1023/A:1006250317940 PG 4 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 239YQ UT WOS:000082798500006 PM 10563427 ER PT J AU Ghiani, CA Yuan, XQ Eisen, AM Knutson, PL DePinho, RA McBain, CJ Gallo, V AF Ghiani, CA Yuan, XQ Eisen, AM Knutson, PL DePinho, RA McBain, CJ Gallo, V TI Voltage-activated K+ channels and membrane depolarization regulate accumulation of the cyclin-dependent kinase inhibitors p277(Kip1) and p21(CIP1) in glial progenitor cells SO JOURNAL OF NEUROSCIENCE LA English DT Article DE oligodendrocyte development; cell cycle; ion channels; G1 arrest; cell proliferation; cyclin D ID CENTRAL NERVOUS-SYSTEM; GLUTAMATE RECEPTORS; POTASSIUM CHANNELS; ION CHANNELS; OPTIC-NERVE; IN-VITRO; OLIGODENDROCYTE DIFFERENTIATION; NEURAL DIFFERENTIATION; PRECURSOR CELLS; SCHWANN-CELLS AB Neural cell development is regulated by membrane ion channel activity. We have previously demonstrated that cell membrane depolarization with veratridine or blockage of K+ channels with tetraethylammonium (TEA) inhibit oligodendrocyte progenitor (OP) proliferation and differentiation (Knutson et al., 1997); however the molecular events involved are largely unknown. Here we show that forskolin (FSK) and its derivative dideoxyforskolin (DFSK) block K+ channels in OPs and inhibit cell proliferation. The antiproliferative effects of TEA, FSK, DFSK, and veratridine were attributable to OP cell cycle arrest in G1 phase. In fact, (1) cyclin D accumulation in synchronized OP cells was not affected by K+ channel blockers or veratridine; (2) these agents prevented OP cell proliferation only if present during G1 phase; and (3) G1 blockers, such as rapamycin and deferoxamine, mimicked the anti-proliferative effects of K+ channel blockers. DFSK also prevented OP differentiation, whereas FSK had no effect. Blockage of K+ channels and membrane depolarization also caused accumulation of the cyclin-dependent kinase inhibitors p27(Kip1) and p21 (CIP1) in OP cells. The antiproliferative effects of K+ channel blockers and veratridine were still present in OP cells isolated from INK4a(-/-) mice, lacking the cyclin-dependent kinase inhibitors p16(INK4a) and p19(ARF). Our results demonstrate that blockage of K+ channels and cell depolarization induce G1 arrest in the OP cell cycle through a mechanism that may involve p27(Kip1) and p21(CIP1) and further support the conclusion that OP cell cycle arrest and differentiation are two uncoupled events. C1 NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gallo, V (reprint author), NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bldg 49,Room 5A-78,49 Convent Dr, Bethesda, MD 20892 USA. OI Ghiani, Cristina/0000-0002-9867-6185 NR 84 TC 101 Z9 101 U1 1 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 1 PY 1999 VL 19 IS 13 BP 5380 EP 5392 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 209PL UT WOS:000081056900021 PM 10377348 ER PT J AU Ikeda, K Saeki, Y Gonzalez-Agosti, C Ramesh, V Chiocca, EA AF Ikeda, K Saeki, Y Gonzalez-Agosti, C Ramesh, V Chiocca, EA TI Inhibition of NF2-negative and NF2-positive primary human meningioma cell proliferation by overexpression of merlin due to vector-mediated gene transfer SO JOURNAL OF NEUROSURGERY LA English DT Article DE gene therapy; neurofibromatosis 2; herpes simplex virus vector; cancer therapy; brain neoplasm ID NEUROFIBROMATOSIS-2 TUMOR-SUPPRESSOR; NF2 GENE; SCHWANNOMIN; RETROVIRUSES; DOMAINS; PRODUCT; GROWTH AB Object. The absence of in vitro models of neurofibromatosis Type 2 (NF2)-defective meningiomas has limited investigative efforts to study the biological effects of this gene in the pathogenesis of these tumors. The goals of this report are to show that gene transfer vectors can efficiently express the wild-type NF2 transgene into primary meningioma cells and to determine effects on cellular proliferation. Methods. In this study, the authors have compared the transducing capacities of a retrovirus, an adenovirus, and a herpes simplex virus amplicon vector for use in primary human meningioma cells harvested from human tumors excised from patients with and without NF2. Transduction efficiencies with the latter vector approached 100% and it was selected to transfer the wild-type NF2 transgene into these cells. Western blot analysis confirmed that vector-mediated gene transfer mediated the expression of the NF2-encoded polypeptide merlin. Overexpression of merlin significantly inhibited the proliferation of both NF2-negative and NF2-positive human meningioma cells when compared to the proliferation of cells transduced with a control vector. Conclusions. This study demonstrates the feasibility of using vector-mediated gene transfer to study wild-type NF2 gene function in short-term cultures of primary human meningioma cells. C1 Massachusetts Gen Hosp, Mol Neurooncol Labs, Neurosurg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Serv Neurol, Boston, MA 02114 USA. RP Chiocca, EA (reprint author), Massachusetts Gen Hosp, Mol Neurooncol Labs, E Bldg,CNY6,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [P01CA 69246] NR 22 TC 50 Z9 50 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JUL PY 1999 VL 91 IS 1 BP 85 EP 92 DI 10.3171/jns.1999.91.1.0085 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 209PM UT WOS:000081057000013 PM 10389885 ER PT J AU Fischman, AJ AF Fischman, AJ TI Radionuclide imaging probes for expressed proteins SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; MYOCARDIAL MUSCARINIC RECEPTORS; LOW-DENSITY LIPOPROTEINS; RABBIT ARTERIAL-WALL; BENZODIAZEPINE RECEPTORS; IN-VIVO; HUMAN-HEART; ATHEROSCLEROTIC LESIONS; NONINVASIVE DETECTION; CHOLINERGIC RECEPTOR C1 Massachusetts Gen Hosp, Div Nucl Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fischman, AJ (reprint author), Massachusetts Gen Hosp, Div Nucl Med, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 58 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD JUL-AUG PY 1999 VL 6 IS 4 BP 438 EP 448 DI 10.1016/S1071-3581(99)90010-7 PG 11 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 229TU UT WOS:000082212500009 PM 10461611 ER PT J AU Emmons, KM Linnan, LA Shadel, WG Marcus, B Abrams, DB AF Emmons, KM Linnan, LA Shadel, WG Marcus, B Abrams, DB TI The Working Healthy Project: A worksite health-promotion trial targeting physical activity, diet, and smoking SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID RISK FACTOR INTERVENTIONS; PUBLIC-HEALTH; BREAST-CANCER; COLON CANCER; WELL TRIAL; EXERCISE; PROGRAMS; MODEL; WORKPLACE; EMPLOYEES AB Worksites are a key channel for delivery of interventions designed to reduce chronic disease among adult populations. Although some evaluations of worksite physical-activity interventions have been conducted, to date very few randomized trials of worksite health promotion have included the goal of increasing physical-activity levels as part of a comprehensive multiple risk factor approach to worksite health promotion. This article presents the results regarding behavior change found among the cohort of 2055 individuals who completed three health-behavior assessments as part of their worksites' participation in The Working Healthy Project (WHP), a multiple risk factor intervention implemented in 26 manufacturing worksites. In this study a randomized matched-pair design was used. Fifty-one percent (n = 2,761) of the employees who completed the baseline assessment also completed the interim survey. Eight-three percent of those who completed the interim assessment also completed the final survey. The WHP intervention targeted smoking, nutrition, and physical activity. At baseline, 38% of the sample reported engaging in regular exercise, and subjects reported consuming an average of 2.7 servings of fruits and vegetables per day, 7.9 grams of fiber per 1000 kilocalories, and 35.4% calories from fat per day: 28% of the sample were smokers. By the time of both the interim, (intervention midpoint) and final (end of intervention) assessments, participants in the intervention condition had significantly increased their exercise behavior, compared with the control condition. There was also increased consumption of fruits and vegetables and fiber in the intervention condition by the time of the final assessment, compared with the control condition. No differences by condition were found with regard to percentage of calories from fat consumed or smoking cessation. These results suggest that among a cohort of participants in a worksite health promotion study, there were significant health behavior changes across two risk factors over time. These data suggest that further investigation of multiple risk factor worksite health promotion is warranted, particularly with a focus on ways to increase participation in these programs and to diffuse intervention effects throughout the entire workforce. C1 Brown Univ, Miriam Hosp, Sch Med, Providence, RI USA. RP Emmons, KM (reprint author), Dana Farber Canc Inst, Div Community Based Res, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [P01 CA50087]; NHLBI NIH HHS [R01HL48180, 1RO1HL50017] NR 70 TC 80 Z9 80 U1 5 U2 27 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 JUL PY 1999 VL 41 IS 7 BP 545 EP 555 DI 10.1097/00043764-199907000-00003 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 215YR UT WOS:000081413400003 PM 10412096 ER PT J AU Kales, SN Polyhronopoulos, GN Aldrich, JM Leitao, EO Christiani, DC AF Kales, SN Polyhronopoulos, GN Aldrich, JM Leitao, EO Christiani, DC TI Correlates of body mass index in hazardous materials firefighters SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID OBSTRUCTIVE SLEEP-APNEA; OBESE PATIENTS; PHYSICAL-FITNESS; WEIGHT; MORTALITY; INJURY AB We analyzed results from the medical examinations of 340 hazardous materials (HAZMAT) firefighters and observed the relationships between selected parameters and body mass index (BMI). Heights and weights were available for 98% of the subjects (333 of 340). The mean BMI was 28.9 +/- 4.1 kg/m(2) . Eighty-seven percent (290 of 333) of subjects were overweight (BMI greater than or equal to 25) and 34% (113 of 333) were obese (BMI greater than or equal to 30). Two percent (7 of 333) were morbidly obese (BMI greater than or equal to 39). For comparison purposes, we divided subjects into low (BMI < 27), medium (BMI 27 to < 30), and high (BMI greater than or equal to 30) BMI groups. The results demonstrated adverse associations between increasing BMI and resting blood pressures, forced vital capacity, alanine aminotransferase, aspartate aminotransferase, serum cholesterol, and overall morbidity scores. The high prevalence of overweight and obesity and the associated adverse health effects support the development and implementation of fitness-promotion programs for firefighters. C1 Cambridge Hosp, Dept Med, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, Pulm Crit Care Unit, Boston, MA 02114 USA. Massachusetts Resp Hosp, Ctr Environm & Occupat Hlth, Braintree, MA USA. RP Kales, SN (reprint author), Cambridge Hosp, Dept Med, 1493 Cambridge St, Cambridge, MA 02139 USA. FU NIEHS NIH HHS [1K07ES00266]; NIOSH CDC HHS [R01 OH03729, 1 K01 OH00156] NR 32 TC 33 Z9 34 U1 0 U2 5 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 JUL PY 1999 VL 41 IS 7 BP 589 EP 595 DI 10.1097/00043764-199907000-00007 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 215YR UT WOS:000081413400007 PM 10412100 ER PT J AU Perciaccante, VJ Ochs, HA Dodson, TB AF Perciaccante, VJ Ochs, HA Dodson, TB TI Head, neck, and facial injuries as markers of domestic violence in women SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article AB Purpose: The diagnosis of domestic violence (DV) is difficult because of a lack of clearly defined signs and symptoms. The goal of this study was to confirm and refine the role of head, neck, and face (HNF) injuries as markers of DV. Patients and Methods: A cross-sectional study design and a sample of female trauma patients treated in an inner-city hospital emergency room (Grady Memorial Hospital, Atlanta, GA) were used. The predictor study variable was injury location (HNF or other location). The outcome variable was traumatic origin (DV or other cause). A victim of DV was defined as a patient who gave a history of being injured by her spouse or sexual partner. Other data included age, nature of the injury (blunt or penetrating), and injury severity score (ISS). Descriptive, bivariate, and logistic regression statistical analyses were performed. Results: The sample consisted of 100 injured women, with a mean age of 40 +/- 16.3 years and a mean ISS of 3.3 +/- 3.0. Thirty-four women were victims of DV. The mean age of the DV victims mras 32.5 +/- 7.3 years, compared with a mean age of 43.9 +/- 18.2 year in the other-causes group (P = .001). The mean ISS for the DV victims was 3.4 +/- 3.0, and the mean ISS for the other-causes group was 3.2 +/- 3.0 (P = .65). DV victims were 7.5 (2.5 < RR < 22.9) times more likely to have HNF injuries than other trauma patients (P < .001). Age was associated with cause and location of injury. After controlling for age, location remained statistically associated with cause (P = .0002). Sensitivity and specificity of HNF injuries and DV were 91% and 59%, respectively. Conclusions: The data suggest that although HNF injuries and age were sensitive predictors of DV, they remain poor in their specificity as markers. C1 Emory Univ, Sch Med, Dept Surg, Div Oral & Maxillofacial Surg, Atlanta, GA USA. RP Dodson, TB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. NR 13 TC 43 Z9 44 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUL PY 1999 VL 57 IS 7 BP 760 EP 762 DI 10.1016/S0278-2391(99)90808-X PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 212QE UT WOS:000081227100002 PM 10416621 ER PT J AU Kaban, LB AF Kaban, LB TI Temporomandibular joint reconstruction in children using costochondral grafts - Discussion SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Editorial Material ID UNPREDICTABLE GROWTH-PATTERN; TERM FOLLOW-UP; CONSTRUCTION; ANKYLOSIS; RAT C1 Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Kaban, LB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. NR 10 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUL PY 1999 VL 57 IS 7 BP 799 EP 800 DI 10.1016/S0278-2391(99)90817-0 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 212QE UT WOS:000081227100011 ER PT J AU Silva, MJ Reed, KL Robertson, DD Bragdon, C Harris, WH Maloney, WJ AF Silva, MJ Reed, KL Robertson, DD Bragdon, C Harris, WH Maloney, WJ TI Reduced bone stress as predicted by composite beam theory correlates with cortical bone loss following cemented total hip arthroplasty SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article ID PROXIMAL FEMUR; SIMULATION AB Clinical and experimental evidence suggest that periprosthetic bone loss following total hip arthroplasty is caused in part by stress-shielding. Changes in bone stress in the proximal femur following implantation can be estimated with use of composite beam theory. We hypothesized that the degree of stress-shielding predicted by beam theory correlates with the magnitude of bone loss following cemented total hip arthroplasty. We analyzed cross sections from the proximal femur of 13 patients who had undergone unilateral cemented total hip arthroplasty. A matching implant was inserted contralaterally, and the cross-sectional properties of the implant and bone and the bone density were determined. Bone loss was calculated on the basis of differences between contralateral (control) and ipsilateral (remodeled) sections and correlated to several beam-theory parameters calculated from the control sections: implant rigidity, bone rigidity, ratio of implant to bone rigidity, and predicted decrease in bone stress. All parameters except implant rigidity were significantly correlated with bone loss (p < 0.05). Parameters that included implant and bone properties were more strongly correlated with bone loss than were those based on bone properties alone. The predicted decrease in bone stress explained 50-60% of the variance in bone loss. The data also indicated that patients were not likely to lose substantial amounts of bone unless the reduction in bone stress exceeded a threshold value. Although limited by a small and heterogeneous sample, these results indicate that beam-theory predictions correlate with the degree of femoral resorption and should be investigated further as a means to identify patients at high risk for bone loss. C1 Washington Univ, Sch Med, Dept Orthopaed Surg, St Louis, MO 63110 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Silva, MJ (reprint author), Washington Univ, Sch Med, Dept Orthopaed Surg, 1 barnes Jewish Hosp Plaza,Suite 11300, St Louis, MO 63110 USA. NR 23 TC 14 Z9 17 U1 0 U2 3 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD JUL PY 1999 VL 17 IS 4 BP 525 EP 531 DI 10.1002/jor.1100170410 PG 7 WC Orthopedics SC Orthopedics GA 226HW UT WOS:000082015400008 PM 10459758 ER PT J AU Fishman, SM Bandman, TB Edwards, A Borsook, D AF Fishman, SM Bandman, TB Edwards, A Borsook, D TI The opioid contract in the management of chronic pain SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE opioids; contract; chronic opioid therapy ID CHRONIC NONMALIGNANT PAIN; SINGLE-VEHICLE CRASHES; ILLICIT DRUG-USE; CANCER PAIN; PSYCHOMOTOR; PREGNANCY; DRIVERS; MORPHINE; ALCOHOL; INFANTS AB Although the "opioid contract" is widely used in the administration of chronic opioid therapy, its use has not been well defined and there are few guidelines for developing or revising such tools. We reviewed opioid contracts from 39 major academic pain centers and analyzed every statement for its core meaning. These statements were grouped into general categories and then into specific statement groups. Substantial diversity in the content of the 39 contracts was found. Statements could be grouped into 12 general categories, 43 statement groups, and 125 individual statements. Each of the 39 contracts reviewed contained 22.5% +/- 10.9% of the entire list of 125 statements and 32.6% +/- 11.2% of the 43 statement categories. Contract length ave-aged less than 3 pages (range: 1 to 1 mean 2.2). We describe frequent and infrequent themes that may be well suited for inclusion in any given contract. While there are many significant issues related to the usage of a formal contract in chronic opioid therapy there was substantial consistency among the contracts in their universal attempts to improve care through dissemination of information, facilitate a mutually agreed-upon course, or enhance compliance. This study serves as an initial step in considering the risks and benefits of an opioid contract as well as its ideal content and presentation J Pain Symptom Manage 1999;18:27-37. (C) U.S. Cancer Pain Relief Committee, 1999. C1 Univ Calif Davis, Pain Management Ctr, Davis Dept Anesthesiol, MGH Pain Ctr, Sacramento, CA 95817 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. RP Fishman, SM (reprint author), Univ Calif Davis, Pain Management Ctr, Davis Dept Anesthesiol, MGH Pain Ctr, 4860 Y St,Suite 2600, Sacramento, CA 95817 USA. NR 52 TC 73 Z9 74 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JUL PY 1999 VL 18 IS 1 BP 27 EP 37 DI 10.1016/S0885-3924(99)00035-4 PG 11 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 219MH UT WOS:000081610700008 PM 10439570 ER PT J AU Shwartz, M Gastfriend, D Mulvey, K Baker, G Woods, D Wheeler, C Zaremba, N Plough, A AF Shwartz, M Gastfriend, D Mulvey, K Baker, G Woods, D Wheeler, C Zaremba, N Plough, A TI The Boston Target Cities program: Overview and evaluation results SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Article C1 Boston Univ, Sch Management, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Psychiat, Addict Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Ctr Subst Abuse Treatment Subst Abuse & Mental Hl, Off Evaluat Sci Anal & Synthesis, Rockville, MD USA. Tewksbury Hosp, Dept Med, Subst Abuse Serv, Tewksbury, MA 01870 USA. Brandeis Univ, Heller Sch Social Policy, Boston, MA USA. Massachusetts Dept Publ Hlth, Bur Subst Abuse Serv, Boston, MA 02111 USA. Seattle King Cty Dept Publ Hlth, Seattle, WA USA. RP Shwartz, M (reprint author), Boston Univ, Sch Management, 595 Commonwealth Ave, Boston, MA 02215 USA. FU PHS HHS [1-U88-T100022] NR 4 TC 3 Z9 3 U1 0 U2 0 PU HAIGHT-ASHBURY PUBL PI SAN FRANCISCO PA 409 CLAYTON ST, SAN FRANCISCO, CA 94117 USA SN 0279-1072 J9 J PSYCHOACTIVE DRUGS JI J. Psychoact. Drugs PD JUL-SEP PY 1999 VL 31 IS 3 BP 265 EP 272 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 245ND UT WOS:000083114300011 PM 10533973 ER PT J AU Wagoner, MD Badr, IA AF Wagoner, MD Badr, IA TI Phototherapeutic keratectomy for macular corneal dystrophy SO JOURNAL OF REFRACTIVE SURGERY LA English DT Article ID KERATOPLASTY AB PURPOSE: To report a case of early intervention with phototherapeutic keratectomy for treatment of macular corneal dystrophy. METHODS: We report a al-year-old Saudi male with early macular corneal dystrophy, recurrent erosions, and decreased visual acuity, who underwent phototherapeutic keratectomy in the right eye and penetrating keratoplasty in the left eye with more than 2 years of follow-up. RESULTS: Following phototherapeutic keratectomy, uncorrected visual acuity in the right eye improved from 20/80 to 20/30. Following penetrating keratoplasty in the left eye, uncorrected visual acuity deteriorated from 20/80 to 20/120 due to irregular astigmatism; the eye was not amenable to improvement with spectacle correction, and the patient declined contact lens therapy. In the right eye, there has been no anterior recurrence, although some mid- to deep stromal haze, which is not visually significant, has developed. CONCLUSIONS: Early intervention for symptomatic, anterior macular corneal dystrophy with phototherapeutic keratectomy is relatively safe and preferable to observation or penetrating keratoplasty. C1 King Khalid Eye Specialist Hosp, Anterior Segment External Dis Div, Riyadh 11462, Saudi Arabia. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea Serv,Dept Ophthalmol, Boston, MA USA. RP Wagoner, MD (reprint author), King Khalid Eye Specialist Hosp, Anterior Segment External Dis Div, POB 7191, Riyadh 11462, Saudi Arabia. NR 16 TC 14 Z9 14 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-597X J9 J REFRACT SURG JI J. Refractive Surg. PD JUL-AUG PY 1999 VL 15 IS 4 BP 481 EP 484 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 220UZ UT WOS:000081687000013 PM 10445722 ER PT J AU Taub, E AF Taub, E TI New discovery equals change in clinical practice SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Editorial Material C1 Birmingham Vet Affairs Med Ctr, Phys Med & Rehabil Serv, Birmingham, AL 35233 USA. Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. RP Taub, E (reprint author), Birmingham Vet Affairs Med Ctr, Phys Med & Rehabil Serv, Birmingham, AL 35233 USA. NR 0 TC 33 Z9 33 U1 0 U2 0 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD JUL PY 1999 VL 36 IS 3 BP VII EP VIII PG 2 WC Rehabilitation SC Rehabilitation GA 288VJ UT WOS:000085584900001 PM 10659797 ER PT J AU Legro, MW Reiber, G del Aguila, M Ajax, MJ Boone, DA Larsen, JA Smith, DG Sangeorzan, B AF Legro, MW Reiber, G del Aguila, M Ajax, MJ Boone, DA Larsen, JA Smith, DG Sangeorzan, B TI Issues of importance reported by persons with lower limb amputations and prostheses SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE lower limb amputation; lower limb prosthesis; quality of life; rehabilitation ID QUESTIONNAIRE; PROFILE; AMPUTEE AB The purpose of this paper is to report prosthesis-related issues of importance that were identified by a diverse group of persons living with lower limb amputations (LLA) and prostheses. These perceptions and themes validate some old assumptions and challenge others, report both common and unusual experiences, and indirectly identify the information level of our respondents concerning prostheses. Persons with LLA were identified from computerized rosters at a level one regional trauma center and at the VA Puget Sound Health Care System-Seattle, Division. Inclusion criteria specified that respondents were to: 1)be one or more years post-unilateral amputation at the Syme's level (ankle disarticulation) or higher, 2) use their prosthesis at least 5 days a week, 3) read English, and 4) be able to provide informed consent. Respondents completed the Prosthesis Evaluation Questionnaire-field version (PEQ) and the standard form (SF)-36, a health status measure. Of 114 persons who agreed to participate, 92 (85% male, mean age 55 years) responded to the questionnaire and graded the personal importance of various characteristics and qualities of their prosthesis. The number of years since their last amputation ranged from 1 to 53 years. Four Themes of Interest were identified from responses to open-ended questions about living with a prosthesis. These themes included the fit of the socket with the residual limb, aspects of the mechanical functioning of the prosthesis, other nonmechanical qualities, and advice about adaptation to life with a prosthesis with support from others. Future research is recommended to adjust aspects of the fit of the prosthesis with the residual limb. Implementing periodic check-up visits could uncover problems and eliminate unnecessary suffering. C1 VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. Washington Dental Serv, Seattle, WA USA. Battelle, Seattle, WA USA. Prosthet Res Study, Seattle, WA 98122 USA. RP Legro, MW (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div, HSR&D 152,1660 S Columbian Way, Seattle, WA 98108 USA. NR 12 TC 89 Z9 93 U1 2 U2 13 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD JUL PY 1999 VL 36 IS 3 BP 155 EP 163 PG 9 WC Rehabilitation SC Rehabilitation GA 288VJ UT WOS:000085584900002 PM 10659798 ER PT J AU McGibbon, CA Krebs, DE AF McGibbon, CA Krebs, DE TI Effects of age and functional limitation on leg joint power and work during stance phase of gait SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE body size; elderly; gait; mechanical power and energy; velocity ID OLDER ADULTS; ELDERLY PEOPLE; WALKING SPEED; STRENGTH; KINEMATICS; BALANCE; FALLS; YOUNG; HIP AB It is commonly accepted that leg muscle power is an important component of functional ability. Paced gait data for 20 healthy young women (27+/-4.2 yrs), 16 healthy old women (72.5+/-5.6 yrs), and 24 functionally limited old women (73.5+/-7.2 yrs) were analyzed during stance phase to investigate whether power calculations from motion analysis data were sensitive to impairments beyond the differences expected with aging. Healthy women included in the study functioned at a high/moderate level with no limitations, while functionally limited women functioned at a much lower level and exhibited one or more functional limitations as defined by the SF36 physical function scale. Single support time (SSUP), stance duration (SDUR), average forward center of gravity velocity (GVEL), and three-dimensional net power and work of the ankle (APOW/AWRK), knee (KPOW/KWRK), and hip (HPOW/ HWRK) were computed for the stance limb during the stance phase of gait. Univariate ANCOVA was used to examine which variables were most sensitive to functional limitations. We found that SDUR and SSUP were not different among the three groups when controlling for height and weight. Although differences in CG velocity between healthy and functionally limited old women were not significant, both elderly groups translated their CG slower than did the younger women (p<0.0001) when walking at the same cadence. Controlling for CG velocity eliminated all significant differences among groups except for APOW and AWRK in late stance phase between healthy and functionally limited elderly women (p<0.003). These results suggest that decreased ankle plantar-flexor power in late stance of gait may be an impairment-related characteristic more than an age-related characteristic. C1 Massachusetts Gen Hosp, Dept Orthopaed, Biomot Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP McGibbon, CA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, Biomot Lab, 40 Parkman St, Boston, MA 02114 USA. NR 35 TC 27 Z9 27 U1 2 U2 6 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD JUL PY 1999 VL 36 IS 3 BP 173 EP 182 PG 10 WC Rehabilitation SC Rehabilitation GA 288VJ UT WOS:000085584900004 PM 10659800 ER PT J AU Franco, JC Perell, KL Gregor, RJ Scremin, AME AF Franco, JC Perell, KL Gregor, RJ Scremin, AME TI Knee kinetics during functional electrical stimulation induced cycling in subjects with spinal cord injury: A preliminary study SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE bicycling; biomechanics; joint reaction forces; kinetics; knee joint; osteopenia; spinal cord injured ID BONE-DENSITY; EXERCISE; OSTEOPOROSIS; MOMENTS; MUSCLE AB The purpose of this preliminary study was to describe pedal effectiveness parameters and knee-joint reaction forces generated by subjects with chronic spinal cord injury (SCI) during functional electrical stimulation (FES)-induced bicycling. Three male subjects (age 33-36 years old), who were post-traumatic SCI (ASIA-modified level A, level T4-C5) and enrolled in an FES rehabilitation program, signed informed consent forms and participated in this study. Kinematic data and pedal forces during bicycling were collected and effective force, knee-joint reaction forces, knee generalized muscle moments, and knee-joint power and work were calculated. There were three critical findings of this study: 1) pedaling effectiveness was severely compromised in this subject population as indicated by a lack of overall positive crank work; 2) knee-joint kinetics were similar in magnitude to data reported for unimpaired individuals pedaling at higher rates and workloads, suggesting excessive knee-joint loading for subjects with SCI; and 3) shear reaction forces and muscle moments were opposite in direction to data reported for unimpaired individuals, revealing an energetically unfavorable knee stabilizing mechanism. The critical findings of this study suggest that knee-joint kinetics may be large enough to produce a fracture in the compromised lower limbs of individuals with SCI. C1 Univ New Mexico, Dept Orthoped, Albuquerque, NM 87131 USA. W Los Angeles Hlthcare Ctr, Dept Phys Med & Rehabil, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Div Phys Med & Rehabil, Los Angeles, CA 90024 USA. Mt St Marys Coll, Dept Phys Therapy, Los Angeles, CA USA. Georgia Inst Technol, Dept Hlth & Performance Sci, Atlanta, GA 30332 USA. RP Perell, KL (reprint author), W Los Angeles Vet Affairs Med Ctr 691, PM&R Gait Lab 117G, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 27 TC 10 Z9 10 U1 1 U2 4 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD JUL PY 1999 VL 36 IS 3 BP 207 EP 216 PG 10 WC Rehabilitation SC Rehabilitation GA 288VJ UT WOS:000085584900008 PM 10659804 ER PT J AU Pazmany, L Mandelboim, O Vales-Gomez, M Davis, DM Becker, TC Reyburn, HT Seebach, JD Hill, JA Strominger, JL AF Pazmany, L Mandelboim, O Vales-Gomez, M Davis, DM Becker, TC Reyburn, HT Seebach, JD Hill, JA Strominger, JL TI Human leucocyte antigen-G and its recognition by natural killer cells SO JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article; Proceedings Paper CT 1st International Conference on HLA-G CY JUL 06-07, 1998 CL PARIS, FRANCE ID HLA-G; INHIBITORY RECEPTOR; NK CELLS; MEDIATED LYSIS; RESISTANCE; EXPRESSION; LIGAND; TROPHOBLAST; PROTECTION; CD94/NKG2A C1 Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. RP Pazmany, L (reprint author), Harvard Univ, Dept Mol & Cellular Biol, Fairchild Biochem Bldg,7 Divin Ave, Cambridge, MA 02138 USA. RI Reyburn, Hugh/B-4338-2009; Vales-Gomez, Mar/F-5351-2012 OI Vales-Gomez, Mar/0000-0001-7424-3206 NR 27 TC 13 Z9 14 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-0378 J9 J REPROD IMMUNOL JI J. Reprod. Immunol. PD JUL PY 1999 VL 43 IS 2 BP 127 EP 137 DI 10.1016/S0165-0378(99)00028-5 PG 11 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA 227TW UT WOS:000082096900003 PM 10479049 ER PT J AU Chan, KY Jupiter, JB Leffert, RD Marti, R AF Chan, KY Jupiter, JB Leffert, RD Marti, R TI Clavicle malunion SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article AB The clavicle fracture that has united with deformity or shortening may have an adverse effect on normal shoulder girdle function. We report on 4 patients in whom a malunited fracture of the clavicle was believed to be a contributing factor to shoulder girdle dysfunction. In each patient, the functional status of the involved limb was improved after corrective osteotomy at the site of deformity realignment, and plate fixation. C1 Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. Univ Amsterdam, Acad Med Ctr, Dept Orthoped Surg, NL-1105 AZ Amsterdam, Netherlands. RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, ACC527A, Boston, MA 02114 USA. NR 12 TC 53 Z9 54 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD JUL-AUG PY 1999 VL 8 IS 4 BP 287 EP 290 DI 10.1016/S1058-2746(99)90146-5 PG 4 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 229KP UT WOS:000082194000001 PM 10471996 ER PT J AU Baer, JS Kivlahan, DR Donovan, DM AF Baer, JS Kivlahan, DR Donovan, DM TI Integrating skills training and motivational therapies - Implications for the treatment of substance dependence SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE motivational enhancement; relapse prevention; skills-training; therapeutic style; treatment integration ID ENHANCING MOTIVATION; PROBLEM DRINKERS; ALCOHOLISM; READINESS; BEHAVIOR; DRINKING; RISK AB Two well-articulated models of substance abuse treatment, skills training and motivational enhancement, have received considerable research attention in recent years. Skills training treatments operate on the underlying rationale of correcting skills deficits, whereas motivational strategies are based on affecting clients' willingness to use skills they already possess. Skills training and motivational enhancement are typically described as distinct treatments and have recently been constructed as different treatments within a large multisite trial in the United States (Project MATCH). This article explores how treatments for substance abuse can draw from and integrate skills training and motivational strategies. Recovery from addictive patterns of behavior often requires learning over time and typically involves slips, relapses, and multiple quit attempts. Therapeutic support for change in addictive behavior, in particular attempting to prevent and minimize relapse, requires assessment and support of both why one might pursue change (motivation) and how one carl best be successful (skills). (C) 1999 Elsevier Science Inc. All rights reserved. C1 Vet Affairs Puget Sound Hlth Care Syst, Natl Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Inst Alcohol & Drug Abuse, Seattle, WA USA. RP Baer, JS (reprint author), Dept Vet Affairs, Puget Sound Hlth Care Syst, 1660 S Columbian Way,116 MATCH, Seattle, WA 98108 USA. NR 44 TC 30 Z9 30 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD JUL-SEP PY 1999 VL 17 IS 1-2 BP 15 EP 23 DI 10.1016/S0740-5472(98)00072-5 PG 9 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 221MJ UT WOS:000081730600003 PM 10435249 ER PT J AU Herzog, DB Dorer, DJ Keel, PK Selwyn, SE Ekeblad, ER Flores, AT Greenwood, DN Burwell, RA Keller, MB AF Herzog, DB Dorer, DJ Keel, PK Selwyn, SE Ekeblad, ER Flores, AT Greenwood, DN Burwell, RA Keller, MB TI Recovery and relapse in anorexia and bulimia nervosa: A 7.5-year follow-up study SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE recovery; relapse; anorexia; bulimia ID SELF-REPORTED WEIGHT; EATING DISORDERS; PREDICTORS; ADOLESCENTS; WOMEN AB Objective: To assess the course and outcome of anorexia nervosa (AN) and bulimia nervosa (BN) at a median of 90 months of follow-up in a large cohort of women with eating disorders. Method: A prospective, naturalistic, longitudinal design was used to map the course of AN and BN in 246 women. Follow-up data are presented in terms of full and partial recovery, predictors of time to recovery, and rates and predictors of relapse. Results: The full recovery rate of women with BN was significantly higher than that of women with AN, with 74% of those with BN and 33% of those with AN achieving full recovery by a median of 90 months of follow-up. Intake diagnosis of AN was the strongest predictor of worse outcome. No predictors of recovery emerged among bulimic subjects. Eighty-three percent of women with AN and 99% of those with BN achieved partial recovery. Approximately one third of both women with AN and women with BN relapsed after full recovery. No predictors of relapse emerged. Conclusions: The findings suggest that the course of AN is characterized by high rates of partial recovery and low rates of full recovery, while the course of BN is characterized by higher rates of both partial and full recovery. C1 Massachusetts Gen Hosp, Eating Disorders Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Eating Disorders Ctr, Boston, MA USA. Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. RP Herzog, DB (reprint author), Massachusetts Gen Hosp, Eating Disorders Unit, ACC 725,15 Parkman St, Boston, MA 02114 USA. FU NIMH NIH HHS [5R01 MH 38333 05] NR 31 TC 187 Z9 192 U1 4 U2 25 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL PY 1999 VL 38 IS 7 BP 829 EP 837 DI 10.1097/00004583-199907000-00012 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 212NQ UT WOS:000081223400012 PM 10405500 ER PT J AU Anstey, AV Taylor, CR AF Anstey, AV Taylor, CR TI Photosensitivity in the Smith-Lemli-Opitz syndrome: The US experience of a new congenital photosensitivity syndrome SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article; Proceedings Paper CT Combined Meeting of the Photomedicine-Society/European-Society-for-Photobiology CY OCT, 1998 CL NICE, FRANCE SP Photomed Soc, European Soc Photobiol ID CHOLESTEROL; MUTATIONS; GENE AB Photosensitivity has been briefly mentioned in several publications on the Smith-Lemli-Opitz (SLO) syndrome, an autosomal recessive mental retardation syndrome. We conducted a questionnaire-based survey to determine the incidence and main features of photosensitivity in SLO. We confirmed a high incidence, and initial evidence suggests that SLO may be the first example of an inherited photosensitivity disorder in which sensitivity to UVA is common. C1 Univ Wales Hosp, Dept Dermatol, Photodermatol Unit, Cardiff, S Glam, Wales. Harvard Univ, Sch Med, Wellman Labs Photomed, Grange Ctr,Massachusetts Gen Hosp,Dept Dermatol, Cambridge, MA 02138 USA. RP Anstey, AV (reprint author), Univ Coll N Wales, Dept Dermatol, Photodermatol Unit, Heath Pk, Cardiff CF4 4XN, S Glam, Wales. NR 10 TC 9 Z9 9 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JUL PY 1999 VL 41 IS 1 BP 121 EP 123 DI 10.1016/S0190-9622(99)70420-2 PG 3 WC Dermatology SC Dermatology GA 213EM UT WOS:000081259600023 PM 10411425 ER PT J AU Schunkert, H Harrell, L Palacios, IF AF Schunkert, H Harrell, L Palacios, IF TI Implications of small reference vessel diameter in patients undergoing percutaneous coronary revascularization SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID BALLOON ANGIOPLASTY; STENT PLACEMENT; ARTERY DISEASE; TASK-FORCE; RESTENOSIS; REGISTRY; DETERMINANTS; ASSOCIATION; PREDICTORS; LESION AB OBJECTIVES The purpose of this study was to determine whether small reference diameter of the culprit coronary artery influences the outcome of an attempted percutaneous revascularization procedure in the current era of interventional cardiology. BACKGROUND Alhough the interventional strategy is largely determined by the size of the culprit coronary artery, earlier quantitative studies have not shown a worse acute outcome for small reference vessel diameter (less than or equal to 2.5 mm). METHODS A total of 2,306 patients undergoing percutaneous coronary revascularization was divided in groups with reference diameters less than or equal to 2.5 mm (n = 813) or >2.5 mm (n = 1,493). Success and in-hospital major adverse cardiac event (death, Q-wave myocardial infarction and emergency coronary artery bypass graft) rates between both groups were compared. RESULTS Patients with lesions in small vessels were older and presented more frequently with female gender, diabetes mellitus, heart failure, peripheral vascular, multivessel coronary disease and American Heart Association/American College of Cardiology (AHA/ACC) lesion type C (p less than or equal to 0.01, each). Further, utilization of interventional devices differed markedly. In contrast to stents (18.5% vs. 41.9%) and directional atherectomy (3.7% vs. 13.5%), conventional balloon angioplasty (73% vs. 50%) and rotational atherectomy (16.1% vs. 8.3%) were used more often in smaller vessels (p less than or equal to 0.0001, each). Success rate was lower in the small vessel group (92% vs. 95%; p = 0.006). Major adverse cardiac events occurred more frequently in small than large vessels (univariate 3.4% vs. 2.0%, p = 0.03; multivariate odds ratio 2.1, p = 0.02), particularly when proximal coronary segments were compared. CONCLUSIONS Lesions in vessels with small reference diameter represent a distinct group with respect re, clinical and morphologic characteristics as well, as device utilization. These lesions have lower chances of successful percutaneous intervention and carry relatively higher risks, specifically when located in proximal coronary segments. (C) 1999 by the American College of Cardiology. C1 Massachusetts Gen Hosp, Cardiac Catheterizat Lab, Cardiac Unit, Dept Med, Boston, MA 02114 USA. Univ Regensburg, Med Klin & Poliklin Innere Med 2, D-8400 Regensburg, Germany. RP Palacios, IF (reprint author), Massachusetts Gen Hosp, Cardiac Catheterizat Lab, Cardiac Unit, Dept Med, Bulfinch 105,Fruit St, Boston, MA 02114 USA. NR 33 TC 79 Z9 82 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL PY 1999 VL 34 IS 1 BP 40 EP 48 DI 10.1016/S0735-1097(99)00181-3 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 213GT UT WOS:000081264900008 PM 10399990 ER PT J AU Pathan, AZ Mahdi, NA Leon, MN Lopez-Cuellar, J Simosa, H Block, PC Harrell, L Palacios, IF AF Pathan, AZ Mahdi, NA Leon, MN Lopez-Cuellar, J Simosa, H Block, PC Harrell, L Palacios, IF TI Is redo percutaneous mitral balloon valvuloplasty (PMV) indicated in patients with post-PMV mitral restenosis? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID FOLLOW-UP; VALVE-REPLACEMENT; RANDOMIZED TRIAL; COMMISSUROTOMY; VALVOTOMY; STENOSIS; PREDICTORS; IMMEDIATE; CATHETER AB OBJECTIVES The purpose of this study was to assess the immediate and long-term outcome of repeat percutaneous mitral balloon valvuloplasty (PMV) for post-PMV mitral restenosis. BACKGROUND Symptomatic mitral restenosis develop in 7% to 21% of patients after PMV. Currently, most of these patients are referred for mitral valve replacement. However, it is unknown if these patients may benefit from repeat PMV. METHODS We report the immediate outcome and long-term clinical follow-up results of 36 patients (mean age 58 +/- 13 years, 75% women) with symptomatic mitral restenosis after prior PMV, who were treated with a repeat PR-IV at 34.6 +/- 28 months after the initial PMV. The mean follow-up period was 30 +/- 33 months with a maximal follow-up of 10 years. RESULTS An immediate procedural success was obtained in 75% patients. The overall survival rate was 74%, 72% and 71% at one, two, and three years respectively. The event-free survival rate was 61%, 54% and 47% at one, two, and three years respectively. In the presence of comorbid diseases (cardiac and noncardiac) the two-year event-free survival was reduced to 29% as compared with 86% in patients without comorbid diseases. Cox regression analysis identified the echocardiographic score (p = 0.03), post-PMV mitral valve area (p = 0.003), post-PMV mitral regurgitation grade (p = 0.02) and post-PMV pulmonary artery pressure (p = 0.0001) as independent predictors of event-free survival after repeat PMV. CONCLUSIONS Repeat PMV for post-PMV mitral restenosis results in good immediate and long-term outcome in patients with low echocardiographic scores and absence of comorbid diseases. Although the results are less favorable in patients with suboptimal characteristics, repeat PMV has a palliative role if the patients are not surgical candidates. (C) 1999 by the American College of Cardiology. C1 Harvard Univ, Cardiac Catheterizat Lab, Cardiac Unit,Med Sch,Dept Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Palacios, IF (reprint author), Harvard Univ, Cardiac Catheterizat Lab, Cardiac Unit,Med Sch,Dept Med, Massachusetts Gen Hosp, Bulfinch 105,55 Fruit St, Boston, MA 02114 USA. NR 27 TC 19 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL PY 1999 VL 34 IS 1 BP 49 EP 54 DI 10.1016/S0735-1097(99)00176-X PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 213GT UT WOS:000081264900009 PM 10399991 ER PT J AU Bozkurt, B Villaneuva, FS Holubkov, R Tokarczyk, T Alvarez, RJ MacGowan, GA Murali, S Rosenblum, WD Feldman, AM McNamara, DM AF Bozkurt, B Villaneuva, FS Holubkov, R Tokarczyk, T Alvarez, RJ MacGowan, GA Murali, S Rosenblum, WD Feldman, AM McNamara, DM TI Intravenous immune globulin in the therapy of peripartum cardiomyopathy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID DILATED CARDIOMYOPATHY; ACUTE MYOCARDITIS; HEART-FAILURE; TRANSPLANTATION; IMMUNOGLOBULIN; PREGNANCY; TRIAL AB OBJECTIVES We sought to evaluate the effect of therapy with intravenous immune globulin on recovery of left ventricular function in women presenting with peripartum cardiomyopathy. BACKGROUND Peripartum cardiomyopathy is a rare complication of pregnancy that results in significant morbidity and mortality in women of childbearing age. Intravenous immune globulin has been reported to improve left ventricular systolic function in patients with acute dilated cardiomyopathy and myocarditis, but its effectiveness in peripartum cardiomyopathy is unknown. METHODS In this retrospective study, we compared the clinical outcomes of six women with peripartum cardiomyopathy treated with intravenous immune globulin (2 g/kg) with those of 11 recent historical control subjects. All women in the study were referred between 1991 and 1998 with class II to IV heart failure and a left ventricular ejection fraction of <0.40. Left ventricular ejection was reassessed during early follow-up (6.1 +/- 2.9 months). RESULTS The two groups did not differ in terms of baseline left ventricular ejection fraction, left ventricular end-diastolic diameter, months to presentation, age or multiparity. The improvement in left ventricular ejection fraction in patients treated with immune globulin was significantly greater than in the conventionally treated group (increase of 26 +/- 8 ejection fraction units vs. 13 +/- 13, p = 0.042). CONCLUSIONS In this small retrospective study of women with peripartum cardiomyopathy, patients treated with immune globulin had a greater improvement in ejection fraction during early follow-up than patients treated conventionally. Given the poor prognosis of women with peripartum cardiomyopathy who do not improve, this therapy merits further study. (C) 1999 by the American College of Cardiology. C1 Univ Pittsburgh, Med Ctr, Div Cardiol, Pittsburgh, PA 15213 USA. Baylor Coll Med, Cardiol Sect, VA Med Ctr, Houston, TX 77030 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. RP McNamara, DM (reprint author), Univ Pittsburgh, Med Ctr, Div Cardiol, 200 Lothrop St,S558 Scaife Hall, Pittsburgh, PA 15213 USA. NR 28 TC 105 Z9 112 U1 0 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 JUL PY 1999 VL 34 IS 1 BP 177 EP 180 DI 10.1016/S0735-1097(99)00161-8 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 213GT UT WOS:000081264900026 PM 10400008 ER PT J AU Campbell, AJ Robertson, MC Gardner, MM Norton, RN Buchner, DM AF Campbell, AJ Robertson, MC Gardner, MM Norton, RN Buchner, DM TI Psychotropic medication withdrawal and a home-based exercise program to prevent falls: A randomized, controlled trial SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE psychotropic medication; exercise; falls ID NURSING-HOME; ELDERLY PEOPLE; FICSIT TRIALS; RISK-FACTORS; OLDER WOMEN; COMMUNITY; BALANCE; ANTIDEPRESSANTS; FRACTURES; RESIDENTS AB OBJECTIVE: To assess the effectiveness of psychotropic medication withdrawal and a home-based exercise program in reducing falls in older people. DESIGN: A randomized controlled trial with a two by two factorial design. SETTING: Seventeen general practices in Dunedin, New Zealand. PARTICIPANTS: Women and men aged 65 years registered with a general practitioner and currently taking psychotropic medication (n = 93). INTERVENTIONS: Two interventions: (1) gradual withdrawal of psychotropic medication versus continuing to take psychotropic medication (double blind) and (2) a home-based exercise program versus no exercise program (single blind). MEASUREMENTS: Number of falls and falls risk during 44 weeks of follow-up. Analysis was on an intent to treat basis. RESULTS: After 44 weeks, the relative hazard for falls in the medication withdrawal group compared with the group taking their original medication was .34 (95% CI, .16-.74). The risk of falling for the exercise program group compared with those not receiving the exercise program was not significantly reduced. CONCLUSIONS: Withdrawal of psychotropic medication significantly reduced the risk of falling, but permanent withdrawal is very difficult to achieve. C1 Dunedin Sch Med, Fac Med, Otago Med Sch, Dunedin, New Zealand. Univ Auckland, Sch Med, Injury Prevent Res Ctr, Auckland 1, New Zealand. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Campbell, AJ (reprint author), Dunedin Sch Med, Fac Med, Otago Med Sch, POB 913, Dunedin, New Zealand. RI Robertson, Mary Clare/A-3964-2009 NR 23 TC 254 Z9 260 U1 4 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUL PY 1999 VL 47 IS 7 BP 850 EP 853 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 214HW UT WOS:000081323400012 PM 10404930 ER PT J AU Ausiello, DA AF Ausiello, DA TI The similarity of effects of vasopressin, adenosine-3 ',5 '-phosphate (cyclic AMP) and theophylline on the toad bladder - Guest commentary SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ausiello, DA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUL PY 1999 VL 10 IS 7 BP 1628 EP 1629 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 211DD UT WOS:000081143900030 ER PT J AU McFall, M Fontana, A Raskind, M Rosenheck, R AF McFall, M Fontana, A Raskind, M Rosenheck, R TI Analysis of violent behavior in Vietnam combat veteran psychiatric inpatients with posttraumatic stress disorder SO JOURNAL OF TRAUMATIC STRESS LA English DT Article DE Vietnam veterans; PTSD; violence ID MENTAL-ILLNESS; ANGER; AGGRESSION; COMMUNITY; ASSAULT; SUPPORT; ABUSE; PTSD; FEAR AB This study tested the hypothesis that male Vietnam veterans seeking inpatient treatment for PTSD (n = 228) exhibit more violent behavior compared with a mixed diagnostic group of male psychiatric inpatients without PTSD (n = 64) and a community sample of Vietnam veterans with PTSD not undergoing inpatient treatment (n = 273). Violent acts assessed included property destruction, threats without a weapon, physical fighting, and threats with a weapon. PTSD inpatients engaged in more types of violent behavior than both comparison conditions Correlates of violence among PTSD inpatients included PTSD symptom severity and to a lesser degree, measures of substance abuse. These findings justify routine assessment of violent behavior among inpatients with PTSD, as well as application of specialized interventions for anger dyscontrol and aggression. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Sch Med, Seattle, WA USA. Vet Affairs Connecticut Hlth Care Syst, New Haven, CT USA. Yale Univ, Sch Med, New Haven, CT USA. RP McFall, M (reprint author), 1660 S Columbian Way, Seattle, WA 98108 USA. NR 37 TC 81 Z9 83 U1 3 U2 7 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUL PY 1999 VL 12 IS 3 BP 501 EP 517 DI 10.1023/A:1024771121189 PG 17 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 227ZM UT WOS:000082110100007 PM 10467558 ER PT J AU Goldberg, SN Stein, MC Gazelle, GS Sheiman, RG Kruskal, JB Clouse, ME AF Goldberg, SN Stein, MC Gazelle, GS Sheiman, RG Kruskal, JB Clouse, ME TI Percutaneous radiofrequency tissue ablation: Optimization of pulsed radiofrequency technique to increase coagulation necrosis SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE neoplasms, therapy; radiofrequency ablation ID LIVER METASTASES; NEEDLE ELECTRODE; EXPERIENCE; TUMORS; SIZE; TEMPERATURE; VOLUME AB PURPOSE: To develop a computerized algorithm for pulsed, high-current percutaneous radiofrequency (RF) ablation, which maximally increases the extent of induced coagulation necrosis. MATERIALS AND METHODS: An automated, Programmable algorithm for pulsed-RF deposition was designed to permit high-current deposition by periodically reducing current for 5-30 seconds during RF application. Two strategies for pulsed-RF deposition were evaluated: (i) constant peak current (900-1,800 mA) of variable duration and (ii) variable peak current (1,200-2,000 mA) for a specified minimum duration. The extent of induced coagulation was compared to results obtained with continuous (lower current) RF application. Trials were performed in ex vivo calf liver (n = 115) and in vivo porcine liver (n = 30) and muscle (n = 18) with use of 2-4-cm tip, internally cooled electrodes. RESULTS: For 3-cm electrodes in ex vivo liver, applying pulsed-RF with constant peak current for 12 minutes produced 3.5 cm +/- 0.2 of necrosis, Greater necrosis was produced with use of the variable current strategy, in which 4.5 cm +/- 0.2 of coagulation was achieved with use of an initial current greater than or equal to 1,500 mA (minimum peak-RF duration of 10 sec, with 15 sec of reduced current to 100 mA between peaks; P < .01). This variable peak current algorithm also produced 3.7 cm +/- 0.6 of necrosis in in vivo liver, and 6.5 cm +/- 0.9 in in vivo muscle. Without pulsing, a maximum of 750 mA, 1,100 mA, and 1,500 mA could be applied in ex vivo liver, in vivo liver, and in vivo muscle, respectively, which resulted in 2.9 cm +/- 0.2, 2.4 cm +/- 0.2, and 5.1 cm +/- 0.4 of coagulation (P < .05, all comparisons). CONCLUSIONS: A variable peak current algorithm for pulsed-RF deposition can increase coagulation necrosis diameter over other ablation strategies. This innovation may ultimately enable the percutaneous treatment of larger tumors. C1 Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. 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 23 TC 196 Z9 209 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JUL-AUG PY 1999 VL 10 IS 7 BP 907 EP 916 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 218NP UT WOS:000081558900010 PM 10435709 ER PT J AU Schenten, D Marcon, L Karlsson, GB Parolin, C Kodama, T Gerard, N Sodroski, J AF Schenten, D Marcon, L Karlsson, GB Parolin, C Kodama, T Gerard, N Sodroski, J TI Effects of soluble CD4 on simian immunodeficiency virus infection of CD4-positive and CD4-negative SO JOURNAL OF VIROLOGY LA English DT Article ID T-LYMPHOTROPIC RETROVIRUS; ENVELOPE GLYCOPROTEIN; CHEMOKINE RECEPTORS; HIV-1 ENTRY; AIDS VIRUS; CD4-INDEPENDENT INFECTION; CONFORMATIONAL-CHANGES; SYNCYTIUM FORMATION; GP120 DISSOCIATION; FUSION COFACTOR AB A soluble form of the CD4 receptor (sCD4) can either enhance or inhibit the infection of cells by simian immunodeficiency virus (SIV) and human immunodeficiency virus. We investigated the basis for these varying effects by studying the entry of three SN isolates into CD4-positive and CD4-negative cells expressing different chemokine receptors. Infection of CD4-negative cells depended upon the viral envelope glycoproteins and upon the chemokine receptor, with CCR5 and gpr15 being more efficient than STRL33. Likewise, enhancement of infection by sCD4 was observed when CCR5- and gpr15-expressing target cells were used but not when those expressing STRL33 were used. The sCD4-mediated enhancement of virus infection of CD4-negative, CCR5-positive cells was related to the sCD4-induced increase in binding of the viral gp120 envelope glycoprotein to CCR5. Inhibitory effects of sCD4 could largely be explained by competition for virus attachment to cellular CD4 rather than other detrimental effects on virus infectivity (e.g., disruption of the envelope glycoprotein spike). Consistent with this, the sCD4-activated SIV envelope glycoprotein intermediate on the virus was long-lived. Thus, the net effect of sCD4 on SIV infectivity appears to depend upon the degree of enhancement of chemokine receptor binding and upon the efficiency of competition for cellular CD4. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Univ Padua, Sch Med, Inst Microbiol, I-35121 Padua, Italy. Oregon Reg Primate Res Ctr, Beaverton, OR 97006 USA. Childrens Hosp, Ina Sue Perlmutter Lab, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Pediat, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. FU NIAID NIH HHS [AI28691, R01 AI041851, AI24755, AI41851, P30 AI028691, R37 AI024755] NR 78 TC 44 Z9 45 U1 0 U2 2 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 JUL PY 1999 VL 73 IS 7 BP 5373 EP 5380 PG 8 WC Virology SC Virology GA 205GT UT WOS:000080813500015 PM 10364284 ER PT J AU Pulitz, JZ Yu, Q Burke, JM Wands, JR AF Pulitz, JZ Yu, Q Burke, JM Wands, JR TI Combinatorial screening and intracellular antiviral activity of hairpin ribozymes directed against hepatitis B virus SO JOURNAL OF VIROLOGY LA English DT Article ID IN-VITRO; RNA MOLECULES; EXPRESSION; CLEAVAGE; SELECTION; CATALYSIS; PROTEIN; COMPLEX; ENZYMES; GROWTH AB A combinatorial screening method has been used to identify hairpin ribozymes that inhibit hepatitis B virus (HBV) replication in transfected human hepatocellular carcinoma (HCG) cells. A hairpin ribozyme library (5 x 10(5) variants) containing a randomized substrate-binding domain was used to identify accessible target sites within 3.3 kb of full-length in vitro-transcribed HBV pregenomic RNA. Forty potential target sites were found within the HBV pregenomic RNA, and 17 sites conserved in all four subtypes of HBV were chosen for intracellular inhibition experiments. Polymerase II and III promoter expression constructs for corresponding hairpin ribozymes were generated and cotransfected into HCC cells together with a replication-competent dimer of HBV DNA. Four ribozymes inhibited HBV replication by 80, 69, 66, and 49%, respectively, while catalytically inactive mutant forms of these ribozymes affected HBV replication by 36, 28, 0, and 0%. These findings indicate that the inhibitory effects on HBV replication were largely mediated by the catalytic activity of the ribozymes. In conclusion, we have identified catalytically active RNAs by combinatorial screening that mediate intracellular antiviral effects on HBV. C1 Massachusetts Gen Hosp, Ctr Canc, Mol Hepatol Lab, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Univ Vermont, Markey Ctr Mol Genet, Dept Microbiol & Mol Genet, Burlington, VT 05405 USA. RP Wands, JR (reprint author), Liver Res Ctr, 55 Claverick St,4th Floor, Providence, RI 02903 USA. NR 36 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 1999 VL 73 IS 7 BP 5381 EP 5387 PG 7 WC Virology SC Virology GA 205GT UT WOS:000080813500016 ER PT J AU Hay, CM Ruhl, DJ Basgoz, NO Wilson, CC Billingsley, JM DePasquale, MP D'Aquila, RT Wolinsky, SM Crawford, JM Montefiori, DC Walker, BD AF Hay, CM Ruhl, DJ Basgoz, NO Wilson, CC Billingsley, JM DePasquale, MP D'Aquila, RT Wolinsky, SM Crawford, JM Montefiori, DC Walker, BD TI Lack of viral escape and defective in vivo activation of human immunodeficiency virus type 1-specific cytotoxic T lymphocytes in rapidly progressive infection SO JOURNAL OF VIROLOGY LA English DT Article ID NEUTRALIZING ANTIBODY-RESPONSES; HIV-1 INFECTION; LONGITUDINAL ANALYSIS; DISEASE PROGRESSION; FINE SPECIFICITY; CELL RESPONSES; VIREMIA; AIDS; LYSIS; GENE AB Human immunodeficiency virus type 1 (HIV-1)-specific immune responses over the course of rapidly progressive infection are not well defined. Detailed longitudinal analyses of neutralizing antibodies, lymphocyte proliferation, in vivo-activated and memory cytotoxic T-lymphocyte (CTL) responses, and viral sequence variation were performed on a patient who presented with acute HIV-1 infection, developed an AIDS-defining illness 13 months later, and died 45 months after presentation. Neutralizing-antibody responses remained weak throughout, and no HIV-1-specific lymphocyte proliferative responses were seen even early in the disease course. Strong in vivo-activated CTL directed against Env and Pol epitopes were present at the time of the initial drop in viremia but were quickly lost. Memory CTL against Env and Pol epitopes were detected throughout the course of infection; however, these CTL were not activated in vivo. Despite an initially narrow CTL response, new epitopes were not targeted as the disease progressed. Viral sequencing showed the emergence of variants within the two targeted CTL epitopes; however, viral variants within the immunodominant Env epitope were well recognized by CTL, and there was no evidence of viral escape from immune system detection within this epitope. These data demonstrate a narrowly directed, static CTL response in a patient with rapidly progressive disease. We also show that disease progression can occur in the presence of persistent memory CTL recognition of autologous epitopes and in the absence of detectable escape from CTL responses, consistent with an in vivo defect in activation of CTL. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Univ Colorado, Hlth Sci Ctr, Div Infect Dis, Denver, CO 80262 USA. Northwestern Univ, Sch Med, Dept Med, Div Infect Dis, Chicago, IL 60611 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Ctr AIDS Res, Durham, NC 27710 USA. RP Walker, BD (reprint author), Partners AIDS Res Ctr, MGH E,149 13th St,Room 5212D, Charlestown, MA 02129 USA. RI Wolinsky, Steven/B-2893-2012; OI Wolinsky, Steven/0000-0002-9625-6697 FU NIAID NIH HHS [AI29193, F32 AI009822, R01 AI029193, R01 AI040873, R01 AI40873, R37 AI028568, R37 AI28568] NR 53 TC 78 Z9 80 U1 0 U2 0 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 JUL PY 1999 VL 73 IS 7 BP 5509 EP 5519 PG 11 WC Virology SC Virology GA 205GT UT WOS:000080813500030 PM 10364299 ER PT J AU Bauer, PH Cui, CQ Stehle, T Harrison, SC DeCaprio, JA Benjamin, TL AF Bauer, PH Cui, CQ Stehle, T Harrison, SC DeCaprio, JA Benjamin, TL TI Discrimination between sialic acid-containing receptors and pseudoreceptors regulates polyomavirus spread in the mouse SO JOURNAL OF VIROLOGY LA English DT Article ID TISSUE-SPECIFIC EXPRESSION; MURINE POLYOMAVIRUS; DNA-REPLICATION; SIALYLOLIGOSACCHARIDE RECEPTORS; ENHANCER REQUIREMENTS; NONCODING SEQUENCES; TUMOR-INDUCTION; VIRUS; MICE; VP1 AB Variations in the polyomavirus major capsid protein VP1 underlie important biological differences between highly pathogenic large-plaque and relatively nonpathogenic small-plaque strains. These polymorphisms constitute major determinants of virus spread in mice and also dictate previously recognized strain differences in sialyloligosaccharide binding. X-ray crystallographic studies have shown that these determinants affect binding to the sialic acids. Here,ve report results of further experiments designed to test the importance of specific contacts between VP1 and the carbohydrate moieties of the receptor. With minor exceptions, substitutions at positions predicted from crystallography to be important in binding the terminal alpha-2,3-linked sialic acid or the penultimate sugar (galactose) destroyed the ability of the virus to replicate in cell culture. Substitutions that prevented binding to a branched disialyloligosaccharide were found to result in viruses that were both viable in culture and tumorigenic in the mouse. Conversely, substitutions that allowed recognition and binding of the branched carbohydrate chain inhibited spread in the mouse, though the viruses remained viable in culture. Mice of five different inbred strains, all highly susceptible to large-plaque virus, showed resistance to the spread of polyomavirus strains bearing the VP1 type which binds the branched-chain receptor, We suggest that glycoproteins bearing the appropriate O-linked branched sialyloligosaccharide chains are effective pseudoreceptors in the host and that they block the spread of potentially tumorigenic or virulent virus strains. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. Harvard Univ, Howard Hughes Med Inst, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Benjamin, TL (reprint author), Harvard Univ, Sch Med, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [R35-CA44343, CA13202, P01 CA050661, P01-CA50661, R01 CA013202, R37 CA013202] NR 34 TC 63 Z9 63 U1 0 U2 6 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 JUL PY 1999 VL 73 IS 7 BP 5826 EP 5832 PG 7 WC Virology SC Virology GA 205GT UT WOS:000080813500065 PM 10364334 ER PT J AU von Gegerfelt, AS Liska, V Ray, NB McClure, HM Ruprecht, RM Felber, BK AF von Gegerfelt, AS Liska, V Ray, NB McClure, HM Ruprecht, RM Felber, BK TI Persistent infection of rhesus macaques by the Rev-independent Nef(-) simian immunodeficiency virus SIVmac239: Replication kinetics and genomic stability SO JOURNAL OF VIROLOGY LA English DT Article ID CONSTITUTIVE TRANSPORT ELEMENT; POLYMERASE CHAIN-REACTION; MESSENGER-RNA EXPORT; POSTTRANSCRIPTIONAL REGULATION; RETROVIRUS TYPE-1; VIRAL LOAD; MONKEYS; DISEASE; SIV; PATHOGENICITY AB We generated previously a Nef(-), replication-competent clone of SIVmac239 in which the Rev protein and the Rev-responsive element were replaced by the constitutive transport element (CTE) of simian retrovirus type 1 (A. S. von Gegerfelt and B. K. Feliber, Virology 232:291-299, 1997). In the present report, we show that this virus was able to infect and replicate in rhesus macaques. The Rev-independent Nef(-) simian immunodeficiency virus induced a persistent humoral immune response in all monkeys, although viral loads were very low. Upon propagation in the monkeys, the genotype remained stable and the virus retained its in vitro growth characteristics. The infected monkeys showed normal hematological values and no signs of disease at more than 18 months post-virus exposure. Therefore, replacement of the essential Rev regulation by the CTE generated a virus variant that retained its replicative capacity both in vitro and in vivo, albeit at low levels. C1 NCI, ABL Basic Res Program, FCRDC, Human Retrovirus Pathogenesis Grp, Frederick, MD 21702 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30322 USA. RP Felber, BK (reprint author), NCI, ABL Basic Res Program, FCRDC, Human Retrovirus Pathogenesis Grp, Bldg 535,Rm 110, Frederick, MD 21702 USA. FU NCRR NIH HHS [RR-00165, P51 RR000165]; PHS HHS [R01 A135533-S1] NR 30 TC 13 Z9 13 U1 0 U2 0 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 JUL PY 1999 VL 73 IS 7 BP 6159 EP 6165 PG 7 WC Virology SC Virology GA 205GT UT WOS:000080813500107 PM 10364376 ER PT J AU LeBlanc, ES Viscoli, CM Henrich, JB AF LeBlanc, ES Viscoli, CM Henrich, JB TI Postmenopausal estrogen replacement therapy is associated with adverse breast cancer prognostic indices SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Article ID UNITED-STATES; HORMONE-THERAPY; WOMEN; RISK; MORTALITY; INDICATORS; RECEPTOR; SURVIVAL; DISEASE; COHORT AB Previous studies have reported that breast cancer patients who used estrogen replacement therapy (ERT) have more favorable tumor characteristics and decreased mortality compared with nonusers. However, these findings may be due partly to increased medical surveillance in ERT users and detection of early stage tumors. Postmenopausal women with biopsy-proven breast cancer (n = 108) were identified based on their participation in screening mammography. Based on self-administered questionnaires completed at the time of mammography, 29 of these were users of ERT. Tumor characteristics (histology size, nodal status, and estrogen receptor content) of ERT users were compared with those of nonusers. After adjusting for potentially confounding variables, the odds ratios (OR) describing the relationship between ERT use and the risk of invasive histopathology (OR = 1.35, 95% CI = 0.48, 3.75), positive nodes (OR = 2.43, 95% CI = 0.59, 10.10), size greater than or equal to 2.0 cm (OR = 2.34, CI = 0.66, 8.27), or negative estrogen receptor status (OR = 1.08, 95% CI = 0.18, 9.38) were >1, although none reached statistical significance. When the subjects were separated into two prognostic groups based on the presence or absence of adverse prognostic indices, ERT users had a statistically significantly increased risk of being in the poor prognostic group (tumor size greater than or equal to 2.0 cm or positive nodes or negative estrogen receptor content) (OR = 4.48, 95% CI = 1.10, 18.30). The risk was highest in current users (OR = 6.28, 95% CI = 1.16, 34.00), users for 5 or more years (OR = 7.77, 95% CI = 1.09, 55.60), and users of nonconjugated estrogen (OR = 9.63, 95% CI = 1.18, 78.60). Although our sample size is small and we do not currently have information on longterm outcomes, the findings from this screening population suggest that ERT may have an adverse effect on important breast cancer prognostic indices. C1 Portland VA Med Ctr, Dept Internal Med, Portland, OR 97207 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. RP LeBlanc, ES (reprint author), Portland VA Med Ctr, Dept Internal Med, 3710 SW US Vet Hosp Rd,Mail Code P3GFEL, Portland, OR 97207 USA. FU NCRR NIH HHS [RR05358] NR 31 TC 10 Z9 10 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PD JUL-AUG PY 1999 VL 8 IS 6 BP 815 EP 823 DI 10.1089/152460999319138 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 232GB UT WOS:000082361600014 PM 10495262 ER PT J AU Rodriguez, M Caravaca, F Fernandez, E Borrego, MJ Lorenzo, V Cubero, J Martin-Malo, A Betriu, A Jimenez, A Torres, A Felsenfeld, AJ AF Rodriguez, M Caravaca, F Fernandez, E Borrego, MJ Lorenzo, V Cubero, J Martin-Malo, A Betriu, A Jimenez, A Torres, A Felsenfeld, AJ TI Parathyroid function as a determinant of the response to calcitriol treatment in the hemodialysis patient SO KIDNEY INTERNATIONAL LA English DT Article DE calcium; hyperparathyroidism; parathyroid hormone; dialysis ID CHRONIC DIALYSIS PATIENTS; CHRONIC-RENAL-FAILURE; SECONDARY HYPERPARATHYROIDISM; INTRAVENOUS CALCITRIOL; SET-POINT; HORMONE RELEASE; UREMIC PATIENTS; IN-VITRO; SURGICAL-TREATMENT; SERUM PHOSPHATE AB Background. Bolus calcitriol (CTR) is used for the treatment of secondary hyperparathyroidism in dialysis patients. Although CTR treatment reduces parathyroid hormone (PTH) levels in many dialysis patients, a significant number fail to respond. Methods. To learn whether or not an analysis of parathyroid function could further illuminate the response to CTR, a PTH-calcium curve was performed before and after at least two months of CTR treatment in 50 hemodialysis patients with a predialysis intact PTH of greater than 300 pg/ml. Results. For the entire group (N = 50), CTR treatment resulted in a 24% reduction in predialysis (basal) PTH from 773 +/- 54 to 583 +/- 71 pg/ml (P < 0.001), whereas ionized calcium increased from 1.10 +/- 0.02 to 1.22 +/- 0.02 mM (P < 0.001): however, maximal and minimal PTH did not change from pre-CTR values. Based on whether or not the basal PTH decreased by 40% or more during CTR treatment, patients were divided into responders (Rs, N = 25) and nonresponders (NRs, N = 25). Before CTR, the NR group was characterized by a greater basal (959 +/- 80 vs. 586 +/- 51 pg/ml, P < 0.001) and maximal (1899 +/- 170 vs. 1172 +/- 108 pg/ml, P < 0.001) PTH and serum phosphorus (6.14 +/- 0.25 vs. 5.14 +/- 0.34 mg/dl, P < 0.01). Logistical regression analysis showed that the pre-CTR basal PTH was the most important predictor of the post-CTR basal PTH. and a pre-CTR basal PTH of 750 pg/ml represented a 50% probability of a response. Basal PTH correlated with the ionized calcium in the NR group (r = 0.59, P = 0.002) but not in the R group (r = 0.06, P = NS). In the R group, an inverse correlation was present between ionized calcium and the basal/maximal PTH ratio, an indicator of whether calcium is suppressing basal PTH secretion relative to the maximal secretory capacity (maximal PTH) r = -0.55, P = 0.004; in the NR group, this correlation approached significance but was positive (r = 0.34, P = 0.09). After CTR treatment, serum calcium increased in both groups, and despite marked differences in basal PTH (Rs, 197 +/- 25 vs. NRs, 969 +/- 85 pg/ml), an inverse correlation between ionized calcium and basal/maximal PTH was present in both groups (Rs, r = -0.61, P = 0.001, and NRs, r = -0.60, P = 0.001). Conclusions. (a) Dynamic testing of parathyroid function provided insights into the pathophysiology of PTH secretion in hemodialysis patients. (b) The magnitude of hyperparathyroidism was the most important predictor of the response to CTR. (c) Before CTR treatment, PTH was sensitive to calcium in Rs, and serum calcium was PTH driven in NRs, and (d) after the CTR-induced increase in serum calcium, calcium suppressed basal PTH relative to maximal PTH in both groups. C1 Hosp Univ Reina Sofia, Serv Nephrol, Cordoba, Spain. Hosp Infanta Cristina, Badajoz, Spain. Hosp Reina Sofia, Unidad Invest, Cordoba 14004, Spain. Hosp Univ, Tenerife, Spain. Univ Lleida, Dept Med, Lleida, Spain. W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. RP Rodriguez, M (reprint author), Hosp Reina Sofia, Unidad Invest, Avda Menendez Pidal S-N, Cordoba 14004, Spain. RI Betriu Bars, Angels/C-3792-2011; Rodriguez, teresa/H-5452-2011; Fernandez Giraldez, Elvira Dolores/D-3358-2009 OI Fernandez Giraldez, Elvira Dolores/0000-0001-5236-1762 NR 43 TC 34 Z9 34 U1 0 U2 3 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUL PY 1999 VL 56 IS 1 BP 306 EP 317 DI 10.1046/j.1523-1755.1999.00538.x PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 209GQ UT WOS:000081040200034 PM 10411707 ER PT J AU Vacanti, JP Langer, R AF Vacanti, JP Langer, R TI Tissue engineering: the design and fabrication of living replacement devices for surgical reconstruction and transplantation SO LANCET LA English DT Article ID MASKING C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 27 TC 113 Z9 118 U1 3 U2 43 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUL PY 1999 VL 354 SU 1 BP SI32 EP SI34 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 223DV UT WOS:000081825900009 PM 10437854 ER PT J AU Kelly, K AF Kelly, K TI The illustrated encyclopedia of body-mind disciplines. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp Lib, Boston, MA USA. RP Kelly, K (reprint author), Massachusetts Gen Hosp Lib, Boston, MA 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 JUL PY 1999 VL 124 IS 12 BP 83 EP 83 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 216WH UT WOS:000081467100063 ER PT J AU Kelly, K AF Kelly, K TI The family encyclopedia of health: The complete family reference guide to alternative & orthodox medical diagnosis, treatment & preventative healthcare. 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 JUL PY 1999 VL 124 IS 12 BP 84 EP 84 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 216WH UT WOS:000081467100068 ER PT J AU Marks, PW Bandura, JL Shieh, DB Foernzler, D Beier, DR Kwiatkowski, DJ AF Marks, PW Bandura, JL Shieh, DB Foernzler, D Beier, DR Kwiatkowski, DJ TI The spontaneous coat color mutant white nose (wn) maps to murine Chromosome 15 SO MAMMALIAN GENOME LA English DT Article ID MOUSE; MUTATIONS; MODEL C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Hematol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Genet, Boston, MA 02115 USA. RP Marks, PW (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL54188, KO8 HL03235]; NIDDK NIH HHS [DK45639] NR 9 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD JUL PY 1999 VL 10 IS 7 BP 750 EP 752 DI 10.1007/s003359901084 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 211FL UT WOS:000081149800018 PM 10384053 ER PT J AU Sachs, RK Ponomarev, AL Hahnfeldt, P Hlatky, LR AF Sachs, RK Ponomarev, AL Hahnfeldt, P Hlatky, LR TI Locations of radiation-produced DNA double strand breaks along chromosomes: a stochastic cluster process formalism SO MATHEMATICAL BIOSCIENCES LA English DT Article DE DNA double strand breaks; non-random chromosome breakage; Poisson cluster point process; ionizing radiation; LET ID FIELD GEL-ELECTROPHORESIS; IONIZING-RADIATION; FUNCTIONAL COMPARTMENTALIZATION; INTERPHASE CHROMOSOMES; ENERGY DEPOSITION; TRACK STRUCTURE; DAMAGE; NUCLEUS; CELLS; ARCHITECTURE AB Ionizing radiation produces DNA double strand breaks (DSBs) in chromosomes. For densely ionizing radiation, the DSBs are not spaced randomly along a chromosome: recent data for size distributions of DNA fragments indicate break clustering on kbp-Mbp scales. Different DSB clusters on a chromosome are typically made by different, statistically independent, stochastically structured radiation tracks, and the average number of tracks involved can be small. We therefore model DSB positions along a chromosome as a stationary Poisson cluster process, i.e. a stochastic process consisting of secondary point processes whose locations are determined by a primary point process that is Poisson, Each secondary process represents a break cluster, typically consisting of 1-10 DSBs in a comparatively localized stochastic pattern determined by chromatin geometry and radiation track structure. Using this Poisson cluster process model, which we call the randomly located clusters (RLC) formalism, theorems are derived for how the DNA fragment-size distribution depends on radiation dose. The RLC dose-response relations become non-linear when the dose becomes so high that DSB clusters from different tracks overlap or adjoin closely. The RLC formalism generalizes previous models, fits current data adequately and facilitates mechanistically based extrapolations from high-dose experiments to the much lower doses of interest for most applications. (C) 1999 Elsevier Science Inc, All rights reserved. C1 Univ Calif Berkeley, Dept Math, Berkeley, CA 94720 USA. Harvard Univ, Sch Med, DFCI, JCRT, Boston, MA 02115 USA. RP Sachs, RK (reprint author), Univ Calif Berkeley, Dept Math, Berkeley, CA 94720 USA. FU NIGMS NIH HHS [GM 57245-01] NR 37 TC 30 Z9 30 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0025-5564 J9 MATH BIOSCI JI Math. Biosci. PD JUL PY 1999 VL 159 IS 2 BP 165 EP 187 DI 10.1016/S0025-5564(99)00019-X PG 23 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 215LX UT WOS:000081384100005 PM 10414032 ER PT J AU Verheijen, MHG Karperien, M Chung, UI van Wijuen, M Heystek, H Hendriks, JAA Velmaat, JM Lanske, B Li, E Lowik, CWGM de Laat, SW Kronenberg, HM Defize, LHK AF Verheijen, MHG Karperien, M Chung, UI van Wijuen, M Heystek, H Hendriks, JAA Velmaat, JM Lanske, B Li, E Lowik, CWGM de Laat, SW Kronenberg, HM Defize, LHK TI Parathyroid hormone-related peptide (PTHrP) induces parietal endoderm formation exclusively via the Type I PTH/PTHrP receptor (vol 81, pg 151, 1999) SO MECHANISMS OF DEVELOPMENT LA English DT Correction C1 Netherlands Inst Dev Biol, Hubrecht Lab, NL-3584 CT Utrecht, Netherlands. Univ Leiden Hosp, Dept Endocrinol, Leiden, Netherlands. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Defize, LHK (reprint author), Netherlands Inst Dev Biol, Hubrecht Lab, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands. NR 1 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD JUL PY 1999 VL 85 IS 1-2 BP 215 EP 215 PG 1 WC Developmental Biology SC Developmental Biology GA 223AW UT WOS:000081818400024 ER PT J AU Smith, AR AF Smith, AR TI Intensity-modulated conformal radiation therapy and 3-dimensional treatment planning will significantly reduce the need for therapeutic approaches with particles such as protons - Against the proposition SO MEDICAL PHYSICS LA English DT Article C1 Massachusetts Gen Hosp, Dept Radiat Oncol, NE Proton Therapy Ctr, Boston, MA 02114 USA. RP Smith, AR (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, NE Proton Therapy Ctr, Boston, MA 02114 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 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 JUL PY 1999 VL 26 IS 7 BP 1187 EP 1187 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 217TL UT WOS:000081515000002 ER PT J AU Koval, JA Maezono, K Patti, ME Pendergrass, M DeFronzo, RA Mandarino, LJ AF Koval, JA Maezono, K Patti, ME Pendergrass, M DeFronzo, RA Mandarino, LJ TI Effects of exercise and insulin on insulin signaling proteins in human skeletal muscle SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE insulin signaling; exercise; skeletal muscle; insulin receptor ID RECEPTOR TYROSINE KINASES; GLYCOGEN-SYNTHASE; INDUCED TRANSLOCATION; GLUCOSE TRANSPORTERS; PHOSPHATIDYLINOSITOL 3-KINASE; STIMULATION; ACTIVATION; CONTRACTIONS; WORTMANNIN; METABOLISM AB Insulin and exercise independently increase glucose metabolism in muscle. Moreover, exercise training or a prior bout of exercise increases insulin-stimulated glucose uptake in resting skeletal muscle. The present study was undertaken to compare how physiological hyperinsulinemia and moderate intensity aerobic exercise affect the tyrosine phosphorylation state and activity of insulin signaling molecules in healthy, physically inactive volunteers. Subjects had biopsies of the vastus lateralis muscle before and immediately after 30 min of either hyperinsulinemia (euglycemic insulin clamp) or moderate-intensity exercise on a cycle ergometer (similar to 60% of (V) over dot O-2max). Insulin receptor and IRS-1 tyrosine phosphorylation, association of the p85 regulatory subunit of PI 3-kinase with IRS-1, IRS-1 associated PIS-kinase activity, and glycogen synthase activity were determined in muscle biopsy specimens taken from healthy subjects before and after insulin or exercise. Physiological hyperinsulinemia increased the rare of glucose disposal from 11.4 +/- 1.5 to 25.6 +/- 6.7 mu mol . kg(-1) . min(-1) (P < 0.01), insulin receptor and IRS-I tyrosine phosphorylation (173 +/- 19% and 159 +/- 35% of basal values, respectively, P < 0.05), association of the p85 regulatory subunit of PI 3-kinase with IRS-1 (159 +/- 10%, P < 0.05), and glycogen synthase fractional velocity (136 +/- 11%, P < 0.01). Exercise also increased glucose disposal, from 10.4 +/- 0.5 to 15.6 +/- 1.7 mu mol . kg(-1) . min(-1) (P < 0.01) and glycogen synthase fractional velocity (253 +/- 35% of basil, P < 0.01. The exercise-induced increase in glycogen synthase was greater than that due to insulin (P < 0.05). In contrast to insulin, exercise decreased tyrosine phosphorylation of the insulin receptor to 72 +/- 10% of basal values (P < 0.05 vs basal and P < 0.05 vs insulin) and had no effect on IRS-1 tyrosine phosphorylation, or association of p85 with IRS-1. The exercise-induced decreased insulin receptor tyrosine phosphorylation could explain the well-known effect of exercise to enhance the sensitivity of muscle to insulin. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Diabet, San Antonio, TX 78284 USA. Joslin Diabet Ctr, Boston, MA USA. RP Mandarino, LJ (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Diabet, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NCRR NIH HHS [RR01346]; NIDDK NIH HHS [R01DK24092, R01DK47936] NR 38 TC 31 Z9 31 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD JUL PY 1999 VL 31 IS 7 BP 998 EP 1004 DI 10.1097/00005768-199907000-00012 PG 7 WC Sport Sciences SC Sport Sciences GA 213TG UT WOS:000081288900012 PM 10416561 ER PT J AU Singh, AK Dobashi, K Gupta, MP Asayama, K Singh, I Orak, JK AF Singh, AK Dobashi, K Gupta, MP Asayama, K Singh, I Orak, JK TI Manganese superoxide dismutase in rat liver peroxisomes: Biochemical and immunochemical evidence SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE peroxisomes; superoxide dismutase; antioxidant enzymes; free radicals; immunolocalization ID TUMOR NECROSIS FACTOR; GLUTATHIONE-PEROXIDASE; ANTIOXIDANT ENZYMES; LOCALIZATION; INDUCTION; INTERLEUKIN-1; PURIFICATION; EXPRESSION; CELLS AB By using highly purified peroxisomes from rat liver, we have shown that peroxisomes contain manganese superoxide dismutase (MnSOD) activity and a 23 kDa protein immunoreactive with antibodies against purified mitochondrial MnSOD. Immunocytochemical studies have also revealed immunoreaction (immunogold) with MnSOD antibodies in mitochondria and peroxisomes. Studies of the intraperoxisomal localization of MnSOD have shown that in peroxisomes MnSOD is a component of the peroxisomal limiting membranes and dense core. Furthermore, the MnSOD level in peroxisomes was modulated by oxidative stress conditions such as ischemia-reperfusion or the treatment with ciprofibrate, a peroxisomal proliferator. These findings suggest that MnSOD in peroxisomes may play an important role in the dismutation of superoxide generated on the peroxisomal membrane for keeping the delicate balance of the redox state. C1 Ralph H Johnson Vet Affairs Med Ctr, Dept Pathol & Lab Med, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Yamanashi Med Univ, Dept Pediat, Yamanashi, Japan. RP Singh, AK (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Dept Pathol & Lab Med, Charleston, SC 29401 USA. FU NINDS NIH HHS [NS-34741, NS-22576, NS-37766] NR 42 TC 12 Z9 13 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD JUL PY 1999 VL 197 IS 1-2 BP 7 EP 12 DI 10.1023/A:1006848113499 PG 6 WC Cell Biology SC Cell Biology GA 237JE UT WOS:000082651700002 PM 10485318 ER PT J AU Nevel-McGarvey, CA Rohrmann, D Levin, RM Hudson, AP AF Nevel-McGarvey, CA Rohrmann, D Levin, RM Hudson, AP TI Mitochondrial and mitochondia-related nuclear genetic function in rabbit urinary bladder following reversal of outlet obstruction SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE outlet obstruction; bladder; mitochondria; transcription; RNA ID EXPRESSION AB Partial outlet obstruction of the rabbit urinary bladder causes increased tissue hypertrophy and decreased contractility of that organ; we showed that, in an experimental rabbit model, both correlate closely with alterations in the status and expression of mitochondrial (mt), and mt-related nuclear, genetic parameters in bladder smooth muscle. Here we investigate the rate and overall level of recovery of mt and nuclear genetic function following reversal of outlet obstruction in the same animal model. Release from outlet obstruction at 28 days resulted in improvement in both level of hypertrophy and contractile function in all bladders studied. However, bladders fell into two groups based on whether relative copy mt genome number per cell was above or below that of unobstructed controls. Bladders with high mt DNA content adjusted organellar genome copy number toward normal post-reversal but did not properly adjust mt transcript levels; mt-related nuclear transcripts in these samples showed recovery. Bladders with low mt DNA content showed no adjustment of those levels toward normal post-reversal but did show some adjustment in other mt and nuclear genetic parameters. Thus, a limiting factor for return of normal bladder function following reversal of outlet obstruction may be recovery of normal mt genetic performance. C1 Allegheny Univ Hlth Sci, MCP Hahnemann Sch Med, Dept Microbiol & Immunol, Philadelphia, PA 19102 USA. Univ Penn, Sch Med, Div Urol, Dept Surg, Philadelphia, PA 19104 USA. Albany Coll Pharm, Albany, NY USA. Vet Affairs Med Ctr, Med Res Serv, Philadelphia, PA USA. RP Wayne State Univ, Sch Med, Dept Immunol & Microbiol, Gordon H Scott Hall,540 E Canfield Ave, Detroit, MI 48201 USA. FU NIDDK NIH HHS [DK-26508, DK-44689, DK-33559] NR 25 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 EI 1573-4919 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD JUL PY 1999 VL 197 IS 1-2 BP 161 EP 172 DI 10.1023/A:1006945732718 PG 12 WC Cell Biology SC Cell Biology GA 237JE UT WOS:000082651700019 PM 10485335 ER PT J AU Xia, K Lee, RS Narsimhan, RP Mukhopadhyay, NK Neel, BG Roberts, TM AF Xia, K Lee, RS Narsimhan, RP Mukhopadhyay, NK Neel, BG Roberts, TM TI Tyrosine phosphorylation of the proto-oncoprotein Raf-1 is regulated by Raf-1 itself and the phosphatase Cdc25A SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INDEPENDENT PATHWAY; ACTIVATES RAF-1; CELL-CYCLE; KINASE; INTERFERON; MEMBRANE; RECEPTOR; HOMOLOG; SHC AB There is a growing body of evidence demonstrating that Raf-1 is phosphorylated on tyrosines upon stimulation of a variety of receptors. Although detection of Raf-1 tyrosine phosphorylation has remained elusive, genetic analyses have demonstrated it to be important for Raf-1 activation. Here we report new findings which indicate that Raf-1 tyrosine phosphorylation is regulated in vivo. In both a mammalian and baculovirus expression system, a kinase inactive allele of Raf-1 was found to be tyrosine phosphorylated at levels much greater than that of wild-type Raf-1. The level of tyrosine phosphate on Raf-1 was markedly increased upon treatment with phosphatase inhibitors either before or after cell lysis. Cdc25A was found to dephosphorylate Raf-1 on tyrosines that resulted in a significant decrease in Raf-1 kinase activity. In NIH 3T3 cells, coexpression of wild-type Raf-1 and phosphatase-inactive Cdc25A led to a marked increase in Raf-1 tyrosine phosphorylation in response to platelet-derived growth factor. These data suggest that the tyrosine phosphorylation of Raf-1 is regulated not only by itself but also by Cdc25A. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div HST, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Canc Biol Program, Boston, MA 02115 USA. RP Roberts, TM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Smith 970, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA049152, 2RO1CA43803-11A1, R37 CA049152, CA49152] NR 33 TC 39 Z9 39 U1 0 U2 0 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 JUL PY 1999 VL 19 IS 7 BP 4819 EP 4824 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 207TR UT WOS:000080952300029 PM 10373531 ER PT J AU Garcia-Higuera, I Kuang, Y Naf, D Wasik, J D'Andrea, AD AF Garcia-Higuera, I Kuang, Y Naf, D Wasik, J D'Andrea, AD TI Fanconi anemia proteins FANCA, FANCC, and FANCG/XRCC9 interact in a functional nuclear complex SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID STRAND-BREAK REPAIR; C-GENE-PRODUCT; CROSS-LINKS; DNA-REPAIR; CELLS; FAC; COMPLEMENTATION; APOPTOSIS; CYTOPLASM; PHOSPHORYLATION AB Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome with at least eight complementation groups (A to H). Three FA genes, corresponding to complementation groups A, C, and G, have been cloned, but their cellular function remains unknown. We have previously demonstrated that the FANCA and FANCC proteins interact and form a nuclear complex in normal cells, suggesting that the proteins cooperate in a nuclear function. In this report, we demonstrate that the recently cloned FANCG/XRCC9 protein is required for binding of the FANCA and FANCC proteins. Moreover, the FANCG protein is a component of a nuclear protein complex containing FANCA and FANCC. The amino-terminal region of the FANCA protein is required for FANCG binding, FANCC binding, nuclear localization, and functional activity of the complex. Our results demonstrate that the three cloned FA proteins cooperate in a large multisubunit complex. Disruption of this complex results in the specific cellular and clinical phenotype common to most FA complementation groups. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. RI Garcia-Higuera, Irene/L-5004-2014 FU NCI NIH HHS [P01 CA039542, P01-CA39542]; NHLBI NIH HHS [R01-HL5725] NR 47 TC 188 Z9 191 U1 1 U2 6 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 JUL PY 1999 VL 19 IS 7 BP 4866 EP 4873 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 207TR UT WOS:000080952300034 PM 10373536 ER PT J AU Liu, JQ Barnett, A Neufeld, EJ Dudley, JP AF Liu, JQ Barnett, A Neufeld, EJ Dudley, JP TI Homeoproteins CDP and SATB1 interact: Potential for tissue-specific regulation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MAMMARY-TUMOR VIRUS; LONG TERMINAL REPEAT; MATRIX-ATTACHMENT REGION; CCAAT DISPLACEMENT PROTEIN; CELL-SPECIFIC ENHANCER; DNA-BINDING PROTEIN; HOMEODOMAIN PROTEIN; NEGATIVE REGULATION; TRANSCRIPTION FACTOR; GENE-TRANSCRIPTION AB Homeoproteins are known to participate in development and cell type specification. The homeoproteins CCAAT displacement protein (CDP) and special AT-rich sequence binding protein 1 (SATB1) have been shown to bind to nuclear matrix-associated regions and to act as repressors of many cellular genes. Moreover, binding of SATB1 to the mouse mammary tumor virus (MMTV) promoter region dramatically affects the tissue-specific transcription of this retrovirus. Because protein-protein interactions are a common means of regulating homeoprotein function, we tested whether SATB1 and CDP interact in vivo and in vitro. SATB1 interacted with CDP through its DNA-binding domain, as demonstrated by glutathione S-transferase (GST) pull-down assays. GST pull-down assays also showed that CDP associated with SATB1 through three of its four DNA-binding domains (CR1, CR2, and the homeodomain). SATB1-specific antisera, but not preimmune sera, precipitated CDP from nuclear extracts, and CDP-specific antisera precipitated SATB1 from the same extracts. Far-Western blotting detected interaction of SATB1 and CDP in several different tissue extracts. Association of purified SATB1 and CDP in vitro resulted in the inability of each protein to bind to DNA in gel retardation assays. CDP overexpression in cultured T cells led to a loss of detectable SATB1 binding to the MMTV promoter region, as measured by gel shift experiments. CDP overexpression also elevated MMTV long terminal repeat reporter gene activity in transient-transfection assays, a result consistent with neutralization of the SATB1 repressor function in T cells. SATB1 is very abundant in certain tissues, particularly thymus, whereas CDP is relatively ubiquitous, except in certain terminally differentiated cell types. Because of the tissue and cell type distribution of SATB1 and CDP, we propose that the SATB1-to-CDP ratio in different tissues is a novel mechanism for homeoproteins to control gene expression and differentiation in mammals. C1 Univ Texas, Dept Microbiol, Austin, TX 78712 USA. Univ Texas, Inst Mol & Cellular Biol, Austin, TX 78712 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Dudley, JP (reprint author), Univ Texas, Dept Microbiol, ESB 226, Austin, TX 78712 USA. RI Neufeld, Ellis/F-9331-2011 FU NCI NIH HHS [CA34780]; NHLBI NIH HHS [HL49196]; NIDDK NIH HHS [DK01977] NR 61 TC 40 Z9 47 U1 0 U2 1 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 JUL PY 1999 VL 19 IS 7 BP 4918 EP 4926 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 207TR UT WOS:000080952300039 PM 10373541 ER PT J AU Novina, CD Kumar, S Bajpai, U Cheriyath, V Zhang, KM Pillai, S Wortis, HH Roy, AL AF Novina, CD Kumar, S Bajpai, U Cheriyath, V Zhang, KM Pillai, S Wortis, HH Roy, AL TI Regulation of nuclear localization and transcriptional activity of TFII-I by Bruton's tyrosine kinase SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID X-LINKED AGAMMAGLOBULINEMIA; B-CELL RECEPTOR; PLECKSTRIN HOMOLOGY DOMAIN; V-BETA PROMOTER; PH DOMAIN; SRC FAMILY; MEMBRANE ASSOCIATION; BINDING PROTEIN; CROSS-LINKING; CBA/N MICE AB Bruton's tyrosine kinase (Btk) is required for normal B-cell development, as defects in Btk lead to X-linked immunodeficiency (xid) in mice and X-linked agammaglobulinemia (XLA) in humans. Here we demonstrate a functional interaction between the multifunctional transcription factor TFII-I and Btk. Ectopic expression of wild-type Btk enhances TFII-I-mediated transcriptional activation and its tyrosine phosphorylation in transient-transfection assays. Mutation of Btk in either the PH domain (R28C, as in the murine rid mutation) or the kinase domain (K430E) compromises its ability to enhance both the tyrosine phosphorylation and the transcriptional activity of TFII-I. TFII-I associates constitutively in vivo with wild-type Btk and kinase-inactive Btk but not rid Btk. However, membrane immunoglobulin M cross-linking in B cells leads to dissociation of TFII-I from Btk. We further show that while TFII-I is found in both the nucleus and cytoplasm of wild-type and rid primary resting B cells, nuclear TFII-I is greater in rid B cells. Most strikingly, receptor cross linking of wild-type (but not xid) B cells results in increased nuclear import of TFII-I. Taken together, these data suggest that although the PH domain of Btk is primarily responsible for its physical interaction with TFII-I, an intact kinase domain of Btk is required to enhance transcriptional activity of TFII-I in the nucleus. Thus, mutations impairing the physical and/or functional association between TFII-I and Btk may result in diminished TFII-I-dependent transcription and contribute to defective B-cell development and/or function. C1 Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA. Tufts Univ, Sch Med, Program Immunol, Boston, MA 02111 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Roy, AL (reprint author), Tufts Univ, Sch Med, Dept Pathol, 136 Harrison Ave, Boston, MA 02111 USA. FU NCI NIH HHS [CA 69618]; NIAID NIH HHS [AI 15803, AI 33507, R01 AI033507] NR 79 TC 84 Z9 85 U1 0 U2 0 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 JUL PY 1999 VL 19 IS 7 BP 5014 EP 5024 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 207TR UT WOS:000080952300049 PM 10373551 ER PT J AU Chen, Q Zhang, Y Johnson, DM Goetinck, PF AF Chen, Q Zhang, Y Johnson, DM Goetinck, PF TI Assembly of a novel cartilage matrix protein filamentous network: Molecular basis of differential requirement of von Willebrand factor A domains SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID I-DOMAIN; A-DOMAIN; LIGAND-BINDING; MONOCLONAL-ANTIBODIES; CRYSTAL-STRUCTURE; CATION-BINDING; INTEGRIN; COLLAGEN; EXPRESSION; SUBUNIT AB Cartilage matrix protein (CMP) is the prototype of the newly discovered matrilin family, all of which contain von Willebrand factor A domains. Although the function of matrilins remain unclear, we have shown that, in primary chondrocyte cultures, CMP (matrilin-1) forms a filamentous network which is made up of two types of filaments, a collagen-dependent one and a collagen-independent one. In this study, we demonstrate that the collagen-independent CMP filaments are enriched in pericellular compartments, extending directly from chondrocyte membranes. Their morphology can be distinguished from that of collagen filaments by immunogold electron microscopy, and mimicked by that of self-assembled purified CMP. The assembly of CMP filaments can occur from transfection of a wild-type CMP transgene alone in skin fibroblasts, which do not produce endogenous CMP. Conversely, assembly of endogenous CMP filaments by chondrocytes can be inhibited specifically by dominant negative CMP transgenes. The two A domains within CMP serve essential but different functions during network formation. Deletion of the A2 domain converts the trimeric CMP into a mixture of monomers, dimers, and trimers, whereas deletion of the Al domain does not affect the trimeric configuration. This suggests that the A2 domain modulates multimerization of CMP. Absence of either A domain from CMP abolishes its ability to form collagen-independent filaments. in particular, Asp(22) in A1 and Asp(255) in A2 are essential; double point mutation of these residues disrupts CMP network formation. These residues are part of the metal ion-dependent adhesion sites, thus a metal ion-dependent adhesion site-mediated adhesion mechanism may be applicable to matrilin assembly. Taken together, our data suggest that CMP is a bridging molecule that connects matrix components in cartilage to form an integrated matrix network. C1 Penn State Univ, Coll Med, Dept Orthopaed & Rehabil, Musculoskeletal Res Lab, Hershey, PA 17033 USA. Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Chen, Q (reprint author), Penn State Univ, Coll Med, Dept Orthopaed & Rehabil, Musculoskeletal Res Lab, Hershey, PA 17033 USA. RI Chen, Qian/C-4354-2011 OI Chen, Qian/0000-0003-4406-5618 FU NIA NIH HHS [R01 AG014399, AG-14399, AG-17021, R01 AG017021, R29 AG014399, Z01 AG000811]; NIGMS NIH HHS [P20 GM104937] NR 34 TC 53 Z9 53 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JUL PY 1999 VL 10 IS 7 BP 2149 EP 2162 PG 14 WC Cell Biology SC Cell Biology GA 217TQ UT WOS:000081515400005 PM 10397755 ER PT J AU Karperien, M Farih-Sips, H Hendriks, JAA Lanske, B Papapoulos, SE Abou-Samra, AB Lowik, CWGM Defize, LHK AF Karperien, M Farih-Sips, H Hendriks, JAA Lanske, B Papapoulos, SE Abou-Samra, AB Lowik, CWGM Defize, LHK TI Identification of a retinoic acid-inducible element in the murine PTH PTHrP (parathyroid hormone parathyroid hormone-related peptide) receptor gene SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID EMBRYONAL CARCINOMA-CELLS; PROMOTER TRANSCRIPTION FACTOR; PROTEIN-LINKED RECEPTOR; (PTH)/PTH-RELATED PEPTIDE; X RECEPTOR; RESPONSE ELEMENT; MESSENGER-RNA; UBIQUITOUS PROMOTERS; RXR HETERODIMERS; ORPHAN RECEPTORS AB We have shown previously that the PTH/PTHrP (PTH-related peptide) receptor mRNA becomes expressed very early in murine embryogenesis, i.e. during the formation of extraembryonic endoderm. Retinoic Acid (RA) is a potent inducer of extraembryonic endoderm formation and PTH/PTHrP-receptor expression in embryonal carcinoma (EC) and embryonal stem (ES) cells. Using the P19 EC cell line, we have characterized promoter elements of the murine PTH/PTHrP-receptor gene that are involved in this RA-induced expression. The data show that RA-induced expression of the PTH/PTHrP-receptor gene is mediated by the downstream P2 promoter. Analysis of promoter reporter constructs in transiently transfected P19 cells treated with RA identified an enhancer region between nucleotides -2714 and -2702 upstream of the P2 transcription start site that is involved in the RA effect. This region matches a consensus hormone response element consisting of a direct repeat with an interspacing of 1 bp (R-DR1). The R-DR1 efficiently binds retinoic acid receptor-alpha (RAR alpha)-retinoid X receptor-alpha (RXR alpha) and chicken ovalbumin upstream promoter (COUP)-transcription factor I (TFI)-RXR alpha heterodimers and RXR alpha and COUP-TFI homodimers in a bandshift assay using extracts of transiently transfected COS-7 cells. RA differentiation of P19 EC cells strongly increases protein binding to the R-DR1 in a bandshift assay. This is caused by increased expression of RXR (alpha, beta, or gamma) and by the induction of expression of RAR beta and COUP TFI/TFII, which bind to the R-DR1 as shown by supershifting antibodies. The presence of RXR (alpha, beta, or gamma) in the complexes binding to the R-DR1 suggests that RXR homodimers are involved in RA-induced expression of the PTH/PTHrP-receptor gene. The importance of the R-DR1 for RA-induced expression of PTH/PTHrP-receptor was shown by an inactivating mutation of the R-DR1, which severely impairs RA-induced expression of PTH/PTHrP-receptor promoter reporter constructs. Since this mutation does not completely abolish RA-induced expression of PTH/PTHrP-receptor promoter reporter constructs, sequences other than the R-DR1 might also be involved in the RA effect. Finally, we show that the RA-responsive promoter region is also able to induce expression of a reporter gene in extraembryonic endoderm of 7.5 day-old transgenic mouse embryos. C1 Leiden Univ, Med Ctr, Dept Endocrinol, NL-2300 RC Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Pediat, NL-2300 RC Leiden, Netherlands. Netherlands Inst Dev Biol, NL-3584 CT Utrecht, Netherlands. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Karperien, M (reprint author), Leiden Univ, Med Ctr, Dept Endocrinol & Metab Dis, Bldg 1,C4-R Albinusdreef 2,OB 9600, NL-2333 ZA Leiden, Netherlands. OI Abou-Samra, Abdul/0000-0001-8735-1142 NR 44 TC 15 Z9 15 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUL PY 1999 VL 13 IS 7 BP 1183 EP 1196 DI 10.1210/me.13.7.1183 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 210UK UT WOS:000081122900012 PM 10406468 ER PT J AU Frank, DA AF Frank, DA TI STAT signaling in the pathogenesis and treatment of cancer SO MOLECULAR MEDICINE LA English DT Review ID EPIDERMAL GROWTH-FACTOR; CHRONIC MYELOGENOUS LEUKEMIA; COLONY-STIMULATING FACTOR; PROTEIN-TYROSINE KINASE; DNA-BINDING ACTIVITY; CHRONIC MYELOMONOCYTIC LEUKEMIA; ANTI-INTERLEUKIN-6 MONOCLONAL-ANTIBODY; CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA AB Exceptional advances have been made recently in our understanding of the signaling pathways that control cellular growth, differentiation, and survival. These processes are regulated by extracellular stimuli such as cytokines, cell-cell interactions, and cell-matrix interactions, which trigger a series of intracellular events culminating in the modulation of specific genes. STATs are a highly homologous group of transcription factors that are activated by various pathways and regulate many of the genes controlling cellular function. STATs are activated by tyrosine phosphorylation and modulated by serine phosphorylation, placing them at a convergence point for numerous intracellular signaling pathways. Given the importance of STATs in the control of normal physiologic processes, it is not surprising that inappropriate activation of these proteins has been found in human malignancies. A number of distinct mechanisms have been elucidated by which STATs are activated inappropriately, including autocrine or paracrine stimulation of normal receptors and increased activity of tyrosine kinases through enhanced expression, mutations, or the presence of activating proteins. Furthermore, inappropriate STAT serine phosphorylation has been found in several tumors as well. The increased understanding of signaling pathways in rumors can be translated into therapeutic strategies that have the potential to be more selective and less to;dc than current anti-cancer treatments. Approaches which may be effective include the development of antagonists of receptors that can trigger STAT activation, inhibitors of the tyrosine and serine kinases that phosphorylate and activate sTATs, agents that decrease STAT levels or inhibit their recruitment to kinases, and molecules that can prevent the binding of STATs to target DNA sequences. Thus, elucidation of cellular and biochemical processes in tumors has enhanced our understanding of the pathogenesis of malignancies and may provide the basis for significant advances in therapy. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Frank, DA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA79547] NR 244 TC 79 Z9 81 U1 0 U2 6 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD JUL PY 1999 VL 5 IS 7 BP 432 EP 456 PG 25 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 227MM UT WOS:000082084200002 PM 10449805 ER PT J AU Harris, RS Feng, G Ross, KJ Sidhu, R Thulin, C Longerich, S Szigety, SK Hastings, PJ Winkler, ME Rosenberg, SM AF Harris, RS Feng, G Ross, KJ Sidhu, R Thulin, C Longerich, S Szigety, SK Hastings, PJ Winkler, ME Rosenberg, SM TI Mismatch repair is diminished during stationary-phase mutation SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH LA English DT Editorial Material DE stationary-phase mutation; adaptive mutation; spontaneous mutation; resting cell; mismatch repair; Escherichia coli, MutL ID ESCHERICHIA-COLI K-12; DEPENDENT ADAPTIVE MUTATION; FRAMESHIFT MUTATION; DNA; RECOMBINATION; MUTD5; CELLS; HYPERMUTATION; MUTAGENESIS; SATURATION AB This paper is an invited Response to a recent Commentary [P.L. Foster, Rev. Mut. Res. 436 (1999) 179-184] entitled "Are adaptive mutations due to a decline in mismatch repair? The evidence is lacking". The Commentary argues that no evidence exists supporting the idea that mismatch repair is limiting specifically during stationary-phase mutation. A primary concern of the author is to question the method that we used previously to measure growth-dependent mutation. In this method, mutation rates are calculated using counts of mutant colonies taken at times when those colonies arise, rather than at a predetermined, fixed time, Here we show further data that illustrate why this must be done to ensure accurate mutation measurements. Such accuracy was necessary for our published determination that mismatch repair proteins are not limiting during growth-dependent mutation, but become so during stationary-phase mutation. We review the evidence supporting the idea that stationary-phase reversion of a lac frameshift mutation occurs in an environment of decreased mismatch repair capacity. Those data are substantial. The data presented in the Commentary, in apparent contradiction to this idea, do not justify the conclusion presented there. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Univ Texas, Sch Med, Dept Microbiol & Mol Genet, Houston, TX 77030 USA. Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT USA. Queens Univ, Sch Med, Kingston, ON, Canada. Univ Alberta, Dept Med Microbiol & Immunol, Edmonton, AB, Canada. Massachusetts Gen Hosp, Dept Hematol & Oncol, Boston, MA 02114 USA. Univ Alberta, Dept Biochem, Edmonton, AB, Canada. RP Rosenberg, SM (reprint author), Baylor Coll Med, Dept Mol & Human Genet, 1 Baylor Plaza T922BCMS-5809-A, Houston, TX 77030 USA. FU NCI NIH HHS [R01CA77193]; NIAID NIH HHS [R01AI43917]; NIGMS NIH HHS [R01GM53158] NR 51 TC 53 Z9 55 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5742 J9 MUTAT RES-REV MUTAT JI Mutat. Res.-Rev. Mutat. Res. PD JUL PY 1999 VL 437 IS 1 BP 51 EP 60 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 227WE UT WOS:000082102300004 PM 10425389 ER PT J AU Brodsky, AS Silver, PA AF Brodsky, AS Silver, PA TI Nuclear transport HEATs up SO NATURE CELL BIOLOGY LA English DT Article ID LOCALIZATION SIGNAL; PROTEIN; IMPORT AB Importins, proteins that transport macromolecules into the nucleus, interact with cargo and regulatory molecules at different times in the transport cycle. We are now closer to understanding the structural basis of these interactions. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Brodsky, AS (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. FU NIGMS NIH HHS [R37 GM036373] NR 16 TC 3 Z9 3 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD JUL PY 1999 VL 1 IS 3 BP E66 EP E67 PG 2 WC Cell Biology SC Cell Biology GA 245HY UT WOS:000083102500007 PM 10559913 ER PT J AU Cargill, M Altshuler, D Ireland, J Sklar, P Ardlie, K Patil, N Lane, CR Lim, EP Kalyanaraman, N Nemesh, J Ziaugra, L Friedland, L Rolfe, A Warrington, J Lipshutz, R Daley, GQ Lander, ES AF Cargill, M Altshuler, D Ireland, J Sklar, P Ardlie, K Patil, N Lane, CR Lim, EP Kalyanaraman, N Nemesh, J Ziaugra, L Friedland, L Rolfe, A Warrington, J Lipshutz, R Daley, GQ Lander, ES TI Characterization of single-nucleotide polymorphisms in coding regions of human genes SO NATURE GENETICS LA English DT Article ID HUMAN LIPOPROTEIN-LIPASE; SEQUENCE VARIATION; HUMAN GENOME; ALLELE; DIVERSITY; MUTATION; DISEASE AB A major goal in human genetics is to understand the role of common genetic variants in susceptibility to common diseases. This will require characterizing the nature of gene variation in human populations, assembling an extensive catalogue of single-nucleotide polymorphisms (SNPs) in candidate genes and performing association studies for particular diseases. At present, our knowledge of human gene variation remains rudimentary. Here we describe a systematic survey of SNPs in the coding regions of human genes. We identified SNPs in 106 genes relevant to cardiovascular disease, endocrinology and neuropsychiatry by screening an average of 114 independent alleles using 2 independent screening methods. To ensure high accuracy, all reported SNPs were confirmed by DNA sequencing. We identified 560 SNPs, including 392 coding-region SNPs (cSNPs) divided roughly equally between those causing synonymous and non-synonymous changes. We observed different rates of polymorphism among classes of sites within genes (non-coding, degenerate and non-degenerate) as well as between genes. The cSNPs most likely to influence disease, those that alter the amino acid sequence of the encoded protein, are found at a lower rate and with lower allele frequencies than silent substitutions. This likely reflects selection acting against deleterious alleles during human evolution. The lower allele frequency of missense cSNPs has implications for the compilation of a comprehensive catalogue, as well as for the subsequent application to disease association. C1 MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Endocrinol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Hematol, Boston, MA 02114 USA. Affymetrix Inc, Santa Clara, CA 95051 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Lander, ES (reprint author), MIT, Whitehead Inst, Ctr Genome Res, 1 Kendall Sq,Bldg 300, Cambridge, MA 02139 USA. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 32 TC 1295 Z9 1427 U1 7 U2 79 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 1999 VL 22 IS 3 BP 231 EP 238 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 210VT UT WOS:000081125900014 PM 10391209 ER PT J AU Pierce, EA Quinn, T Meehan, T McGee, TL Berson, EL Dryja, TP AF Pierce, EA Quinn, T Meehan, T McGee, TL Berson, EL Dryja, TP TI Mutations in a gene encoding a new oxygen-regulated photoreceptor protein cause dominant retinitis pigmentosa SO NATURE GENETICS LA English DT Article ID MESSENGER-RNA; DIFFERENTIAL DISPLAY; RHODOPSIN GENE; ONE FORM; DNA; LINKAGE; REGION; RP1 AB The autosomal dominant retinitis pigmentosa (RP) locus, designated RP1, has been mapped through linkage studies to a 4-cM interval at 8q11-13. Here we describe a new photoreceptor-specific gene that maps in this interval and whose expression is modulated by retinal oxygen levels in vivo. This gene consists of at least 4 exons that encode a predicted protein of 2,156 amino acids. A nonsense mutation at codon 677 of this gene is present in approximately 3% of cases of dominant RP in North America. We also detected two deletion mutations that cause frameshifts and introduce premature termination codons in three other families with dominant RP. Our data suggest that mutations in this gene cause dominant RP, and that the encoded protein has an important but unknown role in photoreceptor biology. C1 Univ Penn, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Stellar Chance Labs 311, Philadelphia, PA 19104 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA 02114 USA. RP Pierce, EA (reprint author), Univ Penn, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Stellar Chance Labs 311, 422 Curie Blvd, Philadelphia, PA 19104 USA. FU NEI NIH HHS [EY00169, EY08689, EY12910] NR 36 TC 113 Z9 124 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 1999 VL 22 IS 3 BP 248 EP 254 DI 10.1038/10305 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 210VT UT WOS:000081125900016 PM 10391211 ER PT J AU Fleming, JC Tartaglini, E Steinkamp, MP Schorderet, DF Cohen, N Neufeld, EJ AF Fleming, JC Tartaglini, E Steinkamp, MP Schorderet, DF Cohen, N Neufeld, EJ TI The gene mutated in thiamine-responsive anaemia with diabetes and deafness (TRMA) encodes a functional thiamine transporter SO NATURE GENETICS LA English DT Article ID MEGALOBLASTIC-ANEMIA SYNDROME; SACCHAROMYCES-CEREVISIAE; DATABASE; CELLS AB Thiamine-responsive megaloblastic anaemia with diabetes and deafness(1) (TRMA; MIM 249270) is an autosomal recessive disease thought to be due to a defect in thiamine (vitamin B1) transport(2,3). Pharmacological doses of thiamine correct the anaemia, and in some cases improve the diabetes, although progressive sensorineural deafness is irreversible(4). Previous studies localized the TRMA gene to a 4-cM region on chromosome 1q23.3 (ref. 5), and fine-mapping has recently narrowed that region further(6,7). We have previously demonstrated that fibroblasts from people with TRMA lack high-affinity thiamine transports. Expression of a gene encoding a known yeast thiamine transporter, THI10 (refs 8-10), in TRMA mutant cells prevents apoptotic cell death in thiamine-depleted medium. On the basis of these studies, we hypothesized that a defective thiamine transporter causes TRMA. We undertook a candidate gene approach to identify putative thiamine transporters in the 1q23.3 critical region. Here we present evidence that the gene SLC19A2 (for solute carrier family 19 (thiamine transporter), member 2) encodes the first known mammalian thiamine transporter, which we designate thiamine transporter-1 (THTR-1). C1 Childrens Hosp, Dana Farber Canc Inst, Div Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Ancona, Inst Biochem, I-60100 Ancona, Italy. CHU Vaudois, Div Med Genet, CH-1011 Lausanne, Switzerland. Technion Israel Inst Technol, Bruce Rappaport Fac Med, Tamkin Human Mol Genet Res Facil, Dept Genet, IL-31096 Haifa, Israel. RP Neufeld, EJ (reprint author), Childrens Hosp, Dana Farber Canc Inst, Div Hematol, Boston, MA 02115 USA. RI Neufeld, Ellis/F-9331-2011; OI Steinkamp, Mara/0000-0003-1226-9325 FU NHLBI NIH HHS [T32 HL07574] NR 18 TC 144 Z9 145 U1 0 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 1999 VL 22 IS 3 BP 305 EP 308 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 210VT UT WOS:000081125900027 PM 10391222 ER PT J AU Moore, RJ Owens, DM Stamp, G Arnott, C Burke, F East, N Holdsworth, H Turner, L Rollins, B Pasparakis, M Kollias, G Balkwill, F AF Moore, RJ Owens, DM Stamp, G Arnott, C Burke, F East, N Holdsworth, H Turner, L Rollins, B Pasparakis, M Kollias, G Balkwill, F TI Mice deficient in tumor necrosis factor-alpha are resistant to skin carcinogenesis SO NATURE MEDICINE LA English DT Article ID MULTISTAGE CARCINOGENESIS; CANCER; EXPRESSION; PROMOTION; PREVENTION; METASTASIS; INHIBITION; FOLLICLES; DISEASE AB Given the associations between chronic inflammation and epithelial cancer(1,2) , we studied susceptibility to skin carcinogenesis(3,4) in mice deficient for the pro-inflammatory cytokine TNF-alpha (refs. 5,6). TNF-alpha(-/-) mice were resistant to development of benign and malignant skin tumors, whether induced by initiation with DMBA and promotion with TPA or by repeated dosing with DMBA. TNF-alpha(-/-) mice developed 5-10% the number of tumors developed by wild-type mice during initiation/promotion and 25% of those in wild-type mice after repeated carcinogen treatment. TNF-alpha could influence tumor and stromal cells during tumor development. The early stages of TPA promotion are characterized by keratinocyte hyperproliferation and inflammation. These were diminished in TNF-alpha(-/-) mice. TNF-alpha was extensively induced in the epidermis, but not the dermis, in TPA-treated wild-type skin, indicating that dermal inflammation is controlled by keratinocyte TNF-a production. Deletion of a TNF-alpha inducible chemokine also conferred some resistance to skin tumor development. TNF-alpha has little influence on later stages of carcinogenesis, as tumors in wild-type and TNF-alpha(-/-) mice had similar rates of malignant progression. These data provide evidence that a pro-inflammatory cytokine is required for de novo carcinogenesis and that TNF-alpha is important to the early stages of tumor promotion. Strategies that neutralize TNF-alpha production may be useful in cancer treatment and prevention. C1 Imperial Canc Res Fund, Biol Therapy Lab, London WC2A 3PX, England. Imperial Canc Res Fund, Keratinocyte Lab, London WC2A 3PX, England. Univ London Imperial Coll Sci Technol & Med, Div Invest Sci, Dept Histopathol, London W12 0NN, England. Imperial Canc Res Fund, Clare Hall Labs, S Mimms EN6 3LD, Herts, England. Hellen Pasteur Inst, Dept Mol Genet, GR-11521 Athens, Greece. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Balkwill, F (reprint author), Imperial Canc Res Fund, Biol Therapy Lab, POB 123, London WC2A 3PX, England. RI Kollias, George/A-7079-2012 OI Kollias, George/0000-0003-1867-3150 NR 21 TC 587 Z9 600 U1 2 U2 10 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 JUL PY 1999 VL 5 IS 7 BP 828 EP 831 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 224YB UT WOS:000081926600040 PM 10395330 ER PT J AU Lewis, J Oyler, GA Ueno, K Fannjiang, YR Chau, BN Vornov, J Korsmeyer, SJ Zou, SF Hardwick, JM AF Lewis, J Oyler, GA Ueno, K Fannjiang, YR Chau, BN Vornov, J Korsmeyer, SJ Zou, SF Hardwick, JM TI Inhibition of virus-induced neuronal apoptosis by Bax SO NATURE MEDICINE LA English DT Article ID DRUG-INDUCED APOPTOSIS; CELL-DEATH; BCL-2; CONVERSION; MODULATION; BCL-X(L); PROTEIN; MICE AB The Bax protein is widely known as a pro-apoptotic Bcl-2 family member that when overexpressed can trigger apoptosis in multiple cell types and is important for the developmental cell death of neurons(1,2). However, Bax was found here to be a potent inhibitor of neuronal cell death in mice infected with Sindbis virus. Newborn mice, which are highly susceptible to a fatal infection with neurotropic Sindbis virus, were significantly protected from neuronal apoptosis and fatal disease when infected with a recombinant Sindbis virus encoding Bax. Deletion of the N terminus of Bax, which mimics cleaved Bax, converted Bax into a pro-apoptotic factor in vivo. As mice mature during the first week after birth, they acquire resistance to a fatal Sindbis virus infection(3,4). However, Bax-deficient mice remained very sensitive to fatal disease compared with their control littermates, indicating that endogenous Bax functions as a survival factor and contributes to age-dependent resistance to Sindbis virus-induced mortality. The protective effects of Bax were reproduced in cultured hippocampal neurons but not in cultured dorsal root ganglia neurons. These findings indicate that cell-specific factors determine the anti-apoptotic versus pro-apoptotic function of Bax. C1 Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. Kagoshima Univ, Fac Med, Ctr Chron Viral Dis, Kagoshima 8908520, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol & Med, Boston, MA 02115 USA. RP Hardwick, JM (reprint author), Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, E5132,SPH,615 N Wolfe St, Baltimore, MD 21205 USA. RI Vornov, James/F-6794-2013 OI Vornov, James/0000-0003-1965-5456 FU NINDS NIH HHS [NS34175] NR 25 TC 82 Z9 85 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 JUL PY 1999 VL 5 IS 7 BP 832 EP 835 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 224YB UT WOS:000081926600041 PM 10395331 ER PT J AU Freund, C Dotsch, V Nishizawa, K Reinherz, EL Wagner, G AF Freund, C Dotsch, V Nishizawa, K Reinherz, EL Wagner, G TI The GYF domain is a novel structural fold that is involved in lymphoid signaling through proline-rich sequences SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID T-CELL ACTIVATION; TANDEM SH2 DOMAINS; CYTOPLASMIC DOMAIN; TYROSINE KINASES; PROTEIN; CD2; ANTIGEN; MOTIF; IDENTIFICATION; BINDING AB T cell activation through the CD2 cell surface receptor is transmitted by proline-rich sequences within its cytoplasmic tail. A membrane-proximal proline-rich tandem repeat, involved in cytokine production, is recognized by the intracellular CD2 binding protein CD2BP2. We solved the solution structure of the CD2 binding domain of CD2BP2, which we name the glycine-tyrosine-phenylalanine (GYF) domain. The GYF sequence is part of a structurally unique bulge-helix-bulge motif that constitutes the major binding site for the CD2 tail. A hydrophobic surface patch is created by motif residues that are highly conserved among a variety of proteins from diverse eukaryotic species. Thus, the architecture of the GYF domain may be widely used in protein-protein associations. C1 Harvard Univ, Sch Med, 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 Freund, C (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RI Doetsch, Volker/D-5697-2011 NR 36 TC 67 Z9 69 U1 0 U2 6 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD JUL PY 1999 VL 6 IS 7 BP 656 EP 660 DI 10.1038/10712 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 212LE UT WOS:000081217500020 PM 10404223 ER PT J AU Segal, AZ Chiu, RI Eggleston-Sexton, PM Beiser, A Greenberg, SM AF Segal, AZ Chiu, RI Eggleston-Sexton, PM Beiser, A Greenberg, SM TI Low cholesterol as a risk factor for primary intracerebral hemorrhage: A case-control study SO NEUROEPIDEMIOLOGY LA English DT Article DE intracerebral hemorrhage; cholesterol; hypertension; amyloid angiopathy ID DENSITY-LIPOPROTEIN CHOLESTEROL; CEREBRAL AMYLOID ANGIOPATHY; ACUTE MYOCARDIAL-INFARCTION; APOLIPOPROTEIN-E EPSILON-4; SERUM-CHOLESTEROL; STROKE; PLASMA; LIPIDS; DISEASE; POPULATION AB We performed a case-control study to assess the relationship between primary intracerebral hemorrhage (ICH) and low serum cholesterol. Prospectively recruited, fully evaluated patients with ICH were compared to two independent control groups, one based in a primary care practice and one population-based. Low cholesterol was defined by the sex-specific lowest quintile of the primary care controls. The proportion of ICH cases with low cholesterol >3 months posthemorrhage was significantly greater than in controls (42 vs. 20% in either control group, p < 0.01). Subgroup analysis showed an overrepresentation of low cholesterols in probable hypertensive hemorrhage (47%, p < 0.05) but not in probable cerebral amyloid angiopathy (27%, p = 0.5). Low cholesterol increased the odds for hemorrhage 2.25-fold (1.12-4.50) after adjustment for age and apolipoprotein E genotype. These data confirm an increased risk for primary ICH associated with low cholesterol, a relationship that may apply specifically to hemorrhages from hypertensive vasculopathy. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Greenberg, SM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Wang ACC 836, Boston, MA 02114 USA. FU NIA NIH HHS [AG0072] NR 32 TC 61 Z9 63 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PD JUL-AUG PY 1999 VL 18 IS 4 BP 185 EP 193 DI 10.1159/000026210 PG 9 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 209XP UT WOS:000081075300003 PM 10364719 ER PT J AU Altshuler, D Hirschhorn, JN AF Altshuler, D Hirschhorn, JN TI Upsetting the balance: VGF and the regulation of body weight SO NEURON LA English DT Article ID OBESITY; MICE C1 MIT, Whitehead Inst Biomed Res, Ctr Genome Res, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Div Endocrinol, Boston, MA 02114 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Altshuler, D (reprint author), MIT, Whitehead Inst Biomed Res, Ctr Genome Res, Cambridge, MA 02139 USA. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 9 TC 2 Z9 2 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JUL PY 1999 VL 23 IS 3 BP 415 EP 417 DI 10.1016/S0896-6273(00)80793-X PG 3 WC Neurosciences SC Neurosciences & Neurology GA 221AA UT WOS:000081701000004 PM 10433252 ER PT J AU Naisbitt, S Kim, E Tu, JC Xiao, B Sala, C Valtschanoff, J Weinberg, RJ Worley, PF Sheng, M AF Naisbitt, S Kim, E Tu, JC Xiao, B Sala, C Valtschanoff, J Weinberg, RJ Worley, PF Sheng, M TI Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin SO NEURON LA English DT Article ID METABOTROPIC GLUTAMATE RECEPTORS; TUMOR-SUPPRESSOR PROTEIN; RAT-BRAIN; EXCITATORY SYNAPSES; HIPPOCAMPAL-NEURONS; WW DOMAINS; INTERACTS; ACTIN; PDZ; RECOGNITION AB NMDA receptors are linked to intracellular cytoskeletal and signaling molecules via the PSD-95 protein complex. We report a novel family of postsynaptic density (PSD) proteins, termed Shank, that binds via its PDZ domain to the C terminus of PSD-95-associated protein GKAP. A ternary complex of Shank/GKAP/PSD-95 assembles in heterologous cells and can be coimmunoprecipitated from rat brain. Synaptic localization of Shank in neurons is inhibited by a GKAP splice variant that lacks the Shank-binding C terminus. In addition to its PDZ domain, Shank contains a proline-rich region that binds to cortactin and a SAM domain that mediates multimerization. Shank may function as a scaffold protein in the PSD, potentially cross-linking NMDA receptor/PSD-95 complexes and coupling them to regulators of the actin cytoskeleton. C1 Massachusetts Gen Hosp, Dept Neurobiol, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA 02114 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Univ N Carolina, Dept Cell Biol & Anat, Chapel Hill, NC 27599 USA. Pusan Natl Univ, Dept Pharmacol, Pusan 609735, South Korea. RP Sheng, M (reprint author), Massachusetts Gen Hosp, Dept Neurobiol, Howard Hughes Med Inst, Boston, MA 02114 USA. RI Kim, Eunjoon/C-1566-2011; Sala, Carlo/A-2493-2009 OI Sala, Carlo/0000-0003-0662-9523 FU NIDA NIH HHS [DA103009]; NINDS NIH HHS [NS29879, NS35050] NR 53 TC 531 Z9 546 U1 1 U2 22 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JUL PY 1999 VL 23 IS 3 BP 569 EP 582 DI 10.1016/S0896-6273(00)80809-0 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 221AA UT WOS:000081701000020 PM 10433268 ER PT J AU Tu, JC Xiao, B Naisbitt, S Yuan, JP Petralia, RS Brakeman, P Doan, A Aakalu, VK Lanahan, AA Sheng, M Worley, PF AF Tu, JC Xiao, B Naisbitt, S Yuan, JP Petralia, RS Brakeman, P Doan, A Aakalu, VK Lanahan, AA Sheng, M Worley, PF TI Coupling of mGluR/Homer and PSD-95 complexes by the shank family of postsynaptic density proteins SO NEURON LA English DT Article ID METABOTROPIC GLUTAMATE RECEPTORS; LONG-TERM POTENTIATION; CEREBELLAR PURKINJE-CELLS; ALDRICH-SYNDROME PROTEIN; DENDRITIC SPINES; ENDOPLASMIC-RETICULUM; SYNAPTIC ACTIVATION; RAT HIPPOCAMPUS; LEUCINE-ZIPPER; INDUCTION AB Shank is a recently described family of postsynaptic proteins that function as part of the NMDA receptor-associated PSD-95 complex (Naisbitt et al., 1999 [this issue of Neuron]). Here, we report that Shank proteins also bind to Homer. Homer proteins form multivalent complexes that bind proline-rich motifs in group 1 metabotropic glutamate receptors and inositol trisphosphate receptors, thereby coupling these receptors in a signaling complex. A single Homer-binding site is identified in Shank, and Shank and Homer coimmunoprecipitate from brain and colocalize at postsynaptic densities. Moreover, Shank clusters mGluR5 in heterologous cells in the presence of Homer and mediates the coclustering of Homer with PSD-95/GKAP. Thus, Shank may cross-link Homer and PSD-95 complexes in the PSD and play a role in the signaling mechanisms of both mGluRs and NMDA receptors. C1 Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA 02114 USA. Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Worley, PF (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. FU NIDA NIH HHS [DA10309, DA11742]; NIMH NIH HHS [KO2 MH01152] NR 45 TC 620 Z9 637 U1 0 U2 21 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JUL PY 1999 VL 23 IS 3 BP 583 EP 592 DI 10.1016/S0896-6273(00)80810-7 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 221AA UT WOS:000081701000021 PM 10433269 ER PT J AU Cutrer, FM Yu, XJ Ayata, G Moskowitz, MA Waeber, C AF Cutrer, FM Yu, XJ Ayata, G Moskowitz, MA Waeber, C TI Effects of PNU-109,291, a selective 5-HT1D receptor agonist, on electrically induced dural plasma extravasation and capsaicin-evoked c-fos immunoreactivity within trigeminal nucleus caudalis SO NEUROPHARMACOLOGY LA English DT Article DE migraine; vascular headache; neurogenic inflammation; meninges; 5-HT1 receptors ID BOVINE CEREBRAL-ARTERIES; SEROTONIN RECEPTOR; ANTIMIGRAINE DRUG; BLOOD-VESSELS; BINDING-SITES; MESSENGER-RNA; GUINEA-PIG; INTRACISTERNAL CAPSAICIN; NEUROGENIC INFLAMMATION; PROTEIN EXTRAVASATION AB We studied the effects of PNU-109 291 [(S)-(-)-1-[2-[4-(4-methoxyphenyl)-1-piperazinyl]ethyl]-N-nethyl-isochroman-6-carbox-amide], a receptor agonist showing 5000-fold selectivity for primate 5-HTT1D versus 5-HT1B receptors (Ennis et al., J. Med. Chem. 41, 2180-2183), on dural neurogenic inflammation and on c-fos like immunoreactivity within trigeminal nucleus caudalis evoked by electrical and chemical activation of trigeminal afferents, respectively. Subcutaneous injection of PNU-109 291 in male guinea pigs dose-dependently reduced dural extravasation of [I-125]-labeled bovine serum albumin evoked by trigeminal ganglion stimulation with an IC50 of 4.2 nmol kg(-1). A dose of 73.3 nmol kg(-1) blocked the response completely. The selective 5-HT1B/1D receptor antagonist GR-127 935 (greater than or equal to 2 mu mol kg(-1) i.v.) prevented this effect. In addition, the number of c-fos immunoreactive cells within guinea pig trigeminal nucleus caudalis induced by chemical meningeal stimulation (intracisternally administered capsaicin) was reduced by more than 50% with PNU-109 291 (greater than or equal to 122.2 nmol kg(-1) administered s.c. 45 min before and 15 min after capsaicin). These data indicate that the 5-HT1D receptor subtype plays a significant role in suppressing meningeal neurogenic inflammation and attenuating trigeminal nociception in these guinea pig models. Since 5-HT1D receptor mRNA and protein are expressed in trigeminal ganglia but not vascular smooth muscle, the 5-HT1D receptor subtype may become a useful therapeutic target for migraine and related headaches. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurol & Neurosurg, Charlestown, MA 02129 USA. RP Cutrer, FM (reprint author), Massachusetts Gen Hosp, Dept Neurol & Neurosurg, CNY 149,Room 6403,149 13th St, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011; Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 FU NINDS NIH HHS [1-P01-NS35611-01, K08-NS-01803] NR 61 TC 25 Z9 27 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JUL PY 1999 VL 38 IS 7 BP 1043 EP 1053 DI 10.1016/S0028-3908(99)00032-5 PG 11 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 210VW UT WOS:000081126200014 PM 10428423 ER PT J AU Filley, CM Young, DA Reardon, MS Wilkening, GN AF Filley, CM Young, DA Reardon, MS Wilkening, GN TI Frontal lobe lesions and executive dysfunction in children SO NEUROPSYCHIATRY NEUROPSYCHOLOGY AND BEHAVIORAL NEUROLOGY LA English DT Article ID CARD SORTING TEST; PREFRONTAL CORTEX; TEST-PERFORMANCE; COGNITION; CHILDHOOD; BEHAVIOR; DAMAGE; INJURY AB Objective: To investigate the relationship of frontal lobe lesions and neuropsychologic performance in school-aged children to determine whether damage to frontal regions results in specific cognitive sequelae. Background: The role of the frontal lobes in executive function remains incompletely understood, particularly in children. Method: This retrospective study included children aged 8 to 17 with brain lesions of various etiology (n = 63) or diverse psychiatric disorders (n = 48). All were evaluated for details of neurologic and medical history and for scores on the Wechsler Intelligence Scale for Children (WISC-III) and the Wisconsin Card Sorting Test, and all but the psychiatric patients had neuroimaging scans. Five groups were analyzed - dorsolateral frontal, medial-orbital frontal, focal nonfrontal, diffuse, and psychiatric - and neuropsychologic test results were compared using a Kruskal-Wallis nonparametric analysis of variance. Results: Children with damage to dorsolateral frontal regions were more impaired on the Wisconsin Card Sorting Test than those in all other groups. Comparable performance on the Wechsler scale was found in all groups, suggesting that intellectual functioning did not account for this difference. Conclusions: These data provide evidence for a prominent role of the dorsolateral frontal regions in the mediation of executive function in children. They also support the use of the Wisconsin Card Sorting Test in children as a measure of dorsolateral frontal integrity. C1 Univ Colorado, Sch Med, Dept Neurol, Behav Neurol Sect, Denver, CO 80262 USA. Univ Colorado, Sch Med, Dept Prevent Med & Biometr, Denver, CO 80262 USA. Univ Colorado, Sch Med, Dept Pediat, Denver, CO 80262 USA. Univ Colorado, Sch Med, Dept Psychiat, Denver, CO 80262 USA. Childrens Hosp, Denver, CO 80218 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Filley, CM (reprint author), Univ Colorado, Sch Med, Dept Neurol, Behav Neurol Sect, UCHSC B-183,4200 E 9th Ave, Denver, CO 80262 USA. NR 25 TC 7 Z9 8 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-878X J9 NEUROPSY NEUROPSY BE JI Neuropsychiatr. Neuropsychol. Behav. Neurol. PD JUL PY 1999 VL 12 IS 3 BP 156 EP 160 PG 5 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 224LF UT WOS:000081900000003 PM 10456798 ER PT J AU Kozora, E Filley, CM Julian, LJ Cullum, M AF Kozora, E Filley, CM Julian, LJ Cullum, M TI Cognitive functioning in patients with chronic obstructive pulmonary disease and mild hypoxemia compared with patients with mild Alzheimer disease and normal controls SO NEUROPSYCHIATRY NEUROPSYCHOLOGY AND BEHAVIORAL NEUROLOGY LA English DT Article ID OXYGEN-THERAPY AB Objective: To examine neuropsychologic functions in patients with chronic obstructive pulmonary disease (COPD) and mild hypoxemia compared with patients with mild Alzheimer disease and normal controls. Background: Cognitive deficits have been documented in patients with COPD, but few studies have compared the neuropsychologic status of these patients with that of other neurologic groups. Method: Cognitive test results from 32 patients with COPD and mild hypoxemia (mean age, 70.3 years; mean education, 13.2 years; mean partial arterial oxygen pressure, 68.8 mm Hg) who had no neurologic symptoms were compared with 31 subjects with mild Alzheimer disease (AD) and 31 normal controls similar in age, education, and sex. Seventy-three percent of the patients with COPD were receiving supplementary oxygen. Results: Significant group differences across 11 cognitive scores were found using analysis of variance, and post hoc analyses indicated that patients with mild AD performed significantly worse than normal controls and patients with COPD on most tests. The group with COPD and the group with AD demonstrated lower letter fluency compared with controls. Although the patients with COPD performed significantly worse than controls on verbal fluency tasks, they were not in the clinically impaired range, and, overall, the group with COPD was similar to the controls on most cognitive tests. Conclusions: These findings suggest that many patients with COPD and mild hypoxemia who don't have neuropsychiatric histories may perform normally on cognitive measures. Oxygen therapy may partially account for preservation of cognitive function in these patients. Results also suggest that patients with COPD and normal controls can be readily distinguished from patients with mild AD based on levels and patterns of neuropsychologic test results. Any significant cognitive deficits in patients with mildly hypoxemic COPD may warrant continued neurologic evaluation. C1 Natl Jewish Med & Res Ctr, Denver, CO 80206 USA. Univ Colorado, Dept Psychiat, Denver, CO 80202 USA. Univ Colorado, Dept Neurol, Denver, CO 80202 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Penn State Univ, University Pk, PA 16802 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Neurol, Dallas, TX USA. RP Kozora, E (reprint author), Natl Jewish Med & Res Ctr, 1400 Jackson St,A111, Denver, CO 80206 USA. FU NIA NIH HHS [P01 AG09417] NR 30 TC 33 Z9 37 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-878X J9 NEUROPSY NEUROPSY BE JI Neuropsychiatr. Neuropsychol. Behav. Neurol. PD JUL PY 1999 VL 12 IS 3 BP 178 EP 183 PG 6 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 224LF UT WOS:000081900000007 PM 10456802 ER PT J AU Ogilvy, CS AF Ogilvy, CS TI Occult cerebral vascular lesions - Preface SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Ogilvy, CS (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, 55 Fruit St, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD JUL PY 1999 VL 10 IS 3 BP XI EP XI PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 220FE UT WOS:000081653200001 ER PT J AU Rabinov, JD AF Rabinov, JD TI Diagnostic imaging of angiographically occult vascular malformations SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article ID DEVELOPMENTAL VENOUS ANOMALIES; CENTRAL-NERVOUS-SYSTEM; MIDDLE CRANIAL FOSSA; FAMILIAL CAVERNOUS MALFORMATIONS; NATURAL-HISTORY; CAPILLARY TELANGIECTASIA; SPINAL-CORD; ARTERIOVENOUS MALFORMATION; BRAIN-STEM; ANGIOMAS AB Occult vascular malformations of the central nervous system include cavernous malformations, capillary telangiectasis, and developmental venous anomalies (DVAs). Cavernous malformations are prone to multiple small hemorrhages and may enlarge with time. They have a heterogeneous appearance on CT and MR imaging with areas of hemorrhage in various states of evolution and sometimes calcifications. Developmental venous anomalies and capillary telangiectasis are usually incidental findings on imaging studies. They usually are not the cause of pathology by themselves, although DVAs can be associated with cavernous malformations in 8% to 33% of cases. C1 Harvard Univ, Dept Neuroradiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Rabinov, JD (reprint author), Harvard Univ, Dept Neuroradiol, Massachusetts Gen Hosp, Sch Med, Gray 2,55 Fruit St, Boston, MA 02114 USA. NR 100 TC 22 Z9 25 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 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD JUL PY 1999 VL 10 IS 3 BP 419 EP + PG 15 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 220FE UT WOS:000081653200004 PM 10419569 ER PT J AU Ojemann, RG Ogilvy, CS AF Ojemann, RG Ogilvy, CS TI Microsurgical treatment of supratentorial cavernous malformations SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article ID SURGICAL-MANAGEMENT; NATURAL-HISTORY; NERVOUS-SYSTEM; ANGIOMAS AB The indications for the surgical management of supratentorial cavernous malformations are outlined and the results following operation are presented in this article. Surgery is indicated for most patients who present with seizures, neurologic deficit, or headache. The surgical approaches to lesions in the cerebrum are described. The operative morbidity and mortality are low. Over 95% of all patients have excellent or good results and return to their previous level of activity. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg,Neurosurg Serv, Boston, MA 02114 USA. RP Ojemann, RG (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, White 5,55 Fruit St, Boston, MA 02114 USA. NR 28 TC 16 Z9 16 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD JUL PY 1999 VL 10 IS 3 BP 433 EP + PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 220FE UT WOS:000081653200005 PM 10419570 ER PT J AU Amin-Hanjani, S Ogilvy, CS AF Amin-Hanjani, S Ogilvy, CS TI Overall surgical results of occult vascular malformations SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article ID INTRAMEDULLARY CAVERNOUS ANGIOMAS; SPINAL-CORD; BRAIN-STEM; CLINICAL PRESENTATION; MANAGEMENT; LESIONECTOMY; FEATURES; SURGERY AB Surgical experience with angiographically occult vascular malformations, specifically cavernous malformations (CMs), has increased substantially over recent years. CMs are generally well-circumscribed, low-pressure vascular lesions amenable to resection. Overall, results obtained with operative management have been favorable; however, the location of the lesion impacts significantly on the outcome and morbidity of surgery, with those located within deep and brain stem regions carrying a higher incidence of persistent neurologic complications. As knowledge emerges regarding the long-term natural history of these lesions, the role of operative intervention in cases where surgical morbidity is high will become better defined. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Ogilvy, CS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 55 Fruit St,VBK710, Boston, MA 02114 USA. NR 42 TC 3 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 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD JUL PY 1999 VL 10 IS 3 BP 475 EP + PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 220FE UT WOS:000081653200007 PM 10419572 ER PT J AU Stiver, SI AF Stiver, SI TI Microarteriovenous malformations SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article ID CEREBRAL ARTERIOVENOUS-MALFORMATIONS; HEREDITARY HEMORRHAGIC TELANGIECTASIA; OCCULT VASCULAR MALFORMATIONS; CEREBROVASCULAR MALFORMATIONS; NATURAL-HISTORY; MARKED GROWTH; BRAIN; SIZE; DIAGNOSIS; MANIFESTATIONS AB Microarteriovenous malformations (micro-AVMs) are a subgroup of brain AVM with a nidus diameter of less than 1 cm. Although many micro-AVMs may appear angiographically occult on cursory review, careful analysis will often reveal a subtle diagnostic feature. Micro-AVMs present with intracranial hemorrhages that are generally large and associated with significant neurologic impairment. An awareness of these lesions as a possible source of hemorrhage in a young person is critical. In general, micro-AVMs are eminently resectable lesions and patient outcome is determined primarily by the hemorrhage that brings them to medical attention. C1 Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Stiver, SI (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, VBK-710,32 Fruit St, Boston, MA 02114 USA. NR 57 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 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD JUL PY 1999 VL 10 IS 3 BP 485 EP + PG 18 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 220FE UT WOS:000081653200008 PM 10419573 ER PT J AU Cosgrove, GR AF Cosgrove, GR TI Occult vascular malformations and seizures SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article ID SUPRATENTORIAL CAVERNOUS MALFORMATIONS; CENTRAL-NERVOUS-SYSTEM; NATURAL-HISTORY; INTRACTABLE EPILEPSY; SURGICAL-TREATMENT; ANGIOMAS; LESIONECTOMY; RESECTION; LESIONS AB Occult vascular malformations are frequently associated with intractable seizures and are a common cause of lesional epilepsy. MR imaging can identify and characterize these lesions with accuracy. The presurgical evaluation must be tailored to the individual patient's presentation and circumstances. Surgical results following lesionectomy plus corticectomy may be slightly superior to lesionectomy alone, but the overall prognosis is excellent. C1 Massachusetts Gen Hosp, Neurosurg Serv, Epilepsy Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Cosgrove, GR (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Epilepsy Ctr, 15 Parkman St,ACC 331, Boston, MA 02114 USA. NR 27 TC 10 Z9 12 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 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD JUL PY 1999 VL 10 IS 3 BP 527 EP + PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 220FE UT WOS:000081653200012 PM 10419577 ER PT J AU Freed, LA Levy, D Levine, RA Larson, MG Evans, JC Fuller, DL Lehman, B Benjamin, EJ AF Freed, LA Levy, D Levine, RA Larson, MG Evans, JC Fuller, DL Lehman, B Benjamin, EJ TI Prevalence and clinical outcome of mitral-valve prolapse SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GENERAL-POPULATION; FOLLOW-UP; REGURGITATION; FEATURES; IDENTIFICATION; ASSOCIATION; DIAGNOSIS; WOMEN; RISK; MEN AB Background Mitral-valve prolapse has been described as a common disease with frequent complications. To determine the prevalence of mitral-valve prolapse in the general population, as diagnosed with the use of current two-dimensional echocardiographic criteria, we examined the echocardiograms of 1845 women and 1646 men (mean [+/-SD] age, 54.7+/-10.0 years) who participated in the fifth examination of the offspring cohort of the Framingham Heart Study. Methods Classic mitral-valve prolapse was defined as superior displacement of the mitral leaf lets of more than 2 mm during systole and as a maximal leaflet thickness of at least 5 mm during diastasis, and nonclassic prolapse was defined as displacement of more than 2 mm, with a maximal thickness of less than 5 mm. Results A total of 84 subjects (2.4 percent) had mitral-valve prolapse: 47 (1.3 percent) had classic prolapse, and 37 (1.1 percent) had nonclassic prolapse. Their age and sex distributions were similar to those of the subjects without prolapse. None of the subjects with prolapse had a history of heart failure, one (1.2 percent) had atrial fibrillation, one (1.2 percent) had cerebrovascular disease, and three (3.6 percent) had syncope, as compared with unadjusted prevalences of these findings in the subjects without prolapse of 0.7, 1.7, 1.5, and 3.0 percent, respectively. The frequencies of chest pain, dyspnea, and electrocardiographic abnormalities were similar among subjects with prolapse and those without prolapse. The subjects with prolapse were leaner (P<0.001) and had a greater degree of mitral regurgitation than those without prolapse, but on average the regurgitation was classified as trace or mild. Conclusions In a community-based sample of the population, the prevalence of mitral-valve prolapse was lower than previously reported. The prevalence of adverse sequelae commonly associated with mitral-valve prolapse in studies of patients referred for that diagnosis was also low. (N Engl J Med 1999;341:1-7.) (C)1999, Massachusetts Medical Society. C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NHLBI, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Div Clin Epidemiol, Boston, MA USA. Boston Univ, Sch Med, Div Cardiol, Boston, MA 02118 USA. Boston Univ, Sch Med, Div Epidemiol & Prevent Med, Boston, MA 02118 USA. RP Benjamin, EJ (reprint author), Boston Univ, Sch Med, Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. OI Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [2-R01-HL-38176-06, N01-HC-38038]; NINDS NIH HHS [5-R01-NS-17950-16] NR 40 TC 411 Z9 424 U1 1 U2 4 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 JUL 1 PY 1999 VL 341 IS 1 BP 1 EP 7 DI 10.1056/NEJM199907013410101 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 212BC UT WOS:000081195600001 PM 10387935 ER PT J AU Gilon, D Buonanno, FS Joffe, MM Leavitt, M Marshall, JE Kistler, JP Levine, RA AF Gilon, D Buonanno, FS Joffe, MM Leavitt, M Marshall, JE Kistler, JP Levine, RA TI Lack of evidence of an association between mitral-valve prolapse and stroke in young patients SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CEREBRAL ISCHEMIC EVENTS; LEAFLET PROLAPSE; EMBOLIC STROKE; RISK-FACTORS; PREVALENCE; DIAGNOSIS; CLASSIFICATION; REGURGITATION; POPULATION AB Background Previous studies have reported a high prevalence of mitral-valve prolapse among patients with embolic stroke (28 to 40 percent), especially among young patients (those less than or equal to 45 years old); this finding has practical implications for prophylaxis. However, diagnostic criteria for prolapse have changed and are now based on three-dimensional analysis of the shape of the valve; use of the current criteria reduces markedly the frequency of such a diagnosis and increases its specificity. Previously described complications must therefore be reconsidered. Methods In a case-control study, we reviewed data on 213 consecutive patients 45 years of age or younger with documented ischemic stroke or transient ischemic attack between 1985 and 1995; they underwent complete neurologic and echocardiographic evaluations. The prevalence of prolapse in these patients was compared with that in 263 control subjects without known heart disease, who were referred to our institution for assessment of ventricular function before receiving chemotherapy. Results Mitral-valve prolapse was present in 4 of the 213 young patients with stroke (1.9 percent), as compared with 7 of the 263 controls (2.7 percent); prolapse was present in 2 of 71 patients (2.8 percent) with otherwise unexplained stroke. The crude odds ratio for mitral-valve prolapse among the patients who had strokes, as compared with those who did not have strokes, was 0.70 (95 percent confidence interval, 0.15 to 2.80; P = 0.80); after adjustment for age and sex, the odds ratio was 0.59 (95 percent confidence interval, 0.12 to 2.50; P = 0.62). Conclusions Mitral-valve prolapse is considerably less common than previously reported among young patients with stroke or transient ischemic attack, including unexplained stroke, and no more common than among controls. Using more specific and currently accepted echocardiographic criteria, therefore, we could not demonstrate an association between the presence of mitral-valve prolapse and acute ischemic neurologic events in young people. (N Engl J Med 1999;341:8-13.) (C)1999, Massachusetts Medical Society. C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Stroke Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Levine, RA (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, VBK-508,32 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL38176, HL53702] NR 40 TC 78 Z9 80 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 JUL 1 PY 1999 VL 341 IS 1 BP 8 EP 13 DI 10.1056/NEJM199907013410102 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 212BC UT WOS:000081195600002 PM 10387936 ER PT J AU Goodfriend, TL Kelley, DE Goodpaster, BH Winters, SJ AF Goodfriend, TL Kelley, DE Goodpaster, BH Winters, SJ TI Visceral obesity and insulin resistance are associated with plasma aldosterone levels in women SO OBESITY RESEARCH LA English DT Article DE adrenal cortex; aldosterone; cardiovascular diseases; dehydroepiandrosterone sulfate; hypertension ID BLOOD-PRESSURE; WEIGHT-REDUCTION; HYPERTENSIVE SUBJECTS; GLOMERULOSA CELLS; ADIPOSE-TISSUE; RESTRICTION; SECRETION; SODIUM; HYPERINSULINEMIA; DENSITY AB Objective: Both obesity and insulin resistance increase the risk of hypertension and other cardiovascular diseases, but the mechanisms linking these abnormalities are unknown. The current study was undertaken to examine the effects of obesity, fat, distribution, and insulin resistance on plasma levels of aldosterone and other adrenal steroids that might contribute to sequelae of obesity. Research Methods and Procedures: Twenty-eight normotensive premenopausal women and 27 normotensive men with a wide range of body fat underwent measurements of visceral adipose tissue by CT scan, total fat mass by dual energy X-ray absorptiometry, blood pressure, insulin sensitivity, and plasma levels of three adrenal steroid hormones. Results: Plasma aldosterone in women correlated directly with visceral adipose tissue (r = 0.66, p < 0.001) and inversely with insulin sensitivity (r = -0.67, p < 0.001), and these associations were independent of plasma renin activity. There were no corresponding correlations in men. Plasma aldosterone was significantly correlated with plasma cortisol and dehydroepiandrosterone sulfate in women. Seventeen women and 15 men completed a weight-reduction regimen, losing an average of 15.1 +/- 1.2 kg. After weight loss, plasma aldosterone was significantly lower and insulin sensitivity higher; however, the correlations of aldosterone with visceral adipose tissue and insulin sensitivity in women persisted (p = 0.09 and 0.07, respectively). Although none of the women were hypertensive, blood pressure correlated with plasma aldosterone both before and after weight loss. Discussion: We conclude that visceral adiposity and insulin resistance are associated with increased plasma aldosterone and other adrenal steroids that may contribute to cardiovascular diseases in obese women. C1 William S Middleton Mem Vet Hosp, Res Serv, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Dept Med, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Dept Pharmacol, Madison, WI 53705 USA. Univ Pittsburgh, Dept Med, Div Endocrinol & Metab, Pittsburgh, PA USA. RP Goodfriend, TL (reprint author), William S Middleton Mem Vet Hosp, Res Serv, Room C-3127,2500 Overlook Terrace, Madison, WI 53705 USA. FU NCRR NIH HHS [5M01RR00056]; NIDDK NIH HHS [R01-DK49200-03, 1P30DK46204] NR 41 TC 104 Z9 104 U1 2 U2 3 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD JUL PY 1999 VL 7 IS 4 BP 355 EP 362 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 217UC UT WOS:000081516500005 PM 10440591 ER PT J AU Grondin, SC Sugarbaker, DJ AF Grondin, SC Sugarbaker, DJ TI Malignant mesothelioma of the pleural space SO ONCOLOGY-NEW YORK LA English DT Article ID MULTIMODALITY THERAPY; CONSECUTIVE PATIENTS; MANAGEMENT; DIAGNOSIS; DIFFUSE AB Malignant pleural mesothelioma is an aggressive tumor associated with exposure to asbestos. Although this disease is rare, with an annual incidence in the United States of 2,000 to 3,000 cases, a steady rise in cases has been reported. Malignant pleural mesothelioma has a variable clinical presentation and may be difficult to diagnose. Pathologically, the disease is subdivided into three microscopic subtypes; epithelial, sarcomatous, and mixed histologies. Although there is no widely accepted staging system for mesothelioma, the Butchart, TNM, and Brigham staging systems have been used most commonly. Diffuse malignant pleural mesothelioma is resistant to standard modes of therapy and, of untreated, results in death 4 to 12 months from the time of diagnosis. For selected patients, an aggressive approach combining radical surgery with chemotherapy and radiotherapy has demonstrated a long-term survival advantage. New and innovative therapeutic modalities are presently being investigated in an attempt to provide viable alternatives for patients with early and advanced disease. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Div Thorac Surg, Boston, MA 02115 USA. RP Sugarbaker, DJ (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. OI Vallieres, Eric/0000-0003-1732-2658 NR 41 TC 25 Z9 25 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUL PY 1999 VL 13 IS 7 BP 919 EP 926 PG 8 WC Oncology SC Oncology GA 392WD UT WOS:000166434800005 PM 10442339 ER PT J AU Wen, PY Loeffler, JS AF Wen, PY Loeffler, JS TI Management of brain metastases SO ONCOLOGY-NEW YORK LA English DT Review ID THERAPY-ONCOLOGY-GROUP; HIGH-DOSE IRRADIATION; CONTRAST-ENHANCED MR; CELL LUNG-CANCER; CEREBRAL METASTASES; RADIATION-THERAPY; SURGICAL-TREATMENT; STEREOTAXIC RADIOSURGERY; SYSTEMIC CHEMOTHERAPY; BREAST-CARCINOMA AB Brain metastases are the most common type of brain tumor in adults and are an increasingly important cause of morbidity and mortality in cancer patients. In recent years, important advances have been made in the diagnosis and management of brain metastases. These advances include the widespread use of magnetic resonance imaging (MRI) enabling small metastases to be detected; the introduction of stereotactic radiosurgery; and the performance of studies that have clarified the role of surgery and postoperative radiation therapy for single brain metastases. As a result, most patients receive effective palliation, and the majority do not die from their brain metastases. However, further studies are needed to define the optimal role of conventional treatments ann to develop more effective no vet therapies. C1 Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Proton Therapy Ctr, Boston, MA 02114 USA. RP Wen, PY (reprint author), Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, 75 Francis St, Boston, MA 02115 USA. NR 131 TC 95 Z9 99 U1 0 U2 1 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUL PY 1999 VL 13 IS 7 BP 941 EP + PG 17 WC Oncology SC Oncology GA 392WD UT WOS:000166434800011 PM 10442342 ER PT J AU Rubin, PAD Rumelt, S AF Rubin, PAD Rumelt, S TI Functional indications for enophthalmos repair SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID COMPUTED-TOMOGRAPHY; POSTTRAUMATIC ENOPHTHALMOS; MAXILLARY SINUSITIS; WHITNALL LIGAMENT; FRACTURES; EXOPHTHALMOMETER; MANAGEMENT; SURGERY; ANATOMY; ORBIT AB Purpose: In general, orbital augmentation to correct enophthalmos is pursued to prevent or address an aesthetic deformity. In some cases, however, functional deficits may accompany enophthalmos and may serve as an indication for surgical intervention. The authors describe a series of patients with such deficits. Methods: A retrospective review at a tertiary health care center of all patients with enophthalmos was conducted to identify a subset of cases in which the enophthalmos was associated with nonaesthetic, functional deficits that could not be attributed to muscular or neural dysfunction, or soft tissue scarring. Results: Six patients with either traumatic enophthalmos (orbital fractures) or nontraumatic enophthalmos (sinus disease and orbital soft tissue atrophy) demonstrated nonaesthetic ocular dysfunction, including gaze-evoked diplopia, eyelid retraction, lagophthalmos, and exposure keratitis. The symptoms and signs resolved in the three patients who underwent orbital augmentation. Conclusions: In some patients with enophthalmos and globe ptosis, globe malposition may alter the underlying eyelid mechanics or extraocular muscle alignment, resulting in functional as well as aesthetic problems. In these patients, restoring the native orbital anatomy through orbital augmentation can reverse eyelid malposition, ocular surface exposure, and symptomatic diplopia, avoiding the need for eyelid or strabismus surgery. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Rubin, PAD (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 54 TC 20 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHALMIC PLAST REC JI Ophthalmic Plast. Reconstr. Surg. PD JUL PY 1999 VL 15 IS 4 BP 284 EP 292 DI 10.1097/00002341-199907000-00010 PG 9 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 219WK UT WOS:000081630900010 PM 10432525 ER PT J AU Melki, SA Safar, A Martin, J Ivanova, A Adi, M AF Melki, SA Safar, A Martin, J Ivanova, A Adi, M TI Potential acuity pinhole - A simple method to measure potential visual acuity in patients with cataracts, comparison to potential acuity meter SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Ophthalmology CY NOV 08-09, 1998 CL NEW ORLEANS, LOUISIANA SP Amer Acad Ophthalmol ID CARD ASSESSMENT AB Objective: To describe the potential acuity pinhole (PAP) test and compare its accuracy to the potential acuity meter (PAM) in predicting visual outcome after cataract surgery, Study Design: Prospective case series. Participants: A total of 56 preoperative patients with cataracts participated. Main Outcome Measures: Accuracy of predicting postoperative distance visual acuity was measured. Methods: Lines of inaccuracy were calculated by subtracting actual postoperative best-corrected distance visual acuity (BCVA) from predicted values. Variables analyzed were method of prediction, preoperative BCVA, and preoperative spherical equivalent, Results: The PAP test predicted visual outcomes within 2 lines in 100%, 100%, and 56% of eyes with preoperative BCVA of 20/50 and better (group I), 20/60 to 20/100 (group II), and 20/200 and worse (group III), respectively, The PAM predictions within 2 lines for the same groups were 42%, 47%, and 0%, respectively. Mean lines of inaccuracy of PAP predictions were 0.83, 1,11, and 3.50 lines for groups I, II, and III, respectively. Mean lines of inaccuracy for PAM predictions were 2.50, 2.68, and 6.22 lines for the same groups. Differences in lines of prediction between PAM and PAP were 1.67 (P = 0.004), 1.58 (P = 0.0002), and 2.72 lines (P = 0.0001) for groups I, II, and III, respectively, There was no statistically significant correlation between PAP predictions and preoperative myopic spherical equivalent. Conclusions: The PAP test is a simple, inexpensive, and relatively reliable method to estimate visual outcome after uncomplicated cataract surgery in eyes with no coexisting disease. It is less accurate in patients with preoperative BCVA worse than 20/200. It appears to be more predictive than PAM. C1 Georgetown Univ, Med Ctr, Ctr Sight, Washington, DC 20007 USA. Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. RP Melki, SA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. NR 16 TC 24 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUL PY 1999 VL 106 IS 7 BP 1262 EP 1267 DI 10.1016/S0161-6420(99)00706-X PG 6 WC Ophthalmology SC Ophthalmology GA 211QQ UT WOS:000081172400015 PM 10406603 ER PT J AU Birnbaum, CS Cohen, LS Bailey, JW Grush, LR Robertson, LM Stowe, ZN AF Birnbaum, CS Cohen, LS Bailey, JW Grush, LR Robertson, LM Stowe, ZN TI Serum concentrations of antidepressants and benzodiazepines in nursing infants: A case series SO PEDIATRICS LA English DT Article DE breastfeeding; antidepressants; benzodiazepines ID HUMAN-BREAST-MILK; FLUOXETINE HYDROCHLORIDE; N-DESMETHYLDOXEPIN; DEPRESSION; PREGNANCY; EXCRETION; DIAZEPAM; NEONATE; WOMEN; AMITRIPTYLINE AB Objective. The relative risk of psychotropic medication use in women with puerperal psychiatric illness who are breastfeeding has yet to be quantified adequately. Although the emotional and medical benefits of breastfeeding and adverse effects of maternal depression on infant development are well described, how these absolute benefits weigh against the potential effects of psychotropic drug use during lactation to ultimately guide clinical decisions is still unclear. The objective of this report was to evaluate the extent that psychotropic medications were present in the serum of infants breastfed by mothers treated with antidepressants and benzodiazepines. Design. Serum samples were obtained from 35 nursing infants whose mothers were treated with psychotropic medications while breastfeeding. When a detectable concentration of medication was reported, information regarding infant behavior was obtained by maternal report. Setting. The Perinatal and Reproductive Psychiatry Program at Massachusetts General Hospital serves as a regional consultation center for the treatment of psychiatric disorders during pregnancy;md the postpartum period. Patients. Subjects were mothers referred to the Perinatal Psychiatry Program for consultation regarding the relative safety of psychotropic medication use while breastfeeding. Primary Outcome Measures. Presence of detectable levels of medication in infants whose mothers breastfed while taking psychotropic medications during pregnancy and/or during the puerperium and the well-being (based on maternal report) of infants who had detectable serum concentrations of medication. Results. Seventy-four percent (n = 26) of infants had serum medication concentrations below the laboratory limit of detection (assay sensitivity 5-50 ng/mL). In the remaining 26% of the sample (n = 9), serum concentrations of psychotropic medications and/or active metabolites were detected. In each of these cases, infants had been exposed to the medication during pregnancy. Medications were not detected in infant serum when mothers had taken these agents solely during the postpartum period. No readily apparent difficulties with the infants were reported by mothers. Conclusions. These data support the low incidence of infant toxicity and adverse effects associated with antidepressant and benzodiazepine use during breastfeeding. These data also suggest that infant serum monitoring is helpful in the assessment of medication exposure in children of mothers who breastfeed while using psychotropic medications. Given the limited accumulated data regarding serum concentrations of psychotropic medications in breastfeeding infants, no single agent seems to be safer than another. Therefore, choice of pharmacologic treatment should be guided by the likelihood that it will result in restoration of maternal psychiatric well-being. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Perinatal Psychiat Program, Boston, MA USA. Emory Univ, Sch Med, Pregnancy & Postpartum Mood Disorders Program, Atlanta, GA USA. RP Cohen, LS (reprint author), Massachusetts Gen Hosp, Perinatal Psychiat Clin Res Program, 15 Parkman St,WACC 812, Boston, MA 02114 USA. NR 50 TC 32 Z9 34 U1 0 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 JUL PY 1999 VL 104 IS 1 AR e11 DI 10.1542/peds.104.1.e11 PG 6 WC Pediatrics SC Pediatrics GA 213EC UT WOS:000081258700026 PM 10390297 ER PT J AU Mikhail, N Golub, MS Tuck, ML AF Mikhail, N Golub, MS Tuck, ML TI Obesity and hypertension SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review ID SYMPATHETIC NERVOUS-SYSTEM; RANDOMIZED CONTROLLED TRIAL; HIGH BLOOD-PRESSURE; BODY-FAT DISTRIBUTION; WEIGHT-REDUCTION; INSULIN RESISTANCE; DIABETES-MELLITUS; ANTIHYPERTENSIVE THERAPY; CARDIOVASCULAR-DISEASE; ARTERIAL-HYPERTENSION C1 Sepulveda Ambulatory Care Ctr, Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. RP Mikhail, N (reprint author), Vet Affairs Med Ctr, Endocrinol Sect, 16111 Plummer St, Sepulveda, CA 91343 USA. NR 152 TC 70 Z9 88 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-0620 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD JUL-AUG PY 1999 VL 42 IS 1 BP 39 EP 58 DI 10.1016/S0033-0620(99)70008-3 PG 20 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 237GW UT WOS:000082648300003 PM 10505492 ER PT J AU Wolfe, J Proctor, SP Erickson, DJ Heeren, T Friedman, MJ Huang, MT Sutker, PB Vasterling, JJ White, RF AF Wolfe, J Proctor, SP Erickson, DJ Heeren, T Friedman, MJ Huang, MT Sutker, PB Vasterling, JJ White, RF TI Relationship of psychiatric status to Gulf War veterans' health problems SO PSYCHOSOMATIC MEDICINE LA English DT Article DE Gulf War veterans; health symptoms; posttraumatic stress disorder; major depressive disorder ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL-COMORBIDITY-SURVEY; MISSISSIPPI SCALE; SOMATIC SYMPTOMS; PREVALENCE; ILLNESS; SOMATIZATION; RELIABILITY; DEPRESSION; DISASTER AB Objective: A growing body of research has shown that there are important links between certain psychiatric disorders and health symptom reporting. Two disorders in particular (posttraumatic stress disorder (PTSD) and major depression) have been the most widely implicated to date, and this association has sometimes been used to explain the occurrence of ill-defined medical problems and increased somatic symptoms in certain groups, most recently Gulf War veterans. Methods: Structured psychiatric diagnostic interviews were used to examine the presence of major psychiatric (axis I) disorders and their relation to health symptom reporting in a well-characterized, stratified subset of Gulf War veterans and a non-Gulf-deployed veteran comparison group, Results: Rates of most psychiatric disorders were substantially lower than national comorbidity estimates, consistent with prior studies showing heightened physical and emotional well-being among active-duty military personnel. Rates of PTSD and major depression, however, were significantly elevated relative to the veteran comparison group. The diagnosis of PTSD showed a small but significant association with increased health symptom reports, However, nearly two-thirds of Gulf participants reporting moderate to high health symptoms had no axis I psychiatric diagnosis. Conclusions: Results suggest that rates of psychiatric illness were generally low with the exception of PTSD and major depression. Although PTSD was associated with higher rates of reported health problems, this disorder did not entirely account for symptoms reported by participants. Factors other than psychiatric status may play a role in Gulf War health problems. C1 Boston VA Med Ctr, Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div 116B3, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. VA Med & Reg Off Ctr, White River Junction, VT USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. Tulane Univ, Sch Med, New Orleans, LA 70112 USA. RP Wolfe, J (reprint author), Boston VA Med Ctr, Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div 116B3, 150 S Huntington Ave, Boston, MA 02130 USA. NR 53 TC 77 Z9 77 U1 5 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JUL-AUG PY 1999 VL 61 IS 4 BP 532 EP 540 PG 9 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 221PC UT WOS:000081734600015 PM 10443762 ER PT J AU Duffy, LS Greenberg, DB Younger, J Ferraro, MG AF Duffy, LS Greenberg, DB Younger, J Ferraro, MG TI Iatrogenic acute estrogen deficiency and psychiatric syndromes in breast cancer patients SO PSYCHOSOMATICS LA English DT Article ID REPLACEMENT THERAPY; WOMEN AB The change of estrogen function, represented by amenorrhea or hot flashes, that results from breast cancer treatment may increase the risk of major depressive disorder in those women under-going treatment for breast cancer. This pilot study describes the course of menopausal symptoms and the incidence of depression in 21 patients who were likely to become acutely estrogen deficient during treatment for breast cancer. These included women who lost menses during chemotherapy who suddenly stopped estrogen replacement therapy (ERT), or who started tamoxifen. Eight patients (38%) developed major depressive disorder the majority within 6 months of starting treatment. Twenty patients (95%) had dysphoria and/or insomnia. Fourteen patients (66%) had hot flashes. While this is only pilot data, these data suggest that breast cancer patients whose treatment precipitates menopausal symptoms should be targeted for diagnosis of depression and treated if diagnosed. C1 Massachusetts Gen Hosp, Ctr Canc, Dept Med Oncol, Boston, MA 02114 USA. RP Greenberg, DB (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Psychiat, WRN 605,Fruit St, Boston, MA 02114 USA. NR 15 TC 30 Z9 31 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JUL-AUG PY 1999 VL 40 IS 4 BP 304 EP 308 PG 5 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 212VJ UT WOS:000081238100005 PM 10402875 ER PT J AU Wu, MT Hsieh, JC Xiong, J Yang, CF Pan, HB Chen, YCI Tsai, GC Rosen, BR Kwong, KK AF Wu, MT Hsieh, JC Xiong, J Yang, CF Pan, HB Chen, YCI Tsai, GC Rosen, BR Kwong, KK TI Central nervous pathway for acupuncture stimulation: Localization of processing with functional MR imaging of the brain - Preliminary experience SO RADIOLOGY LA English DT Article; Proceedings Paper CT 85th Scientific Assembly and Annual Meeting CY NOV 28-DEC 03, 1999 CL CHICAGO, ILLINOIS DE acupuncture; anesthesia; brain, function; brain, MR; magnetic resonance (MR), functional imaging ID POSITRON EMISSION TOMOGRAPHY; ELECTROACUPUNCTURE ANALGESIA; CEREBROSPINAL-FLUID; ANTERIOR CINGULATE; ARCUATE NUCLEUS; MET-ENKEPHALIN; BETA-ENDORPHIN; PAIN; HYPOTHALAMUS; RESPONSES AB PURPOSE: To characterize the central nervous system (CNS) pathway for acupuncture stimulation in the human brain by using functional magnetic resonance (MR) imaging. MATERIALS AND METHODS: Functional MR imaging of the whole brain was performed in two groups of nine healthy subjects during four stimulation paradigms: real acupuncture at acupoints ST.36 (on the leg) and LI.4 (on the hand) and control stimulations (minimal acupuncture and superficial pricking on the leg). Stimulations were performed in semirandomized, balanced order nested within two experiments. Psychophysical responses (pain, De-Qi effect [characteristic acupuncture effect of needle-manipulation sensation], anxiety, and unpleasantness) and autonomic responses were assessed. Talairach coordinates-transformed imaging data were average for a group analysis. RESULTS: Acupuncture at LI.4 and ST.36 resulted in significantly higher scores for De-Qi and in substantial bradycardia. Acupuncture at both acupoints resulted in activation of the hypothalamus and nucleus accumbens and deactivation of the rostral part of the anterior cingulate cortex, amygdala formation, and hippocampal complex; control stimulations did not result in such activations and deactivations. CONCLUSION: Functional MR imaging can demonstrate the CNS pathway for acupuncture stimulation. Acupuncture at ST36 and LI.4 activates structures of descending antinociceptive pathway and deactivates multiple limbic areas subserving pain association. These findings may shed light on the CNS mechanism of acupuncture analgesia and form a basis for future investigations of endogenous pain modulaiton circuits in the human brain. C1 Kaohsiung Vet Gen Hosp, Dept Radiol, Kaohsiung 813, Taiwan. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA USA. Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan. Natl Yang Ming Univ, Sch Life Sci, Inst Neurosci, Taipei 112, Taiwan. Taipei Vet Gen Hosp, Lab Funct Brain Imaging, Taipei, Taiwan. Natl Def Med Coll, Dept Radiol, Taipei, Taiwan. Massachusetts Gen Hosp, Lab Mol & Dev Neurosci, Boston, MA 02114 USA. RP Wu, MT (reprint author), Kaohsiung Vet Gen Hosp, Dept Radiol, 386 Ta Chung 1st Rd, Kaohsiung 813, Taiwan. NR 53 TC 250 Z9 287 U1 7 U2 30 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 1999 VL 212 IS 1 BP 133 EP 141 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 210CE UT WOS:000081086900021 PM 10405732 ER PT J AU Kaufman, JA Geller, SC Bazari, H Waltman, AC AF Kaufman, JA Geller, SC Bazari, H Waltman, AC TI Gadolinium-based contrast agents as an alternative at vena cavography in patients with renal insufficiency - Early experience SO RADIOLOGY LA English DT Article DE angiography, contrast media; venae cavae, angiography; venography ID DIGITAL SUBTRACTION ANGIOGRAPHY; GADOPENTETATE DIMEGLUMINE; CARBON-DIOXIDE; DTPA; MEDIA; DOTA AB The authors reviewed results of digital substraction vena cavography with a gadolinium-based contrast agent in 14 patients with serum creatinine levels greater than or equal to 1.5 mg/dL (133 mu mol/L). All cavograms were diagnostic. In 11 patients, there was no impairment of renal function. In three patients, a rise in serum creatine level of greater than or equal to 0.5 mg/dL (44 mu mol/L) was attributable to concurrent medical problems. Gadolinium-based contrast agents may be suitable for digital subtraction vena cavography in patients with renal insufficiency. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Nephrol, Boston, MA 02114 USA. RP Kaufman, JA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc Radiol, GRB 290,55 Fruit St, Boston, MA 02114 USA. NR 23 TC 33 Z9 37 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 JUL PY 1999 VL 212 IS 1 BP 280 EP 284 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 210CE UT WOS:000081086900043 PM 10405754 ER PT J AU Harris, NL AF Harris, NL TI Hodgkin's lymphomas: Classification, diagnosis, and grading SO SEMINARS IN HEMATOLOGY LA English DT Article ID REED-STERNBERG CELLS; NODULAR LYMPHOCYTE PREDOMINANCE; TRANSFORMED GERMINAL-CENTERS; POLYMERASE CHAIN-REACTION; CENTER B-CELLS; PROGRESSIVE TRANSFORMATION; CLINICOPATHOLOGICAL ENTITY; PROGNOSTIC-SIGNIFICANCE; BCL-2 GENE; DISEASE C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Harris, NL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2, Boston, MA 02114 USA. NR 96 TC 47 Z9 51 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JUL PY 1999 VL 36 IS 3 BP 220 EP 232 PG 13 WC Hematology SC Hematology GA 222FY UT WOS:000081774400002 PM 10462322 ER PT J AU Khaw, BA AF Khaw, BA TI The current role of infarct avid imaging SO SEMINARS IN NUCLEAR MEDICINE LA English DT Review ID ACUTE MYOCARDIAL-INFARCTION; MYOSIN-SPECIFIC ANTIBODY; IN-111 ANTIMYOSIN; CARDIAC MYOSIN; TECHNETIUM-99M PYROPHOSPHATE; LOCALIZATION; TL-201; MULTICENTER; NECROSIS; TRIAL AB Tc-99m pyrophosphate is the grandfather of infarct avid agents, Its value is its clinical availability and ease of use. However, its shortcomings are the delay of 2 to 3 days for reliable interpretation in nonreperfused myocardial infarction (MI) and the overarching bone activity. Antimyosin provides exquisite specificity for the detection of myocardial necrosis irrespective of the cause of the injury. Therefore, diagnosis of equivocal MI or confirmation of diffuse myocardial necrosis would benefit from the availability of In-111 labeled antimyosin Fab. The drawback of antimyosin, like that of Tc-99m pyrophosphate, is the delay, in this case because of the protracted blood clearance of the antibody protein macromolecules. Tc-99m glucaric acid, on the other hand, may fulfill the original role envisioned for antimyosin, which was to enable early, rapid diagnosis of acute MI. However, the window for the use of Tc-99m glucaric acid appears to be limited to within the first day of the acute event. Therefore, there is a potential use of both Tc-99m glucaric acid and In-111 antimyosin in tandem with Tc-99m glucaric acid, which would not only facilitate early detection and diagnosis of acute MI and diagnosis of equivocal MI, but also may permit stratification of the infarct age. Copyright (C) 1999 by W.B. Saunders Company. C1 Northeastern Univ, Bouve Coll Hlth Sci, Dept Pharmaceut Sci, Ctr Cardiovasc Targeting, Boston, MA 02115 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Khaw, BA (reprint author), Northeastern Univ, Bouve Coll Hlth Sci, Dept Pharmaceut Sci, Ctr Cardiovasc Targeting, Boston, MA 02115 USA. NR 57 TC 18 Z9 18 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 0001-2998 J9 SEMIN NUCL MED JI Semin. Nucl. Med. PD JUL PY 1999 VL 29 IS 3 BP 259 EP 270 DI 10.1016/S0001-2998(99)80014-2 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 217JP UT WOS:000081496500007 PM 10433340 ER PT J AU Recht, A AF Recht, A TI Locoregional failure rates in patients with involved axillary nodes after mastectomy and systemic therapy SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID POSITIVE BREAST-CANCER; SURGICAL ADJUVANT BREAST; MODIFIED RADICAL-MASTECTOMY; DOXORUBICIN-CYCLOPHOSPHAMIDE; POSTOPERATIVE RADIOTHERAPY; RANDOMIZED TRIAL; LYMPH-NODES; POSTMENOPAUSAL WOMEN; PREMENOPAUSAL WOMEN; REGIONAL RECURRENCE C1 Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Dept Radiat Oncol, Boston, MA 02115 USA. RP Recht, A (reprint author), Beth Irael Deaconess Med Ctr, Dept Radiat Oncol, East Campus,Finard Bldg B25,330 Brookline Ave, Boston, MA 02215 USA. NR 51 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 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD JUL PY 1999 VL 9 IS 3 BP 223 EP 229 DI 10.1016/S1053-4296(99)80013-7 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 217GD UT WOS:000081490900003 PM 10378960 ER PT J AU Kattapuram, SV Rosol, MS Rosenthal, DI Palmer, WE Mankin, HJ AF Kattapuram, SV Rosol, MS Rosenthal, DI Palmer, WE Mankin, HJ TI Magnetic resonance imaging features of allografts SO SKELETAL RADIOLOGY LA English DT Article DE allografts; osteoarticular; magnetic resonance imaging ID BONE-TUMORS; TRANSPLANTATION; MANAGEMENT; RESECTION AB Objective. To investigate the magnetic resonance imaging (MRI) features of allografts at various time intervals after surgery in patients with osteoarticular allografts. Design and patients. Sixteen patients who were treated with osteoarticular allografts and who were followed over time with MRI studies as part of their long-term follow-up were retrospectively selected for this study. T1-weighted images were obtained both before and after gadolinium administration along with T2-weighted images. All images were reviewed by an experienced musculoskeletal radiologist, with two other experienced radiologists used for consultation. Imaging studies were organized into three groups for ease of discussion: early postoperative period (2 days to 2 months), intermediate postoperative period (3 months to 2 years), and late postoperative period (greater than 2 years). Results. In the early postoperative period, no gadolinium enhancement of the allograft was visible in any of the MR images. A linear, thin layer of periosteal and endosteal tissue enhancement along the margin of the allograft was visible in images obtained at 3-4 months. This enhancement appeared gradually to increase in images from later periods, and appears to have stabilized in the images obtained approximately 2-3 years after allograft placement. The endosteal enhancement diminished after several years, with examinations conducted between 6 and 8 years following surgery showing minimal endosteal enhancement. However, focal enhancement was noted adjacent to areas of pressure erosion or degenerative cysts. All the cases showed inhomogeneity in the marrow signal (scattered low signal foci on T1 with corresponding bright signal on T2), and a diffuse, inhomogeneous marrow enhancement later on. Conclusion. We have characterized the basic MRI features of osteoarticular allografts in 16 patients who underwent imaging studies at various time points as part of routine followup. We believe that the endosteal and periosteal enhancement observed on MRI during the first few months to 2 years following surgery represents vascular ingrowth and early skeletal repair. The zone of periosteal enhancement could also include the new bone laid on the surface of the allograft through which the soft tissues bind to the cortex. The exact reason for the inhomogeneity in the marrow signal, and the diffuse, inhomogeneous marrow enhancement is not clear. This may represent saponified and/or necrotic marrow fat interspersed with the fibrovascular tissue. The features noted here should provide radiologists with useful information regarding imaging characteristics they can expect to see in other allograft replacement patients. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02118 USA. Harvard Univ, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Orthoped, Boston, MA 02118 USA. RP Kattapuram, SV (reprint author), Massachusetts Gen Hosp, Dept Radiol, 15 Parkman St,ACC-515, Boston, MA 02118 USA. NR 22 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD JUL PY 1999 VL 28 IS 7 BP 383 EP 389 PG 7 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 225ZF UT WOS:000081995300002 PM 10478619 ER PT J AU Rowitch, DH Danielian, PS McMahon, AP Zec, N AF Rowitch, DH Danielian, PS McMahon, AP Zec, N TI Cystic malformation of the posterior cerebellar vermis in transgenic mice that ectopically express Engrailed-1, a homeodomain transcription factor SO TERATOLOGY LA English DT Article ID DANDY-WALKER SYNDROME; PROTO-ONCOGENE INT-1; MURINE NEURAL PLATE; GENE-EXPRESSION; WNT-1 EXPRESSION; MOUSE-BRAIN; MUTANT MICE; HOMEO BOX; MIDBRAIN; DELETION AB In WEXPZ-En-1 transgenic mice, Engrailed-1, a homeodomain-containing transcription factor, is ectopically expressed in the developing brain under control of the Wnt-1 enhancer. En-1 is a developmental regulatory control gene which has an essential role in the formation of the midbrain and cerebellum. Approximately 28% of WEXPZ-En-1(+) mice develop cystic malformations of the posterior lobe of the cerebellar vermis, fourth ventricular dilatation, and postnatal hydrocephalus. These anatomic features are also found among the spectrum of posterior fossa malformations in humans. Expression characteristics of the WEXP transgene suggest that the neuropathology observed in WEXPZ-En-1(+) mice stems from overexpression of En-1 during fetal and neonatal phases of cerebellar development. These observations raise the possibility that abnormal regulation of Engrailed genes, or targets of Engrailed, may be involved in the pathogenesis of cystic central nervous system malformations of the posterior fossa in humans. (C) 1999 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Dept Pediat, Div Newborn Med, Boston, MA 02115 USA. Harvard Univ, Dept Cellular & Mol Biol, Cambridge, MA 02138 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Rowitch, DH (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. NR 43 TC 7 Z9 7 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 0040-3709 J9 TERATOLOGY JI Teratology PD JUL PY 1999 VL 60 IS 1 BP 22 EP 28 DI 10.1002/(SICI)1096-9926(199907)60:1<22::AID-TERA7>3.0.CO;2-6 PG 7 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 210UY UT WOS:000081124100007 PM 10413335 ER PT J AU Hershman, JM AF Hershman, JM TI Human chorionic gonadotropin and the thyroid: Hyperemesis gravidarum and trophoblastic tumors SO THYROID LA English DT Article; Proceedings Paper CT Symposium on Thyroid Disease in Pregnancy and the Postpartum Period CY NOV 06-08, 1998 CL AMELIA ISL, FLORIDA ID HUMAN TSH RECEPTORS; HYDATIDIFORM MOLE; THYROTROPIC ACTIVITY; HYPERTHYROIDISM; THYROTOXICOSIS; HORMONE; GENERATION; RESPONSES; CELLS; HCG AB There is abundant evidence that human chorionic gonadotropin (hCG) is a weak thyrotropin (TSH) agonist. In FRTL-5 rat thyroid cells, hCG increases cyclic adenosine monophosphate (cAMP), iodide transport, and cell growth. hCG has thyroid-stimulating activity in bioassays in mice and in clinical studies in man. In cultured cells transfected with the human TSH receptor, hCG increases generation of cAMP. Molecular variants of hCG with increased thyrotropic potency include basic molecules with reduced sialic acid content, truncated molecules lacking the C-terminal tail, or molecules in which the 47-48 peptide bond in the P-subunit loop is nicked. In normal pregnancy, when hCG levels are highest at 10 to 12 weeks gestation, there is suppression of serum TSH levels, presumably due to slight increases in free thyroxine (T-4) concentration. In twin pregnancies, hCG levels tend to be higher and suppressed TSH levels are more frequent. Hyperemesis gravidarum, defined as severe vomiting in early pregnancy that causes 5% weight loss and ketonuria, is usually associated with increased hCG concentration. A high proportion of patients with hyperemesis gravidarum, about one-third to two-thirds in different series, have evidence of increased thyroid function. Only a small proportion of these patients have clinical hyperthyroidism, termed gestational thyrotoxicosis. These patients probably secrete a variant of hCG with increased thyroid-stimulating activity. Trophoblastic tumors, hydatidiform mole, and choriocarcinoma often cause hyperthyroidism because they secrete very large amounts of hCG. When the serum hCG exceeds about 200 IU/mL, hyperthyroidism is likely to be found. There is a correlation between the biochemical severity of hyperthyroidism and the serum hCG in these patients. Removal of the mole or effective chemotherapy of the choriocarcinoma cures the hyperthyroidism. In conclusion, hCG has thyroid-stimulating activity that influences thyroid function early in pregnancy when hCG levels are high. Excessive hCG secretion may cause hyperthyroidism in patients with hyperemesis gravidarum or trophoblastic tumors. C1 W Los Angeles Vet Affairs Med Ctr, Div Endocrinol 111D, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Hershman, JM (reprint author), W Los Angeles Vet Affairs Med Ctr, Div Endocrinol 111D, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 42 TC 69 Z9 75 U1 0 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD JUL PY 1999 VL 9 IS 7 BP 653 EP 657 DI 10.1089/thy.1999.9.653 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 222AF UT WOS:000081759500006 PM 10447009 ER PT J AU Brent, GA AF Brent, GA TI Maternal hypothyroidism: Recognition and management SO THYROID LA English DT Article; Proceedings Paper CT Symposium on Thyroid Disease in Pregnancy and the Postpartum Period CY NOV 06-08, 1998 CL AMELIA ISL, FLORIDA ID THYROID-FUNCTION; PREGNANCY; THYROXINE; WOMEN; THERAPY; REQUIREMENT; DOSAGE AB Women with compensated early thyroid failure, or those from areas of reduced iodine intake, may first be found to be hypothyroid during pregnancy. In women with previously diagnosed hypothyroidism already on thyroxine (T-4) replacement therapy, pregnancy is often associated with an increased dose requirement. The mechanism producing this increased requirement is not known, but it is likely to be the result of a number of factors that may differ depending on the stage of pregnancy. An increased T-4 dose requirement is typically seen by the first trimester, can continue to increase throughout pregnancy, and reverts to the prepregnancy dose requirement after delivery. The magnitude of the increased T-4 requirement is related to the etiology of hypothyroidism. Monitoring thyroid status and adjusting the T-4 dose during pregnancy is a challenge due to changes in T-4 metabolism throughout pregnancy. C1 W Los Angeles Vet Affairs Med Ctr, Div Endocrinol 111D, Los Angeles, CA 90073 USA. RP Brent, GA (reprint author), W Los Angeles Vet Affairs Med Ctr, Div Endocrinol 111D, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [R01-DK43714] NR 29 TC 27 Z9 30 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD JUL PY 1999 VL 9 IS 7 BP 661 EP 665 DI 10.1089/thy.1999.9.661 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 222AF UT WOS:000081759500008 PM 10447011 ER PT J AU Fuchimoto, Y Huang, C Shimizu, A Seebach, J Arn, S Sachs, DH AF Fuchimoto, Y Huang, C Shimizu, A Seebach, J Arn, S Sachs, DH TI An allelic non-histocompatibility antigen with wide tissue distribution as a marker for chimerism in pigs SO TISSUE ANTIGENS LA English DT Article DE alleles; antigens; chimerism; histocompatibility antigens; miniature swine; transplantation ID MINIATURE SWINE; MONOCLONAL-ANTIBODIES; RENAL-ALLOGRAFTS; TRANSPLANTATION; TOLERANCE; SURVIVAL; COMPLEX; MICROCHIMERISM; REJECTION AB It is frequently useful in studies of transplantation to have available an antibody to a cell surface antigen, which is not itself responsible for transplant rejection. In this paper, we identify and describe such an antibody/antigen system in miniature swine. The monoclonal antibody, 1038H10-9, was found to react to a pig allelic antigen (called PAA), found on a variety of pig cells and tissues, including peripheral blood mononuclear cells (PBMC), thymocytes, lymph node, bone marrow, and skin. Analysis for recipient sensitization against PAA was performed by in vitro cell-mediated lympholysis (CML) assay, mixed lymphocyte reaction (MLR) assay, antibody binding studies, and skin graft rejection patterns were examined. No evidence was found to indicate detection of PAA by any of these assays of alloreactivity. We therefore conclude that PAA is an allelic swine cell surface antigen, with wide tissue distribution, and that it is not a histocompatibility antigen. It should provide a powerful tool for studies of transplantation biology in miniature swine, such as identification and quantification of chimerism following organ transplantation. C1 Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. Kantonspital Zurich, Zurich, Switzerland. RP Sachs, DH (reprint author), Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Sch Med, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [2 PO1 HL01846]; NIAID NIH HHS [2R01 AI31046] NR 20 TC 35 Z9 35 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD JUL PY 1999 VL 54 IS 1 BP 43 EP 52 DI 10.1034/j.1399-0039.1999.540105.x PG 10 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 220AT UT WOS:000081642400005 PM 10458322 ER PT J AU Vamvakas, EC Carven, JH AF Vamvakas, EC Carven, JH TI Transfusion and postoperative pneumonia in coronary artery bypass graft surgery: effect of the length of storage of transfused red cells SO TRANSFUSION LA English DT Article ID PERIOPERATIVE BLOOD-TRANSFUSION; STORED HUMAN-BLOOD; ELECTIVE COLORECTAL SURGERY; CATIONIC PROTEINS ECP; LYMPHOCYTE-PROLIFERATION; INFECTIOUS COMPLICATIONS; COMPLEMENT ACTIVATION; SEPTIC COMPLICATIONS; BIOACTIVE SUBSTANCES; LEUKOCYTE DEPLETION AB BACKGROUND: Various bioactive substances are released from white cell (WBC) granules into red cell (RBC) components in a time-dependent manner during blood storage. Some of these substances may have immunosuppressive effects and may contribute to transfusion-induced immunomodulation. RBCs transfused after prolonged storage may be associated with a higher incidence of postoperative infections than fresh RBCs. This hypothesis does not seem to have been investigated in a clinical study. STUDY DESIGN AND METHODS: The records of 416 consecutive patients undergoing coronary artery bypass graft operations at the Massachusetts General Hospital were reviewed. The association between the length of storage of the transfused RBCs, as well as the number of units of non-WBC-reduced allogeneic RBCs and/or platelets transfused, and the occurrence of postoperative pneumonia was calculated by logistic regression analyses adjusting for the effects of confounding factors. Among these were the numbers of days of intubation, days of impaired consciousness, and units of RBCs transfused. RESULTS: By Centers for Disease Control and Prevention criteria, pneumonia developed in 54 patients (13.0%). Among 269 patients given RBCs, the risk of pneumonia increased by 1 percent per day of increase in the mean storage time of the transfused RBCs (p<0.005). In an analysis of all patients, the risk of pneumonia increased by 5 percent per unit of non-WBC-reduced allogeneic RBCs and/or platelets received (p = 0.0584). CONCLUSION: After adjustment for the effects of the risk factors for pneumonia and the number of transfused RBCs, an association was observed between the length of storage of transfused RBCs and the development of postoperative pneumonia. This association should be investigated further in future studies of the outcomes of blood transfusion. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. Dept Vet Affairs Med Ctr, Pathol & Lab Med Serv, New York, NY USA. RP Vamvakas, EC (reprint author), NYU, Med Ctr, Blood Bank, Transfus Serv, RRG17,400 E 34th St, New York, NY 10016 USA. NR 56 TC 235 Z9 237 U1 1 U2 2 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUL PY 1999 VL 39 IS 7 BP 701 EP 710 DI 10.1046/j.1537-2995.1999.39070701.x PG 10 WC Hematology SC Hematology GA 216EK UT WOS:000081428100007 PM 10413277 ER PT J AU Bork, P Doerks, T Springer, TA Snel, B AF Bork, P Doerks, T Springer, TA Snel, B TI Domains in plexins: links to integrins and transcription factors SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID STRUCTURE PREDICTION; LIGAND-BINDING; CELL-ADHESION; A-DOMAIN; SUBUNIT; SEMAPHORIN; TRANSMEMBRANE; DIMERIZATION; PROFILE; FAMILY C1 European Mol Biol Lab, D-69012 Heidelberg, Germany. Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Bork, P (reprint author), European Mol Biol Lab, Meyerhofstr 1, D-69012 Heidelberg, Germany. RI Bork, Peer/F-1813-2013; Snel, Berend/B-8886-2011 OI Bork, Peer/0000-0002-2627-833X; Snel, Berend/0000-0002-5804-8547 NR 23 TC 125 Z9 127 U1 0 U2 4 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JUL PY 1999 VL 24 IS 7 BP 261 EP 263 DI 10.1016/S0968-0004(99)01416-4 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 218FU UT WOS:000081543200004 PM 10390613 ER PT J AU Kodama, T Tatsuno, M Sugimoto, S Uenohara, H Yoshimoto, T Takayama, K AF Kodama, T Tatsuno, M Sugimoto, S Uenohara, H Yoshimoto, T Takayama, K TI Liquid jets, accelerated thrombolysis: A study for revascularization of cerebral embolism SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE liquid jet impact; shock wave; explosive; bubble; thrombolysis; fibrinolysis; recanalization; ablation; cerebral embolism; high-speed photograph ID SHOCK-WAVE; ULTRASOUND; ANGIOPLASTY; TECHNOLOGY; TRANSPORT; UROKINASE; DYNAMICS; THERAPY; BUBBLES; RABBIT AB A prior study has reported that a rapid recanalization therapy of cerebral embolism, using liquid jet impacts generated by the interaction of gas bubbles with shock waves, can potentially penetrate through thrombi in as little as a few mu s with very efficient ablation (Kodama et al, 1997), The present study was undertaken to examine the liquid jet impact effect on fibrinolysis in a tube model of an internal carotid artery. First, the conditions for generating the maximum penetration depth of liquid jets in the tube were investigated. Gelatin was used to mimic thrombi, The shock wave was generated by detonating a silver azide pellet weighing about a few mu g located in a balloon catheter, The collapse of the inserted gas bubbles and the subsequent liquid jet formation were recorded with high-speed photography. Second, thrombi were formed using fresh human blood from healthy volunteers. The fibrinolysis induced by the liquid jet impact with urokinase was explored. This was conducted under selected conditions based on the experiment using the gelatin. Fibrinolysis was calculated as the percentage of the weight loss of the thrombus, Fibrinolysis with urokinase alone and with a single liquid jet impact with urokinase was 1.9 +/- 3.7% (n = 16) and 20.0 +/- 9.0% (n = 35), respectively, for an incubation time of 60 min. Statistical differences were obtained between all groups (ANOVA). These results suggest that liquid jet impact thrombolysis has the potential to be a rapid and effective therapeutic modality in recanalization therapy for patients with cerebral embolism and other clinical conditions of intra-arterial thrombosis. (C) 1999 World Federation for Ultrasound in Medicine & Biology. C1 Tohoku Univ, Sch Med, Inst Fluid Sci, Shock Wave Res Ctr, Sendai, Miyagi 980, Japan. Tohoku Univ, Sch Med, Dept Neurosurg, Sendai, Miyagi 980, Japan. Sendai Natl Hosp, Dept Neurosurg, Sendai, Miyagi, Japan. RP Kodama, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Labs Photomed, 55 Fruit St WEL 224, Boston, MA 02114 USA. OI kodama, tetsuya/0000-0003-4727-9558 NR 21 TC 29 Z9 29 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD JUL PY 1999 VL 25 IS 6 BP 977 EP 983 DI 10.1016/S0301-5629(99)00050-2 PG 7 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 215MU UT WOS:000081386100014 PM 10461727 ER PT J AU Burke, D AF Burke, D TI Allele predicted accelerated rate of cognitive decline in Alzheimer's disease - Commentary SO WESTERN JOURNAL OF MEDICINE LA English DT Article C1 VA Puget Sound Hlth Care Syst, GEriatr Res Educ & Clin Ctr 182B, Seattle, WA 98108 USA. RP Burke, D (reprint author), VA Puget Sound Hlth Care Syst, GEriatr Res Educ & Clin Ctr 182B, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD JUL PY 1999 VL 171 IS 1 BP 23 EP 23 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 229BP UT WOS:000082173900011 PM 10483340 ER PT J AU McGlynn, EA Kerr, EA Asch, SM AF McGlynn, EA Kerr, EA Asch, SM TI New approach to assessing clinical quality of care for women: The QA tool system SO WOMENS HEALTH ISSUES LA English DT Article ID HEALTH C1 RAND Hlth, Ctr Res Qual Hlth Care, Santa Monica, CA USA. Univ Michigan, Dept Med, Ann Arbor Vet Affairs, Ctr Practice Management & Outcomes Res, Ann Arbor, MI 48109 USA. Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. RP McGlynn, EA (reprint author), RAND Hlth, Ctr Res Qual Hlth Care, Santa Monica, CA USA. NR 8 TC 15 Z9 15 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 1999 VL 9 IS 4 BP 184 EP 192 DI 10.1016/S1049-3867(99)00009-2 PG 9 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 216QB UT WOS:000081452400002 PM 10405590 ER PT J AU Pham, HT Rosenblum, BI Lyons, TE Giurini, JM Chrzan, JS Habershaw, GM Veves, A AF Pham, HT Rosenblum, BI Lyons, TE Giurini, JM Chrzan, JS Habershaw, GM Veves, A TI Evaluation of a human skin equivalent for the treatment of diabetic foot ulcers in a prospective, randomized, clinical trial SO WOUNDS-A COMPENDIUM OF CLINICAL RESEARCH AND PRACTICE LA English DT Article ID VENOUS ULCERS; GROWTH-FACTOR; EXPERIENCE; WOUNDS AB The primary objective of this trial was to assess the ability of a human skin equivalent* to improve the median time to wound closure and the wound closure rate in nonischemic, non-infected diabetic foot ulcers. This was a prospective, randomized, placebo-controlled study. Patients in the skin equivalent group received treatment material once a week for a maximum of four weeks (five applications). Skin equivalent treatment was compared to a control treatment consisting of woven gauze kept moist by saline. Proper wound care, including extensive debridement and weight offloading, was provided to all participants. Sixteen patients were treated with a skin equivalent application once a week for a maximum of four weeks and were compared to 17 control patients matched for age, sex, diabetes duration, ulcer size, ABI, HbA1c, and ulcer duration. The Kaplan-Meier median time to complete closure was 38.5 days for skin equivalent, significantly lower than the 91 days observed in the control group (p<0.01). Complete wound closure was achieved in 12 (75 percent) skin equivalent-treated patients compared to seven (41 percent) control-treated patients (p<0.05 Chi-square test). The results demonstrate that weekly application of the skin equivalent, a bilayered living human skin analog, onto diabetic foot ulcers for a maximum of four weeks results in a higher healing rate when compared to currently available state-of-the-art treatment. Treatment with the skin equivalent was not associated with any significant side effects and may prove to be a very useful adjunct for the management of chronic diabetic foot ulcers, which are resistant to the currently available standard care. C1 Harvard Univ, Sch Med, Deaconess Joslin Foot Ctr, Boston, MA 02215 USA. RP Veves, A (reprint author), Harvard Univ, Sch Med, Deaconess Joslin Foot Ctr, 1 Deaconess Rd, Boston, MA 02215 USA. OI Pham, Hau/0000-0003-4583-9873 NR 19 TC 23 Z9 23 U1 2 U2 2 PU HEALTH MANAGEMENT PUBLICATIONSINC PI WAYNE PA 950 WEST VALLEY RD, STE 2800, WAYNE, PA 19087 USA SN 1044-7946 J9 WOUNDS JI Wounds-Compend. Clin. Res. Pract. PD JUL-AUG PY 1999 VL 11 IS 4 BP 79 EP 86 PG 8 WC Dermatology; Surgery SC Dermatology; Surgery GA 226YP UT WOS:000082051000005 ER PT J AU Simon, JA Hudes, ES AF Simon, JA Hudes, ES TI Relationship of ascorbic acid to blood lead levels SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID VITAMIN-C AB Context Some animal studies suggest that orally administered ascorbic acid may chelate lead and decrease the risk of the toxic effects of lead. However, results from. several small studies in humans have yielded inconclusive evidence of a beneficial effect of ascorbic acid on lead toxicity. Objective To examine the relationship between serum ascorbic acid levels and prevalence of elevated blood lead levels. Design, Setting, and Participants Cross-sectional analysis of a probability sample of the US population enrolled in the Third National Health and Nutrition Examination Survey, 1988-1994 (4213 youths aged 6-16 years and 15 365 adults aged greater than or equal to 17 years) without a history of lead poisoning. Main Outcome Measures Elevated and log blood lead levels by serum ascorbic acid level. Results A total of 22 youths (0.5%) and 57 adults (0.4%) had elevated blood lead levels (defined as greater than or equal to 0.72 mu mol/L [15 mu g/dL]) and greater than or equal to 0.97 mu mol/L [20 mu g/dL], respectively). After controlling for the effects of age, race, sex, income level, and dietary energy, fat, calcium, iron, and zinc intake, youths in the highest serum ascorbic acid tertile had an 89% decreased prevalence of elevated blood lead levels compared with youths in the lowest serum ascorbic acid tertile (odds ratio, 0.11; 95% confidence interval, 0.04-0.35; P for trend =.002), Adults in the highest 2 serum ascorbic acid tertiles had a 65% to 68% decreased prevalence of elevated blood lead levels compared with adults in the lowest serum ascorbic acid tertile (P for trend =.03). As a continuous predictor, serum ascorbic acid level was independently associated with decreased log blood lead levels among adults (P<.001), but not among youths (P=.14). Conclusions Our data suggest that high serum levels of ascorbic acid are independently associated with a decreased prevalence of elevated blood lead levels. If these associations are related causally, ascorbic acid intake may have public health implications for control of lead toxicity. C1 San Francisco VA Med Ctr, Med Serv, Gen Internal Med Sect 111A1, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Simon, JA (reprint author), San Francisco VA Med Ctr, Med Serv, Gen Internal Med Sect 111A1, 4150 Clement St, San Francisco, CA 94121 USA. FU NHLBI NIH HHS [HL53479] NR 26 TC 55 Z9 63 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 30 PY 1999 VL 281 IS 24 BP 2289 EP 2293 DI 10.1001/jama.281.24.2289 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 207FN UT WOS:000080925600027 PM 10386552 ER PT J AU Kaufman, MJ Pollack, MH Villafuerte, RA Kukes, TJ Rose, SL Mendelson, JH Cohen, BM Renshaw, PF AF Kaufman, MJ Pollack, MH Villafuerte, RA Kukes, TJ Rose, SL Mendelson, JH Cohen, BM Renshaw, PF TI Cerebral phosphorus metabolite abnormalities in opiate-dependent polydrug abusers in methadone maintenance SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article; Proceedings Paper CT 5th Annual Meeting of the International-Society-of-Magnetic-Resonance-in-Medicine CY APR 12-18, 1997 CL VANCOUVER, CANADA SP Int Soc Magnet Resonance Med DE magnetic resonance spectroscopy; heroin; cerebral metabolism; cerebral blood flow; brain; substance dependence ID MAGNETIC-RESONANCE SPECTROSCOPY; BLOOD-FLOW; COMPUTERIZED-TOMOGRAPHY; OPIOID DEPENDENCE; HEROIN-ADDICTS; ALCOHOL-ABUSE; BRAIN; BUPRENORPHINE; USERS; WITHDRAWAL AB This study evaluated cerebral phosphorus metabolites in opiate-dependent polydrug abusers in methadone maintenance therapy (MMT) and determined whether metabolite profiles differed based on treatment duration. Phosphorus magnetic resonance spectroscopy (P-31-MRS) data were acquired with the ISIS volume localization method from a 50-mm thick axial brain slice through the orbitofrontal and occipital cortices. Study subjects included 15 MMT subjects, seven having undergone treatment for an average of 39 +/- 23 weeks (mean +/- S.D.) and eight having undergone treatment for 137 +/- 53 weeks, as well as an age matched comparison group (n = 16). The methadone dose administered on the study day averaged 70.5 +/- 17.1 mg and was statistically equivalent in short- and long-term subgroups. MMT subjects (n = 15) differed from control subjects in percent phosphocreatine (%PCr) levels (-13%), and in both phosphomonoester (%PME, +13%) and phosphodiester (%PDE, +10%) levels, which likely reflect abnormalities in energy and phospholipid metabolism, respectively. There were no sex effects or group by sex interaction effects on these measures. In short-term MMT treatment subjects, abnormal %PCr (-18%), %PME (+20%) and %PDE (+17%) levels were found compared with control subjects. The only metabolite abnormality detected in long-term MMT subjects was decreased %PCr (-9%), in spite of continued illicit drug abuse. From these data, we conclude that polydrug abusers in MMT have P-31-MRS results consistent with abnormal brain metabolism and phospholipid balance. The nearly normal metabolite profile in long-term MMT subjects suggests that prolonged MMT may be associated with improved neurochemistry. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 McLean Hosp, Brain Imaging Ctr, Belmont, MA 02478 USA. McLean Hosp, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Anxiety Disorders Program, Boston, MA 02114 USA. Habit Management Inst, Boston, MA USA. RP Kaufman, MJ (reprint author), McLean Hosp, Brain Imaging Ctr, 115 Mill St, Belmont, MA 02478 USA. FU NIDA NIH HHS [DA 09448, DA 00329, DA 11231] NR 48 TC 20 Z9 22 U1 1 U2 2 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 JUN 30 PY 1999 VL 90 IS 3 BP 143 EP 152 DI 10.1016/S0925-4927(99)00017-7 PG 10 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 225WQ UT WOS:000081989300001 PM 10466733 ER PT J AU Lee, KM Sif, S Kingston, RE Hayes, JJ AF Lee, KM Sif, S Kingston, RE Hayes, JJ TI hSWI/SNF disrupts interactions between the H2A N-terminal tail and nucleosomal DNA SO BIOCHEMISTRY LA English DT Article ID YEAST SWI/SNF COMPLEX; TRANSCRIPTION FACTORS; REMODELING FACTOR; BINDING; CHROMATIN; CORE; ACTIVATOR; PROTEIN; ENHANCEMENT; COMPONENTS AB We have employed a site-specific core histone-DNA cross-linking approach to investigate the mechanism of hSWI/SNF remodeling of a nucleosome. Remodeling results in the complete loss of canonical contacts between the N-terminal tail of H2A and DNA while new interactions are detected between this domain and DNA near the center of the original nucleosome. The data are consistent with a model in which remodeling results in the unraveling of a region of DNA from the edge of the nucleosome, leading to a repositioning of the H2A/H2B dimer to a noncanonical position near the center of the remodeled complex. Additionally, we find that prior cross-linking of the H2A N-terminal region to nucleosomal DNA does not restrict hSWI/SNF remodeling of the remainder of the nucleosome. Thus, disruption of both H2A-DNA interactions near the edge of the nucleosome is not an obligatory step in remodeling of the remainder of the complex. C1 Univ Rochester, Med Ctr, Dept Biochem & Biophys, Rochester, NY 14642 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Hayes, JJ (reprint author), Univ Rochester, Med Ctr, Dept Biochem & Biophys, Rochester, NY 14642 USA. EM jjhs@uhura.cc.rochester.edu FU NIGMS NIH HHS [GM52426] NR 32 TC 22 Z9 23 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 29 PY 1999 VL 38 IS 26 BP 8423 EP 8429 DI 10.1021/bi990090o PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 213FW UT WOS:000081262900025 PM 10387088 ER PT J AU Cha, JHJ Frey, AS Alsdorf, SA Kerner, JA Kosinski, CM Mangiarini, L Penney, JB Davies, SW Bates, GP Young, AB AF Cha, JHJ Frey, AS Alsdorf, SA Kerner, JA Kosinski, CM Mangiarini, L Penney, JB Davies, SW Bates, GP Young, AB TI Altered neurotransmitter receptor expression in transgenic mouse models of Huntington's disease SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article DE Huntington's disease; transgenic mouse; glutamate; receptor; hybridization in situ; striatum ID NEURONAL INTRANUCLEAR INCLUSIONS; INHERITED NEURODEGENERATIVE DISEASES; GLUTAMATE BINDING-SITES; QUANTITATIVE AUTORADIOGRAPHY; ADENOSINE-A2 RECEPTORS; TRINUCLEOTIDE REPEATS; QUINOLINIC ACID; MESSENGER-RNA; BASAL GANGLIA; BRAIN AB Alterations in neurotransmitter receptors are a pathological hallmark of the neurodegeneration seen in Huntington's disease (HD). However, the significance of these alterations has been uncertain, possibly reflecting simply the loss of brain cells. It is not known for certain whether the alteration of neurotransmitter receptors occurs before the onset of symptoms in human HD. Recently we developed transgenic mice that contain a portion of a human HD gene and develop a progressive abnormal neurological phenotype. Neurotransmitter receptors that are altered in HD (receptors for glutamate, dopamine, acetylcholine and adenosine) are decreased in the brain of transgenic mice, in some cases before the onset of behavioural or motor symptoms. In transgenic mice, neurotransmitter receptor alterations occur before neuronal death. Further, receptor alterations are selective in that certain receptors, namely N-methyl-D-aspartate and gamma-aminobutyric acid receptors! are unaltered. Finally, receptor decreases are preceded by selective decreases in the corresponding mRNA species, suggesting the altered transcription of specific genes. These results suggest that (i) receptor decreases precede, and therefore might contribute to the development of clinical symptoms, and (ii) altered transcription of specific genes might be a key pathological mechanism in HD. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Kings Coll London, GKT Med & Dent Sch, London SE1 9RT, England. UCL, Dept Anat & Dev Biol, London WC1E 6BT, England. RP Cha, JHJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Fruit St, Boston, MA 02114 USA. EM cha@helix.mgh.harvard.edu RI Bates, Gillian/E-1146-2012 OI Bates, Gillian/0000-0002-4041-6305 NR 47 TC 155 Z9 157 U1 0 U2 3 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 J9 PHILOS T R SOC B JI Philos. Trans. R. Soc. B-Biol. Sci. PD JUN 29 PY 1999 VL 354 IS 1386 BP 981 EP 989 DI 10.1098/rstb.1999.0449 PG 9 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 218UM UT WOS:000081570600004 PM 10434296 ER PT J AU Feng, S Quickel, RR Hollister-Lock, J McLeod, M Bonner-Weir, S Mulligan, RC Weir, GC AF Feng, S Quickel, RR Hollister-Lock, J McLeod, M Bonner-Weir, S Mulligan, RC Weir, GC TI Prolonged xenograft survival of islets infected with small doses of adenovirus expressing CTLA4Ig SO TRANSPLANTATION LA English DT Article ID MEDIATED GENE-TRANSFER; LONG-TERM ACCEPTANCE; T-CELL ACTIVATION; RECOMBINANT ADENOVIRUSES; IN-VIVO; ALLOGRAFT-REJECTION; MOUSE-LIVER; CARDIAC ALLOGRAFTS; IMMUNE-RESPONSES; TRANSDUCTION AB Background. Systemic administration of the inhibitor of costimulation, CTLA4Ig, has been shown to prolong islet graft survival. The purpose of this study was to compare local and systemic expression of murine CTLA4Ig in transplants of rat islets into mice. Methods. Murine CTLA4Ig was made by joining two polymerase chain reaction products, the extracellular portion of CTLA4 and the Pc portion of IgG2a. Recombinant adenovirus expressing CTLA4Ig (AdCTLA4Ig) was generated using the strategy of Cre-lox recombination. Isolated rat islets infected with AdCTLA4Ig at multiplicities of infection (MOIs) ranging from 0.1 to 10 were transplanted into streptozocin diabetic male B6AF1 mice. Control islets were mock infected or infected with AdLacZ or AdsIg, a recombinant adenovirus expressing only the Fc portion of IgG2a. Also, AdCTLA4Ig and control viruses were injected intramuscularly into mouse transplant recipients at the time of islet transplantation to provide CTLA41g systemically. Results. Control islets transplanted into diabetic mice were rejected in 13-17 days. Islets infected with AdCTLA4Ig had dose-dependent prolongation of graft survival. Prolonged survival was even found with very low MOIs of 0.1 and 0.5, with survivals of 24+/-4.2 and 25+/-2.2 days, respectively. Survival with an MOI of 10 was 39+/-8.7 days. With intramuscular injection, no prolongation was found at the lowest relative MOIs of 0.2 and 1, but there was dose-dependent prolongation of graft survival with larger doses. At the highest relative MOI of 400, survival was prolonged to 58+/-10 days. Conclusions. Rat islets infected with AdCTLA4Ig transplanted into mice had prolonged graft survival. Prolonged survival with MOIs as low as 0.1 and 0.5 indicates that only a minority of islet cells need to express CTLA4Ig to exert an effect. Moreover, the results suggest that the improved islet graft survival is due to a local influence of CTLA4Ig. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Feng, S (reprint author), Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, 55 Fruit St,Blake 655, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-36836, DK-50657, DK-53087] NR 43 TC 42 Z9 48 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 JUN 27 PY 1999 VL 67 IS 12 BP 1607 EP 1613 DI 10.1097/00007890-199906270-00016 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 213AH UT WOS:000081249500016 PM 10401769 ER PT J AU Moulton, KS Melder, RJ Dharnidharka, VR Hardin-Young, J Jain, RK Briscoe, DM AF Moulton, KS Melder, RJ Dharnidharka, VR Hardin-Young, J Jain, RK Briscoe, DM TI Angiogenesis in the huPBL-SCID model of human transplant rejection SO TRANSPLANTATION LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; LYMPHOCYTE-INDUCED ANGIOGENESIS; MICE; ALLOGRAFTS; ADHESION; VEGF; SKIN AB Background. Angiogenesis is characteristic of chronic inflammatory reactions. The process of angiogenesis is reported to be proinflammatory in part due to enhanced adhesion events and in part due to increased perfusion and permeability to sites of inflammation. However, little is known about the association between angiogenesis and rejection. Methods. Severe combined immune deficient mice are permissive for the growth of human skin allografts and human peripheral blood mononuclear cells (PBMC). Human PBMC were injected into mice by intravenous or intraperitoneal injection. The infiltration of cells and the associated angiogenesis reactions in the skin allografts were analyzed temporally by videomicroscopy and spatially by immunohistochemistry. Results. Human alloreactive mononuclear cells migrated to human skin but not mouse skin within hours after the intravenous infusion of PBMC. Within 3 days, areas of angiogenesis were observed in the skin grafts at the sites of infiltrates. The vessel densities in skin grafts were 24+/-6 vessels per calibrated grid at baseline on the day of the infusion and increased to 55+/-16 vessels per calibrated field by day 10. Skin grafts harvested from humanized severe combined immune deficient mice 7-14 days after the intraperitoneal infusion of human PBMC showed a similar increased density of vessels that were spatially associated with mononuclear cell infiltrates. Conclusions. A significant angiogenesis response was associated with the cell infiltrates in the human skin allografts. The onset uf angiogenesis appeared after the initial development of localized infiltrates and preceded the development of microvascular destruction. These findings suggest that alloreactive T cells and/or monocytes mediate the angiogenesis response in skin allografts. C1 Childrens Hosp, Dept Med, Div Nephrol, Boston, MA 02115 USA. Childrens Hosp, Dept Surg, Surg Res Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. Organogenesis Inc, Canton, MA USA. RP Briscoe, DM (reprint author), Childrens Hosp, Dept Med, Div Nephrol, 300 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [R35 CA 56591]; NIDDK NIH HHS [R21 DK 53606] NR 20 TC 28 Z9 29 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 JUN 27 PY 1999 VL 67 IS 12 BP 1626 EP 1631 DI 10.1097/00007890-199906270-00020 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 213AH UT WOS:000081249500020 PM 10401773 ER PT J AU Freedman, JE Sauter, R Battinelli, EM Ault, K Knowles, C Huang, PL Loscalzo, J AF Freedman, JE Sauter, R Battinelli, EM Ault, K Knowles, C Huang, PL Loscalzo, J TI Deficient platelet-derived nitric oxide and enhanced hemostasis in mice lacking the NOSIII gene SO CIRCULATION RESEARCH LA English DT Article DE selectin; mice; platelet; nitric oxide synthase ID SYNTHASE INHIBITION; ENDOTHELIAL-CELLS; RELAXING FACTOR; AGGREGATION; THROMBOSIS; HYPERTENSION; RECRUITMENT; REACTIVITY; INFARCTION; SECRETION AB Endothelial nitric oxide synthase (eNOS) has been identified inhuman platelets. Although platelet-derived nitric oxide (NO) has been shown to inhibit platelet recruitment in vitro, its role in the regulation of the hemostatic ;response in vivo has not been characterized. To define the role of platelet-derived NO in vivo, we studied mice that lacked a functional eNOS gene (NOSIII). Surface P-selectin expression in platelets from eNOS-deficient mice was not significantly altered; however, bleeding times were markedly decreased in eNOS-deficient versus wild-type mice (77.2+/-3 versus 133.4+/-3 seconds, P<0.00005). To determine the contribution of endothelium- versus platelet-derived NO to the bleeding time, isolated platelets from either eNOS-deficient or wild-type mice were transfused into a thrombocytopenic eNOS-deficient mouse and the bleeding time was measured. The bleeding times in mice transfused with eNOS-deficient platelets were significantly decreased compared with mice transfused with wild-type platelets (Delta bleeding time, -24.6 +/- 9.1 and -3.4+/-5.3 seconds, respectively; P<0.04). Platelet recruitment was studied by measuring serotonin release from a second recruitable population of platelets that were added to stimulated platelets at the peak of NO production. There was 40.3+/-3.7% and 52.0+/-2.1% serotonin release for platelets added to wild-type or eNOS-deficient platelets, respectively (P<0.05). In summary, mice that lacked eNOS had markedly decreased bleeding times even after endothelial NO production was controlled. These data suggest that the lack of platelet-derived NO alters in vivo hemostatic response by increasing platelet recruitment. Thus, these data support a role for platelet-derived NO production in the regulation of hemostasis. C1 Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02215 USA. Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02215 USA. Maine Med Ctr, Res Inst, S Portland, ME USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. RP Freedman, JE (reprint author), Georgetown Univ, Med Ctr, Dept Pharmacol, Med Dent Bldg,Room NE 403,3900 Reservoir Rd NW, Washington, DC 20007 USA. FU NHLBI NIH HHS [HL-48743, K08 HL-03556, HL-55993] NR 34 TC 132 Z9 138 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUN 25 PY 1999 VL 84 IS 12 BP 1416 EP 1421 PG 6 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 211DU UT WOS:000081145300008 PM 10381894 ER PT J AU Lichtenthaler, SF Multhaup, G Masters, CL Beyreuther, K AF Lichtenthaler, SF Multhaup, G Masters, CL Beyreuther, K TI A novel substrate for analyzing Alzheimer's disease gamma-secretase SO FEBS LETTERS LA English DT Article DE signal peptidase; gamma-secretase; Alzheimer's disease; amyloid precursor protein; protein transport ID AMYLOID PRECURSOR PROTEIN; BETA-PEPTIDE; TRANSMEMBRANE DOMAIN; CLEAVAGE; GENERATION; FRAGMENTS; SEQUENCE; CELLS AB Proteolytic processing of Alzheimer's disease amyloid precursor protein (APP) by beta-secretase leads to A4CT (C99), which is further cleaved by the as yet unknown protease called gamma-secretase, To study the enzymatic properties of gamma-secretase independently of beta-secretase, A4CT together with an N-terminal signal peptide (SPA4CT) may be expressed in eukaryotic cells. However, in all existing SPA4CT proteins the signal peptide is not correctly cleaved upon membrane insertion. Here, we report the generation of a mutated SPA4CT protein that is correctly cleaved by signal peptidase and, thus, identical to the APP-derived A4CT. This novel SPA4CT protein is processed by gamma-secretase in the same manner as APP-derived A4CT and might be valuable for the generation of transgenic animals shelving amyloid pathology, (C) 1999 Federation of European Biochemical Societies. C1 Univ Heidelberg, ZMBH, Ctr Mol Biol Heidelberg, D-69120 Heidelberg, Germany. Univ Melbourne, Parkville, Vic 3052, Australia. RP Lichtenthaler, SF (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Wellman Bldg,9th Floor,50 Blossom St, Boston, MA 02114 USA. RI Lichtenthaler, Stefan/B-6587-2016 OI Lichtenthaler, Stefan/0000-0003-2211-2575 NR 33 TC 43 Z9 43 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUN 25 PY 1999 VL 453 IS 3 BP 288 EP 292 DI 10.1016/S0014-5793(99)00730-9 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 212XC UT WOS:000081242100011 PM 10405162 ER PT J AU Dery, O Thoma, MS Wong, H Grady, EF Bunnett, NW AF Dery, O Thoma, MS Wong, H Grady, EF Bunnett, NW TI Trafficking of proteinase-activated receptor-2 and beta-arrestin-1 tagged with green fluorescent protein - beta-arrestin-dependent endocytosis of a proteinase receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAST-CELL TRYPTASE; COUPLED RECEPTOR; ADRENERGIC-RECEPTOR; BETA(2)-ADRENERGIC RECEPTOR; THROMBIN RECEPTOR; MOLECULAR-CLONING; CHOLECYSTOKININ RECEPTOR; MEDIATED ENDOCYTOSIS; PLATELET ACTIVATION; SUBSTANCE-P AB Proteases cleave proteinase-activated receptors (PARs) to expose N-terminal tethered ligands that bind and activate the cleaved receptors. The tethered ligand, once exposed, is always available to interact with its binding site. Thus, efficient mechanisms must prevent continuous activation, including receptor phosphorylation and uncoupling from G-proteins, receptor endocytosis, and lysosomal degradation. beta-Arrestins mediate uncoupling and endocytosis of certain neurotransmitter receptors, which are activated in a reversible manner. However, the role of beta-arrestins in trafficking of PARs, which are irreversibly activated, and the effects of proteases on the subcellular distribution of beta-arrestins have not been examined. We studied trafficking of PARS and beta-arrestin1 coupled to green fluorescent protein. Trypsin induced the following: (a) redistribution of beta-arrestin1 from the cytosol to the plasma membrane, where it co-localized with PAR2; (b) internalization of beta-arrestin1 and PARS into the same early endosomes; (c) redistribution of beta-arrestin1 to the cytosol concurrent with PARS translocation to lysosomes; and (d) mobilization of PARS from the Gels apparatus to the plasma membrane. Overexpression of a C-terminal fragment of beta-arrestin-(319-418), which interacts constitutively with clathrin but does not bind receptors, inhibited agonist-induced endocytosis of PARS. Our results show that p-arrestins mediate endocytosis of PARS and support a role for beta-arrestins in uncoupling of PARs. C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. W Los Angeles Vet Affairs Med Ctr, CURE, Digest Dis Res Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. RP Bunnett, NW (reprint author), Univ Calif San Francisco, Dept Surg, 521 Parnassus Ave, San Francisco, CA 94143 USA. FU NIDDK NIH HHS [DK39957, DK42307]; NINDS NIH HHS [NS21710] NR 54 TC 122 Z9 124 U1 0 U2 3 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 JUN 25 PY 1999 VL 274 IS 26 BP 18524 EP 18535 DI 10.1074/jbc.274.26.18524 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 209PJ UT WOS:000081056700053 PM 10373461 ER PT J AU Shoba, L An, MR Frank, SJ Lowe, WL AF Shoba, L An, MR Frank, SJ Lowe, WL TI Developmental regulation of insulin-like growth factor-I and growth hormone receptor gene expression SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE IGF-1; GH receptor; heart; kidney; IGFI-FPI ID MESSENGER RIBONUCLEIC-ACIDS; TARGETED DISRUPTION; BINDING-PROTEIN; SOMATOMEDIN-C; DIFFERENTIAL EXPRESSION; TISSUE CONCENTRATIONS; MAJOR PROMOTER; NEONATAL RAT; TRANSCRIPTION; SERUM AB During development, the insulin-like growth factor I (IGF-I) gene is expressed in a tissue specific manner; however, the molecular mechanisms governing its developmental regulation remain poorly defined. To examine the hypothesis that expression of the growth hormone (GH) receptor accounts, in part, for the tissue specific expression of the IGF-I gene during development, the developmental regulation of IGF-I and GH receptor gene expression in rat tissues was examined. The level of IGF-I and GH receptor mRNA was quantified in RNA prepared from rats between day 17 of gestation (E17) and 17 months of age (17M) using an RNase protection assay. Developmental regulation of IGF-I gene expression was tissue specific with four different patterns of expression seen. In liver, IGF-I mRNA levels increased markedly between E17 and postnatal day 45 (P45) and declined thereafter. In contrast, in brain, skeletal muscle and testis, IGF-I mRNA levels decreased between P5 and 4M but were relatively unchanged thereafter. In heart and kidney, a small increase in IGF-I mRNA levels was observed between the early postnatal period and 4 months, whereas in lung, minimal changes were observed during development. The changes in GH receptor mRNA levels were, in general, coordinate with the changes in IGF-I mRNA levels, except in skeletal muscle. Interestingly, quantification of GH receptor levels by Western blot analysis in skeletal muscle demonstrated changes coordinate with IGF-I mRNA levels. The levels of the proteins which mediate GH receptor signaling (STAT1, -3, and -5, and JAK2) were quantified by Western blot analysis. These proteins also are expressed in a tissue specific manner during development. In some cases, the pattern of expression was coordinate with IGF-I gene expression, whereas in others it was discordant. To further define molecular mechanisms for the developmental regulation of IGF-I gene expression, protein binding to IGFI-FP1, a protein binding site that is in the major promoter of the rat IGF-I gene and is important for basal promoter activity in vitro, was examined. Gel shift analyses using a 34-base pair oligonucleotide that contained IGFI-FP1 did not demonstrate changes in protein binding that paralleled those in IGF-I gene expression, suggesting that protein binding to IGFI-FP1 does not contribute to the developmental regulation of IGF-I gene expression, at least in brain and liver. In summary, the present studies demonstrate coordinate expression of the IGF-I gene and GH receptor during development and suggest that GH receptor expression contributes to the tissue specific expression of the IGF-I gene during development. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 VA Chicago Healthcare Syst, Dept Med, Ctr Endocrinol Metab & Mol Med, Lakeside Div, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Chicago, IL 60611 USA. Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL 35294 USA. RP Lowe, WL (reprint author), VA Chicago Healthcare Syst, Dept Med, Ctr Endocrinol Metab & Mol Med, Lakeside Div, 303 E Chicago Ave,Tarry 15-703, Chicago, IL 60611 USA. EM wlowe@nwu.edu NR 55 TC 29 Z9 31 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JUN 25 PY 1999 VL 152 IS 1-2 BP 125 EP 136 DI 10.1016/S0303-7207(99)00045-3 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 210TN UT WOS:000081120900013 PM 10432230 ER PT J AU Czeisler, CA Duffy, JF Shanahan, TL Brown, EN Mitchell, JF Rimmer, DW Ronda, JM Silva, EJ Allan, JS Emens, JS Dijk, DJ Kronauer, RE AF Czeisler, CA Duffy, JF Shanahan, TL Brown, EN Mitchell, JF Rimmer, DW Ronda, JM Silva, EJ Allan, JS Emens, JS Dijk, DJ Kronauer, RE TI Stability, precision, and near-24-hour period of the human circadian pacemaker SO SCIENCE LA English DT Article ID FREE-RUNNING PERIOD; DROSOPHILA PERIOD; CLOCK MUTANTS; BRIGHT LIGHT; SUPRACHIASMATIC NUCLEI; MATHEMATICAL-MODEL; BODY-TEMPERATURE; PHASE-SHIFTS; RHYTHMS; SLEEP AB Regulation of circadian period in humans was thought to differ from that of other species, with the period of the activity rhythm reported to range from 13 to 65 hours (median 25.2 hours) and the period of the body temperature rhythm reported to average 25 hours in adulthood, and to shorten with age. However, those observations were based on studies of humans exposed to Light Levels sufficient to confound circadian period estimation. Precise estimation of the periods of the endogenous circadian rhythms of melatonin, core body temperature, and cortisol in healthy young and older individuals Living in carefully controlled Lighting conditions has now revealed that the intrinsic period of the human circadian pacemaker averages 24.18 hours in both age groups, with a tight distribution consistent with other species. These findings have important implications for understanding the pathophysiology of disrupted sleep in older people. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Med,Div Endocrinol, Circadian Neuroendocrine & Sleep Disorders Sect, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Div Engn & Appl Sci, Cambridge, MA 02138 USA. RP Czeisler, CA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Med,Div Endocrinol, Circadian Neuroendocrine & Sleep Disorders Sect, 221 Longwood Ave, Boston, MA 02115 USA. RI Dijk, Derk-Jan/D-8387-2011 FU NCRR NIH HHS [MO1-RR02635]; NIA NIH HHS [P01-AG09975]; NIGMS NIH HHS [R01-GM53559] NR 85 TC 659 Z9 673 U1 9 U2 64 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 JUN 25 PY 1999 VL 284 IS 5423 BP 2177 EP 2181 DI 10.1126/science.284.5423.2177 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 210HP UT WOS:000081099300052 PM 10381883 ER PT J AU Gong, JG Costanzo, A Yang, HQ Melino, G Kaelin, WG Levrero, M Wang, JYJ AF Gong, JG Costanzo, A Yang, HQ Melino, G Kaelin, WG Levrero, M Wang, JYJ TI The tyrosine kinase c-Abl regulates p73 in apoptotic response to cisplatin-induced DNA damage SO NATURE LA English DT Article ID MISMATCH REPAIR DEFICIENCY; FLOW-CYTOMETRY; CELLS; PROTEIN; P53; RADIATION; STRESS; MICE AB Cancer chemotherapeutic agents such as cisplatin exert their cytotoxic effect by inducing DNA damage and activating programmed cell death (apoptosis), The tumour-suppressor protein p53 is an important activator of apoptosis. Although p53-deficient cancer cells are less responsive to chemotherapy, their resistance is not complete, which suggests that other apoptotic pathways may exist. A p53-related gene, p73, which encodes several proteins as a result of alternative splicing(1,2), can also induce apoptosis(3). Here we show that the amount of p73 protein in the cell is increased by cisplatin. This induction of p73 is not seen in cells unable to carry out mismatch repair and in which the nuclear enzyme c-Abl tyrosine kinase is not activated by cisplatin, The half-life of p73 is prolonged by cisplatin and by co-expression with c-Abl tyrosine kinase; the apoptosis-inducing function of p73 is also enhanced by the c-Abl kinase, Mouse embryo fibroblasts deficient in mismatch repair or in c-Abl do not upregulate p73 and are more resistant to killing by cisplatin. Our results indicate that c-Abl and p73 are components ofa mismatch-repair-dependent apoptosis pathway which contributes to cisplatin-induced cytotoxicity. C1 Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA. Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA. Univ Rome La Sapienza, Fdn A Cesalpino, Gene Express Lab, I-00161 Rome, Italy. Univ Roma Tor Vergata, Dept Expt Med, IRCCS, Ist Dermopatico Immacolata,Biochem Lab, I-00133 Rome, Italy. Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wang, JYJ (reprint author), Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA. RI Costanzo, Antonio/D-3896-2012 FU NCI NIH HHS [R37 CA043054] NR 22 TC 727 Z9 744 U1 3 U2 21 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 24 PY 1999 VL 399 IS 6738 BP 806 EP 809 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 210JP UT WOS:000081101600059 PM 10391249 ER PT J AU Yuan, ZM Shioya, H Ishiko, T Sun, XG Gu, JJ Huang, YY Lu, H Kharbanda, S Weichselbaum, R Kufe, D AF Yuan, ZM Shioya, H Ishiko, T Sun, XG Gu, JJ Huang, YY Lu, H Kharbanda, S Weichselbaum, R Kufe, D TI P73 is regulated by tyrosine kinase c-Abl in the apoptotic response to DNA damage SO NATURE LA English DT Article ID PROTEIN; P53; ACTIVATION; RADIATION; AGENTS; GROWTH AB The protein p73 is a structural and functional homologue of the p53 tumour-suppressor protein but, unlike p53, it is not induced in response to DNA damage(1,2). The tyrosine kinase c-Abl is activated by certain DNA-damaging agents(3) and contributes to the induction of programmed cell death (apoptosis) by p53-dependent and p53-independent mechanisms(4). Here we show that c-Abl binds to p73 in cells, interacting through its SH3 domain with the carboxy-terminal homo-oligomerization domain of p73, c-Abl phosphorylates p73 on a tyrosine residue at position 99 both in vitro and in cells that have been exposed to ionizing radiation. Our results show that c-Abl stimulates p73-mediated transactivation and apoptosis. This regulation of p73 by c-Abl in response to PNA damage is also demonstrated by a failure of ionizing-radiation-induced apoptosis after disruption of the c-Abl-p73 interaction. These findings show that p73 is regulated by a c-Abl-dependent mechanism and that p73 participates in the apoptotic response to DNA damage. C1 Harvard Univ, Sch Publ Hlth, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Oregon Hlth Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97201 USA. Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Publ Hlth, Dept Canc Biol, 665 Huntington Ave, Boston, MA 02115 USA. OI Huang, Ying/0000-0003-1145-3606 NR 21 TC 473 Z9 481 U1 0 U2 6 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 24 PY 1999 VL 399 IS 6738 BP 814 EP 817 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 210JP UT WOS:000081101600061 PM 10391251 ER PT J AU Bonmassar, G Anami, K Ives, J Belliveau, JW AF Bonmassar, G Anami, K Ives, J Belliveau, JW TI Visual evoked potential (VEP) measured by simultaneous 64-channel EEG and 3T fMRI SO NEUROREPORT LA English DT Article DE ballistocardiogram; brain imaging; EEG; ERP; fMRI; simultaneous EEG fMRI; spatial filter; VEP; visual evoked potentials ID MRI AB WE present the first simultaneous measurements of evoked potentials (EPs) and fMRI hemodynamic responses to visual stimulation. Visual evoked potentials (VEPs) were recorded both inside and outside the static 3T magnetic field, and during fMRI examination. We designed, constructed, and tested a non-magnetic 64-channel EEG recording cap. By using a large number of EEG channels it is possible to design a spatial filter capable of removing the artifact noise present when recording EEG/EPs within a strong magnetic field. We show that the designed spatial filter is capable of recovering the ballistocardiogram-contaminated original EEG signal. Isopotential plots of the electrode array recordings at the peak of the VEP response (similar to 100 ms) correspond well with simultaneous fMRI observed activated areas of primary and secondary visual cortices. NeuroReport 10:1893-1897 (C) 1999 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Bonmassar, G (reprint author), Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. FU NINDS NIH HHS [R01 NS37462] NR 15 TC 105 Z9 106 U1 2 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUN 23 PY 1999 VL 10 IS 9 BP 1893 EP 1897 DI 10.1097/00001756-199906230-00018 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 212PM UT WOS:000081225500021 PM 10501528 ER PT J AU Lopez-Rodriguez, C Aramburu, J Rakeman, AS Rao, A AF Lopez-Rodriguez, C Aramburu, J Rakeman, AS Rao, A TI NFAT5, a constitutively nuclear NFAT protein that does not cooperate with Fos and Jun SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRANSCRIPTION FACTOR NFAT1; T-CELLS; MICE LACKING; DNA-BINDING; GENE FAMILY; CALCINEURIN; ATC; IL-4; LYMPHOCYTES; ACTIVATION AB NFAT transcription factors are related to NF-kappa B/Rel proteins and form cooperative complexes with Fos and Jun on DNA. We have identified an NFAT-related protein, NFAT5, which differs from the conventional NFAT proteins NFAT1-4 in its structure, DNA binding, and regulation. NFAT5 contains a NFAT-like Rel homology domain, conserves the DNA contact residues of NFAT1-4, and binds DNA sequences similar to those found in the regulatory regions of well-eharacterized NFAT-dependent genes. However, it lacks the majority of Fos/Jun contact residues and does not bind cooperatively with Fos and Jun to DNA. Unlike NFAT1-4 whose nuclear import is tightly regulated by calcineurin-mediated dephosphorylation, NFAT5 is a constitutively nuclear phosphoprotein regardless of calcineurin activation. These features suggest that unlike the conventional NFAT proteins, NFAT1-4, which activate gene transcription by integrating inputs from calcium/calcineurin and protein kinase C/mitogen-activated protein kinase signaling pathways, NFAT5 participates in as-yet-unidentified signaling pathways in diverse immune and nonimmune cells. C1 Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, Boston, MA 02115 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. RI Lopez-Rodriguez, C/G-4482-2014; Aramburu, J/G-8991-2014 OI Lopez-Rodriguez, C/0000-0002-2311-2406; Aramburu, J/0000-0001-9279-9523 FU NCI NIH HHS [CA-42471, R01 CA042471, R37 CA042471]; NIAID NIH HHS [AI-40127, R01 AI040127] NR 41 TC 250 Z9 256 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 JUN 22 PY 1999 VL 96 IS 13 BP 7214 EP 7219 DI 10.1073/pnas.96.13.7214 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 209PB UT WOS:000081056000020 PM 10377394 ER PT J AU Kishimoto, J Ehama, R Wu, L Jiang, SW Jiang, NY Burgeson, RE AF Kishimoto, J Ehama, R Wu, L Jiang, SW Jiang, NY Burgeson, RE TI Selective activation of the versican promoter by epithelial-mesenchymal interactions during hair follicle development SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PG-M; GENE CSPG2; PROTEOGLYCAN; MOUSE; GROWTH; PAPILLA; CELLS; RAT; LOCALIZATION; EXPRESSION AB Interaction between the epithelium and the mesenchyme is an essential feature of organogenesis, including hair follicle formation, The dermal papilla (DP), a dense aggregate of specialized dermis-derived stromal cells located at the bottom of the follicle, is a major component of hair that signals the follicular epithelial cells to prolong the hair growth th process. However, little is known about DP-specific gene activation with regard to hair induction. In this study we demonstrate that a short fragment (839 bp) of the human versican (a core protein of one of the matrix chondroitin sulfate proteoglycans) promoter is sufficient to activate lacZ reporter gene expression in the DP of postnatal transgenic mice and also in the condensed mesenchyme (the origin of the DP) beneath the hair placode during hair follicle embryogenesis, Using the same versican promoter with green fluorescent protein (GFP), large numbers of fresh pelage DP cells were isolated from new born transgenic skin by high-speed cell sorting. These GFP-positive DP cells show ed abundant, versican mRNA confirming that the reporter molecules reflected endogenous versican gene expression, These sorted GFP-positive cells showed DP-like morphology in culture, but both GFP and,versican expression was lost during primary culture. In vivo hair growth assays showed that GFP-positive cells could induce hair when grafted with epithelial cells, whereas GFP-negative cells grafted with epithelium or GFP positive cells alone did not. These results suggest that versican may play an essential role both in mesenchymal condensation and in hair induction. C1 Massachusetts Gen Hosp, Harvard Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Kishimoto, J (reprint author), Massachusetts Gen Hosp, Harvard Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 29 TC 132 Z9 139 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 22 PY 1999 VL 96 IS 13 BP 7336 EP 7341 DI 10.1073/pnas.96.13.7336 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 209PB UT WOS:000081056000041 PM 10377415 ER PT J AU Lauge, A Lefebvre, C Laurent-Puig, P Caux, V Gad, S Eng, C Longy, M Stoppa-Lyonnet, D AF Lauge, A Lefebvre, C Laurent-Puig, P Caux, V Gad, S Eng, C Longy, M Stoppa-Lyonnet, D TI No evidence for germline PTEN mutations in families with breast and brain tumours SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID COWDEN-DISEASE; MENINGIOMA PROGRESSION; PROSTATE-CANCER; SUPPRESSOR GENE; PHOSPHATASE; CHROMOSOME-10; PTEN/MMAC1; CARCINOMAS; BRCA1; MMAC1 AB Germline mutations of the PTEN gene are involved in Cowden disease, a genetic condition associated with an increased risk of breast cancer. Further somatic PTEN mutations have been found in glioblastomas and to a lesser extent in meningiomas. Therefore, PTEN germline mutations were searched for in a series of 20 unrelated women with breast cancer who also had a personal or familial breast-brain tumour history. Inclusion criteria were I. family history of breast cancer; 2, absence of germline BRCAI and p53 mutation; and 3, at least one case of brain tumour (glioblastoma, meningioma, or medulloblastoma) in either the index case or one of their first or second degree relatives. Any stigmata of Cowden disease was an exclusion criteria. Screening of the PTEN gene for point mutations or small rearrangements were performed using the denaturing gradient gel electrophoresis method on the 9 coding exons. No disease-associated mutation of the PTEN gene has been detected in our series, It is, thus, unlikely that PTEN is a significant BRCA predisposing locus, However, one might ask whether breast cancer cases resulting from germline PTEN mutation could occur without any mammary histological feature of Cowden disease. Int. J. Cancer (Pred. Oncol) 84:216-219, 1999. (C) 1999 Wiley-Liss, Inc. C1 Inst Curie, Unite Genet Oncol, F-75231 Paris 5, France. INSERM, U490, Mol Toxicol Lab, Paris, France. Harvard Univ, Sch Med,Dana Farber Canc Inst, Dept Adult Oncol,Charles A Dana Human Canc Genet, Translat Res Lab, Boston, MA 02115 USA. Univ Cambridge, Canc Res Campaign, Human Canc Genet Res Grp, Cambridge, England. Inst Bergonie, Bordeaux, France. RP Stoppa-Lyonnet, D (reprint author), Inst Curie, Unite Genet Oncol, 26 Rue Ulm, F-75231 Paris 5, France. RI Lefebvre, Celine/E-6290-2013; laurent-puig, pierre/B-2226-2013; OI laurent-puig, pierre/0000-0001-8475-5459; Eng, Charis/0000-0002-3693-5145 NR 25 TC 17 Z9 17 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 21 PY 1999 VL 84 IS 3 BP 216 EP 219 DI 10.1002/(SICI)1097-0215(19990621)84:3<216::AID-IJC3>3.3.CO;2-5 PG 4 WC Oncology SC Oncology GA 202MZ UT WOS:000080657600003 PM 10371336 ER PT J AU Le Doux, JM Davis, HE Morgan, JR Yarmush, ML AF Le Doux, JM Davis, HE Morgan, JR Yarmush, ML TI Kinetics of retrovirus production and decay SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE recombinant retroviruses; gene therapy; virus production; virus decay; transduction efficiency; virus titer ID MEDIATED GENE-TRANSFER; HIGH-TITER; CELL-LINE; EFFICIENCY; INFECTION; THERAPY; OPTIMIZATION; TRANSDUCTION; ENHANCEMENT; INVITRO AB There has been only limited success in using recombinant retroviruses to transfer genes for the purposes of human gene therapy, in part because the average number of genes delivered to the target cells (transduction efficiency) is often too low to achieve the desired therapeutic effect [Miller, AD. 1990. Blood 76:271-278; Mulligan RC. 1993. Science 260:926-932; Orkin SH, Motulsky AG. 1995. Report: and recommendations of the panel to assess the NIH investment in research on gene therapy. Bethesda, MD: National Institutes of Health.]. One strategy to improve transduction efficiency is to focus on understanding and improving the processes used to produce recombinant retroviruses. In this report, we characterized the dynamics of retrovirus production and decay in batch cultures of virus producer cells using a simple mathematical model, a recombinant retrovirus encoding the Escherichia coli lacZ gene, and quantitative assays for virus activity and number. We found that the rate at which recombinant retroviruses spontaneously lose their activity (decay) is a strong function of temperature, decreasing roughly 2-fold for every 5 degrees C reduction in temperature, whereas the rate at which retroviruses are produced is only weakly affected by temperature, decreasing about 10% for every 5 degrees C reduction in temperature. In addition, we developed a simple mathematical model of virus production and decay that predicted that the virus titer in batch cultures of virus producer cells would reach a maximum steady-state at a rate that is inversely proportional to the virus decay rate and to a level that is proportional to the ratio of the virus production rate to the virus decay rate. Consistent with the model, we observed that the steady-state levels of virus titer increased more than 3-fold when the cell culture temperature was reduced from 37 to 28 degrees C. Despite their higher titers, virus stocks produced at 28 degrees C, when used in undiluted form so as to mimic human gene transfer protocols, did not transduce substantially more cells than virus stocks produced at 37 degrees C. The implications of our findings on the production of retroviruses for use in human gene therapy protocols are discussed. (C) 1999 John Wiley & Sons, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Serv, Boston, MA 02114 USA. Shriners Burns Hosp, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. OI Morgan, Jeffrey/0000-0002-7546-3443 FU NIAMS NIH HHS [R29 AR42012]; NICHD NIH HHS [P01 HD28528]; NIGMS NIH HHS [GM-08339] NR 26 TC 81 Z9 81 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-3592 EI 1097-0290 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD JUN 20 PY 1999 VL 63 IS 6 BP 654 EP 662 DI 10.1002/(SICI)1097-0290(19990620)63:6<654::AID-BIT3>3.0.CO;2-1 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 189FT UT WOS:000079894400003 PM 10397822 ER PT J AU Gunthard, HF Leigh-Brown, AJ D'Aquila, RT Johnson, VA Kuritzkes, DR Richman, DD Wong, JK AF Gunthard, HF Leigh-Brown, AJ D'Aquila, RT Johnson, VA Kuritzkes, DR Richman, DD Wong, JK TI Higher selection pressure from antiretroviral drugs in vivo results in increased evolutionary distance in HIV-1 pol SO VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN; GENETIC DIVERSITY; MULLER RATCHET; TYPE-1; RESISTANCE; THERAPY; RECOMBINATION; ZIDOVUDINE; MUTATIONS AB We investigated the effect of selection pressures on evolution of HIV-1 pol in 51 patients after switching to a new antiretroviral combination reverse transcriptase (RT) inhibitor therapy. Evolution of the protease (PR) and RT reading frames were analysed separately, Pairwise evolutionary distances (ED) were calculated between sequences from baseline and week 8 and between baseline and week 48 of protocol therapy ED were calculated for all substitutions and for synonymous and nonsynonymous substitutions separately. At week 8 when HIV RNA reduction (selection pressure) was high, significantly more divergence in pol in both synonymous and nonsynonymous substitutions was found in patients with substantial RNA reduction (strong responders). Separate analyses of PR and RT revealed significantly greater ED in the RT (under selection pressure) of strong compared with nonresponders, whereas divergence between PR genes (not under selection pressure) did not differ in those two groups. Such differential evolution indicates that PR and RT were genetically unlinked and suggests recombination. The rapid increase of ED over the first 8 weeks was followed by only a minimal further rise by week 48, suggesting that selection of preexisting quasispecies accounted for the early changes. A disproportionally high number of synonymous substitutions accounted for the observed divergence and indicated that such genetic changes may not be completely silent. (C) 1999 Academic Press. C1 Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. San Diego Vet Affairs Med Ctr, La Jolla, CA 92093 USA. Univ Edinburgh, Ctr HIV Res, Edinburgh EH9 3JN, Midlothian, Scotland. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Alabama, Sch Med, Dept Med, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. RP Gunthard, HF (reprint author), Univ Zurich Hosp, Dept Internal Med, Div Infect Dis, Ramistr 100, CH-8091 Zurich, Switzerland. RI Leigh Brown, Andrew/F-3802-2010; gunthard, huldrych/F-1724-2011 OI gunthard, huldrych/0000-0002-1142-6723 FU FIC NIH HHS [TW-00680]; NIAID NIH HHS [AI-27670, AI-43752] NR 50 TC 28 Z9 28 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 20 PY 1999 VL 259 IS 1 BP 154 EP 165 DI 10.1006/viro.1999.9774 PG 12 WC Virology SC Virology GA 209AT UT WOS:000081025400017 PM 10364500 ER PT J AU Liao, YF Wieder, KG Classen, JM Van De Water, L AF Liao, YF Wieder, KG Classen, JM Van De Water, L TI Identification of two amino acids within the EIIIA (ED-A) segment of fibronectin constituting the epitope for two function-blocking monoclonal antibodies SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR-BETA; SITE-DIRECTED MUTAGENESIS; ALTERNATIVELY SPLICED EIIIB; SMOOTH-MUSCLE CELLS; CRYSTAL-STRUCTURE; MESSENGER-RNAS; TRANSFORMING GROWTH-FACTOR-BETA-1; EMBRYONIC FIBRONECTINS; CELLULAR-FIBRONECTIN; PROLIFERATIVE GLOMERULONEPHRITIS AB Alternative splicing of the fibronectin gene transcript gives rise to a group of adhesive glycoproteins showing restricted spatial and temporal expression during embryonic development, tumor growth, and tissue repair, Alternative splicing occurs in three segments termed EIIIB, EIIIA, and V. The EIIIA (or ED-A) segment of fibronectin is expressed prominently but transiently in healing wounds coincident with fibroblast expression of an activation marker, smooth muscle cell cr-actin. A monoclonal antibody (IST-9) to the EIIIA segment blocks transforming growth factor-a-mediated smooth muscle cell cr-actin expression by fibroblasts in culture. A second monoclonal antibody (DH1) blocks chondrocyte condensation in chicken embryos, We find that IST-9 and DH1 react with. human, rat, and chicken but not with mouse or frog EIIIA, suggesting that His(44) may be important for antibody binding. A series of deletion mutants of rat EIIIA constructed as glutathione S-transferase fusion proteins, do not react with either IST-9, DH1, or a third monoclonal antibody (3E2). Mutations of pairs of amino acids to alanine have little effect, except for either (Val(34)Thr(35)) Or (Tyr(36)Ser(37)), which are located in a beta strand upstream from His(44). For these double mutants, the binding to all three monoclonal antibodies is markedly reduced, By contrast, single mutants at Thr(35), Tyr(36), Or Ser(37) retain full activity, suggesting that the epitope for these antibodies is determined in part by conformation. Alanine-scanning mutagenesis of rat EIIIA demonstrates the importance of Ile(43) and His44 for binding. Mutation of frog EIIIA (normally Val(43)Lys(44)) to rat (Ile(43)His(44)) is sufficient to restore fully IST-9 binding and much of the activity of DH1 and 3E2, Our findings demonstrate that the function-blocking antibodies, IST-9 and DH1, bind to the Ile(43) and His(44) residues in a conformationally dependent fashion, implicating the loop region encompassing both residues as critical for mediating EIIIA function. C1 Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Shriners Burns Hosp, Boston, MA 02114 USA. RP Van De Water, L (reprint author), Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. RI Liao, Yung-Feng/A-9761-2011 FU NIGMS NIH HHS [GM56442] NR 84 TC 18 Z9 18 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 JUN 18 PY 1999 VL 274 IS 25 BP 17876 EP 17884 DI 10.1074/jbc.274.25.17876 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208DE UT WOS:000080974300069 PM 10364233 ER PT J AU Bouret, S Prevot, V Croix, D Jegou, S Vaudry, H Stefano, GB Beauvillain, JC Mitchell, V AF Bouret, S Prevot, V Croix, D Jegou, S Vaudry, H Stefano, GB Beauvillain, JC Mitchell, V TI mu-Opioid receptor mRNA expression in proopiomelanocortin neurons of the rat arcuate nucleus SO MOLECULAR BRAIN RESEARCH LA English DT Article DE proopiomelanocortin; enkephalin; beta-endorphin; mu-opioid receptor; arcuate nucleus; reproduction ID IN-SITU HYBRIDIZATION; GENE-EXPRESSION; BETA-ENDORPHIN; ENDOGENOUS CODEINE; HYPOTHALAMUS; MORPHINE; BRAIN; CORTICOTROPIN; LOCALIZATION; SECRETION AB It has been previously demonstrated that the activity of proopiomelanocortin (POMC)-containing neurons in the rat arcuate nucleus is regulated by opiates, but the expression of opioid receptors in POMC neurons las never been reported. In the present study, we have applied a double-labeling in situ hybridization technique to investigate the occurrence of mu-opioid receptor mRNA on POMC neurons. We have found that 20 +/- 3% of arcuate POMC neurons express mu-opioid receptor mRNA and that the proportion of POMC neurons expressing mu-opioid receptor is higher in the caudal than in the rostral portion of the arcuate nucleus. Our data suggest that POMC neurons might be both auto-regulated by P-endorphin, and regulated by enkephalins. (C) 1999 Elsevier Science B.V. All rights reserved. C1 INSERM, U422, IFR 22, F-590045 Lille, France. INSERM, U413, IFRMP 23, F-76821 Mt St Aignan, France. Beth Isreal Deaconess Med Ctr, Mind Body Med Inst, Boston, MA 02215 USA. SUNY Coll Old Westbury, Neurosci Res Inst, Old Westbury, NY 11568 USA. RP Bouret, S (reprint author), INSERM, U422, IFR 22, Pl Verdun, F-590045 Lille, France. RI Prevot, Vincent/E-5720-2016 NR 26 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD JUN 18 PY 1999 VL 70 IS 1 BP 155 EP 158 DI 10.1016/S0169-328X(99)00132-1 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 209NK UT WOS:000081054500018 ER PT J AU Franc, NC Heitzler, P Ezekowitz, RAB White, K AF Franc, NC Heitzler, P Ezekowitz, RAB White, K TI Requirement for croquemort in phagocytosis of apoptotic cells in Drosophila SO SCIENCE LA English DT Article ID MONOCYTE-DERIVED MACROPHAGES; GENE-EXPRESSION; C-ELEGANS; VITRONECTIN RECEPTOR; SCAVENGER RECEPTOR; DEATH; PROTEIN; CD36; RECOGNITION; MELANOGASTER AB Macrophages in the Drosophila embryo are responsible for the phagocytosis of apoptotic cells and are competent to engulf bacteria. Croquemort (CRQ) is a CD36-related receptor expressed exclusively on these macrophages. Genetic evidence showed that crq was essential for efficient phagocytosis of apoptotic corpses but was not required for the engulfment of bacteria. The expression of CRQ was regulated by the amount of apoptosis. These data define distinct pathways for the phagocytosis of corpses and bacteria in Drosophila. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Dev Immunol, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Charlestown, MA 02129 USA. Univ Strasbourg 1, CNRS, INSERM, IGBMC, F-67404 Illkirch Graffenstaden, France. RP White, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RI Franc, Nathalie/C-2208-2009; White, Kristin/D-7936-2013 NR 38 TC 247 Z9 252 U1 0 U2 8 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 JUN 18 PY 1999 VL 284 IS 5422 BP 1991 EP 1994 DI 10.1126/science.284.5422.1991 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 207JA UT WOS:000080932700048 PM 10373118 ER PT J AU Basbaum, AI Woolf, CJ AF Basbaum, AI Woolf, CJ TI Pain SO CURRENT BIOLOGY LA English DT Article C1 Univ Calif San Francisco, Dept Anat, WM Keck Fdn Ctr Integrat Neurosci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Basbaum, AI (reprint author), Univ Calif San Francisco, Dept Anat, WM Keck Fdn Ctr Integrat Neurosci, San Francisco, CA 94143 USA. NR 5 TC 52 Z9 54 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUN 17 PY 1999 VL 9 IS 12 BP R429 EP R431 DI 10.1016/S0960-9822(99)80273-5 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 207NK UT WOS:000080942800004 PM 10375535 ER PT J AU Rennke, HG Laposata, M AF Rennke, HG Laposata, M TI A 54-year-old woman with acute renal failure and thrombocytopenia - Antiphospholipid-antibody syndrome. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID HEMOLYTIC-UREMIC-SYNDROME; SYSTEMIC LUPUS-ERYTHEMATOSUS; HEPATITIS-C VIRUS; ANTICARDIOLIPIN ANTIBODIES; ANTICOAGULANT; DISEASE; MANIFESTATIONS; PREVALENCE; MANAGEMENT; THROMBOSIS C1 Brigham & Womens Hosp, Renal Pathol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Rennke, HG (reprint author), Brigham & Womens Hosp, Renal Pathol Lab, Boston, MA 02115 USA. NR 34 TC 4 Z9 4 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 JUN 17 PY 1999 VL 340 IS 24 BP 1900 EP 1908 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 206EC UT WOS:000080863500008 ER PT J AU Blumenthal, D AF Blumenthal, D TI Health care reform at the close of the 20th century SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MANAGED CARE; QUALITY; FUTURE; PERFORMANCE; PHYSICIANS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Blumenthal, D (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 34 TC 18 Z9 18 U1 1 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 17 PY 1999 VL 340 IS 24 BP 1916 EP 1920 DI 10.1056/NEJM199906173402412 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 206EC UT WOS:000080863500012 PM 10369858 ER PT J AU Huang, XD Atwood, CS Hartshorn, MA Multhaup, G Goldstein, LE Scarpa, RC Cuajungco, MP Gray, DN Lim, J Moir, RD Tanzi, RE Bush, AI AF Huang, XD Atwood, CS Hartshorn, MA Multhaup, G Goldstein, LE Scarpa, RC Cuajungco, MP Gray, DN Lim, J Moir, RD Tanzi, RE Bush, AI TI The A beta peptide of Alzheimer's disease directly produces hydrogen peroxide through metal ion reduction SO BIOCHEMISTRY LA English DT Article ID OXIDATIVE STRESS; SENILE PLAQUES; HIPPOCAMPAL CULTURES; AMYLOID DEPOSITION; LIPID-PEROXIDATION; RADICAL SCAVENGER; PROTEIN OXIDATION; TRANSGENIC MICE; TOXICITY; ZINC AB Oxidative stress markers characterize the neuropathology both of Alzheimer's disease and of amyloid-bearing transgenic mice. The neurotoxicity of amyloid A beta peptides has been linked to peroxide generation in cell cultures by an unknown mechanism. We now show that human A beta directly produces hydrogen peroxide (H2O2) by a mechanism that involves the reduction of metal ions, Fe(III) or Cu(II), setting up conditions for Fenton-type chemistry. Spectrophotometric experiments establish that the A beta peptide reduces Fe(III) and Cu(II) to Fe(II) and Cu(I), respectively. Spectrochemical techniques are used to show that molecular oxygen is then trapped by A beta and reduced to H2O2 in a reaction that is driven by substoichiometric amounts of Fe(II) or Cu(I), In the presence of Cu(II) or Fe(III), A beta produces a positive thiobarbituric-reactive substance (TEARS) assay, compatible with the generation of the hydroxyl radical (OH). The amounts of both reduced metal and TEARS reactivity are greatest when generated by A beta-42 much greater than A beta 1-40 > rat A beta 1-40, a chemical relationship that correlates with the participation of the native peptides in amyloid pathology, These findings indicate that the accumulation of A beta could be a direct source of oxidative stress in Alzheimer's disease. C1 Harvard Univ, Massachusetts Gen Hosp E, Sch Med, Genet & Aging Unit,Lab Oxidat Biol, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp E, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA. Univ Heidelberg, Ctr Mol Biol, ZMBH, D-69120 Heidelberg, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Unit, Charlestown, MA 02129 USA. RP Bush, AI (reprint author), Harvard Univ, Massachusetts Gen Hosp E, Sch Med, Genet & Aging Unit,Lab Oxidat Biol, Bldg 149,13 St, Charlestown, MA 02129 USA. RI Cuajungco, Math/B-2647-2008; Bush, Ashley/A-1186-2007 OI Cuajungco, Math/0000-0003-0749-9564; Bush, Ashley/0000-0001-8259-9069 FU NIA NIH HHS [1R29AG12686] NR 55 TC 771 Z9 803 U1 17 U2 110 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 15 PY 1999 VL 38 IS 24 BP 7609 EP 7616 DI 10.1021/bi990438f PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208XB UT WOS:000081016200001 PM 10386999 ER PT J AU Bush, G Frazier, JA Rauch, SL Seidman, LJ Whalen, PJ Jenike, MA Rosen, BR Biederman, J AF Bush, G Frazier, JA Rauch, SL Seidman, LJ Whalen, PJ Jenike, MA Rosen, BR Biederman, J TI Anterior cingulate cortex dysfunction in attention-deficit/hyperactivity disorder revealed by fMRI and the counting stroop SO BIOLOGICAL PSYCHIATRY LA English DT Article DE functional magnetic resonance imaging (fMRI); Stroop; cognitive interference; attention; attention-deficit/hyperactivity disorder; cingulate cortex ID DEFICIT-HYPERACTIVITY DISORDER; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL BLOOD-FLOW; FUNCTIONAL MAGNETIC-RESONANCE; WORKING-MEMORY; SELECTIVE ATTENTION; RESPONSE SELECTION; INTERFERENCE TASK; BRAIN ACTIVATION; PET ACTIVATION AB Background: The anterior cingulate cognitive division (ACcd) plays a central role in attentional processing by: 1) modulating stimulus selection (i.e,, focusing attention) and/or 2) mediating response selection. We hypothesized that ACcd dysfunction might therefore contribute to producing core features of attention-defcit/hyperactivity disorder (ADHD), namely inattention and impulsivity. ADHD subjects have indeed shown performance deficits on the Color Stroop, an attentional/cognitive interference task known to recuit. the ACcd. Recently, the Counting Stroop, a Stroop-variant specialized for functional magnetic resonance imaging (fMRI), produced ACcd activation in healthy adults. In the present fMRI study, the Counting Stroop was used to examine the functional integrity of the ACcd in ADHD. Methods: Sixteen unmedicated adults from two groups (8 with ADHD and 8 matched control subjects) performed the Counting Stroop during fMRI Results: While both groups showed an interference effect, the ADHD group, in contrast to control subjects, failed to activate the ACcd during the Counting Stroop. Direct comparisons showed ACcd activity was significantly higher in the control group. ADHD subjects did activate a frontostriatal-insular network indicating ACcd hypoactivity was not caused by globally poor nehrronal responsiveness, Conclusions: The data support a hypothesized dysfunction of the ACcd in ADHD. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Nucl Magnet Resonance Ctr, Boston, MA 02115 USA. MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. RP Bush, G (reprint author), Massachusetts Gen Hosp E, Psychiat Neurosci Program, CNY-9,Bldg 149,13th St, Charlestown, MA 02129 USA. FU NIMH NIH HHS [MH01215, MH01611, MH41314] NR 86 TC 541 Z9 561 U1 34 U2 81 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 JUN 15 PY 1999 VL 45 IS 12 BP 1542 EP 1552 DI 10.1016/S0006-3223(99)00083-9 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 205XC UT WOS:000080845000003 PM 10376114 ER PT J AU Bartzokis, G Beckson, M Wirshing, DA Lu, PH Foster, JA Mintz, J AF Bartzokis, G Beckson, M Wirshing, DA Lu, PH Foster, JA Mintz, J TI Choreoathetoid movements in cocaine dependence SO BIOLOGICAL PSYCHIATRY LA English DT Article DE choreoathetoid; movement; cocaine; amphetamine; aging; crack dancing ID TARDIVE-DYSKINESIA; METHAMPHETAMINE; PREVALENCE; TOXICITY; BENZOYLECGONINE; SCHIZOPHRENICS; DEGENERATION; DISORDERS; DOPAMINE; STRIATUM AB Background: To evaluate the severity of choreoathetoid movements in cocaine dependent (CD) subjects and age-matched normal control subjects, Methods: Choreoathetoid movements were evaluated using the Abnormal Involuntary Movement Scale (AIMS) in samples of 71 CD, 56 normal control, and 9 amphetamine-dependent male subjects. Results: The CD subjects had a significantly increased nonfacial (limbs plus body) AIMS subscore, When the nonfacial AIMS scores of the two groups were compared in relation to age, a significant age by diagnosis interaction was observed, indicating that the differences between groups were most marked in the younger age groups. The facial AIMS scores were also increased but only in the youngest CD cohort (under 32 years of age). The comparison group of 9 younger amphetamine-dependent subjects also showed increased AIMS scores. Conclusions: Increases in choreoathetoid movements in younger cocaine and amphetamine-dependent subjects may be related to their psychostimulant use. The absence of differences in choreoathetoid movements between the older CD subjects and normal control subjects may represent art age-related self-selection effect. (C) 1999 Society of Biological Psychiatry. C1 Little Rock VA Med Ctr, Psychiat Serv, Little Rock, AR USA. Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. RP Bartzokis, G (reprint author), N Little Rock VA Med Ctr, 116A-NLR,2200 Ft Roots Dr,Bldg 170, N Little Rock, AR 72114 USA. RI Bartzokis, George/K-2409-2013 FU NIDA NIH HHS [1YO1 DA 50038] NR 48 TC 22 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 15 PY 1999 VL 45 IS 12 BP 1630 EP 1635 DI 10.1016/S0006-3223(98)00238-8 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 205XC UT WOS:000080845000014 PM 10376125 ER PT J AU Pan, LP Teshima, T Hill, GR Bungard, D Brinson, YS Reddy, VS Cooke, KR Ferrara, LM AF Pan, LP Teshima, T Hill, GR Bungard, D Brinson, YS Reddy, VS Cooke, KR Ferrara, LM TI Granulocyte colony-stimulating factor-mobilized allogeneic stem cell transplantation maintains graft-versus-leukemia effects through a perforin-dependent pathway while preventing graft-versus-host disease SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; BLOOD MONONUCLEAR-CELLS; NECROSIS-FACTOR-ALPHA; DONOR LEUKOCYTE INFUSIONS; CD4(+) T-CELLS; PERIPHERAL-BLOOD; MEDIATED CYTOTOXICITY; PROGENITOR CELLS; FAS-LIGAND; IFN-GAMMA AB Minimization of graft-versus-host disease (GVHD) with preservation of the graft-versus-leukemia (GVL) effect is a crucial step to improve the overall survival of allogeneic bone marrow transplantation (BMT) for patients with hematological malignancies. We and other investigators have shown that granulocyte colony-stimulating factor (G-CSF)-mobilized allogeneic peripheral stem cell transplantation (PBSCT) reduces the severity of acute GVHD in murine models. In this study, we investigated whether G-CSF-mobilized PBSC maintain their GVL effect in a murine allogeneic transplant model (B6 --> B6D2F1). be mice (H-2(b)) were injected subcutaneously with human G-CSF (100 mu g/kg/d) for 6 days and their splenocytes were harvested on day 7 as a source of PBSC. G-CSF mobilization dramatically improved transplant survival compared with nonmobilized controls (95% v 0%, P < .001). Systemic levels of lipopolysaccharide and tumor necrosis factor-cu were markedly reduced in recipients of allogeneic G-CSF-mobilized donors, but cytolytic T lymphocyte (CTL) activity against host tumor target cells p815 was retained in those recipients. When leukemia was induced in recipients by coinjection of p815 tumor cells (H-2(d)) at the time of transplantation, all surviving recipients of G-CSF-mobilized B6 donors were leukemia-free at day 70 after transplant, whereas all mice who received T-cell-depleted (TCD) splenocytes from G-CSF-mobilized B6 donors died of leukemia. When splenocytes from G-CSF-mobilized perforin-deficient (pfp(-/-)) mice were used for transplantation, 90% of recipients died of leukemia, demonstrating that perforin is a crucial pathway mediating GVL effects after G-CSF-mobilized PBSCT. These data illustrate that G-CSF-mobilized allogeneic PBSCT separate GVL from GVHD by preserving perforin-dependent donor CTL activity while reducing systemic inflammation. (C) 1999 by The American Society of Hematology. C1 Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Pediat, Ann Arbor, MI 48109 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. RP Ferrara, LM (reprint author), Univ Michigan, Ctr Canc, Bone Marrow Transplant Program, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. RI teshima, takanori/G-1671-2012; Hill, Geoffrey/O-2630-2016 OI Hill, Geoffrey/0000-0003-2994-0429 FU NCI NIH HHS [CA 29542]; NHLBI NIH HHS [HL 55709] NR 73 TC 89 Z9 94 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1999 VL 93 IS 12 BP 4071 EP 4078 PG 8 WC Hematology SC Hematology GA 204TK UT WOS:000080780200005 PM 10361103 ER PT J AU Ilaria, RL Hawley, RG Van Etten, RA AF Ilaria, RL Hawley, RG Van Etten, RA TI Dominant negative mutants implicate STAT5 in myeloid cell proliferation and neutrophil differentiation SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; DNA-BINDING ACTIVITY; CHRONIC MYELOGENOUS LEUKEMIA; EPIDERMAL GROWTH-FACTOR; TYROSINE PHOSPHORYLATION; TRANSCRIPTION FACTOR; GENE-EXPRESSION; FACTOR-RECEPTOR; CONSTITUTIVE ACTIVATION; SIGNAL TRANSDUCERS AB STAT5 is a member of the signal transducers and activation of transcription (STAT) family of latent transcription factors activated in a variety of cytokine signaling pathways. We introduced alanine substitution mutations in highly conserved regions of murine STAT5A and studied the mutants for dimerization, DNA binding, transactivation, and dominant negative effects on erythropoietin-induced STAT5-dependent transcriptional activation. The mutations included two near the amino-terminus (W255KR-->AAA and R(290)QQ-->AAA), two in the DNA-binding domain (E437E-->AA and V466VV-->AAA), and a carboxy-terminal truncation of STAT5A (STAT5A/Delta 53C) analogous to a naturally occurring isoform of rat STAT5B. All of the STAT mutant proteins were tyrosine phosphorylated by JAK2 and heterodimerized with STAT5B except for the WKR mutant, suggesting an important role for this region in STAT5 for stabilizing dimerization. The WKR, EE, and VVV mutants had no detectable DNA-binding activity, and the WKR and VVV mutants, but not EE, were defective in transcriptional induction. The VVV mutant had a moderate dominant negative effect on erythropoietin-induced STAT5 transcriptional activation, which was likely due to the formation of heterodimers that are defective in DNA binding. Interestingly, the WKR mutant had a potent dominant negative effect, comparable to the transactivation domain deletion mutant, Delta 53C. Stable expression of either the WKR or Delta 53C STAT5 mutants in the murine myeloid cytokine-dependent cell line 32D inhibited both interleukin-3-dependent proliferation and granulocyte colony-stimulating factor (G-CSF)-dependent differentiation, without induction of apoptosis. Expression of these mutants in primary murine bone marrow inhibited G-CSF-dependent granulocyte colony formation in vitro. These results demonstrate that mutations in distinct regions of STAT5 exert dominant negative effects on cytokine signaling, likely through different mechanisms, and suggest a role for STAT5 in proliferation and differentiation of myeloid cells. (C) 1999 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Ctr Blood Res, Dept Genet, Boston, MA 02115 USA. Univ Texas, SW Med Sch, Simmons Canc Ctr, Dallas, TX USA. Amer Red Cross, Holland Lab, Hematopoiesis Dept, Rockville, MD USA. RP Van Etten, RA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Dept Genet, 200 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA57593]; NHLBI NIH HHS [HL03310] NR 65 TC 92 Z9 94 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1999 VL 93 IS 12 BP 4154 EP 4166 PG 13 WC Hematology SC Hematology GA 204TK UT WOS:000080780200015 PM 10361113 ER PT J AU Shcherbina, A Remold-O'Donnell, E AF Shcherbina, A Remold-O'Donnell, E TI Role of caspase in a subset of human platelet activation responses SO BLOOD LA English DT Article ID PLASMA-MEMBRANE; PHOSPHATIDYLSERINE EXTERNALIZATION; PHOSPHOLIPID SCRAMBLASE; PROCOAGULANT ACTIVITY; MOLECULAR-CLONING; SCOTT SYNDROME; CELL-SURFACE; GRANZYME-B; APOPTOSIS; CALPAIN AB Platelets function to protect the integrity of the vascular wall. A subset of platelet activation responses that are especially important for thrombus formation include exposure of phosphatidylserine and release of microparticles, which generate procoagulant surfaces. The resemblance of these platelet activation processes to events occurring in nucleated cells undergoing apoptosis suggests a possible role for caspases, which are major effector enzymes of nucleated cell apoptosis. We demonstrate here the presence of caspase-3 in human platelets and its activation by physiological platelet agonists. Using cell-permeable specific inhibitors, we demonstrate a role for a caspase-3-like protease in the agonist-induced (collagen plus thrombin or Ca2+ ionophore) platelet activation events of phosphatidylserine exposure, microparticle release, and cleavage of moesin, a cytoskeletal-membrane linker protein. The role of caspase-3 in platelet activation is restricted rather than global, because other activation responses, cu granule secretion, shape change, and aggregation were unaffected by caspase-3 inhibitors. Experiments with two classes of protease inhibitors show that caspase-3 function is distinct from that of calpain, which is also involved in late platelet activation events. These findings show novel functions of caspase and provide new insights for understanding of platelet activation. (C) 1999 by The American Society of Hematology. C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Remold-O'Donnell, E (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [AI39574, R01 AI039574] NR 46 TC 121 Z9 122 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1999 VL 93 IS 12 BP 4222 EP 4231 PG 10 WC Hematology SC Hematology GA 204TK UT WOS:000080780200021 PM 10361119 ER PT J AU Ho, JMY Beattie, BK Squire, JA Frank, DA Barber, DL AF Ho, JMY Beattie, BK Squire, JA Frank, DA Barber, DL TI Fusion of the ets transcription factor TEL to Jak2 results in constitutive Jak-Stat signaling SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; COLONY-STIMULATING FACTOR; HEMATOPOIETIC-CELL LINES; CHRONIC MYELOMONOCYTIC LEUKEMIA; PHASE RESPONSE FACTOR/STAT3; PERIPHERAL-BLOOD CELLS; RECEPTOR-ALPHA-CHAIN; DNA-BINDING ACTIVITY; MICE LACKING JAK3; DIFFERENTIAL ACTIVATION AB To study constitutive Janus kinase signaling, chimeric proteins were generated between the pointed domain of the ets transcription factor TEL and the cytosolic tyrosine kinase Jak2. The effects of these proteins on interleukin-3 (IL-3)-dependent proliferation of the hematopoietic cell line, Ba/F3, were studied, Fusion of TEL to the functional kinase (JH1) domain of Jak2 resulted in conversion of Ba/F3 cells to factor-independence. Importantly, fusion of TEL to the Jak2 pseudokinase (JH2) domain or a kinase-inactive Jak2 JH1 domain had no effect on IL-3-dependent proliferation of Ba/F3 cells. Active TEL-Jak2 constructs (consisting of either Jak2 JH1 or Jak2 JH2+JH1 domain fusions) were constitutively tyrosine-phosphorylated but did not affect phosphorylation of endogeneous Jak1, Jak2, or Jak3. TEL-Jak2 activation resulted in the constitutive tyrosine phosphorylation of Stat1, Stat3, and Stat5 as determined by detection of phosphorylation using activation-specific antibodies and by binding of each protein to a preferential GAS sequence in electrophoretic mobility shift assays. Elucidation of signaling events downstream of TEL Jak2 activation may provide insight into the mechanism of leukemogenesis mediated by this oncogenic fusion protein. (C) 1999 by The American Society of Hematology. C1 Ontario Canc Inst, Div Cellular & Mol Biol, Toronto, ON M5G 2M9, Canada. Toronto Hosp, Dept Lab Med & Pathobiol, Toronto, ON M5T 2S8, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. Univ Toronto, Lab Med & Pathobiol, Toronto, ON, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Barber, DL (reprint author), Ontario Canc Inst, Div Cellular & Mol Biol, 610 Univ Ave, Toronto, ON M5G 2M9, Canada. OI Squire, Jeremy/0000-0002-9863-468X NR 64 TC 85 Z9 86 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1999 VL 93 IS 12 BP 4354 EP 4364 PG 11 WC Hematology SC Hematology GA 204TK UT WOS:000080780200036 PM 10361134 ER PT J AU Duska, LR Chang, YC Flynn, CE Chen, AH Goodman, A Fuller, AF Nikrui, N AF Duska, LR Chang, YC Flynn, CE Chen, AH Goodman, A Fuller, AF Nikrui, N TI Epithelial ovarian carcinoma in the reproductive age group SO CANCER LA English DT Article; Proceedings Paper CT New-England-Association-of-Gynecologic-Oncologists Meeting CY JUN, 1998 CL NEW HAMPSHIRE SP New England Assoc Gynecol Oncologists DE ovarian carcinoma; young age; borderline; epithelial; survival; fertility ID PROGNOSTIC FACTOR; BORDERLINE MALIGNANCY; TUMORS; CANCER; WOMEN AB BACKGROUND, A retrospective review of women age less than or equal to 40 years with epithelial ovarian carcinoma was undertaken to determine whether patient age and tumor grade are independent prognostic factors for survival, to investigate the survival rate for young women with ovarian carcinoma, and to characterize these young women in terms of reproductive capability. METHODS, The tumor registry of the Massachusetts General Hospital was used to identify cases of ovarian carcinoma diagnosed between January 1980 and July 1996. Patient records and pathology were reviewed. Survival rates were calculated by the Kaplan-Meier method and Cox proportional hazards models were used to determine the independent effect of each variable on survival. RESULTS. Ninety-two tumors epithelial tumors were identified with 46 (50%) classified as borderline. In the univariate analysis, stage (P < 0.001), grade (P < 0.001), residual disease (less than or equal to 2 cm vs. > 2 cm, P < 0.001), and age (< 30 years vs. 31-40 years; P = 0.019) were found to be significant prognostic factors for survival. However, in the multivariate analysis only tumor grade (with borderline tumors assigned a grade of 0) and stage were significant predictors of survival (P < 0.01 for both). The ii-year survival rate for carcinoma patients with advanced disease was 22.9%. Patients with borderline tumors were more likely be diagnosed during an evaluation for infertility and were more likely to have successful live births after carcinoma treatment. CONCLUSIONS, Young women with advanced epithelial carcinoma have a 5-year survival rate similar to that quoted in the literature, despite the use of more aggressive chemotherapeutic regimens. Patients with borderline tumors of any stage have an excellent prognosis for preserving fertility options. Cancer 1999;85: 2623-9, (C) 1999 American Cancer Society. C1 Massachusetts Gen Hosp, Gillette Ctr Womens Canc, Div Gynecol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Pathol, Boston, MA 02114 USA. RP Duska, LR (reprint author), Massachusetts Gen Hosp, Gillette Ctr Womens Canc, Div Gynecol Oncol, Cox 120,100 Blossom St, Boston, MA 02114 USA. NR 18 TC 70 Z9 74 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 15 PY 1999 VL 85 IS 12 BP 2623 EP 2629 DI 10.1002/(SICI)1097-0142(19990615)85:12<2623::AID-CNCR19>3.0.CO;2-O PG 7 WC Oncology SC Oncology GA 204RL UT WOS:000080777900019 PM 10375111 ER PT J AU Raftery, LA Sutherland, DJ AF Raftery, LA Sutherland, DJ TI TGF-beta family signal transduction in Drosophila development: From Mad to Smads SO DEVELOPMENTAL BIOLOGY LA English DT Review DE Smad; Dpp; TGF-beta; BMP; activin; wing patterning; midgut patterning; transcription factors ID GROWTH-FACTOR-BETA; SERINE/THREONINE KINASE RECEPTORS; TUMOR-SUPPRESSOR; CAENORHABDITIS-ELEGANS; DECAPENTAPLEGIC GENE; PATTERN-FORMATION; I RECEPTORS; EYE DEVELOPMENT; DPP RECEPTORS; THICK VEINS AB The transforming growth factor-beta (TGF-beta) superfamily encompasses a large group of soluble extracellular proteins that are potent regulators of development in both vertebrates and invertebrates. Drosophila TGF-beta family members include three proteins with homology to vertebrate bone morphogenetic proteins (BMPs): Decapentaplegic (Dpp), Screw, and Glass bottom boat-60A. Genetic studies of Dpp signaling led to the identification of Smad proteins as central mediators of signal transduction by TGF-beta family members. Work in mammalian tissue culture has elucidated a biochemical model for signal transduction, in which activation of receptor serine-threonine kinase activity leads to phosphorylation of specific Smad proteins and translocation of heteromeric Smad protein complexes to the nucleus. Once in the nucleus Smad proteins interact with other DNA binding proteins to regulate transcription of specific target genes. Dissection of Dpp-response elements from genes expressed during embryonic mesoderm patterning and midgut morphogenesis provides important insights into the contributions of Smad proteins and tissue-specific transcription factors to spatial regulation of gene expression. Genetic studies in Drosophila are now expanding to include multiple BMP ligands and receptors and have uncovered activities not explained by the current signal transduction model. Identification of more ligand sequences and demonstration of a functional Drosophila activin-like signal transduction pathway suggest that all TGF-beta signal transduction pathways are present in flies. (C) 1999 Academic Press. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. RP Raftery, LA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Bldg 149 13th St, Boston, MA 02129 USA. RI Raftery, Laurel/H-1406-2012 OI Raftery, Laurel/0000-0003-4797-4163 NR 160 TC 216 Z9 223 U1 2 U2 15 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1999 VL 210 IS 2 BP 251 EP 268 DI 10.1006/dbio.1999.9282 PG 18 WC Developmental Biology SC Developmental Biology GA 213AG UT WOS:000081249400001 PM 10357889 ER PT J AU Shimoda, N Knapik, EW Ziniti, J Sim, C Yamada, E Kaplan, S Jackson, D de Sauvage, F Jacob, H Fishman, MC AF Shimoda, N Knapik, EW Ziniti, J Sim, C Yamada, E Kaplan, S Jackson, D de Sauvage, F Jacob, H Fishman, MC TI Zebrafish genetic map with 2000 microsatellite markers SO GENOMICS LA English DT Article DE zebrafish; linkage map; microsatellite repeat; polymorphism; microsatellite expansion ID INTERSPERSED REPETITIVE ELEMENTS; DANIO-RERIO; LINKAGE MAP; GENOME; MUTATIONS; FAMILY; POLYMORPHISMS; MERMAID AB The zebrafish is the first vertebrate organism used for large-scale genetic screens seeking genes critical to development, These screens have been quite successful, with more than 1800 recessive mutations discovered that speak to morphogenesis of the vertebrate embryo. The cloning of the mutant genes depends on a dense genetic map. The 2000 markers we present here, using microsatellite (CA) repeats, provides 1,2-cM average resolution. One centimorgan in zebrafish is about 0.74 megabase, so, for many mutations, these markers are close enough to begin positional cloning by YAC walks. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. GSF, Natl Res Ctr Environm & Hlth, Inst Mammalian Genet, D-85758 Neuherberg, Germany. Genentech Inc, Dept Mol Oncol, S San Francisco, CA 94080 USA. Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA. RP Fishman, MC (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St 149-4201, Charlestown, MA 02129 USA. RI Knapik, Ela/J-6172-2014 FU NCRR NIH HHS [RR08888]; NHLBI NIH HHS [HL49579]; NIDDK NIH HHS [DK55383] NR 23 TC 265 Z9 281 U1 1 U2 18 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JUN 15 PY 1999 VL 58 IS 3 BP 219 EP 232 DI 10.1006/geno.1999.5824 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 211FH UT WOS:000081149500001 PM 10373319 ER PT J AU Chadwick, BP Mull, J Helbling, LA Gill, S Leyne, M Robbins, CM Pinkett, HW Makalowska, I Maayan, C Blumenfeld, A Axelrod, FB Brownstein, N Gusella, JF Slaugenhaupt, SA AF Chadwick, BP Mull, J Helbling, LA Gill, S Leyne, M Robbins, CM Pinkett, HW Makalowska, I Maayan, C Blumenfeld, A Axelrod, FB Brownstein, N Gusella, JF Slaugenhaupt, SA TI Cloning, mapping, and expression of two novel actin genes, actin-like-7A (ACTL7A) and actin-like-7B (ACTL7B), from the familiar dysautonomia candidate region on 9q31 SO GENOMICS LA English DT Article ID SACCHAROMYCES-CEREVISIAE; HUMAN-CHROMOSOME; PROTEIN; SWI/SNF; COMPLEX; CHROMATIN; SEQUENCE AB Two novel human actin-like genes, ACTL7A and ACTL7B, were identified by cDNA selection and direct genomic sequencing from the familial dysautonomia candidate region on 9q31. ACTL7A encodes a 435-amino-acid protein (predicted molecular mass 48.6 kDa) and ACTL7B encodes a 415-amino-acid protein (predicted molecular mass 45.2 kDa) that show greater than 65% amino acid identity to each other. Genomic analysis revealed ACTL7A and ACTL7B to be intronless genes contained on a common 8-kb HindIII fragment in a "head-to-head" orientation. The murine homologues were cloned and mapped by linkage analysis to mouse chromosome 4 in a region of gene order conserved with human chromosome 9q31. No recombinants were observed between the two genes, indicating a close physical proximity in mouse. ACTL7A is expressed in a wide variety of adult tissues, while the ACTL7B message was detected only in the testis and, to a lesser extent, in the prostate. No coding sequence mutations, genomic rearrangements, or differences in expression were detected for either gene in familial dysautonomia patients. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02139 USA. Harvard Univ, Sch Med, Inst Human Genet, Boston, MA 02115 USA. NIMH, Canc Genet Branch, Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. NIMH, Genome Technol Branch, Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. NIMH, Genet Lab, Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. Hadassah Univ Hosp, Unit Dev Mol Biol & Genet Engn, IL-91120 Jerusalem, Israel. Hadassah Univ Hosp, Dept Pediat, IL-91120 Jerusalem, Israel. NYU, Sch Med, Dept Pediat, New York, NY 10016 USA. RP Slaugenhaupt, SA (reprint author), HIM Bldg,Room 422,77 Ave Louis Pasteur, Boston, MA 02115 USA. RI Brownstein, Michael/B-8609-2009; Pinkett, Heather/M-9235-2014 FU NINDS NIH HHS [NS36326] NR 35 TC 19 Z9 24 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JUN 15 PY 1999 VL 58 IS 3 BP 302 EP 309 DI 10.1006/geno.1999.5848 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 211FH UT WOS:000081149500010 PM 10373328 ER PT J AU Zeng, ZH Zhang, ZY Yu, HS Corbley, MJ Tang, ZQ Tong, T AF Zeng, ZH Zhang, ZY Yu, HS Corbley, MJ Tang, ZQ Tong, T TI Mitochondrial DNA deletions are associated with ischemia and aging in Balb c mouse brain SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE mitochondrial DNA; deletion; ischemia; aging; mutation; mouse cerebrum; PCR; carotid artery; stroke ID KEARNS-SAYRE SYNDROME; MICE; DISORDERS; DISEASES; TISSUES; DAMAGE AB Deletions in the mitochondrial DNA (mtDNA) of Balb/c mouse cerebrums, resembling deletions found in elderly humans or in patients with certain disorders, were detected by PCR. Analysis was carried out on mice of various ages and on mice in which the bilateral common carotid arteries had been incompletely ligated to reconstruct cerebral ischemia. A 3,867 bp mtDNA deletion was present only in old or ischemic mouse groups. Among the non-ischemic groups, it was found in 0 of 12 weaning, 0 of 12 young, and four of eight old mice. Among the ischemic groups, it was found in 12 of 17 young and 11 of 11 old mice. Moreover, the percentage of total mtDNA containing deletions was 22% for the old non-ischemic group, 37% for the young ischemic group, and 69% for the old ischemic group. In addition, PCR analysis detected two other deletions of 3,726 bp and 4,236 bp in 4 of the 12 old ischemic cerebrums. The results indicate that mtDNA deletions are associated with aging, that ischemia increases the incidence of mtDNA deletions, and that mtDNA deletions resulting from ischemia are more likely to occur in old mice than in young mice. (C) 1999 Wiley-Liss, Inc. C1 Beijing Med Univ, Dept Biochem & Mol Biol, Beijing 100083, Peoples R China. Dana Farber Canc Inst, Div Cell & Mol Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Zhang, ZY (reprint author), Beijing Med Univ, Dept Biochem & Mol Biol, Beijing 100083, Peoples R China. NR 30 TC 16 Z9 26 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JUN 15 PY 1999 VL 73 IS 4 BP 545 EP 553 DI 10.1002/(SICI)1097-4644(19990615)73:4<545::AID-JCB12>3.0.CO;2-Q PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 199YY UT WOS:000080512700012 PM 10733347 ER PT J AU Finkelstein, DM Schoenfeld, DA AF Finkelstein, DM Schoenfeld, DA TI Combining mortality and longitudinal measures in clinical trials SO STATISTICS IN MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; HIERARCHICAL BAYES MODELS; FAILURE TIME DATA; REGRESSION-ANALYSIS; RANDOMIZED TRIAL; CELL NUMBERS; PROGRESSION; AIDS; SURVIVAL; COUNTS AB Clinical trials often assess therapeutic benefit on the basis of an event such as death or the diagnosis of disease. Usually, there are several additional longitudinal measures of clinical status which are collected to be used in the treatment comparison. This paper proposes a simple non-parametric test which combines a time to event measure and a longitudinal measure so that a substantial treatment difference on either of the measures will reject the null hypothesis. The test is applied on AIDS prophylaxis and paediatric trials. (C) 1999 John Wiley & Sons, Ltd. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Finkelstein, DM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 677 Huntington Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA-74302]; NIAID NIH HHS [N0-AI-95030] NR 25 TC 70 Z9 70 U1 0 U2 5 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 15 PY 1999 VL 18 IS 11 BP 1341 EP 1354 DI 10.1002/(SICI)1097-0258(19990615)18:11<1341::AID-SIM129>3.0.CO;2-7 PG 14 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 204LA UT WOS:000080764700004 PM 10399200 ER PT J AU Hill, GR Cooke, KR Brinson, YS Bungard, D Ferrara, JLM AF Hill, GR Cooke, KR Brinson, YS Bungard, D Ferrara, JLM TI Pretransplant chemotherapy reduces inflammatory cytokine production and acute graft-versus-host disease after allogeneic bone marrow transplantation SO TRANSPLANTATION LA English DT Article ID FACTOR-ALPHA PRODUCTION; TOTAL-BODY IRRADIATION; RELEASE AB Background Tumor necrosis factor-alpha (TNF-alpha) is known to be a critical effector molecule in the pathogenesis of graft-versus-host disease (GVHD), and elevated levels during bone marrow transplantation (BMT) conditioning are associated with more severe GVHD;, Many patients receive chemotherapy prior to BMT, but its effect on subsequent toxicities is controversial. Methods. We studied the effect of prior chemotherapy on GVHD severity and inflammatory cytokine generation in a well-established murine model of allogeneic BMT (B6 --> B6D2F1). Results. Three weeks after a single dose of cyclophosphamide, bone marrow and splenic cellularity was reduced by 50% and the production of TNF-alpha to LPS stimulation by macrophages was also markedly impaired (both before and after total body irradiation). Allogeneic BMT recipients previously treated with cyclophosphamide had significantly less GVHD;VHD and improved survival relative to recipients previously pretreated with diluent only. This survival advantage was associated with reduced systemic levels of both TNF-alpha and interleukin-1 beta 7 days after BMT. This reduction occurred despite equivalent serum levels of lipopolysaccharide, consistent with the reductions in TNF-alpha and interleukin-1 beta production by host macrophages after cyclophosphamide pretreatment. Conclusions. These data support the notion that patients entering BMT conditioning without prior cytotoxic treatment (e,g,, patients with chronic myeloid leukemia) may be at increased risk of posttransplant complications associated with excessive inflammatory cytokine production. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Michigan, Ctr Canc, Dept Internal Med, Div Hematol & Oncol, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Canc, Dept Pediat, Div Hematol & Oncol, Ann Arbor, MI 48109 USA. RP Hill, GR (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. RI Hill, Geoffrey/O-2630-2016 OI Hill, Geoffrey/0000-0003-2994-0429 NR 10 TC 21 Z9 21 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 JUN 15 PY 1999 VL 67 IS 11 BP 1478 EP 1480 DI 10.1097/00007890-199906150-00015 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 207RL UT WOS:000080949500015 PM 10385089 ER PT J AU Fusco, C Guidotti, E Zervos, AS AF Fusco, C Guidotti, E Zervos, AS TI In vivo construction of cDNA libraries for use in the yeast two-hybrid system SO YEAST LA English DT Article DE protein-protein interactions; Mxi1; Max; Da; yeast two-hybrid; cDNA libraries ID PROTEIN-PROTEIN INTERACTIONS; LOOP-HELIX PROTEIN; HOMOLOGOUS RECOMBINATION; 2-HYBRID SYSTEM; CLONING; TRANSFORMATION; AUTOANTIGEN; GENES; ASSAY AB We describe a simple and efficient one-step method to make cDNA libraries using homologous recombination in yeast. cDNA from any source, together with a linear vector, is used to transform yeast. Through homologous recombination and gap repair, the cDNA is unidirectionally incorporated into the yeast expression vector in vivo. The cDNA-encoded proteins can then be screened for potential protein-protein interactions with a bait already present in the yeast. This method allows rapid construction and screening of cDNA libraries, even from extremely small amounts of mRNA, and can replace the use of conventional cDNA libraries. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, CBRC, Charlestown, MA 02129 USA. RP Zervos, AS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, CBRC, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 23 TC 19 Z9 19 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0749-503X J9 YEAST JI Yeast PD JUN 15 PY 1999 VL 15 IS 8 BP 715 EP 720 DI 10.1002/(SICI)1097-0061(19990615)15:8<715::AID-YEA406>3.0.CO;2-K PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA 207WP UT WOS:000080959000008 PM 10392448 ER PT J AU Rigotti, NA AF Rigotti, NA TI Treatment options for the weight-conscious smoker SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material ID SMOKING CESSATION; GAIN C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. RP Rigotti, NA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tobacco Res & Treatment Ctr, S50-9,9th Floor,50 Staniford St, Boston, MA 02114 USA. NR 14 TC 14 Z9 16 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 14 PY 1999 VL 159 IS 11 BP 1169 EP 1171 DI 10.1001/archinte.159.11.1169 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 205LX UT WOS:000080823800002 PM 10371223 ER PT J AU Singh, AK Cydulka, RK Stahmer, SA Woodruff, PG Camargo, CA AF Singh, AK Cydulka, RK Stahmer, SA Woodruff, PG Camargo, CA CA Multicenter Asthma Res Collaboration Investigat TI Sex differences among adults presenting to the emergency department with acute asthma SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID RESPIRATORY SYMPTOMS; GENERAL-POPULATION; GENDER DIFFERENCES; BRONCHIAL-ASTHMA; SWISS CHILDREN; YENTL SYNDROME; PREVALENCE; AGE; ESTROGEN; SAMPLE AB Background: Asthma is an increasing problem worldwide, particularly among women. Sex differences in acute asthma presentation, management, or outcome would have important medical and economic implications. Objective: To compare emergency department (ED) visits for acute asthma among women vs men. Methods: We performed a prospective cohort study as part of the Multicenter Asthma Research Collaboration. Patients in the ED, aged 18 to 54 years, who presented with acute asthma underwent a structured interview in the ED and another by telephone 2 weeks later. The study was performed at 36 EDs in 18 states. Pregnant women with asthma were excluded (n = 53). Results: Of 1228 patients, 64.3% were women. Women did not differ significantly from men by age or education level, but women were more likely to be insured, have a primary care provider, and use inhaled corticosteroids. Women had a higher mean +/- SD peak expiratory flow rate than men, both early (expressed as percent pre dieted) (53% +/- 21% vs 41% +/- 18%; P<.001) and late (77% +/- 24% vs 65% +/- 21%; P<.001) in the ED slay. Despite this, women were more likely to be admitted to a hospital (multivariate odds ratio, 2.2; 95% confidence interval; 1.3-4.0) than men. At 2-week follow-up, women had not experienced more relapse events (odds ratio, 1.1) but were 1.5 times more likely to report an ongoing exacerbation (95% confidence interval; 1.0-2.4). Conclusions: Of adults who presented to the ED with acute asthma, women were almost twice as common as men. Although men received less outpatient care and had worse pulmonary function, women were more likely to be admitted to the hospital and to report an ongoing exacerbation at follow-up. Further studies are needed to better understand the complex relationship between sex and acute asthma. C1 Massachusetts Gen Hosp, Dept Emergency Med, Clin 116, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Case Western Reserve Univ, Metrohlth Med Ctr, Dept Emergency Med, Cleveland, OH USA. Hosp Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Clin 116, 55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-03533, HL-07427] NR 42 TC 66 Z9 66 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 14 PY 1999 VL 159 IS 11 BP 1237 EP 1243 DI 10.1001/archinte.159.11.1237 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 205LX UT WOS:000080823800012 PM 10371232 ER PT J AU Geng, Y Whoriskey, W Park, MY Bronson, RT Medema, RH Li, TS Weinberg, RA Sicinski, P AF Geng, Y Whoriskey, W Park, MY Bronson, RT Medema, RH Li, TS Weinberg, RA Sicinski, P TI Rescue of cyclin D1 deficiency by knockin cyclin E SO CELL LA English DT Article ID RETINOBLASTOMA PROTEIN; CELL-PROLIFERATION; S-PHASE; DEPENDENT KINASES; ESTROGEN-RECEPTOR; MAMMARY-GLAND; G1 CYCLIN; E GENE; TRANSCRIPTION; EXPRESSION AB D-type cyclins and cyclin E represent two very distinct classes of mammalian G1 cyclins. We have generated a mouse strain in which the coding sequences of the cyclin D1 gene (Ccnd1) have been deleted and replaced by those of human cyclin E (CCNE). In the tissues and cells of these mice, the expression pattern of human cyclin E faithfully reproduces that normally associated with mouse cyclin D1. The replacement of cyclin D1 with cyclin E rescues all phenotypic manifestations of cyclin D1 deficiency and restores normal development in cyclin D1-dependent tissues. Thus, cyclin E can functionally replace cyclin D1. Our analyses suggest that cyclin E is the major downstream target of cyclin D1. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA 02142 USA. Tufts Univ, Sch Med & Vet Med, Boston, MA 02111 USA. Univ Utrecht, Med Ctr, Jordan Lab, Dept Hematol, NL-3584 CX Utrecht, Netherlands. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. RP Sicinski, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. OI Medema, Rene/0000-0002-6754-0381 FU NCI NIH HHS [535CA39826] NR 25 TC 260 Z9 262 U1 0 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 JUN 11 PY 1999 VL 97 IS 6 BP 767 EP 777 DI 10.1016/S0092-8674(00)80788-6 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 206NQ UT WOS:000080886300014 PM 10380928 ER PT J AU Wang, J Smolyar, A Tan, KM Liu, J Kim, MY Sun, ZJ Wagner, G Reinherz, EL AF Wang, J Smolyar, A Tan, KM Liu, J Kim, MY Sun, ZJ Wagner, G Reinherz, EL TI Structure of a heterophilic adhesion complex between the human CD2 and CD58 (LFA-3) counterreceptors SO CELL LA English DT Article ID T-CELL ACTIVATION; FUNCTION-ASSOCIATED ANTIGEN-3; PROTEIN-PROTEIN INTERFACES; CRYSTAL-STRUCTURE; MOLECULE CD2; IMMUNOGLOBULIN SUPERFAMILY; RECEPTOR CD2; MOUSE CHROMOSOME-1; GLYCOPROTEIN CD2; LIGAND-BINDING AB Interaction between CD2 and its counterreceptor, CD58 (LFA-3), on opposing cells optimizes immune recognition, facilitating contacts between helper T lymphocytes and antigen-presenting cells as well as between cytolytic effecters and target cells. Here, we report the crystal structure of the heterophilic adhesion complex between the amino-terminal domains of human CD2 and CD58. A strikingly asymmetric, orthogonal, face-to-face interaction involving the major beta sheets of the respective immunoglobulin-like domains with poor shape complementarity is revealed. In the virtual absence of hydrophobic forces, interdigitating charged amino acid side chains form hydrogen bonds and salt links at the interface (similar to 1200 Angstrom(2)), imparting a high degree of specificity albeit with low affinity (K-D of similar to mu M). These features explain CD2-CD58 dynamic binding, offering insights into interactions of related immunoglobulin superfamily receptors. C1 Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Wang, J (reprint author), Dana Farber Canc Inst, Immunobiol Lab, 44 Binney St, Boston, MA 02115 USA. EM jwang@red.dfci.harvard.edu; ellis_reinherz@dfci.harvard.edu FU NIAID NIH HHS [AI37581, AI21226]; NIGMS NIH HHS [GM56008] NR 86 TC 165 Z9 168 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUN 11 PY 1999 VL 97 IS 6 BP 791 EP 803 DI 10.1016/S0092-8674(00)80790-4 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 206NQ UT WOS:000080886300016 PM 10380930 ER PT J AU Chen, HM Wei, SQ Engelman, A AF Chen, HM Wei, SQ Engelman, A TI Multiple integrase functions are required to form the native structure of the human immunodeficiency virus type I intasome SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RETROVIRAL DNA INTEGRATION; PHOTO-CROSS-LINKING; HIV-1 INTEGRASE; CONCERTED INTEGRATION; PREINTEGRATION COMPLEXES; INVITRO; VITRO; PROTEIN; BINDING; MUTAGENESIS AB Mu-mediated polymerase chain reaction footprinting was used to investigate the protein-DNA structure of human immunodeficiency virus type I (HIV-I) preintegration complexes. Preintegration complexes were partially purified from cells after using an established coculture infection technique as well as a novel technique using cell-free supernatant from transfected cells as the source of virus. Footprinting revealed that bound proteins protected the terminal 200-250 base pairs of each viral end from nuclease attack. Bound proteins also caused strong transpositional enhancements near each end of HIV-I. In contrast, regions of viral DNA internal to the ends did not show evidence of strong protein binding. The end regions of preintegrative HIV-I apparently form a unique nucleoprotein structure, which we term the intasome to distinguish it from the greater preintegration complex. Our novel system also allowed us to analyze the structure and function of preintegration complexes isolated from cells infected with integrase mutant viruses. Complexes were derived from viruses defective for either integrase catalysis, integrase binding to the viral DNA substrate, or an unknown function in the carboxyl-terminal domain of the integrase protein. None of these mutant complexes supported detectable integration activity. Despite the presence of the mutant integrase proteins in purified samples, none of these nucleoprotein complexes displayed the native intasome structure detected in wildtype preintegration complexes. We conclude that multiple integrase functions are required to form the native structure of the HIV-I intasome in infected cells. C1 Dana Farber Canc Inst, Dept Canc Immunol & Aids, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Engelman, A (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & Aids, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI39394] NR 40 TC 59 Z9 61 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 JUN 11 PY 1999 VL 274 IS 24 BP 17358 EP 17364 DI 10.1074/jbc.274.24.17358 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 204TL UT WOS:000080780400096 PM 10358097 ER PT J AU Mhashilkar, AM LaVecchio, J Eberhardt, B Porter-Brooks, J Boisot, S Dove, JH Pumphrey, C Li, XG Weissmahr, RN Ring, DB Ramstedt, U Marasco, WA AF Mhashilkar, AM LaVecchio, J Eberhardt, B Porter-Brooks, J Boisot, S Dove, JH Pumphrey, C Li, XG Weissmahr, RN Ring, DB Ramstedt, U Marasco, WA TI Inhibition of human immunodeficiency virus type 1 replication in vitro in acutely and persistently infected human CD4(+) mononuclear cells expressing murine and humanized anti-human immunodeficiency virus type 1 Tat single-chain variable fragment intrabodies SO HUMAN GENE THERAPY LA English DT Article ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; PERIPHERAL-BLOOD LYMPHOCYTES; LONG TERMINAL REPEAT; MEDIATED GENE-TRANSFER; HIV-1 TAT; T-CELLS; FACTOR-ALPHA; INFLAMMATORY CYTOKINES; ANTIRETROVIRAL THERAPY AB We have previously reported that a murine anti-Tat sFv intrabody, termed sFvtat1Ck, directed against the proline-rich N-terminal activation domain of HIV-1, is a potent inhibitor of HIV-1 replication [Mhashilkar, A, M., et nl, (1995), EMBO J, 14, 1542-1551], In this study, the protective effect of sFvtat1Ck expression on HIV-1 replication in both acutely infected and persistently infected CD4(+) cells was examined, Stably transfected CD4(+) SupT1 cells were resistant to HIV-1 infection at high MOI with both the laboratory isolate HxB2 and six syncytium-inducing (SI) primary isolates. Persistently infected U1 cells, which can be induced to increase HIV-1 mRNA synthesis on addition of PMA or TNF-alpha, showed decreased production of HIV-1 in the presence of sFvtat1Ck. In transduced CD4(+)-selected, CD8(+)-depleted, and total PMBCs, the sFvtat1Ck-expressing cells showed marked inhibition of HIV-1 replication. The anti-Tat sFv was subsequently humanized by substituting compatible human framework regions that were chosen from a large database of human VH and VL sequences on the basis of high overall framework matching, similar CDR length, and minimal mismatching of canonical and V-H/V-L contact residues. One humanized anti-Tat sFv intrabody, termed sFvhutat2, demonstrated a level of anti-HIV-1 activity that was comparable to the parental murine sFv when transduced PBMCs expressing the murine or humanized sFv intrabodies were challenged with HxB2 and two SI primary isolates. Because Tat is likely to have both direct and indirect effects in the pathogenesis of AIDS through its multiple roles in the HIV-1 life cycle and through its effects on the immune system, the strategy of genetically blocking Tat protein function with a humanized anti-Tat sFv intrabody may prove useful for the treatment of HIV-1 infection and AIDS, particularly when used as an adjuvant gene therapy together with highly active antiretroviral therapies that are currently available. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol AIDS, Boston, MA 02115 USA. Inst Virus Res, Cambridge, MA 02138 USA. Chiron Corp, Emeryville, CA 94608 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Canc Immunol AIDS, Dana Farber Canc Inst, Boston, MA USA. RP Marasco, WA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol AIDS, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [P30 CA06516]; NIAID NIH HHS [P30 AI28691, AI28785] NR 76 TC 31 Z9 33 U1 1 U2 2 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 JUN 10 PY 1999 VL 10 IS 9 BP 1453 EP 1467 DI 10.1089/10430349950017798 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 211FM UT WOS:000081149900005 PM 10395371 ER PT J AU Ay, H Buonanno, FS Rordorf, G Schaefer, PW Schwamm, LH Wu, O Gonzalez, RG Yamada, K Sorensen, GA Koroshetz, WJ AF Ay, H Buonanno, FS Rordorf, G Schaefer, PW Schwamm, LH Wu, O Gonzalez, RG Yamada, K Sorensen, GA Koroshetz, WJ TI Normal diffusion-weighted MRI during stroke-like deficits SO NEUROLOGY LA English DT Article ID CEREBRAL BLOOD-FLOW; SPREADING DEPRESSION; FOCAL ISCHEMIA; RAT-BRAIN; THRESHOLDS; WATER; COEFFICIENT; RESOLUTION; INFARCTION; OCCLUSION AB Background Diffusion-weighted MRI (DWI) represents a major advance in the early diagnosis of acute ischemic,stroke. When abnormal in patients with stroke-like deficit, DWI usually establishes the presence and location of ischemic: brain. injury. However, this: is not always the case. Objective: To investigate patients with stroke-like deficits occurring without DWI abnormalities in brain regions clinically suspected to be responsible. Methods: We identified 27 of 782 consecutive patients scanned when stroke-like neurologic deficits were still present and who had normal DWI in the brain region(s) clinically implicated.. Based on all the clinical and radiologic data, we attempted to arrive at a pathophysiologic diagnosis in each. Results: Best final diagnosis was a stroke mimic in 37% and a cerebral ischemic event in 63%. Stroke mimics (10 patients) included migraine, seizures, functional disorder, transient global amnesia, and brain tumor. The remaining patients were considered to have had cerebral ischemic events: lacunar syndrome (7 patients; 3 with infarcts demonstrated subsequently) and hemispheric cortical syndrome (10 patients; 5 with TLA, 2 with prolonged reversible deficits, 3 with infarction on follow-up imaging). In each of the latter three patients, the regions destined to infarct showed decreased perfusion on the initial hemodynamically weighted MRI (HWI). Conclusions: Normal DWI in patients with stroke-like deficits should stimulate a search for nonischemic cause of symptoms. However, more than one-half of such patients have an ischemic cause as the best clinical diagnosis. Small brainstem lacunar infarctions may escape detection. Concomitant HWI can identify some-patients with brain ischemia that is symptomatic but not yet to the stage of causing DWI abnormality. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Stroke Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroradiol Div, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Koroshetz, WJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Stroke Serv, VBK-915,32 Fruit St, Boston, MA 02114 USA. OI Schwamm, Lee/0000-0003-0592-9145 FU NINDS NIH HHS [5 P50 NS108288-22, 5 RO1 NS35284, R01-NS28371] NR 35 TC 150 Z9 151 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN 10 PY 1999 VL 52 IS 9 BP 1784 EP 1792 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 204HP UT WOS:000080758500013 PM 10371524 ER PT J AU Berezovska, O Frosch, M McLean, P Knowles, R Koo, E Kang, D Shen, J Lu, FM Lux, SE Tonegawa, S Hyman, BT AF Berezovska, O Frosch, M McLean, P Knowles, R Koo, E Kang, D Shen, J Lu, FM Lux, SE Tonegawa, S Hyman, BT TI The Alzheimer-related gene presenilin 1 facilitates notch 1 in primary mammalian neurons SO MOLECULAR BRAIN RESEARCH LA English DT Article DE presenilin 1; notch1; PS1 knockout mice; PS1 transgenics; primary neurons ID CAENORHABDITIS-ELEGANS; CELL FATE; TRANSFECTED CELLS; EXPRESSION; DISEASE; NEUROGENESIS; DROSOPHILA; MICE; TRANSCRIPTION; MYOGENESIS AB The normal functional neurobiology of the Alzheimer's disease (AD) related gene presenilin 1 (PS1) is unknown. One clue comes from a genetic screen of Caenorhabditis elegans, which reveals that the presenilin homologue sel-12 facilitates lin-12 function [D. Levitan, I. Greenwald, Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis elegans S182 Alzheimer's disease gene, Nature 377 (1995) 351-355]. The mammalian homologue of lin-12, Notch1, is a transmembrane receptor that plays an important role in cell fate decisions during development, including neurogenesis, but does not have a known function in fully differentiated cells. To better understand the potential role of Notch1 in mammalian postmitotic neurons and to test the hypothesis that Notch and PS 1 interact, we studied the effect of Notch1 transfection on neurite outgrowth in primary cultures of hippocampal/cortical neurons. We demonstrate that Notch1 inhibits neurite extension, and thus has a function in postmitotic mature neurons in the mammalian CNS. Furthermore, we present evidence demonstrating that there is a functional interaction between PS1 and Notch1 in mammalian neurons, analogous to the sel-12/lin-12 interaction in vulval development in C. elegans [D. Levitan, T. Doyle, D. Brousseau, M. Lee, G. Thinakaran, H. Slunt, S. Sisodia, I. Greenwald, Assessment of normal and mutant human presenilin function in Caenorhabditis elegans, Proc. Natl. Acad. Sci. U.S.A. 93 (1996) 14940-14944; D. Levitan, I. Greenwald, Effect of Sel-12 presenilin on Lin-12 localization and function in Caenorhabditis elegans, Development, 125 (1998) 3599-3606]. The inhibitory effect of Notch1 on neurite outgrowth is markedly attenuated in neurons from PS1 knockout mice, and enhanced in neurons from transgenic mice overexpressing wild type PS1, but not mutant PS1. These data suggest that PS1 facilitates Notch1 function in mammalian neurons, and support the hypothesis that a functional interaction exists between PS1 and Notch1 in postmitotic mammalian neurons. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Neurol Serv, Alzheimers Res Unit, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Div Neuropathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. MIT, Ctr Canc Res, Ctr Learning & Memory, Howard Hughes Med Inst,Dept Biol, Cambridge, MA 02139 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Neurol Serv, Alzheimers Res Unit, Rm 6405,149 13th St, Charlestown, MA 02129 USA. RI Kang, David/E-5234-2012 NR 38 TC 45 Z9 45 U1 3 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD JUN 8 PY 1999 VL 69 IS 2 BP 273 EP 280 DI 10.1016/S0169-328X(99)00119-9 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 205TL UT WOS:000080836600012 ER PT J AU Kawamura, A Guo, JS Itagaki, Y Bell, C Wang, Y Haupert, GT Magil, S Gallagher, RT Berova, N Nakanishi, K AF Kawamura, A Guo, JS Itagaki, Y Bell, C Wang, Y Haupert, GT Magil, S Gallagher, RT Berova, N Nakanishi, K TI On the structure of endogenous ouabain SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NA+-K+-ATPASE; HUMAN PLASMA; BOVINE HYPOTHALAMUS; HYPERTENSIVE RATS; ROTATING FRAME; INHIBITOR; COMPOUND; PUMP AB The ouabain-like sodium pump inhibitor in mammals (so-called "endogenous ouabain") has been considered a subtle structural isomer of ouabain. Its structural investigation, however, has long been hindered by the paucity of sample material, Our recent purification of endogenous ouabain (3 mu g) from bovine hypothalamus allowed the measurement of its H-1-NMR, The obtained spectrum as well as reexamination of past microscale structural studies on endogenous ouabain led us to identify the purified material as ouabain in an unusual manner. It turned out that the structural analysis had been complicated by a facile ouabain-borate complexation in borosilicate glassware. In retrospect, it is not surprising that the polyhydroxylated ouabain molecule serves as a polydentate ligand to inorganic species. In its physiological environment, ouabain may exist as some unknown complex, The chemical species giving rise to the reported biological activities of hypothalamic inhibitory factor preparations remain to be clarified. C1 Columbia Univ, Dept Chem, New York, NY 10027 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv,Renal Unit, Charlestown, MA 02129 USA. BION Inc, Riverside Technol Ctr, Cambridge, MA 02139 USA. RP Nakanishi, K (reprint author), Columbia Univ, Dept Chem, New York, NY 10027 USA. FU NHLBI NIH HHS [HL 52282] NR 36 TC 138 Z9 147 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 8 PY 1999 VL 96 IS 12 BP 6654 EP 6659 DI 10.1073/pnas.96.12.6654 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 205VX UT WOS:000080842200016 PM 10359767 ER PT J AU Hausmann, DHF Yu, B Hausmann, S Wucherpfennig, KW AF Hausmann, DHF Yu, B Hausmann, S Wucherpfennig, KW TI pH-dependent peptide binding properties of the type I diabetes-associated I-A(g7) molecule: Rapid release of CLIP at an endosomal pH SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE major histocompatibility complex; autoimmunity; antigen presentation; I-A(g7); type I diabetes ID MHC CLASS-II; HLA-DR MOLECULES; INVARIANT CHAIN PEPTIDES; ALPHA-BETA-HETERODIMERS; CRYSTAL-STRUCTURE; NOD MICE; COMPLEX; PROTEIN; DM; MOTIF AB MHC class II molecules and invariant chain assemble at a neutral pH in the endoplasmic reticulum and are transported to a low pH compartment where the invariant chain is trimmed to the class II-associated invariant chain peptide (CLIP). For many major histocompatibility complex class II molecules, DM is required for rapid removal of CLIP, which allows binding of antigenic peptides. Since I-A(g7) confers susceptibility to type I diabetes in NOD mice, the biochemical requirements for peptide loading were examined using soluble I-A(g7) expressed in insect cells. I-A(g7) formed long-lived complexes with naturally processed peptides from transferrin and albumin, whereas several peptides that represent T cell epitopes of islet autoantigens were poor binders. I-A(g7)-peptide complexes were not sodium dodecyl sulfate (SDS) resistant, indicating that SDS sensitivity may be an intrinsic property of I-A(g7). Complexes of I-A(g7) and CLIP formed at a neutral pH, but rapidly dissociated at pH 5. This rapid dissociation was due to a poor fit of M98 of CLIP in the P9 pocket of I-A(g7), since substitution of M98 by a negatively charged residue greatly enhanced the stability of the complex. These biochemical properties of I-A(g7) result in the rapid generation of empty molecules at an endosomal pH and have a global effect on peptide binding by I-A(g7). C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI39619] NR 44 TC 64 Z9 65 U1 0 U2 0 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 JUN 7 PY 1999 VL 189 IS 11 BP 1723 EP 1733 DI 10.1084/jem.189.11.1723 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 206BB UT WOS:000080855200006 PM 10359576 ER PT J AU Yang, IH Kim, SY Rubash, HE Shanbhag, AS AF Yang, IH Kim, SY Rubash, HE Shanbhag, AS TI Fabrication of submicron titanium-alloy particles for biological response studies SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article DE TiAlV debris; fabrication; characterization; osteolysis; total hip replacement ID WEAR PARTICLES; SURFACE-AREA; IN-VIVO; SIZE; DEBRIS AB Biologic response to generated wear particles and subsequent aseptic loosening is a critical factor limiting the long-term survival of total hip replacements. To better understand the sequence of events leading to aseptic loosening and the role of the individual material components, fabricating metal particles similar to those present clinically is very important, We describe a simple milling technique to generate significant amounts of fine titanium-alloy (TiAlV) debris. A TiAlV rod was milled against a TiAlV plate in distilled water supplemented with antibiotics, The resulting debris were sedimented in alcohol and the fine debris were separated. Scanning electron microscopy analysis and particle size analysis demonstrated that the mean size of particles was 1.1 +/- 0.9 mu m (range 0.2-4.2 mu m), Sixty-two percent were smaller than 1.0 mu m, and 85% were smaller than 2.0 mu m. The particles generated had varying shapes, including angular or shardlike shapes with jagged and irregular outlines, (C) 1999 John Wiley & Sons, Inc. C1 Univ Pittsburgh, Musculoskeletal Res Ctr, Dept Orthoped Surg, Pittsburgh, PA 15260 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Shanbhag, AS (reprint author), 1126 GRJ,55 Fruit St, Boston, MA 02114 USA. NR 19 TC 5 Z9 7 U1 0 U2 0 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 JUN 5 PY 1999 VL 48 IS 3 BP 220 EP 223 DI 10.1002/(SICI)1097-4636(1999)48:3<220::AID-JBM4>3.0.CO;2-P PG 4 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 199KT UT WOS:000080480900004 PM 10398024 ER PT J AU Woolf, CJ Mannion, RJ AF Woolf, CJ Mannion, RJ TI Neuropathic pain: aetiology, symptoms, mechanisms, and management SO LANCET LA English DT Article ID PERIPHERAL-NERVE INJURY; SUPERFICIAL DORSAL HORN; POSTHERPETIC NEURALGIA; SENSORY NEURONS; SCIATIC-NERVE; HYPERALGESIA; AMPUTATION; EXPRESSION; CHANNELS; FIBERS AB We highlight current theories about peripheral neuropathic pain and show that progress in management is contingent on targeting treatment not at the aetiological factors or the symptoms but at the mechanisms that operate to produce the symptoms. This approach will require substantial progress in our understanding of the pathophysiology of neuropathic pain, the development of accurate diagnostic tools to discover what mechanisms contribute to the pain syndrome in an individual, and effective treatments aimed specifically at the mechanisms. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. NR 34 TC 1155 Z9 1214 U1 15 U2 116 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUN 5 PY 1999 VL 353 IS 9168 BP 1959 EP 1964 DI 10.1016/S0140-6736(99)01307-0 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 202TP UT WOS:000080668500046 PM 10371588 ER PT J AU Jones, DL Thompson, DA Suh-Burgmann, E Grace, M Munger, K AF Jones, DL Thompson, DA Suh-Burgmann, E Grace, M Munger, K TI Expression of the HPV E7 oncoprotein mimics but does not evoke a p53-dependent cellular DNA damage response pathway SO VIROLOGY LA English DT Article ID HUMAN PAPILLOMAVIRUS TYPE-16; RETINOBLASTOMA GENE-PRODUCT; CYCLIN-DEPENDENT KINASES; TUMOR-SUPPRESSOR PROTEIN; GROWTH ARREST; TRANSCRIPTION FACTOR; RETROVIRAL VECTORS; ADENOVIRUS E1A; G(1) ARREST; P53 AB Acute expression of the human papillomavirus E7 oncoprotein in preimmortal human fibroblasts induces changes in the abundances of multiple cellular regulatory proteins. These alterations include a destabilization of the retinoblastoma tumor suppressor protein pRB, stabilization of the tumor suppressor protein p53, and increases in the level of the cyclin-dependent kinase inhibitor p21(clp1) Since the HPV E7 oncoproteins can interfere with several cell cycle checkpoints and similar alterations in the levels of pRB, p53, and p21(clp1) are also observed in a p53-dependent response to DNA damage, we investigated whether E7 expression triggers this signal transduction pathway. The results demonstrate that E7-mediated destabilization of pRB does not require p53 activity and is independent of the ability of E7 to induce apoptosis. Moreover, E7-mediated increases in p21(clp1) levels are largely p53-independent and involve stabilization of the p21(clp1) protein. In contrast the decreases in pRB expression in response to DNA damage involve transcriptional downregulation of RE gene expression. (C) 1999 Academic Press. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Ctr Canc Biol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Biol & Biomed Sci, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Biol Sci Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02115 USA. RP Munger, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, 200 Longwood Ave,Goldenson Bldg,Room 113A, Boston, MA 02115 USA. OI Munger, Karl/0000-0003-3288-9935 NR 63 TC 35 Z9 37 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 5 PY 1999 VL 258 IS 2 BP 406 EP 414 DI 10.1006/viro.1999.9733 PG 9 WC Virology SC Virology GA 206YN UT WOS:000080908300022 PM 10366578 ER PT J AU McConalogue, K Dery, O Lovett, M Wong, H Walsh, JH Grady, EF Bunnett, NW AF McConalogue, K Dery, O Lovett, M Wong, H Walsh, JH Grady, EF Bunnett, NW TI Substance P-induced trafficking of beta-arrestins - The role of beta-arrestins in endocytosis of the neutrokinin-1 receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; GREEN FLUORESCENT PROTEIN; MUSCARINIC ACETYLCHOLINE-RECEPTOR; AGONIST-INDUCED DESENSITIZATION; ADRENERGIC-RECEPTOR; BETA(2)-ADRENERGIC RECEPTOR; NEUROKININ-1 RECEPTOR; ARRESTIN/CLATHRIN INTERACTION; CHOLECYSTOKININ RECEPTOR; INDUCED INTERNALIZATION AB Agonist-induced redistribution of G-protein-coupled receptors (GPCRs) and beta-arrestins determines the subsequent cellular responsiveness to agonists and is important for signal transduction. We examined substance P (SP)-induced trafficking of beta-arrestin1 and the neurokinin-1 receptor (NK1R) in KNRK cells in real time using green fluorescent protein. Green fluorescent protein did not alter function or localization of the NK1R or beta-arrestin1, SP induced (a) striking and rapid (<1 min) translocation of beta-arrestin1 from the cytosol to the plasma membrane, which preceded NK1R endocytosis; (b) redistribution of the NK1R and beta-arrestin1 into the same endosomes containing SP and the transferrin receptor (2-10 min); (c) prolonged colocalization of the NK1R and beta-arrestin1 in endosomes (>60 min); (d) gradual resumption of the steady state distribution of the NK1R at the plasma membrane and beta-arrestin1 in the cytosol (4-6 h), SP stimulated a similar redistribution of immunoreactive beta-arrestin1 and beta-arrestin2. In contrast, SP did not affect G alpha(q/11) distribution, which remained at the plasma membrane. Expression of the dominant negative beta-arrestin(319-418) inhibited SP-induced endocytosis of the NK1R, Thus, SP induces rapid translocation of beta-arrestins to the plasma membrane, where they participate in NK1R endocytosis. beta-Arrestins colocalize with the NK1R in endosomes until the NK1R recycles and beta-arrestins return to the cytosol. C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. RP Bunnett, NW (reprint author), Univ Calif San Francisco, Dept Surg, 521 Parnassus Ave, San Francisco, CA 94143 USA. FU NIDDK NIH HHS [DK43207, DK39957]; NINDS NIH HHS [NS21710] NR 55 TC 78 Z9 78 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 JUN 4 PY 1999 VL 274 IS 23 BP 16257 EP 16268 DI 10.1074/jbc.274.23.16257 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 202TQ UT WOS:000080668600042 PM 10347182 ER PT J AU Guinan, EC Boussiotis, VA Neuberg, D Brennan, LL Hirano, N Nadler, LM Gribben, JG AF Guinan, EC Boussiotis, VA Neuberg, D Brennan, LL Hirano, N Nadler, LM Gribben, JG TI Transplantation of anergic histoincompatible bone marrow allografts SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID VERSUS-HOST DISEASE; MISMATCHED RELATED DONORS; ACUTE MYELOID-LEUKEMIA; ACUTE GRAFT; RISK-FACTORS; LYMPHOPROLIFERATIVE DISORDERS; LYMPHOCYTES-T; CELLS; CYCLOSPORINE; PROPHYLAXIS AB Background Successful allogeneic bone marrow transplantation relies on global immunosuppression or elimination of T cells. In contrast, the induction of anergy can inactivate specific sets of alloreactive T cells in the donor marrow. Previous work has shown that anergy can be induced by blocking the interaction of the B7 molecule on the surface of antigen-presenting cells with the CD28 molecule on the surface of T cells, thus preventing key signaling events essential for the activation of T cells. To investigate the feasibility of this approach with respect to transplantation of histoincompatible bone marrow, we undertook a clinical trial of ex vivo induction of anergy in T cells present in donor marrow to recipient alloantigens. Methods Outcomes in 12 transplant recipients were evaluated. The recipients' peripheral-blood lymphocytes were collected before myeloablation and served as alloantigen-presenting cells. To induce alloantigen-specific anergy, bone marrow from a donor mismatched with the recipient for one HLA haplotype was cocultured with irradiated cells from the recipient for 36 hours in the presence of CTLA-4-Ig, an agent that inhibits B7:CD28-mediated costimulation. After conventional myeloablation and immunoprophylaxis, the treated donor cells were transfused into the recipient. Results After the induction of anergy, the frequency of T cells capable of recognizing alloantigens of the recipient in donor marrow was sharply reduced (P<0.001), whereas the responsiveness to alloantigens from persons unrelated to the recipient or the donor was unaffected (P=0.51). In the 11 patients who could be evaluated, the haploidentical bone marrow cells engrafted. Of these 11 patients, 3 had acute graft-versus-host disease (GVHD) confined to the gastrointestinal tract. No deaths were attributable to GVHD. Five of the 12 patients were alive and in remission 4.5 to 29 months after transplantation. Conclusions Donor bone marrow treated ex vivo to induce anergy to alloantigens from the recipient can reconstitute hematopoiesis in vivo with a relatively low risk of GVHD. (N Engl J Med 1999;340: 1704-14.) (C) 1999, Massachusetts Medical Society. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Childrens Hosp, Div Hematol & Oncol, Boston, MA USA. Brigham & Womens Hosp, Div Med Oncol, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Guinan, EC (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [P50 HL54785]; NIAID NIH HHS [P01 AI41584] NR 63 TC 301 Z9 321 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 3 PY 1999 VL 340 IS 22 BP 1704 EP 1714 DI 10.1056/NEJM199906033402202 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 201WQ UT WOS:000080620200002 PM 10352162 ER PT J AU Burstein, HJ Gelber, S Guadagnoli, E Weeks, JC AF Burstein, HJ Gelber, S Guadagnoli, E Weeks, JC TI Use of alternative medicine by women with early-stage breast cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID QUALITY-OF-LIFE; UNITED-STATES; COMPLEMENTARY THERAPIES; CONVENTIONAL TREATMENT; CONSERVING SURGERY; RISK; PREVALENCE; DISTRESS AB Background We analyzed the use of alternative medicine by women who had received standard therapy for early-stage breast cancer diagnosed between September 1993 and September 1995. Methods A cohort of 480 patients with newly diagnosed early-stage breast cancer was recruited from a Massachusetts statewide cohort of women participating in a study of how women choose treatment for cancer. Alternative medical treatments, conventional therapies, and health-related quality of life were examined. Results New use of alternative medicine after surgery for breast cancer was common (reported by 28.1 percent of the women); such use was not associated with choices about standard medical therapies after we controlled for clinical and sociodemographic variables. A total of 10.6 percent of the women had used alternative medicine before they were given a diagnosis of breast cancer. Women who initiated the use of alternative medicine after surgery reported a worse quality of life than women who never used alternative medicine. Mental health scores were similar at base line among women who decided to use alternative medicine and those who did not, but three months after surgery the use of alternative medicine was independently associated with depression, fear of recurrence of cancer, lower scores for mental health and sexual satisfaction, and more physical symptoms as well as symptoms of greater intensity. All groups of women reported improving quality of life one year after surgery. Conclusions Among women with newly diagnosed early-stage breast cancer who had been treated with standard therapies, new use of alternative medicine was a marker of greater psychosocial distress and worse quality of life. (N Engl J Med 1999; 340:1733-9.) (C) 1999, Massachusetts Medical Society. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA USA. RP Weeks, JC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 59408] NR 33 TC 374 Z9 378 U1 4 U2 14 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 JUN 3 PY 1999 VL 340 IS 22 BP 1733 EP 1739 DI 10.1056/NEJM199906033402206 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 201WQ UT WOS:000080620200006 PM 10352166 ER PT J AU Corcoran, C Grinspoon, S AF Corcoran, C Grinspoon, S TI Treatments for wasting in patients with the acquired immunodeficiency syndrome SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID HUMAN GROWTH-HORMONE; PLACEBO-CONTROLLED TRIAL; TOTAL PARENTERAL-NUTRITION; VIRUS-INFECTED PATIENTS; LEAN BODY-MASS; MEGESTROL-ACETATE; ENERGY-EXPENDITURE; HIV-INFECTION; DOUBLE-BLIND; WEIGHT-LOSS C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. FU NCRR NIH HHS [MO1-RR01066]; NIDDK NIH HHS [R01-DK49302, R01-DK54167] NR 80 TC 68 Z9 71 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 3 PY 1999 VL 340 IS 22 BP 1740 EP 1750 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 201WQ UT WOS:000080620200007 PM 10352167 ER PT J AU Uemura, N Salgia, R Ewaniuk, DS Little, MT Griffin, JD AF Uemura, N Salgia, R Ewaniuk, DS Little, MT Griffin, JD TI Involvement of the adapter protein CRKL in integrin-mediated adhesion SO ONCOGENE LA English DT Article DE adhesion; integrins; BCR ABL; signal transduction; adapter proteins; CRKL ID CHRONIC MYELOGENOUS LEUKEMIA; TYROSINE PHOSPHORYLATION; HEMATOPOIETIC-CELLS; V-CRK; C-ABL; SIGNAL-TRANSDUCTION; CELLULAR PROTEINS; BCR/ABL ONCOGENE; SH3 DOMAIN; IN-VIVO AB CRKL, an SH2-SH3-SH3 adapter protein, is one of the major tyrosine phosphoproteins detected in primary leukemic neutrophils from patients with CML. CRKL binds directly to BCR/ABL through its N-terminal SH3 domain, suggesting it may be involved in BCR/ABL signal transduction. However, the biological function of CRKL in either normal or leukemic cells is still largely unknown. In this study, we have examined the effects of overexpressing full length or deletion mutants of CRKL in hematopoietic cell Lines. Full length, SH2- and SH3(N)-domain deletion mutants of CRKL were transfected into an interleukin-3-dependent hematopoietic cell line, Ba/F3, and 3-5 individual sublines which stably overexpressed each transgene were obtained [Bal F-CRKL, Ba/F-CRKL Delta SH2, and Ba/F-CRKL Delta SH3(N)]. The growth properties of these transfected cells in the presence or absence of IL-3 were not different from mock transfected or untransfected Ba/F3 cells. However, Ba/F3 cells overexpressing full length CRKL, but not deletion mutants of CRKL, were found to have an increase in their ability to bind to fibronectin-coated surfaces. Further, expression of full length, but not Delta SH2- or Delta SH3-CRKL deletion mutants, was found to alter cell morphology on fibronectin-coated plates, an effect which was further enhanced by certain kinds of stress stimuli, such as ionizing radiation. Similar results were obtained when CRKL was transiently overexpressed in Ba/F3 cells, and were also obtained in a second IL-3 dependent hematopoietic cell line, 32Dcl3. Adhesion to fibronectin was blocked by anti-beta 1 integrin monoclonal antibody, but overexpression of CRKL did not affect surface expression of beta 1 integrins, nor did it spontaneously induce expression of the beta 1 integrin 'activation' epitope recognized by the 9EG7 monoclonal antibody. These data suggest a role for CRKL in signaling pathways which regulate adhesion to fibronectin. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Griffin, JD (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA36167]; NIDDK NIH HHS [DK560654] NR 56 TC 26 Z9 28 U1 1 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 3 PY 1999 VL 18 IS 22 BP 3343 EP 3353 DI 10.1038/sj.onc.1202689 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 201HL UT WOS:000080589300005 PM 10362355 ER PT J AU Goldfrank, L Henneman, PL Ling, LJ Prescott, JE Rosen, C Sama, A AF Goldfrank, L Henneman, PL Ling, LJ Prescott, JE Rosen, C Sama, A CA EC Categorization Task Force TI Emergency center categorization standards SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE emergency departments; emergency centers; categorization; standards; SAEM AB The SAEM EC Categorization Task Force was developed in response to the 1994 Macy Foundation's recommendation that emergency medicine (EM) organizations "should revise the classification of emergency departments... to reflect the level of care available in emergency departments,and indicate whether or not facilities are adequate and whether appropriately qualified and credentialed emergency physicians are available 24 hours a day." By holding Level 1 emergency centers (ECs) to objective standards based on the quality of care delivered as well as administrative, research, and educational efforts, SAEM hopes to improve patient care. The SAEM EC Categorization Task Force is now beginning the process of reviewing ECs that provide comprehensive emergency care and serve as regional resources for education, research, and administration in EM. This standards document describes relative and critical criteria to be met in order to receive designation as a Level 1 emergency center. Such centers must meet all critical criteria, and be in sufficient compliance with most or all relative criteria, in order to achieve this designation. This process is entirely voluntary. Any EC is eligible for review. Any institution can initiate the review process by applying. Application materials and further information, including the policies and procedures of the SAEM EC Categorization Task Force, are available from SAEM. C1 Bellevue Hosp Ctr, Dept Emergency Med, New York, NY 10016 USA. Harbor UCLA Med Ctr, Dept Emergency Med, Torrance, CA 90509 USA. Hennepin Cty Med Ctr, Dept Emergency Med, Minneapolis, MN 55415 USA. W Virginia Univ, Dept Emergency Med, Morgantown, WV 26506 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. N Shore Univ Hosp, Dept Emergency Med, Manhasset, NY 11030 USA. RP Goldfrank, L (reprint author), Soc Acad Emergency Med, 901 N Washington Ave, Lansing, MI 48906 USA. NR 0 TC 12 Z9 12 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD JUN PY 1999 VL 6 IS 6 BP 638 EP 655 PG 18 WC Emergency Medicine SC Emergency Medicine GA 206EH UT WOS:000080864000013 PM 10386683 ER PT J AU Beresin, EV AF Beresin, EV TI Media violence and youth SO ACADEMIC PSYCHIATRY LA English DT Article ID TELEVISION AB This column reviews the literature on violence in the media and its effects on youth. The author summarizes the findings of naturalistic, longitudinal, and population-based studies conducted over the last 30 years. The literature provides compelling evidence that exposure of media violence to children plays a major role in the etiology of aggressive behavior. Psychiatrists can facilitate primary prevention of violence in our society by discussing the problem of media violence with parents, medical students, residents, and allied health and school professionals. C1 Massachusetts Gen Hosp, McLean Hosp, Boston, MA 02116 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Beresin, EV (reprint author), Massachusetts Gen Hosp, McLean Hosp, 55 Fruit St,Bulfinch 449, Boston, MA 02116 USA. NR 19 TC 3 Z9 3 U1 3 U2 3 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD SUM PY 1999 VL 23 IS 2 BP 111 EP 114 PG 4 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 201NN UT WOS:000080601800010 PM 25416018 ER PT J AU Corless, IB Stowell, CP Fulton, R Weeks, OD AF Corless, IB Stowell, CP Fulton, R Weeks, OD TI Perspectives in conflict: The response to transfusion-associated AIDS SO AIDS & PUBLIC POLICY JOURNAL LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; UNITED-STATES; SCREENED BLOOD; HEMOPHILIACS; INFECTION; RISK C1 Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. Inst Hlth Profess, Boston, MA USA. Univ Minnesota, Minneapolis, MN USA. Mt Ida Coll, W Newton, MA USA. RP Corless, IB (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. OI Corless, Inge/0000-0003-0438-2037 NR 77 TC 0 Z9 0 U1 0 U2 0 PU UNIV PUBLISHING GROUP PI HAGERSTOWN PA 17100 COLE RD #312, HAGERSTOWN, MD 21740-6901 USA SN 0887-3852 J9 AIDS PUBLIC POLICY J JI Aids Public Policy J. PD SUM PY 1999 VL 14 IS 2 BP 47 EP 67 PG 21 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 309RG UT WOS:000086782600001 PM 10915286 ER PT J AU George, MS Teneback, CC Malcolm, RJ Moore, J Stallings, LE Spicer, KM Anton, RF Ballenger, JC AF George, MS Teneback, CC Malcolm, RJ Moore, J Stallings, LE Spicer, KM Anton, RF Ballenger, JC TI Multiple previous alcohol detoxifications are associated with decreased medial temporal and paralimbic function in the postwithdrawal period SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Research-Society-on-Alcoholism CY JUN 20-25, 1998 CL HILTON HEAD ISL, SOUTH CAROLINA SP Res Soc Alcoholism DE alcoholism; detoxification; sensitization; imaging; medial temporal lobes ID CEREBRAL BLOOD-FLOW; ETHANOL WITHDRAWAL; KINDLING HYPOTHESIS; SEIZURES; EPISODES; SMOKING; BRAIN; CONSUMPTION; METABOLISM; NICOTINE AB Background: Functional neuroimaging studies after alcohol cessation have demonstrated that chronic alcohol use globally reduces neuronal activity for several weeks. Less is known about the effects of previous alcohol use patterns on regional brain activity. Multiple previous alcohol detoxifications are associated with a worse clinical course and increased risk of seizures, perhaps due to sensitization of key brain structures. We performed the following imaging study in alcoholics in the postwithdrawal period to determine if blood now in medial temporal structures would differ as a function of previous alcohol use (i.e., whether regions were kindled or sensitized due to multiple detoxifications). Methods: Fourteen adults meeting DSM-IV criteria for alcohol dependence (mean age 35, 8 SD; 10 men) and participating in a double-blind detoxification medication study underwent a brain perfusion Tc99 m-ECD (Neurolite) single photon emission computed tomography scan on days 7 through 9 (mean 7.6, .5 SD) after their last drink and 2 to 3 days since their last detoxification medication. Seven nonpsychiatrically ill, nonalcohol-dependent healthy adults were scanned as control subjects. Results: Alcoholics compared with controls had widely reduced relative activity in cortical secondary association areas and relatively increased activity in the medial temporal lobes (p < 0.01). Five alcoholic patients with greater than or equal to 2 previous detoxifications were compared with five patients in their first detoxification (age and detoxification medication matched). Multiple detoxification patients had significantly lower relative activity in bilateral anterior temporal poles and medial temporal lobes and in visual cortex (p < 0.01) compared with first episode patients. Conclusions: These studies are consistent with other studies comparing alcoholics and controls. They also suggest that on day 7 of detoxification, alcoholic subjects with multiple previous detoxifications have decreased visual cortex, medial temporal lobes, and anterior paralimbic blood flow, compared with those in their first detoxification. Further studies seem warranted to confirm these initial exploratory results. C1 Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Alcohol Res Ctr, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Dept Psychiat, Charleston, SC USA. RP George, MS (reprint author), Med Univ S Carolina, Dept Radiol, 171 Ashley Ave, Charleston, SC 29425 USA. FU NIAAA NIH HHS [AA10761-03] NR 33 TC 10 Z9 10 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 JUN PY 1999 VL 23 IS 6 BP 1077 EP 1084 DI 10.1097/00000374-199906000-00017 PG 8 WC Substance Abuse SC Substance Abuse GA 208KB UT WOS:000080989000018 PM 10397294 ER PT J AU Cave, DR Van Zanten, SV Carter, E Halpern, EF Klein, S Prather, C Stolte, M Laine, L AF Cave, DR Van Zanten, SV Carter, E Halpern, EF Klein, S Prather, C Stolte, M Laine, L TI A multicentre evaluation of the laser assisted ratio analyser (LARA): A novel device for measurement of (CO2)-C-13 in the C-13-urea breath test for the detection of Helicobacter pylori infection SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID NONINVASIVE TESTS; ACCURACY; GASTRITIS; DIAGNOSIS AB Background: The laser assisted ratio analyser (LARA) was developed as a novel device to measure (CO2)-C-13 in the urea breath test for the detection of H. pylori infection. The analyser was tested in a prospective multicentre study in 444 patients in North America (Phase 1) followed by second study involving 160 patients (Phase 2). Methods: Patients undergoing endoscopy for clinical indications had antral and gastric biopsies taken for histological examination, culture and CLO test. One hour after endoscopy, a baseline breath sample was obtained, 100 mg of C-13-urea were ingested and breath samples were obtained at 30 and 60 min post ingestion. Data obtained with the LARA were compared with the results of culture, rapid urease testing and central pathology in two different combinations {reference standards}. The study was conducted in two phases: in Phase 2, a modification was made to the LARA that improved the removal of water vapour from the breath sample. Results: In Phase I, data from 331 patients were analysed using a cut off of (delta) 7.8 +/- 0.8, the sensitivity of the method was 91.7% and the specificity was 86.5%, using the reference standard of 2 of 3 tests (CLO, culture or histology) being positive. Positive and negative predictive values were, respectively, 85.2% and 92.5%. In Phase 2 of the study, 160 patients were enrolled and 141 patients were analysed using the same standards. We used the same reference standards but with a cut off of (delta) 6.1 +/- 0.6. The sensitivity and specificity increased to 96.8% and 98.6%, respectively. Positive and negative predictive values were, respectively, 98.4% and 97.3%. The detection rates for H. pylori were similar in patients with peptic ulcer or H. pylori associated gastritis. Conclusions: The LARA provides an accurate noninvasive means of detecting (CO2)-C-13 in the C-13-urea breath test for H. pylori in a multicentre clinical environment that compares well with invasive 'gold standard' methods. C1 St Elizabeths Med Ctr Boston, Brighton, MA 02135 USA. QE II Hlth Sci Ctr, Halifax, NS, Canada. Massachusetts Gen Hosp, Ctr Imaging & Pharmaceut Res, Boston, MA 02114 USA. Washington Univ, Sch Med, St Louis, MO USA. Mayo Clin, Rochester, MN USA. USC Sch Med, Los Angeles, CA USA. Klinicum Bayreuth, Inst Pathol, Bayreuth, Germany. RP Cave, DR (reprint author), St Elizabeths Med Ctr Boston, 736 Cambridge St, Brighton, MA 02135 USA. NR 16 TC 26 Z9 26 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD JUN PY 1999 VL 13 IS 6 BP 747 EP 752 DI 10.1046/j.1365-2036.1999.00534.x PG 6 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 211NE UT WOS:000081166500007 PM 10383503 ER PT J AU Richter, JE Kovacs, TOG Greski-Rose, PA Huang, B Fisher, R AF Richter, JE Kovacs, TOG Greski-Rose, PA Huang, B Fisher, R TI Lansoprazole in the treatment of heartburn in patients without erosive oesophagitis SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID GASTROESOPHAGEAL REFLUX DISEASE; INTRAGASTRIC ACIDITY; DOUBLE-BLIND; ESOPHAGITIS RESISTANT; ORAL OMEPRAZOLE; MANAGEMENT; RANITIDINE AB Background: This randomized, double-blind, multicentre study compared lansoprazole with placebo for symptomatic relief of patients with non-erosive gastrooesophageal reflux disease (GERD). Methods: 214 patients with symptomatic, non-erosive GERD (moderate to severe daytime and/or night-time heartburn greater than half the days over the past 6 months and during the 7- to 10-day pre-treatment period) were randomized to either lansoprazole 15 mg or lansoprazole 30 mg, or placebo o.d. for 8 weeks. Results: Daily diary data indicated that on the first treatment day a statistically significantly smaller percentage of lansoprazole patients reported daytime and night-time heartburn and antacid usage, compared with placebo patients. Lansoprazole patients also reported statistically significant less severe daytime and night-time heartburn on the first treatment day. During 0-4, 4-8, and 0-8 weeks of therapy, a statistically significant smaller percentage of days and nights with heartburn, less severe daytime and nighttime heartburn, and less antacid usage were observed in the lansoprazole group compared to the placebo group. The percentages of patients with adverse reactions were similar in the lansoprazole and placebo groups. Conclusions: The results of this study demonstrate that lansoprazole is an appropriate therapy for patients with symptomatic non-erosive GERD. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Cleveland Clin, Dept Gastroenterol, Cleveland, OH 44195 USA. TAP Holdings Inc, Deerfield, IL USA. Abbott Labs, Abbott Pk, IL 60064 USA. Temple Univ Hosp, Philadelphia, PA 19140 USA. RP Richter, JE (reprint author), Cleveland Clin, Dept Gastroenterol, 95 Euclid Ave, Cleveland, OH 44195 USA. NR 30 TC 56 Z9 59 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD JUN PY 1999 VL 13 IS 6 BP 795 EP 804 DI 10.1046/j.1365-2036.1999.00558.x PG 10 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 211NE UT WOS:000081166500014 PM 10383510 ER PT J AU Levine, EG Cirrincione, CT Szatrowski, TP Canellos, G Norton, L Henderson, IC AF Levine, EG Cirrincione, CT Szatrowski, TP Canellos, G Norton, L Henderson, IC TI Phase II trial of topotecan in advanced breast cancer - A Cancer and Leukemia Group B study SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE topotecan; breast neoplasms; clinical trials; phase II ID ANTHRACYCLINE-RESISTANT; PHARMACOKINETICS; PHARMACODYNAMICS; CAMPTOTHECIN; PACLITAXEL; INHIBITORS; DOCETAXEL; TUMORS AB The topoisomerase I inhibitor topotecan had demonstrated good antitumor activity in several murine tumor systems and in human clonogenic assays by 1993. In that year, the Cancer and Leukemia Group B (CALGB) began a phase II trial to determine its activity in patients with breast cancer who had previously received one course of chemotherapy for advanced breast cancer. Between April 1993 and June 1994. 53 patients of performance status 0-2 entered the study, of whom 47 were eligible and 40 were evaluable. Topotecan was given at a dose of 1.5 mg/m(2) over 30 minutes daily for 5 days every 21 days. In the absence of progression or withdrawal of consent, therapy was. continued indefinitely. The median age was 58 years (range 30-79). There were no complete responses and fi,ur partial responses, resulting in an objective response rate of 10% (95% CI: 3-24%). Responses were noted in lymph nodes, liver, and skin. The median duration of response was 5 months. The median survival was 12 months. Life-threatening toxicities were almost exclusively hematologic, However, myelosuppression was not cumulative. It was concluded that topotecan has only modest activity among women with advanced breast cancer who have previously received one course of chemotherapy. Given its modest activity and predominant hematologic toxicity, it does not appear to be a promising drug for either single-agent or combination chemotherapy in the salvage setting of advanced breast cancer. C1 Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. CALGB Stat Off, Durham, NC USA. Cornell Univ, Med Ctr, New York Hosp, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Levine, EG (reprint author), Roswell Pk Canc Inst, Dept Med, Elm & Carlton St, Buffalo, NY 14263 USA. FU NCI NIH HHS [CA07968, CA33601, CA02599] NR 23 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD JUN PY 1999 VL 22 IS 3 BP 218 EP 222 DI 10.1097/00000421-199906000-00002 PG 5 WC Oncology SC Oncology GA 200TF UT WOS:000080555600003 PM 10362325 ER PT J AU Reid, AE Koziel, MJ Aiza, I Jeffers, L Reddy, R Schiff, E Lau, JYN Dienstag, JL Liang, TJ AF Reid, AE Koziel, MJ Aiza, I Jeffers, L Reddy, R Schiff, E Lau, JYN Dienstag, JL Liang, TJ TI Hepatitis C virus genotypes and viremia and hepatocellular carcinoma in the United States SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID CHRONIC LIVER-DISEASE; POLYMERASE CHAIN-REACTION; VIRAL GENOTYPES; INFECTION; RNA; CIRRHOSIS; RISK; VARIABILITY; MORTALITY; SEVERITY AB OBJECTIVE: Hepatitis C virus (HCV) is a well recognized cause of hepatocellular carcinoma (HCC). The pathogenic significance of HCV genotypes in hepatocarcinogenesis is undefined. The aim of this study was to investigate the genotypic distribution and viremic level of HCV in patients with HCV-associated cirrhosis with or without HCC. METHODS: A total of 28 HCV-infected patients with HCC (HCC+) and 38 patients with HCV-associated cirrhosis without HCC (HCC-) were studied. HCV genotype was assessed by the genotype-specific polymerase chain reaction (PCR) method of Okamoto and restriction fragment length polymorphism (RFLP) of the 5' untranslated region (5' UTR). Hepatitis C viremia was quantitated with the branched-chain DNA (bDNA) assay. RESULTS: Using the Okamoto method, we found genotype Ib in 63% of the HCC+ group and 74% of the HCC- group, 36% of the HCC+ group and 16% of the HCC- group were coinfected with a combination of genotype Ib and another genotype. Using the RFLP method, we found genotype Ib in 41% of the HCC+ group and in 24% of the HCC- group. Other genotypes accounted for 18% of the HCC+ group and 55% of the HCC- group; no combination genotypes were identified. Poor concordance occurred between the two genotyping methods. Mean bDNA levels were not significantly different between the two groups. CONCLUSIONS: Our study demonstrates that no particular HCV genotypes were associated with HCC and genotype did not appear to influence the development of HCV-associated HCC. (Am J Gastroenterol 1999;94:1619-1626. (C) 1999 by Am. Cell. of Gastroenterology). C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NIDDKD, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. Univ Miami, Sch Med, Ctr Liver Dis, Miami, FL USA. Univ Florida, Div Gastroenterol Hepatol & Nutr, Gainesville, FL USA. RP Reid, AE (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GI Unit GJ724,Fruit St, Boston, MA 02114 USA. FU NIAID NIH HHS [K08AI01210]; NIDDK NIH HHS [P30DK43351-08, T32DK07191-23] NR 37 TC 29 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JUN PY 1999 VL 94 IS 6 BP 1619 EP 1626 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 203NQ UT WOS:000080714100033 PM 10364034 ER PT J AU Lew, EA Lewin, KJ Zarchy, T Pisegna, JR AF Lew, EA Lewin, KJ Zarchy, T Pisegna, JR TI Adenocarcinoma of the colon with neuroendocrine features and secretory diarrhea SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID ENDOCRINE-CELLS; CARCINOMA; MARKERS; RECTUM AB We report the case of a 63-yr-old man who had severe secretory diarrhea associated with colonic adenocarcinoma, with a prominent signet ring cell component and numerous endocrine cells as demonstrated by positive chromogranin-A staining. Improvement in the secretory diarrhea by the somatostatin analog Sandostatin suggested that the diarrhea was related to a functional neuroendocrine tumor within the colonic tumor, the first case to be reported in the literature. (Am J Gastroenterol 1999;94:1692-1694. (C) 1999 by Am. Cell. of Gastroenterology). C1 W Los Angeles Vet Affairs Med Ctr, CURE, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Med Ctr, CURE, Div Digest Dis,Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Med Ctr, Dept Pathol, Los Angeles, CA 90024 USA. RP Pisegna, JR (reprint author), W Los Angeles Vet Affairs Med Ctr, CURE, Digest Dis Res Ctr, Bldg 115,Room 316,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 14 TC 2 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JUN PY 1999 VL 94 IS 6 BP 1692 EP 1694 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 203NQ UT WOS:000080714100048 PM 10364049 ER PT J AU Sleat, DE Gin, RM Sohar, I Wisniewski, K Sklower-Brooks, S Pullarkat, RK Palmer, DN Lerner, TJ Boustany, RM Uldall, P Siakotos, AN Donnelly, RJ Lobel, P AF Sleat, DE Gin, RM Sohar, I Wisniewski, K Sklower-Brooks, S Pullarkat, RK Palmer, DN Lerner, TJ Boustany, RM Uldall, P Siakotos, AN Donnelly, RJ Lobel, P TI Mutational analysis of the defective protease in classic late-infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disorder SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID BATTEN-DISEASE; THIOESTERASE DEFICIENCY; GENE; VARIANT; GLYCOPROTEINS; FORMS; CLN3 AB The late-infantile form of neuronal ceroid lipofuscinosis (LINCL) is a progressive and ultimately fatal neurodegenerative disease of childhood. The defective gene in this hereditary disorder, CLN2, encodes a recently identified lysosomal pepstatin-insensitive acid protease. To better understand the molecular pathology of LINCL, we conducted a genetic survey of CLN2 in 74 LINCL families. In 14 patients, CLN2 protease activities were normal and no mutations were identified, suggesting other forms of NCL. Both pathogenic alleles were identified in 57 of the other 60 LINCL families studied. In total, 24 mutations were associated with LINCL, comprising six splice-junction mutations, 11 missense mutations, 3 nonsense mutations, 3 small deletions, and 1 single-nucleotide insertion. Two mutations were particularly common: an intronic G-->C transversion in the invariant AG of a 3' splice junction, found in 38 of 115 alleles, and a C-->T transition in 32 of 115 alleles, which prematurely terminates translation at amino acid 208 of 563. An Arg-->His substitution was identified, which was associated with a late age at onset and protracted clinical phenotype, in a number of other patients originally diagnosed with juvenile NCL. C1 Univ Med & Dent New Jersey, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. Univ Med & Dent New Jersey, Dept Pharmacol, Piscataway, NJ 08854 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Lab Med & Pathol, Newark, NJ 07103 USA. New York State Inst Basic Res Dev Disabil, Dept Pathol Neurobiol, Staten Isl, NY 10314 USA. New York State Inst Basic Res Dev Disabil, Dept Human Genet, Staten Isl, NY 10314 USA. New York State Inst Basic Res Dev Disabil, Dept Neurochem, Staten Isl, NY 10314 USA. SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. Lincoln Univ, Anim & Food Sci Div, Canterbury, New Zealand. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Duke Univ, Med Ctr, Dept Pediat & Neurobiol, Durham, NC USA. Juliane Marie Ctr, Neuropediat Clin, Copenhagen, Denmark. Indiana Univ, Sch Med, Dept Pathol, Indianapolis, IN 46202 USA. RP Lobel, P (reprint author), Univ Med & Dent New Jersey, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. RI Palmer, David/B-7344-2008 FU NIDDK NIH HHS [DK45992]; NINDS NIH HHS [NS37918] NR 29 TC 96 Z9 99 U1 0 U2 0 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 JUN PY 1999 VL 64 IS 6 BP 1511 EP 1523 DI 10.1086/302427 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 203FA UT WOS:000080696200004 PM 10330339 ER PT J AU Chuang, HY Lee, MLT Chao, KY Wang, JD Hu, H AF Chuang, HY Lee, MLT Chao, KY Wang, JD Hu, H TI Relationship of blood lead levels to personal hygiene habits in lead battery workers: Taiwan, 1991-1997 SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE blood lead; lead battery; health promotion; personal hygiene ID LONGITUDINAL DATA; DETERMINANTS; SURVEILLANCE AB Background: The blood lead concentrations of workers in lead battery factories are more than 4 times higher than those of the general population in Taiwan. Therefore, efforts are needed to reduce lead exposure in this high-risk population. A health promotion program on personal habits that reduce lead exposure has been carried out in a lead battery factory since 1991. This study investigated the longitudinal relationship of workers' blood lead concentrations and personal hygiene habits from 1991 through 1997 Methods: In each of the 7 years of the study, occupational physicians questioned workers regarding nine personal hygiene items, personal information and medical history before their annual health examination The relationship between blood lead concentrations and personal hygiene habits was analyzed by longitudinal multiple regression in a mixed effect model with adjustment for potential confounders. In addition, the risk ratio of a blood lead concentration exceeding 40 mu g/dL in men and 30 mu g/dL in women (the action levels set by the Department of Health, Taiwan) was estimated by generalized estimating equations. Results: Blood lead levels decreased significantly in the first 5 years of the study. The personal habits most closely related to blood lead concentrations were smoking at work sites (estimated coefficient = 3.13, P < 0.001), and eating at work sites (estimated coefficient = 1.38, P = 0.069). The risk ratio for workers with both these habits exceeding the action level of blood lead was 2.93 (95% CI 1.27-6.77). Difference in job titles, however accounted for a major portion of the variance in blood lead For example, working in "pasting" and "plate-cutting" was associated with blood lead elevations >20 mu g/dL in comparison to the "low- or no-exposure jobs. Conclusions: Health promotion programs cart decrease exposure of lend workers; reducing the practices of smoking and eating at work sites should be the core of such programs. However; a major reduction in lead exposure for some jobs (e.g., "pasting" and "plate-cutting") in lead battery factories in Taiwan is unlikely to occur without major engineering changes. Am. J. Ind. Med. 35:595-603, 1999. (C) 1999 Wiley-Liss, Inc. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Bur Hlth, Tao Yuan, Taiwan. Natl Taiwan Univ, Coll Publ Hlth, Inst Occupat Med & Ind Hyg, Taipei, Taiwan. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Hu, H (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. RI Chuang, Hung-Yi/C-9143-2009 OI Chuang, Hung-Yi/0000-0002-8321-8720 FU NIEHS NIH HHS [ES-00002] NR 18 TC 35 Z9 41 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 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUN PY 1999 VL 35 IS 6 BP 595 EP 603 DI 10.1002/(SICI)1097-0274(199906)35:6<595::AID-AJIM7>3.0.CO;2-5 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 194DJ UT WOS:000080176600007 PM 10332513 ER PT J AU Saint, S Scholes, D Fihn, SD Farrell, RG Stamm, WE AF Saint, S Scholes, D Fihn, SD Farrell, RG Stamm, WE TI The effectiveness of a clinical practice guideline for the management of presumed uncomplicated urinary tract infection in women SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID CARE; INTERVENTION; STRATEGIES; CYSTITIS; ADULTS; RULES; TRIAL; COSTS AB PURPOSE: Acute uncomplicated urinary tract infection is a common and costly disorder in women. To reduce potentially unnecessary expense and inconvenience, a large staff-model health maintenance organization instituted a telephone-based clinical practice guideline for managing presumed cystitis in which women 18 to 55 years of age who met specific criteria were managed without a clinic visit or laboratory testing. We sought to evaluate the effects of the guideline. SUBJECTS AND METHODS: We performed a population-based, before-and-after study with concurrent control groups at 24 primary care clinics to assess the effect of guideline implementation on resource utilization and on the occurrence of potential adverse outcomes. We measured the proportion of patients with presumed uncomplicated cystitis who had a return office visit for cystitis or sexually transmitted disease or who developed pyelonephritis within 60 days of the initial diagnosis. Relative risks (RR) and 95% confidence intervals (CI) were estimated, adjusting for the effects of clustering within clinics. RESULTS: A total of 3,889 eligible patients with presumed acute uncomplicated cystitis were evaluated. As compared with baseline, guideline implementation significantly decreased the proportion of patients with presumed cystitis who received urinalysis (RR = 0.75; CI, 0.70 to 0.80), urine culture (RR = 0.73; CI, 0.68 to 0.79), and an initial office visit (RR = 0.67; CI, 0.62 to 0.73), while increasing the proportion who received a guideline-recommended antibiotic 2.9-fold (CI, 2.4 to 3.7-fold). In the prospective comparison of the 22 intervention and two control clinics, the guideline decreased the proportion of patients who had urinalyses performed (RR = 0.80; CI, 0.65 to 0.98) and increased the proportion of patients who were prescribed a guideline-recommended antibiotic (RR = 1.53; CI, 1.01 to 2.33). Adverse outcomes did not increase significantly in either comparison. CONCLUSION: Guideline use decreased laboratory utilization and overall costs while maintaining or improving the quality of care for patients who were presumptively treated for acute uncomplicated cystitis. Am J Med. 1999;106:636-641. (C) 1999 by Excerpta Medica, Inc. C1 Univ Washington, Dept Med, Seattle, WA USA. Grp Hlth Cooperat, Emergency Dept, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, NW Hlth Serv Res & Dev Program, Seattle, WA USA. RP Saint, S (reprint author), Univ Michigan, Med Ctr, 3116 Taubman Ctr,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. NR 28 TC 70 Z9 71 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUN PY 1999 VL 106 IS 6 BP 636 EP 641 DI 10.1016/S0002-9343(99)00122-9 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 204VE UT WOS:000080784600007 PM 10378621 ER PT J AU Schiff, I Bell, WR Davis, V Kessler, CM Meyers, C Nakajima, S Sexton, BJ AF Schiff, I Bell, WR Davis, V Kessler, CM Meyers, C Nakajima, S Sexton, BJ TI Oral contraceptives and smoking, current considerations: Recommendations of a consensus panel SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT Womens Health Consensus Conference on Oral Contraceptives and Smoking - Current Considerations CY NOV 07-09, 1997 CL MONTREAL, CANADA SP Univ Maryland Women's Hlth Res Grp, Dept Epidemiol & Preventive Med DE oral contraceptives; smoking; smoking cessation; thrombotic disease AB In a closed meeting, members of the consensus panel evaluated the presentations of the scientific panel and developed a series of recommendations. They outlined clinical imperatives related to the identification and education of patients who smoke, the physician's role in smoking cessation, and the prescription of oral contraceptives for patients who smoke. They also outlined research objectives for the future. The most important suggestions include the following: All patients should be asked about their smoking status at every visit, and all smokers should be encouraged and helped to quit. The decision to prescribe an oral contraceptive requires a detailed personal and family history of thrombotic disease. Measurement of lipid profile should be considered, along with exercise and dietary intervention, for smokers >35 years old who use or request oral contraceptives. Patients >35 years old who smoke heavily (>15 cigarettes/d) should be denied the use of oral contraceptives. Preliminary data suggest that an oral contraceptive with the very low dose of 20 mu g ethinyl estradiol may be safer for oral contraceptive users who smoke, even for those >35 years old who have an occasional cigarette, but these laboratory findings require clinical corroboration. C1 Harvard Univ, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. Johns Hopkins Univ, Sch Med, Div Hematol, Baltimore, MD USA. Univ Toronto, Toronto, ON, Canada. Georgetown Univ, Med Ctr, Div Hematol & Oncol, Washington, DC 20007 USA. Univ Louisville, Sch Med, Dept Obstet & Gynecol, Louisville, KY 40292 USA. Univ Maryland, Womens Hlth Res Grp, College Pk, MD 20742 USA. RP Schiff, I (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, VBK-1, Boston, MA 02114 USA. NR 0 TC 9 Z9 9 U1 0 U2 0 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 JUN PY 1999 VL 180 IS 6 SU S BP S383 EP S384 DI 10.1016/S0002-9378(99)70700-3 PN 2 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 211QY UT WOS:000081173500008 PM 10368525 ER PT J AU Labow, BI Souba, WW Abcouwer, SF AF Labow, BI Souba, WW Abcouwer, SF TI Glutamine synthetase expression in muscle is regulated by transcriptional and posttranscriptional mechanisms SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE glutamate-ammonia ligase; dexamethasone; methionine sulfoximine; starvation; gene expression regulation ID SKELETAL-MUSCLE; AMINO-ACIDS; METABOLISM; RATS; GLUCOCORTICOIDS AB Skeletal muscle exports glutamine (Gln) and increases the expression of the enzyme glutamine synthetase (GS) in response to physiological stress. Acute stress or direct glucocorticoid administration raises muscle GS mRNA levels dramatically without a parallel increase in GS protein levels. In the lung, this discrepancy is caused by feedback destabilization of the GS protein by its product Gin. It was hypothesized that muscle GS protein levels increase during stress only when the intracellular Gin pool has been depleted. Adult male rats were injected with the glucocorticoid hormone dexamethasone (DEX) to mimic the acute stress response and with the GS inhibitor methionine sulfoximine (MSO) to deplete muscle Gin stores. DEX increased GS mRNA levels by 2.8-fold but increased GS protein levels by an average of only 40%. MSO diminished muscle GLN levels by 68% and caused GS protein levels to rise in accordance with GS mRNA. Chronic stress was mimicked using 6 days of MSO treatment, which produced anorexia, 23% loss of body weight, and 64% decrease in muscle Gin levels, as well as pronounced in creases in both muscle GS mRNA(26-fold) and protein levels (35-fold) without elevation of plasma glucocorticoid levels. Calorie-restricted pair-fed animals exhibited lesser increases in muscle GS mRNA (8-fold) and protein levels (5-fold) without a decline in muscle Gin content. Thus regulation of GS expression in both acute and chronic stress involved both transcriptional and posttranscriptional mechanisms, perhaps affected by muscle Gin content. C1 Massachusetts Gen Hosp, Surg Oncol Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Abcouwer, SF (reprint author), Massachusetts Gen Hosp, Surg Oncol Res Labs, Jackson Bldg,Rm 91855,Fruit St, Boston, MA 02114 USA. EM abcouwer.steven@mgh.harvard.edu FU NHLBI NIH HHS [R01-HL-44986] NR 26 TC 29 Z9 31 U1 2 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUN PY 1999 VL 276 IS 6 BP E1136 EP E1145 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 205LN UT WOS:000080822900020 PM 10362628 ER PT J AU Lefer, DJ Jones, SP Girod, WG Baines, A Grisham, MB Cockrell, AS Huang, PL Scalia, R AF Lefer, DJ Jones, SP Girod, WG Baines, A Grisham, MB Cockrell, AS Huang, PL Scalia, R TI Leukocyte-endothelial cell interactions in nitric oxide synthase-deficient mice SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE P-selectin; gene-targeted mice; endothelium; neutrophil; microcirculation ID SMOOTH-MUSCLE CELLS; ISCHEMIA-REPERFUSION; TARGETED DISRUPTION; NITROXIDERGIC NERVE; VASCULAR TONE; LACKING; INJURY; GENE; RAT; HYPERTENSION AB Nitric oxide (NO) is known to be an important endogenous modulator of leukocyte-endothelial cell interactions within the microcirculation. We examined leukocyte rolling and adhesion under baseline conditions and following thrombin (0.25 U/ml) superfusion in the mesentery of wildtype, inducible NOS (iNOS)-deficient (-/-), neuronal NOS (nNOS) -/-, and endothelial cell NOS (ecNOS) -/- mice to further our understanding of NO and leukocyte function. Baseline leukocyte rolling (cells/min) was significantly elevated in both the nNOS -/- (30.0 +/- 4.0) and ecNOS -/- mice (67.0 +/- 12.0) compared with wild-type mice (11.0 +/- 1.4). In addition, baseline leukocyte adherence (cells/100 mu m of vessel). was also significantly elevated in the nNOS -/- (5.2 +/- 1.0) and ecNOS -/- (13.0 +/- 1.3) compared with wild-type animals (1.3 +/- 0.5). Deficiency of iNOS had no effect on baseline leukocyte rolling or adhesion in the mesentery. Baseline surface expression of P-selectin was observed in 68.0 +/- 9.0% of intestinal venules in ecNOS -/- mice compared with 10.0 +/- 2.0% in wild-type mice. Additional studies demonstrated that administration of an anti-P-selectin monoclonal antibody (RB40.34) or the soluble P-selectin ligand, PSGL-1, completely inhibited the increased rolling and firm adhesion response in nNOS -/- and ecNOS -/- mice. Transmigration of neutrophils into the peritoneum following thioglycollate injection was also significantly augmented in nNOS -/- and ecNOS -/- mice. These studies clearly indicate the NO derived from both nNOS and ecNOS is critical in the regulation of leukocyte-endothelial cell interactions. C1 Louisiana State Univ, Med Ctr, Dept Mol & Cellular Physiol, Shreveport, LA 71130 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA. Thomas Jefferson Univ, Dept Physiol, Philadelphia, PA 19107 USA. RP Lefer, DJ (reprint author), Louisiana State Univ, Med Ctr, Dept Mol & Cellular Physiol, 1501 Kings Highway, Shreveport, LA 71130 USA. EM dlefer@mail.sh.lsumc.edu RI Lefer, David/A-6372-2012; Jones, Steven/D-5092-2009 OI Jones, Steven/0000-0001-5376-8089 FU NIDDK NIH HHS [P01-DK-43785, R01-DK-47663] NR 49 TC 121 Z9 122 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUN PY 1999 VL 276 IS 6 BP H1943 EP H1950 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 205LU UT WOS:000080823500018 PM 10362674 ER PT J AU Grewal, JS Mukhin, YV Garnovskaya, MN Raymond, JR Greene, EL AF Grewal, JS Mukhin, YV Garnovskaya, MN Raymond, JR Greene, EL TI Serotonin 5-HT(2A) receptor induces TGF-beta 1 expression in mesangial cells via ERK: proliferative and fibrotic signals SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE proliferation; fibrosis; mesangial cell; serotonin; transforming growth factor ID GROWTH-FACTOR-BETA; HEART-DISEASE; PROTEIN; ACTIVATION; KINASE; FACTOR-BETA-1; TRANSCRIPTION; ANTIOXIDANT; GLOMERULONEPHRITIS; TRANSFORMATION AB We examined the links between fibrotic and proliferative pathways for the 5-HT(2A) receptor in rat mesangial cells. Serotonin (5-hydroxytryptamine, 5-MT) induced transforming growth factor-beta 1 (TGF-beta 1) mRNA in a concentration-dependent (peak at 30 nM 5-MT) and time-dependent fashion. For 10 nM 5-HT, the effect was noticeable at 1 h and maximal by 6 h. Inhibition of 1) protein kinase C (PKC), 2) mitogen- and extracellular signal-regulated kinase kinase (MEK1) with 2'-amino-3'-methoxyflavone (PD-90859), and 3) extracellular signal-regulated kinase (ERK) with apigenin attenuated this effect. The effect was blocked by antioxidants, N-acetyl-L-cysteine (NAC) and cr-lipoic acid, and mimicked by direct application of H(2)O(2). TGF-beta 1 mRNA induction was also blocked by diphenyleneiodonium and 4-(2-aminoethyl)-benzenesulfonyl fluoride, which inhibit NAD(P)H oxidase, a source of oxidants. 5-HT increased the amount of TGF-P 1 protein, validating the mRNA studies and demonstrating that 5-HT potently activates ERK and induces TGF-beta 1 mRNA and protein in mesangial cells. Mapping studies strongly supported relative positions of the components of the signaling cascade as follow: 5-HT(2A) receptor --> PKC --> NAD(P)H oxidase/reactive oxygen species --> MEK --> ERK --> TGF-beta 1 mRNA. These studies demonstrate that mitogenic signaling components (PKC, MEK, and oxidants) are directly linked to the regulation of TGF-beta 1, a key mediator of fibrosis. Thus a single stimulus can direct both proliferative and fibrotic signals in renal mesangial cells. C1 Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Greene, EL (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, Rm 829C CSB,171 Ashley Ave, Charleston, SC 29425 USA. EM greeneel@musc.edu FU NHLBI NIH HHS [HL-03710]; NIDDK NIH HHS [DK-52448] NR 46 TC 91 Z9 93 U1 0 U2 2 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 JUN PY 1999 VL 276 IS 6 BP F922 EP F930 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 205LQ UT WOS:000080823200013 PM 10362781 ER PT J AU Ghaffar, O Hamid, Q Renzi, PM Allakhverdi, Z Molet, S Hogg, JC Shore, SA Luster, AD Lamkhioued, B AF Ghaffar, O Hamid, Q Renzi, PM Allakhverdi, Z Molet, S Hogg, JC Shore, SA Luster, AD Lamkhioued, B TI Constitutive and cytokine-stimulated expression of eotaxin by human airway smooth muscle cells SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID CHEMOKINE RECEPTOR CCR3; TUMOR-NECROSIS-FACTOR; GUINEA-PIG MODEL; BRONCHOALVEOLAR LAVAGE; ALLERGIC INFLAMMATION; T-CELLS; EOSINOPHIL CHEMOATTRACTANT; GENE-EXPRESSION; MESSENGER-RNA; IN-VIVO AB Airway eosinophilia is a prominent feature of asthma that is believed to be mediated in part through the expression of specific chemokines such as eotaxin, a potent eosinophil chemoattractant that is highly expressed by epithelial cells and inflammatory cells in asthmatic airways. Airway smooth muscle (ASM) has been identified as a potential source of cytokines and chemokines. The aim of the present study was to examine the capacity of human ASM to express eotaxin. We demonstrate that airway myocytes constitutively express eotaxin mRNA as detected by RT-PCR. Treatment of ASM for 24 h with different concentrations of TNF-alpha and IL-1 beta alone or in combination enhanced the accumulation of eotaxin transcripts. Maximal mRNA expression of eotaxin was shown at 12 and 24 h following IL-1 beta and TNF-alpha stimulation, respectively. The presence of immunoreactive eotaxin was demonstrated by immunocytochemistry, and constitutive and cytokine-stimulated release of eotaxin was confirmed in ASM culture supernatants by ELISA. Strong signals for eotaxin mRNA and immunoreactivity were observed in vivo in smooth muscle in asthmatic airways. In addition, chemotaxis assays demonstrated the presence of chemoattractant activity for eosinophils and PBMCs in ASM supernatants. The chemotactic responses of eosinophils were partly inhibited with antibodies directed against eotaxin or RANTES, and a combined blockade of both chemokines causes >70% inhibition of eosinophil chemotaxis. The results of this study suggest that ASM may contribute to airway inflammation in asthma through the production and release of eotaxin. C1 McGill Univ, Meakins Christie Labs, Montreal, PQ H2X 2P2, Canada. CHUM Res Ctr, Montreal, PQ, Canada. Univ British Columbia, Pulm Res Lab, Vancouver, BC, Canada. Harvard Univ, Sch Publ Hlth, Boston, MA USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hamid, Q (reprint author), McGill Univ, Meakins Christie Labs, 3626 St Urbain St, Montreal, PQ H2X 2P2, Canada. NR 48 TC 134 Z9 137 U1 1 U2 5 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 JUN PY 1999 VL 159 IS 6 BP 1933 EP 1942 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 204TH UT WOS:000080780000038 PM 10351942 ER PT J AU Kradin, RL Liu, HW van Rooijen, N Springer, K Zhao, LH Leary, CP AF Kradin, RL Liu, HW van Rooijen, N Springer, K Zhao, LH Leary, CP TI Pulmonary immunity to Listeria is enhanced by elimination of alveolar macrophages SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID PRESENTING CELL FUNCTION(S); DENDRITIC CELLS; ACCESSORY CELLS; INHALED ANTIGEN; DOWN-REGULATION; NITRIC-OXIDE; RAT LUNG; RESPONSES; INVIVO; POPULATIONS AB To determine how resident alveolar macrophages (AM) regulate the antigen-presenting-cell (APC) activities of pulmonary dendritic cells (DC) in the response to particulate antigen, we pretreated Lewis rats intratracheally with liposomes containing clodronate (LIP-CLOD), which eliminated AM in vivo. Controls received saline encapsulated in liposomes (LIP-SAL) or saline alone intratracheally. At Day 3, rats were injected intratracheally with 1 x 10(7) heat-killed Listeria (HKL) and DC purified from lung were examined for their ability to stimulate HKL-immune T cells without added HKL. Only DC from LIP-CLOD-treated rats displayed enhanced APC activities for HKL. A second intratracheal HKL challenge at Day 14 yielded lymphocytic cuffing of the microvasculature in LIP-CLOD-treated lungs only. Intratracheal adoptive transfer of normal syngeneic AM into LIP-CLOD-treated rats suppressed APC activities of DC in vitro and the lymphocytic response in vivo. Bronchoalveolar macrophages from rats treated with LIP-CLOD and HKL showed decreased production of nitric oxide (NO), a potent suppressor of DC and T-helper 1 lymphocyte activities as compared with those of controls. We conclude that eliminating AM in vivo reduces local production of NO and promotes pulmonary cell-mediated immunity to HKL. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Dept Histol, Amsterdam, Netherlands. RP Kradin, RL (reprint author), Massachusetts Gen Hosp, Dept Pathol, 100 Blossom St,Cox Bldg 5, Boston, MA 02114 USA. FU PHS HHS [R01A139054] NR 24 TC 25 Z9 25 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 JUN PY 1999 VL 159 IS 6 BP 1967 EP 1974 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 204TH UT WOS:000080780000042 PM 10351946 ER PT J AU Ayas, NT McCool, FD Gore, R Lieberman, SL Brown, R AF Ayas, NT McCool, FD Gore, R Lieberman, SL Brown, R TI Prevention of human diaphragm atrophy with short periods of electrical stimulation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID IMMOBILIZATION AB We determined whether prolonged complete inactivation of the human diaphragm results in atrophy and whether this could be prevented by brief periods of electrical phrenic nerve stimulation. We studied a subject with high spinal cord injury who required removal of his left phrenic nerve pacemaker (PNP) and the reinstitution of positive-pressure ventilation for 8 mo. During this time, the right phrenic nerve was stimulated 30 min per day. Thickness of each diaphragm (tdi) was determined by ultrasonography. Maximal tidal volume (VT) was measured during stimulation of each diaphragm separately. After left PNP reimplantation, VT and tdi were measured just before the resumption of electrical stimulation and serially for 33 wk. On the previously nonfunctioning side, there were substantial changes in VT (from 220 to 600 mi) and tdi (from 0.18 to 0.34 cm). On the side that had been stimulated, neither VT nor tdi changed appreciably (VT from 770 to 900 mi; tdi from 0.25 to 0.28 cm). We conclude that prolonged inactivation of the diaphragm causes atrophy which may be prevented by brief periods of daily phrenic nerve stimulation. C1 Mem Hosp, Div Pulm, Dept Med, Pawtucket, RI 02860 USA. Brockton W Roxbury Vet Affairs Med Ctr, Pulm & Crit Care Med Sect, Serv Radiol, W Roxbury, MA USA. Brockton W Roxbury Vet Affairs Med Ctr, Spinal Cord Injury Serv, W Roxbury, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Brown Univ, Sch Med, Providence, RI 02912 USA. RP McCool, FD (reprint author), Mem Hosp, Div Pulm, Dept Med, 111 Brewster St, Pawtucket, RI 02860 USA. NR 8 TC 34 Z9 37 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 JUN PY 1999 VL 159 IS 6 BP 2018 EP 2020 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 204TH UT WOS:000080780000051 PM 10351955 ER PT J AU Kaufman, JA Hu, S Geller, SC Waltman, AC AF Kaufman, JA Hu, S Geller, SC Waltman, AC TI Selective angiography of the common carotid artery with gadopentetate dimeglumine in a patient with renal insufficiency SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CONTRAST MATERIAL; CARBON-DIOXIDE; AGENTS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Radiol, Boston, MA 02114 USA. RP Kaufman, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Radiol, GRB 290,Fruit St, Boston, MA 02114 USA. NR 8 TC 16 Z9 16 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 JUN PY 1999 VL 172 IS 6 BP 1613 EP 1614 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 198ML UT WOS:000080427900029 PM 10350300 ER PT J AU Milberger, S Faraone, SV Biederman, J Chu, MP Feighner, JA AF Milberger, S Faraone, SV Biederman, J Chu, MP Feighner, JA TI Substance use disorders in high-risk adolescent offspring SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID ATTENTION-DEFICIT HYPERACTIVITY; PSYCHIATRIC-DISORDERS; DRUG-USE; ABUSE; ALCOHOLISM; RELATIVES; PROBANDS; FAMILY; PSYCHOPATHOLOGY; PATTERNS AB Objective: To examine the risk for substance use disorders (SUD) in offspring of SUD parents who were not selected due to referral to SUD treatment centers. Method: The original sample was ascertained through two groups of index children: 140 ADHD probands and 120 non-ADHD comparison probands. These groups had 174 and 129 biological siblings and 279 and 240 parents, respectively. Results: We found that: 1) parental SUD was associated with SUD and all SUD subtypes in the offspring; 2) parental alcohol use disorders were associated with alcohol use disorders in the offspring as well as co-occurring alcohol and drug use disorders but not drug use disorders alone in the offspring; and 3) drug use disorders in the parents were associated with drug use disorders but not alcohol use disorders in the offspring. Conclusions: I;These findings suggest that alcoholism and drug abuse may breed true from parents to their offspring, but further work! with larger samples is needed to confirm this idea. Our findings also suggest a possible common diathesis that is expressed as comorbid alcohol and drug use in the offspring of alcoholic parents. If confirmed, these findings may be useful for the development of preventive and early intervention strategies for adolescents at high risk for SUD based on parental history of SUD. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, ACC-725,15 Parkman St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIDA NIH HHS [1 K01 DA00294-01]; NIMH NIH HHS [R01 MH41314-07] NR 38 TC 16 Z9 16 U1 2 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD SUM PY 1999 VL 8 IS 3 BP 211 EP 219 DI 10.1080/105504999305820 PG 9 WC Substance Abuse SC Substance Abuse GA 230JW UT WOS:000082248900005 PM 10506902 ER PT J AU Tanner, ACR Taubman, MA AF Tanner, ACR Taubman, MA TI Microbiota of initial periodontitis in adults SO ANAEROBE LA English DT Article DE periodontitis; adult ID ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; GINGIVITIS; DISEASE; ANTIBODY; HEALTHY; RISK; POPULATION; PATTERNS; BACTERIA; SEROLOGY AB This paper reviews our recent studies of the microbiota and host response of initial periodontitis. Understanding the initial stages of periodontitis will allow appropriate early treatment and prevention strategies. Out studies aimed to determine the major bacterial species that differentiated initial periodontitis from health, and evaluate whether subjects with initial periodontitis differed in serum IgG reactivity to putative initial periodontitis pathogens compared with healthy subjects. Initial periodontitis was characterized clinically using longitudinal periodontial attachment level measurements. Progressing periodontal loss was detected at interproximal (initial periodontitis), and buccal (progressing recession) locations from the study population of minimally periodontally diseased subjects. Initial periodontitis was characterized microbiologically by elevated proportions of Bacteroides forsythus, Selenomonas noxia and Campylobacter rectus when compared with non-periodontitis sites. The immunological checkerboard assay did not detect differences in serum IgG reactivity among healthy, gingivitis or initial periodontitis subjects, or changes in reactivity coincident with detection of initial peridontitis. Clinical, microbiological and immunological characterization of initial periodontitis was consistent with infection-associated Gram-negative anaerobic periodontal species. Progressing recession sites were colonized by Actinomyces and Streptococcus species, as were healthy sites. Progressing recession sites demonstrated periodontal loss that appeared unrelated to infection and appeared to be consistent with a traumatic tooth brushing etiology. Different types of lesions will require different approaches to therapy and prevention. (C) 1999 Academic Press. C1 Forsyth Inst, Dept Bioadhes, Boston, MA 02115 USA. Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. RP Tanner, ACR (reprint author), Forsyth Inst, Dept Bioadhes, 140 Fenway, Boston, MA 02115 USA. NR 36 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1075-9964 J9 ANAEROBE JI Anaerobe PD JUN-AUG PY 1999 VL 5 IS 3-4 BP 229 EP 235 DI 10.1006/anae.1999.0289 PG 7 WC Microbiology SC Microbiology GA 289LX UT WOS:000085624200032 ER PT J AU Vollmar, B Olinger, A Hildebrandt, U Menger, MD AF Vollmar, B Olinger, A Hildebrandt, U Menger, MD TI Cardiopulmonary dysfunction during minimally invasive thoraco-lumboendoscopic spine surgery SO ANESTHESIA AND ANALGESIA LA English DT Article ID LAPAROSCOPIC CHOLECYSTECTOMY; GENERAL-ANESTHESIA; CARBON-DIOXIDE; PORCINE MODEL; INSUFFLATION; OXYGEN; PIGS AB The endoscopic retroperitoneal approach to thoracolumbar anterior spine fusion is associated with CO, insufflation into the thoracic space. We studied the cardiopulmonary effects of this CO2 thoraco-retroperitoneal insufflation compared with the conventional open surgical procedure using thoraco-phreno-lumbotomy in 12 pigs under balanced anesthesia, paralysis, and mechanical ventilation. During open surgery of the thoracolumbar spine, animals exhibited unchanged systemic and pulmonary hemodynamics, as well as ventilation and oxygenation variables. Animals retroperitoneally insufflated with CO, (12 mm Hg) exhibited a significant increase of Paco(2) and a moderate decrease of PaO2, SaO(2), and pH, with insignificant changes of central venous filling pressures and systemic hemodynamics. Endoscopic phrenotomy with thoracic CO2 insufflation instantaneously and drastically affected hemodynamic status and pulmonary gas exchange with marked hypoxia, hypercapnia, systemic hypotension, tachycardia, and pulmonary hypertension within minutes. An increase of minute ventilation, inspiratory oxygen fraction, and positive end-expiratory pressure promptly reversed these cardiopulmonary effects. CO2 evacuation allowed the animals to completely recover and regain almost baseline cardiopulmonary status, except for a reduced arterial blood pressure. Appropriate monitoring and immediate CO2 desufflation may be beneficial in cases of therapy-resistent hemodynamic, oxygenation, and ventilation difficulties. Implications: For endoscopic thoraco-lumbar spine fusion, CO2 thoraco-retroperitoneum-induced cardiopulmonary dysfunction must be of: concern, especially in patients with cardiopulmonary compromise. Appropriate monitoring and immediate CO2 desufflation may be beneficial in cases of therapy-resistant hemodynamic, oxygenation, and ventilation difficulties. C1 Univ Saarland, Inst Clin & Expt Surg, D-6650 Homburg, Germany. Univ Saarland, Dept Trauma Surg, D-6650 Homburg, Germany. Univ Saarland, Dept Gen Surg, D-6650 Homburg, Germany. RP Vollmar, B (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. NR 25 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JUN PY 1999 VL 88 IS 6 BP 1244 EP 1251 DI 10.1097/00000539-199906000-00011 PG 8 WC Anesthesiology SC Anesthesiology GA 199VV UT WOS:000080505500011 PM 10357326 ER PT J AU Rappaport, JM Bhatt, SM Kimura, RS Lauretano, AM Levine, RA AF Rappaport, JM Bhatt, SM Kimura, RS Lauretano, AM Levine, RA TI Electron microscopic temporal bone histopathology in experimental pneumococcal meningitis SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT 19th Midwinter Meeting of the Association-for-Research-in-Otolaryngology CY FEB 04-08, 1996 CL ST PETERSBURG BEACH, FLORIDA SP Assoc Res Otolaryngol DE electron microscopy; labyrinthitis; pneumococcal meningitis; rabbit; sensorineural hearing loss; temporal bone histopathology ID PEDIATRIC BACTERIAL-MENINGITIS; BRAIN-STEM RESPONSES; INFLUENZAE TYPE-B; HAIR CELL LOSS; HEARING-LOSS; GUINEA-PIG; MENINGOGENIC LABYRINTHITIS; STREPTOCOCCUS-PNEUMONIAE; OTOACOUSTIC EMISSIONS; INNER-EAR AB Bacterial meningitis is one of the most common causes of acquired profound sensorineural deafness in children. Measurement of hearing and examination of the cochlea is limited in patients suffering from acute meningitis. A rabbit model of pneumococcal meningitis was developed to identify the temporal bone histopathologic changes that occur in meningogenic labyrinthitis caused by Streptococcus pneumoniae. Light microscopy was previously performed on temporal bones from acutely meningitic rabbits with profound hearing loss as determined electrophysiologically. Extensive inflammation of the cochlea with endolymphatic hydrops was observed. The organ of Corti, however, showed preserved architecture in the majority of these animals. In order to further investigate these findings, a protocol was used to create meningitic rabbits with hearing loss ranging from early high-frequency loss to profound deafness. The temporal bones from 7 rabbits were examined by transmission electron microscopy. In cases of mild hearing loss, partial degeneration of the inner row of outer hair cells, as well as edema of efferent cochlear nerve endings and marginal cells of the stria vascularis, was seen. With increasing degrees of hearing loss, the remainder of the organ of Corti and intermediate cells of the stria showed ultrastructural abnormalities. Spiral ganglion cells and basal cells of the stria vascularis remained intact in all subjects. This study provides unique information regarding the histology and pathophysiology of meningogenic dearness. The clinical implications of these findings are discussed, with an emphasis on potentially reversible changes and therapeutic intervention. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Beth Israel Hosp, Dept Otolaryngol, Boston, MA 02215 USA. RP Rappaport, JM (reprint author), Sir Mortimer B Davis Jewish Hosp, 3755 Cote St Catherine Rd, Montreal, PQ H3T 1E2, Canada. NR 43 TC 11 Z9 12 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JUN PY 1999 VL 108 IS 6 BP 537 EP 547 PG 11 WC Otorhinolaryngology SC Otorhinolaryngology GA 205DZ UT WOS:000080807200003 PM 10378520 ER PT J AU Goodman, CM Cohen, V Armenta, A Thornby, J Netscher, DT AF Goodman, CM Cohen, V Armenta, A Thornby, J Netscher, DT TI Evaluation of results and treatment variables for pressure ulcers in veteran spinal cord-injured patients SO ANNALS OF PLASTIC SURGERY LA English DT Article ID DECUBITUS ULCERS; SORES; MANAGEMENT; RISK AB This retrospective study of 48 spinal cord-injured patients with pressure ulcers seen at a tertiary referral Veterans Hospital spinal cord injury unit between 1992 and 1997 correlates a number of variables (co-morbid conditions, nutritional status, smoking history, type of repair performed, type of bed used postoperatively, ulcer location and severity, duration of postoperative antibiotic therapy, time elapsed before sitting rehabilitation began, and length of hospital stay) with ulcer repair outcome measures, including postoperative systemic and wound-healing complications, recurrence rates, and the development of new ulcers at different sites. Surgical complication rates were high, occurring in 19 patients (39.6%), and ulcer recurrence or new ulcer development occurred in 38 patients (79.2%). Correlations were found between ulcer location and postoperative wound separation and the length of hospitalization. The hospital course was shorter if the ulcer was new rather than recurrent. Other than the finding that chronic smokers had longer courses of antibiotic therapy, smoking did not correlate statistically with other outcome variables, including wound-healing complications. No significant correlations were found between any postoperative systemic or wound complications, ulcer recurrence, or new ulcer development and patient age, level of spinal cord injury, number of ulcers and grade, laboratory values, mental status, cardiac or pulmonary disease, diabetes, and presence or absence of osteomyelitis. C1 Baylor Coll Med, Div Plast Surg, Houston, TX 77030 USA. Dept Vet Affairs Med Ctr, Houston, TX USA. RP Netscher, DT (reprint author), 6560 Fannin,Suite 800, Houston, TX 77030 USA. NR 23 TC 28 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD JUN PY 1999 VL 42 IS 6 BP 665 EP 672 DI 10.1097/00000637-199906000-00015 PG 8 WC Surgery SC Surgery GA 203VE UT WOS:000080727900017 PM 10382806 ER PT J AU Shebani, KO Souba, WW Finkelstein, DM Stark, PC Elgadi, KM Tanabe, KK Ott, MJ AF Shebani, KO Souba, WW Finkelstein, DM Stark, PC Elgadi, KM Tanabe, KK Ott, MJ TI Prognosis and survival in patients with gastrointestinal tract carcinoid tumors SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 110th Annual Meeting of the Southern Surgical Association CY DEC 06-09, 1998 CL W PALM BEACH, FLORIDA SP SO Surg Assoc ID NEUROENDOCRINE TUMORS; EXPERIENCE; MANAGEMENT C1 Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. RP Ott, MJ (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, 626 Cox Bldg,100 Blossom St, Boston, MA 02114 USA. NR 28 TC 153 Z9 164 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JUN PY 1999 VL 229 IS 6 BP 815 EP 821 DI 10.1097/00000658-199906000-00008 PG 7 WC Surgery SC Surgery GA 201FZ UT WOS:000080585500015 PM 10363895 ER PT J AU Werner, J Z'graggen, K Fernandez-del Castillo, C Lewandrowski, KB Compton, CC Warshaw, AL AF Werner, J Z'graggen, K Fernandez-del Castillo, C Lewandrowski, KB Compton, CC Warshaw, AL TI Specific therapy for local and systemic complications of acute pancreatitis with monoclonal antibodies against ICAM-1 SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 110th Annual Meeting of the Southern Surgical Association CY DEC 06-09, 1998 CL W PALM BEACH, FLORIDA SP SO Surg Assoc ID TRYPSINOGEN-ACTIVATION PEPTIDES; NECROTIZING PANCREATITIS; RAT; ADHESION; INJURY; INFLAMMATION; PROGRESSION; ENDOTHELIUM; MECHANISMS; CELLS AB Objective To analyze the lime points and levels of the expression of adhesion molecules in the pancreas and lung in pancreatitis of different severities, and to assess whether treatment with a monoclonal antibody against intercellular adhesion molecule-1 (ICAM-1) can reduce local and systemic complications, Background The outcome of severe acute pancreatitis relates to its pulmonary and septic complications. Leukocyte adhesion and infiltration, both mediated by ICAM-1, are central events in the pathogenesis of necrotizing pancreatitis. Methods Expression of ICAM-1 at different time points was assessed by immunohistochemistry and Western blot analysis in pancreas and lungs from rats with mild edematous or severe necrotizing pancreatitis. ICAM-1 expression was correlated with leukocyte infiltration and histologic changes. The possible therapeutic effect of monoclonal antibodies against ICAM-1 was assessed by measuring pancreatic and lung injury, Results In edematous pancreatitis, increased ICAM-1 expression in pancreas was evident by 8 hours but did not occur in lung. In contrast, ICAM-1 was upregulated at 3 hours in the pancreas and at 12 hours in lung in necrotizing pancreatitis. Increased expression of ICAM-1 preceded leukocyte infiltration. Treatment of severe necrotizing pancreatitis with monoclonal antibodies against ICAM-1 decreased both local pancreatic injury and systemic lung injury compared with untreated controls, Conclusions Upregulation of ICAM-1 and subsequent leukocyte infiltration appear to be significant mediators of pancreatic and pulmonary injury in pancreatitis, and both the onset and extent correlate with severity, The time course should permit effective prevention of tissue damage by treatment with ICAM-1 antibodies. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,WHT 506, Boston, MA 02114 USA. NR 37 TC 89 Z9 101 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JUN PY 1999 VL 229 IS 6 BP 834 EP 840 DI 10.1097/00000658-199906000-00010 PG 7 WC Surgery SC Surgery GA 201FZ UT WOS:000080585500019 PM 10363897 ER PT J AU Putlitz, JZ Wands, JR AF Putlitz, JZ Wands, JR TI Specific inhibition of hepatitis B virus replication by sense RNA SO ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT LA English DT Article ID POSTTRANSCRIPTIONAL REGULATORY ELEMENT; GENE-EXPRESSION; ANTISENSE RNA; VIRAL REPLICATION; CORE PROTEIN; MUTANTS; COSUPPRESSION; DEHYDROGENASE; TRANSCRIPTS; SEQUENCES AB We describe effects of sense RNA molecules on hepatitis B virus (HBV) replication and antigen synthesis in transiently transfected cells. When certain subgenomic fragments of HBV were expressed as sense RNA together with a replication-competent genome of HBV, they inhibited HBV replication by up to 75 % and HBsAg secretion by up to 60%. The corresponding antisense sequences had a 50% inhibitory effect in one case and no effect in another case, The sense RNA species did not inhibit duck hepatitis B virus (DHBV) replication, suggesting specific inhibitory effects. HBV transcript levels were unaltered in the presence of sense RNA species, consistent with an inhibitory effect mediated at the posttranscriptional level. The inhibition of HBV replication by overexpression of sense RNA derived from the viral genome represents an example of sense cosuppression of an animal virus. C1 Massachusetts Gen Hosp, Ctr Canc, Mol Hepatol Lab, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Wands, JR (reprint author), Brown Univ, Rhode Isl Hosp, Sch Med, Liver Res Ctr, 55 Claverick St, Providence, RI 02903 USA. NR 39 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2906 J9 ANTISENSE NUCLEIC A JI Antisense Nucleic Acid Drug Dev. PD JUN PY 1999 VL 9 IS 3 BP 241 EP 252 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 216KB UT WOS:000081440300001 ER PT J AU Dierickx, CC Goldenhersh, M Dwyer, P Stratigos, A Mihm, M Anderson, RR AF Dierickx, CC Goldenhersh, M Dwyer, P Stratigos, A Mihm, M Anderson, RR TI Photodynamic therapy for nevus sebaceus with topical delta-aminolevulinic acid SO ARCHIVES OF DERMATOLOGY LA English DT Article ID BASAL-CELL CARCINOMA; 5-AMINOLEVULINIC ACID; PROTOPORPHYRIN-IX; ENDOGENOUS PROTOPORPHYRIN; PORPHYRINS; DESFERRIOXAMINE; FLUORESCENCE; TUMOR; SKIN C1 Wellman Labs Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Anderson, RR (reprint author), Wellman Labs Photomed, Massachusetts Gen Hosp, Bartlett Extens 6,50 Blossom St, Boston, MA 02114 USA. NR 20 TC 34 Z9 34 U1 0 U2 2 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 JUN PY 1999 VL 135 IS 6 BP 637 EP 640 DI 10.1001/archderm.135.6.637 PG 4 WC Dermatology SC Dermatology GA 205EH UT WOS:000080808000001 PM 10376688 ER PT J AU Crits-Christoph, P Siqueland, L Blaine, J Frank, A Luborsky, L Onken, LS Muenz, LR Thase, ME Weiss, RD Gastfriend, DR Woody, GE Barber, JP Butler, SF Daley, D Salloum, I Bishop, S Najavits, LM Lis, J Mercer, D Griffin, ML Moras, K Beck, AT AF Crits-Christoph, P Siqueland, L Blaine, J Frank, A Luborsky, L Onken, LS Muenz, LR Thase, ME Weiss, RD Gastfriend, DR Woody, GE Barber, JP Butler, SF Daley, D Salloum, I Bishop, S Najavits, LM Lis, J Mercer, D Griffin, ML Moras, K Beck, AT TI Psychosocial treatments for cocaine dependence - National Institute on Drug Abuse Collaborative Cocaine Treatment Study SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 151st Annual Meeting of the American-Psychiatric-Association CY MAY 30-JUN 05, 1998 CL TORONTO, CANADA SP Amer Psychiat Assoc ID INTERPERSONAL PSYCHOTHERAPY; OPIATE ADDICTS; RATING-SCALE; THERAPIES; SEVERITY; PHARMACOTHERAPY; ABSTINENCE AB Background: This was a multicenter investigation examining the efficacy of 4 psychosocial treatments for cocaine-dependent patients. Methods: Four hundred eighty-seven patients were randomly assigned to 1 of 4 manual-guided treatments: individual drug counseling plus group drug counseling (GDC), cognitive therapy plus GDC, supportive-expressive therapy plus GDC, or GDC alone. Treatment was intensive, including 36 possible individual sessions and 24 group sessions for 6 months. Patients were assessed monthly during active treatment and at 9 and 12 months after baseline. Primary outcome measures were the Addiction Severity Index-Drug Use Composite score and the number of days of cocaine use in the past month. Results: Compared with the 2 psychotherapies and with GDC alone, individual drug counseling plus GDC showed the greatest improvement on the Addiction Severity Index-Drug Use Composite score. Individual group counseling plus GDC was also superior to the 2 psychotherapies on the number of days of cocaine use in the past month. Hypotheses regarding the superiority of psychotherapy to GDC for patients with greater psychiatric severity and the superiority of cognitive therapy plus GDC compared with supportive-expressive therapy plus GDC for patients with antisocial personality traits or external coping style were not confirmed. Conclusion: Compared with professional psychotherapy, a manual-guided combination of intensive individual drug counseling and GDC has promise for the treatment of cocaine dependence. C1 Univ Penn, Dept Psychiat, Sch Med, Philadelphia, PA 19104 USA. NIDA, Treatment Res Branch, Div Clin & Res Serv, Rockville, MD USA. Harvard Univ, Sch Med, Brookside Hosp, Nashua, NH USA. McLean Hosp, Belmont, MA 02178 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Grp Drug Counseling Unit, Pittsburgh, PA 15213 USA. Univ Penn, Cognit Therapy Training Unit, Sch Med, Philadelphia, PA 19104 USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Univ Penn, Vet Affairs, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Treatment Res Unit, Philadelphia, PA 19104 USA. Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. Brown Univ, Butler Hosp, Providence, RI 02912 USA. Univ Penn, Express Therapy Training Unit, Sch Med, Philadelphia, PA 19104 USA. RP Crits-Christoph, P (reprint author), Univ Penn, Dept Psychiat, Sch Med, 3600 Market St,Room 700, Philadelphia, PA 19104 USA. OI Butler, Stephen/0000-0002-6132-5883 FU NIDA NIH HHS [U01-DA07090, K02-DA00326, R01 DA012249, K05-DA00168, U18 DA007090] NR 43 TC 296 Z9 298 U1 2 U2 18 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUN PY 1999 VL 56 IS 6 BP 493 EP 502 DI 10.1001/archpsyc.56.6.493 PG 10 WC Psychiatry SC Psychiatry GA 201NL UT WOS:000080601600001 PM 10359461 ER PT J AU Goldstein, JM Goodman, JM Seidman, LJ Kennedy, DN Makris, N Lee, H Tourville, J Caviness, VS Faraone, SV Tsuang, MT AF Goldstein, JM Goodman, JM Seidman, LJ Kennedy, DN Makris, N Lee, H Tourville, J Caviness, VS Faraone, SV Tsuang, MT TI Cortical abnormalities in schizophrenia identified by structural magnetic resonance imaging SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID FIRST-EPISODE SCHIZOPHRENIA; GRAY-MATTER VOLUME; SUPERIOR TEMPORAL GYRUS; ANTERIOR CINGULATE CORTEX; PREFRONTAL CORTEX; SEX-DIFFERENCES; BRAIN MORPHOLOGY; FUNCTIONAL-ANATOMY; PLANUM TEMPORALE; CEREBRAL-CORTEX AB Background: Relatively few magnetic resonance imaging studies of schizophrenia have investigated the entire cerebral cortex. Most focus on only a few areas within a lobe or an entire lobe. To assess expected regional alterations in cortical volumes, we used a new method to segment the entire neocortex into 48 topographically defined brain regions. We hypothesized, based on previous empirical and theoretical work, that dorsolateral prefrontal and paralimbic cortices would be significantly volumetrically reduced in patients with schizophrenia compared with normal controls. Methods: Twenty-nine patients with DSM-III-R schizophrenia were systematically sampled from 3 public outpatient service networks in the Boston, Mass, area. Healthy subjects, recruited from catchment areas from which the patients were drawn, were screened for psychopathologic disorders and proportionately matched to patients by age, sex, ethnicity, parental socioeconomic status, reading ability, and handedness. Analyses of covariance of the volumes of brain regions, adjusted for age- and sex-corrected head size, were used to compare patients and controls. Results: The greatest volumetric reductions and largest effect sizes were in the middle frontal gyrus and paralimbic brain regions, such as the frontomedial and frontoorbital cortices, anterior cingulate and paracingulate gyri, and the insula. In addition, the supramarginal gyrus, which is densely connected to prefrontal and cingulate cortices, was also significantly reduced in patients. Patients also had subtle volumetric increases in other cortical areas with strong reciprocal connections to the paralimbic areas that were volumetrically reduced. Conclusion: Findings using our methods have implications for understanding brain abnormalities in schizophrenia and suggest the importance of the paralimbic areas and their connections with prefrontal brain regions. C1 Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Ctr Morphometr Anal, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol Serv,Ctr Morphometr Anal, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brockton W Roxbury Vet Affairs Med Ctr, Brockton, MA USA. RP Goldstein, JM (reprint author), Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Inst Psychiat Epidemiol & Genet, 74 Fenwood Rd, Boston, MA 02115 USA. RI Kennedy, David/H-3627-2012; OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [K21 MH00976, MH 43518, R01 MH56956] NR 87 TC 267 Z9 271 U1 1 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUN PY 1999 VL 56 IS 6 BP 537 EP 547 DI 10.1001/archpsyc.56.6.537 PG 11 WC Psychiatry SC Psychiatry GA 201NL UT WOS:000080601600008 PM 10359468 ER PT J AU Parboosingh, JS Meininger, V McKenna-Yasek, D Brown, RH Rouleau, GA AF Parboosingh, JS Meininger, V McKenna-Yasek, D Brown, RH Rouleau, GA TI Deletions causing spinal muscular atrophy do not predispose to amyotrophic lateral sclerosis SO ARCHIVES OF NEUROLOGY LA English DT Article ID MOTOR-NEURON DISEASE; GENETIC HOMOGENEITY; CHILDHOOD-ONSET; SMN; DIAGNOSIS; PROTEIN; ALS AB Background: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, invariably lethal disease resulting from the premature death of motor neurons of the motor cortex, brainstem, and spinal cord. In approximately 15% of familial ALS cases, the copper/zinc superoxide dismutase gene is mutated; a juvenile form of familial ALS has been linked to chromosome 2. No cause has been identified in the remaining familial ALS cases or in sporadic cases and the selective neurodegenerative mechanism remains unknown. Deletions in 2 genes on chromosome 5q, SMN (survival motor neuron gene) and NAIP (neuronal apoptosis inhibitory protein gene), have been identified in spinal muscular atrophy, a disease also characterized by the loss of motor neurons. These genes are implicated in the regulation of apoptosis,a mechanism that may explain the cell loss found in the brains and spinal cords of patients with ALS. Objective: To determine whether the mutations causing neurodegeneration in spinal muscular atrophy are present in patients with ALS in whom the copper/zinc superoxide dismutase gene is not mutated. Patients and Methods: Patients in whom ALS was diagnosed were screened for mutations in the SMN and NAIP genes by single strand conformation analysis. Results: We found 1 patient with an exon 7 deletion iu the SMN gene; review of clinical status confirmed the molecular diagnosis of spinal muscular atrophy. No mutations were found in the remaining patients. Conclusion: The SMN and NAIP gene mutations are specific for spinal muscular atrophy and do not predispose individuals to ALS. C1 Montreal Gen Hosp, Res Inst, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada. McGill Univ, Ctr Res Neurosci, Montreal, PQ H3A 2T5, Canada. Hotel Dieu, Ctr SLA, Paris, France. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Day Neuromuscular Lab, Boston, MA USA. RP Rouleau, GA (reprint author), Montreal Gen Hosp, Res Inst, Ctr Res Neurosci, 1650 Cedar Ave, Montreal, PQ H3G 1A4, Canada. NR 20 TC 27 Z9 28 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUN PY 1999 VL 56 IS 6 BP 710 EP 712 DI 10.1001/archneur.56.6.710 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 203AR UT WOS:000080685300011 PM 10369311 ER PT J AU Haroutunian, V Purohit, DP Perl, DP Marin, D Khan, K Lantz, M Davis, KL Mohs, RC AF Haroutunian, V Purohit, DP Perl, DP Marin, D Khan, K Lantz, M Davis, KL Mohs, RC TI Neurofibrillary tangles in nondemented elderly subjects and mild Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID REGIONAL DISTRIBUTION; DEMENTIA SEVERITY; SENILE PLAQUES; DEGENERATION; MARKERS; CORTEX; ONSET; SCALE; AGE AB Background: The relationship between neuropathological lesions and mild, "preclinical," cognitive impairments of Alzheimer disease is poorly understood. Identification of the lesions that are most closely associated with the earliest symptoms of Alzheimer disease is crucial to the understanding of the disease process and the development of treatment strategies to affect its progression. Design and Main Outcome Measures: We examined the extent of neurofibrillary tangles (NFTs) in 4 neocortical regions, the hippocampus, the entorhinal cortex, and the amygdala in 65 elderly subjects with no dementia, questionable dementia, mild dementia, or moderate dementia as assessed using the Clinical Dementia Rating Scale (CDR). Setting and Patients: Postmortem study of nursing home residents. Results: Neurofibrillary tangles were present in the entorhinal cortex and the hippocampus of all subjects, including those without cognitive deficits. Neocortical NFTs were mostly absent in the nondemented (CDR score, 0.0) subjects. The density of NFTs in the questionably demented (CDR score, 0.5) subjects was not significantly increased (P>.20) relative to the nondemented group in any of the brain regions studied. Significant increases (P<.04) in NFT density become apparent first in the amygdala and the temporal cortex in subjects rated to be mildly impaired (CDR score, 1.0). By the time that cognitive impairments were judged to be moderately severe (CDR score, 2.0), all regions of the brain examined, except for the occipital cortex, were significantly (P<.05) involved. Conclusions: Some NFTs are present in the entorhinal cortex and hippocampus of most elderly individuals irrespective of their cognitive status, but the density of NFTs increases as a function of dementia severity. C1 Bronx Vet Affairs Med Ctr, Psychiat Serv, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Mt Sinai Sch Med, Dept Pathol, New York, NY USA. Jewish Home & Hosp, New York, NY USA. RP Haroutunian, V (reprint author), Bronx Vet Affairs Med Ctr, Psychiat Serv, Room 3-F02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. FU NIA NIH HHS [P01-AG02219] NR 36 TC 141 Z9 143 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUN PY 1999 VL 56 IS 6 BP 713 EP 718 DI 10.1001/archneur.56.6.713 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 203AR UT WOS:000080685300012 PM 10369312 ER PT J AU Regan, S Judge, HE Gragoudas, ES Egan, KM AF Regan, S Judge, HE Gragoudas, ES Egan, KM TI Iris color as a prognostic factor in ocular melanoma SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID MALIGNANT-MELANOMA; UVEAL MELANOMA; HOST FACTORS; RISK FACTOR; EXPOSURE AB Background: Ocular melanoma may be more prevalent among patients with light irises than those with dark irises. Objective: To examine a large clinical series of patients with intraocular melanoma to determine if light irises are associated with increased risk of death from these tumors. Methods: A total of 1162 patients treated with proton irradiation between 1984 and 1996 were observed through 1997. Results: Iris color in the patients was blue or gray in 48%, green or hazel. in 30%, and brown in 23%. Tumors in patients with blue or gray irises were less headily pigmented (P < .001) and closer to the optic disc and macula (P < .001). Five- and 10-year metastasis-related death rates were 0.14 and 0.21, respectively, for those with blue or gray irises and 0.10 and 0.15, respectively, for those with darker irises (P = .02). In a Cox proportional hazards regression controlling for tumor characteristics, patients with blue or gray irises died of metastatic disease at a rate 1.90 times (95% confidence interval, 1.26-2.85) that of patients with brown irises. The rate of metastatic death was not significantly elevated for those with green or hazel irises (relative risk, 1.43; 95% confidence interval, 0.91-2.23). Conclusion: Patients with blue or gray irises appear to be at increased risk of metastatic death from choroidal melanoma, independent of other risk factors. C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. RP Gragoudas, ES (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 241 Charles St, Boston, MA 02114 USA. NR 12 TC 22 Z9 22 U1 0 U2 3 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 JUN PY 1999 VL 117 IS 6 BP 811 EP 814 PG 4 WC Ophthalmology SC Ophthalmology GA 204VH UT WOS:000080785000017 PM 10369595 ER PT J AU Khadem, JJ Buzney, SM Alich, KS AF Khadem, JJ Buzney, SM Alich, KS TI Practice patterns in diabetic retinopathy part 1: Analysis of retinopathy follow-up SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT 100th Annual Meeting of the American-Academy-of-Ophthalmology CY OCT 27-NOV 01, 1996 CL CHICAGO, IL SP Amer Acad Ophthalmol ID 4-YEAR INCIDENCE; PROGRESSION; DIAGNOSIS; AGE AB Objective: To evaluate ophthalmologists' management of diabetic patients. Methods: A multiple-choice questionnaire was mailed to all ophthalmologists in New York (1985), Florida (1990), and Massachusetts (1993 and 1996). Questions included practice patterns, methods used in examination, use of photography and fluorescein angiography, indications for laser treatment, and intervals for follow-up of selected conditions. Responses were tabulated and compared between surveys and with the American Academy of Ophthalmology Preferred Practice Pattern. Results: In this first report, we detail follow-up patterns of various grades of retinopathy. Physicians increasingly used duration of diabetes as a criterion in determining the length of follow-up for adults, despite persistent ambiguities for children. There were notable changes over time in nearly all aspects of follow-up for both general ophthalmologists and retina specialists. Retina specialists were less likely to treat proliferative disease, more likely to follow up patients with preproliferative disease sooner, and used longer followup intervals for short-duration diabetic patients, whereas a small percentage of general ophthalmologists continued to recommend treatment for background disease. Conclusion: There were noticeable trends toward Diabetes 2000 recommendations over time, although there remained many areas where further education appeared warranted. C1 Harvard Univ, Massachusetts Society Eye Physicians & Surg, Retina Specialists Boston, Massachusetts Eye & Ear Infirm,Med Sch, Boston, MA 02114 USA. Massachusetts Dept Publ Hlth, Boston, MA USA. RP Khadem, JJ (reprint author), Harvard Univ, Massachusetts Society Eye Physicians & Surg, Retina Specialists Boston, Massachusetts Eye & Ear Infirm,Med Sch, 100 Charles River Plaza,4th Floor, Boston, MA 02114 USA. EM jkhadem@vision.eri.harvard.edu NR 12 TC 18 Z9 19 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-9950 EI 1538-3601 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUN PY 1999 VL 117 IS 6 BP 815 EP 820 PG 6 WC Ophthalmology SC Ophthalmology GA 204VH UT WOS:000080785000018 PM 10369596 ER PT J AU Broker, BJ Chakrabarti, R Blynman, T Roesler, J Wang, MB Srivatsan, ES AF Broker, BJ Chakrabarti, R Blynman, T Roesler, J Wang, MB Srivatsan, ES TI Comparison of growth factor expression in fetal and adult fibroblasts - A preliminary report SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID NUCLEOTIDE-SEQUENCE; CELL-GROWTH; FACTOR-BETA; LOCALIZATION; CLONING; CDNA; MATRIX; REPAIR; CHAIN; SKIN AB Background: Fetal wounds can heal without any histological evidence of scarring. Fetal wounds lack the inflammatory infiltrate characteristic of adult wounds, and the fetal environment is not necessary for scarless healing to occur. Recent evidence suggests that fibroblasts are the main effector of scarless healing in fetal tissue. What has not been shown is what profile of growth factors the fibroblast uses to influence wound repair. Objective: To determine the expression of growth factors (transforming growth factors beta 1, beta 2, and beta 3; acidic and basic fibroblast growth factors; keratinocyte growth factor; and platelet-derived growth factor AA, BE, and AB) of fetal and adult fibroblasts in vitro. Design: Adult and fetal fibroblasts were grown in culture, and messenger RNA was extracted by standard techniques. Northern hybridization was used to identify messenger RNA transcripts for the aforementioned growth factors. Densitometry was used to compare growth factor messenger RNA expression with that of a ubiquitously expressed control, glyceraldehyde phosphate dehydrogenase. Results: The data suggest that fetal and adult fibroblasts express acidic and basic fibroblast growth factor and transforming growth factor pi. Adult fibroblasts show twice the relative expression of these growth factors compared with fetal fibroblasts. Conclusions: The adult fibroblasts demonstrate a relative excess production of cytokines compared with fetal fibroblasts. This is thought to contribute to suboptimal wound healing in adult wounds compared with the scarless healing of fetal wounds. C1 Univ Calif Los Angeles, Sch Med, Div Head & Neck Surg, Sect Facial Plast Surg, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Surg, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Broker, BJ (reprint author), Inst Appl Laser Surg, 2 Bala Plaza,Suite PL 13, Bala Cynwyd, PA 19004 USA. NR 23 TC 13 Z9 15 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JUN PY 1999 VL 125 IS 6 BP 676 EP 680 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 205XJ UT WOS:000080845900011 PM 10367926 ER PT J AU Chedid, A Ryan, LM Dayal, Y Wolf, BC Falkson, G AF Chedid, A Ryan, LM Dayal, Y Wolf, BC Falkson, G TI Morphology and other prognostic factors of hepatocellular carcinoma SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID NORTH-AMERICAN PATIENTS; RISK-FACTORS; FEATURES; SURVIVAL; LIVER; RESECTION AB Objective.-Hepatocellular carcinoma is a malignancy found worldwide that has typically poor prognosis despite treatment. Although several studies have dealt with prognostic factors, just a few detailed analyses of large series correlating the pathology of hepatocellular carcinoma with prognosis are available. The present study was undertaken to address this limitation. Patients and Methods.-Our prior clinical study described 432 patients, but sufficient tissue was available for evaluation in only 299 patients. Of these, 224 samples contained primary hepatocellular carcinoma, while the remainder contained only metastatic tumor. Characteristics evaluated included degree of tumor differentiation, associated cirrhosis or hepatitis, presence of cytoplasmic inclusion bodies, and blood vessel invasion by the neoplasm. Results.-Of the 224 patients, 71% were male, 65% white, and 73% over the age of 45 years. Ninety-one percent were from North America. A total of 42 patients were found to have cirrhosis. Thirty-five percent had cytoplasmic inclusion bodies, and 25% showed evidence of blood vessel invasion. Tumor response rates (tumor shrinkage) were low (8%) regardless of treatment. Presence of cytoplasmic eosinophilic inclusion bodies and blood vessel invasion were not associated with increased survival. Some histopathologies (pelioid, spindle cell, fibrolamellar) were associated with a better prognosis. Patients with a predominant trabecular pattern (43%) did particularly poorly. Although sex was significantly associated with survival using a univariate analysis, this effect disappeared in a multivariate Cox model that adjusted simultaneously for other factors. Conclusion.-This investigation suggests that histologic subtype and clinical features may provide useful prognostic information in hepatocellular carcinoma. Poorer survival was observed in males, older patients with poorly differentiated tumors, or when associated with cirrhosis. Age younger than 45 years was a good prognostic factor, and presence of cirrhosis had an adverse effect on survival. C1 Finch Univ Hlth Sci Chicago Med Sch, Dept Pathol, N Chicago, IL 60064 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. New England Med Ctr, Dept Pathol, Boston, MA 02111 USA. Med Ctr, Dept Pathol, Albany, NY USA. Univ Pretoria, Dept Med Oncol, ZA-0001 Pretoria, South Africa. RP Chedid, A (reprint author), Finch Univ Hlth Sci Chicago Med Sch, Dept Pathol, 3333 Green Bay Rd, N Chicago, IL 60064 USA. FU NCI NIH HHS [CA 07190, CA 14144, CA 23318] NR 29 TC 28 Z9 30 U1 0 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JUN PY 1999 VL 123 IS 6 BP 524 EP 528 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 201YB UT WOS:000080623900018 PM 10383806 ER PT J AU Baek, KH AF Baek, KH TI Application of temperature-sensitive mutations to oncogene studies in Drosophila SO ARCHIVES OF PHARMACAL RESEARCH LA English DT Review DE lethal (2) giant larvae; cadherin; cell adhesion molecule; intragenic complementation ID TUMOR-SUPPRESSOR GENE; II HEAVY-CHAIN; RECESSIVE ONCOGENE; MELANOGASTER; HOMOLOG; L(2)GL; MAPS AB Recessive oncogenes are genetic functions important in the regulation of tissue growth and differentiation. These genetic functions are defined on the basis of the phenotype expressed by homozygotes. Defining the role of these genes in normal developmental and physiological processes is important to the development of accurate models of the normal regulation of growth and differentiation. Drosophila can be a good system to investigate the neoplastic mechanism of oncogenes and provide a greater understanding in the developmental progression of both invertebrates and vertebrates. The lethal (2) giant larvae gene is a recessive oncogene of Drosophila and temperature sensitive mutations of this gene have been isolated. Here, the application of temperature-sensitive mutations in Drosophila oncogene studies is discussed. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. RP Baek, KH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. OI Baek, Kwang-Hyun/0000-0001-7662-7190 NR 26 TC 1 Z9 1 U1 2 U2 2 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 JUN PY 1999 VL 22 IS 3 BP 229 EP 231 DI 10.1007/BF02976354 PG 3 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 210CT UT WOS:000081088100001 PM 10403122 ER PT J AU Shen, WT Lim, RC Siperstein, AE Clark, OH Schecter, WP Hunt, TK Horn, JK Duh, QY AF Shen, WT Lim, RC Siperstein, AE Clark, OH Schecter, WP Hunt, TK Horn, JK Duh, QY TI Laparoscopic vs open adrenalectomy for the treatment of primary hyperaldosteronism SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 106th Scientific Session of the Western-Sugical-Association CY NOV 16-18, 1998 CL INDIANAPOLIS, INDIANA SP Western Surg Assoc ID PRIMARY ALDOSTERONISM; SURGICAL-TREATMENT; DIAGNOSIS AB Hypothesis: That the clinical presentations, biochemical profiles, and surgical outcomes of patients treated with laparoscopic vs open adrenalectomy for primary hyperaldosteronism are different. Design, Settings, patients, and Interventions: The medical records of 80 patients with primary hyperaldosteronism who underwent open adrenalectomy between 1975 and 1986 or laparoscopic adrenalectomy between 1993 and 1998 at the University of California-San Francisco were reviewed by a single unblinded researcher (W.T.S.). Main Outcome Measures: Severity of hypertension and hypokalemia at diagnosis, their improvement after adrenalectomy, and operative complications. Results: Thirty-eight patients underwent open adrenalectomy and 42 patients underwent laparoscopic adrenalectomy. The patients who underwent open adrenalectomy had documented hypertension for a median of 5 years before surgery; all had diastolic blood pressures greater than 100 mm Hg. Laparoscopically treated patients had documented hypertension for a median of 2.5 years preoperatively, and 20 (48%) had diastolic blood pressures greater than 100 mm Hg. The median preoperative serum potassium levels for the open and laparoscopic groups were 2.6 mmol/L and 3.3 mmol/L, respectively; the mean serum aldosterone levels were 1.47 nmol/L and 1.30 nmol/L. Thirty-two (84%) of the 38 patients who underwent open surgery and 41 (98%) of the 42 patients treated laparoscopically had adrenal adenomas. The sensitivity of preoperative computed tomographic scanning for adenomas was 83% for the patients treated with open adrenalectomy and 93% for those treated laparoscopically. There were 4 postoperative complications in the open surgery group and none in the laparoscopic group. Postoperatively, 30 (81%) of 37 patients (excluding 1 patient who died of adrenocortical carcinoma) in the open surgery group and 37 (88%) of 42 patients treated laparoscopically were normotensive. Postoperative values were 3.6 to 5.0 of serum potassium per liter and 3.5 to 4.9 of serum potassium per liter in the open and laparoscopic groups, respectively. Conclusions: Patients who are treated with laparoscopic adrenalectomy for primary hyperaldosteronism are being referred with less severe hypertension and hypokalemia than patients formerly treated with open adrenalectomy. Patients treated laparoscopically had fewer postoperative complications and were equally likely to improve in blood pressure and hypokalemia. Laparoscopic adrenalectomy has become the treatment of choice for patients with primary hyperaldosteronism because of lower morbidity. C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. UCSF, Mt Zion Med Ctr, San Francisco, CA USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. San Francisco Gen Hosp, San Francisco, CA USA. RP Duh, QY (reprint author), Surg Serv 112, 4150 Clement St, San Francisco, CA 94121 USA. NR 14 TC 65 Z9 67 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD JUN PY 1999 VL 134 IS 6 BP 628 EP 631 DI 10.1001/archsurg.134.6.628 PG 4 WC Surgery SC Surgery GA 202YG UT WOS:000080679300012 PM 10367872 ER PT J AU Aiello, RJ Bourassa, PAK Lindsey, S Weng, WF Natoli, E Rollins, BJ Milos, PM AF Aiello, RJ Bourassa, PAK Lindsey, S Weng, WF Natoli, E Rollins, BJ Milos, PM TI Monocyte chemoattractant protein-1 accelerates atherosclerosis in apolipoprotein E-deficient mice SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE bone marrow; CD11b; F4/80; oxidized lipid; chemokines ID LOW-DENSITY-LIPOPROTEIN; BONE-MARROW TRANSPLANTATION; COLONY-STIMULATING FACTOR; FOAM CELLS; SEVERE HYPERCHOLESTEROLEMIA; LESIONS; ATHEROGENESIS; EXPRESSION; OXIDATION; MACROPHAGES AB The pro-inflammatory chemokine, monocyte chemoattractant protein-1 (MCP-1), plays a fundamental role in monocyte recruitment and has been implicated as a contributing factor to atherosclerosis. The predominant cell types within the vessel wall-endothelial cells, smooth muscle cells, and macrophages-all contribute to overexpression of MCP-1 in atherosclerotic tissue. In this report we assess the role of MCP-1 expression by leukocytes on lesion progression in a murine model susceptible to atherosclerosis. Bone marrow cells from mice overexpressing a murine MCP-1 transgene on a background of apoE-deficiency or from control mice were transplanted into irradiated apoE-knockout mice. After repopulation of apoE-knockout mice with bone marrow containing the MCP-1 transgene, macrophages expressing the MCP-1 transgene were found in several tissues, including the aorta, Qualitative assessment of atherosclerosis in these mice revealed increased lipid staining, a 3-fold (P<0.001) increase in the amount of oxidized lipid, and increased immunostaining for macrophage cell surface markers with anti-F4/80 and anti-CD11b antibodies. There were no differences in plasma lipids, plasma lipoprotein profiles, or body weight between the 2 groups. These results provide the first direct evidence that MCP-1 expression by leukocytes, predominately macrophages, increases the progression of atherosclerosis by increasing both macrophage numbers and oxidized lipid accumulation. C1 Pfizer Inc, Div Cent Res, Groton, CT 06340 USA. Pfizer Inc, Dept Metab Dis, Groton, CT 06340 USA. Pfizer Inc, Dept Mol Sci, Groton, CT 06340 USA. Pfizer Inc, Dept Anim Hlth, Groton, CT 06340 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Aiello, RJ (reprint author), Pfizer Inc, Div Cent Res, Eastern Point Rd, Groton, CT 06340 USA. NR 39 TC 292 Z9 304 U1 0 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 1999 VL 19 IS 6 BP 1518 EP 1525 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 206XF UT WOS:000080905100020 PM 10364084 ER PT J AU Schumacher, HR Arayssi, T Crane, M Lee, J Gerard, H Hudson, AP Klippel, J AF Schumacher, HR Arayssi, T Crane, M Lee, J Gerard, H Hudson, AP Klippel, J TI Chlamydia trachomatis nucleic acids can be found in the synovium of some asymptomatic subjects SO ARTHRITIS AND RHEUMATISM LA English DT Article ID POLYMERASE-CHAIN-REACTION; BORRELIA-BURGDORFERI; REITERS-SYNDROME; BACTERIAL-DNA; LYME-DISEASE; ARTHRITIS; FLUID; IDENTIFICATION; AMPLIFICATION; PNEUMONIAE AB Objective. The recent identification of antigens or nucleic acids of infectious agents in the joints of patients with reactive arthritis has raised questions about whether chlamydial or other infectious agent nucleic acids are also present in normal joints, We had the opportunity to study synovium from 30 asymptomatic volunteer subjects by use of polymerase chain reaction (PCR) for attempted identification of Chlamydia and other infectious agents, Methods, All subjects had blind needle synovial biopsies with the Parker-Pearson needle. DNA was extracted and PCR performed using primers for Chlamydia trachomatis, Chlamydia pneumoniae, Borrelia burgdorferi, and pan bacterial 16S ribosomal RNA (rRNA), Results. Two subjects were identified with nucleic acid for the 16S rRNA gene of C trachomatis. All other PCR reactions were negative except for the pan bacterial 16S rRNA in the C trachomatis-positive subjects. Both subjects, although symptom free, had some evidence of synovial reaction. Conclusion. C trachomatis appears to occasionally be disseminated to joints without producing overt disease. C1 Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Schumacher, HR (reprint author), Dept Vet Affairs Med Ctr, Univ & Woodland Ave, Philadelphia, PA 19104 USA. OI Arayssi, Thurayya/0000-0003-2469-0272 FU NIAMS NIH HHS [AR-42541] NR 27 TC 73 Z9 74 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1999 VL 42 IS 6 BP 1281 EP 1284 DI 10.1002/1529-0131(199906)42:6<1281::AID-ANR27>3.0.CO;2-8 PG 4 WC Rheumatology SC Rheumatology GA 204VU UT WOS:000080786000027 PM 10366123 ER PT J AU Gow, DW Rodkin, PC AF Gow, DW Rodkin, PC TI Can current methods of pathonormal inference tell us anything about modularity? SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material AB This commentary on Muller's target article is designed to help bridge the gap between method and theory in neurobiological approaches to language. We focus on pathonormal inference as reflective of broader conceptual issues concerning universality and modularity. Our commentary directs attention to how current methodological and analytic procedures are less than optimal and minimize possibilities for reaching theoretical consensus. We make suggestions about alternative analytic strategies that provide a direction for future scientific progress. C1 Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. Duke Univ, Dept Psychol Social & Hlth Sci, Durham, NC 27708 USA. RP Gow, DW (reprint author), Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD JUN PY 1999 VL 22 IS 3 BP 571 EP + PG 4 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA 229UH UT WOS:000082213800097 ER PT J AU Tsuang, MT Stone, WS Seidman, LJ Faraone, SV Zimmet, S Wojcik, J Kelleher, JP Green, AI AF Tsuang, MT Stone, WS Seidman, LJ Faraone, SV Zimmet, S Wojcik, J Kelleher, JP Green, AI TI Treatment of nonpsychotic relatives of patients with schizophrenia: Four case studies SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; risperidone; negative symptoms; attention; neuropsychology; genetics ID RISPERIDONE; CLOZAPINE; SIBLINGS; DEFICIT; BRAIN AB Background: Substantial evidence now shows that the genetic vulnerability to schizophrenia can be manifested clinically in first-degree relatives of people with schizophrenia, even without the full manifestations of the disorder. One pattern of problems observed involves the combination of negative symptoms and neuropsychological deficits. We have investigated whether a low dose of a novel antipsychotic medication, risperidone, could attenuate these clinical problems in non-psychotic, first-degree relatives, and report here findings from our first 4 cases. Methods: Twelve adults who were first-degree relatives of patients with schizophrenia were evaluated for the presence of negative symptoms and neuropsychological deficits:(in attention and working memory, long-term verbal memory and executive functions). Four subjects who met our predetermined criteria, and who did not demonstrate medical contraindications, were enrolled in a 6-week trial of risperidone. Clinical and medical measures were assessed before, during and after treatment Doses of risperidone started at 0.25 mg and were increased to 1.0-2.0 mg/day. Results: Three subjects showed substantial reductions in negative symptoms, and one subject showed modest reductions. All four subjects showed substantial improvements on some tests of attention and working memory. Side effects of risperidone were temporary and mainly mild Conclusions: These initial findings support two conclusions, First, clinical deficits in non-psychotic first-degree relatives of people with schizophrenia are identifiable, and to a significant extent, reversible. Second, risperidone may eventually serve as an effective treatment for people whose lives are impaired by similar or related problems. (C) 1999 Society of Biological Psychiatry. C1 Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Brockton W Roxbury VA Med Ctr, Boston, MA USA. MMHC, Commonwealth Res Ctr, Boston, MA USA. Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Tsuang, MT (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Mental Hlth Ctr, 74 Fenwood Rd, Boston, MA 02115 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [1R37MH43518] NR 30 TC 63 Z9 64 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 JUN 1 PY 1999 VL 45 IS 11 BP 1412 EP 1418 DI 10.1016/S0006-3223(98)00364-3 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 199VK UT WOS:000080504600003 PM 10356622 ER PT J AU Yao, JK Reddy, RD van Kammen, DP AF Yao, JK Reddy, RD van Kammen, DP TI Human plasma glutathione peroxidase and symptom severity in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE human plasma glutathione peroxidase; haloperidol; oxidative stress; psychosis; schizophrenia ID CELL MEMBRANE DYNAMICS; ARACHIDONIC-ACID AB Background: Previous studies have shown impaired antioxidant defense system in schizophrenia, including alterations in glutathione peroxidase (GSH-Px) activity in erythrocytes. There exists a related enzyme, human plasma GSH-Px (hpGSH-Px), that has not been previously examined in schizophrenia. Methods: An enzyme-linked immunoassay was used to determine hpGSH-Px levels in male schizophrenic patients (n = 39), using a within-subject, on-off haloperidol (HD) treatment design, compared with age- and gender-matched normal control subjects (n = 37). Results: hpGSH-Px was not significantly different between normal control subjects and patients, consistent with our previous findings in erythrocyte GSH-Px. There were no significant treatment effects. hpGSH-Px was significantly and positively correlated with psychosis rating scores in patients both on and off HD treatment. Conclusions: Although not different from normal controls, hpGSH-Px levels in patients may reflect oxidative stress associated with greater psychosis severity. The present findings thus suggest that schizophrenic patients, without obvious increase of endogenous antioxidant enzymes (e.g., hpGSH-Px), may be at risk for oxidative damage. (C) 1999 Society of Biological Psychiatry. C1 VA Pittsburgh Hlthcare Syst, Pittsburgh, PA 15206 USA. Univ Penn, Med Ctr, Dept Psychiat, Western Psychiat Inst & Clin, Pittsburgh, PA USA. RP Yao, JK (reprint author), VA Pittsburgh Hlthcare Syst, 7180 Highland Dr, Pittsburgh, PA 15206 USA. NR 23 TC 43 Z9 44 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 JUN 1 PY 1999 VL 45 IS 11 BP 1512 EP 1515 DI 10.1016/S0006-3223(98)00184-X PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 199VK UT WOS:000080504600016 PM 10356635 ER PT J AU Goggins, WB Finkelstein, DM Zaslavsky, AM AF Goggins, WB Finkelstein, DM Zaslavsky, AM TI Applying the Cox proportional hazards model when the change time of a binary time-varying covariate is interval censored SO BIOMETRICS LA English DT Article DE HIV; missing data; survival ID EM ALGORITHM; DATA AUGMENTATION; REGRESSION AB This paper develops methodology for estimation of the effect of a binary time-varying covariate on failure times when the change time of the covariate is interval censored. The motivating example is a study of cytomegalovirus (CMV) disease in patients with human immunodeficiency virus (HIV) disease. We are interested in determining whether CMV shedding predicts an increased hazard for developing active CMV disease. Since a clinical screening test is needed to detect CMV shedding, the time that shedding begins is only known to lie in an interval bounded by the patient's last negative and first positive tests. In a Cox proportional hazards model with a time-varying covariate for CMV shedding, the partial likelihood depends on the covariate status of every individual in the risk set at each failure time. Due to interval censoring, this is not always known. To solve this problem, we use a Monte Carlo EM algorithm with a Gibbs sampler embedded in the E-step. We generate multiple completed data sets by drawing imputed exact shedding times based on the joint likelihood of the shedding times and event times under the Cox model. The method is evaluated using a simulation study and is applied to the data set described above. C1 Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Goggins, WB (reprint author), Massachusetts Gen Hosp, 677 Huntington Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA 74302]; NIAID NIH HHS [N0-AI 38855] NR 13 TC 21 Z9 21 U1 1 U2 4 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 JUN PY 1999 VL 55 IS 2 BP 445 EP 451 DI 10.1111/j.0006-341X.1999.00445.x PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 214GT UT WOS:000081320800015 PM 11318198 ER PT J AU Parzen, M Lipsitz, SR AF Parzen, M Lipsitz, SR TI A global goodness-of-fit statistic for Cox regression models SO BIOMETRICS LA English DT Article DE Hosmer-Lemeshow statistic; score test; survival time ID PROPORTIONAL HAZARDS MODEL; TESTS AB In this paper, a global goodness-of-fit test statistic for a Cox regression model, which has an approximate chi-squared distribution when the model has been correctly specified, is proposed. Our goodness-of-fit statistic is global and has power to detect if interactions or higher order powers of covariates in the model are needed. The proposed statistic is similar to the Hosmer and Lemeshow (1980, Communications in Statistics A10, 1043-1069) goodness-of-fit statistic for binary data as well as Schoenfeld's (1980, Biometrika 67, 145-153) statistic for the Cox model. The methods are illustrated using data from a Mayo Clinic trial in primary billiary cirrhosis of the liver (Fleming and Harrington, 1991, Counting Processes and Survival Analysis), in which the outcome is the time until liver transplantation or death. The are 17 possible covariates. Two Cox proportional hazards models are fit to the data, and the proposed goodness-of-fit statistic is applied to the fitted models. C1 Univ Chicago, Grad Sch Business, Chicago, IL 60637 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Parzen, M (reprint author), Univ Chicago, Grad Sch Business, 1101 E 58th St, Chicago, IL 60637 USA. FU NCI NIH HHS [CA 55576, CA 57253] NR 16 TC 35 Z9 35 U1 0 U2 5 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 JUN PY 1999 VL 55 IS 2 BP 580 EP 584 DI 10.1111/j.0006-341X.1999.00580.x PG 5 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 214GT UT WOS:000081320800034 PM 11318217 ER PT J AU Ibrahim, JG Chen, MH Lipsitz, SR AF Ibrahim, JG Chen, MH Lipsitz, SR TI Monte Carlo EM for missing covariates in parametric regression models SO BIOMETRICS LA English DT Article DE EM algorithm; generalized linear model; Gibbs sampler; maximum likelihood estimation; missing data mechanism; Poisson regression; proportional hazards; Weibull regression ID RANDOMIZED PHASE-II; HEPATOCELLULAR-CARCINOMA; INCOMPLETE DATA AB We propose a method for estimating parameters for general parametric regression models with an arbitrary number of missing covariates. We allow any pattern of missing data and assume that the missing data mechanism is ignorable throughout. When the missing covariates are categorical, a useful technique for obtaining parameter estimates is the EM algorithm by the method of weights proposed in Ibrahim (1990, Journal of the American Statistical Association 85, 765-769). We extend this method to continuous or mixed categorical and continuous covariates, and for arbitrary parametric regression models, by adapting a Monte Carlo version of the EM algorithm as discussed by Wei and Tanner (1990, Journal of the American, Statistical Association 85, 699-704). In addition, we discuss the Gibbs sampler for sampling from the conditional distribution of the missing covariates given the observed data and show that the appropriate complete conditionals are log-concave. The log-concavity property of the conditional distributions will facilitate a straightforward implementation of the Gibbs sampler via the adaptive rejection algorithm of Gilks and Wild (1992, Applied Statistics 41, 337-348). We assume the model for the response given the covariates is an arbitrary parametric regression model, such as a generalized linear model, a parametric survival model, or a nonlinear model. We model the marginal distribution of the covariates as a product of one-dimensional conditional distributions. This allows us a great deal of flexibility in modeling the distribution of the covariates and reduces the number of nuisance parameters that are introduced in the E-step. We present examples involving both simulated and real data. 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 Sci, Worcester, MA 01609 USA. RP Ibrahim, JG (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 4 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 70101-01, CA 74015-01] NR 10 TC 64 Z9 66 U1 0 U2 8 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 JUN PY 1999 VL 55 IS 2 BP 591 EP 596 DI 10.1111/j.0006-341X.1999.00591.x PG 6 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 214GT UT WOS:000081320800036 PM 11318219 ER EF