FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Oliveira-Filho, J Ezzeddine, M Segal, AZ Buonanno, FS Koroshetz, WJ Rordorf, G Schwamm, L McDonald, C AF Oliveira-Filho, J Ezzeddine, M Segal, AZ Buonanno, FS Koroshetz, WJ Rordorf, G Schwamm, L McDonald, C TI Causes of fever in subarachnoid hemorrhage SO STROKE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2000 VL 31 IS 1 MA 107 BP 296 EP 296 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 271HX UT WOS:000084589100164 ER PT J AU Shafqat, S Furie, K Kurina, A Stein, J AF Shafqat, S Furie, K Kurina, A Stein, J TI Functional recovery in brain hemorrhage versus infarction: Distinct trajectories of cognitive and motor recovery during inpatient rehabilitation SO STROKE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Spaulding Rehabil Hosp, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2000 VL 31 IS 1 MA P20 BP 300 EP 300 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 271HX UT WOS:000084589100186 ER PT J AU Kelly, PJ Shafqat, S Doherty, D Stein, J Furie, KL AF Kelly, PJ Shafqat, S Doherty, D Stein, J Furie, KL TI Functional recovery following cerebellar strobe SO STROKE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Spaulding Rehabil Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2000 VL 31 IS 1 MA P28 BP 302 EP 302 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 271HX UT WOS:000084589100194 ER PT J AU Szegedi, N May, Z Ovary, C Voko, Z Nagy, Z AF Szegedi, N May, Z Ovary, C Voko, Z Nagy, Z TI Dose exact indication prevent hemorrhagic complications using streptokinase in acute ischemic stroke? SO STROKE LA English DT Meeting Abstract C1 Natl Stroke Ctr, Budapest, Hungary. Imre Univ, Budapest, Hungary. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2000 VL 31 IS 1 MA P66 BP 309 EP 309 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 271HX UT WOS:000084589100231 ER PT J AU Rordorf, G Segal, AZ Ezzeddine, M McDonald, CT Oliveira-Filho, J Koroshetz, WJ Schwamm, LH Buonanno, F AF Rordorf, G Segal, AZ Ezzeddine, M McDonald, CT Oliveira-Filho, J Koroshetz, WJ Schwamm, LH Buonanno, F TI Induced hypertension in acute ischemic stroke management SO STROKE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2000 VL 31 IS 1 MA P133 BP 323 EP 323 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 271HX UT WOS:000084589100298 ER PT J AU Cohen, SN Muthukamaran, A El-Saden, S Hathout, G AF Cohen, SN Muthukamaran, A El-Saden, S Hathout, G TI Spread of negative symptoms to contiguous body areas: A clinical marker of amyloid angiopathy? SO STROKE LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2000 VL 31 IS 1 MA P202 BP 337 EP 337 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 271HX UT WOS:000084589100367 ER PT J AU Gastfriend, DR Lu, SH Sharon, E AF Gastfriend, DR Lu, SH Sharon, E TI Placement matching: Challenges and technical progress SO SUBSTANCE USE & MISUSE LA English DT Article DE treatment matching; placement matching; substance dependency treatment; American Society of Addiction Medicine; patient placement criteria ID SUBSTANCE-ABUSE TREATMENT; USER NEEDS ASSESSMENT; ALCOHOL WITHDRAWAL; CRITERIA; DISORDERS; INPATIENT; SCALE; WOMEN; ASAM; DETOXIFICATION AB Although it is highly desirable, standardized placement matching for substance use disorders poses challenges due to variability in settings, services, and syndromes; multidimensionality of clinical problems; multiplicity of outcome constructs; and temporal phenomena in the course of recovery. Despite these obstacles, progress is being made in developing patient placement criteria that are comprehensive with adequate reliability, feasibility, and resolution. With these methodological advances, it has been possible to initiate controlled research with placement criteria. The first such studies provide early evidence supporting such criteria and indicate areas for refinement. C1 Massachusetts Gen Hosp, Addict Serv, Dept Psychiat, Boston, MA 02114 USA. RP Gastfriend, DR (reprint author), Massachusetts Gen Hosp, Addict Serv, Dept Psychiat, 15 Parkman St, Boston, MA 02114 USA. FU NIDA NIH HHS [DA08781] NR 71 TC 11 Z9 11 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2000 VL 35 IS 12-14 BP 2191 EP 2213 DI 10.3109/10826080009148254 PG 23 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 384TK UT WOS:000165961500021 PM 11138721 ER PT B AU Lee, MMC AF Lee, MMC BE Goldberg, E TI MIS actions in the developing testis SO TESTIS: FROM STEM CELL TO SPERM FUNCTION SE SERONO SYMPOSIA, USA LA English DT Proceedings Paper CT XVth Testis Workshop on the Testis - From Stem Cell to Sperm Function CY APR 07-10, 1999 CL LOUISVILLE, KY SP Serono Symposia USA Inc ID MULLERIAN-INHIBITING SUBSTANCE; RAT LEYDIG-CELLS; FOLLICLE-STIMULATING-HORMONE; MESSENGER-RIBONUCLEIC-ACID; LUTEINIZING-HORMONE; STEROIDOGENIC ENZYMES; II RECEPTOR; SEXUAL DEVELOPMENT; TRANSGENIC MICE; EXPRESSION C1 Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. RP Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. NR 40 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-95024-9 J9 SERONO SYMP PY 2000 BP 30 EP 42 PG 5 WC Reproductive Biology SC Reproductive Biology GA BQ84K UT WOS:000089810900004 ER PT J AU Hovell, MF Zakarian, JM Wahlgren, DR Matt, GE Emmons, KM AF Hovell, MF Zakarian, JM Wahlgren, DR Matt, GE Emmons, KM TI Reported measures of environmental tobacco smoke exposure: trials and tribulations SO TOBACCO CONTROL LA English DT Article DE environmental tobacco smoke; children; nicotine; cotinine ID ASTHMATIC-CHILDREN; URINARY COTININE; PARENTAL SMOKING; PASSIVE SMOKING; PRESCHOOL-CHILDREN; NATIONAL-HEALTH; NICOTINE; EPIDEMIOLOGY; INTERVENTION; NONSMOKERS AB Objective-This report extends previous summaries of reported environmental tobacco smoke (ETS) exposure measures, reviews the empirical evidence of their validity for children's exposure, and discusses future research. Data sources-Studies were identified by computer search and from the authors' research. Study selection-Studies were selected for inclusion of nicotine and/or cotinine and quantitative reported measures of ETS exposure. Data synthesis-Five studies found significant associations between reported quantitative exposure of children to ETS and either environmental nicotine or urine cotinine assays. Correlation coefficients between parent reports and nicotine ranged from 0.22 to 0.75. Coefficients for cotinine ranged from 0.28 to 0.71. Correlations increased over time and were stronger for parents' reports of their own smoking as a source of children's exposure than for reports of exposure from others. Conclusions-Empirical studies general concordance of reported ana either environmental or biological measures of ETS exposure. Relationships were moderate, and suggest sufficient validity to be employed in research and service programs. Future studies need to identify the differences in types of reported or objective measures, population characteristics, etc, contributing to observed variability in order to understand better the conditions under which more valid reported ETS exposure and other measures can be obtained. Reported and either environmental or biological measures should be used in combination, and existing measures should be directed to interventions that may reduce ETS exposure among children. C1 San Diego State Univ, Grad Sch Publ Hlth, Ctr Behav Epidemiol & Community Hlth, San Diego, CA 92182 USA. San Diego State Univ, Dept Psychol, San Diego, CA 92182 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hovell, MF (reprint author), MPH, C BEACH, 9245 Sky Pk Court,Suite 230, San Diego, CA 92123 USA. NR 53 TC 59 Z9 59 U1 1 U2 4 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 J9 TOB CONTROL JI Tob. Control PY 2000 VL 9 SU 3 BP 22 EP 28 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 357VA UT WOS:000089520400006 ER PT J AU Velasquez, MM Hecht, J Quinn, VP Emmons, KM DiClemente, CC Dolan-Mullen, P AF Velasquez, MM Hecht, J Quinn, VP Emmons, KM DiClemente, CC Dolan-Mullen, P TI Application of motivational interviewing to prenatal smoking cessation: training and implementation issues SO TOBACCO CONTROL LA English DT Article DE pregnancy; smoking; motivational interviewing AB Objective-Three of the Smoke-Free Families projects incorporated motivational interviewing (MI) into prenatal smoking cessation interventions. This paper describes the process involved in training healthcare providers to use MI and the issues encountered in implementing the protocols. Design-Health care providers at all three sites attended local training workshops in which they learned to apply the basics of MI to their study protocol. All sites followed a similar outline and schedule for training and monitoring, Settings-The MI interventions were delivered through home visits in Boston, Massachusetts; phone based counselling calls to patients' homes in Southern California; and in urban and rural prenatal clinics throughout East Texas. Participants-Public health nurse and social work case managers, who were already employed by health care agencies, delivered the MI interventions. Measures-Pre- and postintervention assessments and feedback from trainers and investigators at all three sites. Results-Providers were enthusiastic about the training workshops, which they rated as effective in preparing them to deliver the intervention. Barriers to implementation included difficulty in contacting patients and competing demands on providers' time. Conclusions-Conducting initial training for providers is the first step in developing skills to deliver motivational interventions. Additional time and resources are needed for ongoing skill building and monitoring of intervention delivery. C1 Univ Texas, Sch Med, Dept Family Practice & Community Med, Houston, TX 77030 USA. Miriam Hosp, Ctr Behav & Prevent Med, Providence, RI 02906 USA. Kaiser Permanente, Pasadena, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Maryland Baltimore Cty, Dept Psychol, Baltimore, MD 21228 USA. Univ Texas, Hlth Sci Ctr, Sch Publ Hlth, Ctr Hlth Promot Res & Prevent, Houston, TX 77225 USA. RP Velasquez, MM (reprint author), Univ Texas, Sch Med, Dept Family Practice & Community Med, 6431 Fannin,Suite 2-112, Houston, TX 77030 USA. NR 9 TC 42 Z9 42 U1 0 U2 6 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 J9 TOB CONTROL JI Tob. Control PY 2000 VL 9 SU 3 BP 36 EP 40 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 357VA UT WOS:000089520400008 ER PT J AU Rigotti, NA AF Rigotti, NA TI II. Smoking cessation in the hospital setting - a new opportunity for managed care SO TOBACCO CONTROL LA English DT Editorial Material ID ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED TRIAL; COST-EFFECTIVENESS; INTERVENTION; PROGRAM; SURGERY; PREDICTORS; SMOKERS C1 Massachusetts Gen Hosp, Dept Med, Tobacco Res & Treatment Program, Boston, MA 02114 USA. RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, Dept Med, Tobacco Res & Treatment Program, 50 Staniford St,9th Floor, Boston, MA 02114 USA. NR 19 TC 4 Z9 4 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 J9 TOB CONTROL JI Tob. Control PY 2000 VL 9 SU 1 BP 54 EP 55 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 292NB UT WOS:000085800100020 ER PT J AU Emmons, KM Sorensen, G Klar, N Digianni, L Barclay, G Schmidt, K Hammond, SK AF Emmons, KM Sorensen, G Klar, N Digianni, L Barclay, G Schmidt, K Hammond, SK TI Healthy Baby Second-Hand Smoke Study: project brief SO TOBACCO CONTROL LA English DT Article C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Boston Publ Hlth Commiss, Boston, MA USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. RP Emmons, KM (reprint author), Harvard Univ, Sch Publ Hlth, 44 Binney St, Boston, MA 02115 USA. RI Travers, Mark/C-7832-2011 NR 5 TC 11 Z9 11 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 J9 TOB CONTROL JI Tob. Control PY 2000 VL 9 SU 3 BP 58 EP 60 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 357VA UT WOS:000089520400013 ER PT J AU Vamvakas, EC Carven, JH AF Vamvakas, EC Carven, JH TI Length of storage of transfused red cells and postoperative morbidity in patients undergoing coronary artery bypass graft surgery SO TRANSFUSION LA English DT Article ID STORED HUMAN-BLOOD; BIOACTIVE SUBSTANCES; PLATELET; PLASMA; TIME; RELEASE; LIPIDS AB BACKGROUND: The transfusion of old red cells (RBCs) may be associated with reduced delivery of oxygen to tissues and an increased risk of transfusion complications. The association of postoperative morbidity with the length of storage of perioperatively transfused RBCs was studied in 268 consecutive patients receiving a blood transfusion for coronary artery bypass graft surgery. STUDY DESIGN AND METHODS: The postoperative length of hospitalization, the postoperative length of stay in the intensive care unit, and the length of endotracheal intubation after the day of the operation were used as surrogate measures of global postoperative morbidity. The length of storage of the oldest transfused RBC unit, the mean length of storage of the oldest and second oldest RBC units, and the mean length of storage of all RBC units transfused to each patient were tested for association with the three outcome variables. Multiple linear regression analysis and Cox proportional-hazard analysis were used to adjust for the effects of confounding factors that pertained to each patient's severity of illness and the difficulty of each operation. RESULTS: There were no significant associations after adjustment for the effects of confounding factors. CONCLUSION: This study did not corroborate the previously reported association between transfusion of old RBCs and increased morbidity. However, there is surprisingly little research on the clinical outcomes of the transfusions of old RBCs, and this hypothesis should be investigated further. C1 Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. New York Dept Vet Affairs, Pathol & Lab Med Serv, New York, NY USA. RP Vamvakas, EC (reprint author), NYU Med Ctr, Blood Bank & Transfus Serv, RRG-17,400 E 34th St, New York, NY 10016 USA. NR 31 TC 117 Z9 118 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JAN PY 2000 VL 40 IS 1 BP 101 EP 109 DI 10.1046/j.1537-2995.2000.40010101.x PG 9 WC Hematology SC Hematology GA 274ZE UT WOS:000084794300018 PM 10644819 ER PT J AU Dzik, S Aubuchon, J Jeffries, L Kleinman, S Manno, C Murphy, MF Popovsky, MA Sayers, M Silberstein, LE Slichter, SJ Vamvakas, EC AF Dzik, S Aubuchon, J Jeffries, L Kleinman, S Manno, C Murphy, MF Popovsky, MA Sayers, M Silberstein, LE Slichter, SJ Vamvakas, EC TI Leukocyte reduction of blood components: Public policy and new technology SO TRANSFUSION MEDICINE REVIEWS LA English DT Review ID CREUTZFELDT-JAKOB-DISEASE; WHITE CELL-REDUCTION; FEBRILE TRANSFUSION REACTIONS; ELECTIVE COLORECTAL SURGERY; POLYMERASE CHAIN-REACTION; NECROSIS-FACTOR-ALPHA; RED-CELLS; COST-EFFECTIVENESS; PLATELET TRANSFUSION; HLA-ALLOIMMUNIZATION C1 Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. Dartmouth Hitchcock Med Ctr, Transfus Serv, Lebanon, NH 03766 USA. Hosp Univ Penn, Dept Transfus Med, Philadelphia, PA 19104 USA. Univ British Columbia, Dept Transfus Med, Vancouver, BC V5Z 1M9, Canada. Childrens Hosp Philadelphia, Transfus Serv, Philadelphia, PA 19104 USA. John Radcliffe Hosp, Natl Blood Serv, Oxford OX3 9DU, England. Amer Red Cross Blood Serv, New England Reg, Dedham, MA USA. Carter Bloodcare, Dallas, TX USA. Hosp Univ Penn, Transfus Med Sect, Philadelphia, PA 19104 USA. Puget Sound Blood Ctr, Seattle, WA 98104 USA. Vet Affairs Med Ctr, Dept Pathol & Lab Med, New York, NY USA. RP Dzik, S (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, J-224,55 Fruit St, Boston, MA 02114 USA. NR 101 TC 84 Z9 85 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 0887-7963 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD JAN PY 2000 VL 14 IS 1 BP 34 EP 52 DI 10.1016/S0887-7963(00)80114-5 PG 19 WC Hematology SC Hematology GA 276QW UT WOS:000084889700005 PM 10669939 ER PT J AU Childress, AR O'Brien, CP AF Childress, AR O'Brien, CP TI Dopamine receptor partial agonists could address the duality of cocaine craving SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Editorial Material ID NUCLEUS-ACCUMBENS; METHYLPHENIDATE TREATMENT; EXTRACELLULAR DOPAMINE; SQUIRREL-MONKEYS; SEEKING BEHAVIOR; MODULATION; ADDICTION; REINFORCEMENT; ABUSERS; RATS C1 Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Behav Hlth Div, Philadelphia, PA 19104 USA. RP Childress, AR (reprint author), Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. NR 55 TC 44 Z9 46 U1 2 U2 4 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD JAN PY 2000 VL 21 IS 1 BP 6 EP 9 DI 10.1016/S0165-6147(99)01422-4 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 271HZ UT WOS:000084589300001 PM 10637646 ER PT J AU Kim, J Park, JN Shin, DW Dickersin, GR AF Kim, J Park, JN Shin, DW Dickersin, GR TI Numerous small vesicles in a case of clear cell leiomyoma of deep soft tissue: An ultrastructural study SO ULTRASTRUCTURAL PATHOLOGY LA English DT Article ID SMOOTH-MUSCLE TUMORS; CARCINOID-TUMOR; LEIOMYOBLASTOMA; UTERUS C1 Yonsei Univ, Coll Med, Dept Pathol, Seoul, South Korea. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, James Homer Wright Labs, Boston, MA 02114 USA. RP Kim, J (reprint author), Yonsei Univ, Coll Med, Dept Pathol, Seoul, South Korea. NR 16 TC 1 Z9 1 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 USA SN 0191-3123 J9 ULTRASTRUCT PATHOL JI Ultrastruct. Pathol. PD JAN-FEB PY 2000 VL 24 IS 1 BP 41 EP 45 PG 5 WC Microscopy; Pathology SC Microscopy; Pathology GA 291KQ UT WOS:000085733600006 ER PT S AU Nadol, JB Shiao, JY AF Nadol, JB Shiao, JY BE Kim, CS Chang, SO Lim, D TI Histopathology of cochlear implants SO UPDATES IN COCHLEAR IMPLANTATION SE ADVANCES IN OTO-RHINO-LARYNGOLOGY LA English DT Proceedings Paper CT 2nd Asia Pacific Congress on Cochlear Implant and Related Sciences CY APR 02-04, 1999 CL SEOUL, SOUTH KOREA ID HUMAN TEMPORAL BONES; GUINEA-PIG COCHLEA; SPIRAL GANGLION; ELECTRODE ARRAY; PATIENT C1 Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Nadol, JB (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 16 TC 4 Z9 4 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 3-8055-7070-8 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2000 VL 57 BP 1 EP 6 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA BS87T UT WOS:000171311300001 PM 11892117 ER PT J AU Oh, WK Manola, J Renshaw, AA Brodkin, D Loughlin, KR Richie, JP Shapiro, CL Kantoff, PW AF Oh, WK Manola, J Renshaw, AA Brodkin, D Loughlin, KR Richie, JP Shapiro, CL Kantoff, PW TI Smoking and alcohol use may be risk factors for poorer outcome in patients with clear cell renal carcinoma SO UROLOGY LA English DT Article ID EPIDEMIOLOGY; EXPRESSION; HISTORY; CANCER; P53 AB Objectives. To correlate the clinical outcomes of 148 patients with clear cell renal carcinoma treated at a single institution with a variety of other factors. Methods. Cases were derived from a consecutive series of nephrectomy specimens obtained from 1980 to 1994. A retrospective review of clinical records was performed, with tobacco use, alcohol use, recurrence, and survival noted. Results. The median age of the patients was 62 years. The median follow-up was 4.4 years. Of 148 patients, 82% had localized disease (MO), and 18% had suspected metastases (M1) at the time of nephrectomy. Of 121 patients without metastases at diagnosis, T classification was assessed for 117: 48 (41%) had T1 disease, 18 (15%) T2, 46 (39%) T3, and 5 (4%) T4. The Fuhrman grade was 1 or 2 in 51% of patients and 5 or 4 in 45%. Both clinical stage and grade were significantly associated with overall survival (P <0.0001 and P = 0.0028, respectively) and recurrence-free survival (P = 0.0002 and P = 0.0011, respectively). Smoking and alcohol use history was determined in 70% and 63% of patients, respectively. In patients with Stage MO, smokers had a significantly worse overall survival rate compared with nonsmokers (P = 0.039). Also, in patients with Stage MO, a trend toward a worse recurrence-free survival rate was noted in alcohol users compared with those who never used alcohol regularly (P = 0.06). Conclusions. The prognosis of clear cell renal carcinoma depends on the pathologic stage at diagnosis and the Fuhrman grade. Smoking is a known risk factor for developing renal cancer and may be associated with increased mortality from clear cell carcinoma in patients with Stage MO. Also, regular alcohol use may decrease the recurrence-free survival rate. (C) 2000, Elsevier Science Inc. C1 Dana Farber Canc Inst, Dept Adult Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Urol, Boston, MA 02115 USA. Ohio State Univ, Arthur G James Canc Ctr, Div Med Oncol, Columbus, OH 43210 USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 20 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD JAN PY 2000 VL 55 IS 1 BP 31 EP 35 DI 10.1016/S0090-4295(99)00408-2 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 275BL UT WOS:000084799500009 PM 10654890 ER PT B AU Kooy, H Oelfke, U Lomax, T Paganetti, H Newhauser, W Bortfeld, T Goitein, M AF Kooy, H Oelfke, U Lomax, T Paganetti, H Newhauser, W Bortfeld, T Goitein, M BE Schlegel, W Bortfeld, T TI Design considerations for intensity modulated proton therapy treatment planning SO USE OF COMPUTERS IN RADIATION THERAPY LA English DT Proceedings Paper CT 13th International Conference on the Use of Computers in Radiation Therapy CY MAY 22-25, 2000 CL HEIDELBERG, GERMANY SP Direx Syst GmbH, Gammex RMI GmbH, MDS Nordion Therapy Syst, Multidata Syst Duetschland GmbH, Phys Med & Biol, Siemens Med Technik, Varian Med Syst Int AG C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Kooy, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 3-540-67176-5 PY 2000 BP 71 EP 72 PG 2 WC Computer Science, Interdisciplinary Applications; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging GA BQ45R UT WOS:000088386600026 ER PT B AU Kung, JH Chen, GTY AF Kung, JH Chen, GTY BE Schlegel, W Bortfeld, T TI Monitor units verification calculation in IMRT as a patient specific dosimetry QA. SO USE OF COMPUTERS IN RADIATION THERAPY LA English DT Proceedings Paper CT 13th International Conference on the Use of Computers in Radiation Therapy CY MAY 22-25, 2000 CL HEIDELBERG, GERMANY SP Direx Syst GmbH, Gammex RMI GmbH, MDS Nordion Therapy Syst, Multidata Syst Duetschland GmbH, Phys Med & Biol, Siemens Med Technik, Varian Med Syst Int AG C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kung, JH (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 3-540-67176-5 PY 2000 BP 292 EP 293 PG 2 WC Computer Science, Interdisciplinary Applications; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging GA BQ45R UT WOS:000088386600111 ER PT B AU Bues, M Kooy, HM Hoban, P AF Bues, M Kooy, HM Hoban, P BE Schlegel, W Bortfeld, T TI Fluence segmentation for micro intensity modulated radiotherapy with a miniature multileaf collimator SO USE OF COMPUTERS IN RADIATION THERAPY LA English DT Proceedings Paper CT 13th International Conference on the Use of Computers in Radiation Therapy CY MAY 22-25, 2000 CL HEIDELBERG, GERMANY SP Direx Syst GmbH, Gammex RMI GmbH, MDS Nordion Therapy Syst, Multidata Syst Duetschland GmbH, Phys Med & Biol, Siemens Med Technik, Varian Med Syst Int AG C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. RP Bues, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. NR 6 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 3-540-67176-5 PY 2000 BP 303 EP 304 PG 2 WC Computer Science, Interdisciplinary Applications; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging GA BQ45R UT WOS:000088386600115 ER PT B AU Paganetti, H Goitein, M AF Paganetti, H Goitein, M BE Schlegel, W Bortfeld, T TI Physical and biological dose distribution due to primary protons and secondary particles from nuclear interactions SO USE OF COMPUTERS IN RADIATION THERAPY LA English DT Proceedings Paper CT 13th International Conference on the Use of Computers in Radiation Therapy CY MAY 22-25, 2000 CL HEIDELBERG, GERMANY SP Direx Syst GmbH, Gammex RMI GmbH, MDS Nordion Therapy Syst, Multidata Syst Duetschland GmbH, Phys Med & Biol, Siemens Med Technik, Varian Med Syst Int AG C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Paganetti, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 8 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 3-540-67176-5 PY 2000 BP 323 EP 325 PG 3 WC Computer Science, Interdisciplinary Applications; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging GA BQ45R UT WOS:000088386600122 ER PT B AU Zygmanski, P Rosenthal, S AF Zygmanski, P Rosenthal, S BE Schlegel, W Bortfeld, T TI Patient set-up for proton radiotherapy using digital X-ray images of implanted fiducials SO USE OF COMPUTERS IN RADIATION THERAPY LA English DT Proceedings Paper CT 13th International Conference on the Use of Computers in Radiation Therapy CY MAY 22-25, 2000 CL HEIDELBERG, GERMANY SP Direx Syst GmbH, Gammex RMI GmbH, MDS Nordion Therapy Syst, Multidata Syst Duetschland GmbH, Phys Med & Biol, Siemens Med Technik, Varian Med Syst Int AG C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Zygmanski, P (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 3-540-67176-5 PY 2000 BP 332 EP 333 PG 2 WC Computer Science, Interdisciplinary Applications; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging GA BQ45R UT WOS:000088386600125 ER PT S AU de la Monte, SM Sohn, YK Etienne, D Kraft, J Wands, JR AF de la Monte, SM Sohn, YK Etienne, D Kraft, J Wands, JR BE Kalaria, RN Ince, P TI Role of aberrant nitric oxide synthase-3 expression in cerebrovascular degeneration and vascular-mediated injury in Alzheimer's disease SO VASCULAR FACTORS IN ALZHEIMER'S DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Vascular Factors in Alzheimers Disease CY MAY 25-28, 1999 CL NEWCASTLE TYNE, ENGLAND SP Bayer AG, Eisai Ltd, GJ Livanos Trust, Alzheimers Report, Hoechst Marrion Roussel, Janssen Pharmaceut, Novartis Pharma AG, Parke Davis, Pfizer Inc, SmithKline Beecham Pharmaceut, Zeneca, Med Res Council, Inst Brain & Blood Vessels, Akita, Inst Hlth Elderly, Univ Newcastle Upon Tyne ID SPECIAL EXTRACT EGB-761; WHITE-MATTER LESIONS; SMOOTH-MUSCLE CELLS; CEREBRAL BLOOD-FLOW; GINKGO-BILOBA; NEUROTROPHIC FACTOR; GUANYLATE-CYCLASE; NADPH-DIAPHORASE; PHOSPHOLIPASE-C; DEMENTIA AB Nitric oxide (NO) is an important signaling molecule that is generated through the catalytic activity of nitric oxide synthase (NOS), In the brain, NO mediates neuronal survival, synaptic plasticity, vascular smooth muscle relaxation, and endothelial cell permeability, Previous studies demonstrated aberrant expression of the NOS-III gene in neurons and glial cells in brains with Alzheimer's disease (AD), Since NOS-ID is also expressed in vascular cells, and cerebrovascular disease (CVD) frequently complicates the pathology of AD, we investigated the role of NOS-III in relation to CVD in AD, Vasculopathy in AD+CVD was characterized by thickening and hyalinization of the media of small and medium-size vessels, variable degrees of beta-amyloid (A beta) deposition, and increased apoptosis of vascular smooth muscle and endothelial cells, particularly involving white matter vessels, These abnormalities were correlated with reduced levels of NOS-III expression in cerebral vessels, Double-labeling studies demonstrated that the low levels of cerebrovascular NOS-III were associated with increased levels of the pro-apoptosis gene product, p53 in smooth muscle and endothelial cells, suggesting a role for altered NOS-ID expression in AD-associated vascular degeneration, Constitutively reduced cerebrovascular NOS-III expression and NO production could also lead to cerebral hypoperfusion due to impaired vasodilation responses, and diminished capacity to remove respiratory waste products and toxins from the extracellular space due to reduced capillary permeability, The role for phosphodiesterases as modulators of NOS activity is discussed, as these molecules represent potential therapeutic targets given their cell type and cyclic nucleotide specificities of action. C1 Brown Univ, Rhode Isl Hosp, Sch Med, Dept Med, Providence, RI 02903 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH E Canc Ctr,Dept Pathol, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH E Canc Ctr,Dept Med, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Dept Pathol, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Dept Med, Boston, MA 02129 USA. RP de la Monte, SM (reprint author), Brown Univ, Rhode Isl Hosp, Sch Med, Dept Med, 55 Claverick St, Providence, RI 02903 USA. NR 76 TC 11 Z9 12 U1 1 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-251-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 903 BP 61 EP 71 DI 10.1111/j.1749-6632.2000.tb06351.x PG 11 WC Multidisciplinary Sciences; Clinical Neurology; Peripheral Vascular Disease SC Science & Technology - Other Topics; Neurosciences & Neurology; Cardiovascular System & Cardiology GA BQ26Z UT WOS:000087756800010 PM 10818490 ER PT S AU Greenberg, SM Cho, HS O'Donnell, HC Rosand, J Segal, AZ Younkin, LH Younkin, SG Rebeck, GW AF Greenberg, SM Cho, HS O'Donnell, HC Rosand, J Segal, AZ Younkin, LH Younkin, SG Rebeck, GW BE Kalaria, RN Ince, P TI Plasma beta-amyloid peptide, transforming growth factor-beta 1, and risk for cerebral amyloid angiopathy SO VASCULAR FACTORS IN ALZHEIMER'S DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Vascular Factors in Alzheimers Disease CY MAY 25-28, 1999 CL NEWCASTLE TYNE, ENGLAND SP Bayer AG, Eisai Ltd, GJ Livanos Trust, Alzheimers Report, Hoechst Marrion Roussel, Janssen Pharmaceut, Novartis Pharma AG, Parke Davis, Pfizer Inc, SmithKline Beecham Pharmaceut, Zeneca, Med Res Council, Inst Brain & Blood Vessels, Akita, Inst Hlth Elderly, Univ Newcastle Upon Tyne ID ONSET ALZHEIMER-DISEASE; APOLIPOPROTEIN-E EPSILON-2; CEREBROSPINAL-FLUID; TRANSGENIC MICE; IN-VIVO; HEMORRHAGE; PROTEIN; PLAQUES; DEPOSITION; TGF-BETA-1 AB Despite the documented association between apolipoprotein E genotype and cerebral amyloid angiopathy (CAA), a substantial proportion of CAA-related hemorrhages occur in patients without known risks for this disorder, Two other factors implicated in the pathogenesis of CAA are the amyloid-beta peptide (preferentially deposited in vessels as a 40-amino acid species) and the multifunctional cytokine transforming growth factor-beta 1 (a specific promoter of vascular amyloid deposition in transgenic models), We measured plasma concentrations of these factors in a series of 25 patients diagnosed with probable or definite CAA-related hemorrhage and compared them with 21 patients with hemorrhage due to probable hypertensive vasculopathy and 42 elderly control subjects without hemorrhage. We found no differences among the groups in concentrations of the 40- or 42-amino acid species of beta-amyloid or either the active or latent form of transforming growth factor-beta 1. While the data do not exclude important roles for these molecules as risks for CAA, they indicate that plasma measurements are not useful in its diagnosis. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Mayo Clin, Jacksonville, FL 32224 USA. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Wang ACC 836, Boston, MA 02114 USA. FU NIA NIH HHS [AG00725] NR 30 TC 14 Z9 15 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-251-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 903 BP 144 EP 149 DI 10.1111/j.1749-6632.2000.tb06361.x PG 6 WC Multidisciplinary Sciences; Clinical Neurology; Peripheral Vascular Disease SC Science & Technology - Other Topics; Neurosciences & Neurology; Cardiovascular System & Cardiology GA BQ26Z UT WOS:000087756800020 PM 10818500 ER PT S AU Craft, S Asthana, S Schellenberg, G Baker, L Cherrier, M Boyt, AA Martins, RN Raskind, M Peskind, E Plymate, S AF Craft, S Asthana, S Schellenberg, G Baker, L Cherrier, M Boyt, AA Martins, RN Raskind, M Peskind, E Plymate, S BE Kalaria, RN Ince, P TI Insulin effects on glucose metabolism, memory, and plasma amyloid precursor protein in Alzheimer's disease differ according to apolipoprotein-E genotype SO VASCULAR FACTORS IN ALZHEIMER'S DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Vascular Factors in Alzheimers Disease CY MAY 25-28, 1999 CL NEWCASTLE TYNE, ENGLAND SP Bayer AG, Eisai Ltd, GJ Livanos Trust, Alzheimers Report, Hoechst Marrion Roussel, Janssen Pharmaceut, Novartis Pharma AG, Parke Davis, Pfizer Inc, SmithKline Beecham Pharmaceut, Zeneca, Med Res Council, Inst Brain & Blood Vessels, Akita, Inst Hlth Elderly, Univ Newcastle Upon Tyne ID RECEPTOR-RELATED PROTEIN; HYPERINSULINEMIA; DEGRADATION AB Higher lasting 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 4 allele, Insulin has also been implicated in processing of beta-amyloid and amyloid precursor protein (APP), We examined the effects of intravenous insulin administration while maintaining euglycemia on insulin-mediated glucose disposal, memory, and plasma APP in patients with AD and normal adults of varying ApoE genotypes, AD subjects without an epsilon 4 allele had significantly lower insulin-mediated glucose disposal rates than did AD patients with an epsilon 4 allele (p < 0.03) or than did normal adults without an epsilon 4 allele (p < 0.02). AD subjects without an e4 allele also showed significant memory facilitation with insulin administration (p < 0.04), whereas the AD-epsilon 4 group did not, Insulin reduced APP levels for AD patients without an ApoE epsilon 4 allele, but raised APP for AD patients with an ApoE epsilon H4 allele These results document ApoE-related differences in insulin metabolism in AD that may relate to disease pathogenesis. C1 VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98108 USA. Univ Western Australia, Sir James McCusker Alzheimers Dis Res Unit, Dept Surg, Perth, WA 6009, Australia. RP Craft, S (reprint author), VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, 182B,1660 S Columbian Way, Seattle, WA 98108 USA. FU NIA NIH HHS [AG-10880, AG-05136] NR 13 TC 100 Z9 106 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-251-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 903 BP 222 EP 228 DI 10.1111/j.1749-6632.2000.tb06371.x PG 7 WC Multidisciplinary Sciences; Clinical Neurology; Peripheral Vascular Disease SC Science & Technology - Other Topics; Neurosciences & Neurology; Cardiovascular System & Cardiology GA BQ26Z UT WOS:000087756800030 PM 10818510 ER PT S AU Johnston, JP Aparicio, JG Applebury, ML AF Johnston, JP Aparicio, JG Applebury, ML BE Palczewski, K TI Purification and autophosphorylation of retinal guanylate cyclase SO VERTEBRATE PHOTOTRANSDUCTION AND THE VISUAL CYCLE, PART A SE Methods in Enzymology LA English DT Review ID NATRIURETIC-PEPTIDE RECEPTOR; KINASE HOMOLOGY DOMAIN; ROD OUTER SEGMENTS; PROTEIN-KINASE; FUNCTIONAL-CHARACTERIZATION; ACTIVATING PROTEIN; CRYSTAL-STRUCTURE; ADENYLYL-CYCLASE; MOLECULAR-CLONING; MEMBRANE C1 Harvard Univ, Sch Med, Howe Lab, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Harvard Univ, Sch Med, Howe Lab, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 63 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182216-8 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2000 VL 315 BP 673 EP 689 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BQ69G UT WOS:000089206300044 PM 10736733 ER PT S AU Pisegna, JR Lyu, RM Germano, PM AF Pisegna, JR Lyu, RM Germano, PM BE Fahrenkrug, J Said, SI TI Essential structural motif in the C-terminus of the PACAP type I receptor for signal transduction and internalization SO VIP, PACAP, GLUCAGON, AND RELATED PEPTIDES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Symposium on VIP, PACAP, GLUCAGON, and Related Peptides CY SEP 02-04, 1999 CL ELSINORE, DENMARK SP Amersham Pharmacia Biotech, ASTRA AB, BACHEM AG, Biotechnol Ctr Cellular Commun, Clinalfa AG, Danish Canc Fdn, Eli Lilly Danmark AS, Euro Diagnost, Fujifilm Sverige AB, Interneuron Pharmaceut Inc, Novex Kem En Tec AS, Leica, Neurosci Pharmabiotec, Neosystem SA, NOVO Nordist AS, Roche Molec Biochem, Schering AG, Sigma Genosys Ltd, Danish Med Res Council, Plasmid Fdn AB The objectives of the study reported here were to identify amino acid residues of the C-terminus that are critical for intracellular signaling. A total of nine amino acid substitution and truncation mutants were constructed by PCR and confirmed by sequencing. Mutant and wildtype receptors were stably transfected into NIH/3T3 fibroblasts and studied for their ability to bind PACAP-27 and activate phospholipase C (PLC) and adenylyl cyclase (AC). Receptor affinity of I-125-PACAP-27 for the widtype and mutants were similar (K-d = 0.6-1.5 nM). However, truncation of the entire 63 amino acids of the hPAC(1) resulted in no signaling to either AC or IP. Addition of the proximal 10 amino acids of the C-terminus failed to restore AC or IP signaling, whereas addition of the proximal 27 amino acids of the C-terminus resulted in reconstitution of complete AC and IP responses, identical to the WT. Point mutations within this 17 amino acid region identified specific amino acids involved in PAC(1) signaling. These results indicate that a structural motif within the proximal region of the carboxyl terminus is critical for G protein coupling. C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Div Gastroenterol & Hepatol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Div Digest Dis, Los Angeles, CA 90073 USA. RP Pisegna, JR (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Div Gastroenterol & Hepatol, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK 52274-0 1] NR 0 TC 3 Z9 3 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-273-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 921 BP 195 EP 201 PG 7 WC Biochemistry & Molecular Biology; Gastroenterology & Hepatology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Gastroenterology & Hepatology; Science & Technology - Other Topics GA BT09Y UT WOS:000171939800021 PM 11193823 ER PT S AU Pisegna, JR Ohning, GV Athmann, C Zeng, NX Walsh, JH Sachs, G AF Pisegna, JR Ohning, GV Athmann, C Zeng, NX Walsh, JH Sachs, G BE Fahrenkrug, J Said, SI TI Role of PACAP, receptor in regulation of ECL cells and gastric acid secretion by pituitary adenylate cyclase activating peptide SO VIP, PACAP, GLUCAGON, AND RELATED PEPTIDES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Symposium on VIP, PACAP, GLUCAGON, and Related Peptides CY SEP 02-04, 1999 CL ELSINORE, DENMARK SP Amersham Pharmacia Biotech, ASTRA AB, BACHEM AG, Biotechnol Ctr Cellular Commun, Clinalfa AG, Danish Canc Fdn, Eli Lilly Danmark AS, Euro Diagnost, Fujifilm Sverige AB, Interneuron Pharmaceut Inc, Novex Kem En Tec AS, Leica, Neurosci Pharmabiotec, Neosystem SA, NOVO Nordist AS, Roche Molec Biochem, Schering AG, Sigma Genosys Ltd, Danish Med Res Council, Plasmid Fdn ID VASOACTIVE-INTESTINAL-PEPTIDE; POLYPEPTIDE PACAP; RAT-BRAIN; HYPOTHALAMIC POLYPEPTIDE; I RECEPTOR; NEUROPEPTIDE; VIP; PROLIFERATION; HISTAMINE; LUNG AB We previously reported that PAC, is expressed on ECL cells resulting in stimulation of [Ca2+](i), histamine and acid secretion. The study reported here characterized the signaling by PAC, on ECL cells; determined the effects of PACAP on the gastric acid secretion if: vivo, and determined the effects of chronic administration of PACAP-27 on ECL cell proliferation. PACAP-27 dose dependently stimulated ECL cell Ca2+ and AC with detectable stimulation at 1 nM and maximal stimulation at 100 nM (six-fold). In rats PACAP-27 administration (10 pmol/kg/h) increased the rate of gastric acid secretion when an antisomatostatin antibody was co-administered. Chronic administration of PACAP (10 pmol/h for seven days) via osmotic pump resulted in a more than twofold increase in BrdU incorporation into ECL cells. PACAP acting at the PAC, results in dual signaling responses to both [Ca2+](i). AC in ECL cells stimulates gastric acid secretion via the actions of histamine acting at the parietal cell and in whole animals leads to proliferation of ECL cells when administered chronically. C1 Univ Calif Los Angeles, W LA VA Med Ctr, CURE, VA UCLA Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Physiol & Med, Los Angeles, CA 90073 USA. RP Pisegna, JR (reprint author), VA Greater Los Angeles Healthcare Syst, 111C, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK41301, DK17294, DK 52274-01, DK40615] NR 30 TC 13 Z9 13 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-273-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 921 BP 233 EP 241 PG 9 WC Biochemistry & Molecular Biology; Gastroenterology & Hepatology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Gastroenterology & Hepatology; Science & Technology - Other Topics GA BT09Y UT WOS:000171939800026 PM 11193828 ER PT J AU Matthews, N Geesaman, BJ Qian, N AF Matthews, N Geesaman, BJ Qian, N TI The dependence of motion repulsion and rivalry on the distance between moving elements SO VISION RESEARCH LA English DT Article DE motion perception; binocular rivalry; attraction and repulsion ID BINOCULAR-RIVALRY; DIRECTION DISCRIMINATION; SPEED DISCRIMINATION; PERCEPTION; SIGNALS; INTERFERENCE; DEPTH AB We investigated the extent to which motion repulsion and binocular motion rivalry depend on the distance between moving elements. The stimuli consisted of two sets of spatially intermingled, finite-life random dots that moved across each other. The distance between the dots moving in different directions was manipulated by spatially pairing the dot trajectories with various precisions. Data from experiment 1 indicated that motion repulsion occurred reliably only when the average distance between orthogonally moving elements was at least 21.0 are min. When the dots were precisely paired, a single global direction intermediate to the two actual directions was perceived. This result suggests that, at a relatively small spatial scale, interaction between different directions favors motion attraction or coherence, while interaction at a somewhat larger scale generates motion repulsion. Similarly, data from experiment 2 indicated that binocular motion rivalry was significantly diminished by spatially pairing the dots, which moved in opposite directions in the two eyes. This supports the recent proposal that rivalry occurs at or after the stage of binocular convergence, since monocular cells could not have directly responded to our interocular pairing manipulation. Together, these findings suggest that the neural mechanisms underlying motion perception are highly sensitive to the fine spatial relationship between moving elements. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA. Massachusetts Gen Hosp, Dept Med, Cambridge, MA 02138 USA. RP Qian, N (reprint author), Columbia Univ, Ctr Neurobiol & Behav, Room A730,722 W 168th St, New York, NY 10032 USA. NR 28 TC 4 Z9 4 U1 0 U2 0 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. PY 2000 VL 40 IS 15 BP 2025 EP 2036 DI 10.1016/S0042-6989(00)00043-2 PG 12 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 320NY UT WOS:000087408300007 PM 10828469 ER PT J AU Chiao, CC Vorobyev, M Cronin, TW Osorio, D AF Chiao, CC Vorobyev, M Cronin, TW Osorio, D TI Spectral tuning of dichromats to natural scenes SO VISION RESEARCH LA English DT Article DE spectral tuning; natural scene; color vision; dichromacy; visual ecology ID SHREW TUPAIA-BELANGERI; COLOR-VISION; VISUAL PIGMENTS; CONE PHOTORECEPTORS; RABBIT RETINA; PHOTOPIGMENTS; SENSITIVITY; ADAPTATION; MECHANISMS; FRUGIVORY AB Multispectral images of natural scenes were collected from both forests and coral reefs. We varied the wavelength position of receptors in hypothetical dichromatic visual systems and, for each receptor pair estimated the percentage of discriminable points in natural scenes. The optimal spectral tuning predicted by this model results in photoreceptor pairs very like those of forest dwelling, dichromatic mammals and of coral reef fishes. Variations of the natural illuminants in forests have little or no effect on optimal spectral tuning, but variations of depth in coral reefs have moderate effects on the spectral placement of S and L cones. The ratio of S and L cones typically found in dichromatic mammals reduces the discriminability of forest scenes; in contrast, the typical ratio of S and L cones in coral reef fishes achieves nearly the optimal discrimination in coral reef scenes. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Univ Maryland Baltimore Cty, Dept Biol Sci, Baltimore, MD 21250 USA. Free Univ Berlin, Inst Neurobiol, D-14195 Berlin, Germany. Univ Sussex, Sch Biol Sci, Brighton BN1 9QG, E Sussex, England. RP Chiao, CC (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, 50 Blossom St,Wellman 429, Boston, MA 02114 USA. NR 51 TC 42 Z9 45 U1 0 U2 10 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. PY 2000 VL 40 IS 23 BP 3257 EP 3271 DI 10.1016/S0042-6989(00)00156-5 PG 15 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 362AR UT WOS:000089756900008 PM 11008142 ER PT J AU Biederman, I Bar, M AF Biederman, I Bar, M TI Differing views on views: response to Hayward and Tarr (2000) SO VISION RESEARCH LA English DT Article ID VISUAL OBJECT RECOGNITION; VIEWPOINT INVARIANCE; 3-DIMENSIONAL OBJECTS C1 Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. Univ So Calif, 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, Hedco Neurosci Bldg,MC 2520, Los Angeles, CA 90089 USA. NR 23 TC 8 Z9 8 U1 0 U2 1 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. PY 2000 VL 40 IS 28 BP 3901 EP 3905 DI 10.1016/S0042-6989(00)00180-2 PG 5 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 379QD UT WOS:000165653200010 PM 11090680 ER PT J AU Dzik, WH AF Dzik, WH TI Leukocyte counting during process control of leukoreduced blood components SO VOX SANGUINIS LA English DT Article; Proceedings Paper CT 26th Congress of the International-Society-of-Blood-Transfusion CY JUL 09-14, 2000 CL VIENNA, AUSTRIA SP Int Soc Blood Transfus, German Soc Transfus Med & Immunohematol, Austrian Soc Blood Grp Serol & Transfus Med ID LOW NUMBERS; CELLS AB Background and Objectives: To describe the characteristics of counting assays used for process control of leukoreduction. Materials and Methods: Literature review. Results: Counting assays with good performance characteristics are an essential element of the process control of leukoreduction. A recent multicenter study by a Working Party of the ISBT has evaluated three widely used methods for counting low numbers of leukocytes in leukoreduced blood. Conclusion: Automated methods provide greater accuracy and better inter-laboratory precision than Nageotte hematocytometry. However, deterioration of performance as a result of prolonged sample shipment remains an obstacle to centralized testing services. Although several mathematical approaches have been used to model the distribution of residual leukocytes in leukoreduced blood, no single model has been shown to be clearly superior. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Blood Transfus Serv, Boston, MA 02114 USA. RP Dzik, WH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Blood Transfus Serv, Boston, MA 02114 USA. NR 7 TC 18 Z9 18 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PY 2000 VL 78 SU 2 BP 223 EP 226 PG 4 WC Hematology SC Hematology GA 341DV UT WOS:000088576500041 PM 10938957 ER PT J AU Brown, AM Dolan, JW Willi, SM Garvey, WT Argyropoulos, G AF Brown, AM Dolan, JW Willi, SM Garvey, WT Argyropoulos, G TI Endogenous mutations in human uncoupling protein 3 alter its functional properties SO FEBS LETTERS LA English DT Article DE mitochondrion; obesity; membrane potential; UCP3 ID THYROID-HORMONE; GENE-EXPRESSION; OBESITY; ORGANIZATION; MEMBER; FAMILY; TISSUE; LEPTIN; MUSCLE; UCP3 AB Human uncoupling protein 3 (UCP3) is a mitochondrial transmembrane carrier that uncouples oxidative phosphorylation and is a candidate gene for obesity. Expression of native human UCP3 mutations in yeast showed complete loss (R70W), significant reduction (R143X), or no effect (V102I and IVS6+1G>A) on the uncoupling activity of UCP3, It is concluded that certain mutations in UCP3 alter its functional impact on membrane potential (Delta Psi), possibly conferring susceptibility to develop metabolic diseases, (C) 1999 Federation of European Biochemical Societies. C1 Med Univ S Carolina, Dept Med, Div Endocrinol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. RP Med Univ S Carolina, Dept Med, Div Endocrinol, 114 Doughty St, Charleston, SC 29425 USA. EM argyrog@musc.edu FU NHLBI NIH HHS [HL 07260]; NIDDK NIH HHS [DK-47461] NR 26 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 EI 1873-3468 J9 FEBS LETT JI FEBS Lett. PD DEC 31 PY 1999 VL 464 IS 3 BP 189 EP 193 DI 10.1016/S0014-5793(99)01708-1 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 272MR UT WOS:000084654800018 PM 10618503 ER PT J AU Uemura, N Griffin, JD AF Uemura, N Griffin, JD TI The adapter protein Crkl links Cbl to C3G after integrin ligation and enhances cell migration SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; PROTOONCOGENE PRODUCT P120(CBL); HUMAN B-CELLS; TYROSINE PHOSPHORYLATION; HEMATOPOIETIC-CELLS; BCR-ABL; C-CBL; SIGNALING PATHWAY; ANTIGEN RECEPTOR; BCR/ABL ONCOGENE AB Crkl, an SH2-SH3-SH3 adapter protein, is one of the major tyrosine phosphoproteins detected in cells from patients with chronic myelogenous leukemia. Crkl binds to BCR/ABL through its N-terminal SH3 domain and is known to interact with several signaling proteins that have been implicated in integrin signaling, including Cb1, Cas, Hef-1, and paxillin. We have previously shown that overexpression of Crkl enhances adhesion to extracellular matrix proteins through beta(1) integrins. In this study, the effects of Crkl on spontaneous and chemokine-directed migration of the hematopoietic cell line Ba/F3 were examined. Full-length, SH2-, and SH3(N)-domain deletion mutants of Crkl were expressed transiently as fusion proteins with green fluorescent protein. Successfully transfected cells were isolated by fluorescence-activated cell sorting. The ability of these cells to migrate across a fibronectin-coated membrane, either spontaneously or in response to the chemokine stromal-derived factor-1 alpha, was determined. Cells expressing green fluorescent protein alone were mot distinguishable from untransfected or mock transfected Ba/F3 cells. However, Ba/F3 cells overexpressing full-length Crkl were found to have an increase in spontaneous migration of 2.8 +/- 0.6-fold in seven independent assays. The enhancement of migration required both the SH2 domain and the N-terminal SH3 domain. Migration in response to stromal-derived factor-1 alpha was not significantly enhanced by overexpression of Crkl. Overexpression of Crkii also augmented spontaneous migration but to a lesser degree than did Crkl. Because the SH2 domain was required for enhanced migration, we looked for changes in phosphotyrosine containing proteins coprecipitating with Crkl, but not Crkl Delta SH2, after integrin cross-linking. Full-length Crkl, but not Crkl Delta SH2, coprecipitated with a single major tyrosine phosphoprotein with an M-r of approximately 120 kDa, identified as chi. The major Crkl SH3-binding protein in these cells was found to be the guanine nucleotide exchange factor, C3G. Interestingly, overexpression of C3G; also enhanced migration, suggesting that a CbI-Crkl-C3G complex may be involved in migration signaling in Ba/F3 cells. These data suggest that Crkl is involved in signaling pathways that regulate migration, possibly through a complex with Cbl and C3G. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP 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 60 TC 83 Z9 87 U1 1 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 DEC 31 PY 1999 VL 274 IS 53 BP 37525 EP 37532 DI 10.1074/jbc.274.53.37525 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 270GW UT WOS:000084528000004 PM 10608804 ER PT J AU Boyce, JA Mark, EJ Bramson, RT Shannon, DC Youth, B AF Boyce, JA Mark, EJ Bramson, RT Shannon, DC Youth, B TI A four-month-old girl with chronic cyanosis and diffuse pulmonary infiltrates. Cellular interstitial pneumonitis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID LUNG-DISEASE; DOWNS-SYNDROME; CHLOROQUINE TREATMENT; CHILDREN; INFANTS; INFECTION; BIOPSY; CHILDHOOD; DIAGNOSIS C1 Brigham & Womens Hosp, Lab Human Eosinophil & Mast Cell Biol, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Boyce, JA (reprint author), Brigham & Womens Hosp, Lab Human Eosinophil & Mast Cell Biol, Div Rheumatol Immunol & Allergy, 75 Francis St, Boston, MA 02115 USA. NR 51 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 DEC 30 PY 1999 VL 341 IS 27 BP 2075 EP 2083 DI 10.1056/NEJM199912303412708 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 271BR UT WOS:000084573300008 ER PT J AU Huang, XD Cuajungco, MP Atwood, CS Hartshorn, MA Tyndall, JDA Hanson, GR Stokes, KC Leopold, M Multhaup, G Goldstein, LE Scarpa, RC Saunders, AJ Lim, J Moir, RD Glabe, C Bowden, EF Masters, CL Fairlie, DP Tanzi, RE Bush, AI AF Huang, XD Cuajungco, MP Atwood, CS Hartshorn, MA Tyndall, JDA Hanson, GR Stokes, KC Leopold, M Multhaup, G Goldstein, LE Scarpa, RC Saunders, AJ Lim, J Moir, RD Glabe, C Bowden, EF Masters, CL Fairlie, DP Tanzi, RE Bush, AI TI Cu(II) potentiation of Alzheimer A beta neurotoxicity - Correlation with cell-free hydrogen peroxide production and metal reduction SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CEREBROSPINAL-FLUID; LIPID-PEROXIDATION; OXIDATIVE STRESS; SENILE PLAQUES; IN-VIVO; DISEASE; PROTEIN; TOXICITY; PRECURSOR; PEPTIDE AB Oxidative stress markers as well as high concentrations of copper are found in the vicinity of A beta amyloid deposits in Alzheimer's disease. The neurotoxicity of A beta in cell culture has been linked to H2O2 generation by an unknown mechanism. We now report that Cu(II) markedly potentiates the neurotoxicity exhibited by A beta in cell culture. The potentiation of toxicity is greatest for A beta 1-42 > A beta 1-40 >> mouse/rat A beta 1-40, corresponding to their relative capacities to reduce Cu(II) to Cu(I), form H2O2 in cell-free assays and to exhibit amyloid pathology. The copper complex of A beta 1-42 has a highly positive formal reduction potential (approximate to+500-550 mV versus Ag/AgCl) characteristic of strongly reducing cupro-proteins. These findings suggest that certain redox active metal ions may be important in exacerbating and perhaps facilitating A beta-mediated oxidative damage in Alzheimer's disease. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Oxidat Biol,Genet & Aging Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Univ Heidelberg, ZMBH, Ctr Mol Biol, D-69120 Heidelberg, Germany. N Carolina State Univ, Dept Chem, Raleigh, NC 27695 USA. Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92717 USA. Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. Mental Hlth Res Inst Victoria, Neuropathol Lab, Parkville, Vic 3052, Australia. Univ Queensland, Ctr Drug Design & Dev, Brisbane, Qld 4072, Australia. Univ Queensland, Ctr Magnet Resonance, Brisbane, Qld 4072, Australia. RP Huang, XD (reprint author), Massachusetts Gen Hosp E, Lab Oxidat Biol, Genet & Aging Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. RI tyndall, joel/C-2803-2008; Hanson, Graeme/C-3940-2008; Cuajungco, Math/B-2647-2008; Fairlie, David/F-8865-2014; Bush, Ashley/A-1186-2007 OI Hanson, Graeme/0000-0003-0306-4360; Cuajungco, Math/0000-0003-0749-9564; Bush, Ashley/0000-0001-8259-9069 NR 40 TC 583 Z9 603 U1 2 U2 60 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 24 PY 1999 VL 274 IS 52 BP 37111 EP 37116 DI 10.1074/jbc.274.52.37111 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 267WR UT WOS:000084382700042 PM 10601271 ER PT J AU Balendran, A Currie, R Armstrong, CG Avruch, J Alessi, DR AF Balendran, A Currie, R Armstrong, CG Avruch, J Alessi, DR TI Evidence that 3-phosphoinositide-dependent protein kinase-1 mediates phosphorylation of p70 56 kinase in vivo at Thr-412 as well as Thr-252 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID S6 KINASE; PHOSPHOINOSITIDE 3-KINASE; MAPKAP KINASE-1; B-ALPHA; IN-VIVO; ACTIVATION; MECHANISM; P70(S6K); INSULIN; PDK1 AB Protein kinase B and p70 S6 kinase are members of the cyclic AMP-dependent/cyclic GMP-dependent/protein kinase C subfamily of protein kinases and are activated by a phosphatidylinositol 3-kinase-dependent pathway when cells are stimulated with insulin or growth factors. Both of these kinases are activated in cells by phosphorylation of a conserved residue in the kinase domain (Thr-308 of protein kinase B (PKB) and Thr-252 of p70 S6 kinase) and another conserved residue located C-terminal to the kinase domain (Ser-473 of PKB and Thr-412 of p70 S6 kinase). Thr-308 of PKB alpha and Thr-252 of p70 S6 kinase are phosphorylated by 3-phosphoinositide-dependent protein kinase-1 (PDK1) in vitro. Recent work has shown that PDK1 interacts with a region of protein kinase C-related kinase-2, termed the PDK1 interacting fragment (PIF). Interaction with PIF converts PDK1 from a form that phosphorylates PKB at Thr-308 alone to a species capable of phosphorylating Ser-473 as well as Thr-308. This suggests that PDK1 may be the enzyme that phosphorylates both residues in vivo. Here we demonstrate that PDK1 is capable of phosphorylating p70 S6 kinase at Thr-412 in vitro. We study the effect of PIF on the ability of PDK1 to phosphorylate p70 S6 kinase. Surprisingly, we find that PDK1 bound to PIF is no longer able to interact with or phosphorylate p70 S6 kinase in vitro at either Thr-252 or Thr-412, The expression of PIF in cells prevents insulin-like growth factor 1 from inducing the activation of the p70 S6 kinase and its phosphorylation at Thr-412, Overexpression of PDK1 in cells induces the phosphorylation of p70 S6 kinase at Thr-412 in unstimulated cells, and a catalytically inactive mutant of PDK1 prevents the phosphorylation of p70 S6K at Thr-412 in insulin-like growth factor 1-stimulated cells. These observations indicate that PDK1 regulates the activation of p70 S6 kinase and provides evidence that PDK1 mediates the phosphorylation of p70 S6 kinase at Thr-412. C1 Univ Dundee, Dept Biochem, MRC, Prot Phosphorylat Unit, Dundee DD1 5EH, Scotland. Univ Dundee, Dept Biochem, Div Signal Transduct Therapy Unit, Dundee DD1 5EH, Scotland. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Diabet Unit, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv, Boston, MA 02129 USA. RP Alessi, DR (reprint author), Univ Dundee, Dept Biochem, MRC, Prot Phosphorylat Unit, Dundee DD1 5EH, Scotland. NR 37 TC 110 Z9 110 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 24 PY 1999 VL 274 IS 52 BP 37400 EP 37406 DI 10.1074/jbc.274.52.37400 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 267WR UT WOS:000084382700082 PM 10601311 ER PT J AU Bell, DW Varley, JM Szydlo, TE Kang, DH Wahrer, DCR Shannon, KE Lubratovich, M Verselis, SJ Isselbacher, KJ Fraumeni, JF Birch, JM Li, FP Garber, JE Haber, DA AF Bell, DW Varley, JM Szydlo, TE Kang, DH Wahrer, DCR Shannon, KE Lubratovich, M Verselis, SJ Isselbacher, KJ Fraumeni, JF Birch, JM Li, FP Garber, JE Haber, DA TI Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome SO SCIENCE LA English DT Article ID DNA-DAMAGE CHECKPOINT; FISSION YEAST; PROTEIN-KINASE; HUMAN CANCERS; CELL-CYCLE; S-PHASE; ANTICANCER AGENTS; MISMATCH REPAIR; P53 MUTATIONS; PATHWAY AB The hCHK2 gene encodes the human homolog of the yeast Cds1 and Rad53 G(2) checkpoint kinases, whose activation in response to DNA damage prevents cellular entry into mitosis. Here, it is shown that heterozygous germ Line mutations in hCHK2 occur in Li-Fraumeni syndrome, a highly penetrant Familiar cancer phenotype usually associated with inherited mutations in the TP53 gene. These observations suggest that hCHK2 is a tumor suppressor gene conferring predisposition to sarcoma, breast cancer, and brain tumors, and they also provide a link between the central role of p53 inactivation in human cancer and the well-defined G(2) checkpoint in yeast. C1 Massachusetts Gen Hosp, Ctr Canc Risk Anal, Charlestown, MA 02139 USA. Harvard Univ, Sch Med, Charlestown, MA 02139 USA. Paterson Inst Canc Res, Canc Res Campaign, Dept Canc Genet, Manchester M20 4BX, Lancs, England. Harvard Univ, Sch Med, Boston, MA 02114 USA. Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02114 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Royal Manchester Childrens Hosp, Canc Res Campaign, Paediat & Familial Canc Res Grp, Manchester M27 1HA, Lancs, England. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc Risk Anal, Bldg 149, Charlestown, MA 02139 USA. NR 55 TC 612 Z9 624 U1 1 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 DEC 24 PY 1999 VL 286 IS 5449 BP 2528 EP 2531 DI 10.1126/science.286.5449.2528 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 268RQ UT WOS:000084429700056 PM 10617473 ER PT J AU Schwartz, MW Kahn, SE AF Schwartz, MW Kahn, SE TI Diabetes - Insulin resistance and obesity SO NATURE LA English DT Editorial Material ID PPAR-GAMMA; SENSITIVITY C1 Univ Washington, Harborview Med Ctr, Dept Med, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Schwartz, MW (reprint author), Univ Washington, Harborview Med Ctr, Dept Med, Seattle, WA 98108 USA. RI Schwartz, Michael/H-9950-2012 NR 10 TC 26 Z9 26 U1 0 U2 4 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 23 PY 1999 VL 402 IS 6764 BP 860 EP 861 DI 10.1038/47209 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 269ML UT WOS:000084482000024 PM 10622250 ER PT J AU St Peter, RF Reed, MC Kemper, P Blumenthal, D AF St Peter, RF Reed, MC Kemper, P Blumenthal, D TI Changes in the scope of care provided by primary care physicians SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 14th Annual Meeting of the Association-of-Health-Services-Research CY JUN 15-17, 1997 CL CHICAGO, ILLINOIS SP Assoc Hlth Serv Res ID HEALTH MAINTENANCE ORGANIZATIONS; FINANCIAL INCENTIVES; MANAGED-CARE; CONSULTATION AB Background: Strategies to control medical costs and improve the quality of care often translate into decisions affecting the range of services primary care physicians provide to patients, which patients are referred for specialty care, and the points in disease processes at which referrals are made. This study focused on physicians' assessments of changes in the scope of care provided by primary care physicians and their assessments of the appropriateness of the scope of the care that primary care physicians are expected to provide. Methods: We analyzed data from the 1996-1997 Community Tracking Study Physician Survey. Telephone interviews were conducted with 12,385 physicians (reflecting a response rate of 65 percent) who were drawn from a representative random sample of physicians providing direct patient care in the continental United States and not employed by the federal government. The analysis was based on responses from the 7015 primary care physicians and 5092 specialists who had been in practice for at least two years. Results: Thirty percent of the primary care physicians and 50 percent of the specialists reported that the scope of care provided by primary care physicians had increased during the previous two years. Twenty-four percent of the primary care physicians and 38 percent of the specialists reported that the scope of care expected to be provided by primary care physicians was greater than it should be. According to multivariate analysis, primary care physicians other than general or family practitioners (i.e., pediatricians and general internists), those who were in one- or two-physician practices, those who received revenues from capitation, and those who served as gatekeepers for their patients' care were significantly more likely to report that the scope of care they were expected to provide was greater than it should be. Conclusions: The finding that nearly one in four primary care physicians reported that the scope of care they were expected to provide was greater than it should be arouses concern about the potential impact of changes in the delivery of health care. The associations we found between financial and administrative aspects of managed care and physicians' concern about the scope of care they provide to their patients deserve careful consideration. (N Engl J Med 1999;341:1980-5.) (C)1999, Massachusetts Medical Society. C1 Kansas Hlth Inst, Topeka, KS 66612 USA. Ctr Study Hlth Syst Change, Washington, DC USA. Massachusetts Gen Hosp, Partners Healthcare Syst, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP St Peter, RF (reprint author), Kansas Hlth Inst, 100 SE 9th St,3rd Fl, Topeka, KS 66612 USA. NR 20 TC 83 Z9 85 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 23 PY 1999 VL 341 IS 26 BP 1980 EP 1985 DI 10.1056/NEJM199912233412606 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 268DQ UT WOS:000084399400006 PM 10607816 ER PT J AU Kahn, J Lagakos, S Wulfsohn, M Cherng, D Miller, M Cherrington, J Hardy, D Beall, G Cooper, R Murphy, R Basgoz, N Ng, E Deeks, S Winslow, D Toole, JJ Coakley, D AF Kahn, J Lagakos, S Wulfsohn, M Cherng, D Miller, M Cherrington, J Hardy, D Beall, G Cooper, R Murphy, R Basgoz, N Ng, E Deeks, S Winslow, D Toole, JJ Coakley, D CA GS-408 Study Team TI Efficacy and safety of adefovir dipivoxil with antiretroviral therapy - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIGH-LEVEL RESISTANCE; HIV-INFECTED ADULTS; CD4 CELL COUNTS; COMBINATION THERAPY; ANTIVIRAL ACTIVITY; CUBIC MILLIMETER; ZIDOVUDINE; ANALOGS; LYMPHOCYTES AB Context Adefovir dipivoxil is a nucleotide analog that has demonstrated effective antiretroviral activity against human immunodeficiency virus (HIV) with once-daily administration. Objective To determine if adefovir confers antiretroviral or immunologic benefit when added to stable antiretroviral therapy. Design Multicenter, 24-week, randomized, double-blind, placebo-controlled study. Enrollment was conducted from June 3, 1996, through May 6, 1997. Setting Thirty-three US HIV treatment centers. Participants Of 1171 patients screened, 442 patients infected with HIV receiving stable antiretroviral therapy for at least 8 weeks with plasma HIV RNA greater than 2500 copies/mL and CD4(+) cell count above 0.20 x 10(9)/L were randomized. Intervention Patients were randomized to receive either a single 120-mg/d dose of adefovir dipivoxil (n = 219) or an indistinguishable placebo (n = 223), All patients received L-carnitine, 500 mg/d, Open-label adefovir was offered after 24 weeks and was continued until the end of the study. Main Outcome Measures Changes in HIV RNA from baseline, based on area under the curve and CD4(+) cell levels, adverse events, and effect of baseline genotypic resistance on response to adefovir, Results Patients assigned to adefovir demonstrated a 0.4-log(10) decline from baseline in HIV RNA compared with no change in the placebo group (P < .001), which continued through 48 weeks. CD4(+) cell counts did not change. During the initial 24 weeks, elevated hepatic enzyme levels (P < .001), gastrointestinal tract complaints (P < .001), and weight loss (P < .001) were associated with use of adefovir, Between 24 weeks and 48 weeks elevations in serum creatinine occurred in 60% of patients, usually returning to baseline after discontinuation of adefovir. Patients with lamivudine or lamivudine and zidovudine resistance mutations demonstrated anti-HIV effects with adefovir(P less than or equal to.01 vs placebo group). Conclusions This study suggests that once-daily adefovir therapy reduces HIV RNA and is active against isolates resistant to lamivudine or lamivudine and zidovudine, Nephrotoxicity occurred when treatment extended beyond 24 weeks but was reversible. C1 Gilead Sci Inc, Foster City, CA 94404 USA. Pacific Oak Res, Beverly Hills, CA USA. Univ Calif Los Angeles, Harbor Med Ctr, Torrance, CA 90509 USA. Kraus Med Partners, Los Angeles, CA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Northwestern Univ, Sch Med, Chicago, IL USA. Univ Calif San Francisco, San Francisco Gen Hosp, Posit Hlth Program, San Francisco, CA 94110 USA. RP Kahn, J (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Posit Hlth Program, 995 Potrero Ave, San Francisco, CA 94110 USA. OI Murphy, Robert/0000-0003-3936-2052 NR 32 TC 141 Z9 151 U1 0 U2 4 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 DEC 22 PY 1999 VL 282 IS 24 BP 2305 EP 2312 DI 10.1001/jama.282.24.2305 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 265TK UT WOS:000084261700023 PM 10612317 ER PT J AU Braddock, CH Edwards, KA Hasenberg, NM Laidley, TL Levinson, W AF Braddock, CH Edwards, KA Hasenberg, NM Laidley, TL Levinson, W TI Informed decision making in outpatient practice - Time to get back to basics SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CLINICAL DECISIONS; PRIMARY-CARE; CONSENT; DISCLOSURE; PHYSICIANS AB Context Many clinicians have called for an increased emphasis on the patient's role in clinical decision making. However, little is known about the extent to which physicians foster patient involvement in decision making, particularly in routine office practice. Objective To characterize the nature and completeness of informed decision making in routine office visits of both primary care physicians and surgeons. Design Cross-sectional descriptive evaluation of audiotaped office visits during 1993, Setting and Participants A total of 1057 encounters among 59 primary care physicians (general internists and family practitioners) and 65 general and orthopedic surgeons; 2 to 12 patients were recruited from each physician's community-based private office. Main Outcome Measures Analysis of audiotaped patient-physician discussions for elements of informed decision making, using criteria that varied with the level of decision complexity: basic (eg, laboratory test), intermediate (eg, new medication), or complex (eg, procedure), Criteria for basic decisions included discussion of the nature of the decision and asking the patient to voice a preference; other categories had criteria that were progressively more stringent, Results The 1057 audiotaped encounters contained 3552 clinical decisions. Overall, 9.0% of decisions met our definition of completeness for informed decision making, Basic decisions were most often completely informed (17.2%), while no intermediate decisions were completely informed, and only 1 (0.5%) complex decision was completely informed. Among the elements of informed decision making, discussion of the nature of the intervention occurred most frequently (71%) and assessment of patient understanding least frequently (1.5%). Conclusions Informed decision making among this group of primary care physicians and surgeons was often incomplete. This deficit was present even when criteria for informed decision making were tailored to expect less extensive discussion for decisions of lower complexity. These findings signal the need for efforts to encourage informed decision making in clinical practice. C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Med Hist & Eth, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Ctr Educ & Dev, Hlth Serv Res & Dev Field Program, Seattle, WA 98108 USA. Cascade Physicians, Portland, OR USA. Univ Chicago, Div Gen Internal Med & Geriatr, Chicago, IL 60637 USA. RP Braddock, CH (reprint author), VA Puget Sound Hlth Care Syst, Ctr Educ & Dev, Hlth Serv Res & Dev Field Program, 1660 S Columbian Way, Seattle, WA 98108 USA. FU AHRQ HHS [R01-HS0728 9] NR 26 TC 642 Z9 648 U1 4 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 DEC 22 PY 1999 VL 282 IS 24 BP 2313 EP 2320 DI 10.1001/jama.282.24.2313 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 265TK UT WOS:000084261700024 PM 10612318 ER PT J AU Barry, MJ AF Barry, MJ TI Involving patients in medical decisions - How can physicians do better? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Gen Med Unit, Boston, MA 02114 USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Gen Med Unit, 50 Staniford St,9th Floor, Boston, MA 02114 USA. NR 9 TC 58 Z9 58 U1 2 U2 3 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 DEC 22 PY 1999 VL 282 IS 24 BP 2356 EP 2357 DI 10.1001/jama.282.24.2356 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 265TK UT WOS:000084261700032 PM 10612326 ER PT J AU Go, AS Hylek, EM Borowsky, LH Phillips, KA Selby, JV Singer, DE AF Go, AS Hylek, EM Borowsky, LH Phillips, KA Selby, JV Singer, DE TI Warfarin use among ambulatory patients with nonvalvular atrial fibrillation: The AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID STROKE PREVENTION; PHYSICIAN ATTITUDES; NATIONAL PATTERNS; COMMUNITY; PROPHYLAXIS; PREVALENCE; HOSPITALS; ASPIRIN AB Background: Warfarin dramatically reduces the risk for ischemic stroke in nonvalvular atrial fibrillation, but its use among ambulatory patients with atrial fibrillation has not been widely studied. Objective: To assess the rates and predictors of warfarin use in ambulatory patients with nonvalvular atrial fibrillation. Design: Cross-sectional study. Setting: Large health maintenance organization. Patients: 13428 patients with a confirmed ambulatory diagnosis of nonvalvular atrial fibrillation and known warfarin status between 1 July 1996 and 31 December 1997. Measurements: Data from automated pharmacy, laboratory, and clinical-administrative databases were used to determine the prevalence and determinants of warfarin use in the 3 months before or after the identified diagnosis of atrial fibrillation. Results: Of 11082 patients with nonvalvular atrial fibrillation and no known contraindications, 55% received warfarin. Warfarin use was substantially lower in patients who were younger than 55 years of age (44.3%) and those who were 85 years of age or older (35.4%). Only 59.3% of patients with one or more risk factors for stroke and no contraindications were receiving warfarin. Among a subset of "ideal" candidates to receive warfarin (persons 65 to 74 years of age who had no contraindications and had previous stroke, hypertension, or both), 62.1% had evidence of warfarin use. Among our entire cohort, the strongest predictors of receiving warfarin were previous stroke (adjusted odds ratio, 2.55 [95% CI, 2.23 to 2.92]), heart failure (odds ratio, 1.63 [CI, 1.51 to 1.77]), previous intracranial hemorrhage (odds ratio, 0.33 [CI, 0.21 to 0.52]), age 85 years or older (odds ratio, 0.35 [CI, 0.31 to 0.40]), and previous gastrointestinal hemorrhage (odds ratio, 0.47 [CI, 0.40 to 0.57]). Conclusions: In a large, contemporary cohort of ambulatory patients with atrial fibrillation who received care within a health maintenance organization, warfarin use was considerably higher than in other reported studies. Although the reasons why physicians did not prescribe warfarin could not be elucidated, many apparently eligible patients with atrial fibrillation and at least one additional risk factor for stroke, especially hypertension, did not receive anticoagulation. Interventions are needed to increase the use of warfarin for stroke prevention among appropriate candidates. C1 Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Go, AS (reprint author), Kaiser Permanente Med Care Program, Div Res, 3505 Broadway St,12th Floor, Oakland, CA 94611 USA. FU NIA NIH HHS [AG15478] NR 48 TC 373 Z9 381 U1 1 U2 10 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 21 PY 1999 VL 131 IS 12 BP 927 EP + PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 267TB UT WOS:000084374400003 PM 10610643 ER PT J AU McAlister, FA Clark, HD van Walraven, C Straus, SE Lawson, FME Moher, D Mulrow, CD AF McAlister, FA Clark, HD van Walraven, C Straus, SE Lawson, FME Moher, D Mulrow, CD TI The medical review article revisited: Has the science improved? SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID RANDOMIZED CONTROL TRIALS; METAANALYSES; QUALITY; BIAS AB Background: The validity of a review depends on its methodologic quality. Objective: To determine the methodologic quality of recently published review articles. Design: Critical appraisal. Setting: All reviews of clinical topics published in six general medical journals in 1996. Measurements: Explicit criteria that have been published and validated were used. Results: Of 158 review articles, only 2 satisfied all 10 methodologic criteria (median number of criteria satisfied, 1), Less than a quarter of the articles described how evidence was identified, evaluated, or integrated; 34% addressed a focused clinical question; and 39% identified gaps in existing knowledge. Of the 111 reviews that made treatment recommendations, 48% provided an estimate of the magnitude of potential benefits (and 34%, the potential adverse effects) of the treatment options, 45% cited randomized clinical trials to support their recommendations, and only 6% made any reference to costs. Conclusions: The methodologic quality of clinical review articles is highly variable, and many of these articles do not specify systematic methods. C1 Univ Oxford, Oxford, England. Univ Alberta, Edmonton, AB, Canada. Univ Ottawa, Loeb Hlth Res Inst, Ottawa, ON, Canada. Childrens Hosp Eastern Ontario, Res Inst, Thomas C Chalmers Ctr Systemat Reviews, Ottawa, ON K1H 8L1, Canada. Univ Toronto, Toronto, ON, Canada. Audie L Murphy Vet Affairs Hosp, San Antonio, TX USA. RP McAlister, FA (reprint author), Univ Alberta Hosp, 2E3-24 WMC,8440 112 St, Edmonton, AB T6G 2R7, Canada. RI McAlister, Finlay/C-4151-2013; OI Moher , David /0000-0003-2434-4206 NR 20 TC 87 Z9 89 U1 0 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 21 PY 1999 VL 131 IS 12 BP 947 EP 951 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 267TB UT WOS:000084374400006 PM 10610646 ER PT J AU Streit, M Riccardi, L Velasco, P Brown, LF Hawighorst, T Bornstein, P Detmar, M AF Streit, M Riccardi, L Velasco, P Brown, LF Hawighorst, T Bornstein, P Detmar, M TI Thrombospondin-2: A potent endogenous inhibitor of tumor growth and angiogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ENDOTHELIAL-CELLS; PROTEIN THROMBOSPONDIN-2; EXPRESSION; MOUSE; GENE; TISSUES; MICE; RECEPTORS; ADHESION; PEPTIDES AB Recent evidence suggests a potential role for thrombospondin-2 (TSP-2), a matricellular glycoprotein, in the regulation of primary angiogenesis. To directly examine the biological effect of TSP-2 expression on tumor growth and angiogenesis, human A431 squamous cell carcinoma cells, which do not express TSP-2, were stably transfected with a murine TSP-2 expression vector or with vector alone. A431 cells expressing TSP-2 did not show an altered growth rate, colony-forming ability, or susceptibility to induction of apoptosis in vitro. However, injection of TSP-2-transfected clones into the dermis of nude mice resulted in pronounced inhibition of tumor growth that was significantly stronger than the inhibition observed in A431 clones stably transfected with a thrombospondin-1 (TSP-1) expression vector, and combined overexpression of TSP-1 and TSP-2 completely prevented tumor formation. Extensive areas of necrosis were observed in TSP-2-expressing tumors, and both the density and the size of tumor vessels were significantly reduced, although tumor cell expression of the major tumor angiogenesis factor, vascular endothelial growth factor, was maintained at high levels. These findings establish TSP-2 as a potent endogenous inhibitor of tumor growth and angiogenesis. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Dermatol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Univ Washington, Dept Biochem, Seattle, WA 98195 USA. RP Detmar, M (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA69184, R01 CA069184]; NIAMS NIH HHS [AR45418, R01 AR045418] NR 41 TC 203 Z9 211 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 21 PY 1999 VL 96 IS 26 BP 14888 EP 14893 DI 10.1073/pnas.96.26.14888 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 267TM UT WOS:000084375400041 PM 10611308 ER PT J AU Zhu, JH Tseng, YH Kantor, JD Rhodes, CJ Zetter, BR Moyers, JS Kahn, CR AF Zhu, JH Tseng, YH Kantor, JD Rhodes, CJ Zetter, BR Moyers, JS Kahn, CR TI Interaction of the Ras-related protein associated with diabetes Rad and the putative tumor metastasis suppressor NM23 provides a novel mechanism of GTPase regulation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NUCLEOSIDE-DIPHOSPHATE KINASE; SITE-DIRECTED MUTAGENESIS; BINDING PROTEINS; SACCHAROMYCES-CEREVISIAE; NUCLEOTIDE-BINDING; ACTIVATING PROTEIN; CELLS; DROSOPHILA; GENE; MEMBER AB Rad is the prototypic member of a new class of Ras-related GTPases, Purification of the GTPase-activating protein (CAP) for Rad revealed nm23, a putative tumor metastasis suppressor and a development gene in Drosophila. Antibodies against nm23 depleted Rad-CAP activity from human skeletal muscle cytosol, and bacterially expressed nm23 reconstituted the activity. The GAP activity of nm23 was specific for Rad, was absent with the S105N putative dominant negative mutant of Rad, and was reduced with mutations of nm23, In the presence of ATP, GDP Rad was also reconverted to CTP Rad by the nucleoside diphosphate (NDP) kinase activity of nm23. Simultaneously, Rad regulated nm23 by enhancing its NDP kinase activity and decreasing its autophosphorylation. Melanoma cells transfected with wild-type Rad, but not the S105N-Rad, showed enhanced DNA synthesis in response to serum; this effect was lost with coexpression of nm23, Thus, the interaction of nm23 and Rad provides a potential novel mechanism for bidirectional, bimolecular regulation in which nm23 stimulates both CTP hydrolysis and GTP loading of Rad whereas Rad regulates activity of nm23. This interaction may play important roles in the effects of Rad on glucose metabolism and the effects of nm23 on tumor metastasis and developmental regulation. C1 Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Res Div, Boston, MA 02215 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Res Div, 1 Joslin Pl, Boston, MA 02215 USA. FU NCI NIH HHS [R01 CA 37393, R01 CA037393]; NIDDK NIH HHS [F32 DK009193, P30 DK036836, R01 DK 47919, R01 DK045935, R01 DK047919, T32 DK007260, DK 45935] NR 45 TC 95 Z9 97 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 21 PY 1999 VL 96 IS 26 BP 14911 EP 14918 DI 10.1073/pnas.96.26.14911 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 267TM UT WOS:000084375400045 PM 10611312 ER PT J AU Inoue, G Cheatham, B Kahn, CR AF Inoue, G Cheatham, B Kahn, CR TI Development of an in vitro reconstitution assay for glucose transporter 4 translocation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INSULIN-STIMULATED TRANSLOCATION; DEPENDENT DIABETES-MELLITUS; RAT ADIPOSE-CELLS; 3T3-L1 ADIPOCYTES; PLASMA-MEMBRANE; SKELETAL-MUSCLE; PHOSPHATIDYLINOSITOL 3-KINASE; HEXOSE-TRANSPORT; SNAP RECEPTORS; MAST-CELLS AB In an attempt to define the mechanism of insulin-regulated glucose transporter 4 (Glut4) translocation, we have developed an in vitro reconstitution assay. Donor membranes from 3T3-L1 adipocytes transfected with mycGlut4 were incubated with plasma membrane (PM) from nontransfected 3T3-L1 cells, and the association was assessed by using two types of centrifugation assays. Association of mycGlut4 vesicles derived from donor membranes with the PM was concentration-, temperature-, time-, and Ca2+-dependent but ATP-independent. Addition of a syntaxin 4 fusion protein produced a biphasic response, increasing association at low concentration and inhibiting association at higher concentrations. PM from insulin-stimulated cells showed an enhanced association as compared with those from untreated cells, Use of donor membranes from insulin-stimulated cells further enhanced the association and also enhanced association to the PM from isolated rat adipocytes. Addition of cytosol, GTP, or guanosine 5'-[gamma-thio]triphosphate decreased the association, In summary, insulin-induced Glut4 translocation can be reconstituted in vitro to a limited extent by using isolated membranes. This association appears to involve protein-protein interactions among the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex proteins, Finally, the ability of insulin to enhance association depends on insulin-induced changes in the PM and, to a lesser extent, in the donor membranes. C1 Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK 31036, DK 51668, P30 DK036836, 5 P30 DK 36836, R01 DK031036, R37 DK031036] NR 45 TC 13 Z9 13 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 21 PY 1999 VL 96 IS 26 BP 14919 EP 14924 DI 10.1073/pnas.96.26.14919 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 267TM UT WOS:000084375400046 PM 10611313 ER PT J AU Santambrogio, L Sato, AK Carven, GJ Belyanskaya, SL Strominger, JL Stern, LJ AF Santambrogio, L Sato, AK Carven, GJ Belyanskaya, SL Strominger, JL Stern, LJ TI Extracellular antigen processing and presentation by immature dendritic cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE class II MHC; antigen presentation; HLA-DM; H-2M; invariant chain ID CLASS-II COMPARTMENT; HLA-DR MOLECULES; INVARIANT CHAIN; MHC MOLECULES; DEVELOPMENTAL REGULATION; MATURATION; COMPLEXES; BINDING; RECEPTOR; PATHWAY AB In antigen presentation to CD4(+) T cells, proteins are degraded to peptide fragments and loaded onto class II MHC molecules in a process involving the peptide exchange factors H-2M (murine) or HLA-DM (human), In many antigen-presenting cells these processes occur in intracellular endosomal compartments, where peptides are generated and loaded onto class II MHC proteins for subsequent transport to the surface and presentation to T cells. Here, we provide evidence for an additional antigen-processing pathway in immature dendritic cells (DC), Immature DC express at the cell surface empty or peptide-receptive class II MHC molecules, as well as H-2M or HLA-DM. Secreted DC proteases act extracellularly to process intact proteins into antigenic peptides. Peptides produced by such activity are efficiently loaded onto cell surface class II MHC molecules, Together these elements comprise an unusual extracellular presentation pathway in which antigen processing and peptide loading can occur entirely outside of the cell. C1 Dana Farber Canc Inst, Dept Canc Immunol AIDS, Boston, MA 02115 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. MIT, Dept Chem, Cambridge, MA 02139 USA. RP Santambrogio, L (reprint author), Dana Farber Canc Inst, Dept Canc Immunol AIDS, Boston, MA 02115 USA. FU NCI NIH HHS [R35-CA47554]; NIAID NIH HHS [R01 AI038996, R01-AI38996] NR 39 TC 139 Z9 142 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 21 PY 1999 VL 96 IS 26 BP 15056 EP 15061 DI 10.1073/pnas.96.26.15056 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 267TM UT WOS:000084375400070 PM 10611337 ER PT J AU Goldstein, G Allen, DN Weiner, CL AF Goldstein, G Allen, DN Weiner, CL TI Lateralized brain dysfunction in schizophrenia: a comparison with patients with lateralized structural lesions SO SCHIZOPHRENIA RESEARCH LA English DT Article DE cognitive function; laterality; neuropsychology AB A comparison was made among participants with schizophrenia and those with structural lateralized or diffuse brain damage in order to determine the extent to which the cognitive profile of the schizophrenia sample resembled the profiles obtained from patients with left-hemisphere, right-hemisphere, and diffuse brain damage. The Halstead-Reitan Neuropsychological Battery was used as the testing procedure. The data were subjected to discriminant analysis in order to obtain frequencies of predicted classification of the participants with schizophrenia into schizophrenia, left-hemisphere, right-hemisphere, and diffuse groups. Half of the participants with schizophrenia were classified into the schizophrenia group. The other half was evenly distributed across the left-hemisphere, right-hemisphere, and diffuse brain damage groups. There was not a disproportionately large number of participants classified into the left-hemisphere group. Comparisons among these four predicted groups were accomplished for each of the Halstead-Reitan Battery measures using one-way analysis of variance. The comparison of the subtest scores among the predicted groups indicated that the patients classified into the left-hemisphere group were characterized by a pattern of language dysfunction thought to be developmental in nature, and an abnormal lack of asymmetry in tapping speed favoring the right hand. (C) 1999 Elsevier Science B.V. All rights reserved. C1 VA Pittsburgh Healthcare Syst, Highland Dr Div, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Pittsburgh, PA 15213 USA. RP Goldstein, G (reprint author), VA Pittsburgh Healthcare Syst, Highland Dr Div, 7180 Highland Dr, Pittsburgh, PA 15206 USA. NR 23 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC 21 PY 1999 VL 40 IS 3 BP 179 EP 187 DI 10.1016/S0920-9964(99)00050-X PG 9 WC Psychiatry SC Psychiatry GA 261RP UT WOS:000084023000002 PM 10638856 ER PT J AU Keire, DA Solomon, TE Reeve, JR AF Keire, DA Solomon, TE Reeve, JR TI Identical primary sequence but different conformations of the bioactive regions of canine CCK-8 and CCK-58 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID FLUORESCENCE-TRANSFER MEASUREMENTS; H-1-NMR SPECTROSCOPY; CHOLECYSTOKININ; FRAGMENTS; BRAIN; BLOOD AB The C-terminal bioactive regions of CCK-8 and CCK-58 are identical (DY*MGWMDF-NH2, Y* denotes a sulfated tyrosine residue), but these peptides have different patterns of bioactivity. Specifically, CCK-58 binds more avidly to the CCKA receptor while CCK-8 is more potent for stimulation of amylase secretion from pancreatic acini. We postulate that these seemingly contradictory observations reflect a stable conformational change in CCK-58 that enhances binding, but diminishes activation of second messenger. We used CD and NMR spectra to evaluate postulated structural differences between CCK-8 and the carboxy-terminus of synthetic CCK-58. The CD spectra indicate the presence of turns in CCK-8 but a mixture of helical and random coil structures for CCK-58. Comparisons of partial NMR chemical shift assignments of CCK-58 and full assignments for CCK-8 also indicate differences in the backbone conformations for these residues. The data support the hypothesis that these peptides have different, stable, carboxy-terminal structures that may influence bioactivity. (C) 1999 Academic Press. C1 Greater Los Angeles Vet Hlth Care Syst, CURE, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Div Digest Dis, Los Angeles, CA 90023 USA. RP Reeve, JR (reprint author), Greater Los Angeles Vet Hlth Care Syst, CURE, Digest Dis Res Ctr, Room 115,Bldg 115, Los Angeles, CA 90073 USA. NR 20 TC 15 Z9 15 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 20 PY 1999 VL 266 IS 2 BP 400 EP 404 DI 10.1006/bbrc.1999.1825 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 271FG UT WOS:000084583100021 PM 10600515 ER PT J AU Tesch, GH Maifert, S Schwarting, A Rollins, BJ Kelley, VR AF Tesch, GH Maifert, S Schwarting, A Rollins, BJ Kelley, VR TI Monocyte chemoattractant protein 1-dependent leukocytic infiltrates are responsible for autoimmune disease in MRL-Fas(lpr) mice SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE mouse; kidney; lung; chemokine; gene disruption ID CENTRAL-NERVOUS-SYSTEM; T-CELL ACTIVATION; IFN-GAMMA; ALLERGIC INFLAMMATION; CC CHEMOKINES; GENE-TRANSFER; MRL/LPR MICE; LPR/LPR MICE; RENAL INJURY; EXPRESSION AB Infiltrating leukocytes may be responsible far autoimmune disease. We hypothesized that the chemokine monocyte chemoattractant protein (MCP)-1 recruits macrophages and T cells into tissues that, in turn, are required for autoimmune disease. Using the MRL-Fas(lpr) strain with spontaneous, fatal autoimmune disease, we constructed MCP-1-deficient MRL-Fas(lpr) mice. In MCP-1-intact MRL-Fas(lpr) mice, macrophages and T cells accumulate at sites (kidney tubules, glomeruli, pulmonary bronchioli, lymph nodes) in proportion to MCP-1 expression. Deleting MCP-1 dramatically reduces macrophage and T cell recruitment but not proliferation, protects from kidney, lung, skin, and lymph node pathology, reduces proteinuria, and prolongs survival. Notably, serum immunoglobulin (Ig) isotypes and kidney Ig/C3 deposits are not diminished in MCP-1-deficient MRL-Fas(lpr) mice, highlighting the requirement for MCP-1-dependent leukocyte recruitment to initiate autoimmune disease. However, MCP-1-deficient mice are not completely protected from leukocytic invasion. T cells surrounding vessels with meager MCP-1 expression remain. In addition, downstream effector cytokines/chemokines are decreased in MCP-1-deficient mice, perhaps reflecting a reduction of cytokine-expressing leukocytes. Thus, MCP-1 promotes MRL-Fas(lpr) autoimmune disease through macrophage and T cell recruitment, amplified by increasing local cytokines/chemokines. We suggest that MCP-1 is a principal therapeutic target with which to combat autoimmune diseases. C1 Brigham & Womens Hosp, Div Renal, Lab Mol Autoimmune Dis, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Kelley, VR (reprint author), Harvard Inst Med, 77 Ave Louis Pasteur, Boston, MA 02115 USA. RI Tesch, Greg/I-1444-2013 OI Tesch, Greg/0000-0002-6137-3092 FU NIDDK NIH HHS [DK 52369, DK-36149, R01 DK036149, R01 DK052369, Z01 DK036149] NR 46 TC 234 Z9 249 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 20 PY 1999 VL 190 IS 12 BP 1813 EP 1824 DI 10.1084/jem.190.12.1813 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 268MC UT WOS:000084419300010 PM 10601356 ER PT J AU Weiss, AP Heckers, S AF Weiss, AP Heckers, S TI Neuroimaging of hallucinations: a review of the literature SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Review DE schizophrenia; psychosis; neuroanatomy; neurophysiology ID AUDITORY HALLUCINATIONS; VISUAL HALLUCINATIONS; BLOOD-FLOW; ALZHEIMERS-DISEASE; CORTICAL RESPONSE; TEMPORAL-LOBE; SCHIZOPHRENIA; SPECT; ABNORMALITIES; TOMOGRAPHY AB While hallucinations have been described for over two millennia, their cause remains unclear. Brain-based models suggest that abnormal cerebral excitation and a lack of normal cerebral inhibition may play primary roles, but evaluation of these hypotheses has been hampered by difficulty in studying the hallucinatory state. Recent advances in neuroimaging have provided researchers with tools to study a variety of mental states, including hallucinations. We review the literature regarding the structural and functional neural correlates of hallucinations. Despite small sample sizes and methodological differences, several studies describe similar results: hallucinations are associated with sensory modality-specific activation in cerebral areas involved in normal sensory processing. Furthermore, neural activation may be specifically related to distinct phenomenological features of the hallucinatory experience. Further work is needed to better understand the neural basis of hallucinations. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Weiss, AP (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Wang ACC 812, Boston, MA 02114 USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 NR 54 TC 73 Z9 76 U1 1 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD DEC 20 PY 1999 VL 92 IS 2-3 BP 61 EP 74 DI 10.1016/S0925-4927(99)00041-4 PG 14 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 278QN UT WOS:000085000600001 PM 10674360 ER PT J AU Kopans, DB AF Kopans, DB TI Breast-cancer screening with ultrasonography SO LANCET LA English DT Editorial Material ID US; WOMEN C1 Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kopans, DB (reprint author), Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. NR 9 TC 27 Z9 27 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 DEC 18 PY 1999 VL 354 IS 9196 BP 2096 EP 2097 DI 10.1016/S0140-6736(99)90400-2 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 266UG UT WOS:000084318200004 PM 10609810 ER PT J AU Dougherty, DD Bonab, AA Spencer, TJ Rauch, SL Madras, BK Fischman, AJ AF Dougherty, DD Bonab, AA Spencer, TJ Rauch, SL Madras, BK Fischman, AJ TI Dopamine transporter density in patients with attention deficit hyperactivity disorder SO LANCET LA English DT Article AB Dopamine transporter density was measured in vivo in six adult patients with attention deficit hyperactivity disorder. We have shown a 70% increase in age-corrected dopamine transporter density in patients with attention hyperactivity disorder compared with healthy controls. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Fischman, AJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. FU NIDA NIH HHS [DA00304, DA11558]; NINDS NIH HHS [NS30556] NR 5 TC 394 Z9 401 U1 3 U2 15 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD DEC 18 PY 1999 VL 354 IS 9196 BP 2132 EP 2133 DI 10.1016/S0140-6736(99)04030-1 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 266UG UT WOS:000084318200018 PM 10609822 ER PT J AU Chang, MS Sasaki, H Campbell, MS Kraeft, SK Sutherland, R Yang, CY Liu, Y Auclair, D Hao, LN Sonoda, H Ferland, LH Chen, LB AF Chang, MS Sasaki, H Campbell, MS Kraeft, SK Sutherland, R Yang, CY Liu, Y Auclair, D Hao, LN Sonoda, H Ferland, LH Chen, LB TI HRad17 colocalizes with NHP2L1 in the nucleolus and redistributes after UV irradiation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ATAXIA-TELANGIECTASIA GENE; DNA-DAMAGE CHECKPOINT; SCHIZOSACCHAROMYCES-POMBE RAD1(+); DEPENDENT PROTEIN-KINASE; SACCHAROMYCES-CEREVISIAE; CELL-CYCLE; NUCLEAR-PROTEIN; FISSION YEAST; HUMAN HOMOLOG; RNA AB The rad17 gene of Schizosaccharomyces pombe plays an important role as a checkpoint protein following DNA damage and during DNA replication. The human homologue of S, pombe rad17, Hrad17, was recently identified, but its function has not yet been established. Using the yeast two-hybrid system, we determined that HRad17 can interact with a nucleolar protein, NHP2L1. This interaction was also demonstrated biochemically, in human cells. Immunofluorescence studies revealed that HRad17 and NHP2L1 colocalize to the nucleolus, and immunogold labeling further resolved the location of NHP2L1 to the dense fibrillar component of the nucleolus. Interestingly, the localization of HRad17 in the nucleolus was altered in response to UV irradiation. These results provide some insight into the DNA damage and replication checkpoint mechanisms of HRad17. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Chen, LB (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Rm SM1058,44 Binney St, Boston, MA 02115 USA. OI CHANG, MAU-SUN/0000-0002-3703-2386 FU NCI NIH HHS [CA38493-12] NR 51 TC 37 Z9 40 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 17 PY 1999 VL 274 IS 51 BP 36544 EP 36549 DI 10.1074/jbc.274.51.36544 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 266AV UT WOS:000084279200072 PM 10593953 ER PT J AU Thomas, JW Cooley, MA Broome, JM Salgia, R Griffin, JD Lombardo, CR Schaller, MD AF Thomas, JW Cooley, MA Broome, JM Salgia, R Griffin, JD Lombardo, CR Schaller, MD TI The role of focal adhesion kinase binding in the regulation of tyrosine phosphorylation of paxillin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SRC HOMOLOGY-2 DOMAIN; CELL-ADHESION; HIGH-AFFINITY; SH3 DOMAIN; LIM DOMAIN; V-SRC; DIRECT ASSOCIATION; DEPENDENT BINDING; FAMILY KINASES; PROTEIN BINDS AB Focal adhesion kinase (FAK) and paxillin are focal adhesion-associated phosphotyrosine-containing proteins that physically interact. A previous study has demonstrated that paxillin contains two binding sites for FAB Ne have further characterized these two binding sites and have demonstrated that the binding affinity of the carboxyl-terminal domain of FAR is the same for each of the two binding sites. The presence of both binding sites increases the affinity for FAR by 5-10-fold. A conserved paxillin sequence called the LD motif has been implicated in FAK binding. We show that mutations in the LD motifs in both FAK-binding sites are required to dramatically impair FAR binding in vitro. A paxillin mutant containing point mutations in both FAK-binding sites was characterized. The mutant exhibited reduced levels of phosphotyrosine relative to wild type paxillin in subconfluent cells growing in culture, following cell adhesion to fibronectin and in src-transformed fibroblasts. These results suggest that paxillin must bind FAK for maximal phosphorylation in response to cell adhesion and that FAK may function to direct tyrosine phosphorylation of paxillin in the process of transformation by the src oncogene. C1 Univ N Carolina, Dept Cell Biol & Anat, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Macromol Interact Facil, Chapel Hill, NC 27599 USA. Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Schaller, MD (reprint author), Univ N Carolina, Dept Cell Biol & Anat, Taylor Hall CB 7090, Chapel Hill, NC 27599 USA. FU NCI NIH HHS [1F32CA74490]; NIGMS NIH HHS [GM53668] NR 69 TC 101 Z9 102 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 17 PY 1999 VL 274 IS 51 BP 36684 EP 36692 DI 10.1074/jbc.274.51.36684 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 266AV UT WOS:000084279200092 PM 10593973 ER PT J AU Lin, HB Jurk, M Gulick, T Cooper, GM AF Lin, HB Jurk, M Gulick, T Cooper, GM TI Identification of COUP-TF as a transcriptional repressor of the c-mos proto-oncogene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ORPHAN NUCLEAR RECEPTOR; THYROID-HORMONE; XENOPUS OOCYTES; SARCOMA-VIRUS; MOUSE-TISSUES; SOMATIC-CELLS; GERM-CELLS; MEIOSIS-II; EXPRESSION; PROMOTER AB The c-mos proto-oncogene is specifically expressed in the male and female germ cells of the mouse and other vertebrates. We previously identified a 15-base pair sequence element (B2) as the binding site of a candidate repressor of c-mos transcription in somatic cells. In the present study, we used the yeast one-hybrid system to isolate HeLa cell cDNAs encoding proteins that specifically bound to the c-mos B2 element. Nucleotide sequencing identified several of the clones isolated in this screen as the orphan nuclear receptors COUP-TFI and COUP-TFII. A COUP-TF-binding site was then identified within the B2 sequence. Complexes formed between purified COUP-TFs and the c-mos B2 probe comigrated in electrophoretic mobility shift assays with those formed using whole nuclear extracts of NIH 3T3 or HeLa cells. Moreover, the complexes formed with NIH 3T3 nuclear extracts and B2 probe were supershifted with antibody against COUP-TF, identifying COUP-TF as the candidate repressor previously detected in these somatic cell extracts. Substitution of a consensus COUP-TF-binding site for the c-mos negative regulatory element suppressed expression from the c-mos promoter in transfected somatic cells, demonstrating the functional activity of COUP-TF as a repressor of c-mos transcription. C1 Boston Univ, Dept Biol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Diabet Res Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Med Serv, Charlestown, MA 02129 USA. RP Cooper, GM (reprint author), Boston Univ, Dept Biol, 5 Cummington St, Boston, MA 02215 USA. FU NICHD NIH HHS [R01-HD26594, R01-HD35685]; NIDDK NIH HHS [K02-DK02461] NR 38 TC 7 Z9 7 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 17 PY 1999 VL 274 IS 51 BP 36796 EP 36800 DI 10.1074/jbc.274.51.36796 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 266AV UT WOS:000084279200108 PM 10593989 ER PT J AU Kohen, R AF Kohen, R TI Technology transfer SO SCIENCE LA English DT Article C1 Univ Washington, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, GRECC 182B, Seattle, WA 98108 USA. RP Kohen, R (reprint author), Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 17 PY 1999 VL 286 IS 5448 BP 2296 EP 2298 DI 10.1126/science.286.5448.2296 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 266UK UT WOS:000084318500046 ER PT J AU Kosinski, CM Cha, JH Young, AB Mangiarini, L Bates, G Schiefer, J Schwarz, M AF Kosinski, CM Cha, JH Young, AB Mangiarini, L Bates, G Schiefer, J Schwarz, M TI Intranuclear inclusions in subtypes of striatal neurons in Huntington's disease transgenic mice SO NEUROREPORT LA English DT Article DE basal ganglia; Calbindin-D28K; choline acetyltransferase; Huntington's disease; immunohistochemistry; mice; transgenic; nuclear inclusion; ubiquitin ID BRAIN; INTERNEURONS; DEGENERATION; LESIONS; REPEAT; ACID; GENE AB R6/2 transgenic mice express exon 1 of an abnormal human Huntington's disease (HD) gene and develop a neurological phenotype similar to HD. These mice develop ubiquitinated neuronal intranuclear inclusions (NII) which might play a central role in the pathophysiology of HD. We studied the distribution of NII in subpopulations of striatal neurons in 12-week-old R6/2 transgenic mice using fluorescent double label immunohistochemistry. We observed that most of the Calbindin-D28K positive projection neurons (89%) and the Parvalbumin positive interneurons (86%) showed ubiquitinated NII. In interneurons, however, which contain either choline acetyltransferase, neuronal nitric oxide synthase, or Calretinin, the frequency of NII was much lower (22%, 8%, 9%, respectively). Our data suggest that subpopulations of striatal neurons differ remarkably in their capability of forming ubiquitinated NII. Interneurons which are known to resist neurodegeneration in HD show less NII. (C) 1999 Lippincott Williams & Wilkins. C1 Rhein Westfal TH Aachen, United Hosp, Dept Neurol, D-52074 Aachen, Germany. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ London Kings Coll, Guys Hosp, GKT Sch Med, Div Med & Mol Genet, London SE1 9RT, England. RP Kosinski, CM (reprint author), Rhein Westfal TH Aachen, United Hosp, Dept Neurol, Pauwelsstr 30, D-52074 Aachen, Germany. RI Bates, Gillian/E-1146-2012 OI Bates, Gillian/0000-0002-4041-6305 NR 19 TC 18 Z9 18 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD DEC 16 PY 1999 VL 10 IS 18 BP 3891 EP 3896 DI 10.1097/00001756-199912160-00031 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 266MB UT WOS:000084302800033 PM 10716229 ER PT J AU Faraone, SV Meyer, J Matise, T Svrakic, D Pepple, J Malaspina, D Suarez, B Hampe, C Chan, G Aelony, A Friedman, JH Kaufmann, C Cloninger, CR Tsuang, MT AF Faraone, SV Meyer, J Matise, T Svrakic, D Pepple, J Malaspina, D Suarez, B Hampe, C Chan, G Aelony, A Friedman, JH Kaufmann, C Cloninger, CR Tsuang, MT TI Suggestive linkage of chromosome 10p to schizophrenia is not due to transmission ratio distortion SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE schizophrenia; linkage; transmission ratio distortion; chromosome 10 ID MILLENNIUM-CONSORTIUM; GENOME SCAN; PEDIGREES; LOCUS AB The genome scan of the European-American schizophrenia families from the Human Genetics Initiative of the National Institute of Mental Health (NIMH) reported a suggestive linkage to chromosome 10p. Subsequently, Paterson and Petronis [1999] reported evidence for transmission ratio distortion on 10p to females. They suggested that transmission ratio distortion to females might have created spurious evidence for linkage to 10p. To address this issue, we reanalyzed our 10p data using only male-male affected sibling pairs. The two chromosome 10p markers that gave the most evidence for linkage in our prior report continued to show evidence for linkage: D10S1423 (NPL Z = 3.0, P = 0.001) and its neighbor D10S582 (NPL Z = 2.9, P = 0.002). These data suggest that our prior report of suggestive linkage of schizophrenia to markers on 10p cannot be attributed to the transmission ratio distortion to females reported by Paterson and Petronis. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:607-608, 1999. (C) 1999 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Brockton W Roxbury Vet Affairs Med Ctr, Brockton, MA USA. Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Millennium Pharmaceut, Cambridge, MA USA. Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Columbia Univ, Dept Psychiat, New York, NY USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Faraone, SV (reprint author), Harvard Univ, Sch Med, Suite 255,750 Washington St, S Easton, MA 02375 USA. RI Cloninger, Claude/F-5357-2012; OI Cloninger, Claude/0000-0003-3096-4807; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [1 R37MH43518, 1 RO1MH41874-01, 5 UOMH46318] NR 9 TC 12 Z9 12 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD DEC 15 PY 1999 VL 88 IS 6 BP 607 EP 608 DI 10.1002/(SICI)1096-8628(19991215)88:6<607::AID-AJMG6>3.0.CO;2-Q PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 261KE UT WOS:000084007700006 PM 10581477 ER PT J AU Cousin, SP Hugl, SR Myers, MG White, MF Reifel-Miller, A Rhodes, CJ AF Cousin, SP Hugl, SR Myers, MG White, MF Reifel-Miller, A Rhodes, CJ TI Stimulation of pancreatic beta-cell proliferation by growth hormone is glucose-dependent: signal transduction via Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) with no crosstalk to insulin receptor substrate-mediated mitogenic signalling SO BIOCHEMICAL JOURNAL LA English DT Article DE MAP kinase; nutrient stimulus-response coupling; phosphatidylinositol-3 '-kinase; tyrosine phosphorylation ID PROTEIN-KINASE; FACTOR-I; TYROSINE PHOSPHORYLATION; IGF-I; PROLACTIN; BIOSYNTHESIS; ISLETS; INS-1; DIFFERENTIATION; MECHANISMS AB Mitogenic signal-transduction pathways have not been well defined in pancreatic beta-cells. In the glucose-sensitive rat beta-cell line, INS-1, glucose (6-18 mM) increased INS-1 cell proliferation (> 20-fold at 15 mM glucose). Rat growth hormone (rGH) also induced INS-1 cell proliferation, but this was glucose-dependent in the physiologically relevant concentration range (6-18 mM glucose). The combination of rGH (10 nM) and glucose(15 mM) was synergistic, maximally increasing INS-1 cell proliferation by > 50-fold. Moreover, glucose-dependent rGH-induced INS-1 cell proliferation was increased further by addition of insulin-like growth factor 1 (IGF-1; 10 nM) to > 90-fold at 12 mM glucose. Glucose metabolism and phosphatidylinositol-3'-kinase (PI3'K) activation were necessary for both glucose- and rGH-stimulated INS-1 cell proliferation. Glucose (> 3 mM) independently increased tyrosine-phosphorylation-mediated recruitment of growth-factor-bound protein 2 (Grb2)/murine sons of sevenless-1 protein (mSOS) and PI3'K to insulin receptor substrate (IRS)-1 and IRS-2, as well as SH2-containing protein (Shc) association with Grb2/mSOS and downstream activation of mitogen-activated protein kinase and 70 kDa S6 kinase. Glucose-induced IRS- and Shc-mediated signal transduction was enhanced further by the addition of IGF-1, but not rGH. In contrast, rGH was able to activate Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) signal transduction at glucose concentrations above 3 mM, but neither glucose independently, nor glucose with added IGF-1, were able to activate the JAK2/STAT5 signalling pathway. Thus rGH-mediated proliferation of beta-cells is directly via the JAK2/STAT5 pathway without engaging the Shc or IRS signal-transduction pathways, although activation of PI3'K may play an important permissive role in the glucose-dependent aspect of rGH-induced beta-cell mitogensis. The additive effect of rGH and IGF-1 on glucose-dependent beta-cell proliferation is therefore reflective of rGH and IGF-1 activating distinctly different mitogenic signalling pathways in beta-cells with minimal crosstalk between them. C1 Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75235 USA. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Rhodes, CJ (reprint author), Univ Texas, SW Med Ctr, Dept Internal Med, 5323 Harry Hines Blvd, Dallas, TX 75235 USA. FU NIDDK NIH HHS [DK 55267] NR 39 TC 71 Z9 72 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD DEC 15 PY 1999 VL 344 BP 649 EP 658 DI 10.1042/0264-6021:3440649 PN 3 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 273BW UT WOS:000084688200004 PM 10585851 ER PT J AU Nierenberg, AA Burt, T Matthews, J Weiss, AP AF Nierenberg, AA Burt, T Matthews, J Weiss, AP TI Mania associated with St. John's wort SO BIOLOGICAL PSYCHIATRY LA English DT Article DE St. John's wort; major depression; bipolar depression; secondary mania; alternative medicine; psychopharmacology ID ANTIDEPRESSANTS; ILLNESS AB Background: St. John's wort, the popular herbal remedy touted as an antidepressant, is generally thought to be benign, with few reported side effects. Given its possible efficacy as an antidepressant, evaluation of its propensity to cause affective switching should be evaluated. Methods: This report presents two cases of mania tempor- ally associated with the use of St. John's wort (hypericum). Results: As with other antidepressant agents, St. John's wort may precipitate hypomania, mania, or an increased cycling of mood states, particularly in patients with occult bipolar disorder. Conclusions: Because the majority of people who take this popular over-the-counter preparation. do so without formal psychiatric evaluations, risk of hypericum-induced mania may be significant. Physicians should screen patients for a history of hypomania or mania before recommending use of St. John's wort for depression, Biol Psychiatry 1999;46:1707-1708 (C) 1999 Society of Biological Psychiatry. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program,Clin Psychopharmacol U, Boston, MA 02114 USA. Columbia Univ, New York State Psychiatr Inst, New York, NY USA. RP Nierenberg, AA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program,Clin Psychopharmacol U, WACC 812,15 Parkman St, Boston, MA 02114 USA. RI Burt, Tal/O-1951-2013 OI Burt, Tal/0000-0002-5853-6110 NR 11 TC 46 Z9 47 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 1999 VL 46 IS 12 BP 1707 EP 1708 DI 10.1016/S0006-3223(99)00233-4 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 267BU UT WOS:000084335400015 PM 10624554 ER PT J AU Salgia, R Quackenbush, E Lin, J Souchkova, N Sattler, M Ewaniuk, DS Klucher, KM Daley, GQ Kraeft, SK Sackstein, R Alyea, EP von Andrian, UH Chen, LB Gutierrez-Ramos, JC Pendergast, AM Griffin, JD AF Salgia, R Quackenbush, E Lin, J Souchkova, N Sattler, M Ewaniuk, DS Klucher, KM Daley, GQ Kraeft, SK Sackstein, R Alyea, EP von Andrian, UH Chen, LB Gutierrez-Ramos, JC Pendergast, AM Griffin, JD TI The BCR/ABL oncogene alters the chemotactic response to stromal-derived factor-1 alpha SO BLOOD LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; HEMATOPOIETIC PROGENITOR CELLS; CHRONIC GRANULOCYTIC LEUKEMIA; CHEMOKINE RECEPTOR CXCR4; CHRONIC MYELOID-LEUKEMIA; MOLECULAR-CLONING; P210(BCR/ABL); ADHESION; CHEMOATTRACTANT; EXPRESSION AB The chemokine stromal-derived factor-1 alpha (SDF-1 alpha) is a chemoattractant for CD34(+) progenitor cells, in vitro and in vivo. The receptor for SDF-1 alpha, CXCR-4, is a 7 transmembrane domain receptor, which is also a coreceptor for human immunodeficiency virus (HIV). Here we show that transformation of hematopoietic cell lines by BCR/ABL significantly impairs their response to SDF-1 alpha. Three different hematopoietic cell lines, Ba/F3, 32Dcl3, and Mo7e, were found to express CXCR-4 and to respond to SDF-1 alpha with increased migration in a transwell assay. In contrast, after transformation by the BCR/ABL oncogene, the chemotactic response to SDF-1 alpha was reduced in all 3 lines. This effect was directly due to BCR/ABL, because Ba/F3 cells, in which the expression of BCR/ABL could be regulated by a tetracycline-inducible promoter, also had reduced chemotaxis to SDF-1 alpha when BCR/ABL was induced. The reduced response to SDF-1 alpha was not due to an inability of BCR/ABL-transformed cell lines to migrate in general, as spontaneous motility of BCR/ABL-transformed cells was increased, in mice, injection of SDF-1 alpha into the spleen resulted in a transient accumulation of untransformed Ba/F3 cells, but not Ba/F3.p210(BCR/ABL) cells administered simultaneously. The mechanism may involve inhibition of CXCR-4 receptor function, because in BCR/ABL-transformed cells, CXCR-4 receptors were expressed on the cell surface, but SDF-1 alpha calcium flux was inhibited. Because SDF-1 alpha and CXCR-4 are felt to be involved in progenitor cell homing to marrow, the abnormality decribed here could contribute to the homing and retention defects typical of immature myeloid cells in chronic myelogenous leukemia. (C) 1999 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Cellular & Mol Biol, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Duke Univ, Med Ctr, Levine Sci Res Ctr, Dept Pharmacol & Canc Biol, Durham, NC USA. Millennium Pharmaceut Inc, Cambridge, MA USA. Massachusetts Gen Hosp, Brigham & Womens Hosp, Dept Med, Boston, MA 02114 USA. RP Salgia, R (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Dana 530C,44 Binney St, Boston, MA 02115 USA. RI von Andrian, Ulrich/A-5775-2008 FU NCI NIH HHS [CA 75348]; NIDDK NIH HHS [DK 560654] NR 31 TC 83 Z9 83 U1 0 U2 5 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 DEC 15 PY 1999 VL 94 IS 12 BP 4233 EP 4246 PG 14 WC Hematology SC Hematology GA 263TD UT WOS:000084140600030 PM 10590068 ER PT J AU Iinuma, S Schomacker, KT Wagnieres, G Rajadhyaksha, M Bamberg, M Momma, T Hasan, T AF Iinuma, S Schomacker, KT Wagnieres, G Rajadhyaksha, M Bamberg, M Momma, T Hasan, T TI In vivo fluence rate and fractionation effects on tumor response and photobleaching: Photodynamic therapy with two photosensitizers in an orthotopic rat tumor model SO CANCER RESEARCH LA English DT Article ID 5-AMINOLEVULINIC ACID; PROTOPORPHYRIN-IX; NUDE-MICE; OXYGEN-CONSUMPTION; OPTICAL-PROPERTIES; BLADDER-CANCER; MURINE TUMOR; FLUORESCENCE; CELLS; LIGHT AB The effect of fluence rate and light fractionation on phototoxicity was investigated in vivo in an orthotopic rat bladder tumor model. Two photosensitizers, benzoporphyrin derivative monoacid ring A and 5-aminoevulinic acid-induced protoporphyrin IX, were studied. For a given cumulative light dose of 30 J/cm(2), enhanced tumor destruction was observed from both photosensitizers when using either lower fluence rates or fractionated light delivery. Photobleaching experiments in vivo demonstrated that the photobleaching rate, however, was not fluence rate dependent. The fluence rate and light fractionation effects on tumor phototoxicity lead to rapid local depletion in oxygen concentration that inhibited subsequent photochemical reactions necessary for efficient photodestruction of tumor cells. Nicotinamide did not enhance photodynamic therapy efficacy, suggesting that the added increase of oxygen within the tumor was not sufficient to enhance photodestruction of hypoxic cell fractions. The independence of the photobleaching rate with fluence rate suggests distinct mechanisms, at least in part, of photodestruction of the tumor and the photosensitizer and that the rate of photosensitizer photobleaching may not always be an appropriate monitor for singlet oxygen availability and photodynamic therapy dosimetry. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Urol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Hasan, T (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02115 USA. OI Wagnieres, Georges/0000-0002-9082-3099 FU NIAMS NIH HHS [R01-AR40352] NR 55 TC 78 Z9 81 U1 2 U2 11 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1999 VL 59 IS 24 BP 6164 EP 6170 PG 7 WC Oncology SC Oncology GA 270HT UT WOS:000084530400027 PM 10626808 ER PT J AU Morgan, JA Yin, Y Borowsky, AD Kuo, F Nourmand, N Koontz, JI Reynolds, C Soreng, L Griffin, CA Graeme-Cook, F Harris, NL Weisenburger, D Pinkus, GS Fletcher, JA Sklar, J AF Morgan, JA Yin, Y Borowsky, AD Kuo, F Nourmand, N Koontz, JI Reynolds, C Soreng, L Griffin, CA Graeme-Cook, F Harris, NL Weisenburger, D Pinkus, GS Fletcher, JA Sklar, J TI Breakpoints of the t(11;18)(q21;q21) in mucosa-associated lymphoid tissue (MALT) lymphoma lie within or near the previously undescribed gene MALT1 in chromosome 18 SO CANCER RESEARCH LA English DT Article ID B-CELL LYMPHOMA; HELICOBACTER-PYLORI; GASTRIC LYMPHOMA; LOW-GRADE; MALIGNANT-LYMPHOMA; BIOPSY SPECIMENS; HUMAN GENOME; TRANSLOCATION; REGRESSION; DNA AB Lymphomas arising in mucosa-associated lymphoid tissue (MALT) are indolent B-cell tumors that have a predilection for epithelial sites and often develop in a setting of chronic inflammation or autoimmunity, As many as 50% of low-grade MALT Lymphomas contain an (11;18)(q21;q21) chromosomal translocation, Using fluorescence in situ hybridization, we have analyzed the position of recombination within chromosome 18 DNA in three examples of MALT lymphoma bearing this translocation. In all three cases, the breakpoint maps to DNA in BAC b357H2, covering about 150 kb of sequence. A previously undescribed, ubiquitously expressed gene, which we refer to as MALT1, was identified within this sequence and was found to be broken in one case for which we have definitively located the position of recombination between chromosomes 18 and 11, The sequence of this gene indicates the presence of two immunoglobulin-like C2 domains and a region of partial homology to caspases, suggesting a possible role for MALT1 in the regulation of apoptosis. C1 Brigham & Womens Hosp, Dept Pathol, Div Mol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. RP Brigham & Womens Hosp, Dept Pathol, Div Mol Oncol, 75 Francis St, Boston, MA 02115 USA. EM jsklar@rics.bwh.harvard.edu FU NCI NIH HHS [CA75354, CA72744]; NIAID NIH HHS [AI013575] NR 27 TC 132 Z9 134 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1999 VL 59 IS 24 BP 6205 EP 6213 PG 9 WC Oncology SC Oncology GA 270HT UT WOS:000084530400033 PM 10626814 ER PT J AU Yoon, SS Eto, H Lin, CM Nakamura, H Pawlik, TM Song, SU Tanabe, KK AF Yoon, SS Eto, H Lin, CM Nakamura, H Pawlik, TM Song, SU Tanabe, KK TI Mouse endostatin inhibits the formation of lung and liver metastases SO CANCER RESEARCH LA English DT Article ID CANCER; ANGIOGENESIS; CARCINOMAS; THERAPY AB Angiogenesis is required fur tumor formation, Several studies have demonstrated that tumor angiogenesis is regulated by a balance between proangiogenesis and antiangiogenesis factors and that this balance varies in different organ environments, To investigate whether expression of an angiogenesis inhibitor by cancer cells could alter this balance and prevent tumor formation in different organ environments, we engineered stable transfectants from RenCa mouse renal carcinoma cells and SW620 human colon carcinoma cells to constitutively secrete a mouse endostatin protein with c-myc and polyhistidine (His) tags, Production and secretion of the endostatin-c-myc-His fusion protein by endostatin-transfected cells were confirmed by immunofluorescence staining and Western blot analysis. The endostatin transfectants and control transfectants, stably transfected with a control plasmid, had similar in vitro growth rates compared with their parental cell lines. Conditioned medium from endostatin-transfected cells inhibited human umbilical vein endothelial cell proliferation by 36-51% compared with conditioned medium from control cells. After inoculation into mice, flank tumors from endostatin-transfected cells were 73-91% smaller than flank tumors from control cells after 3 weeks. Inoculation of a cell mixture containing 25% endostatin-transfected cells and 75% control cells resulted in inhibition of flank tumor formation as effective as after inoculation of 100% endostatin-transfected cells. Formation of lung metastases by RenCa endostatin-transfected cells and formation of liver metastases by SW620 endostatin-transfected cells were dramatically inhibited compared with formation of metastases by control cells. These findings demonstrate that endostatin can inhibit tumor formation in different organ environments and that gene delivery of endostatin into even a minority of tumor cells may be an effective strategy to prevent progression of micrometastases to macroscopic disease. C1 Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Cox 626,100 Blossom St, Boston, MA 02114 USA. FU NCI NIH HHS [CA64454]; NIDDK NIH HHS [DK43352]; NIGMS NIH HHS [GM21700] NR 20 TC 122 Z9 137 U1 2 U2 5 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1999 VL 59 IS 24 BP 6251 EP 6256 PG 6 WC Oncology SC Oncology GA 270HT UT WOS:000084530400039 PM 10626820 ER PT J AU Zhang, HJ Yan, T Oberley, TD Oberley, LW AF Zhang, HJ Yan, T Oberley, TD Oberley, LW TI Comparison of effects of two polymorphic variants of manganese superoxide dismutase on human breast MCF-7 cancer cell phenotype SO CANCER RESEARCH LA English DT Article ID MALIGNANT PHENOTYPE; LUNG FIBROBLASTS; OVEREXPRESSION; SUPPRESSION; EXPRESSION; CARCINOGENESIS; MUTATION; RADICALS; GENE AB Two polymorphic variants of manganese superoxide dismutase (MnSOD), vMh either lie or Thr at amino acid 58, (Ile(58)MnSOD or Thr(58)MnSOD), have been found in the human population. The MnSOD activity of these two variants and their effects on the malignant phenotype of human breast cancer MCF-7 cells were compared. It,vas demonstrated that MnSOD-overexpressing: clones obtained from transfection of the two MnSOD cDNAs into MCF-7 cells had increased MnSOD immunoreactive protein and increased MnSOD activity. Cells overexpressing Ile(58)MnSOD had 3-fold higher MnSOD activity than cells overexpressing Thr(58)MnSOD irt vivo at an equal MnSOD protein level Tumor-suppressive effects of MnSOD-overexpressing cells were indicated by: (a) decreased plating efficiency; (b) elongated cell population doubling time; (c) lower clonogenic fraction in soft agar; and (d) complete inhibition or delayed onset of tumor formation in nude mice. When compared on the same activity basis, the suppressive effects of Ile(58)MnSOD were similar to those of Thr(58)MnSOD, However, far more Thr(58)MnSOD protein was required to obtain the same amount of MnSOD activity, making the Thr(58)MnSOD far less effective, A dose-response suppressive effect was observed when the increase of MnSOD activity was moderate. We conclude that MnSOD is a tumor suppressor in human breast cancer, but the Thr(58) form of the protein is a much less effective tumor suppressor than the Ile(58) form of the protein. C1 Univ Iowa, Coll Med, Radiat Res Lab, Med Labs B180, Iowa City, IA 52242 USA. William S Middleton Mem Vet Hosp, Pathol & Lab Med Serv, Madison, WI 53705 USA. Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53705 USA. RP Oberley, LW (reprint author), Univ Iowa, Coll Med, Radiat Res Lab, Med Labs B180, Iowa City, IA 52242 USA. FU NCI NIH HHS [CA66081] NR 35 TC 71 Z9 75 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1999 VL 59 IS 24 BP 6276 EP 6283 PG 8 WC Oncology SC Oncology GA 270HT UT WOS:000084530400042 PM 10626823 ER PT J AU Ozelius, LJ Page, CE Klein, C Hewett, JW Mineta, M Leung, J Shalish, C Bressman, SB de Leon, D Brin, MF Fahn, S Corey, DP Breakefield, XO AF Ozelius, LJ Page, CE Klein, C Hewett, JW Mineta, M Leung, J Shalish, C Bressman, SB de Leon, D Brin, MF Fahn, S Corey, DP Breakefield, XO TI The TOR1A (DYT1) gene family and its role in early onset torsion dystonia SO GENOMICS LA English DT Article ID TYROSINE-HYDROXYLASE GENE; ASHKENAZI JEWS; POINT MUTATION; PROTEIN; INCLUSIONS; PROTEASES; MECHANISM; FUSION; DOMAIN; BRAIN AB Most cases of early onset torsion dystonia are caused by a 3-bp deletion (GAG) in the coding region of the TOR1A gene (alias DYT1, DQ2), resulting in loss of a glutamic acid in the carboxy terminal of the encoded protein, torsin A. TOR1A and its homologue TOR1B (alias DQ1) are located adjacent to each other on human chromosome 9q34, Both genes comprise five similar exons; each gene spans a 10-kb region. Mutational analysis of most of the coding region and splice junctions of TOR1A and TOR1B did not reveal additional mutations in typical early onset cases lacking the GAG deletion (N = 17), in dystonic individuals with apparent homozygosity in the 9q34 chromosomal region (N = 5), or in a representative Ashkenazic Jewish individual with late onset dystonia, who shared a common haplotype in the 9q34 region with other late onset individuals in this ethnic group. A database search revealed a family of nine related genes (50-70% similarity) and their orthologues in species including human, mouse, rat, pig, zebrafish, fruitfly, and nematode, At least four of these genes occur in the human genome. Proteins encoded by this gene family share functional domains with the AAA/HSP/Clp-ATPase superfamily of chaperone-like proteins, but appear to represent a distinct evolutionary branch. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Beth Israel Med Ctr, Dept Neurol, New York, NY 10003 USA. Mt Sinai Sch Med, Movement Disorders Ctr, New York, NY 10029 USA. Columbia Presbyterian Med Ctr, Dept Neurol, Dystonia Clin Res Ctr, New York, NY 10032 USA. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp E, Dept Mol Neurogenet, 13th St,Bldg 149, Charlestown, MA 02129 USA. OI Corey, David/0000-0003-4497-6016 FU NINDS NIH HHS [NS37409, NS28384, NS381424] NR 45 TC 94 Z9 99 U1 0 U2 6 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 DEC 15 PY 1999 VL 62 IS 3 BP 377 EP 384 DI 10.1006/geno.1999.6039 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 280EN UT WOS:000085089400007 PM 10644435 ER PT J AU Peterfy, M Phan, J Oswell, GM Xu, P Reue, K AF Peterfy, M Phan, J Oswell, GM Xu, P Reue, K TI Genetic, physical, and transcript map of the fld region on mouse chromosome 12 SO GENOMICS LA English DT Article ID MUTANT MOUSE; E2F FAMILY; MUTATION; MICE; AMPLIFICATION; METABOLISM; REPRESSOR; MEMBER AB The fatty liver dystrophy (fld) mutation is manifested in abnormalities of lipid and glucose metabolism and peripheral neuropathy, To identify the gene affected by this mutation, we generated a genetic map of the fld region on chromosome 12 by the analysis of F2 offspring from an intersubspecific cross between strains BALB/cByJ-fld and CAST/EiJ, The results localize fld to the 0.42-cM interval between the microsatellite markers D12Mit170 and D12Mit184. A contig of YACs and BACs covering the nonrecombinant genomic region has been constructed and used for the identification of genes. Expressed sequence tag mapping and exon trapping identified three transcripts within the critical interval: Ctla2b, which encodes a cysteine protease inhibitor, and mouse homologs of KIAA0188 and KIAA0575, two long human transcripts of unknown function. Expression analysis revealed that Kiaa0188 is expressed in wildtype but not in fld liver, implicating this gene as a candidate for harboring the fld mutation. (C) 1999 Academic Press. C1 Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Lipid Res Lab, Los Angeles, CA 90073 USA. RP Reue, K (reprint author), VA Greater Los Angeles Healthcare Ctr, Bldg 113,Room 312,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NHLBI NIH HHS [HL28481, HL58627] NR 26 TC 13 Z9 15 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 DEC 15 PY 1999 VL 62 IS 3 BP 436 EP 444 DI 10.1006/geno.1999.6023 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 280EN UT WOS:000085089400013 PM 10644441 ER PT J AU Tremblay, C Merrill, DP Chou, TC Hirsch, MS AF Tremblay, C Merrill, DP Chou, TC Hirsch, MS TI Interactions among combinations of two and three protease inhibitors against drug-susceptible and drug-resistant HIV-1 isolates SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 12th International Conference on AIDS CY JUN-JUL -, 1998 CL GENEVA, SWITZERLAND DE protease inhibitors; combination therapy; drug interactions ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE; INFECTION; INDINAVIR AB Protease inhibitors used in combination with reverse transcriptase inhibitors have demonstrated potent anti-HIV-1 activity in vitro as well as in vivo. We evaluated interactions among five protease inhibitors: indinavir (IDV), ritonavir (RTV), saquinavir (SQV), amprenavir (APV), and nelfinavir (NFV), when used in combinations of two and three drugs in vitro against several HIV-1 isolates, including those susceptible and resistant to various nucleoside and nonnucleoside reverse transcriptase inhibitors. Interactions ranged from synergy to slight antagonism depending on the viral isolates and the experimental conditions employed. Further clinical evaluation of protease inhibitor combinations is warranted. C1 Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Hirsch, MS (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Gray 5,Fruit St, Boston, MA 02114 USA. RI Chou, Ting-Chao/B-4111-2009 OI Chou, Ting-Chao/0000-0002-3340-1594 FU NCI NIH HHS [CA-12464] NR 21 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD DEC 15 PY 1999 VL 22 IS 5 BP 430 EP 436 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 284MR UT WOS:000085336600002 PM 10961603 ER PT J AU Miller, LG Simon, PA Miller, ME Long, A Yu, EI Asch, SM AF Miller, LG Simon, PA Miller, ME Long, A Yu, EI Asch, SM TI High-risk sexual behavior in Los Angeles: Who receives testing for HIV? SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV testing; high-risk sexual behavior ID HUMAN-IMMUNODEFICIENCY-VIRUS; UNITED-STATES; AIDS; PREDICTORS; TRENDS AB No recent population-based data on HN testing in people with high-risk sexual behavior are available. We sought predictors of testing using data from the 1997 Los Angeles County Health Survey, a random-digit telephone survey of 8004 county households. An estimated 2.3 million (35.5%) adults were tested for HIV in the past 2 years and approximately 370,000 (5.6%) engaged in high-risk sexual behavior (defined as having greater than or equal to 2 partners in the past 12 months and not always using condoms). Among high-risk persons, an estimated 46% of heterosexual men, 56% of heterosexual women, and 72% of men who had sex with men (MSM) were tested for HIV. In a multivariable model of high-risk people, both heterosexual men (odds ratio [OR], 0.31; 95% confidence interval [CI], 0.16-0.61) and women (OR, 0.41; 95% CI, 0.19-0.87) had significantly lower proportions of testing than MSM. Although African Americans and Hispanics had significantly higher testing proportions than whites overall among all county residents, those reporting high-risk sexual behavior did not test at higher proportions. We conclude that the proportion of adults with high-risk sexual behavior tested for HIV is higher than almost a decade ago. However, testing among this group remains suboptimal. Future public health campaigns should intensify efforts to encourage HIV testing among this population. C1 Univ Calif Los Angeles, Med Ctr, Div Infect Dis, VA Greater Los Angeles Healthcare Syst, Torrance, CA 90509 USA. Univ Calif Los Angeles, AIDS Inst, Torrance, CA 90509 USA. Los Angeles Cty Dept Hlth Serv, Off AIDS Programs & Policy, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Div Gen Internal Med, Los Angeles, CA USA. RP Miller, LG (reprint author), Univ Calif Los Angeles, Harbor Med Ctr, Div Infect Dis, 1124 W Carson St,Box 466, Torrance, CA 90509 USA. NR 25 TC 12 Z9 12 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD DEC 15 PY 1999 VL 22 IS 5 BP 490 EP 497 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 284MR UT WOS:000085336600010 PM 10961611 ER PT J AU McKay, DB Irie, HY Hollander, G Ferrara, JLMF Strom, TB Li, YS Burakoff, SJ AF McKay, DB Irie, HY Hollander, G Ferrara, JLMF Strom, TB Li, YS Burakoff, SJ TI Antigen-induced unresponsiveness results in altered T cell signaling SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BLOOD-TRANSFUSION; CLASS-I; GRAFT SURVIVAL; LYMPHOCYTES-T; TOLERANCE; INDUCTION; RECEPTOR; ALLOGRAFTS; ACTIVATION; MICE AB Pretransplant exposure to allogeneic lymphocytes can result in donor-specific unresponsiveness and prolonged allograft survival. Intracellular signaling events have been described in anergic T cell clones, but the biochemical events underlying in vivo induced unresponsiveness have not been studied in detail. We employed a TCR transgenic mouse, bearing the ZC TCR, providing adequate numbers of homogenous peripheral T cells to study biochemical aspects of T cell unresponsiveness in vivo. 2C mice exposed to semiallogeneic lymphocytes (H-2(b) x H-2(d)) experienced prolonged H-2d cardiac allograft survival, and cells from these mice did not proliferate or make IL-2 in response to alloantigen (H-2d). Importantly, there were marked differences in TCR-associated tyrosine phosphorylation activation patterns, The targets for the unresponsive state appear to be diminished Lck activation and absent ZAP-70 and LAT (linker for activation of T cells) phosphorylation, Our study demonstrates that Ag-induced tolerance in vivo is accompanied by altered early TCR-mediated signaling events. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Kantonsspital, Dept Pediat Res, CH-4031 Basel, Switzerland. Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Renal, Boston, MA 02115 USA. RP McKay, DB (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Mayer 653,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [P01CA39542]; NIDDK NIH HHS [DK02472] NR 39 TC 14 Z9 15 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 1999 VL 163 IS 12 BP 6455 EP 6461 PG 7 WC Immunology SC Immunology GA 263PJ UT WOS:000084134200014 PM 10586036 ER PT J AU Alam, MN Szymusiak, R Gong, H King, J McGinty, D AF Alam, MN Szymusiak, R Gong, H King, J McGinty, D TI Adenosinergic modulation of rat basal forebrain neurons during sleep and waking: neuronal recording with microdialysis SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; NUCLEUS BASALIS; ACETYLCHOLINE-RELEASE; SUBSTANTIA INNOMINATA; POSSIBLE INVOLVEMENT; CHOLINERGIC NEURONS; CEREBRAL-CORTEX; DIAGONAL BAND; STIMULATION; WAKEFULNESS AB 1. The cholinergic system of the basal forebrain (BF) is hypothesized to play an important role in behavioural and electrocortical arousal. Adenosine has been proposed as a sleep-promoting substance that induces sleep by inhibiting cholinergic neurons of the BF and brainstem. However, adenosinergic influences on the activity of BF neurons in naturally awake and sleeping animals have not been demonstrated. 2. We recorded the sleep-make discharge profile of BF neurons and simultaneously assessed adenosinergic influences on wake- and sleep-related activity of these neurons by delivering adenosinergic agents adjacent to the recorded neurons with a microdialysis probe. Discharge rates of BF neurons were recorded through two to three sleep-wake episodes during baseline (artificial cerebrospinal fluid perfusion), and after delivering an adenosine transport inhibitor (s-(p-nitrobenzyl)-6-thioinosine; NBTI), or exogenous adenosine, or a selective adenosine A1. receptor antagonist (8-cyclopentyl-1,3-dimethylxanthine; CPDX). 3. NBTI and adenosine decreased the discharge rate of BF neurons during both waking and non-rapid eye movement (NREM) sleep. In contrast, CPDX increased the discharge rate of BF neurons during both waking and NREM sleep. These results suggest that in naturally awake and sleeping animals, adenosine exerts tonic inhibitory influences on BF neurons, supporting the hypothesized role of adenosine in sleep regulation. 4. However, in the presence of exogenous adenosine, NBTI or CPDX, BF neurons retained their wake- and sleep-related discharge patterns, i.e. still exhibited changes in discharge rate during transitions between waking and NREM sleep. This suggests that other neuro transmitters/neuromodulators also contribute to the sleep-wake discharge modulation of BF neurons. C1 Vet Affairs Greater Los Angeles Hlth Care Syst, North Hills, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90033 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90033 USA. RP McGinty, D (reprint author), Vet Affairs Greater Los Angeles Hlth Care Syst, 16111 Plummer St, North Hills, CA 91343 USA. EM dmcginty@ucla.edu FU NHLBI NIH HHS [HC 60296]; NIMH NIH HHS [MH 47480, R01 MH047480] NR 54 TC 114 Z9 120 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD DEC 15 PY 1999 VL 521 IS 3 BP 679 EP 690 DI 10.1111/j.1469-7793.1999.00679.x PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 273DB UT WOS:000084691200011 PM 10601498 ER PT J AU Gopalkrishnan, RV Christiansen, KA Goldstein, NI DePinho, RA Fisher, PB AF Gopalkrishnan, RV Christiansen, KA Goldstein, NI DePinho, RA Fisher, PB TI Use of the human EF-1 alpha promoter for expression can significantly increase success in establishing stable cell lines with consistent expression: a study using the tetracycline-inducible system in human cancer cells SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CONTROLLED GENE-EXPRESSION; EMBRYONAL CARCINOMA-CELLS; TRANSGENIC MICE; MAMMALIAN-CELLS; MELANOMA DIFFERENTIATION; REGULATED SYSTEM; VECTORS; GROWTH; TRANSACTIVATOR; DOXYCYCLINE AB Establishing cells with an exogenously introduced gene of interest under the inducible control of tetracycline (Tc) initially requires clonal cell lines stably expressing the tetracycline activator (tTA or rtTA). The originally described plasmid vectors expressing tTA/rtTA are driven by the cytomegalovirus (CMV) immediate early (IE) promoter-enhancer, known for its robust activity in a wide spectrum of cell types. While many reports testify to the utility and efficacy of this construct, instances of inexplicable failure to establish cell lines having inducible expression of the cDNA under study are encountered. Spontaneous extinction of CMV promoter activity in cells has been observed in a temporal and cell type-dependent manner. This could be a contributing factor in the failure to establish Tc-responsive cell lines. We here report that a change of the expression cassette to the human elongation factor-1 alpha (EF-1 alpha) promoter has permitted successful establishment of several inducible cell lines from diverse human tumor tissue origins. We interpret these results to imply that extinction of rtTA (or tTA) expression might be a significant factor in the lack of success in establishing Tc-inducible cell lines. Moreover, the present findings have general relevance to experiments requiring the use of stable cell lines. C1 Columbia Univ Coll Phys & Surg, Dept Urol, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Pathol, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Neurosurg, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Fisher, PB (reprint author), Columbia Univ Coll Phys & Surg, Dept Urol, Herbert Irving Comprehens Canc Ctr, 630 W 168th St, New York, NY 10032 USA. FU NCI NIH HHS [CA74468, CA35675] NR 46 TC 57 Z9 57 U1 2 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 15 PY 1999 VL 27 IS 24 BP 4775 EP 4782 DI 10.1093/nar/27.24.4775 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 270QN UT WOS:000084547200014 PM 10572178 ER PT J AU Yamada, K Shimizu, A Ierino, FL Utsugi, R Barth, RN Esnaola, N Colvin, RB Sachs, DH AF Yamada, K Shimizu, A Ierino, FL Utsugi, R Barth, RN Esnaola, N Colvin, RB Sachs, DH TI Thymic transplantation in miniature swine - I. Development and function of the "thymokidney" SO TRANSPLANTATION LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; DISPARATE RENAL-ALLOGRAFTS; BONE-MARROW; T-CELLS; NATURAL ANTIBODIES; MONOCLONAL-ANTIBODIES; ENDOTHELIAL-CELLS; SELF-TOLERANCE; INDUCTION; PIG AB Background. Previous studies in our laboratory have demonstrated the importance of the thymus for rapid and stable tolerance induction in an allotransplant model, The focus of the present study was to explore the feasibility of autologous thymic transplantation to produce a new transplantable organ (thymokidney) and to examine the function of subsequent vascularized thymokidney transplants in T cell development. Materials and Methods. Eight juvenile swine received autologous thymic grafts under the renal capsule. Thymic tissue was obtained through a partial (n=6) or complete (n=2) thymectomy, and growth of the autologous thymic graft was compared between partially and completely thymectomized animals. Two of the partially thymectomized animals received irradiated (1000 cGy) as well as non-irradiated autologous thymic grafts. Graft survival, growth and evidence of thymocyte development was determined by (a) macroscopic examination of the implanted tissue, (b) histological examination, and (c) flow cytometry, Naive CD4 SP T cells were identified by CD45RA-expression. Results. Growth of transplanted thymic tissue was demonstrated in all thymic graft recipients. No difference was seen between partially and completely thymectomized animals. By POD 60, the thymic grafts exhibited normal macroscopic and microscopic structure, and normal thymocyte composition, irradiated thymic tissue displayed a similar pattern of development, but growth was markedly delayed. To evaluate thymic function of the graft, a composite thymokidney was transplanted into a recipient which had previously been thymectomized, had few circulating CD4-single positive cells and had lost MLR reactivity. The number of CD4+/CD45RA+ cells in this animal increased steadily from POD 30 to POD 150, indicating that the thymus of the composite thymokidney allograft was functional; in addition, MLR assays demonstrated that the recipient recovered immunocompetence. Conclusions. The establishment of a thymokidney by thymic autografting to the renal subcapsular space results in normal thymic growth and function, and may provide a valuable tool for studying the role of the thymus in tolerance induction, As far as we are aware, we provide the first evidence of functional vascularized thymic graft reconstituting T cells and leading to a return of a immunocompetence in a large animal model. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02114 USA. RP Sachs, DH (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. RI Barth, Rolf/B-2542-2014 FU NHLBI NIH HHS [2PO1 HL01846-21A1]; NIAID NIH HHS [2RO1 AI31046B08] NR 44 TC 52 Z9 54 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 15 PY 1999 VL 68 IS 11 BP 1684 EP 1692 DI 10.1097/00007890-199912150-00011 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 266NJ UT WOS:000084305800011 PM 10609944 ER PT J AU Bartholomew, AM Powelson, J Sachs, DH Bailin, M Boskovic, S Colvin, R Hong, HZ Johnson, M Kimikawa, M LeGuern, A Meehan, S Sablinski, T Wee, SL Cosimi, AB AF Bartholomew, AM Powelson, J Sachs, DH Bailin, M Boskovic, S Colvin, R Hong, HZ Johnson, M Kimikawa, M LeGuern, A Meehan, S Sablinski, T Wee, SL Cosimi, AB TI Tolerance in a concordant nonhuman primate model SO TRANSPLANTATION LA English DT Article ID NONLETHAL PREPARATIVE REGIMEN; MONOCLONAL-ANTIBODIES; MARROW ENGRAFTMENT; NATURAL ANTIBODY; IMMUNE-RESPONSE; 15-DEOXYSPERGUALIN; DEOXYSPERGUALIN; REJECTION; PROLIFERATION; CHIMERISM AB Background. We have previously demonstrated that induction of mixed lymphohematopoietic chimerism resulted in donor specific renal allograft tolerance without the need for chronic immunosuppression in nonhuman primates. Here we have tested whether tolerance can be similarly induced for baboon to cynomolgus renal xenografts. Methods. After preconditioning with anti-thymocyte globulin (ATG), nonlethal total body irradiation, and thymic irradiation, cynomolgus monkeys underwent splenectomy, native nephrectomies, and baboon marrow and renal transplants. Postoperative cyclosporine was given for 28 days. Results. In Group 1 (n=2, survival=13, 14 days), both animals developed anti-donor immunoglobulin G, had biopsy findings consistent with humoral rejection, and showed rapidly progressive xenograft failure. In Group 2 (n=5, survival=1, 16, 33, 112, 190 days), 15-deoxyspergualine was added to the regimen (Day 0-13). In one long-term survivor, donor specific hyporesponsiveness was first observed (mixed lymphocyte culture [(MLR]) on Day 48. MLR reactivity returned on Day 64 together with the development of anti-donor antibody and subsequent xenograft failure on Day 112. Donor specific T-cell hyporesponsiveness was detected in the other long-term survivor for the first 133 days, after which a donor-specific skin xenograft was placed, (survival 24 days). Following the skin graft rejection, a rise in the MLR, development of anti-donor antibody and progressive rejection of the renal xenograft were observed. Conclusions. Antibody-mediated rejection seems to constitute the major difference between concordant xenografts and allografts. Addition of 15-deoxyspergualine for 2 weeks posttransplant extended concordant primate xenograft survival to 6 months without chronic immunosuppression. In contrast to the allogeneic model, renal transplant acceptance in this xenogeneic system was interrupted by placement of a donor-specific skin graft. C1 Massachusetts Gen Hosp, Gen Surg Serv, Transplantat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02114 USA. Biotransplant Inc, Charlestown, MA 02129 USA. RP Bartholomew, AM (reprint author), Univ Illinois Hosp, Dept Surg, 840 S Wood St M-C 958, Chicago, IL 60612 USA. FU NHLBI NIH HHS [HL-18646] NR 20 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 15 PY 1999 VL 68 IS 11 BP 1708 EP 1716 DI 10.1097/00007890-199912150-00014 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 266NJ UT WOS:000084305800014 PM 10609947 ER PT J AU Kawai, T Poncelet, A Sachs, DH Mauiyyedi, S Boskovic, S Wee, SL Ko, DSC Bartholomew, A Kimikawa, M Hong, HZ Abrahamian, G Colvin, RB Cosimi, AB AF Kawai, T Poncelet, A Sachs, DH Mauiyyedi, S Boskovic, S Wee, SL Ko, DSC Bartholomew, A Kimikawa, M Hong, HZ Abrahamian, G Colvin, RB Cosimi, AB TI Long-term outcome and alloantibody production in a non-myeloablative regimen for induction of renal allograft tolerance SO TRANSPLANTATION LA English DT Article ID MIXED ALLOGENEIC CHIMERISM; TRANSPLANTATION TOLERANCE; MYCOPHENOLATE MOFETIL; CARDIAC ALLOGRAFTS; PROLONGED SURVIVAL; CYNOMOLGUS MONKEYS; BLOOD-TRANSFUSION; SPLENECTOMY; RECIPIENTS; REJECTION AB Background. Multilineage chimerism and long-term acceptance of renal allografts has been produced in non-human primates conditioned with a nonmyeloablative regimen. Our study was undertaken to evaluate the immunological and pathological status of longterm survivors and to define the role of splenectomy and of the primarily vascularized kidney in the regimen. Method, Monkeys were treated with the basic regimen, including: total body irradiation, thymic irradiation, antithymocyte globulin, donor bone marrow transplantation, and a 4-week course of cyclosporine after which no further immunosuppression was given. They were divided into four groups according to the timing of kidney transplantation (KTx) and splenectomy as follows; group A (n=13): KTx and splenectomy on the day of donor bone marrow transplantation (day 0); group B (n=3): KTx on day 0 without splenectomy; group C (n=7): splenectomy on day 0 but delayed KTx until 3 to 16 weeks post-donor bone marrow transplantation; group D (n=3): both splenectomy and KTx delayed until day 120 post-donor bone marrow transplantation. Results. In group A, 11 of 13 monkeys developed chimerism and 9 monkeys achieved long-term survival of 4 to 70 months without evidence of chronic vascular rejection. Alloantibodies were detected in only one long-term survivor. In contrast, all three monkeys in group B developed alloantibodies and rejected their allografts, In group C, long-term survival without alloantibody production was observed in two of three monkeys that had developed chimerism, In group D, all three recipients were sensitized and rejected the kidney allografts rapidly after transplantation. Conclusions. 1) Production of anti-donor antibody was prevented in most recipients that developed mixed chimerism in the regimens with splenectomy at the time of donor bone marrow transplantation. 2) If splenectomy is not included in the initial conditioning regimen, induction of B cell tolerance is less likely and the result is late onset of alloantibody production and allograft rejection. 3) Immediate transplantation of the kidney at the time of recipient conditioning is not essential for induction of donor specific hyporesponsiveness by bone marrow transplantation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplantat Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Kawai, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplantat Unit, White 510,55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [P0I-HL 18646]; NIAID NIH HHS [R21 AI037692, R21 AI037692-06]; PHS HHS [R0I A137692-05] NR 31 TC 110 Z9 112 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 15 PY 1999 VL 68 IS 11 BP 1767 EP 1775 DI 10.1097/00007890-199912150-00022 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 266NJ UT WOS:000084305800022 PM 10609955 ER PT J AU Alexander, M Tekawa, I Hunkeler, E Fireman, B Rowell, R Selby, JV Massie, BM Cooper, W AF Alexander, M Tekawa, I Hunkeler, E Fireman, B Rowell, R Selby, JV Massie, BM Cooper, W TI Evaluating hypertension control in a managed care setting SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID BLOOD-PRESSURE AB Background: We conducted a retrospective cohort study on a random sample of adult patients with hypertension in a large health maintenance organization to assess the feasibility of documenting blood pressure (BP) control and to compare different measures for defining BP control. Methods: Three criteria for BP control were assessed: systolic BP less than 140 mm Hg; diastolic BP less than 90 mm Hg; and combined BP control, with systolic BP less than 140 mm Hg and diastolic BP less than 90 mm Hg. Four methods of assessing hypertension control by the above criteria were examined: proportion of patients with BP under control at 75% and 50% or more of their office visits; the mean of all pressures during the study period; and the BP from the last visit during the study period. Results: The proportion of patients meeting each criterion for control was similar whether we used the mean BP for all visits, the last recorded BP, or control at 50% or more of visits. Control rates were substantially lower when the more stringent assessment, 75% of visits, was used. The proportion of patients with combined BP control at 75% or more of their visits was half that of the other methods. Conclusions: In this health maintenance organization population, results with the use of the simplest approach, the last BP measurement recorded, were similar to results with the mean BP. Our findings indicate that evaluation of BP control in a large health maintenance organization will find substantial room for improvement, and clinicians should be encouraged to be more aggressive in their management of hypertension, especially with regard to the systolic BP, which until recent years has been underemphasized. C1 Kaiser Permanente, Div Res, Med Care Program, Oakland, CA 94611 USA. Univ Calif San Francisco, Med Effectiveness Res Ctr, Ctr Aging Diverse Communities, Div Gen Internal Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Astra Pharmaceut LP, Wayne, PA USA. RP Alexander, M (reprint author), Kaiser Permanente, Div Res, Med Care Program, 3505 Broadway,No Calif Reg, Oakland, CA 94611 USA. FU AHRQ HHS [HS07373]; NIA NIH HHS [1 P30 AG15272] NR 13 TC 76 Z9 77 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 DEC 13 PY 1999 VL 159 IS 22 BP 2673 EP 2677 DI 10.1001/archinte.159.22.2673 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 262EM UT WOS:000084052700007 PM 10597757 ER PT J AU Italiano, JE Lecine, P Shivdasani, RA Hartwig, JH AF Italiano, JE Lecine, P Shivdasani, RA Hartwig, JH TI Blood platelets are assembled principally at the ends of proplatelet processes produced by differentiated megakaryocytes SO JOURNAL OF CELL BIOLOGY LA English DT Article DE blood platelet; megakaryocyte; microtubules; actin cytoskeleton; thrombopoiesis ID MOUSE MEGAKARYOCYTES; IN-VITRO; ACTIN; RELEASE; CYTOSKELETON; THROMBIN; INVITRO; THROMBOCYTOPOIESIS; ORGANIZATION; INHIBITION AB Megakaryocytes release mature platelets in a complex process. Platelets are known to be released from intermediate structures, designated proplatelets, which are long, tubelike extensions of the megakaryocyte cytoplasm. We have resolved the ultrastructure of the megakaryocyte cytoskeleton at specific stages of proplatelet morphogenesis and correlated these structures with cytoplasmic remodeling events defined by video microscopy. Platelet production begins with the extension of large pseudopodia that use unique cortical bundles of microtubules to elongate and form thin proplatelet processes with bulbous ends; these contain a peripheral bundle of microtubules that loops upon itself and forms a teardrop-shaped structure. Contrary to prior observations and assumptions, time-lapse microscopy reveals proplatelet processes to be extremely dynamic structures that interconvert reversibly between spread and tubular forms. Microtubule coils similar to those observed in blood platelets are detected only at the ends of proplatelets and not within the platelet-sized beads found along the length of proplatelet extensions. Growth and extension of proplatelet processes is associated with repeated bending and bifurcation, which results in considerable amplification of free ends. These aspects are inhibited by cytochalasin B and, therefore, are dependent on actin. We propose that mature platelets are assembled de novo and released only at the ends of proplatelets, and that the complex bending and branching observed during proplatelet morphogenesis represents an elegant mechanism to increase the numbers of proplatelet ends. C1 Brigham & Womens Hosp, Div Hematol, Longwood Med Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Italiano, JE (reprint author), Brigham & Womens Hosp, Div Hematol, Longwood Med Res Ctr, 221 Longwood Ave,Room 609, Boston, MA 02115 USA. RI Lecine, Patrick/H-9338-2016 FU NHLBI NIH HHS [HL07680, HL56252, R01 HL056252] NR 48 TC 281 Z9 287 U1 2 U2 11 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 13 PY 1999 VL 147 IS 6 BP 1299 EP 1312 DI 10.1083/jcb.147.6.1299 PG 14 WC Cell Biology SC Cell Biology GA 266VM UT WOS:000084321000016 PM 10601342 ER PT J AU Kuppenbender, KD Albers, DS Iadarola, MJ Landwehrmeyer, GB Standaert, DG AF Kuppenbender, KD Albers, DS Iadarola, MJ Landwehrmeyer, GB Standaert, DG TI Localization of alternatively spliced NMDAR1 glutamate receptor isoforms in rat striatal neurons SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Review DE glutamate receptors; projection neurons; interneurons; striatum; cholinergic; calbindin ID D-ASPARTATE RECEPTOR; NITRIC-OXIDE SYNTHASE; PROTEIN-KINASE-C; SUBUNIT MESSENGER-RNA; PARVALBUMIN-IMMUNOREACTIVE NEURONS; CALCIUM-BINDING PROTEIN; EXCITATORY AMINO-ACIDS; HUNTINGTONS-DISEASE; BASAL GANGLIA; PROJECTION NEURONS AB Alternative splicing of the mRNA encoding the N-methyl-D-aspartate (NMDA) receptor subunit NR1 changes the structural, physiologic, and pharmacologic properties of the resultant NMDA receptors. We used dual label immunocytochemistry and confocal microscopy to localize the four alternatively spliced segments of the NR1 subunit (N1, C1, C2, and C2') in rat striatal neurons. Striatofugal projection neurons and four populations of interneurons were studied. Projection neurons, which were identified by immunolabeling for calbindin and by retrograde tracing from the globus pallidus and the substantia nigra, were the only striatal neurons containing C1 segment immunoreactivity. Projection neurons were also C2 segment immunopositive, as were all other neuronal populations studied. Projection neurons were C2' segment immunonegative. In contrast, each of the interneuron types were labeled by the antibody to the C2' segment: nitric oxide synthase interneurons were labeled intensely, calretinin and parvalbumin neurons were labeled moderately strongly, and cholinergic neurons were also labeled but less strongly than the other types of interneurons. Parvalbumin interneurons showed distinct N1 segment immunolabeling, which was not found in other types of striatal neurons. Our results suggest that all striatal neurons studied synthesize NR1 subunit proteins, but the isoforms of the protein present in projection neurons and the several types of interneurons are distinct. This differential expression of NR1 isoforms may affect both neuronal function and selective vulnerability of neurons to injury. (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Neurol Serv, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Freiburg, Dept Neurol, D-79106 Freiburg, Germany. NIDR, Pain & Neurosensory Mechanisms Branch, Bethesda, MD 20892 USA. RP Standaert, DG (reprint author), Massachusetts Gen Hosp, Neurol Serv, Dept Neurol, Warren 408,Fruit St, Boston, MA 02114 USA. OI Standaert, David/0000-0003-2921-8348 FU NINDS NIH HHS [NS31579, NS34361] NR 122 TC 23 Z9 23 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD DEC 13 PY 1999 VL 415 IS 2 BP 204 EP 217 PG 14 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 252TP UT WOS:000083518600005 PM 10545160 ER PT J AU Kosinski, CM Bradley, SR Conn, PJ Levey, AI Landwehrmeyer, GB Penney, JB Young, AB Standaert, DG AF Kosinski, CM Bradley, SR Conn, PJ Levey, AI Landwehrmeyer, GB Penney, JB Young, AB Standaert, DG TI Localization of metabotropic glutamate receptor 7 mRNA and mGluR7a protein in the rat basal ganglia SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE globus pallidus; corticostriatal pathway; presynaptic receptors; confocal microscopy; electron microscopy ID QUINOLINIC ACID LESIONS; MESSENGER-RNA; SUBTHALAMIC NUCLEUS; MOLECULAR CHARACTERIZATION; PRESYNAPTIC LOCALIZATION; FUNCTIONAL-ANATOMY; SUBSTANTIA-NIGRA; STRIATAL NEURONS; PHA-L; EXPRESSION AB Metabotropic glutamate receptors (mCluRs) coupled to G-proteins have important roles in the regulation of basal ganglia function. We have examined the localization of the mGluR7 mRNA and mGluR7a protein in the basal ganglia of the rat. Strong mGluR7 hybridization signals are found in cerebral cortex and striatum, but much less intense signals are present in other components of the basal ganglia. Abundant mGluR7a immunoreactivity was found in striatum, globus pallidus (GP), and substantia nigra pars reticulata (SNr). Examination using confocal microscopy together with dendritic and presynaptic markers as well as studies in lesion models provided evidence for the presence of mGluR7a on presynaptic terminals in all three structures. Electron microscopic studies confirmed the presence of mGluR7a in axon terminals in both the striatum and the GP and also revealed the presence of mGluR7a at postsynaptic sites in both of these regions. Our data demonstrate that mGluR7a is located not only on presynaptic glutamatergic terminals of the corticostriatal pathway, where it may serve as an autoreceptor, but also on terminals of striatopallidal and striatonigral projections, where it may modulate the release of gamma-aminobutyric acid (GABA). The presence of mGluR7 at these multiple sites in the basal ganglia suggests that this receptor has a particularly crucial role in modulating neurotransmitter release in major basal ganglia pathways. (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Harvard Med Sch, Neurol Serv, Boston, MA 02114 USA. Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. Univ Freiburg, Dept Neurol, D-79106 Freiburg, Germany. RP Standaert, DG (reprint author), Massachusetts Gen Hosp, Neurol Serv, Warren 408,Fruit St, Boston, MA 02114 USA. RI Conn, Peter/D-7848-2012; Levey, Allan/F-2104-2011; OI Levey, Allan/0000-0002-3153-502X; Standaert, David/0000-0003-2921-8348 FU NINDS NIH HHS [NS31373, NS31579, NS34361] NR 61 TC 108 Z9 111 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD DEC 13 PY 1999 VL 415 IS 2 BP 266 EP 284 PG 19 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 252TP UT WOS:000083518600009 PM 10545164 ER PT J AU Kaelin, WG AF Kaelin, WG TI The p53 gene family SO ONCOGENE LA English DT Review DE p53; p73; p63; KET; p51; p40 ID P53-RELATED PROTEIN; P73 GENE; EXPRESSION; HOMOLOG; NEUROBLASTOMA; ONCOPROTEINS; MUTATIONS; APOPTOSIS; CANCERS; TUMORS AB p73 and p63 are two recently discovered p53 homologs, Like p53, these proteins can recognize canonical p53 DNA-binding sites and, when overproduced, can activate p53-responsive target genes and induce apoptosis. Unlike p53, these genes undergo complex alternative splicing which, at least in the case of p63, yields proteins with widely divergent biological properties. In addition p73 and p63 are, in contrast to p53, rarely mutated in human cancer. Furthermore, p73 inactivation is not required for viral transformation. Thus, there is currently no firm evidence that p63 and p73 should be considered tumor suppressors, The early suggestion that monoallelic expression of p73 contributed to carcinogenesis needs to be interpreted cautiously in light of data showing interindividual and intraindividual variation with respect to monoallelic expression of p73 and the finding that p73 mRNA levels are generally increased, rather than decreased, in a host of tumors relative to normal cells. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. NR 33 TC 146 Z9 151 U1 0 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 13 PY 1999 VL 18 IS 53 BP 7701 EP 7705 DI 10.1038/sj.onc.1202955 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 272DD UT WOS:000084634500009 PM 10618710 ER PT J AU Walker, B AF Walker, B TI Effects of therapy on helper T cell responses in acute and chronic HIV infection SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 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 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD DEC 10 PY 1999 VL 15 IS 18 BP 1599 EP 1599 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 263VV UT WOS:000084146700003 ER PT J AU Lieberman, J AF Lieberman, J TI Immunotherapy with HIV-specific cytotoxic T lymphocytes SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 0 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 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD DEC 10 PY 1999 VL 15 IS 18 BP 1616 EP 1616 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 263VV UT WOS:000084146700032 ER PT J AU Lewin, M Bredow, S Sergeyev, N Marecos, E Bogdanov, A Weissleder, R AF Lewin, M Bredow, S Sergeyev, N Marecos, E Bogdanov, A Weissleder, R TI In vivo assessment of vascular endothelial growth factor-induced angiogenesis SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID TUMOR BLOOD-FLOW; BREAST-CARCINOMA; CONTRAST AGENTS; PERMEABILITY; INDICATOR; VOLUME; MODEL; RAT AB To determine whether vascular endothelial growth factor NMR imaging, an experimental study was conducted in nude mice. Human breast cancer cells (MCF-7) and MCF-7 cells stably transfected with the cDNA for the VEGF(165) isoform (MV165) were grown in nude mice and models were characterized by RT-PCR, Western blotting, ELISA, immunohistochemistry and NMR imaging using a novel synthetic protected graft copolymer (PGC) as a vascular probe, MV165 tumors showed a 1.6-fold higher microvascular density by histology, Both tumors showed identical MR signal intensities on non-contrast and Gd-DTPA enhanced images. PGC enhanced MR imaging of tumoral vascular volume fraction (VVF), however, revealed significant differences between the 2 tumor types (MV165: 8.9 +/- 2.1; MCF-7: 1.7 +/- 0.5; p < 0.003), as expected from histology, VVF changes were more heterogeneous in the MV165 model both among tumors as well as within tumors as determined 3-dimensionally at submillimeter resolutions. Our results have potential applications for non-invasive assessment of angiogenesis by in vivo imaging and for clinical monitoring during angiogenic therapies. (C) 1999 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Weissleder, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, 149 13th St,5403, Charlestown, MA 02129 USA. FU NCI NIH HHS [1RO1 CA74424-01]; NINDS NIH HHS [5RO1 NS35258-03] NR 32 TC 39 Z9 41 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 10 PY 1999 VL 83 IS 6 BP 798 EP 802 DI 10.1002/(SICI)1097-0215(19991210)83:6<798::AID-IJC16>3.0.CO;2-W PG 5 WC Oncology SC Oncology GA 260FP UT WOS:000083939100017 PM 10597197 ER PT J AU Zhu, QA Zeng, CM Huhalov, A Yao, J Turi, TG Danley, D Hynes, T Cong, Y DiMattia, D Kennedy, S Daumy, G Schaeffer, E Marasco, WA Huston, JS AF Zhu, QA Zeng, CM Huhalov, A Yao, J Turi, TG Danley, D Hynes, T Cong, Y DiMattia, D Kennedy, S Daumy, G Schaeffer, E Marasco, WA Huston, JS TI Extended half-life and elevated steady-state level of a single-chain Fv intrabody are critical for specific intracellular retargeting of its antigen, caspase-7 SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE sFv intrabody; protein turnover; intracellular targeting; caspase-7; apoptosis ID ANTIBODY-BINDING SITES; GENE-THERAPY; INTERLEUKIN-2 RECEPTOR; ENGINEERED ANTIBODIES; CELL-LINES; IN-VITRO; EXPRESSION; PROTEINS; ERBB-2; PHAGE AB Two single-chain Fv (sFv) antibodies (C8 and H2) specific for Mch3/caspase-7, a component in the signaling pathway for induction of apoptosis, were genetically fused to different intracellular targeting signals and analyzed by expression in mammalian cells. Immunofluorescence microscopy confirmed that these anti-caspase-7 intrabodies were expressed in the cellular compartments dictated by their C-terminal trafficking signals. Cytosolic caspase-7 was successfully retargeted to different subcellular compartments by specific intrabodies through direct association of antigen with intrabody. Sequestration of caspase-7 in nuclei had a significant biological impact in that the expression of a nuclear-targeted anti-caspase-7 intrabody in a stable Jurkat cell Line markedly inhibited staurosporine-induced apoptosis. The criteria for choosing an optimal intrabody were also evaluated in this study. A gene dosage titration study demonstrated that the C8 intrabody was more potent in retargeting of caspase-7 than the H2 intrabody, even though the H2 sFv had a higher affinity for caspase-7 than the C8. Pulse-chase experiments and western blot analysis revealed that the anti-caspase-7 C8 sFv intrabodies exhibited a long half-life (>8 h) and high steady-state levels of protein accumulation, while the H2 intrabodies had a half-life of 2 h and less protein at steady state. These results suggest that the choice of sFv as an intrabody depends critically on the intracellular sFv protein having an extended half-life and elevated steady-state level, Thus, extended half-life must be considered together with sFv antibody specificity and affinity when choosing an optimal sFv intrabody for functional studies of cellular proteins. (C) 1999 Elsevier Science B.V. All rights reserved. C1 IntraImmune Therapies Inc, Boston, MA 02215 USA. Pfizer Inc, Cent Res, Groton, CT 06340 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Zhu, QA (reprint author), IntraImmune Therapies Inc, POB 15599, Boston, MA 02215 USA. NR 47 TC 41 Z9 44 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD DEC 10 PY 1999 VL 231 IS 1-2 BP 207 EP 222 DI 10.1016/S0022-1759(99)00158-1 PG 16 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 290JU UT WOS:000085673800018 PM 10648939 ER PT J AU Marasco, WA LaVecchio, J Winkler, A AF Marasco, WA LaVecchio, J Winkler, A TI Human anti-HIV-1 tat sFv intrabodies for gene therapy of advanced HIV-1-infection and AIDS SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE AIDS; gene therapy; intrabodies; intracellular antibodies; HIV infection; AD, activation domain of Tat; ARM, arginine-rich motif of Tat ID HUMAN-IMMUNODEFICIENCY-VIRUS; NF-KAPPA-B; ACTIVE ANTIRETROVIRAL THERAPY; SINGLE-CHAIN INTRABODIES; CYTOTOXIC T-LYMPHOCYTES; GRAFT-VERSUS-LEUKEMIA; LONG TERMINAL REPEAT; HIV-1 TAT; CD28 COSTIMULATION; TRANS-ACTIVATOR AB The early successes of highly active anti-retroviral therapies (HAART) for the treatment of HIV-1-infection and AIDS have raised the question as to whether there is a legitimate role for gene therapy in the treatment of this chronic infectious disease. However, in many patients the profound suppression of viral replication is short lived, particularly if patients have been treated with sequential monotherapies in the past, have been infected with a highly drug resistant isolate of HIV-1, or have temporarily discontinued therapy as a "holiday" or because of drug intolerance. In addition, life-long adherence to maintenance HAART will probably be required even in responding patients with undetectable viremia because of the reservoirs of latently infected cells that can persist for years. Gene therapy through the introduction of anti-retroviral "resistance" genes into CD4(+) T cells is one approach that could give long term protection to these HIV-1 susceptible cells in vivo. We have explored this approach by developing intrabodies to the critical HIV-1 transactivator protein, Tat that is absolutely required for HIV-1 replication. This provocative treatment approach, that will be tested in a clinical gene therapy trial, sets the groundwork for determining if anti-Tat intrabody gene therapy together with HAART can provide a treatment strategy for the immune reconstitution of HIV-1-infected patients with advanced disease. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Marasco, WA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. FU NCI NIH HHS [P30 CA06516]; NIAID NIH HHS [AI28785, AI28691] NR 90 TC 50 Z9 51 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD DEC 10 PY 1999 VL 231 IS 1-2 BP 223 EP 238 DI 10.1016/S0022-1759(99)00159-3 PG 16 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 290JU UT WOS:000085673800019 PM 10648940 ER PT J AU Nishizawa, K Nishizawa, M Kim, KS AF Nishizawa, K Nishizawa, M Kim, KS TI Tendency for local repetitiveness in amino acid usages in modern proteins SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE microsatellite; coding regions; peptide motif; triplet repeat ID CODING SEQUENCES; MICROSATELLITE LOCI; SYNTHETIC PEPTIDES; TRANSPORT PROTEIN; EVOLUTION; PSEUDOGENES; SPECIFICITY; MUTATION; REPEATS; GENES AB Systematic analyses of human proteins show that neural and immune system-specific, and therefore, relatively "modern" proteins have a tendency for repetitive use of amino acids at a local scale (similar to 1-20 residues), while ancient proteins (human homologues of Escherichia coli proteins) do not. Those protein subsegments which are unique based on homology search account for the repetitiveness. Simulation shows that such repetitiveness can be maintained by frequent duplication on a very short scale tone to two codons) in the presence of substitutive point mutation, while the latter tends to mitigate the repetitiveness. DNA analyses also show the presence of cryptic (i.e. "out of the codon frame") repetitiveness, which cannot fully be explained by features in protein sequences. Simulative modification of the amino acid sequences of immune system-specific proteins estimate that 2.4 duplication events occur during the period equivalent to ten events of substitution mutation. It is also suggested that the repetitiveness leads to longitudinal unevenness within a given peptide domain. Those peptide motifs which contain similarly charged residues are likely to be generated more frequently in the presence of the tendency for repetitiveness than in its absence. Therefore, the neutral propensity of DNA for duplication, which can also tend to generate repetitiveness in amino acid sequences, seems to be manifested primarily when the constraints on amino acid sequences are relatively weak, and yet may be positively contributing to generation of unevenness in modem proteins. (C) 1999 Academic Press. C1 Teikyo Univ, Sch Med, Dept Biochem, Tokyo 173, Japan. Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. RP Nishizawa, K (reprint author), Teikyo Univ, Sch Med, Dept Biochem, Tokyo 173, Japan. NR 41 TC 13 Z9 13 U1 0 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD DEC 10 PY 1999 VL 294 IS 4 BP 937 EP 953 DI 10.1006/jmbi.1999.3275 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 264NM UT WOS:000084188400009 PM 10588898 ER PT J AU Zylka, MJ Reppert, SM AF Zylka, MJ Reppert, SM TI Discovery of a putative heme-binding protein family (SOUL/HBP) by two-tissue suppression subtractive hybridization and database searches SO MOLECULAR BRAIN RESEARCH LA English DT Article DE circadian rhythm; melatonin; PCR select; suppression subtractive hybridization; heme-binding protein ID ACETYLTRANSFERASE MESSENGER-RNA; CHICKEN PINEAL-GLAND; CIRCADIAN CLOCK; MELATONIN RECEPTORS; GENE-EXPRESSION; CELL-CULTURE; BRAIN; DIFFERENTIATION; ENTRAINMENT; RHYTHMS AB In the domestic chicken, Gallus gallus, the retina and pineal gland contain circadian clocks that are directly entrained by environmental light-dark cycles. To identify novel genes that are expressed in the retina and pineal gland, we performed two-tissue suppression subtractive hybridization (SSH). Two-tissue SSH is designed to identify genes expressed in common between two RNA samples while at the same time subtracting out abundant transcripts. Using this method, we identified a novel chicken gene, named ckSoul, that is strongly expressed in the retina and pineal gland. The protein product of ckSoul is similar to a novel heme-binding protein (p22 HBP) and to an uncharacterized mammalian gene in the expressed sequence tag (EST) database. The mouse transcript of this new gene is expressed in the retina and may represent the mammalian ortholog of ckSoul. Molecular analysis of the mammalian and chicken proteins suggests SOUL and HBP are members of a new family of heme-binding proteins, (C) 1999 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Serv Pediat, Lab Dev Chronobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Reppert, SM (reprint author), Massachusetts Gen Hosp, Serv Pediat, Lab Dev Chronobiol, Jackson 1226, Boston, MA 02114 USA. NR 31 TC 48 Z9 52 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 DEC 10 PY 1999 VL 74 IS 1-2 BP 175 EP 181 DI 10.1016/S0169-328X(99)00277-6 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 269WA UT WOS:000084499500018 ER PT J AU Gomez-Isla, T Growdon, WB McNamara, M Newell, K Gomez-Tortosa, E Hedley-Whyte, ET Hyman, BT AF Gomez-Isla, T Growdon, WB McNamara, M Newell, K Gomez-Tortosa, E Hedley-Whyte, ET Hyman, BT TI Clinicopathologic correlates in temporal cortex in dementia with Lewy bodies SO NEUROLOGY LA English DT Article DE superior temporal sulcus; stereology; Lewy bodies; neuronal loss; neurofibrillary tangles; amyloid deposition; dementia with Lewy bodies ID ALZHEIMER-TYPE PATHOLOGY; BODY DISEASE; PARKINSONS-DISEASE; SENILE DEMENTIA; NEUROFIBRILLARY TANGLES; NEURITIC PLAQUES; ALPHA-SYNUCLEIN; CONSORTIUM; DIAGNOSIS; MUTATION AB Objective: To address the relationship between dementia and neuropathologic findings in dementia with Lewy bodies (DLB) in comparison with AD. Methods: We evaluated the clinical presentation of autopsy-confirmed DLB in comparison with AD according to new Consortium on DLB criteria and compared the two conditions using quantitative neuropathologic techniques. This clinicopathologic series included 81 individuals with AD, 20 with DLB (7 "pure" DLB and 13 "DLB/AD"), and 33 controls. We counted number of LB, neurons, senile plaques (SP), and neurofibrillary tangles (NFT) in a high order association cortex, the superior temporal sulcus (STS), using stereologic counting techniques. Results: The sensitivity and specificity of Consortium on DLB clinical criteria in this series for dementia, hallucinations, and parkinsonism are 53% and 83%, respectively, at the patient's initial visit and 90% and 68%, respectively, if data from all clinic visits are considered. In pathologically confirmed DLB brains, LB formation in an association cortical area does not significantly correlate with duration of illness, neuronal loss, or concomitant AD-type pathology. Unlike AD, there is no significant neuronal loss in the STS of DLB brains unless there is concomitant AD pathology (neuritic SP and NFT). Conclusions: The evaluation of new Consortium on DLB criteria in this series highlights their utility and applicability in clinicopathologic studies but suggests that sensitivity and specificity, especially at the time of the first clinical evaluation, are modest. The lack of a relationship of LB formation to the amount of Alzheimer-type changes in this series suggests that DLB is a distinct pathology rather than a variant of AD. C1 Dept Neurol, Minneapolis, MN 55455 USA. Massachusetts Gen Hosp, Serv Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. RP Gomez-Isla, T (reprint author), Dept Neurol, Mayo Bldg,Box 295,420 Delaware St, Minneapolis, MN 55455 USA. FU NIA NIH HHS [AG06786, AG08031, AG05134] NR 43 TC 69 Z9 70 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 10 PY 1999 VL 53 IS 9 BP 2003 EP 2009 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 265QR UT WOS:000084255300018 PM 10599772 ER PT J AU Schwartz, RL Barrett, AM Kim, M Heilman, KM AF Schwartz, RL Barrett, AM Kim, M Heilman, KM TI Ipsilesional intentional neglect and the effect of cueing SO NEUROLOGY LA English DT Article DE neglect; attention; intention; cueing ID UNILATERAL FRONTAL LESION; RIGHT-HEMISPHERE; DIRECTIONAL HYPOKINESIA; MOTOR NEGLECT; ATTENTION; INATTENTION; HEMINEGLECT; LATERALITY; BEHAVIOR; DAMAGE AB Background: Contralesional hemispatial neglect may be induced by an attentional deficit where patients are inattentive to or unaware of stimuli in contralesional hemispace, an intentional deficit where patients are unable to act in or towards contralesional hemispace, or both. The deficits associated with ipsilesional neglect have not been as well chararacterized. Because cueing may be used as a rehabilitative assistive device, we wanted to learn whether the efficacy of an attentional or intentional cue was related to the type of bias. Methods: We studied a patient with a right frontotemporal stroke who had ipsilesional neglect by using a video apparatus that dissociates sensory-attentional and motor-intentional systems. We also performed a cueing experiment with primarily sensory-attentional cues (i.e., read the letter at the end of the line) and primarily motor-intentional cues (i.e., touch the end of the line). Results and Conclusions: Ipsilesional neglect was primarily a motor-intentional deficit with a motor-action bias to the left and a secondary sensory-attentional bias for stimuli to the right. With cueing we found a double dissociation: the rightwards motor-intentional cue improved the primary left-sided intentional bias and the leftwards sensory-attentional cue improved the secondary right-sided attentional bias. Effective rehabilitation strategies need to address both sensory-attentional and motor-intentional deficits in patients with neglect. C1 Univ Florida, Hlth Sci Ctr, Dept Neurol, Gainesville, FL 32610 USA. St Barnabas Med Ctr, Inst Neurol & Neurosurg, Livingston, NJ USA. Dept Vet Affairs Med Ctr, Neurol Serv, Gainesville, FL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Heilman, KM (reprint author), Univ Florida, Hlth Sci Ctr, Dept Neurol, POB 286, Gainesville, FL 32610 USA. RI Kim, Manho/J-2738-2012; OI Barrett, A.M./0000-0002-0789-2887 FU NINDS NIH HHS [K08 NS002085] NR 32 TC 16 Z9 16 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 10 PY 1999 VL 53 IS 9 BP 2017 EP 2022 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 265QR UT WOS:000084255300020 PM 10599774 ER PT J AU Aylward, EH Minshew, NJ Goldstein, G Honeycutt, NA Augustine, AM Yates, KO Barta, PE Pearlson, GD AF Aylward, EH Minshew, NJ Goldstein, G Honeycutt, NA Augustine, AM Yates, KO Barta, PE Pearlson, GD TI MRI volumes of amygdala and hippocampus in non-mentally retarded autistic adolescents and adults SO NEUROLOGY LA English DT Article DE limbic; hippocampus; amygdala; autism; brain volume; neuroimaging; MRI ID PERVASIVE DEVELOPMENTAL DISORDERS; DIAGNOSTIC INTERVIEW; FACIAL EXPRESSIONS; INFANTILE-AUTISM; BRAIN; ABNORMALITIES; INDIVIDUALS; DEFICITS AB Objective: To determine whether volumes of hippocampus and amygdala are abnormal in people with autism. Background: Neuropathologic studies of the limbic system in autism have found decreased neuronal size, increased neuronal packing density, and decreased complexity of dendritic arbors in hippocampus, amygdala, and other limbic structures. These findings are suggestive of a developmental curtailment in the maturation of the neurons and neuropil. Methods: Measurement of hippocampus, amygdala, and total brain volumes from 1.5-mm coronal, spoiled gradient-recalled echo MRI scans in 14 non-mentally retarded autistic male adolescents and young adults and 14 individually matched, healthy community volunteers. Results: Amygdala volume was significantly smaller in the autistic subjects, both with (p = 0.006) and without (p = 0.01) correcting for total brain volume. Total brain volume and absolute hippocampal volume did not differ significantly between groups, but hippocampal volume, when corrected for total brain volume, was significantly reduced (p = 0.04) in the autistic subjects. Conclusions: There is a reduction in the volume of amygdala and hippocampus in people with autism, particularly in relation to total brain volume. The histopathology of autism suggests that these volume reductions are related to a reduction in dendritic tree and neuropil development, and likely reflect the underdevelopment of the neural connections of limbic structures with other parts of the brain, particularly cerebral cortex. C1 Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Div Psychiat Neuroimaging, Baltimore, MD 21205 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Highland Dr Div, Pittsburgh, PA USA. RP Aylward, EH (reprint author), Univ Washington, Sch Med, Dept Radiol, Box 357115, Seattle, WA 98195 USA. FU NICHD NIH HHS [HD 35469]; NINDS NIH HHS [NS 33355] NR 34 TC 294 Z9 299 U1 6 U2 25 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 10 PY 1999 VL 53 IS 9 BP 2145 EP 2150 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 265QR UT WOS:000084255300042 PM 10599796 ER PT J AU Yuan, PQ Yang, H AF Yuan, PQ Yang, H TI Hyperthyroidism decreases thyrotropin-releasing hormone gene expression in the caudal raphe nuclei and the parapyramidal regions in rats SO NEUROSCIENCE LETTERS LA English DT Article DE autonomic disorders; hypothyroid; substance P; in situ hybridization; thyroid hormones; feedback regulation ID PROJECTIONS; BRAIN AB Altered thyroid statuses are associated with autonomic disorders. Medullary thyrotropin-releasing hormone (TRH) and substance P (SP) regulate autonomic nervous activity. The influences of thyroid statuses on TRH and SP gene expressions in the caudal raphe nuclei and the parapyramidal regions were studied using quantitative in situ hybridization histochemistry. In male rats thyroidectomized (Tx) for 30 days, the serum T-4 levels decreased by 64% and the medullary pro-TRH mRNA signals (silver grains per neuron) significantly increased by 32-45%. These changes were prevented by daily i.p. T-4 (2 mu g/100 g) injection in Tx rats. In sham operated/T-4 (20 mu g/100 g, daily) injected rats, T-4 levels significantly increased by 88% and the silver g rains decreased by 38-40%. Medullary SP mRNA signals were not significantly:changed by altering thyroid status. These results support the concept that thyroid hormone regulates medullary TRH gene expression by negative feedback. (C) 1999 Elsevier Science Ireland Ltd. Ail rights reserved. C1 W Los Angeles Vet Affairs Med Ctr, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Brain Res Inst, Los Angeles, CA 90073 USA. Dept Med, Div Digest Dis, Los Angeles, CA 90073 USA. RP Yang, H (reprint author), W Los Angeles Vet Affairs Med Ctr, CURE Digest Dis Res Ctr, Room 203,Bldg 115,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-41301, DK-50255] NR 19 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD DEC 10 PY 1999 VL 276 IS 3 BP 189 EP 192 DI 10.1016/S0304-3940(99)00830-7 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 264GA UT WOS:000084171200013 PM 10612637 ER PT J AU Patrick, GN Zukerberg, L Nikolic, M de la Monte, S Dikkes, P Tsai, LH AF Patrick, GN Zukerberg, L Nikolic, M de la Monte, S Dikkes, P Tsai, LH TI Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration SO NATURE LA English DT Article ID CYCLIN-DEPENDENT KINASE-5; NEURONAL-SPECIFIC ACTIVATOR; GLYCOGEN-SYNTHASE KINASE-3; DIRECTED PROTEIN-KINASE; CENTRAL-NERVOUS-SYSTEM; APOPTOTIC CELL-DEATH; TAU-PROTEIN; ALZHEIMERS-DISEASE; REGULATORY SUBUNIT; CEREBRAL-CORTEX AB Cyclin-dependent kinase 5 (Cdk5) is required for proper development of the mammalian central nervous system. To be activated, Cdk5 has to associate with its regulatory subunit, p35, We have found that p25, a truncated form of p35, accumulates in neurons in the brains of patients with Alzheimer's disease. This accumulation correlates with an increase in Cdk5 kinase activity. Unlike p35, p25 is not readily degraded, and binding of p25 to Cdk5 constitutively activates Cdk5, changes its cellular location and alters its substrate specificity, In vivo the p25/Cdk5 complex hyperphosphorylates tau, which reduces tau's ability to associate with microtubules, Moreover, expression of the p25/Cdk5 complex in cultured primary neurons induces cytoskeletal disruption, morphological degeneration and apoptosis, These findings indicate that cleavage of p35, followed by accumulation of p25, may be involved in the pathogenesis of cytoskeletal abnormalities and neuronal death in neurodegenerative diseases. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp E, Ctr Canc, Charlestown, MA 02119 USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Tsai, LH (reprint author), Harvard Univ, Sch Med, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. NR 49 TC 974 Z9 1033 U1 7 U2 40 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 9 PY 1999 VL 402 IS 6762 BP 615 EP 622 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 264PC UT WOS:000084189800054 PM 10604467 ER PT J AU Messing, EM Manola, J Sarosdy, M Wilding, G Crawford, ED Trump, D AF Messing, EM Manola, J Sarosdy, M Wilding, G Crawford, ED Trump, D TI Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RADIATION-THERAPY; ONCOLOGY GROUP; DEFINITIVE RADIOTHERAPY; ANDROGEN SUPPRESSION; DOUBLE-BLIND; LYMPH-NODES; CARCINOMA; TRIAL; FLUTAMIDE; ANTIGEN AB Background: Because the optimal timing of the institution of antiandrogen therapy for prostate cancer is controversial, we compared immediate and delayed treatment in patients who had minimal residual disease after radical prostatectomy. Methods: Ninety-eight men who underwent radical prostatectomy and pelvic lymphadenectomy and who were found to have nodal metastases were randomly assigned to receive immediate antiandrogen therapy, with either goserelin, a synthetic agonist of gonadotropin-releasing hormone, or bilateral orchiectomy, or to be followed until disease progression. The patients were assessed quarterly during the first year and then semiannually. Results: After a median of 7.1 years of follow-up, 7 of 47 men who received immediate antiandrogen treatment had died, as compared with 18 of 51 men in the observation group (P = 0.02). The cause of death was prostate cancer in 3 men in the immediate-treatment group and in 16 men in the observation group (P<0.01). At the time of the last follow-up, 36 men in the immediate-treatment group (77 percent) and 9 men in the observation group (18 percent) were alive and had no evidence of recurrent disease, including undetectable serum prostate-specific antigen levels (P<0.001). In the observation group, the disease recurred in 42 men; 13 of the 36 who were treated had a complete response to local treatment or hormonal therapy (or both), 16 died of prostate cancer, and 1 died of another disease. The remaining men in this group were alive with progressive disease at the time of the last follow-up or had had a recent relapse. Except for the treatment group (immediate therapy or observation), no clinical or histologic characteristic significantly influenced the outcome. Conclusions: Immediate antiandrogen therapy after radical prostatectomy and pelvic lymphadenectomy improves survival and reduces the risk of recurrence in patients with node-positive prostate cancer. (N Engl J Med 1999;341:1781-8.) (C)1999, Massachusetts Medical Society. C1 Univ Rochester, Med Ctr, Dept Urol, Rochester, NY 14642 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas San Antonio, San Antonio, TX 78285 USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. RP Messing, EM (reprint author), Univ Rochester, Med Ctr, Dept Urol, 601 Elmwood Ave,Box 656, Rochester, NY 14642 USA. EM edward_messing@urmc.rochester.edu FU NCI NIH HHS [CA11083, CA22433, CA23318] NR 53 TC 798 Z9 818 U1 4 U2 8 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 9 PY 1999 VL 341 IS 24 BP 1781 EP 1788 DI 10.1056/NEJM199912093412401 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 262NU UT WOS:000084074000001 PM 10588962 ER PT J AU Brugge, WR Van Dam, J AF Brugge, WR Van Dam, J TI Medical progress: Pancreatic and biliary endoscopy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID FINE-NEEDLE ASPIRATION; COMMON BILE-DUCT; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; PRIMARY SCLEROSING CHOLANGITIS; CONTROLLED CLINICAL-TRIAL; CYSTIC-FIBROSIS GENE; RETROGRADE CHOLANGIOPANCREATOGRAPHY; LAPAROSCOPIC CHOLECYSTECTOMY; COMPUTED-TOMOGRAPHY; ODDI DYSFUNCTION C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, Gastrointestinal Endoscopy Unit, Blake 452C, Boston, MA 02114 USA. NR 124 TC 33 Z9 34 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 9 PY 1999 VL 341 IS 24 BP 1808 EP 1816 DI 10.1056/NEJM199912093412406 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 262NU UT WOS:000084074000006 PM 10588967 ER PT J AU Masur, H Kaplan, JE Holmes, KK Alston, BL Ampel, N Anderson, JR Baker, AC Barr, D Bartlett, JG Bennett, JE Benson, CA Bozzette, SA Chaisson, RE Crumpacker, CS Currier, JS Deyton, L Drew, WL Duncan, WR Eisinger, RW El-Sadr, W Feinberg, J Freedberg, KA Furrer, H Gnann, JW Goldberger, MJ Goldie, S Goosby, EP Gross, PA Hafner, R Havlir, D Hooton, TM Jabs, DA Jacobson, MA Janoff, E Kitahata, M Kovacs, JV Leport, C Levin, MJ Lopez, JC Marco, M Mayers, DL Melnick, DA Mofenson, LM Montaner, JSG Moore, R Neaton, J Nelson, C O'Neill, JF Palefsky, J Pau, A Phair, JP Piscitelli, S Polis, MA Quinn, TC Reiss, P Rimland, D Sears, CL Seeff, L Sepkowitz, KA Slama, TG Sloand, EM Spector, SA Thomas, DL Van Dyke, RB Watts, DH Wheat, LJ Whitcup, SM Williams, P Wright, TC Castro, KG DeCock, KM Dowell, SF Dworkin, MS Dykewicz, C Ellerbrock, T Hajjeh, R Holmberg, S Holtgrave, DR Jaffe, HW Jones, JL Juranek, DD Mast, E Navin, T Pellett, PE Reeves, WC Stewart, JA Villarino, ME Kaplan, JE AF Masur, H Kaplan, JE Holmes, KK Alston, BL Ampel, N Anderson, JR Baker, AC Barr, D Bartlett, JG Bennett, JE Benson, CA Bozzette, SA Chaisson, RE Crumpacker, CS Currier, JS Deyton, L Drew, WL Duncan, WR Eisinger, RW El-Sadr, W Feinberg, J Freedberg, KA Furrer, H Gnann, JW Goldberger, MJ Goldie, S Goosby, EP Gross, PA Hafner, R Havlir, D Hooton, TM Jabs, DA Jacobson, MA Janoff, E Kitahata, M Kovacs, JV Leport, C Levin, MJ Lopez, JC Marco, M Mayers, DL Melnick, DA Mofenson, LM Montaner, JSG Moore, R Neaton, J Nelson, C O'Neill, JF Palefsky, J Pau, A Phair, JP Piscitelli, S Polis, MA Quinn, TC Reiss, P Rimland, D Sears, CL Seeff, L Sepkowitz, KA Slama, TG Sloand, EM Spector, SA Thomas, DL Van Dyke, RB Watts, DH Wheat, LJ Whitcup, SM Williams, P Wright, TC Castro, KG DeCock, KM Dowell, SF Dworkin, MS Dykewicz, C Ellerbrock, T Hajjeh, R Holmberg, S Holtgrave, DR Jaffe, HW Jones, JL Juranek, DD Mast, E Navin, T Pellett, PE Reeves, WC Stewart, JA Villarino, ME Kaplan, JE CA USPHS IDSA Prevention Oportunisti TI 1999 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; MYCOBACTERIUM-AVIUM COMPLEX; PLACEBO-CONTROLLED TRIAL; ACTIVE ANTIRETROVIRAL THERAPY; TRIMETHOPRIM-SULFAMETHOXAZOLE; CYTOMEGALOVIRUS RETINITIS; RANDOMIZED TRIAL; TOXOPLASMIC ENCEPHALITIS; AEROSOLIZED PENTAMIDINE; MAINTENANCE THERAPY C1 NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ Washington, Seattle, WA 98195 USA. Univ Arizona, Tucson, AZ USA. Johns Hopkins Univ, Baltimore, MD USA. Natl Assoc People AIDS, Washington, DC USA. Forum Collaborat HIV Res, Washington, DC USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Harvard Univ, Med Ctr, Boston, MA 02115 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. US Dept Vet Affairs, Washington, DC USA. Univ Calif San Francisco, Mt Zion Med Ctr, San Francisco, CA 94120 USA. Harlem Hosp, New York, NY USA. Holmes Hosp, Cincinnati, OH USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Univ Hosp Bern, CH-3010 Bern, Switzerland. Univ Alabama, Birmingham, AL USA. US FDA, Rockville, MD 20857 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. US Dept Hlth & Human Serv, Washington, DC USA. Hackensack Med Ctr, Hackensack, NJ 07604 USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. Vet Adm Med Ctr, Minneapolis, MN 55417 USA. Univ Washington, Seattle, WA 98195 USA. Hop Bichat Claude Bernard, F-75877 Paris 18, France. Hosp Univ Gregorio Maranon, Madrid, Spain. Treatment Act Grp, New York, NY USA. Henry Ford Hosp, Detroit, MI 48202 USA. Kaiser Permanente, Springfield, VA USA. St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada. Univ Minnesota, Minneapolis, MN USA. US Hlth Resources & Serv Adm, Rockville, MD 20857 USA. Northwestern Univ, Chicago, IL 60611 USA. Johns Hopkins Hosp, Baltimore, MD 21287 USA. Univ Amsterdam, Amsterdam, Netherlands. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Natl Fdn Infect Dis, Indianapolis, IN USA. Tulane Univ, Sch Med, New Orleans, LA 70112 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. RP Masur, H (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. RI Furrer, Hansjakob/G-6768-2013 OI Furrer, Hansjakob/0000-0002-1375-3146 NR 90 TC 19 Z9 19 U1 0 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 7 PY 1999 VL 131 IS 11 BP 873 EP 908 PG 36 WC Medicine, General & Internal SC General & Internal Medicine GA 262ET UT WOS:000084053200019 ER PT J AU del Monte, F Harding, SE Schmidt, U Matsui, T Kang, ZB Dec, W Gwathmey, JK Rosenzweig, A Hajjar, RJ AF del Monte, F Harding, SE Schmidt, U Matsui, T Kang, ZB Dec, W Gwathmey, JK Rosenzweig, A Hajjar, RJ TI Restoration of contractile function in isolated cardiomyocytes from failing human hearts by gene transfer of SERCA2a SO CIRCULATION LA English DT Article DE contractility; myocytes; gene therapy; sarcoplasmic reticulum ID SARCOPLASMIC-RETICULUM CA2+-ATPASE; ISOLATED VENTRICULAR MYOCYTES; DILATED CARDIOMYOPATHY; FAILURE; EXPRESSION; MYOCARDIUM; PHOSPHOLAMBAN; ATPASE AB Background-Failing human myocardium is characterized by abnormal relaxation, a deficient sarcoplasmic reticulum (SR) Ca2+ uptake, and a negative frequency response, which have all been related to a deficiency in the SR Ca2+ ATPase (SERCA2a) pump. Methods and Results-To test the hypothesis that an increase in SERCA2a could improve contractile function in cardiomyocytes, we overexpressed SERCA2a in human ventricular myocytes from 10 patients with end-stage heart failure and examined intracellular Ca2+ handling and contractile function. Overexpression of SERCA2a resulted in an increase in both protein expression and pump activity and induced a faster contraction velocity (26.7 +/- 6.7% versus 16.6 +/- 2.7% shortening per second, P < 0.005) and enhanced relaxation velocity (32.0 +/- 10.1% versus 15.1 +/- 2.4%, P < 0.005). Diastolic Ca2+ was decreased in failing cardiomyocytes overexpressing SERCA2a (270 +/- 26 versus 347 +/- 30 nmol/L, P < 0.005), whereas systolic Ca2+ was increased (601 +/- 38 versus 508 +/- 25 nmol/L, P < 0.05), In addition, the frequency response was normalized in cardiomyocytes overexpressing SERCA2a. Conclusions-These results support the premise that gene-based therapies and targeting of specific pathways in human heart failure may offer a new modality for the treatment of this disease. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Heart Failure & Cardiac Transplantat Ctr, Boston, MA 02129 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Univ London Imperial Coll Sci Technol & Med, London, England. RP Hajjar, RJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, 149 13th St,CNY 4, Boston, MA 02129 USA. NR 19 TC 273 Z9 274 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 7 PY 1999 VL 100 IS 23 BP 2308 EP 2311 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 263LM UT WOS:000084126200003 ER PT J AU Matsui, T Li, L del Monte, F Fukui, Y Franke, TF Hajjar, RJ Rosenzweig, A AF Matsui, T Li, L del Monte, F Fukui, Y Franke, TF Hajjar, RJ Rosenzweig, A TI Adenoviral gene transfer of activated phosphatidylinositol 3 '-kinase and Akt inhibits apoptosis of hypoxic cardiomyocytes in vitro SO CIRCULATION LA English DT Article DE kinase; viruses; growth substances; signal transduction ID GROWTH-FACTOR-I; PROGRAMMED CELL-DEATH; 3-KINASE; MYOCYTES; KINASE; PHOSPHORYLATION; EXPRESSION; SURVIVAL; PROTEIN; SYSTEM AB Background-The intracellular signaling pathways that control cardiomyocyte apoptosis have not been fully defined. Because insulin-like growth factor-1 (IGF-1) prevents cardiomyocyte apoptosis, we examined the role of its downstream signaling molecules in an in vitro model of hypoxia-induced cardiomyocyte apoptosis. Methods and Results-Treatment of rat neonatal cardiomyocytes with IGF-1 increased activity of both phosphatidylinositol 3' (PI 3)-kinase and its downstream target, Akt (also known as protein kinase B or PKB). Cardiomyocytes were subjected to hypoxia for 24 hours, and apoptosis was assessed by DNA laddering, TUNEL staining, and ELISA for histone-associated DNA fragments, IGF-1 treatment (100 nmol/L) reduced cardiomyocyte apoptosis, and this effect was inhibited by simultaneous treatment with a PI 3-kinase inhibitor. Cardiomyocytes were infected with either a control adenovirus (Ad.EGFP) or adenoviruses carrying constitutively active forms of PI 3-kinase (Ad.BD110) or Akt (Ad.myr-Akt-HA), Ad.BD110 significantly inhibited apoptosis of hypoxic cardiomyocytes compared with Ad.EGFP (61.0 +/- 4.6% less DNA fragmentation than in Ad.EGFP-infected cells, P < 0.0001). Ad.myr-Akt-HA even more dramatically inhibited apoptosis of hypoxic cardiomyocytes (90.9 +/- 1.4% less DNA fragmentation than in controls, P < 0.0001), Conclusions-IGF-1 activates PI 3-kinase and Akt in cardiomyocytes. Activated PI 3-kinase and Akt are each sufficient to protect hypoxic cardiomyocytes against apoptosis in vitro. Adenoviral gene transfer provides a useful tool for investigating the role of these signaling pathways in cardiomyocyte apoptosis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. Columbia Univ, Dept Pharmacol, New York, NY USA. Univ Tokyo, Biol Chem Lab, Tokyo, Japan. RP Rosenzweig, A (reprint author), Massachusetts Gen Hosp East, Cardiovasc Res Ctr, 149 13th St,Room 4214, Boston, MA 02129 USA. RI Fukui, Yasuhisa/E-8806-2010 FU NHLBI NIH HHS [HL-50361, HL-57623, HL-59521] NR 20 TC 268 Z9 290 U1 4 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 7 PY 1999 VL 100 IS 23 BP 2373 EP 2379 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 263LM UT WOS:000084126200013 PM 10587343 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 MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE aging; rat; T cell; calcineurin; CaMK-IV ID CA2+/CALMODULIN-DEPENDENT PROTEIN-KINASE; TRANSCRIPTION FACTOR NFAT; SIGNAL TRANSDUCTION; IMMUNE FUNCTION; DNA-BINDING; KAPPA-B; EXPRESSION; CALMODULIN; CALCIUM; PHOSPHORYLATION AB We have previously shown that the DNA binding activity of the transcription factor NFAT which plays a predominant role in IL-2 transcription decreases with age. Because the transactivation (dephosphorylation and nuclear translocation) of the NFAT-c (cytoplasmic component of the NFAT complex) is mediated by the calcium/calmodulin-dependent phosphatase, calcineurin (CaN), and because Ca2+ /calmodulin-dependent kinases (CaMK-II and IV/Gr) have been shown to play a critical role in calcium signaling in T cells, it was of interest to determine what effect aging has on the activation and the levels of these calcium regulating enzymes. The induction of calcineurin phosphatase activity, and CaMK-II and IV/Gr activities, were studied in splenic T cells isolated from Fischer 344 rats at 6, 15, and 24 months of age. In addition, the changes in the protein levels of these enzymes were measured by Western blot. The calcineurin phosphatase activity and CaMK-II and IV kinase activities were at a maximum after the cells were incubated with anti-CD3 antibody for 5-10 minutes. The induction of calcineurin activity by anti-CD3 and by calcium ionophore (A23187) declined 65 and 55%, respectively, between 6 and 24 months of age. The induction of CaMK-IV activity, but not CaMK-II activity by anti-CD3, was significantly less (by 54%) in T cells from old rats compared to T cells from young rats. The decline in the activation of these enzymes with age was not associated with changes in their corresponding protein levels. These results demonstrate that alterations in calcineurin phosphatase activity and CaMK-IV activity may contribute to the well-documented age-related decline in T cell function. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 S Texas Vet Hlth Care Syst, Audie L Murphy Vet Hosp, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. RP Pahlavani, MA (reprint author), S Texas Vet Hlth Care Syst, Audie L Murphy Vet Hosp, Ctr Geriatr Res Educ & Clin, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NIA NIH HHS [AG00677, AG14088] NR 53 TC 21 Z9 21 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing. Dev. PD DEC 7 PY 1999 VL 112 IS 1 BP 59 EP 74 DI 10.1016/S0047-6374(99)00077-9 PG 16 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 269ZX UT WOS:000084511700005 PM 10656183 ER PT J AU Hanson, RD Hess, JL Yu, BD Ernst, P van Lohuizen, M Berns, A van der Lugt, NMT Shashikant, CS Ruddle, FH Seto, M Korsmeyer, SJ AF Hanson, RD Hess, JL Yu, BD Ernst, P van Lohuizen, M Berns, A van der Lugt, NMT Shashikant, CS Ruddle, FH Seto, M Korsmeyer, SJ TI Mammalian Trithorax and Polycomb-group homologues are antagonistic regulators of homeotic development SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MYC TRANSGENIC MICE; GROUP GENE ENHANCER; BITHORAX COMPLEX; EXPRESSION; DROSOPHILA; IDENTIFICATION; BMI-1; MOUSE; MLL; TRANSFORMATION AB Control of cell identity during development is specified in large part by the unique expression patterns of multiple homeobox-containing (Hox) genes in specific segments of an embryo. Trithorax and Polycomb-group (Trx-G and Pc-G) proteins in Drosophila maintain Hox expression or repression, respectively. Mixed lineage leukemia (MLL) is frequently involved in chromosomal translocations associated with acute leukemia and is the one established mammalian homologue of Trx. Bmi-l was first identified as a collaborator in c-myc-induced murine lymphomagenesis and is homologous to the Drosophila Pc-G member Posterior sex combs. Here, we note the axial-skeletal transformations and altered Hox expression patterns of Mll-deficient and Bmi-1-deficient mice were normalized when both MII and Bmi-1 were deleted, demonstrating their antagonistic role in determining segmental identity. Embryonic fibroblasts from MII-deficient compared with Bmi-l-deficient mice demonstrate reciprocal regulation of Hox genes as well as an integrated Hoxc8-lacZ reporter construct. Reexpression of MLL was able to overcome repression, rescuing expression of Hoxc8-lacZ in MII-deficient cells. Consistent with this, MLL and BMI-I display discrete subnuclear colocalization. Although Drosophila Pc-G and Trx-G members have been shown to maintain a previously established transcriptional pattern, we demonstrate that MLL can also dynamically regulate a target Hox gene. C1 Harvard Univ, Dept Canc Immunol AIDS, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Washington Univ, Sch Med, Howard Hughes Med Inst, Dept Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Howard Hughes Med Inst, Dept Pediat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Howard Hughes Med Inst, Dept Pathol, St Louis, MO 63110 USA. Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands. Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA. Aichi Canc Ctr, Res Inst, Lab Chemotherapy, Nagoya, Aichi 4648681, Japan. RP Korsmeyer, SJ (reprint author), Harvard Univ, Dept Canc Immunol AIDS, Sch Med, Dana Farber Canc Inst, 44 Binney St,Room SM 758, Boston, MA 02115 USA. NR 30 TC 176 Z9 190 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 7 PY 1999 VL 96 IS 25 BP 14372 EP 14377 DI 10.1073/pnas.96.25.14372 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 263XC UT WOS:000084149700043 PM 10588712 ER PT J AU Warshawsky, D Stavropoulos, N Lee, JT AF Warshawsky, D Stavropoulos, N Lee, JT TI Further examination of the Xist promoter-switch hypothesis in X inactivation: Evidence against the existence and function of a P-0 promoter SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CHROMOSOME INACTIVATION; MEDIATES INITIATION; MOUSE; GENE; RNA; IDENTIFICATION; STABILIZATION; NUCLEUS; REGION; CELLS AB The onset of X inactivation coincides with accumulation of Xist RNA along the future inactive X chromosome. A recent hypothesis proposed that accumulation is initiated by a promoter switch within Xist. in this hypothesis, an upstream promoter (P-0) produces an unstable transcript, while the known downstream promoter (P-1) produces a stable RNA. To test this hypothesis, we examined expression and half-life of Xist RNA produced from an Xist transgene lacking P-0 but retaining P-1. We confirm the previous finding that P-0 is dispensable for Xist expression in undifferentiated cells and that P-1 can be used in both undifferentiated and differentiated cells. Herein, we show that Xist RNA initiated at P-1 is unstable and does not accumulate. Further analysis indicates that the transcriptional boundary at P-0 does not represent the 5' end of a distinct Xist isoform. Instead, P-0 is an artifact of cross-amplification caused by a pseudogene of the highly expressed ribosomal protein S12 gene Rps12. Using strand-specific techniques, we find that transcription upstream of P-1 originates from the DNA strand opposite Xist and represents the 3' end of the antisense Tsix RNA. Thus, these data do not support the existence of a P-0 promoter and suggest that mechanisms other than switching of functionally distinct promoters control the up-regulation of Xist. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Lee, JT (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. FU NIGMS NIH HHS [F32 GM019846, F32-GM19846A01, R01 GM058839, R01-GM58839] NR 27 TC 21 Z9 21 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 7 PY 1999 VL 96 IS 25 BP 14424 EP 14429 DI 10.1073/pnas.96.25.14424 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 263XC UT WOS:000084149700052 PM 10588721 ER PT J AU Hotchkiss, RS Tinsley, KW Swanson, PE Chang, KC Cobb, JP Buchman, TG Korsmeyer, SJ Karl, IE AF Hotchkiss, RS Tinsley, KW Swanson, PE Chang, KC Cobb, JP Buchman, TG Korsmeyer, SJ Karl, IE TI Prevention of lymphocyte cell death in sepsis improves survival in mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE apoptosis; shock; endotoxin; mortality; programmed cell death ID APOPTOSIS; BCL-2; INDUCTION; PROTEASE; INHIBITORS; ACTIVATION; THYMOCYTES; CASPASES; FAMILY; IL-2 AB Sepsis induces extensive lymphocyte apoptosis, a process which may be beneficial to host survival by down-regulating the inflammatory response or, alternatively, harmful by impairing host defenses. To determine the beneficial vs. adverse effects of lymphocyte apoptosis in sepsis, we blocked lymphocyte apoptosis either by N-benzyloxycarbonyl-Val-Ala-Asp(O-methyl) fluoromethyl ketone (z-VAD). a broad-spectrum caspase inhibitor, or by use of Bcl-2 Ig transgenic mice that selectively overexpress the antiapoptotic protein Bcl-2 in a lymphoid pattern. Both z-VAD and Bcl-2 prevented lymphocyte apoptosis and resulted in a marked improvement in survival. z-VAD did not decrease lymphocyte tumor necrosis factor-alpha production. Considered together, these two studies employing different methods of blocking lymphocyte apoptosis provide compelling evidence that immunodepression resulting from the loss of lymphocytes is a central pathogenic event in sepsis. and they challenge the current paradigm that regards sepsis as a disorder resulting from an uncontrolled inflammatory response. Caspase inhibitors may represent a treatment strategy in this highly lethal disorder. C1 Washington Univ, Sch Med, Dept Anesthesiol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Hotchkiss, RS (reprint author), Washington Univ, Sch Med, Dept Anesthesiol, 660 S Euclid Ave, St Louis, MO 63110 USA. OI Buchman, Timothy/0000-0001-7350-5921 FU NIGMS NIH HHS [GM44118, GM55194, R01 GM044118, R01 GM055194, R37 GM044118] NR 41 TC 317 Z9 327 U1 1 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 7 PY 1999 VL 96 IS 25 BP 14541 EP 14546 DI 10.1073/pnas.96.25.14541 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 263XC UT WOS:000084149700072 PM 10588741 ER PT J AU Berger, UV Luthi-Carter, R Passani, LA Elkabes, S Black, I Konradi, C Coyle, JT AF Berger, UV Luthi-Carter, R Passani, LA Elkabes, S Black, I Konradi, C Coyle, JT TI Glutamate carboxypeptidase II is expressed by astrocytes in the adult rat nervous system SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE NAALADase; prostate-specific membrane antigen; folylpoly-gamma-glutamate carboxypeptidase; gliosis; in situ hybridization; glutamate carboxypeptidase II ID LINKED ACIDIC DIPEPTIDASE; AMYOTROPHIC-LATERAL-SCLEROSIS; ACETYL-ASPARTYL-GLUTAMATE; IN-SITU HYBRIDIZATION; N-ACETYLASPARTYLGLUTAMATE; MOLECULAR CHARACTERIZATION; MEMBRANE ANTIGEN; BRAIN; HYDROLYSIS; CLONING AB The enzyme glutamate carboxypeptidase II (GCP II) has been cloned from rat brain and human prostate. This enzyme, which catabolizes the neuropeptide N-acetylaspartylglutamate, has also been known as N-acetylated alpha-linked acidic dipeptidase (NAALADase), and is identical to the prostate-specific membrane antigen and to the jejunal folylpoly-gamma-glutamate carboxypeptidase. The goals of the present study were to elucidate the cell specificity and regional pattern of GCP II expression in the rat nervous system by using Northern blots and enzymatic assays of brain and subfractionated primary neuronal and glial cultures together with in situ hybridization histochemistry (ISHH) in sections of adult rat tissue. GCP II activity was assayed in astrocyte cultures (4.4 pmol/mg protein per minute), neuronal-glial cocultures (2.5 pmol/mg protein per minute) and neuron-enriched cultures (0.38 pmol/mg protein per minute), with the activity in each preparation correlating to its astrocytic content (r = 0.99). No activity was detected in cultured oligodendrocytes or microglia. Northern blots probed with a GCP II cDNA detected mRNAs exclusively in activity-positive cell preparations. ISHH results show that GCP II is expressed by virtually all astrocytes, by Bergmann glial cells in cerebellum, by Muller cells in retina and by the satellite cells in dorsal root ganglia. Astrocytes in select groups of nuclei (e.g., habenula, supraoptic nucleus, pontine nucleus) contained pronounced levels of GCP II message. The data of the present study suggest that GCP II is expressed in the adult rat nervous system exclusively in astrocytic glial cells. (C) 1999 Wiley-Liss, Inc. C1 Harvard Med Sch, Dept Psychiat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp East, Neurogenet Unit, Charlestown, MA 02129 USA. Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA. Massachusetts Gen Hosp East, Lab Mol & Dev Neurosci, Charlestown, MA 02129 USA. RP Coyle, JT (reprint author), McLean Hosp, 115 Mill St, Belmont, MA 02178 USA. FU NIDDK NIH HHS [2T32DK07527]; NIMH NIH HHS [MH-57901]; NINDS NIH HHS [NS 32001] NR 43 TC 74 Z9 75 U1 1 U2 7 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD DEC 6 PY 1999 VL 415 IS 1 BP 52 EP 64 DI 10.1002/(SICI)1096-9861(19991206)415:1<52::AID-CNE4>3.0.CO;2-K PG 13 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 252TM UT WOS:000083518400004 PM 10540357 ER PT J AU Horsch, D Kahn, CR AF Horsch, D Kahn, CR TI Region-specific mRNA expression of phosphatidylinositol 3-kinase regulatory isoforms in the central nervous system of C57BL/6J mice SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE receptor tyrosine kinase; central nervous system; in situ hybridization; insulinlike growth factor ID INSULIN-RECEPTOR SUBSTRATE-1; GROWTH-HORMONE RECEPTOR; MESSENGER-RNA; RAT-BRAIN; TYROSINE KINASES; P85-ALPHA GENE; NEURONS; PROTEIN; SURVIVAL; CLONING AB Activation of phosphatidylinositol S-kinase (PI 3-kinase) by receptor tyrosine kinases for growth factors is crucial for neuronal cell survival and proliferation. This class of kinases is comprised of heterodimers, each consisting of one regulatory and one catalytic subunit. Multiple isoforms of regulatory subunits exist, including p85 alpha and its alternative splice products p50 alpha and AS53/p55 alpha, and p85 beta and p55(PIK), which are derived from different genes. The regional distribution of these PI 5-kinase regulatory isoforms was mapped in the adult murine brain by in situ hybridization histochemistry. All isoforms were demonstrated in abundance in choroid plexus and anterior pituitary. In neuronal compartments, however, PI 3-kinase isoforms were distributed in a regionally specific manner. In general, the mRNAs for p85 alpha, p50 alpha, AS53, and p85 beta were widespread, with the highest level in the olfactory system, in neuronal groups of the forebrain and hypothalamus, in the hippocampus, cortex, inferior and superior colliculus, pituitary, and cerebellum. However, each isoform had specific variations. Lower expression levels of these isoforms were found in the thalamus, diencepha-- ion, mesencephalon, and brainstem. In contrast, abundant mRNA expression of p55(PIK) was limited to cerebellum and anterior pituitary, with moderate levels of p55(PIK) in the olfactory bulb and hippocampus and low levels elsewhere. The distribution pattern of PI 3-kinase isoforms in the brain indicates pluripotent signaling properties for PI 3-kinase isoforms p85 alpha, p50 alpha, AS53/p55 alpha, and p85 beta for a variety of receptor tyrosine kinases, whereas the restricted expression of p55PIK implies a regionally specific role for this isoform in neuronal signaling. The unique integrated expression profiles of PI 3-kinase isoforms in distinct neuronal compartments denote complex intracellular signaling pathways for each neuronal region to ensure specificity of receptor tyrosine kinase signal transduction. (C) 1999 Wiley-Liss, Inc. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [2 P30 DK 36836, DK 33201] NR 48 TC 29 Z9 30 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD DEC 6 PY 1999 VL 415 IS 1 BP 105 EP 120 PG 16 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 252TM UT WOS:000083518400008 PM 10540361 ER PT J AU Adamec, E Vonsattel, JP Nixon, RA AF Adamec, E Vonsattel, JP Nixon, RA TI DNA strand breaks in Alzheimer's disease SO BRAIN RESEARCH LA English DT Article DE neurodegeneration; TUNEL assay; Klenow assay; ISEL; cell death; hippocampus ID APOPTOTIC CELL-DEATH; END LABELING TUNEL; IN-SITU; HUNTINGTONS-DISEASE; BRAIN INJURY; TANGLE FORMATION; FRAGMENTED DNA; SYNAPSE LOSS; DAMAGE; NEURONS AB The goal of this study was to investigate the presence of DNA damage in Alzheimer's disease (AD) utilizing independent assays for three different types of DNA strand breaks. Sections from hippocampi of AD brains, brains with Alzheimer neurofibrillary changes (Ch) from non-demented individuals, and controls (C) were labeled with (1) the TUNEL assay to identify blunt-ended and 3' protruding termini of breaks in double-stranded DNA, (2) the Klenow assay to detect single-stranded and double-stranded breaks with protruding 5' termini, and (3) the Apostain assay which utilizes a monoclonal antibody to single-stranded DNA and is based on the decreased stability of apoptotic DNA to thermal denaturation caused by DNA breaks. The highest incidence of nuclei positive for either molecular form of DNA strand breaks was detected in AD, followed by Ch, and controls (C). Zn either AD and Ch, the incidence of TUNEL- or Klenow-positive nuclei did not differ significantly, but was higher than the incidence of Apostain-positive nuclei. With all three assays, the highest incidence of positive nuclei was in the molecular layer of CA1, In the majority of nuclei positive for either the Klenow or the Apostain assay, the product of the labeling reaction was localized either to the periphery of the nucleus or to distinct clumps of chromatin (or both). With the TUNEL assay, the majority of positive nuclei were diffusely labeled. In both AD and Ch, the individual positive nuclei were labeled with both the Klenow and the TUNEL assays. The results indicate high incidence of nuclei with either double-stranded or single-stranded DNA breaks in AD, which, for the forms detectable with the Klenow or TUNEL assays, were colocalized. (C) 1999 Elsevier Science B.V. All rights reserved. C1 McLean Hosp, Mailman Res Ctr, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Lab Mol Neuropathol, Charlestown, MA 02129 USA. Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. RP Adamec, E (reprint author), McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. FU NIA NIH HHS [AG05134, AG000764]; NINDS NIH HHS [NS 31862] NR 61 TC 84 Z9 86 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 4 PY 1999 VL 849 IS 1-2 BP 67 EP 77 DI 10.1016/S0006-8993(99)02004-1 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 269PN UT WOS:000084486900007 PM 10592288 ER PT J AU Kula, NS Baldessarini, RJ Tarazi, FI Fisser, R Wang, SY Trometer, J Neumeyer, JL AF Kula, NS Baldessarini, RJ Tarazi, FI Fisser, R Wang, SY Trometer, J Neumeyer, JL TI [H-3]beta-CIT: a radioligand for dopamine transporters in rat brain tissue SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE autoradiography; [H-3]beta-CIT; dopamine; monoamine; transporter; tropane ID POSITRON EMISSION TOMOGRAPHY; NOREPINEPHRINE UPTAKE SITES; UPTAKE COMPLEX; BINDING; DERIVATIVES; MEMBRANES; RECEPTORS; CIT AB [H-3]2-beta-carbomethoxy-3-beta-[4'-iodophenyl]tropane (beta-CIT) was prepared and evaluated. With rat forebrain tissue, [H-3]beta-CIT showed high affinity for dopamine transporters (DAT), with selectivity for DAT over norepinephrine transporters, but not serotonin transporters, as well as DAT-stereoselectivity with beta-CIT, amphetamine and methylphenidate. Affinity and selectivity for 53 compounds assayed with [H-3]beta-CIT and standard DAT radioligand [H-3]GBR-12935 were highly correlated (r > 0.95). [H-3]beta-CIT is proposed as a useful, high-affinity DAT radioprobe. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02478 USA. Massachusetts Gen Hosp, McLean Div, Addict Res Ctr, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. Res Biochem Int, Natick, MA USA. New England Nucl, Boston, MA USA. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. FU NIMH NIH HHS [MH-47370, MH-19905, MH-34006] NR 16 TC 40 Z9 41 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD DEC 3 PY 1999 VL 385 IS 2-3 BP 291 EP 294 DI 10.1016/S0014-2999(99)00695-0 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 266GV UT WOS:000084293000027 PM 10607889 ER PT J AU Yoshida, K Kharbanda, S Kufe, D AF Yoshida, K Kharbanda, S Kufe, D TI Functional interaction between SHPTP1 and the Lyn tyrosine kinase in the apoptotic response to DNA damage SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; C-ABL; IONIZING-RADIATION; STRESS-RESPONSE; PHOSPHATIDYLINOSITOL 3-KINASE; CELLS; 1-BETA-D-ARABINOFURANOSYLCYTOSINE; PHOSPHORYLATION; ASSOCIATION; DOMAINS AB The Lyn protein-tyrosine kinase is activated in the cellular response to DNA-damaging agents. Here we demonstrate that Lyn associates constitutively with the SHPTP1 protein-tyrosine phosphatase. The SH3 domain of Lyn interacts directly with SHPTP1. The results show that Lyn phosphorylates SHPTP1 at the C-terminal Tyr-564 site. Lyn-mediated phosphorylation of SHPTP1 stimulates SHPTP1 tyrosine phosphatase activity. We also demonstrate that treatment of cells with 1-beta-D-arabinofuranosylcytosine and other genotoxic agents induces Lyn-dependent phosphorylation and activation of SHPTP1. The significance of the Lyn-SHPTP1 interaction is supported by the demonstration that activation of Lyn contributes in part to the apoptotic response to ara-C treatment and that SHPTP1 attenuates this response. These findings support a functional interaction between Lyn and SHPTP1 in the response to DNA damage. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA29431] NR 27 TC 43 Z9 45 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 3 PY 1999 VL 274 IS 49 BP 34663 EP 34668 DI 10.1074/jbc.274.49.34663 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 260XW UT WOS:000083979600025 PM 10574931 ER PT J AU Klein, J Fasshauer, M Ito, M Lowell, BB Benito, M Kahn, CR AF Klein, J Fasshauer, M Ito, M Lowell, BB Benito, M Kahn, CR TI beta(3)-adrenergic stimulation differentially inhibits insulin signaling and decreases insulin-induced glucose uptake in brown adipocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; RECEPTOR TYROSINE KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; RAT ADIPOCYTES; 3T3-L1 ADIPOCYTES; C-ALPHA; BETA; TRANSPORT; CELLS; PHOSPHORYLATION AB Activity of the sympathetic nervous system is an important factor involved in the pathogenesis of insulin resistance and associated metabolic and vascular abnormalities. In this study, we investigate the molecular basis of cross-talk between beta(2)-adrenergic and insulin signaling systems in mouse brown adipocytes immortalized by SV40 T infection. Insulin-induced tyrosine phosphorylation of the insulin receptor, insulin receptor substrate 1 (IRS-1), and IRS-S was reduced by prestimulation of beta(3)-adrenergic receptors (CL316243). Similarly, insulin-induced IRS-1-associated and phosphotyrosine-associated phosphatidylinositol S-kinase (PI 3-kinase) activity, but not IRS-2-associated PI 3-kinase activity, was reduced by beta(3)-adrenergic prestimulation, Furthermore, insulin-stimulated activation of Akt, but not mitogen-activated protein kinase, was diminished. Insulin-induced glucose uptake was completely inhibited by beta(3)-adrenersc prestimulation. These effects appear to be protein kinase A-dependent. Furthermore inhibition of protein kinase C restored the beta(3)-receptor-mediated reductions in insulin-induced IRS-1 tyrosine phosphorylation and IRS-1-associated PI 3-kinase activity. Together, these findings indicate cross-talk between adrenergic and insulin signaling pathways. This interaction is protein kinase A-dependent and, at least in part, protein kinase C-dependent, and could play an important role in the pathogenesis of insulin resistance associated with sympathetic overactivity and regulation of brown fat metabolism. C1 Univ Complutense, Fac Farm, E-28040 Madrid, Spain. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Univ Complutense, Fac Farm, E-28040 Madrid, Spain. FU NIDDK NIH HHS [DK 33201, DK 36836] NR 43 TC 136 Z9 136 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 3 PY 1999 VL 274 IS 49 BP 34795 EP 34802 DI 10.1074/jbc.274.49.34795 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 260XW UT WOS:000083979600044 PM 10574950 ER PT J AU Reinherz, EL Tan, KM Tang, L Kern, P Liu, JH Xiong, Y Hussey, RE Smolyar, A Hare, B Zhang, RG Joachimiak, A Chang, HC Wagner, G Wang, JH AF Reinherz, EL Tan, KM Tang, L Kern, P Liu, JH Xiong, Y Hussey, RE Smolyar, A Hare, B Zhang, RG Joachimiak, A Chang, HC Wagner, G Wang, JH TI The crystal structure of a T cell receptor in complex with peptide and MHC class II SO SCIENCE LA English DT Review ID TOXIC LYMPHOCYTES-T; BOUND SINGLE PEPTIDES; MYELIN BASIC-PROTEIN; TCR FAB FRAGMENT; ALPHA-CHAIN; ANTIGEN RECEPTOR; 3-DIMENSIONAL STRUCTURE; BETA-CHAIN; SUPERANTIGEN RECOGNITION; POSITIVE SELECTION AB The crystal structure of a complex involving the D10 T cell receptor (TCR), 16-residue foreign peptide antigen, and the I-A(k) self major histocompatibility complex (MHC) class II molecule is reported at 3.2 angstrom resolution. The D10 TCR is oriented in an orthogonal mode relative to its peptide-MHC (pMHC) Ligand, necessitated by the amino-terminal extension of peptide residues projecting from the MHC class II antigen-binding groove as part of a mini beta sheet. Consequently, the disposition of D10 complementarity-determining region Loops is altered relative to that of most pMHCI-specific TCRs; the Latter TCRs assume a diagonal orientation, although with substantial variability. Peptide recognition, which involves P-1 to P8 residues, is dominated by the V alpha domain, which also binds to the class II MHC beta(1) helix. That docking is Limited to one segment of MHC-bound peptide offers an explanation for epitope recognition and altered peptide Ligand effects, suggests a structural basis for alloreactivity, and illustrates how bacterial superantigens can span the TCR-pMHCII surface. 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 Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Argonne Natl Lab, Biosci Div, Argonne, IL 60439 USA. RP Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, 44 Binney St, Boston, MA 02115 USA. EM ellis_reinherz@dfci.harvard.edu; jwang@red.dfci.harvard.edu FU NIAID NIH HHS [AI19807, AI/CA37581]; NIGMS NIH HHS [GM56008] NR 127 TC 322 Z9 330 U1 3 U2 11 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD DEC 3 PY 1999 VL 286 IS 5446 BP 1913 EP 1921 DI 10.1126/science.286.5446.1913 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 261HH UT WOS:000084003400040 PM 10583947 ER PT J AU Towner, D Castro, MA Eby-Wilkens, E Gilbert, WM AF Towner, D Castro, MA Eby-Wilkens, E Gilbert, WM TI Effect of mode of delivery in nulliparous women on neonatal intracranial injury. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID VACUUM EXTRACTION DELIVERY; SILICONE-RUBBER CUP; SUBGALEAL HEMATOMA; FORCEPS DELIVERY; RISK-FACTORS; CALIFORNIA; HEMORRHAGE; BIRTH; TRIAL AB Background: Infants delivered by vacuum extraction or other operative techniques may be more likely to sustain major injuries than those delivered spontaneously, but the extent of the risk is unknown. Methods: From a California data base, we identified 583,340 live-born singleton infants born to nulliparous women between 1992 and 1994 and weighing between 2500 and 4000 g. One third of the infants were delivered by operative techniques. We evaluated the relation between the mode of delivery and morbidity in the infants. Results: Intracranial hemorrhage occurred in 1 of 860 infants delivered by vacuum extraction, 1 of 664 delivered with the use of forceps, 1 of 907 delivered by cesarean section during labor, 1 of 2750 delivered by cesarean section with no labor, and 1 of 1900 delivered spontaneously. As compared with the infants delivered spontaneously, those delivered by vacuum extraction had a significantly higher rate of subdural or cerebral hemorrhage (odds ratio, 2.7; 95 percent confidence interval, 1.9 to 3.9), as did the infants delivered with the use of forceps (odds ratio, 3.4; 95 percent confidence interval, 1.9 to 5.9) or cesarean section during labor (odds ratio, 2.5; 95 percent confidence interval, 1.8 to 3.4), but the rate of subdural or cerebral hemorrhage associated with vacuum extraction did not differ significantly from that associated with forceps use (odds ratio for the comparison with vacuum extraction, 1.2; 95 percent confidence interval, 0.7 to 2.2) or cesarean section during labor (odds ratio, 0.9; 95 percent confidence interval, 0.6 to 1.4). Conclusions: The rate of intracranial hemorrhage is higher among infants delivered by vacuum extraction, forceps, or cesarean section during labor than among infants delivered spontaneously, but the rate among infants delivered by cesarean section before labor is not higher, suggesting that the common risk factor for hemorrhage is abnormal labor. (N Engl J Med 1999;341:1709-14.) (C) 1999, Massachusetts Medical Society. C1 Univ Calif Davis, Med Ctr, Dept Obstet & Gynecol, Div Mat Fetal Med, Sacramento, CA 95817 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Towner, D (reprint author), Univ Calif Davis, Med Ctr, Dept Obstet & Gynecol, Div Mat Fetal Med, 4860 Y St,Suite 2500, Sacramento, CA 95817 USA. NR 26 TC 313 Z9 320 U1 0 U2 7 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 2 PY 1999 VL 341 IS 23 BP 1709 EP 1714 DI 10.1056/NEJM199912023412301 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 260NB UT WOS:000083955800001 PM 10580069 ER PT J AU Van Dam, J Brugge, WR AF Van Dam, J Brugge, WR TI Medical progress: Endoscopy of the upper gastrointestinal tract. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID EXPANDABLE METAL STENTS; EARLY GASTRIC-CANCER; CISPLATIN/EPINEPHRINE-INJECTABLE GEL; MALIGNANT ESOPHAGEAL OBSTRUCTION; DIGESTIVE-RESPIRATORY FISTULAS; OPEN-ACCESS ENDOSCOPY; HIGH-GRADE DYSPLASIA; BARRETTS-ESOPHAGUS; PHOTODYNAMIC THERAPY; BOTULINUM TOXIN C1 Brigham & Womens Hosp, Dept Med, Div Gastroenterol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Van Dam, J (reprint author), Brigham & Womens Hosp, Dept Med, Div Gastroenterol, 75 Francis St, Boston, MA 02115 USA. NR 124 TC 43 Z9 43 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 2 PY 1999 VL 341 IS 23 BP 1738 EP 1748 DI 10.1056/NEJM199912023412306 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 260NB UT WOS:000083955800006 PM 10580074 ER PT J AU Pritchard, DM Potten, CS Korsmeyer, SJ Roberts, S Hickman, JA AF Pritchard, DM Potten, CS Korsmeyer, SJ Roberts, S Hickman, JA TI Damage-induced apoptosis in intestinal epithelia from bcl-2-null and bax-null mice: investigations of the mechanistic determinants of epithelial apoptosis in vivo SO ONCOGENE LA English DT Article DE apoptosis; bcl-2; bax; 5-fluorouracil; gamma-irradiation; intestinal epithelia ID RADIATION-INDUCED APOPTOSIS; HUMAN COLORECTAL ADENOMAS; MURINE SMALL-INTESTINE; CELL-DEATH; GAMMA-IRRADIATION; P53-DEPENDENT APOPTOSIS; GASTROINTESTINAL-TRACT; HIERARCHICAL STATUS; CRYPT CELLS; P53 AB The influence of bcl-2 and bax expression on apoptotic cell death in mouse intestinal epithelia was assessed using homozygously null mice. Apoptosis was induced in vivo by the enterotoxin 5-fluorouracil (5FU) or by gamma-irradiation and its cell positional incidence was assessed. 5FU and gamma-radiation treated bax-null mice surprisingly showed no reductions in apoptotic yield in the small intestine or midcolon at 4.5 h at cell positions in which both agents had previously been shown to strongly induce p53 protein expression. The colonic epithelia of 5FU treated bcl-2-null mice showed elevated levels of apoptosis at 4.5 h: from 48 apoptotic events in wild-type mice to 273 in the nulls, scoring 200 half crypts. The increase occurred specifically in the cell positions considered to harbour colonic stem cells, at the base of crypts, where there is selective expression of bcl-2. There was a modest but significant increase in apoptosis in the small intestine of the bcl-2-null mice although the epithelia of wild-type mice here are not immunohistochemically positive for bcl-2 protein. These findings show that bcl-2 plays a key role in determining the sensitivity of colonic stem cells to damage-induced death but that bax is not responsible for the p53-dependent induction of apoptosis in this context. C1 Univ Manchester, Sch Biol Sci, CRC, Mol & Cellular Pharmacol Grp, Manchester M13 9PT, Lancs, England. Christie Hosp NHS Trust, Paterson Inst, Dept Epithelial Biol, CRC, Manchester M20 9BX, Lancs, England. Dana Farber Canc Inst, Boston, MA 02115 USA. Christie Hosp NHS Trust, Paterson Inst, CRC, Biomath & Comp Unit, Manchester M20 9BX, Lancs, England. RP Hickman, JA (reprint author), Univ Manchester, Sch Biol Sci, CRC, Mol & Cellular Pharmacol Grp, Stopford Bldg G38, Manchester M13 9PT, Lancs, England. OI Pritchard, David Mark/0000-0001-7971-3561 NR 38 TC 80 Z9 81 U1 1 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 2 PY 1999 VL 18 IS 51 BP 7287 EP 7293 DI 10.1038/sj.onc.1203150 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 263HN UT WOS:000084119400013 PM 10602483 ER PT J AU Palayoor, ST Youmell, MY Calderwood, SK Coleman, CN Price, BD AF Palayoor, ST Youmell, MY Calderwood, SK Coleman, CN Price, BD TI Constitutive activation of I kappa B kinase alpha and NF-kappa B in prostate cancer cells is inhibited by ibuprofen SO ONCOGENE LA English DT Article DE NF-kappa B; ibuprofen; prostate; tumor; IKK alpha; androgen ID ANDROGEN RECEPTOR GENE; IKK-ALPHA; PHOSPHORYLATION; PROTEIN; BETA; SALICYLATE; EXPRESSION; APOPTOSIS; ASPIRIN; STIMULI AB Apoptotic pathways controlled by the Rel/NF-kappa B family of transcription factors may regulate the response of cells to DNA damage. Here, we have examined the NF-kappa B status Of several prostate tumor cell lines. In the androgen-independent prostate tumor cells PC-3 and DU-145, the DNA-binding activity of NF-kappa B was constitutively activated and I kappa B-alpha levels were decreased, In contrast, the androgen-sensitive prostate tumor cell line LNCaP had low levels of NF-kappa B which were upregulated following exposure to cytokines or DNA damage, The activity of the I kappa B-alpha kinase, IKK alpha, which mediates NF-kappa B activation, was also measured. In PC-3 cells, IKK alpha activity was constitutively active, whereas LNCaP cells had minimal IKK alpha activity that was activated by cytokines. The anti-inflammatory agent ibuprofen inhibited the constitutive activation of NF-kappa B and IKK alpha in PC-3 and DU-145 cells, and blocked stimulated activation of NF-kappa B in LNCaP cells. However, ibuprofen did not directly inhibit I kappa B-alpha kinase, The results demonstrate that NF-kappa B is constitutively activated in the hormone-insensitive prostate tumor cell lines PC-3 and DU-145, but not in the hormone responsive LNCaP cell line. The constitutive activation of NF-kappa B in prostate tumor cells may increase expression of anti-apoptotic proteins, thereby decreasing the effectiveness of anti-tumor therapy and contributing to the development of the malignant phenotype. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Joint Ctr Radiat Therapy,Dept Adult Oncol, Boston, MA 02115 USA. NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Price, BD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Joint Ctr Radiat Therapy,Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA64585] NR 31 TC 243 Z9 247 U1 0 U2 7 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 2 PY 1999 VL 18 IS 51 BP 7389 EP 7394 DI 10.1038/sj.onc.1203160 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 263HN UT WOS:000084119400026 PM 10602496 ER PT J AU Kutner, L Beresin, EV AF Kutner, L Beresin, EV TI Media training for psychiatry residents SO ACADEMIC PSYCHIATRY LA English DT Editorial Material AB Psychiatric residency training programs rarely prepare residents for exposure to the media. Increasingly, however, physicians are called upon to disseminate current knowledge about a wide range of topics pertinent to mental health and illness. The authors describe a model seminar used in a psychiatric residency training program providing residents with skills in effective communication through the mass media. The goal of the seminar is to prepare residents for an important role in public health psychiatry. C1 Massachusetts Gen Hosp, Dept Psychiat, McLean Hosp, Child & Adolescent Psychiat Residency Training, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Beresin, EV (reprint author), Massachusetts Gen Hosp, Dept Psychiat, McLean Hosp, Child & Adolescent Psychiat Residency Training, 55 Fruit St,Bulfinch 449, Boston, MA 02114 USA. NR 10 TC 5 Z9 5 U1 0 U2 0 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 WIN PY 1999 VL 23 IS 4 BP 227 EP 232 PG 6 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 263WD UT WOS:000084147500011 ER PT J AU Walker, WA AF Walker, WA TI What is the role of nucleotides and polyamines in breast milk? SO ACTA PAEDIATRICA LA English DT Editorial Material ID MUCOSAL GROWTH; INTESTINE C1 Harvard Univ, Sch Med, Combined Program Pediat Gastroenterol & Nutr, Boston, MA USA. RP Walker, WA (reprint author), Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02129 USA. NR 16 TC 0 Z9 1 U1 0 U2 1 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD DEC PY 1999 VL 88 IS 12 BP 1313 EP 1315 DI 10.1080/080352599750029989 PG 3 WC Pediatrics SC Pediatrics GA 268KU UT WOS:000084413500004 PM 10626512 ER PT J AU Buckman, JF Meshul, CK AF Buckman, JF Meshul, CK TI Glial differences between naive withdrawal seizure-prone and -resistant mice SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE immunocytochemistry; glutamate; glial fibrillary acidic protein; cytochrome oxidase; excitatory amino acid transporters ID GLUTAMATE-ASPARTATE TRANSPORTER; QUANTITATIVE EM ANALYSIS; CYTOCHROME OXIDASE-RICH; MACAQUE STRIATE CORTEX; CENTRAL-NERVOUS-SYSTEM; ETHANOL-WITHDRAWAL; RAT-BRAIN; INDUCED CONVULSIONS; CNS TRANSMITTER; GABA AB Background: Withdrawal seizure-prone (WSP) and withdrawal seizure-resistant (WSR) mice were bred in replicate (i.e., WSP-1 and WSP-2) to exhibit differences in handling-induced convulsion severity during ethanol withdrawal. Methods: We examined the role of the glutamatergic system in susceptibility to ethanol-withdrawal convulsions in naive mice by measuring the density of immunolabeling for several glutamate transporters and the glutamate-metabolizing enzyme, glutamine synthetase. The density of glial fibrillary acidic protein immunolabeling (a marker of glial structure) and cytochrome oxidase activity (a marker of neuronal activity) were also characterized in naive mice. Results: We observed a significantly greater density of immunolabeling for the glial transporter, glutamate/aspartate transporter, in CA1 subfield of the hippocampus (CA1) of naive WSP-2 mice as compared to WSR-2 mice. No other significant differences were observed. However, as compared to WSR mice, naive WSP mice exhibited a trend toward (a) greater immunolabeling for the glial glutamate transporter, glutamate transporter-1, in CA3, (b) greater immunolabeling for glial-specific glutamate-metabolizing enzyme, glutamine synthetase, in CA1 (replicate-2 only), and (c) less immunolabeling for the glial structural protein, glial fibrillary acidic protein, in all brain regions tested. In contrast, ng trends or significant differences in the labeling density for the neuronal transporter, excitatory amino acid carrier 1, or the neuronal activity marker, cytochrome oxidase, were observed between the selected lines. Conclusions: These data suggest that the glutamatergic system and glia may play a pivotal role in the increased susceptibility to handling-induced convulsions observed in WSP mice. C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. RP Meshul, CK (reprint author), Portland VA Med Ctr, Mail Code RD-29,3710 SW Vet Hosp Rd, Portland, OR 97201 USA. FU NIAAA NIH HHS [AA05507-01, P60 AA010760, AA07468]; NIDA NIH HHS [DA07262-06] NR 48 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 1999 VL 23 IS 12 BP 1905 EP 1913 PG 9 WC Substance Abuse SC Substance Abuse GA 271GE UT WOS:000084585200008 PM 10630609 ER PT J AU Charness, ME AF Charness, ME TI Intracranial voyeurism: Revealing the mammillary Bodies in alcoholism SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Editorial Material ID BRAIN-LESIONS; WERNICKES ENCEPHALOPATHY; IDENTIFICATION; AMNESIA; BODY C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Neurol 127,Neurol Serv, Boston, MA 02132 USA. RP Charness, ME (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Neurol 127,Neurol Serv, 1400 VFW Pkwy, Boston, MA 02132 USA. FU NIAAA NIH HHS [AA09669, AA11297] NR 21 TC 6 Z9 7 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 1999 VL 23 IS 12 BP 1941 EP 1944 DI 10.1111/j.1530-0277.1999.tb04095.x PG 4 WC Substance Abuse SC Substance Abuse GA 271GE UT WOS:000084585200013 PM 10630614 ER PT J AU Roman, GC AF Roman, GC TI A historical review of the concept of vascular dementia: Lessons from the past for the future SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article; Proceedings Paper CT 1st International Conference on Development of Drug Treatment for Vascular Dementia CY OCT 07-09, 1998 CL OSAKA, JAPAN DE history of medicine; history of neurology; Thomas Willis; Alois Alzheimer; Otto Binswanger; Emil Kraepelin; senile dementia; vascular dementia ID ALZHEIMERS-DISEASE; BINSWANGER,OTTO AB The history of senile dementia begins in the Greco-Roman period with basic concepts of senility by Pythagoras and Hippocrates. During the Middle Ages, the main contribution was by Roger Bacon in 1290. The first textbook of neurology, De cerebri morbis, by Jaso de Pratis (1549), included a chapter on dementia ("De memoriae detrimento'). Tn the 17th century, Thomas Willis recognized intellectual loss with aging. In the 19th century, Philippe Pinel removed chains from the mentally ill; his student Esquirol wrote the first modem classification of mental disease, including senile dementia. In 1860, Morel recognized brain atrophy with aging. The modem history of vascular dementia began in 1896, when Emil Kraepelin in his textbook Psychiatrie included "arteriosclerotic dementia" among the senile dementias, following the ideas of Otto Binswanger and Alois Alzheimer, who had differentiated clinically and pathologically arteriosclerotic brain lesions from senile dementia and from neurosyphilitic general paresis of the insane. Binswanger's and Alzheimer's contributions are reviewed in detail. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Neurol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Roman, GC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Neurol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 20 TC 22 Z9 27 U1 1 U2 3 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 DEC PY 1999 VL 13 SU 3 BP S4 EP S8 PG 5 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 269HZ UT WOS:000084471900002 PM 10609675 ER PT J AU Roman, GC Royall, DR AF Roman, GC Royall, DR TI Executive control function: A rational basis for the diagnosis of vascular dementia SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article; Proceedings Paper CT 1st International Conference on Development of Drug Treatment for Vascular Dementia CY OCT 07-09, 1998 CL OSAKA, JAPAN DE Alzheimer disease; Binswanger disease; dementia; diagnostic criteria; executive control functions; vascular dementia; controlled clinical trials ID POSITRON EMISSION TOMOGRAPHY; ENCEPHALOPATHY BINSWANGER DISEASE; FRONTAL-SUBCORTICAL CIRCUITS; ANTERIOR CINGULATE CORTEX; WHITE-MATTER CHANGES; ALZHEIMERS-DISEASE; COGNITIVE IMPAIRMENT; HUNTINGTONS-DISEASE; CARDIOVASCULAR HEALTH; BEDSIDE ASSESSMENT AB Problems with diagnostic criteria for vascular dementia (VaD) stem from the inadequacy of the current dementia concept, a paradigm based on amnestic and other cortical deficits typical of Alzheimer disease (AD). However, most cases of VaD are due to subcortical lesions such as Binswanger-type periventricular white matter ischemia, or strokes causing decreased frontal activation and diaschisis-mediated cerebral hypoperfusion. Wie propose a new definition of dementia based on executive dysfunction and a formal assessment of executive control functions (ECF) for the diagnosis of VaD. The instruments proposed are the rapid screening executive clock-drawing task (CLOX; Royall et al. J Neurol Neurosurg Psychiatry 1998;64.588-94), and the more comprehensive Executive Interview Test (EXIT25; Royall et al. J Am Geriatr Soc 1992;40:1221-6). Extensive application of these tests in elderly subjects in retirement communities has shown that both are brief, simple to administer, and more sensitive case-finding tools for cognitively impaired individuals than the Mini-Mental State Examination (MMSE). These three tests (CLOX, EXIT25, MMSE) accurately separate nondemented subjects from those with cortical or subcortical (frontal system) dementias. In addition, for controlled clinical trials of VaD, formal evaluation of motor and frontal sphincter functions-usually not considered part of the dementia syndrome-should also be included. Evaluation of gait and falls, timed-walk, manual dexterity, timed finger-lapping, and frontal bladder control (urge incontinence and nocturia) should improve determination of functional status and disability, and more accurately measure the effects of potential therapies. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Neurol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Roman, GC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Neurol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 152 TC 89 Z9 96 U1 1 U2 2 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 DEC PY 1999 VL 13 SU 3 BP S69 EP S80 PG 12 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 269HZ UT WOS:000084471900012 PM 10609685 ER PT J AU Cohen, MC Stafford, RS Misra, B AF Cohen, MC Stafford, RS Misra, B TI Stress testing: National patterns and predictors of test ordering SO AMERICAN HEART JOURNAL LA English DT Article; Proceedings Paper CT 70th Scientific Session of the American-Heart-Association Meeting CY NOV 09-13, 1997 CL ORLANDO, FLORIDA SP Amer Heart Assoc ID ACUTE MYOCARDIAL-INFARCTION; NEW-YORK-STATE; CARDIAC-CATHETERIZATION FACILITIES; CORONARY-ARTERY DISEASE; GENDER DIFFERENCES; HEART-DISEASE; UNITED-STATES; ASSOCIATION; MANAGEMENT; APPROPRIATENESS AB Objective To determine predictors of ordering of exercise stress tests. Background Because exercise stress testing is routinely used and widely available and may have an effect on subsequent evaluation of and therapy for heart disease, understanding current patterns of ordering exercise stress rests may have important implications for national health care costs. We hypothesized that factors other than clinical condition exert an influence on ordering of exercise stress tests. Methods Data from the 1991 and 1992 National Ambulatory Medical Core Surveys conducted by the National Center for Health Statistics were analyzed by means of multivariate logistic regression. Results In an estimated 1.12 billion adult visits to office-based physicians in the United Stares (95% confidence interval [CI], 1.07-1.16 billion), 6.2 million (95% CI, 4.8-7.6 million) exercise stress tests were ordered. After adjustment for clinical and nonclinical variables associated with the office visit, cardiologists were 3.7 (95% CI, 2.7-5.1) times more likely to order exercise stress tests than were internists, who were more likely to order an exercise stress test than were family and general practitioners (0.5, 95% CI, 0.3-0.7). Nonclinical factors associated with increased ordering of exercise stress tests included male sex (odds ratio 2.5; 95% CI, 2.0-3.2), white race (odds ratio 1.6; 95% CI, 1.1-2.3), new referral status (odds ratio 3.8; 95% CI, 2.5-5.8), and private insurance (odds ratio 1.4; 95% CI, 1.1-1.8). Medicare recipients were about half (95% CI, 0.4-0.9) as likely as other patients to have an exercise stress test ordered. Conclusions Factors other than clinical condition exert an influence on ordering of exercise stress tests and may represent modifiable elements associated with appropriate practice. C1 Maine Med Ctr, Div Cardiol, Portland, ME 04102 USA. Univ Vermont, Coll Med, Burlington, VT USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, Boston, MA USA. RP Cohen, MC (reprint author), Maine Cardiol Associates, 66 Bramhall St, Portland, ME 04102 USA. NR 35 TC 14 Z9 15 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD DEC PY 1999 VL 138 IS 6 BP 1019 EP 1024 DI 10.1016/S0002-8703(99)70065-7 PN 1 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 262EU UT WOS:000084053300009 PM 10577430 ER PT J AU Lehmann, KG Heath-Lange, SJ Ferris, ST AF Lehmann, KG Heath-Lange, SJ Ferris, ST TI Randomized comparison of hemostasis techniques after invasive cardiovascular procedures SO AMERICAN HEART JOURNAL LA English DT Article ID CONVENTIONAL MANUAL COMPRESSION; ARTERIAL PUNCTURE SITES; CARDIAC-CATHETERIZATION; CORONARY ANGIOGRAPHY; OUTPATIENT CATHETERIZATION; STENT IMPLANTATION; GUIDING CATHETERS; BRACHIAL APPROACH; TRIAL; ANGIOPLASTY AB Background The arterial access required during most invasive vascular procedures provides a common source of complications and morbidity. This problem has been made worse by recent trends in earlier ambulation and more aggressive antihemostatic drug regimens. Despite these trends, no randomized trials have been reported comparing the 3 most commonly used techniques in achieving hemostasis at the arterial puncture site. Methods A cohort of 400 patients undergoing catheterization laboratory procedures were randomly assigned to 1 of 3 groups of arterial compression:manual compression, mechanical clamp, and pneumatic compression device. Standard requirements of the trial included uniformity in initial compression times, patient instructions, nursing follow-up, and timing of ambulation as well as a structured interview and physical examination at 24 hours. Results Prolonged compression was required in 13% of the manual group, 20% of the clamp group, and 35% of the pneumatic group (P < .0001). In-lab bleeding was more common in the pneumatic group (3%, 4%, and 16%, respectively, P < .0001), as was the need for an alternate compression technique (1%, 1%, and 27%, P < .0001). The groups also differed in respect to mean hematoma size (3.9 cm(2), 7.8 cm(2), and 19.8 cm(2), P = .036) and level of discomfort during compression (1.9, 2.2, and 3.1 on a 1- to 10-point scale, P < .0001). Comparable findings were observed in the subgroup of patients eligible for outpatient procedures. Conclusions Use of the pneumatic compression device leads to longer compression times, greater discomfort, more bleeding,, and larger hematomas. Differences between manual compression and the mechanical clamp were more subtle but tend to favor use of the manual technique. C1 Vet Affairs Puget Sound Hlth Care Syst, Sect Cardiol 111C, Seattle, WA 98108 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. RP Lehmann, KG (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Sect Cardiol 111C, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 24 TC 26 Z9 29 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD DEC PY 1999 VL 138 IS 6 BP 1118 EP 1125 DI 10.1016/S0002-8703(99)70078-5 PN 1 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 262EU UT WOS:000084053300022 PM 10577443 ER PT J AU Weir, MM Rosenberg, AE Bell, DA AF Weir, MM Rosenberg, AE Bell, DA TI Grading of spindle cell sarcomas in fine-needle aspiration biopsy specimens SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE grading; spindle cell sarcomas; aspiration biopsy ID SOFT-TISSUE SARCOMAS; PROGNOSTIC-SIGNIFICANCE; MULTIVARIATE-ANALYSIS; CYTOLOGY; TUMORS; LESIONS; SYSTEM AB We studied whether histologic criteria for grading sarcomas could be applied to fine-needle aspiration biopsy (FNAB) specimens of adult spindle cell sarcomas, without knowledge of the sarcoma subtype, by reviewing 36 specimens. Grade 1 was assigned for minimal nuclear atypia and overlap, no necrosis, and rare mitotic figures, and grade 2 for moderate nuclear atypia, at least moderate nuclear overlap, appreciable mitotic figures, and necrosis. Severe nuclear atypia distinguished grade 3 from grade 2. A major noncorrelation between FNAB and histologic grades was defined as a misclassification of grade 1 vs grade 2 or 3 FNAB grades assigned were grade 1, 1; grade 2 25; and grade 3 10. There was 1 major noncorrelaton due to a probable FNAB interpretation error In 15 of 16 FNAB specimens of grade 2 or 3 sarcomas lacking mitotic figures, necrosis, or both, the nuclear atypia reflected the grade In the remaining case, the degree of nuclear overlap and necrosis determined the grade. The histololgic grading of sarcomas can be applied accurately to most FNAB specimens of spindle cell sarcomas without knowledge of the sarcoma subtype. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Dept Pathol, Boston, MA 02115 USA. RP Bell, DA (reprint author), Massachusetts Gen Hosp, Dept Pathol, 32 Fruit St, Boston, MA 02114 USA. NR 21 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD DEC PY 1999 VL 112 IS 6 BP 784 EP 790 PG 7 WC Pathology SC Pathology GA 258XL UT WOS:000083864900008 PM 10587701 ER PT J AU El-Serag, HB AF El-Serag, HB TI Barrett's esophagus, hiatal hernia, and logistic regression analysis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Editorial Material ID MODELS C1 Houston Vet Affairs Med Ctr, Dept Gastroenterol, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Dept Hlth Serv Res, Houston, TX USA. RP El-Serag, HB (reprint author), 2002 Holcombe Blvd 152, Houston, TX 77030 USA. NR 11 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 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD DEC PY 1999 VL 94 IS 12 BP 3395 EP 3396 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 263PL UT WOS:000084134400001 PM 10606286 ER PT J AU Zusman, RM AF Zusman, RM TI Are there differences among angiotensin receptor blockers? SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE angiotensin receptor blockers; bioavailability; half-life; hypertension; pharmacologic properties ID CONVERTING ENZYME-INHIBITORS; TO-MODERATE HYPERTENSION; LOSARTAN POTASSIUM; INSULIN-RESISTANCE; DOUBLE-BLIND; IRBESARTAN; EFFICACY; ANTAGONISTS; ENALAPRIL; TOLERABILITY AB Pharmacologic effects of specific drugs are frequently attributed to their therapeutic class because all agents within a particular class have the same mechanism of action. Because "head-to-head" comparisons in trials are rare, any differentiation between drugs of the same class is usually limited to comparisons of their pharmacokinetic profiles, and it is usually assumed that most of the drugs in a therapeutic class have similar efficacies. Two recent randomized clinical trials demonstrated that the antihypertensive agents irbesartan and losartan, both angiotensin receptor blockers, are not equally effective in reducing blood pressure among: patients with hypertension. In both a fixed-dose trial and a titration-protocol trial, patients treated with irbesartan achieved a greater reduction in blood pressure than did those treated with losartan, The response rate was also higher among patients treated with irbesartan. Therefore, irbesartan, used either alone or as a component of response-based combination therapy with a diuretic, is a more potent antihypertensive agent than losartan. These results and the previously published pharmacologic profiles of these drugs demonstrate that angiotensin receptor blockers are, like many other classes of antihypertensive agents, more different than alike. Am J Hypertens 1999;12:231S-235S (C) 1999 American Journal of Hypertension, Ltd. C1 Massachusetts Gen Hosp, Dept Hypertens & Vasc Med, Boston, MA 02114 USA. RP Zusman, RM (reprint author), Massachusetts Gen Hosp, Dept Hypertens & Vasc Med, 15 Parkman St, Boston, MA 02114 USA. NR 29 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD DEC PY 1999 VL 12 IS 12 SU S BP 231S EP 235S PN 3 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 268AB UT WOS:000084390500008 PM 10619576 ER PT J AU Kales, SN Aldrich, JM Polyhronopoulos, GN Leitao, EO Artzerounian, D Gassert, TH Hu, H Kelsey, KT Sweet, C Christiani, DC AF Kales, SN Aldrich, JM Polyhronopoulos, GN Leitao, EO Artzerounian, D Gassert, TH Hu, H Kelsey, KT Sweet, C Christiani, DC TI Correlates of fitness for duty in hazardous materials firefighters SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE firefighters; fitness for duty; morbidity; body mass index; pulmonary function; cardiac/coronary risk predictors ID FIRE FIGHTERS; PROFILE AB Background and Methods From a statewide medical examination program, we identified firefighters who were deemed unfit for duty by attending physicians (ATTENDING FAIL, n = 9) and those who would have been disqualified by the application of selected numerical criteria from title 1997 National Fire Protection Association (NFPA) guidelines (NFPA FAIL, n = 27) and criteria from a Medical Workshop (WORK FAIL, n = 16). The subjects who were unfit for duty or failed numerical criteria were compared with those who were fit for duty and passed all objective criteria (FIT group, n = 302). All subjects were given an overall morbidity rating by a board certified internist. Comparisons on two surrogate measures of fitness, VO2 max predicted and predicted coronary heart disease (CHD) risk, were also performed. Results We found a significant tendency towards worse results (e.g. higher blood pressure or lower spirometric function) among the three FAIL groups compared with the FIT group. The FAIL groups shared only a small overlap, however; with the firefighters with the highest morbidity ratings, lowest predicted VO2 max, and highest CHD risks. Increasing morbidity was associated with higher age, fewer spirometric function, lower predicted VO2 max, increasing cholesterol, greater BMI, and higher predicted 10 year CHD risk. Conclusion Although the presence of a single serious or poorly controlled condition may render an individual unfit for safe performance as a firefighter; examination of our cohort suggests that multiple risk factor models or overall clinical assessments are superior means of identifying firefighters with poor health status and increased CMD risk. (C) 1999 Wiley-Liss, Inc. C1 Cambridge Hosp, Dept Med, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Holyoke Hosp, Holyoke, MA USA. UMASS Med Ctr, Dept Family & Community Med, Worcester, MA USA. Massachuesetts Resp Hosp, Ctr Occupat & Environm Med, Braintree, MA USA. Harvard Univ, Sch Publ Hlth, Dept Canc Cell Biol, Boston, MA 02115 USA. Marlborough Hosp, UMASS Hlth Syst, Marlborough, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm Crit Care Unit, Boston, MA USA. RP Kales, SN (reprint author), Cambridge Hosp, Dept Med, 1493 Cambridge St, Cambridge, MA 02139 USA. RI Kelsey, Karl/I-1252-2014 FU NIEHS NIH HHS [ES00002, 1K07ES00266]; NIOSH CDC HHS [1 K01 OH00156] NR 21 TC 12 Z9 12 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD DEC PY 1999 VL 36 IS 6 BP 618 EP 629 DI 10.1002/(SICI)1097-0274(199912)36:6<618::AID-AJIM4>3.0.CO;2-7 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 253LY UT WOS:000083559100004 PM 10561682 ER PT J AU Rosenblatt, L Harwitz, DG AF Rosenblatt, L Harwitz, DG TI Fairness and rationing implications of medical necessity decisions SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID MANAGED CARE; ETHICAL ISSUES; HEALTH-CARE AB When healthcare coverage entails medical necessity review, patients, providers, payers, and government agencies must confront issues of fairness and rationing. To explore the ethical ramifications of medical necessity decisions, we provide 2 illustrative cases. In the first case, we;discuss the implications of rule-based rationing and in the second we consider the influence of a medical group's internal review council on decisions of medical necessity. Both case examples illustrate why there are no agreed-on rules for setting a threshold for approving or denying care based on medical necessity and suggest that more complex medical cases require a move complex review process. C1 Cleveland Clin, Florida Hlth Network, Ft Lauderdale, FL 33309 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Harwitz, DG (reprint author), Cleveland Clin, Florida Hlth Network, 2900 W Cyprss Rd,Suite 103, Ft Lauderdale, FL 33309 USA. NR 26 TC 3 Z9 3 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 DEC PY 1999 VL 5 IS 12 BP 1525 EP 1531 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 267BL UT WOS:000084334700003 PM 11066619 ER PT J AU Nielsen, GP Stemmer-Rachamimov, AO Ino, Y Moller, MB Rosenberg, AE Louis, DN AF Nielsen, GP Stemmer-Rachamimov, AO Ino, Y Moller, MB Rosenberg, AE Louis, DN TI Malignant transformation of neurofibromas in neurofibromatosis 1 is associated with CDKN2A/p16 inactivation SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID NERVE SHEATH TUMORS; SOFT-TISSUE SARCOMAS; CELL-CYCLE CONTROL; HOMOZYGOUS DELETIONS; GENETIC ALTERATIONS; HUMAN ASTROCYTOMAS; MTS1 P16(INK4A); P16 EXPRESSION; RB ALTERATIONS; MUTATIONS AB Patients with neurofibromatosis 1 (NF1) are predisposed to develop multiple neurofibromas (NFs) and are at risk for transformation of NFs to malignant peripheral nerve sheath tumors (MPNSTs). Little is known, however, about the biological events involved in the malignant transformation of NFs. We examined the CDKN2A/p16 gene and p16 protein in NFs and MPNSTs from patients with NF1. On immunohistochemical analysis, all NFs expressed p16 protein. The MPNSTs, however, were essentially immunonegative for p16, with striking transitions in cases that contained both benign and malignant elements. None of the benign tumors had CDKN2A/p16 deletions, whereas three of six MPNSTs appeared to have homozygous CDKN2A/p16 deletions. Methylation analysis and mutation analysis of CDKN2A/p16 in MPNSTs did not reveal any abnormalities. These results show that malignant transformation of NF is associated with loss of p16 expression, which is often secondary to homozygous deletion of the CDKN2A/ p16 gene. The findings suggest that CDKN2A/p16 inactivation occurs during the malignant transformation of NFs in NF1 patients and raises the possibility that p16 immunohistochemistry may provide ancillary information in the distinction of NF from MPNST. C1 Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Neurooncol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Odense Univ, Univ So Denmark, Dept Pathol, Odense, Denmark. RP Nielsen, GP (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Fruit St, Boston, MA 02114 USA. EM gnielsen@partners.org RI Moller, Michael/G-8340-2016 OI Moller, Michael/0000-0003-2041-3630 NR 49 TC 133 Z9 136 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 1999 VL 155 IS 6 BP 1879 EP 1884 DI 10.1016/S0002-9440(10)65507-1 PG 6 WC Pathology SC Pathology GA 262XD UT WOS:000084092800014 PM 10595918 ER PT J AU Prat, AG Cunningham, CC Jackson, GR Borkan, SC Wang, YH Ausiello, DA Cantiello, HF AF Prat, AG Cunningham, CC Jackson, GR Borkan, SC Wang, YH Ausiello, DA Cantiello, HF TI Actin filament organization is required for proper cAMP-dependent activation of CFTR SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE ABP-280 cystic fibrosis transmembrane conductance regulator; actin cytoskeleton; adenosine 3 ',5 '-cyclic monophosphate ID TRANSMEMBRANE CONDUCTANCE REGULATOR; EPITHELIAL NA+ CHANNELS; BINDING-PROTEIN; CHLORIDE CHANNEL; KINASE; CELLS; IDENTIFICATION; CYTOSKELETON; VASOPRESSIN; EXPRESSION AB Previous studies have indicated a role of the actin cytoskeleton in the regulation of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel. However, the exact molecular nature of this regulation is still largely unknown. In this report human epithelial CFTR was expressed in human melanoma cells genetically devoid of the filamin homologue act-in-cross-linking protein ABP-280 [ABP(-)]. cAMP stimulation of ABP(-) cells or cells genetically rescued with ABP-280 cDNA [ABP(+)] was without effect on whole cell Cl- currents. In ABP(-) cells expressing CFTR, cAMP was also without effect on Cl- conductance. In contrast, cAMP induced a 10-fold increase in the diphenylamine-2-carboxylate (DPC)-sensitive whole cell Cl- currents of ABP(+)/CFTR(+) cells. Further, in cells expressing both CFTR and a truncated form of ABP-280 unable to cross-link actin filaments, cAMP was also without effect on CFTR activation. Dialysis of ABP-280 or filamin through the patch pipette, however, resulted in a DPC-inhibitable increase in the whole cell currents of ABP(-)/CFTR(+) cells. At the single-channel let el, protein kinase A plus ATP activated single Cl- channels only in excised patches fi om ABP(+)/CFTR(+) cells. Furthermore, filamin alone also induced Cl- channel activity in excised patches of ABP( - )/CFTR( +) cells. The present data indicate that an organized actin cytoskeletan is required for cAMP-dependent activation of CFTR. C1 Massachusetts Gen Hosp East, Renal Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Boston Med Ctr, Renal Sect, Boston, MA 02118 USA. RP Cantiello, HF (reprint author), Massachusetts Gen Hosp East, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK-48040] NR 35 TC 45 Z9 46 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD DEC PY 1999 VL 277 IS 6 BP C1160 EP C1169 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 265LE UT WOS:000084245100017 PM 10600767 ER PT J AU Nagatomo, Y Carabello, BA Hamawaki, M Nemoto, S Matsuo, T McDermott, PJ AF Nagatomo, Y Carabello, BA Hamawaki, M Nemoto, S Matsuo, T McDermott, PJ TI Translational mechanisms accelerate the rate of protein synthesis during canine pressure-overload hypertrophy SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE pressure overload; translation; eukaryotic initiation factor 4E ID MYOSIN HEAVY-CHAIN; LEFT-VENTRICULAR HYPERTROPHY; INITIATION-FACTOR EIF-4E; RIBOSOMAL-RNA SYNTHESIS; CARDIAC-HYPERTROPHY; GENE-EXPRESSION; VOLUME OVERLOAD; TRANSCRIPTIONAL REGULATION; GROWTH; HEART AB This study examined how translational mechanisms regulate the rate of cardiac protein synthesis during canine pressure overload in vivo. Acute aortic stenosis (AS) was produced by inflating a balloon catheter in the ascending aorta for 6 h; sustained AS was created by controlled banding of the ascending aorta. AS caused significant hypertrophy as reflected by increased left ventricular (LV) mass after 5 and 10 days. To monitor LV protein synthesis in vivo, myosin heavy chain (MHC) synthesis was measured by continuous infusion of radiolabeled leucine. Acute AS accelerated the rate of myosin synthesis without a corresponding increase in ribosomal RNA, indicating an increase in translational efficiency. Total MHC synthesis (mg MHC/LV per day) was significantly increased at 5 and 10 days of sustained AS. Total MHC degradation was not significantly altered at 5 days of AS but increased at 10 days of AS in concordance with a new steady state with respect to growth. Translational capacity (mg total RNA/LV) was significantly increased after 5 and 10 days of AS and was preceded by an increase in the rate of ribosome formation. MHC mRNA levels remained unchanged during AS. These findings demonstrate that cardiac protein synthesis is accelerated in response to pressure overload by an initial increase in translational efficiency, followed by an adaptive increase in translational capacity during sustained hypertrophic growth. C1 Med Univ S Carolina, Gazes Cardiac Res Inst, Charleston, SC 29403 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29403 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29403 USA. RP McDermott, PJ (reprint author), Med Univ S Carolina, Gazes Cardiac Res Inst, Rm 303,Strom Thurmond Biomed Res Bldg,114 Doughty, Charleston, SC 29403 USA. FU NHLBI NIH HHS [P01-HL-48788] NR 41 TC 27 Z9 27 U1 2 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 DEC PY 1999 VL 277 IS 6 BP H2176 EP H2184 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 263UE UT WOS:000084143000009 PM 10600835 ER PT J AU Yao, ZH Tong, J Tan, XH Li, CQ Sha, ZH Kim, WC Vanden Hoek, TL Becker, LB Head, CA Schumacker, PT AF Yao, ZH Tong, J Tan, XH Li, CQ Sha, ZH Kim, WC Vanden Hoek, TL Becker, LB Head, CA Schumacker, PT TI Role of reactive oxygen species in acetylcholine-induced preconditioning in cardiomyocytes SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE signal transduction; adenosine 5 '-triphosphate-dependent potassium; channels; reactive oxygen species; mitochondria ID SENSITIVE POTASSIUM CHANNELS; K-ATP CHANNEL; SODIUM 5-HYDROXYDECANOATE; MUSCARINIC RECEPTORS; DOG HEART; G-PROTEIN; HYPOXIA; MECHANISM; BLOCKADE; ISCHEMIA AB We examined the ability of ACh to mimic ischemic preconditioning in cardiomyocytes and the role of ATP-sensitive potassium (K-ATP) channels and mitochondrial reactive oxygen species (ROS) in mediating this effect. Chick embryonic ventricular myocytes were studied in a flow-through chamber while flow rate, pH, PO2, and PCO2 were controlled. Cell viability was quantified with propidium iodide (5 mu M), and production of ROS was measured using 2',7'-dichlorofluorescin diacetate. Data were expressed as means +/- SE. Preconditioning with 10 min of ischemia followed by 10 min of reoxygenation or 10 min of ACh (1 mM) followed by a drug-free period before 1 h of ischemia and 3 h of reoxygenation reduced cell death to the same extent [preconditioning 19 +/- 2% (n = 6, P < 0.05) ACh 21 +/- 5% (n = 6, P < 0.05) vs controls 42 +/- 5% (n = 9)]. Like preconditioning, ACh increased ROS production threefold before ischemia [0.60 +/- 0.16 (n = 7, P < 0.05) vs, controls, 0.16 +/- 0.03 (n = 6); arbitrary units]. Protection and increased ROS production during ACh preconditioning were abolished with 5-hydroxydecanoate (5-HD, 100 mu M), a selective mitochondrial KATP channel antagonist, and the thiol reductant 2-mercaptopropionyl glycine (2-MPG, 1 mM), an antioxidant [cell death: 5-HD+ACh 37 +/- 7% (n = 5), 2-MPG+ACh 47 +/- 6% (n = 6); ROS signals: 5-HD+ACh 0.09 +/- 0.03 (n = 5), 2-MPG+ACh 0.01 +/- 0.04 (12 = 4)]. In addition, ACh-induced ROS signaling was blocked by the mitochondrial site III electron transport inhibitor myxothiazol (0.02 +/- 0.07, n = 5). These results demonstrate that activation of mitochondrial KATP channels and increased ROS production from mitochondria are important intracellular signals that participate in ACh-induced preconditioning in cardiomyocytes. C1 Univ Chicago, Dept Anesthesia & Crit Care, Chicago, IL 60637 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Yao, ZH (reprint author), Univ Chicago, Dept Anesthesia & Crit Care, 5841 S Maryland Ave,MC 4028, Chicago, IL 60637 USA. FU NHLBI NIH HHS [HL-32646, HL-35440, HL-03881-02] NR 37 TC 98 Z9 106 U1 1 U2 3 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 DEC PY 1999 VL 277 IS 6 BP H2504 EP H2509 PG 6 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 263UE UT WOS:000084143000049 PM 10600875 ER PT J AU Silva, P Solomon, RJ Epstein, FH AF Silva, P Solomon, RJ Epstein, FH TI Mode of activation of salt secretion by C-type natriuretic peptide in the shark rectal gland SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE chloride secretion; guanylyl cyclase; guanosine 3 ',5 '-cyclic monophosphate; protein kinase C; phorbol esters ID CHLORIDE SECRETION; SQUALUS-ACANTHIAS; VOLUME EXPANSION; INHIBITION; STAUROSPORINE; SOMATOSTATIN; RECEPTORS; TRANSPORT; DOGFISH; CELLS AB We studied the modes of activation of the salt-secreting rectal gland of the spiny dogfish, Squalus acanthias, by the native cardiac peptide CNP. The stimulatory action of CNP in isolated perfused glands is inhibited by 10 mM procaine, presumably by blocking release of vasoactive intestinal peptide (VIP) from nerves. Procaine reduces the slope of the dose-response curve of human CNP and that of shark CNP teach P < 0.0001). CNP increases short-circuit current in cultured rectal gland cells from 4.8 +/- 1.6 to 27.0 +/- 7.8 mu A/cm(2). it also stimulates the secretion of chloride in isolated perfused glands in the presence of 10 mM procaine from 72 +/- 31 to 652 +/- 173 mu eq . h(-1) . g(-1). These results suggest that CNP has a direct cellular action not mediated by the neural release of Vip. The residual stimulation of perfused glands in the presence of procaine was almost completely inhibited by staurosporine [10 nM; an inhibitor of protein kinase C (PKC)] from 652 +/- 173 to 237 +/- 61 mu eq . h(-1) . g(-1). Although CNP stimulates guanylyl cyclase in shark rectal gland, chloride secretion of perfused glands was not elicited by 8-bromoadenosine-cGMP (8-BrcGMP) alone nor by the activator of PKC phorbol ester. The combination of PKC activation and 8-BrcGMP infusion, however, stimulated chloride secretion in perfused glands from 94 +/- 30 to 506 +/- 61 . mu eq . h(-1) . g(-1), a level comparable to that observed in glands blocked with procaine. Several parallel pathways appear to be synergistic in activating chloride secretion stimulated by CNP in the rectal gland. C1 Temple Univ Hosp, Dept Med, Philadelphia, PA 19140 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Mt Desert Isl Biol Lab, Salsbury Cove, ME 04672 USA. RP Silva, P (reprint author), Temple Univ, Nephrol Sect, Sch Med, 5th Floor Parkinson Pavil,3401 N Broad St, Philadelphia, PA 19140 USA. FU NCEH CDC HHS [NIEHS-ESO-3828]; NIDDK NIH HHS [DK-18078, DK-16684] NR 33 TC 27 Z9 27 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD DEC PY 1999 VL 277 IS 6 BP R1725 EP R1732 PG 8 WC Physiology SC Physiology GA 265DB UT WOS:000084225100024 PM 10600920 ER PT J AU Wilens, TE Biederman, J Spencer, TJ Bostic, J Prince, J Monuteaux, MC Soriano, J Fine, C Abrams, A Rater, M Polisner, D AF Wilens, TE Biederman, J Spencer, TJ Bostic, J Prince, J Monuteaux, MC Soriano, J Fine, C Abrams, A Rater, M Polisner, D TI A pilot controlled clinical trial of ABT-418, a cholinergic agonist, in the treatment of adults with attention deficit hyperactivity disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CIGARETTE-SMOKING; (S)-3-METHYL-5-(1-METHYL-2-PYRROLIDINYL)ISOXAZOLE ABT-418; DEFICIT/HYPERACTIVITY DISORDER; ANXIOLYTIC ACTIVITIES; NICOTINIC SYSTEMS; DOUBLE-BLIND; COGNITION; MEMORY; PERFORMANCE; DIAGNOSIS AB Objective:: Despite the increasing recognition of attention deficit hyperactivity disorder (ADHD) in adults, there is a paucity of controlled pharmacological trials. Recent reports have suggested the potential usefulness of cholinergic agents for ADHD. To this end, the authors completed a controlled study of ABT-418, a novel cholinergic activating agent, for the treatment of adults with ADHD. Method: This was a double-blind, placebo-controlled, randomized, crossover trial that compared a transdermal patch of ABT-418 (75 mg/day) to placebo in adults who met DSM-IV criteria for ADHD. There were two 3-week treatment periods separated by 1 week of washout. Results: Of the 32 subjects enrolled in the study (88% were men; mean age=40 years, SD=9), 29 completed the study. At the endpoint of each active arm (last observation carried forward), a significantly higher proportion of subjects was considered improved while receiving ABT-418 than while receiving placebo (40% versus 13%). Similarly, at endpoint there was a significantly greater reduction in ADHD symptom checklist scores (28% versus 15%). Symptoms reflective of attention, and subjects with less severe ADHD, responded more robustly to ABT-418. Treatment with ABT-418 was relatively well tolerated; dizziness and nausea were the most frequently reported adverse effects. Conclusions: The results of this investigation indicate that ABT-418, a nicotinic analog, may be a potentially useful agent for the treatment of ADHD. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Clin, Boston, MA 02114 USA. RP Wilens, TE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Clin, ACC 725, Boston, MA 02114 USA. FU NIMH NIH HHS [MH-01175] NR 56 TC 161 Z9 166 U1 2 U2 5 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 1999 VL 156 IS 12 BP 1931 EP 1937 PG 7 WC Psychiatry SC Psychiatry GA 260DT UT WOS:000083934800014 PM 10588407 ER PT J AU Nakamura, H Weiss, ST Israel, E Luster, AD Drazen, JM Lilly, CM AF Nakamura, H Weiss, ST Israel, E Luster, AD Drazen, JM Lilly, CM TI Eotaxin and impaired lung function in asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID GUINEA-PIG MODEL; RECEPTOR CCR3; IN-VIVO; AIRWAY HYPERRESPONSIVENESS; BRONCHOALVEOLAR LAVAGE; TISSUE EOSINOPHILIA; BRONCHIAL-ASTHMA; ATOPIC ASTHMA; SERUM IGE; EXPRESSION AB We performed an association study of plasma eotaxin levels, eosinophil counts, total IgE levels, asthma diagnosis, and lung function in an ethnically diverse and geographically dispersed population. We studied 515 asthmatic and 519 normal subjects, none of whom was taking inhaled or oral corticosteroids. Logistic regression analysis demonstrated a direct relationship between asthma diagnosis and eotaxin levels (p < 0.0001). The odds of an asthma diagnosis increased with eotaxin quartile, with the highest quartile having an odds ratio of 5.4 (95% CI 3.2 to 9.2, p < 0.001) compared with the lowest eotaxin quartile. Eotaxin levels were inversely related to lung function (p < 0.001), with the mean percent predicted FEV1 in the highest eotaxin quartile being 13.5 percentage paints (SEM 2.1, p < 0.001) less than that in the lowest quartile, Plasma eotaxin levels were associated with asthma and inversely related to lung function independent of age, race, sex, or smoking status. When combined with eosinophil counts and IgE levels, eotaxin levels contributed to the odds of an asthma diagnosis and of impaired lung function. Our results are the first to associate eotaxin levers with asthma diagnosis and compromised lung function in a large geographically and ethnically diverse population. C1 Brigham & Womens Hosp, Div Resp, Dept Med, Combined Program Pulm & Crit Care Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lilly, CM (reprint author), Brigham & Womens Hosp, Div Resp, Dept Med, Combined Program Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA. RI Drazen, Jeffrey/E-5841-2012 FU NHLBI NIH HHS [HL-03283]; NIAID NIH HHS [AI-40618] NR 35 TC 73 Z9 74 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC PY 1999 VL 160 IS 6 BP 1952 EP 1956 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 265MM UT WOS:000084248000026 PM 10588612 ER PT J AU Provenzale, JM Sorensen, AG AF Provenzale, JM Sorensen, AG TI Diffusion-weighted MR imaging in acute stroke: Theoretic considerations and clinical applications SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review ID CEREBRAL-ISCHEMIA; T2-WEIGHTED MRI; BRAIN; SPECTROSCOPY; REPERFUSION; WATER; RATS; CATS C1 Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Provenzale, JM (reprint author), Duke Univ, Med Ctr, Dept Radiol, Box 3808, Durham, NC 27710 USA. NR 36 TC 95 Z9 99 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 1999 VL 173 IS 6 BP 1459 EP 1467 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 258BQ UT WOS:000083818500007 PM 10584783 ER PT J AU O'Malley, ME Boland, GWL Wood, BJ Fernandez-del Castillo, C Warshaw, AL Mueller, PR AF O'Malley, ME Boland, GWL Wood, BJ Fernandez-del Castillo, C Warshaw, AL Mueller, PR TI Adenocarcinoma of the head of the pancreas: Determination of surgical unresectability with thin-section pancreatic-phase helical CT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID PERIPANCREATIC VEINS; DYNAMIC CT; CANCER; CARCINOMA; RESECTABILITY; DIAGNOSIS; ANATOMY; TUMOR AB OBJECTIVE. This study was conducted to evaluate newly introduced criteria for unresectability of pancreatic cancer with thin-section pancreatic-phase helical CT. MATERIALS AND METHODS. Twenty-five patients with adenocarcinoma in the head of the pancreas underwent thin-section pancreatic-phase helical CT. The major peripancreatic vessels were categorized on a scale of 1-4, according to the degree of circumferential involvement by tumor. The maximum diameters of the small peripancreatic veins-gastrocolic trunk, anterosuperior pancreaticoduodenal vein, and posterosuperior pancreatidoduodenal vein-were recorded. Findings on CT were compared with the results of surgery in each patient. RESULTS. Sixteen patients had surgically resectable tumors, and nine patients had surgically unresectable tumors. CT and surgical correlation was available for 98 major peripancreatic vessels; 85 were resectable and 13 were unresectable. Of category 1 vessels, 72 (97%) of 74 were resectable at surgery. Of category 2 vessels, 12 (71%) of 17 were resectable. One (50%) of two category 3 vessels and none (0%) of five category 4 vessels were resectable at surgery. CT showed a dilated gastrocolic trunk in two patients; one of these patients had a surgically resectable tumor, but the other patient had a surgically unresectable tumor. CONCLUSION. In patients with adenocarcinoma in the head of the pancreas, the degree of circumferential vessel involvement by tumor as shown by CT is useful in predicting which patients will have surgically unresectable tumors. A dilated gastrocolic trunk should not be used as an independent sign of surgical unresectability. C1 Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP O'Malley, ME (reprint author), Toronto Gen Hosp, Dept Med Imaging, 200 Elizabeth St, Toronto, ON M5G 2C4, Canada. NR 26 TC 105 Z9 112 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 1999 VL 173 IS 6 BP 1513 EP 1518 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 258BQ UT WOS:000083818500018 PM 10584794 ER PT J AU Bigatello, LM Hurford, WE Pesenti, A AF Bigatello, LM Hurford, WE Pesenti, A TI Ventilatory management of severe acute respiratory failure for Y2K SO ANESTHESIOLOGY LA English DT Editorial Material DE ARDS; barotrauma; mechanical ventilation ID DISTRESS SYNDROME; BAROTRAUMA; STRATEGY; POSITION; RISK C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Univ Milan, Osped San Gerardo, Monza, Italy. RP Bigatello, LM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 20 TC 5 Z9 5 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 DEC PY 1999 VL 91 IS 6 BP 1567 EP 1570 DI 10.1097/00000542-199912000-00005 PG 4 WC Anesthesiology SC Anesthesiology GA 262WX UT WOS:000084092200002 PM 10598595 ER PT J AU Weimann, J Bloch, KD Takata, M Steudel, W Zapol, WM AF Weimann, J Bloch, KD Takata, M Steudel, W Zapol, WM TI Congenital NOS2 deficiency protects mice from LPS-induced hyporesponsiveness to inhaled nitric oxide SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT 10th European Congress of Anesthesiology CY JUN 30-JUL 04, 1998 CL FRANKFURT, GERMANY DE gene deletion; lipopolysaccharide; mouse; pulmonary circulation ID RESPIRATORY-DISTRESS-SYNDROME; SELECTIVE PULMONARY VASODILATOR; SYNTHASE; INHALATION; VASOCONSTRICTION; OXYGENATION; ENDOTOXEMIA; INHIBITION; SUPEROXIDE; INJURY AB Background: In animal models, endotoxin (lipopolysaccharide) challenge impairs the pulmonary vasodilator response to inhaled nitric oxide (NO). This impairment is prevented by treatment with inhibitors of NO synthase 2 (NOS2), including glucocorticoids and L-arginine analogs. However, because these inhibitors are not specific for NOS2, the role of this enzyme in the impairment of NO responsiveness by lipopolysaccharide remains incompletely defined. Methods: To investigate the role of NOS2 in the development of lipopolysaccharide-induced impairment of NO responsiveness, the authors measured the vasodilator response to inhalation of 0.4, 4, and 40 ppm NO in isolated, perfused, and ventilated lungs obtained from lipopolysaccharide-pretreated (50 mg/kg intraperitoneally 16 h before lung perfusion) and untreated wild-type and NOS2-deficient mice. The authors also evaluated the effects of breathing NO for 16 h on pulmonary vascular responsiveness during subsequent ventilation with NO. Results: In wild-type mice, lipopolysaccharide challenge impaired the pulmonary vasodilator response to 0.4 and 4 ppm NO (reduced 79% and 45%, respectively, P < 0.001), but not to 40 ppm. In contrast, lipopolysaccharide administration did not impair the vasodilator response to inhaled NO in NOS2-deficient mice. Breathing 20 ppm NO for 16 h decreased the vasodilator response to subsequent ventilation with NO in Lipopolysaccharide-pretreated NOS2-deficient mice, but not in lipopolysaccharide-pretreated wild-type, untreated NOS2-deficient or untreated wild-type mice. Conclusions: In response to endotoxin challenge, NO, either endogenously produced by NOS2 in wild-type mice or added to the air inhaled by NOS2-deficient mice, is necessary to impair vascular responsiveness to inhaled NO. Prolonged NO breathing, without endotoxin, does not impair vasodilation in response to subsequent NO inhalation. These results suggest that NO, plus other lipopolysaccharide-induced products, are necessary to impair responsiveness to inhaled NO in a murine sepsis model. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Zapol, WM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 32 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL 42397, HL 55377] NR 33 TC 20 Z9 20 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD DEC PY 1999 VL 91 IS 6 BP 1744 EP 1753 DI 10.1097/00000542-199912000-00028 PG 10 WC Anesthesiology SC Anesthesiology GA 262WX UT WOS:000084092200025 PM 10598618 ER PT J AU Kuemmerle, S Gutekunst, CA Klein, AM Li, XJ Li, SH Beal, MF Hersch, SM Ferrante, RJ AF Kuemmerle, S Gutekunst, CA Klein, AM Li, XJ Li, SH Beal, MF Hersch, SM Ferrante, RJ TI Huntingtin aggregates may not predict neuronal death in Huntington's disease SO ANNALS OF NEUROLOGY LA English DT Article ID INTRANUCLEAR INCLUSIONS; REPEAT DISORDERS; STRIATAL NEURONS; NUCLEAR; LOCALIZATION; NEOSTRIATUM; PROJECTION; LENGTH; MICE AB The mechanism by which polyglutamine expansion in Huntington's disease (HD) results in selective neuronal degeneration remains unclear. We previously reported that the immunohistochemical distribution of N-terminal huntingtin in HD does not correspond to the severity of neuropathology, such that significantly greater numbers of huntingtin aggregates are present within the cortex than in the striatum. We now show a dissociation between huntingtin aggregation and the selective pattern of striatal neuron loss observed in HD. Aggregate formation was predominantly observed in spared interneurons, with few or no aggregates found within vulnerable spiny striatal neurons. Multiple perikaryal aggregates were present in almost all cortical NADPH-diaphorase neurons and in approximately 50% of the spared NADPH-diaphorase striatal neurons from early grade HD cases. In severe grade HD patients, aggregates were more prominent as nuclear inclusions in NADPH-diaphorase neurons, with less perikaryal and neuropil aggregation. In contrast, nuclear or perikaryal huntingtin aggregates were present in less than 4% of the vulnerable calbindin striatal neurons in all HD cases. These findings support the hypothesis that polyglutamine aggregation may not be a predictor of cell loss. Rather than a harbinger of neuronal death, mutant huntingtin aggregation may be a cytoprotective mechanism against polyglutamine-induced neurotoxicity. C1 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. Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Vet Affairs Med Ctr, Geriatr Res Educ Clin Ctr, Unit 182B, Bedford, MA 01730 USA. Tech Univ Munich, Sch Med, D-8000 Munich, Germany. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Genet, Atlanta, GA 30322 USA. Cornell Univ, Coll Med, Dept Neurol & Neurosci, New York, NY 10021 USA. RP Ferrante, RJ (reprint author), Vet Affairs Med Ctr, Geriatr Res Educ Clin Ctr, Unit 182B, 200 Springs Rd, Bedford, MA 01730 USA. FU NINDS NIH HHS [NS35255, NS36232, NS37102] NR 31 TC 253 Z9 257 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 1999 VL 46 IS 6 BP 842 EP 849 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 261EY UT WOS:000083997300006 PM 10589536 ER PT J AU Harris, NL Jaffe, ES Diebold, J Flandrin, G Muller-Hermelink, HK Vardiman, J Lister, TA Bloomfield, CD AF Harris, NL Jaffe, ES Diebold, J Flandrin, G Muller-Hermelink, HK Vardiman, J Lister, TA Bloomfield, CD TI The World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues SO ANNALS OF ONCOLOGY LA English DT Editorial Material DE classification; histiocytic; lymphoma; leukemia; myeloid; mast cell AB Introduction: Since 1995, the European Association of Pathologists (EAHP) and the Society for Hematopathology (SH) have been developing a new World Health Organization (WHO) Classification of hematologic malignancies. The classification includes lymphoid, myeloid, histiocytic, and mast cell neoplasms. Design: The WHO project involves 10 committees of pathologists, who have developed lists and definitions of disease entities. A Clinical Advisory Committee (CAC) ) of international hematologists and oncologists was formed to ensure that the classification will be useful to clinicians. A meeting was held in November, 1997, to discuss clinical issues related to the classification. Results: The WHO has adopted the 'Revised European-American Classification of Lymphoid Neoplasms' (R.E.A.L.), published in 1994 by the International Lymphoma Study Group (ILSG), as the classification of lymphoid neoplasms. This approach to classification is based on the principle that a classification is a list of 'real' disease entities, which are defined by a combination of morphology, immunophenotype, genetic features, and clinical features. The relative importance of each of these features varies among diseases, and there is no one 'gold standard'. The WHO Classification has applied the principles of the R.E.A.L. Classification to myeloid and histiocytic neoplasms. The classification of myeloid neoplasms recognizes distinct entities defined by a combination of morphology and cytogenetic abnormalities. The CAC meeting, which was organized around a series of clinical questions, was able to reach a consensus on most of the questions posed. The questions and the consensus are discussed in detail below. Among other things, the CAC concluded that clinical groupings of lymphoid neoplasms were neither necessary nor desirable. Patient treatment is determined by the specific type of lymphoma, with the addition of grade within the tumor type, if applicable, and clinical prognostic factors such as the international prognostic index (IPI). Conclusion: The experience of developing the WHO Classification has produced a new and exciting degree of cooperation and communication between oncologists and pathologists from around the world, which should facilitate progress in the understanding and treatment of hematologic malignancies. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. NCI, Bethesda, MD 20892 USA. Hotel Dieu, Paris, France. Hop Necker, Paris, France. Univ Wurzburg, Wurzburg, Germany. Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. St Bartholomews Hosp, Dept Med Oncol, London, England. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. RP Harris, NL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2,Fruit St, Boston, MA 02114 USA. NR 4 TC 345 Z9 368 U1 1 U2 7 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 1999 VL 10 IS 12 BP 1419 EP 1432 DI 10.1023/A:1008375931236 PG 14 WC Oncology SC Oncology GA 278TL UT WOS:000085005000014 PM 10643532 ER PT J AU Zeitels, SM Hillman, RE Desloge, RB Bunting, GA AF Zeitels, SM Hillman, RE Desloge, RB Bunting, GA TI Cricothyroid subluxation: A new innovation for enhancing the voice with laryngoplastic phonosurgery SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Broncho-Esophagological-Association CY APR 26-27, 1999 CL PALM DESERT, CALIFORNIA SP Amer Broncho Esophagol Assoc DE adduction; arytenoid; arytenopexy; cricothyroid joint; dysphonia; Gore-Tex; laryngoplasty; medialization; paralysis; phonosurgery; vocal cord; vocal fold; voice ID MEDIALIZATION AB Laryngoplastic phonosurgery has evolved to become a:dominant treatment modality for paralytic dysphonia. Current surgical procedures have addressed primarily the position of the musculomembranous vocal fold and the arytenoid in the axial and vertical planes. However, dynamic range capabilities and vocal flexibility have been limited secondary to the flaccid, denervated vocal fold tissue. Therefore, a new procedure was conceived to enhance the acoustic vocal outcome from operations that reposition the vocal edge. Cricothyroid (CT) subluxation was designed as a technique to increase the distance between the cricoarytenoid joint and the insertion of the anterior commissure ligament. Cricothyroid subluxation was done without complication in 9 patient's who underwent combined adduction arytenopexy and medialization laryngoplasty, and in 4 patients with medialization laryngoplasty alone. Postoperative stroboscopic assessment was done in all of the 13 patients, while complete analysis of vocal function was available in Ib of the 13 patients; this revealed improvement (as a group) on almost all objective measures over the preoperative state. All patients who underwent CT subluxation had a normal maximum frequency range (pitch variation of more than 2 octaves), as compared with 22% of a prior similar cohort of patients who did not undergo CT subluxation. All patients who underwent CT subluxation had normal glottal airflow and a normal noise-to-harmonics ratio. Cricothyroid subluxation is a relatively easily adjustable procedure that increases the length and viscoelastic tension of the denervated vocal fold. The modified biomechanical properties resulted in improved vocal outcome in all of our patients, which was most remarkable in terms of maximal range capabilities, Cricothyroid subluxation enhanced the postoperative voice of patients regardless of whether they required medialization laryngoplasty alone or whether they also required adduction arytenopexy. C1 Massachusetts Eye & Ear Infirm, Div Laryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Voice & Speech Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Zeitels, SM (reprint author), Massachusetts Eye & Ear Infirm, Div Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 19 TC 23 Z9 23 U1 0 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD DEC PY 1999 VL 108 IS 12 BP 1126 EP 1131 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 264XD UT WOS:000084207600005 PM 10605916 ER PT J AU Norton, JA AF Norton, JA TI The role of surgery in adrenal cancer SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material ID ADRENOCORTICAL CARCINOMA; RESECTION; DISEASE C1 Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. RP Norton, JA (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, 4150 clement St, San Francisco, CA 94121 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 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 DEC PY 1999 VL 6 IS 8 BP 713 EP 714 DI 10.1007/s10434-999-0713-0 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 268FA UT WOS:000084402600001 PM 10622495 ER PT J AU Koletar, SL Berry, AJ Cynamon, MH Jacobson, J Currier, JS MacGregor, RR Dunne, MW Williams, DJ AF Koletar, SL Berry, AJ Cynamon, MH Jacobson, J Currier, JS MacGregor, RR Dunne, MW Williams, DJ TI Azithromycin as treatment for disseminated Mycobacterium avium complex in AIDS patients SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; VIRUS INFECTION; CLARITHROMYCIN; THERAPY; ETHAMBUTOL; BACTEREMIA; RESISTANT; DISEASE; INVITRO; INVIVO AB This multicenter, randomized, dose-ranging study was performed to determine the safety and efficacy of two different doses of azithromycin for treating disseminated Mycobacterium avium complex (MAC) in patients with AIDS. Eighty-eight AIDS patients with symptoms and blood cultures consistent with disseminated MAC were treated with 600 or 1,200 mg of azithromycin daily for 6 weeks; 62 patients completed the entire 6 weeks of study, Of note, this study was done prior to the time when combination antiretroviral or anti-MAC regimens were the standard of care. Over the 6-week study period, symptomatic improvement was noted in both dose groups, Microbiological responses were comparable, with mean decreases of 1.5 and 2.0 log CFU/ml in the high- and low-dose groups, respectively, Sterilization of blood cultures occurred in 54% of samples; patients with lower baseline colony counts were more likely to achieve culture negativity, Resistance developed in one patient. Gastrointestinal symptoms were the most common side effects and were more frequent in patients receiving 1,200 mg. Azithromycin is a useful alternative treatment for disseminated MAC infection in AIDS patients. Symptomatic improvement correlates with measurable decreases in mycobacterial load. C1 Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX USA. SUNY, Syracuse, NY USA. Dept Vet Affairs Med Ctr, Bronx, NY USA. Beth Israel Hosp, Boston, MA 02215 USA. Univ Penn, Philadelphia, PA 19104 USA. Pfizer Inc, Pfizer Cent Res, Groton, CT 06340 USA. RP Koletar, SL (reprint author), N-1135 Doan Hall,410 W 10th Ave, Columbus, OH 43210 USA. EM koletar.1@osu.edu NR 22 TC 18 Z9 21 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 1999 VL 43 IS 12 BP 2869 EP 2872 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 261YE UT WOS:000084037900007 PM 10582873 ER PT J AU Al-Abdely, HM Graybill, JR Loebenberg, D Melby, PC AF Al-Abdely, HM Graybill, JR Loebenberg, D Melby, PC TI Efficacy of the triazole SCH 56592 against Leishmania amazonensis and Leishmania donovani in experimental murine cutaneous and visceral leishmaniases SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID KETOCONAZOLE; ITRACONAZOLE; STIBOGLUCONATE; PANCREATITIS; AMPHOTERICIN; COINFECTION AB Current therapy for leishmaniasis is unsatisfactory. Efficacious and safe oral therapy would be ideal. We examined the efficacy of SCH 56592, an investigational triazole antifungal agent, against cutaneous infection with Leishmania amazonensis and visceral infection with Leishmania donovani in BALB/c mice. Mice were infected in the ear pinna and tail with L, amazonensis promastigotes and were treated with oral SCI-I 56592 or intraperitoneal amphotericin B for 21 days. At doses of 60 and 30 mg/kg/day, SCH 56592 was highly efficacious in treating cutaneous disease, and at a dose of 60 mg/kg/day, it was superior to amphotericin B at a dose of 1 mg/kg/day, The means of tail lesion sizes were 0.32 +/- 0.12, 0.11 +/- 0.06, 0.17 +/- 0.07, and 0.19 +/- 0.08 mm for controls, SCH 56592 at 60 and 30 mg/kg/day, and amphotericin B recipients, respectively (P = 0.00113, 0.005, and 0.01, respectively). Parasite burden in draining lymph nodes confirmed these efficacy findings. In visceral leishmaniasis due to L. donovani infection, mice treated with SCH 56592 showed a 0.5- to 1-log-unit reduction in parasite burdens in the liver and the spleen compared to untreated mice. Amphotericin B at 1 mg/kg/day was superior to SCH 56592 in the treatment of visceral infection, with a 2-log-unit reduction in parasite burdens in both the liver and spleen. These studies indicate very good activity of SCH 56592 against cutaneous leishmaniasis due to L, amazonensis infection and, to a lesser degree, against visceral leishmaniasis due to L. donovani infection in susceptible BALB/c mice. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, San Antonio, TX 78284 USA. Audie Murphy Vet Adm Hosp, Med Serv, San Antonio, TX 78284 USA. Schering Plough Res Inst, Kenilworth, NJ 07833 USA. RP Al-Abdely, HM (reprint author), King Faisal Specialist Hosp & Res Ctr, Dept Med MBC 46, Div Infect Dis, POB 3354, Riyadh 11211, Saudi Arabia. NR 15 TC 54 Z9 55 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 1999 VL 43 IS 12 BP 2910 EP 2914 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 261YE UT WOS:000084037900015 PM 10582881 ER PT J AU Tompkins, CA Spencer, KA Schulz, R AF Tompkins, CA Spencer, KA Schulz, R TI Evaluating stresses and interventions for informal carers of aphasic adults: taking a broader perspective. A commentary on Servaes, Draper, Conroy, and Bowing (1999) SO APHASIOLOGY LA English DT Article ID CARDIOVASCULAR HEALTH; STROKE; CAREGIVERS; OUTCOMES; SUPPORT; PEOPLE C1 Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Ctr Social & Urban Res, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Aphasia Rehabil Res Lab & Clin, Pittsburgh, PA USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. RP Tompkins, CA (reprint author), Univ Pittsburgh, Dept Commun Sci & Disorders, 4033 Forbes Tower, Pittsburgh, PA 15260 USA. NR 24 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PD DEC PY 1999 VL 13 IS 12 BP 902 EP 907 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 267CX UT WOS:000084338400003 ER PT J AU Heckers, S Goff, D Schacter, DL Savage, CR Fischman, AJ Alpert, NM Rauch, SL AF Heckers, S Goff, D Schacter, DL Savage, CR Fischman, AJ Alpert, NM Rauch, SL TI Functional imaging of memory retrieval in deficit vs nondeficit schizophrenia SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID CEREBRAL BLOOD-FLOW; DORSOLATERAL PREFRONTAL CORTEX; EMISSION COMPUTED-TOMOGRAPHY; EPISODIC MEMORY; PHYSIOLOGICAL DYSFUNCTION; CONSCIOUS RECOLLECTION; HIPPOCAMPAL FUNCTION; GLUCOSE-METABOLISM; RECOGNITION MEMORY; NEUROLEPTIC-NAIVE AB Background: Neuroimaging studies have provided evidence of abnormal frontal and temporal lobe function in schizophrenia. Frontal cortex abnormalities have been associated with negative symptoms and temporal lobe abnormalities with positive symptoms. The deficit and nondeficit forms of schizophrenia were predicted to differ in prefrontal cortical activity, but not in medial temporal lobe activity. Methods: Regional cerebral blood flow was studied using oxygen 15 positron emission tomography during 3 different memory retrieval conditions in 8 control subjects, 8 patients with the deficit syndrome, and 8 patients without the deficit syndrome. Behavioral and positron emission tomography data were analyzed using a mixed-effects model to test for population differences. Results: In all memory conditions, frontal cortex activity was higher in patients without the deficit syndrome than in patients with the deficit syndrome. During the attempt to retrieve poorly encoded words, patients without the deficit syndrome recruited the left frontal cortex to a significantly greater degree than did patients with the deficit syndrome. The 2 schizophrenia subtypes did not differ in the activity or recruitment of the hippocampus during memory retrieval. Conclusion: Frontal cortex function during memory retrieval is differentially impaired in deficit and nondeficit schizophrenia, whereas hippocampal recruitment deficits are not significantly different between the 2 schizophrenia groups. C1 Massachusetts Gen Hosp, Dept Psychiat, Psychot Disorders Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Psychiat Neuroimaging Res Grp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Positron Emiss Tomog Lab, Div Nucl Med, Boston, MA 02114 USA. Harvard Univ, Dept Psychol, Boston, MA 02115 USA. RP Heckers, S (reprint author), Massachusetts Gen Hosp E, Dept Psychiat, CNY-9132,Bldg 149,13th St, Charlestown, MA 02129 USA. EM heckers@psych.mgh.harvard.edu RI Heckers, Stephan/F-3051-2010; OI Heckers, Stephan/0000-0003-3601-9910; Schacter, Daniel/0000-0002-2460-6061 FU NIMH NIH HHS [K20MH01215, R01MH57915] NR 79 TC 128 Z9 132 U1 5 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD DEC PY 1999 VL 56 IS 12 BP 1117 EP 1123 DI 10.1001/archpsyc.56.12.1117 PG 7 WC Psychiatry SC Psychiatry GA 262ER UT WOS:000084053100007 PM 10591289 ER PT J AU Craft, S Asthana, S Newcomer, JW Wilkinson, CW Matos, IT Baker, LD Cherrier, M Lofgreen, C Latendresse, S Petrova, A Plymate, S Raskind, M Grimwood, K Veith, RC AF Craft, S Asthana, S Newcomer, JW Wilkinson, CW Matos, IT Baker, LD Cherrier, M Lofgreen, C Latendresse, S Petrova, A Plymate, S Raskind, M Grimwood, K Veith, RC TI Enhancement of memory in Alzheimer disease with insulin and somatostatin, but not glucose SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID MILD SENILE DEMENTIA; RAT HIPPOCAMPUS; NERVOUS-SYSTEM; RECEPTOR; BRAIN; METABOLISM; DEFICITS; HYPERINSULINEMIA; RESPONSES; PITUITARY AB Background: Increasing plasma glucose levels improves memory in patients with Alzheimer disease (AD). Increasing plasma glucose levels also increases endogenous insulin levels, raising the question of whether memory improvement is due to changes in insulin, independent of hyperglycemia. We address this question by examining memory and counterregulatory hormone response during hyperglycemia when endogenous insulin was suppressed by concomitant infusion of the somatostatin analogue octreotide (Sandostatin). Methods: Twenty-three patients with AD and 14 similarly aged healthy adults participated in 4 metabolic conditions on separate days: (1) hyperinsulinemia (538 pmol/L) with fasting glucose (5.6 mmol/L [100 mg/dL]), achieved by insulin and variable dextrose infusion; (2) hyperglycemia (12.5 mmol/L [225 mg/dL]) with fasting insulin (57 pmol/L), achieved by dextrose and somatostatin (octreotide) infusion (150 mg/h); (3) placebo with isotonic sodium chloride solution (saline) infusion (fasting insulin and glucose); and (4) an active control condition in which somatostatin alone was infused (150 mg/h). Declarative memory (story recall) and selective attention (Stroop interference test) were measured during steady metabolic states. Results: Patients with AD showed improved memory during hyperinsulinemia relative to placebo (P = .05) and relative to hyperglycemia (P<.005). Memory did not improve during hyperglycemia when insulin was suppressed. Somatostatin analogue infusion alone also improved memory for patients with AD (P<.05). Hyperinsulinemia increased cortisol levels in subjects with AD, whereas somatostatin alone lowered cortisol concentrations. Conclusions: These results confirm that elevated insulin without hyperglycemia enhances memory in adults with AD, and indicate that insulin is essential for hyperglycemic memory facilitation. These results also suggest a potential therapeutic role for somatostatin in AD. C1 Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr 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. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. RP Craft, S (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr 182B, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIA NIH HHS [R01-AG-10880] NR 39 TC 196 Z9 211 U1 0 U2 4 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 DEC PY 1999 VL 56 IS 12 BP 1135 EP 1140 DI 10.1001/archpsyc.56.12.1135 PG 6 WC Psychiatry SC Psychiatry GA 262ER UT WOS:000084053100009 PM 10591291 ER PT J AU Tsuang, D Larson, EB Bowen, J McCormick, W Teri, L Nochlin, D Leverenz, JB Peskind, ER Lim, A Raskind, MA Thompson, ML Mirra, SS Gearing, M Schellenberg, GD Kukull, W AF Tsuang, D Larson, EB Bowen, J McCormick, W Teri, L Nochlin, D Leverenz, JB Peskind, ER Lim, A Raskind, MA Thompson, ML Mirra, SS Gearing, M Schellenberg, GD Kukull, W TI The utility of apolipoprotein E genotyping in the diagnosis of Alzheimer disease in a community-based case series SO ARCHIVES OF NEUROLOGY LA English DT Article ID CLINICAL-DIAGNOSIS; DEMENTIA; ALLELE; ASSOCIATION; SENSITIVITY; SPECIFICITY; CONSORTIUM; ESTABLISH; EPSILON-4; REGISTRY AB Context: A recent collaborative study found that apolipoprotein E (APOE) genotype, in conjunction with the clinical diagnosis of Alzheimer disease (AD), was useful in improving diagnostic specificity (correctly not diagnosing AD) relative to the clinical diagnosis alone. Since these samples are particularly enriched with patients with AD and the APOE epsilon 4 allele, results may not be generalizable to patients seen in the general medical community. Objective: To evaluate the diagnostic utility of the APOE genotype in diagnosing AD in a community-based case series from the largest health maintenance organization in an urban area. Design: We examined the effect of including APOE genotype on the diagnosis of AD in a community-based case series of patients presenting with memory complaints. Patients: Clinical and neuropathologic diagnoses and APOE genotype were obtained from 132 patients who underwent evaluation for dementia and subsequent autopsy. Main Outcome Measures: Sensitivity, specificity, and positive and negative predictive values given various combinations of clinical diagnoses and the presence of an APOE epsilon 4 allele. Results: Of the 132 patients, 94 had neuropathologically confirmed AD, yielding a prevalence of 71%. The clinical diagnosis alone yielded a sensitivity of 84%, an estimated specificity of 50%, and positive and negative predictive values of 81% and 56%, respectively. The presence of an epsilon 4 allele alone was associated with an estimated sensitivity of 59%, specificity of 71%, and positive and negative predictive values of 83% and 41%, respectively. Using the presence of clinical AD and an epsilon 4 allele decreased the sensitivity to 49% and increased the specificity to 84%. The positive and negative predictive values were 88% and 40%, respectively. Alternatively, the clinical diagnosis of AD or the presence of an epsilon 4 allele in individuals not meeting clinical criteria for AD increases the estimated sensitivity to 94% but decreases the specificity to 37%. The positive and negative predictive values were 79% and 70%, respectively. The changes in the sensitivity and specificity for the combined tests relative to clinical diagnosis alone offset each other. For lower prevalence communities, the positive predictive value will be much lower than those observed herein. Conclusions: Our findings do not support the use of APOE gene typing alone in the diagnosis of AD in the general medical community. Although the presence of an epsilon 4 allele in older persons with clinical AD increased the probability of having AD and the absence of an epsilon 4 allele in this group decreased the probability of having AD, the association is not strong enough in the differential diagnosis of non-Alzheimer dementia and AD. C1 Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Internal Med, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Sch Nursing, Seattle, WA 98195 USA. Univ Washington, Dept Pathol, Neuropathol Lab, Seattle, WA 98195 USA. Talbert Med Grp, Phoenix, AZ USA. SUNY Hlth Sci Ctr, Dept Pathol, Brooklyn, NY 11203 USA. Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. RP Tsuang, D (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Mail Stop 116 MIRECC,1660 S Columbian Way, Seattle, WA 98108 USA. RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 FU NIA NIH HHS [R01-AG10845, U01AG06781, U01AG10130] NR 38 TC 28 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 DEC PY 1999 VL 56 IS 12 BP 1489 EP 1495 DI 10.1001/archneur.56.12.1489 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 262LD UT WOS:000084068000009 PM 10593304 ER PT J AU Anderson, CA Sandberg, E Filley, CM Harris, SL Tyler, KL AF Anderson, CA Sandberg, E Filley, CM Harris, SL Tyler, KL TI One and one-half syndrome with supranuclear facial weakness - Magnetic resonance imaging localization SO ARCHIVES OF NEUROLOGY LA English DT Article ID PALSY; INFARCTION AB Objective: To provide clinicoanatomical correlation for a small pontine tegmental ischemic stroke producing the one and one-half syndrome associated with supranuclear facial weakness. Design: Case report. Setting: Tertiary care center. Patients: A 70-year-old man developed left-sided facial weakness sparing the forehead, a left internuclear ophthalmoplegia, and a complete left horizontal gaze palsy immediately after percutaneous transluminal coronary angioplasty. Magnetic resonance imaging demonstrated a small lesion in the left paramedian aspect of the dorsal pontine tegmentum. Main Outcome and Results: Electromyographic findings were consistent with supranuclear facial involvement. The patient had nearly complete recovery after 1 year. Conclusions: To our knowledge, this is the first report of supranuclear facial weakness in association with the one and one-half syndrome. The location of the lesion provides evidence of the existence of corticofugal fibers that extend to the facial nucleus in the dorsal paramedian pontine tegmentum. C1 Univ Colorado, Hlth Sci Ctr, Sch Med, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Sch Med, Dept Surg, Div Emergency Med, Denver, CO 80262 USA. Univ Colorado, Sch Med, Dept Radiol, Denver, CO 80262 USA. Univ Colorado, Sch Med, Dept Psychiat, Denver, CO 80262 USA. Univ Colorado, Sch Med, Dept Med, Denver, CO 80262 USA. Univ Colorado, Sch Med, Dept Microbiol, Denver, CO 80262 USA. Univ Colorado, Sch Med, Dept Immunol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Anderson, CA (reprint author), Univ Colorado, Hlth Sci Ctr, Sch Med, Dept Neurol, Neurol B-182,4200 E 9th Ave, Denver, CO 80262 USA. OI Tyler, Kenneth/0000-0003-3294-5888 NR 11 TC 4 Z9 6 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 DEC PY 1999 VL 56 IS 12 BP 1509 EP 1511 DI 10.1001/archneur.56.12.1509 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 262LD UT WOS:000084068000013 PM 10593308 ER PT J AU Slominski, A Wortsman, J Carlson, A Mihm, M Nickoloff, B McClatchey, K AF Slominski, A Wortsman, J Carlson, A Mihm, M Nickoloff, B McClatchey, K TI Molecular pathology of soft tissue and bone tumors - A review SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Review ID GROWTH-FACTOR-I; PRIMITIVE NEUROECTODERMAL TUMOR; ROUND-CELL LIPOSARCOMA; MULTIDRUG-RESISTANCE; SYNOVIAL SARCOMA; P53 PROTEIN; DERMATOFIBROSARCOMA PROTUBERANS; CHROMOSOMAL-ABNORMALITIES; RETINOBLASTOMA PROTEIN; HUMAN OSTEOSARCOMA AB Objective.--To present recent concepts on the molecular pathogenesis of tumors of soft tissue and bone, and on the use of molecular genetic methods, including their significance as diagnostic markers and prognostic indicators. Data Sources and Study Selection.--Reports on tumors of bone and/or soft tissue published in the English language literature and observations made using specimens available at the Departments of Pathology at Albany Medical College and Loyola University Medical Center. Data Extraction and Synthesis.--Studies on bone and soft tissue tumors containing chromosomal or genetic evaluation were selected for further analysis. Specific chromosomal abnormalities, such as numerical aberrations or translocations with production of fusion genes, were classified according to the tumor of origin. Data were also collected on mutations in tumor suppressor genes, genes coding for growth factors or their receptors, and genes coding for tyrosine kinases. Also noted were mutations of uncertain significance, for which the pathogenic connection between tumor production and mutated gene function is still unclear. Conclusions.--In general, the mutations reported interfere with the action of peptide growth factors coordinating mesenchyme proliferation and differentiation, although membrane-bound receptors expressing the intracellular signaling modifier, tyrosine kinase activity, have also been involved. Functional types of genes most commonly affected include tumor suppressors, oncogenes, and nuclear transcription factors. Thus, the mutations involved in the pathogenesis of soft tissue and bone tumors have affected multiple genes. Moreover, aberrant fusion gene products may be formed in tumoral tissue and may then act as transcription regulators stimulating cellular proliferation. Cytogenetic studies help at the clinical level by demonstrating aneuploidy and increased ploidy, which may correlate with malignant behavior. Diagnostic tumor-specific chromosomal translocations may be detected with Southern hybridization analysis, polymerase chain reaction, reverse-transcription polymerase chain reaction, or with the fluorescence in situ hybridization technique. Notably, early metastatic disease may be detectable in blood specimens using polymerase chain reaction or reverse-transcription polymerase chain reaction techniques. C1 Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. So Illinois Univ, Dept Med, Springfield, IL USA. Albany Med Ctr, Dept Pathol & Lab Med, Albany, NY USA. Massachusetts Gen Hosp, Dept Dermatopathol, Boston, MA 02114 USA. Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. RP Slominski, A (reprint author), Loyola Univ, Med Ctr, Dept Pathol, 2160 S 1st Ave, Maywood, IL 60153 USA. OI Carlson, John Andrew/0000-0002-6866-6314 NR 104 TC 23 Z9 26 U1 0 U2 2 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 DEC PY 1999 VL 123 IS 12 BP 1246 EP 1259 PG 14 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 263XJ UT WOS:000084150300017 PM 10583931 ER PT J AU Scremin, AME Kurta, L Gentili, A Wiseman, B Perell, K Kunkel, C Scremin, OU AF Scremin, AME Kurta, L Gentili, A Wiseman, B Perell, K Kunkel, C Scremin, OU TI Increasing muscle mass in spinal cord injured persons with a functional electrical stimulation exercise program SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article ID CROSS-SECTIONAL AREA; SKELETAL-MUSCLE; RESISTANCE EXERCISE; FIBER AREA; STRENGTH; CAPILLARIZATION; HYPERTROPHY; TOMOGRAPHY; PATIENT; RATS AB Objective: To determine the magnitude of changes in muscle mass and lower extremity body composition that could be induced with a regular regimen of functional electrical stimulation (FES)-induced lower-extremity cycling, as well as the distribution of changes in muscle mass among the thigh muscles in persons with spinal cord injury (SCI). Study Design: Thirteen men with neurologically complete motor sensory SCI underwent a 3-phase, FES-induced, ergometry exercise program: phase 1, quadriceps strengthening; phase 2, progressive sequential stimulation to achieve a rhythmic pedaling motion (surface electrodes placed over the quadriceps, hamstrings, and gluteal muscles); phase 3, FES-induced cycling for 30 minutes. Participants moved from one phase to the next when they met the objectives for the current phase. Measures: Computed tomography of legs to assess muscle cross-sectional area and proportion of muscle and adipose tissue. Scans were done at baseline (before subjects started the program), at first follow-up, typically after 65.4 +/- 5.6 (SD) weekly sessions, and at second follow-up, typically after 98.1 +/- 9.1 sessions. Results: Increases in cross-sectional areas were found in the following muscles: rectus femoris (31%, p < .001), sartorius (22%, p < .025), adductor magnus-hamstrings (26%, p < .001), vastus lateralis (39%, p = .001), vastus medialis-intermedius (31%, p = .025). Cross-sectional area of adductor longus and gracilis muscles did not change. The ratio of muscle to adipose tissue increased significantly in thighs and calves. There was no correlation among the total number of exercise sessions and the magnitude of muscle hypertrophy. Conclusions: Muscle cross-sectional area and the muscle to adipose tissue ratio of the lower extremities increased during a regular regimen of 2.3 FES-induced lower extremity cycling sessions weekly. The distribution of changes was related to the proximity of muscles to the stimulating electrodes. (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, Dept Phys Med & Rehabil, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Res Dept, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. Albuquerque Vet Affairs Med Ctr, Albuquerque, NM USA. RP Scremin, AME (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Phys Med & Rehabil, Bldg 115,Room 319,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Winstein, Carolee/A-8375-2008; Gentili, Amilcare/G-1238-2013 OI Gentili, Amilcare/0000-0002-5623-7512 NR 36 TC 71 Z9 73 U1 4 U2 13 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD DEC PY 1999 VL 80 IS 12 BP 1531 EP 1536 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 262WZ UT WOS:000084092400002 PM 10597802 ER PT J AU Wong, JS AF Wong, JS TI Spontaneous suprachoroidal haemorrhage in a patient receiving low-molecular-weight heparin (fraxiparine) therapy SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF OPHTHALMOLOGY LA English DT Article DE anticoagulation; choroidal haemorrhage; ocular complication ID MACULAR DEGENERATION; HEMORRHAGE AB Spontaneous suprachoroidal bleeding is a rare event. Of the six previously reported cases, five had identifiable mechanisms for the development of choroidal bleeding in addition to concurrent systemic anticoagulation/thrombolytic therapy. We report a case of spontaneous suprachoroidal haemorrhage in a patient who received subcutaneous low-molecular-weight heparin therapy but without any identifiable ocular condition predisposing to choroidal bleeding. C1 Natl Univ Singapore Hosp, Dept Ophthalmol, Singapore 117548, Singapore. RP Wong, JS (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM jun.wong@joslin.harvard.edu NR 12 TC 13 Z9 13 U1 0 U2 0 PU BLACKWELL PUBLISHING ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0814-9763 J9 AUST NZ J OPHTHALMOL JI Aust. N. Z. J. Ophthalmol. PD DEC PY 1999 VL 27 IS 6 BP 433 EP 434 PG 2 WC Ophthalmology SC Ophthalmology GA 272PV UT WOS:000084660900013 PM 10641904 ER PT J AU Goodwin, FK Ghaemi, SN AF Goodwin, FK Ghaemi, SN TI The impact of the discovery of lithium on psychiatric thought and practice in the USA and Europe SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Article DE bipolar disorder; lithium; pharmaco-economic data; psychopharmacology ID BIPOLAR AFFECTIVE-DISORDER; PROPHYLACTIC LITHIUM; FOLLOW-UP; SUICIDAL-BEHAVIOR; SEROTONIN; MAINTENANCE; ILLNESS; TERM; RAT; TRANSDUCTION AB The discovery of lithium has had a major impact on modern psychiatry. By launching the psychopharmacology revolution, lithium forced psychiatrists to become more adept at diagnosis. Lithium research has also provided a window into secular changes in bipolar illness which adversely impact response, produced pharmacoeconomic data on the social costs of psychiatric illness, and played a role in the birth of patient-run advocacy movements, in addition, the development of lithium has demonstrated the closely intertwined purposes of clinical and basic research, and the continued importance of research in the clinical setting. C1 George Washington Univ, Ctr Neurosci Med Progress & Soc, Dept Psychiat, Washington, DC 20037 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. RP Goodwin, FK (reprint author), George Washington Univ, Ctr Neurosci Med Progress & Soc, Dept Psychiat, 2150 Penn Ave NW, Washington, DC 20037 USA. NR 62 TC 10 Z9 10 U1 1 U2 2 PU BLACKWELL SCIENCE ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0004-8674 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD DEC PY 1999 VL 33 SU S BP S54 EP S64 DI 10.1111/j.1440-1614.1999.00669.x PG 11 WC Psychiatry SC Psychiatry GA 268VM UT WOS:000084437300011 PM 10622181 ER PT J AU Whittal, ML AF Whittal, ML TI Bulimia nervosa: A meta-analysis of psychosocial and pharmacological treatments SO BEHAVIOR THERAPY LA English DT Article ID COGNITIVE-BEHAVIORAL TREATMENT; 2 PSYCHOLOGICAL TREATMENTS; DOUBLE-BLIND; CONTROLLED TRIAL; RESPONSE-PREVENTION; SOCIAL PHOBIA; THERAPY; PLACEBO; METAANALYSIS; PSYCHOTHERAPY AB Nine double-blind, placebo-controlled medication trials (870 subjects) and 26 randomized psychosocial studies (460 subjects) were included in a meta-analysis of bulimia nervosa (BN). Four treatment outcomes were analyzed. binge and purge frequency, depression (self-reported and interviewer-rated), and self-reported eating attitudes. When compared to medication, cognitive behavioral therapy (CBT) studies produced significantly larger-weighted effect sizes for all treatment outcomes. These quantitative results correspond to qualitative reviews and suggest that CBT is the treatment of choice for BN. C1 Univ British Columbia Hosp, Vancouver, BC, Canada. Stanford Univ, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Whittal, ML (reprint author), Vancouver Hosp & Hlth Sci Ctr, UBC Site,2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada. OI Agras, Stewart/0000-0002-3116-8194 NR 62 TC 48 Z9 49 U1 9 U2 16 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 J9 BEHAV THER JI Behav. Therapy PD WIN PY 1999 VL 30 IS 1 BP 117 EP 135 DI 10.1016/S0005-7894(99)80049-5 PG 19 WC Psychology, Clinical SC Psychology GA 174ME UT WOS:000079038300008 ER PT J AU Lee, MLT Whitmore, GA AF Lee, MLT Whitmore, GA TI Statistical inference for serial dilution assay data SO BIOMETRICS LA English DT Article DE bacterial toxin; data analysis; EM algorithm; interval censoring; log-normal models; maximum likelihood estimation; minimum inhibitory concentration; serial dilution assay; statistical inference; stool cytotoxicity assay ID IMMUNOASSAY AB Serial dilution assays are widely employed for estimating substance concentrations and minimum inhibitory concentrations. The Poisson-Bernoulli model for such assays is appropriate for count data but not for continuous measurements that are encountered in applications involving substance concentrations. This paper presents practical inference methods based on a log-normal model and illustrates these methods using a case application involving bacterial toxins. C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. McGill Univ, Fac Management, Montreal, PQ H3A 1G5, Canada. RP Lee, MLT (reprint author), Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. NR 9 TC 13 Z9 13 U1 0 U2 3 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 1999 VL 55 IS 4 BP 1215 EP 1220 DI 10.1111/j.0006-341X.1999.01215.x PG 6 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 265BB UT WOS:000084218000031 PM 11315070 ER PT J AU Raimondi, SC Chang, MN Ravindranath, Y Behm, FG Gresik, MV Steuber, CP Weinstein, HJ Carroll, AJ AF Raimondi, SC Chang, MN Ravindranath, Y Behm, FG Gresik, MV Steuber, CP Weinstein, HJ Carroll, AJ CA Pediat Oncology Grp TI Chromosomal abnormalities in 478 children with acute myeloid leukemia: Clinical characteristics and treatment outcome in a cooperative pediatric oncology group Study - POG 8821 SO BLOOD LA English DT Article ID ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; MYELODYSPLASTIC SYNDROME; PROGNOSTIC-SIGNIFICANCE; MLL GENE; DE-NOVO; CHILDHOOD; CYTOGENETICS; IDENTIFICATION; CLASSIFICATION AB We determined the type and frequency of chromosomal aberrations in leukemic cells of 478 children diagnosed with acute myeloid leukemia and enrolled in the Pediatric Oncology Group study 8821. Of the 478 cases, 109 (22.8%) had normal karyotypes. Chromosomal abnormalities of 280 patients (58.6%) were classified into subgroups: 11q23 abnormalities (n = 88, 18.4%), t(8;21) (n = 56, 11.7%), t(15;17) (n = 55, 11.5%), inv(16)/t(16;16) (n = 28, 5.9%), trisomy 8 alone (n = 10, 2.1%). monosomy 7 (n = 9, 1.9%), non-Down-associated trisomy 21 alone (n = 7, 1.5%), and rare recurrent chromosomal translocations (n = 27, 5.6%). The remaining 89 patients (18.6%) had miscellaneous clonal abnormalities. Overall, 84.9% of the children achieved a complete remission; the 4-year event-free survival (EFS) estimate was 33.8% +/- 2.4%. Remission rates were significantly higher (96.4%, P = .011) for patients with t(8;21) and inv(16)/t(16: 16) but significantly lower (74.5%, P = .022) for those with t(15;17). The 4-year survival rate for all patients was 43.5% +/- 2.4%; for those with an inv(16)/t(16;16), 75.0% +/- 8.6%; a normal karyotype, 53.8% +/- 4.9%; a t(8;21). 51.6% +/- 7.3%; a t(15;17), 39.8% +/- 6.9%; and an 11q23 abnormality, 32.9% +/- 5.1%. Four-year EFS estimates for patients with inv(16)/t(16; 16) (58.2% +/- 10.9%. P = .007), t(8;21) (45.1% +/- 7.7%, P = .014), or normal karyotypes (43.1% +/- 5.0%, P = .012) were higher than the 4-year EFS estimate for all patients, but EFS estimates for patients with t(15;17) (19.6% +/- 8.0%, P = .033) or 11q23 abnormalities (23.8% +/- 4.8%, P = .0013) were lower. EFS estimates did not differ significantly among 11q23 subgroups. Limited analysis suggested that patients with inv(16) can be salvaged better following relapse than those with t(8;21). Thus, patients with an inv(16)/t(16;16) may have high survival rates when treated with chemotherapy alone. (C) 1999 by The American Society of Hematology. C1 St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. St Jude Childrens Res Hosp, Dept Lab Med, Memphis, TN 38105 USA. Univ Tennessee, Memphis, TN USA. Childrens Hosp Michigan, Barbara Ann Karmanos Canc Inst, Detroit, MI 48201 USA. Wayne State Univ, Inst Canc, Detroit, MI 48201 USA. Univ Florida, POG Stat Off, Gainesville, FL 32611 USA. Univ Florida, Dept Stat, Gainesville, FL 32611 USA. Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Alabama, Birmingham, AL USA. RP Raimondi, SC (reprint author), St Jude Childrens Res Hosp, Dept Pathol, 332 N Lauderdale St, Memphis, TN 38105 USA. FU NCI NIH HHS [CA-21765, CA-05587, CA-03161] NR 37 TC 225 Z9 230 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 DEC 1 PY 1999 VL 94 IS 11 BP 3707 EP 3716 PG 10 WC Hematology SC Hematology GA 260MB UT WOS:000083953500011 PM 10572083 ER PT J AU Richardson, P Guinan, E AF Richardson, P Guinan, E TI The pathology, diagnosis, and treatment of hepatic veno-occlusive disease: Current status and novel approaches SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review ID BONE-MARROW-TRANSPLANTATION; TISSUE-PLASMINOGEN-ACTIVATOR; SEVERE VENOOCCLUSIVE DISEASE; ACUTE-RENAL-FAILURE; TOTAL-BODY IRRADIATION; ANTITHROMBOTIC AGENT; VENOCCLUSIVE DISEASE; CONTROLLED TRIAL; PHASE-II; LIVER C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Paediat Oncol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. RP Richardson, P (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 86 TC 61 Z9 64 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 1999 VL 107 IS 3 BP 485 EP 493 DI 10.1046/j.1365-2141.1999.01680.x PG 9 WC Hematology SC Hematology GA 269HR UT WOS:000084471100003 PM 10583247 ER PT J AU Arico, M Nichols, K Whitlock, JA Arceci, R Haupt, R Mittler, U Kuhne, T Lombardi, A Ishii, E Egeler, RM Danesino, C AF Arico, M Nichols, K Whitlock, JA Arceci, R Haupt, R Mittler, U Kuhne, T Lombardi, A Ishii, E Egeler, RM Danesino, C TI Familial clustering of Langerhans cell histiocytosis SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Langerhans cell histiocytosis; familial cases; hereditary disease ID IDENTICAL-TWINS; CHILDREN; DISEASE AB Langerhans cell histiocytosis (LCH) is considered a non-hereditary disorder. Evaluation of the few familial cases might provide insight into its aetiology and pathogenesis. We conducted a survey to identify familial LCH cases. Data on family history, zygosity assessment in twins, clinical and laboratory features, treatment outcome, and present status were collected. According to variable confidence for twins monozygosity assessment, we termed these pairs 'presumed monozygotic' (pMZ). Nine families had more than one affected relative: five with LCH-concordant twin pairs, four with LCH in siblings or cousins. Three twin pairs not concordant for LCH were also studied. Overall, four of five pMZ twin pairs and one of three dizygotic (DZ) pairs were concordant for LCH. The pMZ twins had simultaneous and early disease onset (mean age 5.4 months); onset was at 21 months in the DZ pair. Clinical features were similar in the pMZ pairs. One pair of DZ twins had disseminated LCH. The three healthy twins tone pMZ, two DZ) remain asymptomatic 0.3, 5.9 and 4.7 years, respectively, after disease onset in their co-twins. Of the two families with affected non-twin siblings, one had known parental consanguinity and the other possible consanguinity. Potential consanguinity was also present in one of the two families with affected first cousins. Our data support high LCH concordance rates in pMZ twins and add the finding of LCH concordance in one of three dizygotic pairs studied. Taken together with our identification of LCH in siblings and first cousins from known or possibly consanguineous families, and with prior reports of three affected parent-child pairs, the data support a role for genetic factor(s) in LCH. The work-up of newly diagnosed patients should include a careful, extensive family history and chromosome studies. When possible, constitutional and/or lesional DNA should be obtained for future study. C1 Policlin San Matteo, Pediat Clin, IRCCS, Dept Paediat, I-27100 Pavia, Italy. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. Vanderbilt Univ, Sch Med, Div Pediat Hematol Oncol, Nashville, TN 37212 USA. Childrens Hosp, Med Ctr, Dept Hematol Oncol, Cincinnati, OH 45229 USA. Ist Giannina Gaslini, I-16148 Genoa, Italy. Univ Magdeburg, Klin Padiat Hamatol & Onkol, D-39106 Magdeburg, Germany. Childrens Univ Hosp, Dept Haematol Oncol, Basel, Switzerland. Osped Pediat Bambino Gesu, IRCCS, Dept Haematol, Rome, Italy. Hamanoumachi Hosp, Div Paediat, Fukuoka 810, Japan. Alberta Childrens Hosp, Childrens Canc Program, Calgary, AB, Canada. Univ Pavia, Dept Biol Gen & Genet Med, I-27100 Pavia, Italy. RP Arico, M (reprint author), Policlin San Matteo, Pediat Clin, IRCCS, Dept Paediat, I-27100 Pavia, Italy. RI Haupt, Riccardo/C-2237-2012 FU Telethon [E.0755] NR 32 TC 81 Z9 91 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 1999 VL 107 IS 4 BP 883 EP 888 DI 10.1046/j.1365-2141.1999.01777.x PG 6 WC Hematology SC Hematology GA 268VK UT WOS:000084437100031 PM 10606898 ER PT J AU Kloen, P AF Kloen, P TI New insights in the development of Dupuytren's contracture: a review SO BRITISH JOURNAL OF PLASTIC SURGERY LA English DT Article DE Dupuytren's contracture; myofibroblast; cytokines; extracellular matrix; free radicals ID GROWTH-FACTOR-BETA; NODULAR PALMAR FIBROMATOSIS; SMOOTH MUSCLE ACTIN; GRANULATION-TISSUE FORMATION; CONNECTIVE-TISSUE; MYOFIBROBLAST ACCUMULATION; CULTURED FIBROBLASTS; FIBROGENIC CYTOKINES; HYPERTROPHIC SCARS; GAMMA-INTERFERON AB Recent advances in the understanding of myofibroblast histology and function, the activity of fibrogenic cytokines, the role of the extracellular matrix and of free radicals are contributing to an understanding of the aetiology of Dupuytren's disease but not yet to its treatment. Surgical excision remains the best treatment. (C) 1999 The British Association of Plastic Surgeons. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. RP Kloen, P (reprint author), Acad Med Ctr, Dept Orthopaed Surg, Meibergdreef 9, NL-1100 DD Amsterdam, Netherlands. NR 93 TC 32 Z9 32 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 0007-1226 J9 BRIT J PLAST SURG JI Br. J. Plast. Surg. PD DEC PY 1999 VL 52 IS 8 BP 629 EP 635 DI 10.1054/bjps.1999.3187 PG 7 WC Surgery SC Surgery GA 259NN UT WOS:000083900100005 PM 10658134 ER PT J AU Jesser, CA Boppart, SA Pitris, C Stamper, DL Nielsen, GP Brezinski, ME Fujimoto, JG AF Jesser, CA Boppart, SA Pitris, C Stamper, DL Nielsen, GP Brezinski, ME Fujimoto, JG TI High resolution imaging of transitional cell carcinoma with optical coherence tomography: feasibility for the evaluation of bladder pathology SO BRITISH JOURNAL OF RADIOLOGY LA English DT Article ID BIOPSY; CANCER AB Significant challenges regarding patient morbidity and mortality remain in the management of transitional cell carcinoma (TCC). Among the most important of these challenges is the inability to identify early neoplastic changes and to assess the degree of tumour invasion into the bladder wall in vivo. Optical coherence tomography (OCT) has been recently developed to provide in situ, high resolution, catheter/endoscope based imaging. This study explored the feasibility of OCT for the evaluation of bladder pathology. Both in vitro and in vivo studies were performed. lit vitro imaging of pathological human bladder was performed and compared with normal specimens and histopathology. In vivo imaging of normal rabbit bladder was also performed with our current catheter/endoscope based systems. In the in vitro studies, OCT was able to delineate normal microstructure of the bladder, such as the mucosa, submucosa and muscularis layers. This was in contrast to specimens of invasive carcinoma, where a disruption of the normal bladder wall architecture was seen. The in vivo experiment demonstrated current limitations of the catheter/endoscope based systems and provided valuable information for developing an improved system for bladder imaging. The ability of OCT to delineate microstructure of the bladder wall suggests feasibility for endoscopic based imaging. In particular, there is a potential role envisioned for OCT in the management of TCC, identifying pre-malignant states and the depth of tumour invasion. C1 MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Kings Coll, Wilkes Barre, PA USA. RP Brezinski, ME (reprint author), MIT, Dept Elect Engn & Comp Sci, Bldg 36-357,50 Vassar St, Cambridge, MA 02139 USA. RI Boppart, Stephen/C-7338-2009; OI Pitris, Costas/0000-0002-5559-1050 FU NEI NIH HHS [9-R01-EY11289-10]; NHLBI NIH HHS [1-R29-HL55686-01A1]; NIAMS NIH HHS [1RO1AR44812-01] NR 19 TC 54 Z9 56 U1 0 U2 0 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD DEC PY 1999 VL 72 IS 864 BP 1170 EP 1176 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 272YQ UT WOS:000084679400006 PM 10703474 ER PT J AU Livingston, JA AF Livingston, JA TI Something old and something new: Love, creativity, and the enduring relationship SO BULLETIN OF THE MENNINGER CLINIC LA English DT Article AB In the initial phase of a romantic relationship, excitement often reflects the reawakening of early narcissistic fantasy. For most narcissism fades, the expansiveness of a developing sense of self that is a by-product Of the creative process can, in turn, revitalize the partnership. Arieti's work on creativity is applied to understanding how some passionate intensity can be retained over the lifetime of a marriage. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Livingston, JA (reprint author), 58 Lexington Ave, Cambridge, MA 02138 USA. NR 11 TC 6 Z9 7 U1 0 U2 2 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0025-9284 J9 B MENNINGER CLIN JI Bull. Menninger Clin. PD WIN PY 1999 VL 63 IS 1 BP 40 EP 52 PG 13 WC Psychiatry; Psychology, Psychoanalysis SC Psychiatry; Psychology GA 163WB UT WOS:000078428400005 PM 10028745 ER PT J AU Febbo, PG Kantoff, PW Platz, EA Casey, D Batter, S Giovannucci, E Hennekens, CH Stampfer, MJ AF Febbo, PG Kantoff, PW Platz, EA Casey, D Batter, S Giovannucci, E Hennekens, CH Stampfer, MJ TI The V89L polymorphism in the 5 alpha-reductase type 2 gene and risk of prostate cancer SO CANCER RESEARCH LA English DT Article ID HUMAN STEROID 5-ALPHA-REDUCTASE; TESTOSTERONE; DEFICIENCY; CARCINOMA; SRD5A2; WHITE; BLACK; RATS AB 5 alpha-Reductase type 2, the predominant prostatic isozyme of this protein, converts testosterone to dihydrotestosterone. It has been hypothesized that individuals with greater 5 alpha-reductase activity are at increased risk for prostate cancer (CaP). A single nucleotide polymorphism of the 5 alpha-reductase type 2 gene (SRD5A2) gives rise to a substitution of leucine (leu) for valine (val) at codon 89 (V89L), the, presence of which may affect serum androstanediol glucuronide (AAG) levels. We studied the effect. of this polymorphism on the risk of prostate cancer in a prospective, nested, case-control design within the Physicians' Health Study. In all controls (n = 799), the leu allele frequency was 0.30. Among the 386 controls with plasma AAG levels available, there mac; no significant association between AAG levels and V89L genotype. We also detected no significant association between risk for CaP and genotype [odds ratio: val/val = 1.0 (reference), leu/val = 0.96 (95% confidence interval, 0.76-1.20), and leu/ leu = 0.84 (95% confidence interval, 0.57-1.24)]. These data do not support a moderate to large effect of the SRD5A2 V89L polymorphism on plasma AAG levels or CaP risk in this predominantly Caucasian cohort, although a small effect cannot be completely excluded. C1 Dana Farber Canc Inst, Dept Adult Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Phys Hlth Study, Sch Publ Hlth, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Kantoff, PW (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA58684, CA42182, CA72036] NR 24 TC 80 Z9 83 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 1999 VL 59 IS 23 BP 5878 EP 5881 PG 4 WC Oncology SC Oncology GA 266JL UT WOS:000084296800005 PM 10606227 ER PT J AU Sohn, KJ Puchyr, M Salomon, RN Graeme-Cook, F Fung, L Choi, SW Mason, JB Medline, A Kim, YI AF Sohn, KJ Puchyr, M Salomon, RN Graeme-Cook, F Fung, L Choi, SW Mason, JB Medline, A Kim, YI TI The effect of dietary folate on Apc and p53 mutations in the dimethylhydrazine rat model of colorectal cancer SO CARCINOGENESIS LA English DT Article; Proceedings Paper CT Annual Digestive Disease Week / 97th Annual Meeting of the American-Gastroenterological-Association CY MAY 17-20, 1998 CL NEW ORLEANS, LOUISIANA SP Amer Gastroenterol Assoc ID HAMSTER OVARY CELLS; DEOXYNUCLEOTIDE POOL IMBALANCE; MOUSE COLON TUMORS; GENE-MUTATIONS; METHYLAZOXYMETHANOL ACETATE; DNA HYPOMETHYLATION; ALKYLATING-AGENTS; NO INVOLVEMENT; TREATED RATS; KI-RAS AB Dietary inadequacy of folate enhances and folate supplementation suppresses colorectal carcinogenesis in the dimethylhydrazine rat model. Folate is an essential factor for DNA methylation and the de novo biosynthesis of nucleotides, aberrations of which play important roles in mutagenesis, This study investigated whether the mutational hot spots of the Ape and p53 genes for human colorectal cancer are mutated in dimethylhydrazine-induced colorectal neoplasms and whether dietary folate can modulate mutations in these regions. Rats were fed diets containing 0, 2 (basal requirement), 8 or 40 mg folate/ kg diet. Five weeks after diet initiation, dimethylhydrazine was injected weekly for 15 weeks. Mutations were determined by direct sequencing in 11 low and seven high grade dysplasias and 13 invasive adenocarcinomas. A total of six Ape mutations were found in four dysplastic and carcinomatous lesions: two in two low grade dysplasias, two in one high grade dysplasia and two in one adenocarcinoma. All mutations were single base substitutions, four of which were A:T-->G:C transitions. Five of the six mutations were located upstream from the region corresponding to the human APC mutation cluster region. Dietary folate had no effect on the frequency and type of Ape mutations. No mutations were detected in exons 5-9 of the p53 gene in neoplastic lesions. These data suggest that in the dimethylhydrazine rat model of colorectal cancer, the Ape gene is mutated in early stages, albeit to a lesser degree than observed in human colorectal cancer, whereas the mutational hot spot of the p53 gene for human colorectal cancer is not commonly mutated. Although the low frequency of Ape mutations and the small number of neoplasms studied in this study might have precluded our ability to observe modulatory effects of folate, dietary folate appears to have no significant effect on Ape and p53 mutations. C1 St Michaels Hosp, Dept Med, Div Gastroenterol, Toronto, ON M5S 1A8, Canada. Univ Toronto, Toronto, ON M5S 1A8, Canada. Tufts Univ, Vitamin Metab Lab, Jean Mayer USDA Human Nutr Res Ctr Aging, Medford, MA 02155 USA. Tufts Univ, Sch Med, New England Med Ctr, Dept Pathol, Medford, MA 02155 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Cambridge, MA 02138 USA. Tufts Univ, Sch Med, New England Med Ctr, Dept Internal Med,Div Gastroenterol, Boston, MA 02111 USA. Tufts Univ, Sch Med, New England Med Ctr, Dept Internal Med,Div Clin Nutr, Boston, MA 02111 USA. Univ Toronto, Dept Pathol, Toronto, ON, Canada. RP Kim, YI (reprint author), St Michaels Hosp, Dept Med, Div Gastroenterol, Room 7258,Med Sci Bldg,1 Kings Coll Circle, Toronto, ON M5S 1A8, Canada. FU NCI NIH HHS [1-UO1 CA63812-01] NR 45 TC 22 Z9 23 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 1999 VL 20 IS 12 BP 2345 EP 2350 DI 10.1093/carcin/20.12.2345 PG 6 WC Oncology SC Oncology GA 270GB UT WOS:000084526100022 PM 10590231 ER PT J AU Murray, DR Prabhu, SD Freeman, GL AF Murray, DR Prabhu, SD Freeman, GL TI Hemodynamic effects of nitric oxide synthase inhibition at steady state and following tumor necrosis factor-alpha-induced myodepression SO CARDIOVASCULAR RESEARCH LA English DT Article DE cytokines; hemodynamics; nitric oxide; ventricular function; angiotensin ID PRESSURE-VOLUME RELATION; CLOSED-CHEST DOGS; CONSCIOUS DOGS; CELL-FUNCTION; SEPTIC SHOCK; HEART; ENDOTOXIN; INDUCTION; HUMANS; CONTRACTILITY AB Objective: Nitric oxide (NO) has been proposed as a common mediator of tumor necrosis factor-alpha (TNF alpha)-induced vasodilation and myocardial dysfunction. Accordingly, we performed an extensive assessment of the influence of NO synthase inhibition on left ventricle (LV) and circulatory performance in conscious dogs at steady state and after establishment of TNF alpha mediated myodepression. Methods: Autonomically blocked, chronically instrumented dogs were studied at steady state and 6 h after initiation of a l-h rhTNF alpha infusion (40 mu g/kg). Ventricular performance was evaluated using the pressure-volume framework. Dogs were then treated with either N-G-nitro-L-arginine methylester (L-NAME, 40 mg/kg bolus) or angiotensin II (250-500 ng/kg). Results: L-NAME, under control conditions or following recombinant human (rh)TNF alpha-induced ventricular dysfunction, produced marked increases in afterload with attendant increases in LV pressure, volume, and prolonged isovolumic relaxation without adversely influencing coronary blood flow. Regardless of whether the dogs received rhTNF alpha, L-NAME did not affect the slopes of the end-systolic pressure-volume and stroke-work (SW)-end-diastolic volume (EDV) relations (force-based measure of contractility), whereas the slope of the dP/dt(max)-EDV relation, a velocity dependent parameter of LV systolic function, declined. Overall ventricular performance, as seen by the circulation, was reduced by L-NAME in control as well as rhTNF alpha-treated dogs, evidenced by rightward shifts of the SW-EDV and dP/dt(max)-EDV relations. Similar findings were observed in the separate cohorts of dogs, at steady state and 6 h after rhTNF alpha, following angiotensin II at matched systolic pressure. Conclusions: Systemic NO synthase inhibition with L-NAME does not acutely reverse rhTNF alpha-induced myocardial dysfunction. The detrimental influence of L-NAME on LV size, relaxation, and velocity-based measures of contractility is likely attributable to its effects on increasing afterload. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Murray, DR (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. RI Prabhu, Sumanth/D-5223-2009 NR 36 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD DEC PY 1999 VL 44 IS 3 BP 527 EP 535 DI 10.1016/S0008-6363(99)00226-6 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 262HA UT WOS:000084060100012 PM 10690284 ER PT J AU Juo, P Woo, MSA Kuo, CJ Signorelli, P Biemann, HP Hannun, YA Blenis, J AF Juo, P Woo, MSA Kuo, CJ Signorelli, P Biemann, HP Hannun, YA Blenis, J TI FADD is required for multiple signaling events downstream of the receptor Fas SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; ICE/CED-3 FAMILY PROTEASES; DEATH DOMAIN; CELL-DEATH; INDUCED APOPTOSIS; CD95 FAS/APO-1; LYMPHOPROLIFERATIVE SYNDROME; ACIDIC SPHINGOMYELINASE; MONOCLONAL-ANTIBODY AB To identify essential components of the Fas-induced apoptotic signaling pathway, Jurkat T lymphocytes were chemically mutagenized and selected for clones that were resistant to Fas-induced apoptosis, We obtained five cell lines that contain mutations in the adaptor FADD. All five cell lines did not express FADD by immunoblot analysis and were completely resistant to Fas-induced death. Complementation of the FADD mutant cell lines with wild-type FADD restored Fas-mediated apoptosis, Fas activation of caspase-2, caspase-3, caspase-7, and caspase-8 and the proteolytic cleavage of substrates such as BID, protein kinase C delta, and poly(ADP-ribose) polymerase were completely defective in the FADD mutant cell lines. In addition, Fas activation of the stress kinases p38 and c-Jun NH2 kinase and the generation of ceramide in response to Fas ligation were blocked in the FADD mutant cell lines. These data indicate that FADD is essential for multiple signaling events downstream of Fas. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Med Univ S Carolina, Charleston, SC 29403 USA. Genzyme Corp, Cambridge, MA 02139 USA. RP Blenis, J (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. OI signorelli, paola/0000-0003-2368-2393 FU NCI NIH HHS [CA46595]; NIGMS NIH HHS [GM-43825] NR 59 TC 145 Z9 150 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD DEC PY 1999 VL 10 IS 12 BP 797 EP 804 PG 8 WC Cell Biology SC Cell Biology GA 268MX UT WOS:000084421100003 PM 10616904 ER PT J AU Denis, CV Wagner, DD AF Denis, CV Wagner, DD TI Insights from von Willebrand disease animal models SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE von Willebrand disease; von Willebrand factor; animal models; hemostasis; thrombosis; atherosclerosis ID HUMAN VONWILLEBRAND-FACTOR; SELECTIN-DEFICIENT MICE; FACTOR-VIII ACTIVITY; PLATELET-ADHESION; ARTERIAL THROMBOSIS; ENDOTHELIAL-CELLS; BLEEDING-TIME; MESSENGER-RNA; HEMOPHILIA-A; BONE-MARROW AB von Willebrand disease is a genetic bleeding disorder that arises from abnormalities in von Willebrand factor, an adhesive glycoprotein involved in both primary hemostasis and coagulation. It is the most common inherited bleeding disorder in humans, and over the years several animal species have also been described as suffering from this disease whether through a spontaneous mutation (pigs, dogs) or a genetically engineered one (mouse). These different animal models are extremely useful in exploring the characteristics of von Willebrand disease and in testing new treatments. This review provides an update of the various von Willebrand disease models and the contribution that these models can make to st better understanding of human von Willebrand disease. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Denis , Cecile/A-7649-2011 OI Denis , Cecile/0000-0001-5152-9156 FU NHLBI NIH HHS [R01 HL41002] NR 137 TC 28 Z9 28 U1 1 U2 4 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD DEC PY 1999 VL 56 IS 11-12 BP 977 EP 990 DI 10.1007/s000180050487 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 271XE UT WOS:000084619500007 PM 11212329 ER PT J AU Bracy, JL Cretin, N Cooper, DKC Iacomini, J AF Bracy, JL Cretin, N Cooper, DKC Iacomini, J TI Xenoreactive natural antibodies SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE natural antibodies; xenotransplantation; humoral rejection ID ALPHA-GALACTOSYL EPITOPES; DECAY-ACCELERATING FACTOR; ANTI-GAL ANTIBODY; NONLETHAL PREPARATIVE REGIMEN; BOVINE CARTILAGE TRANSPLANTS; HUMAN-COMPLEMENT INHIBITOR; BONE-MARROW TRANSPLANTS; TRANSGENIC PIGS; XENOGRAFT REJECTION; CYNOMOLGUS MONKEY AB Shortages of human organs for transplantation have made it necessary to examine the possibility of using nonhuman organs for xenotransplantation-the transplantation of tissues between different species. Pigs are now regarded as the most likely species to serve as donors for clinical xenotransplantation. However, rejection of pig tissues and organs, mediated by the host's immune system, remains a major barrier to successful xenotransplantation. The primary immunological hurdle to overcome is rejection mediated by antibodies in the host that recognize antigens present on xenogeneic tissues. Since these antibodies are produced naturally in the host without immunization, they are termed natural antibodies. Here, we review the nature of xenoreactive natural antibodies directed toward pig tissues, and summarize recent progress in the field of xenotransplantation directed at overcoming humoral rejection of porcine xenografts. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Iacomini, J (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, 149 13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [T32 AI07529, R01 AI41081, R01 AI44268] NR 81 TC 15 Z9 15 U1 2 U2 3 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD DEC PY 1999 VL 56 IS 11-12 BP 1001 EP 1007 DI 10.1007/s000180050489 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 271XE UT WOS:000084619500009 PM 11212318 ER PT J AU Delalle, I Takahashi, T Nowakowski, RS Tsai, LH Caviness, VS AF Delalle, I Takahashi, T Nowakowski, RS Tsai, LH Caviness, VS TI Cyclin E-p27 opposition and regulation of the G1 phase of the cell cycle in the murine neocortical PVE: A quantitative analysis of mRNA in situ hybridization SO CEREBRAL CORTEX LA English DT Article ID DEPENDENT KINASE INHIBITOR; CORTICAL PROGENITOR CELLS; NERVOUS-SYSTEM; CEREBRAL WALL; PROLIFERATIVE EPITHELIUM; VENTRICULAR ZONE; MICE LACKING; P27(KIP1); MOUSE; GROWTH AB We have analyzed the expression patterns of mRNAs of five cell cycle related proteins in the ventricular zone of the neocortical cerebral wall over the course of the neuronogenetic interval in the mouse. One set of mRNAs (cyclin E and p21) are initially expressed at high levels but expression then falls to a low asymptote. A second set (p27, cyclin B and cdk2) are initially expressed at low levels but ascend to peak levels only to decline again. These patterns divide the overall neuronogenetic interval into three phases. In phase 1 cyclin E and p21 levels of mRNA expression are high, while those of mRNAs of p27, cdk2 and cyclin B are low. In this phase the fraction of cells leaving the cycle after each mitosis, Q, is low and the duration of the G1 phase, T-G1, is short. In phase 2 levels of expression of cyclin E and p21 fall to asymptote while levels of expression of mRNA of the other three proteins reach their peaks. Q increases to approach 0.5 and T-G1 increases even more rapidly to approach its maximum length. In phase 3 levels of expression of cyclin E and p21 mRNAs remain low and those of the mRNAs of the other three proteins fall. T-G1 becomes maximum and a rapidly increases to 1.0. The character of these phases can be understood in part as consequences of the reciprocal regulatory influence of p27 and cyclin E and of the rate limiting functions of p27 at the restriction point and of cyclin E at the G1 to S transition. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Keio Univ, Sch Med, Dept Pediat, Tokyo 160, Japan. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Delalle, I (reprint author), Massachusetts Gen Hosp, Dept Neuropathol, WRN3 Fruit St, Boston, MA 02114 USA. RI Nowakowski, Richard/C-3217-2016; OI Nowakowski, Richard/0000-0002-5006-3670 FU NINDS NIH HHS [NS12005, NS33433] NR 59 TC 31 Z9 33 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD DEC PY 1999 VL 9 IS 8 BP 824 EP 832 DI 10.1093/cercor/9.8.824 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 263FH UT WOS:000084114400007 PM 10601001 ER PT J AU Wright, CD AF Wright, CD TI Multimodality therapy of esophageal cancer SO CHEST LA English DT Article; Proceedings Paper CT Symposium on Multimodality Therapy of Chest Malignancies - Update 1998 CY MAR 12-14, 1998 CL CAMBRIDGE, MASSACHUSETTS SP Harvard Med Sch, Dept Oncol, Dana Farber Canc Inst, Div Thorac Surg & Harvard Joint Ctr Radiat Therapy, Brigham & Womens Hosp ID ADENOCARCINOMA; RADIOTHERAPY AB Multimodality therapy of esophageal cancer has been evaluated in several clinical trials, with positive results in terms of improved survival compared with single-modality therapy. A case report is presented describing the use of paclitaxel in a multimodality regimen for a patient with a bulky esophageal tumor. In addition, results are described of a clinical trial in which patients received a paclitaxel-based regimen as part of multimodality therapy for esophageal cancer. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wright, CD (reprint author), Massachusetts Gen Hosp, Fruit St, Boston, MA 02114 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 1999 VL 116 IS 6 SU S BP 461S EP 462S DI 10.1378/chest.116.suppl_3.461S PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 268AE UT WOS:000084390800006 PM 10619508 ER PT J AU Mentzer, SJ Swanson, SJ AF Mentzer, SJ Swanson, SJ TI Treatment of patients with lung cancer and severe emphysema SO CHEST LA English DT Article; Proceedings Paper CT Symposium on Multimodality Therapy of Chest Malignancies - Update 1998 CY MAR 12-14, 1998 CL CAMBRIDGE, MASSACHUSETTS SP Harvard Med Sch, Dept Oncol, Dana Farber Canc Inst, Div Thorac Surg & Harvard Joint Ctr Radiat Therapy, Brigham & Womens Hosp ID VOLUME-REDUCTION SURGERY AB The development of lung cancer and emphysema is associated with the destructive chemical milieu that occurs with smoking. The recent interest in lung volume reduction surgery (LVRS) has stimulated a reassessment of the indications for surgery in patients with early stage lung cancer or emphysema. For patients with both diseases, the issues surrounding LVRS are simplified. The major concern is that the lung cancer can be surgically removed without the need for postoperative ventilation or mortality. A secondary consideration is the potential for long-term postoperative respiratory morbidity. These risks can be estimated by evaluating the anatomic location of the tumor, as well as the physiology of the underlying emphysema. Early results of combined LVRS and lung cancer resections suggest a favorable outcome in carefully selected patients. C1 Brigham & Womens Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Mentzer, SJ (reprint author), Brigham & Womens Hosp, Dept Surg, Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. NR 16 TC 15 Z9 16 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 1999 VL 116 IS 6 SU S BP 477S EP 479S DI 10.1378/chest.116.suppl_3.477S PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 268AE UT WOS:000084390800011 PM 10619513 ER PT J AU Emmons, KM AF Emmons, KM TI Smoking cessation and tobacco control - An overview SO CHEST LA English DT Article; Proceedings Paper CT Symposium on Multimodality Therapy of Chest Malignancies - Update 1998 CY MAR 12-14, 1998 CL CAMBRIDGE, MASSACHUSETTS SP Harvard Med Sch, Dept Oncol, Dana Farber Canc Inst, Div Thorac Surg & Harvard Joint Ctr Radiat Therapy, Brigham & Womens Hosp ID DEPRESSION AB Cigarette smoking is an intractable public health problem and the single largest risk factor for a variety of malignancies, including lung cancer. Worldwide, about 3 million people die each year of smoking-related disease, and this is expected to increase to > 10 million deaths per year. The Agency for Health Care Policy and Research has published a clinical practice guideline detailing available outcome data for various smoking cessation strategies. In particular, it has been recommended that all patients be screened for smoking status on every health-care visit, and that all patients who smoke be strongly advised to quit and offered assistance to do so. Health-care providers play a vital role in the effort to reduce the prevalence of smoking by delivering smoking cessation advice, supporting community-based efforts to control tobacco, and becoming involved in the tobacco control debate. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Emmons, KM (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [1RO1CA77780, 1RO1CA73242]; NHLBI NIH HHS [1RO1HL50017] NR 16 TC 19 Z9 21 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 1999 VL 116 IS 6 SU S BP 490S EP 492S DI 10.1378/chest.116.suppl_3.490S PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 268AE UT WOS:000084390800014 PM 10619516 ER PT J AU Strauss, GM AF Strauss, GM TI Role of chemotherapy in stages I to III non-small cell lung cancer SO CHEST LA English DT Article; Proceedings Paper CT Symposium on Multimodality Therapy of Chest Malignancies - Update 1998 CY MAR 12-14, 1998 CL CAMBRIDGE, MASSACHUSETTS SP Harvard Med Sch, Dept Oncol, Dana Farber Canc Inst, Div Thorac Surg & Harvard Joint Ctr Radiat Therapy, Brigham & Womens Hosp ID HYPERFRACTIONATED RADIATION-THERAPY; GROUP-B PROTOCOL-8935; RANDOMIZED TRIAL; PHASE-II; PREOPERATIVE CHEMOTHERAPY; ADJUVANT THERAPY; NEOADJUVANT CHEMOTHERAPY; CONCURRENT CHEMOTHERAPY; INDUCTION CHEMOTHERAPY; FOLLOW-UP AB The management of resectable non-small cell lung cancer (NSCLC) has been the focus of extensive investigation over the last decade. Nonetheless, existing management strategies are suboptimal for all stage groupings. The only exception is complete resection for stage IA NSCLC, in which a cure is achieved in 70 to 85% of patients. A number of studies demonstrate that adjuvant chemotherapy may be associated with some biological effect. Nonetheless, chemotherapy remains experimental and cannot be definitively recommended outside the contest of a randomized trial. Radiation therapy appears to be associated with a reduction in local recurrence in stage II NSCLC, With regard to potentially resectable stage IIIA NSCLC, the results of randomized trials support the conclusion that induction chemotherapy followed by resection (with or without postoperative radiation) may enhance survival compared to that achieved with resection alone. Among patients with stage IIIA and IIIB NSCLC who are treated without resection, numerous phase III studies demonstrate that induction chemotherapy with definitive radiation improves outcome when compared to thoracic radiation therapy alone. While there may be an advantage for concurrent chemoradiation compared to sequential therapy, definitive results are not yet available to support this conclusion. While the magnitude of benefit associated with induction chemotherapy or chemoradiation in regionally advanced NSCLC is debatable, the results of multimodality studies provide a basis for optimism that real therapeutic progress is being achieved, Further study of therapeutic strategics that incorporate aggressive systemic treatment and local-regional therapy in stage IIIA and IIIB NSCLC is warranted. Moreover, completion of randomized studies focusing on the role of adjuvant chemotherapy in stage IB and stage II NSCLC should be given priority. C1 Dana Farber Canc Inst, Div Thorac Surg, Dept Adult Oncol, Boston, MA 02115 USA. RP Strauss, GM (reprint author), Dana Farber Canc Inst, Div Thorac Surg, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 45 TC 6 Z9 7 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 1999 VL 116 IS 6 SU S BP 509S EP 516S DI 10.1378/chest.116.suppl_3.509S PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 268AE UT WOS:000084390800019 PM 10619521 ER PT J AU Shaffer, K AF Shaffer, K TI Role of radiology for imaging and biopsy of solitary pulmonary nodules SO CHEST LA English DT Article; Proceedings Paper CT Symposium on Multimodality Therapy of Chest Malignancies - Update 1998 CY MAR 12-14, 1998 CL CAMBRIDGE, MASSACHUSETTS SP Harvard Med Sch, Dept Oncol, Dana Farber Canc Inst, Div Thorac Surg & Harvard Joint Ctr Radiat Therapy, Brigham & Womens Hosp ID FINE-NEEDLE ASPIRATION; COMPUTER-AIDED DIAGNOSIS; COST-EFFECTIVENESS; GUIDANCE TECHNIQUE; LUNG-BIOPSY; CT; LESIONS; PNEUMOTHORAX; CHEST; SENSITIVITY AB Both imaging and image-directed biopsy play a major:role in evaluating solitary pulmonary nodules. Imaging is used to determine whether the nodule is actually, solitary or if multiple nodules are present. Once a nodule has been detected, imaging techniques can be used to characterize the nodule in terms of whether it is likely benign or malignant. As technology has improved, smaller nodules are now more easily detected, which may create a management dilemma, With the advent of video-assisted thoracoscopic techniques, however, sampling of these lesions has become much easier. Once a solitary pulmonary nodule is detected, image-guided biopsy is often considered, which can be undertaken using CT or fluoroscopy. Technical limitations, the location of the solitary pulmonary nodules, and clinical conditions must be considered when determining the role of image-guided biopsy. Other concerns include:thf role of on-site cytology and the use of mole recent technical advances. Image-guided biopsy should be used as part of a multimodality approach to patient management, and decisions should be-discussed with the radiologist and other caregivers to determine the cost-effectiveness and safety of the procedure for each patient. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Shaffer, K (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 39 TC 15 Z9 15 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 1999 VL 116 IS 6 SU S BP 519S EP 522S DI 10.1378/chest.116.suppl_3.519S PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 268AE UT WOS:000084390800021 PM 10619523 ER PT J AU Swanson, SJ Jaklitsch, MT Mentzer, SJ Bueno, R Lukanich, JM Sugarbaker, DJ AF Swanson, SJ Jaklitsch, MT Mentzer, SJ Bueno, R Lukanich, JM Sugarbaker, DJ TI Management of the solitary pulmonary nodule: Role of thoracoscopy in diagnosis and therapy SO CHEST LA English DT Article; Proceedings Paper CT Symposium on Multimodality Therapy of Chest Malignancies - Update 1998 CY MAR 12-14, 1998 CL CAMBRIDGE, MASSACHUSETTS SP Harvard Med Sch, Dept Oncol, Dana Farber Canc Inst, Div Thorac Surg & Harvard Joint Ctr Radiat Therapy, Brigham & Womens Hosp ID RESECTION; LESIONS; COST; CT AB Objectives: The solitary pulmonary nodule remains a common clinical problem, The essential question is whether the lesion is malignant or not. This discussion presents the clinical practice and looks at the problem. Design: Didactic. Setting: Academic tertiary-care hospital. Patients: Prospective thoracic database. Interventions: Minimally invasive technique. Results: The workup and treatment of the solitary pulmonary nodule is presented with particular emphasis on the role of minimally invasive techniques. A small single-institution series is referenced. Conclusions: The approach is safe and highly effective in diagnosing and often in treating solitary pulmonary nodules. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Div Thorac Surg, Boston, MA 02115 USA. RP Swanson, SJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. NR 12 TC 23 Z9 24 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 1999 VL 116 IS 6 SU S BP 523S EP 524S DI 10.1378/chest.116.suppl_3.523S PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 268AE UT WOS:000084390800022 PM 10619524 ER PT J AU Elias, A AF Elias, A TI Hematopoietic stem cell transplantation for small cell lung cancer SO CHEST LA English DT Article; Proceedings Paper CT Symposium on Multimodality Therapy of Chest Malignancies - Update 1998 CY MAR 12-14, 1998 CL CAMBRIDGE, MASSACHUSETTS SP Harvard Med Sch, Dept Oncol, Dana Farber Canc Inst, Div Thorac Surg & Harvard Joint Ctr Radiat Therapy, Brigham & Womens Hosp ID AUTOLOGOUS BONE-MARROW; HIGH-DOSE CHEMOTHERAPY; COLONY-STIMULATING FACTOR; COMBINED MODALITY THERAPY; METASTATIC BREAST-CANCER; DISEASE-FREE SURVIVAL; PHASE-I; PERIPHERAL-BLOOD; INTENSIVE CHEMOTHERAPY; BRONCHOGENIC-CARCINOMA AB Treatment for small cell lung cancer has not improved substantially in the past 15 years. Some advances are being made in supportive care and by use of more intense concurrent thoracic radiotherapy. New agents such as the taxanes and the topoisomerase I inhibitors hold promise and are currently in phase III evaluation. The question whether dose intensity can improve the outcome of patients with small cell lung cancer has been raised for many years. Improving supportive care enhances our ability to test this question more thoroughly. This paper reviews the historical and current experience using high-dose therapy with hematopoietic stem cell support for the treatment of small lung cancer. Future directions are identified. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Elias, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA13849] NR 95 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 DEC PY 1999 VL 116 IS 6 SU S BP 531S EP 538S DI 10.1378/chest.116.suppl_3.531S PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 268AE UT WOS:000084390800024 PM 10619526 ER PT J AU Recklitis, CJ Noam, GG AF Recklitis, CJ Noam, GG TI Clinical and developmental perspectives on adolescent coping SO CHILD PSYCHIATRY & HUMAN DEVELOPMENT LA English DT Article DE coping strategies; ego development; adjustment; psychopathology; adolescents ID EGO DEVELOPMENT; COMPETENCE; CHILDREN; PATTERNS; STRESS; LEVEL AB Although the development of appropriate coping strategies has been understood as an essential element of healthy adjustment, few studies have demonstrated the link between coping and psychological development. Similarly, research on adolescents with behavioral problems has neglected coping as an important variable in understanding and treating these conditions. This study examines the relationships between psychological development, coping strategies and symptoms in a sample of 302 psychiatrically hospitalized adolescents, ages 12-16. Subjects completed the Adolescent Coping Orientation for Problem Strategies Questionnaire, (A-COPE),(1) the Youth Self Report symptom checklist (YSR),(2) and Loevinger's measure of ego development.(3) Results showed that Avoidance and Ventilation were associated with increased behavior problems and lower levels of ego development. Problem solving and interpersonal strategies were associated with fewer symptoms and higher levels of development. Significant gender differences were found with girls using more interpersonal coping and boys using more physically active strategies. Gender differences were also found in the relationship of coping strategies to both symptomatic behavior and development. The results are discussed in the context of a developmental approach to adolescent psychopathology. C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. McLean Hosp, Belmont, MA 02178 USA. RP Recklitis, CJ (reprint author), Dana Farber Canc Inst, David B Perini Jr Qual Life Clin, 44 Binney St, Boston, MA 02115 USA. NR 38 TC 35 Z9 36 U1 0 U2 0 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0009-398X J9 CHILD PSYCHIAT HUM D JI Child Psychiat. Hum. Dev. PD WIN PY 1999 VL 30 IS 2 BP 87 EP 101 DI 10.1023/A:1021998217862 PG 15 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 276YL UT WOS:000084905900002 PM 10668305 ER PT J AU Pearson, AS Koch, PE Atkinson, N Xiong, MM Finberg, RW Roth, JA Fang, BL AF Pearson, AS Koch, PE Atkinson, N Xiong, MM Finberg, RW Roth, JA Fang, BL TI Factors limiting adenovirus-mediated gene transfer into human lung and pancreatic cancer cell lines SO CLINICAL CANCER RESEARCH LA English DT Article ID NONDIVIDING CELLS; ADENOASSOCIATED VIRUS; TRANSGENE EXPRESSION; INTEGRIN; DELIVERY; TRANSDUCTION; RECEPTOR; VECTORS; THERAPY; COXSACKIEVIRUS AB Adenoviral vectors are a widely used means of gene transfer. However, transgene expression after adenoviral administration varies among different carcinoma cell lines. We hypothesized that this variation is attributable, in part, to the presence of cell surface molecules involved in adenoviral infection. To test this, we first assessed adenovirus-mediated transgene expression in four human lung carcinoma cell lines and four human pancreatic carcinoma cell lines in terms of luciferase activities and found it to vary from 4.8 x 10(4) to 6.1 x 10(7) relative light units/mu g of protein. Then, to determine whether the molecules involved in the entry of adenovirus into host cells were responsible for this variation, we evaluated the expression of alpha v beta 5, alpha v, beta 3, alpha 5, and beta 1 integrins and that of coxsackievirus and adenovirus receptor (CAR) in these cell lines. Statistical analysis revealed that the levels of beta 3 were associated with the levels of transgene expression. Blocking analysis showed that adenovirus-mediated gene transfer could be blocked by antibodies against these six molecules but not by the antibodies against alpha 2 or alpha 3 integrins, thus suggesting that the integrins alpha v beta 5, alpha v, beta 3, alpha 5, and beta 1 and CAR molecules could limit adenovirus-mediated gene transfer when their levels fell below a certain threshold. Furthermore, cells expressing low levels of beta 3 and resistant to conventional adenoviral vectors were susceptible to a vector containing the heparin-binding domain in its fiber, thus suggesting that redirecting vectors to receptors other than CAR may bypass the integrin pathway. These findings may have implications for improving the efficiency of adenovirus-mediated gene transfer and developing novel adenoviral vectors. C1 Univ Texas, MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biomath, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Ctr Human Genet, Houston, TX 77030 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Infect Dis, Boston, MA 02115 USA. RP Fang, BL (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, 1515 Holcombe Blvd,Box 109, Houston, TX 77030 USA. RI Finberg, Robert/E-3323-2010 FU NCI NIH HHS [CA 16672, P50-CA70907] NR 25 TC 78 Z9 82 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC PY 1999 VL 5 IS 12 BP 4208 EP 4213 PG 6 WC Oncology SC Oncology GA 267TR UT WOS:000084375800045 PM 10632362 ER PT J AU Soderberg, BL Sicinska, ET Blodget, E Cluette-Brown, JE Suter, PM Schuppisser, T Vetter, W Laposata, M AF Soderberg, BL Sicinska, ET Blodget, E Cluette-Brown, JE Suter, PM Schuppisser, T Vetter, W Laposata, M TI Preanalytical variables affecting the quantification of fatty acid ethyl esters in plasma and serum samples SO CLINICAL CHEMISTRY LA English DT Article ID ETHANOL; ALCOHOL; BLOOD; SYNTHASE; CELLS AB Background: Fatty acid ethyl esters (FAEEs) are cytotoxic nonoxidative ethanol metabolites produced by esterification of fatty acids and ethanol. FAEEs are detectable in blood up to 24 h after ethanol consumption. The objective of this study was to assess the impact of gender, serum or plasma triglyceride concentration, time and temperature of specimen storage, type of alcoholic beverage ingested, and the rate of ethanol consumption on FAEE concentrations in plasma or serum. Methods: For some studies, subject were recruited volunteers; in others, residual blood samples after ethanol quantification were used. FAEEs were isolated by solid-phase extraction and quantified by gas chromatography-mass spectrometry. Results: For weight-adjusted amounts of ethanol intake, FAEE concentrations were twofold greater for men than women (P less than or equal to 0.05). Accounting for triglycerides improved the correlation between blood ethanol concentrations acid FAEE concentrations for both men (from r = 0.640 to r = 0.874) and women (from r = 0.619 to r = 0.673). FAEE concentrations did not change when samples were stored at or below 4 degrees C, but doubled when stored at room temperature for greater than or equal to 24 h. The type of alcoholic beverage and rate of consumption did not affect FAEE concentrations. Conclusion: These studies advance plasma and serum FAEE measurements closer to implementation as a clinical test for ethanol intake. (C) 1999 American Association for Clinical Chemistry. C1 Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Zurich Hosp, Med Policlin, CH-8091 Zurich, Switzerland. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Room 235,Gray Bldg, Boston, MA 02114 USA. FU NCRR NIH HHS [MO1RRO1066] NR 16 TC 25 Z9 27 U1 1 U2 3 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD DEC PY 1999 VL 45 IS 12 BP 2183 EP 2190 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 262MQ UT WOS:000084071400018 PM 10585351 ER PT J AU Goetz, MB AF Goetz, MB TI Editorial response: Discordance between virological, immunologic, and clinical outcomes of therapy with protease inhibitors among human immunodeficiency virus-infected patients SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID ACTIVE ANTIRETROVIRAL THERAPY; T-CELL RESPONSES; HIV-1 INFECTION; GENETIC RESTRICTION; DISEASE PROGRESSION; VIRAL-LOAD; AIDS; PATHOGENESIS; LYMPHOCYTES; VARIANT C1 Vet Adm Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. RP Goetz, MB (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, Dept Med, 111-F,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. OI Goetz, Matthew/0000-0003-4542-992X NR 46 TC 6 Z9 6 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC PY 1999 VL 29 IS 6 BP 1431 EP 1434 DI 10.1086/313563 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 273DW UT WOS:000084693400020 PM 10585791 ER PT J AU Maloney, WJ Galante, JO Anderson, M Goldberg, V Harris, WH Jacobs, J Kraay, M Lachiewicz, P Rubash, HE Schutzer, S Woolson, ST AF Maloney, WJ Galante, JO Anderson, M Goldberg, V Harris, WH Jacobs, J Kraay, M Lachiewicz, P Rubash, HE Schutzer, S Woolson, ST TI Fixation, polyethylene wear, and pelvic osteolysis in primary total hip replacement SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT 27th Meeting of the Hip-Society CY FEB 07, 1999 CL ANAHEIM, CA SP Amer Assoc Hip & Knee Surgeons ID COMPONENT AB A multicenter retrospective review was performed analyzing 1081 primary total hip replacements in 944 patients using the Harris Galante-I cementless acetabular component with screw fixation. All patients were followed up for a minimum of 5 years with a mean followup of 81 months, Linear polyethylene wear averaged 0.11 mm/year (range, 0-0.86 mm/year). Pelvic osteolysis was seen in 25 patients (2.3%). Migration of the acetabular component was seen in four hips. A subgroup of patients was reanalyzed at a minimum followup of 10 years. The mean linear polyethylene wear rate remained 0.11 mm/year. rn this group, only one socket had migrated. There was an association between wear rate and age. On average, younger patients had higher wear rates. The risk for having pelvic osteolysis develop and the need for revision surgery also was age-related. Twenty-two percent of hip replacements (15 hips) in patients younger than 50 years of age at the time of their index operation had pelvic osteolysis develop, In contrast, for patients older than 50 years of age at the time of surgery only 7.8% (eight hips) had osteolysis of the pelvis develop. For patients older than 70 years of age at the time of primary total hip replacement, none had pelvic osteolysis develop. C1 Washington Univ, Sch Med, Dept Orthopaed Surg, St Louis, MO 63130 USA. Rush Presbyterian St Lukes Med Ctr, Dept Orthopaed Surg, Chicago, IL 60612 USA. Case Western Reserve Univ, Dept Orthopaed Surg, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Univ N Carolina, Dept Orthopaed Surg, Chapel Hill, NC 27514 USA. Hartford Hosp, Hartford, CT 06115 USA. Stanford Univ Hosp, Palo Alto, CA USA. RP 1 Barnes Hosp Plaza,Suite 11300, St Louis, MO 63110 USA. OI Jacobs, Joshua/0000-0003-3902-7334 NR 23 TC 104 Z9 105 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 1999 IS 369 BP 157 EP 164 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 263BK UT WOS:000084102600017 PM 10611870 ER PT J AU Ring, D Jupiter, JB Gan, BS Israeli, R Yaremchuk, MJ AF Ring, D Jupiter, JB Gan, BS Israeli, R Yaremchuk, MJ TI Infected nonunion of the tibia SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID OPEN FRACTURES AB The treatment of infected nonunited fractures of the tibia using the techniques of Ilizarov was compared with autogenous cancellous bone graft application under a well vascularized soft tissue envelope. There were 10 patients in the Ilizarov group and 17 in the bone graft group. Soft tissue coverage with a free vascularized or a rotational muscle flap was used more frequently among the patients having bone graft (71%) than the Ilizarov group (30%). All 27 patients had bony defects (average, 3.7 cm; range, 1-18 cm), At an average followup of 6 years, 26 patients had a functional limb, and one patient (Ilizarov group) ultimately required a below knee amputation. Three patients in each group required a second plate and bone graft procedure to gain union. Infection persisted in four patients (all in the Ilizarov group). If a well vascularized soft tissue envelope is present (particularly after flap coverage), bone grafting procedures are safe and efficacious. The Ilizarov technique may be best suited for the treatment of very proximal or distal metaphyseal nonunions and nonunions associated with large leg length discrepancies. C1 Massachusetts Gen Hosp, Dept Hand Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Plast Surg, Boston, MA 02114 USA. St Josephs Hlth Ctr, Hand & Upper Limb Ctr, London, ON, Canada. RP Ring, D (reprint author), 11 Hancock St,Unit 4, Boston, MA 02114 USA. NR 27 TC 33 Z9 34 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 1999 IS 369 BP 302 EP 311 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 263BK UT WOS:000084102600033 PM 10611886 ER PT J AU Wolfe, J AF Wolfe, J TI Overcoming barriers to evidence-based practice: Lessons from medical practitioners SO CLINICAL PSYCHOLOGY-SCIENCE AND PRACTICE LA English DT Article DE manual-based treatment; mental health; practitioners; psychotherapy ID HEALTH-CARE AB A growing number of studies support the use of evidence-based treatments in psychotherapy. Empirically derived methods have proven especially useful for certain disorders and may offer cost efficiencies as well. Despite there data, mental health practitioners often express concerns about treatment protocols, reporting that these approaches impede clinician judgment and constrain appropriate care. In reviewing this topic, Addis, Wade, and Hatgis (this issue) describe six domains of common practitioner concerns and offer a series of recommendations for addressing these issues. Building on that work, the present article extends Addis et al.'s formulation, directing attention to broader themes in the rapidly changing health care field. Certain parallels with the experiences of medical practitioners facing challenger of quality and standardization may offer a framework for challenges currently facing psychotherapy practitioners. Skilled mental health clinicians are likely to be especially well suited to meeting these challenges and to guiding advancer in new types of psychotherapy care. C1 VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Wolfe, J (reprint author), Natl Ctr PTSD 116B3, Womens Hlth Sci Div, 150 S Huntington Ave, Boston, MA 02130 USA. NR 14 TC 8 Z9 8 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0969-5893 J9 CLIN PSYCHOL-SCI PR JI Clin. Psychol.-Sci. Pract. PD WIN PY 1999 VL 6 IS 4 BP 445 EP 448 DI 10.1093/clipsy/6.4.445 PG 4 WC Psychology, Clinical SC Psychology GA 344TF UT WOS:000088774400009 ER PT J AU McLoud, TC AF McLoud, TC TI Imaging - Preface SO CLINICS IN CHEST MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. RP McLoud, TC (reprint author), Massachusetts Gen Hosp, Dept Radiol, FND 216,POB 9567, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-5231 J9 CLIN CHEST MED JI Clin. Chest Med. PD DEC PY 1999 VL 20 IS 4 BP XI EP XII DI 10.1016/S0272-5231(05)70247-1 PG 2 WC Respiratory System SC Respiratory System GA 262XV UT WOS:000084094300001 ER PT J AU McLoud, TC Swenson, SJ AF McLoud, TC Swenson, SJ TI Lung carcinoma SO CLINICS IN CHEST MEDICINE LA English DT Article ID SOLITARY PULMONARY NODULES; NEEDLE ASPIRATION BIOPSY; HIGH-RESOLUTION CT; THIN-SECTION CT; BRONCHOGENIC-CARCINOMA; FIBEROPTIC BRONCHOSCOPY; COMPUTED-TOMOGRAPHY; REFERENCE PHANTOM; BRONCHUS SIGN; DYNAMIC CT AB Lung cancer is the leading cause of cancer mortality in the United States. Imaging is helpful in the diagnosis of peripheral lung cancers and in the staging of lung neoplasms. CT may establish the benign nature of a solitary pulmonary nodule by detecting either benign types of calcification or fat. Contrast enhancement is a new and innovative method that can be used to distinguish benign from malignant peripheral lung lesions. Both CT and MR play important roles in the preoperative staging of lung carcinoma. Both have significant limitations, however, and surgical staging is often required. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Mayo Clin & Mayo Fdn, Dept Radiol, Rochester, MN 55905 USA. RP McLoud, TC (reprint author), Massachusetts Gen Hosp, Dept Radiol, FND 216,POB 9567, Boston, MA 02114 USA. NR 63 TC 15 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 0272-5231 J9 CLIN CHEST MED JI Clin. Chest Med. PD DEC PY 1999 VL 20 IS 4 BP 697 EP + DI 10.1016/S0272-5231(05)70249-5 PG 18 WC Respiratory System SC Respiratory System GA 262XV UT WOS:000084094300002 PM 10587792 ER PT J AU Aquino, SL Vining, DJ AF Aquino, SL Vining, DJ TI Virtual bronchoscopy SO CLINICS IN CHEST MEDICINE LA English DT Article ID BREATH-HOLD TECHNIQUE; SPIRAL VOLUMETRIC CT; TRACHEOBRONCHIAL TREE; HELICAL CT; ANGIOGRAPHY; CARCINOMA; PROTOCOLS; CHILDREN; LUNG AB The sophistication of three-dimensional (3-D) radiographic imaging from CT data has accelerated with the development and ongoing advances of helical CT. Virtual bronchoscopy (VB), the ability to create 3-D models of the airways and navigate through the tracheobronchial tree lumen in realtime simulated bronchoscopy, has gained popularity over the Fast 3 years. The ability of VB to image the airway and mediastinal structures simultaneously and in a 3-D format has helped revolutionize CT imaging. Unlike conventional bronchoscopy, VB can display the extent of narrowing caused by an airway lesion, the presence of patentcy beyond a stenosis, and the relationship between an airway lesion and the adjacent mediastinal structures. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Radiol, Winston Salem, NC USA. RP Aquino, SL (reprint author), Massachusetts Gen Hosp, Dept Radiol, FND 202,55 Fruit St, Boston, MA 02114 USA. NR 19 TC 35 Z9 35 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-5231 J9 CLIN CHEST MED JI Clin. Chest Med. PD DEC PY 1999 VL 20 IS 4 BP 725 EP + DI 10.1016/S0272-5231(05)70251-3 PG 8 WC Respiratory System SC Respiratory System GA 262XV UT WOS:000084094300004 PM 10587794 ER PT J AU Shepard, JAO AF Shepard, JAO TI Imaging of lung transplantation SO CLINICS IN CHEST MEDICINE LA English DT Article ID PULMONARY ALLOGRAFT RECIPIENTS; HIGH-RESOLUTION CT; BRONCHIOLITIS OBLITERANS; LYMPHOPROLIFERATIVE DISORDERS; CHEST RADIOGRAPHY; TRANSBRONCHIAL BIOPSY; BRONCHIAL DEHISCENCE; RADIOLOGIC FINDINGS; PRIMARY DISEASE; COMPLICATIONS AB Lung transplantation is an accepted treatment for a large number of endstage pulmonary diseases. There are several complications that pertain specifically to lung transplant recipients, including airway ischemia, reperfusion edema, infections, acute rejection, obliterative bronchiolitis, and other postoperative problems relating to surgical technique and immunosuppressive therapy. Imaging procedures play an important role in the diagnosis and management of these problems. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Shepard, JAO (reprint author), Massachusetts Gen Hosp, Dept Radiol, FND 202, Boston, MA 02114 USA. NR 74 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 0272-5231 J9 CLIN CHEST MED JI Clin. Chest Med. PD DEC PY 1999 VL 20 IS 4 BP 827 EP + DI 10.1016/S0272-5231(05)70257-4 PG 19 WC Respiratory System SC Respiratory System GA 262XV UT WOS:000084094300010 PM 10587800 ER PT J AU Chabris, CF AF Chabris, CF TI Myth of the first three years: A new understanding of early brain development and lifelong learning SO COMMENTARY LA English DT Book Review C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Chabris, CF (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU AMER JEWISH COMMITTEE PI NEW YORK PA 165 E 56TH ST, NEW YORK, NY 10022 USA SN 0010-2601 J9 COMMENTARY JI Commentary PD DEC PY 1999 VL 108 IS 5 BP 74 EP 77 PG 4 WC Political Science; Social Issues SC Government & Law; Social Issues GA 259NW UT WOS:000083900800026 ER PT J AU Kassoff, A Kieval, S Mehu, M Buehler, J Eglow, M Kaufman, F Margherio, RR Cox, MS Garretson, B Hassan, T Ruby, A Trese, MT Werner, JC Williams, GA Regan, V Manatrey, P Cumming, K Zajechowski, M Falk, R Streasick, P Szydlowski, L Dreyer, RF Ma, C Beardsley, C Crider, H Capone, A Aaberg, TM Martin, D Saperstein, D Sternberg, P Curtis, L Stribling, B Gilman, J Myles, B Swords, R Orth, DH Flood, TP Civantos, J deBustros, S Packo, KH MacLeod, C Morrison, C Bryant, DA Doherty, D Sandoval, S Seddon, JM Pinnolis, MK Jones-Devonish, DA Crouse, VD Snow, KK Evans, C Davis, N Callahan, C Walsh, D Dubois, J Burton, I Ferris, FL Chew, EY Csaky, K McCarthy, SA Dabas, KH Goodman, L Kim, YJ Lopez, P Mercer, R Ayres, LM LaRean, T Randall, A Chicca, M Ciatto, PF Kuehl, E Kivitz, I Koutsandreas, D Friberg, TR Eller, A Gorin, MB Alexander, J Mack, B Bressler, SB Bressler, NM Cassel, G Goldberg, M Haller, JA Ratner, L Schachat, AP Sherman, SH Sunness, JS Schenning, S Sackett, C Cain, D Emmert, D George, T Wheeler, S Elman, MJ Ballinger, R Betancourt, A Glasser, D Lammlein, J Seff, R Shuman, M Starr, J Carrigan, A Ringrose, C Mathews, T Sotirakos, P Cain, T Chandra, SR Myers, FL Nork, TM Stevens, T Blodi, B Gottlieb, J Perkins, T Blatz, M Walker, W Harrison, B Knutson, G Krolnik, D Somers, G Davis, MD Klein, BEK Klein, R Hubbard, L Magli, YL Brickbauer, J Ansay, S Armstrong, J Neider, M Wabers, H Baliker, J Kastorff, L Laher, K Badal, D Geithman, PL Miner, KD King, WN Osterly, KR Dohm, KL Onofrey, JA Esser, B Hurtenback, C Fisher, MR Robinson, NL Reimers, J Miller, D Bowman, B Gunter, E Sowell, A Lindblad, AS Ederer, F Milton, RC Gensler, G Anand, R Entler, G Stine, E Berlin, SH Scholl, PR Mengers, SA Ferris, FL Chew, EY Sperduto, R Kurinij, N AF Kassoff, A Kieval, S Mehu, M Buehler, J Eglow, M Kaufman, F Margherio, RR Cox, MS Garretson, B Hassan, T Ruby, A Trese, MT Werner, JC Williams, GA Regan, V Manatrey, P Cumming, K Zajechowski, M Falk, R Streasick, P Szydlowski, L Dreyer, RF Ma, C Beardsley, C Crider, H Capone, A Aaberg, TM Martin, D Saperstein, D Sternberg, P Curtis, L Stribling, B Gilman, J Myles, B Swords, R Orth, DH Flood, TP Civantos, J deBustros, S Packo, KH MacLeod, C Morrison, C Bryant, DA Doherty, D Sandoval, S Seddon, JM Pinnolis, MK Jones-Devonish, DA Crouse, VD Snow, KK Evans, C Davis, N Callahan, C Walsh, D Dubois, J Burton, I Ferris, FL Chew, EY Csaky, K McCarthy, SA Dabas, KH Goodman, L Kim, YJ Lopez, P Mercer, R Ayres, LM LaRean, T Randall, A Chicca, M Ciatto, PF Kuehl, E Kivitz, I Koutsandreas, D Friberg, TR Eller, A Gorin, MB Alexander, J Mack, B Bressler, SB Bressler, NM Cassel, G Goldberg, M Haller, JA Ratner, L Schachat, AP Sherman, SH Sunness, JS Schenning, S Sackett, C Cain, D Emmert, D George, T Wheeler, S Elman, MJ Ballinger, R Betancourt, A Glasser, D Lammlein, J Seff, R Shuman, M Starr, J Carrigan, A Ringrose, C Mathews, T Sotirakos, P Cain, T Chandra, SR Myers, FL Nork, TM Stevens, T Blodi, B Gottlieb, J Perkins, T Blatz, M Walker, W Harrison, B Knutson, G Krolnik, D Somers, G Davis, MD Klein, BEK Klein, R Hubbard, L Magli, YL Brickbauer, J Ansay, S Armstrong, J Neider, M Wabers, H Baliker, J Kastorff, L Laher, K Badal, D Geithman, PL Miner, KD King, WN Osterly, KR Dohm, KL Onofrey, JA Esser, B Hurtenback, C Fisher, MR Robinson, NL Reimers, J Miller, D Bowman, B Gunter, E Sowell, A Lindblad, AS Ederer, F Milton, RC Gensler, G Anand, R Entler, G Stine, E Berlin, SH Scholl, PR Mengers, SA Ferris, FL Chew, EY Sperduto, R Kurinij, N CA Age-Related Eye Dis Study Res Grp TI The Age-Related Eye Disease Study (AREDS): Design implications AREDS report no. 1 SO CONTROLLED CLINICAL TRIALS LA English DT Article DE age-related macular degeneration; cataract; clinical trial; clinical course; antioxidants; zinc; vitamin C; vitamin E; beta-carotene ID DENSITY LIPOPROTEIN-CHOLESTEROL; SENILE MACULAR DEGENERATION; FAILURE TIME DATA; CARDIOVASCULAR-DISEASE; CLINICAL-TRIALS; BETA-CAROTENE; RISK-FACTORS; ZINC; SUPPLEMENTATION; MACULOPATHY AB The Age-Related Eye Disease Study (AREDS) was initially conceived as a long-term multicenter, prospective study of the clinical course of age-related macular degeneration (AMD) and age-related cataract. Data on progression rates and risk factors from the study will increase understanding of the clinical course of both conditions, generate hypotheses about etiology, and aid in the design of clinical trials of potential interventions. In addition to collecting natural history data, AREDS includes a clinical trial of high-dose vitamin and mineral supplements for AMD and a clinical trial of high-dose vitamin supplements for cataract. The clinical trials were initiated largely because of the widespread public use in the United States of commercially available pharmacologic doses of vitamins and minerals to treat these two eye conditions and the absence of definitive studies on the safety and efficacy of their use. Important design issues for the clinical trials include: defining cataract and AMD, estimating event rates, determining the type and dosage of vitamins and minerals to be tested for each condition, and identifying the parameters necessary for monitoring safety and efficacy. This paper describes the AREDS design, including the study rationale and operational structure, and the approach adopted to combine, for two diseases, clinical trials with a natural history study. (C) Elsevier Science Inc. 1999. C1 Devers Eye Inst, Portland, OR USA. Emory Univ, Atlanta, GA 30322 USA. Ingalls Mem Hosp, Harvey, IL USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NEI, Ctr Clin, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Univ Wisconsin, Reading Ctr, Madison, WI USA. Ctr Dis Control & Prevent, Cent Lab, Atlanta, GA USA. NEI, Project Off, Bethesda, MD 20892 USA. Natl Inst Hlth, Div Contracts & Grants, Bethesda, MD 20892 USA. Bausch & Lomb Pharmaceut, Rochester, NY 14601 USA. RP Lindblad, AS (reprint author), EMMES Corp, AREDS Coordinating Ctr, 11325 7 Locks Rd,Suite 214, Potomac, MD 20854 USA. NR 54 TC 178 Z9 180 U1 2 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-2456 EI 1879-050X J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD DEC PY 1999 VL 20 IS 6 BP 573 EP 600 PG 28 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 258LV UT WOS:000083841400009 ER PT J AU Whalen, MJ Carlos, TM Dixon, E Robichaud, P Clark, RSB Marion, DW Kochanek, PM AF Whalen, MJ Carlos, TM Dixon, E Robichaud, P Clark, RSB Marion, DW Kochanek, PM TI Reduced brain edema after traumatic brain injury in mice deficient in P-selectin and intercellular adhesion molecule-1 SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Pittsburgh, Pittsburgh, PA USA. Safar Ctr Resuscitat Res, Pittsburgh, PA USA. RI Kochanek, Patrick/D-2371-2015 OI Kochanek, Patrick/0000-0002-2627-913X NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 1999 VL 27 IS 12 SU S MA 149 BP A64 EP A64 DI 10.1097/00003246-199912001-00149 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 276RX UT WOS:000084892100150 ER PT J AU Olson, E Spiegelman, BM AF Olson, E Spiegelman, BM TI Cell differentiation SO CURRENT OPINION IN CELL BIOLOGY LA English DT Editorial Material C1 Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX 75235 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Cell Biol, Boston, MA 02115 USA. RP Olson, E (reprint author), Univ Texas, SW Med Ctr, Dept Mol Biol, 6000 Harry Hines Blvd, Dallas, TX 75235 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD DEC PY 1999 VL 11 IS 6 BP 653 EP 654 DI 10.1016/S0955-0674(99)00031-9 PG 2 WC Cell Biology SC Cell Biology GA 261LE UT WOS:000084010000001 ER PT J AU Wu, ZD Puigserver, P Spiegelman, BM AF Wu, ZD Puigserver, P Spiegelman, BM TI Transcriptional activation of adipogenesis SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID PROMOTES ADIPOCYTE DIFFERENTIATION; GENE-EXPRESSION; PPAR-GAMMA; RECEPTOR-GAMMA; ECTOPIC EXPRESSION; NUCLEAR RECEPTORS; 3T3-L1 CELLS; C/EBP-ALPHA; PROTEIN; LIGAND AB Studies from the past several years have revealed that adipogenesis is controlled by an interplay of transcription factors, including members of the CCAAT/enhancer binding protein family and peroxisome proliferator activated receptor gamma. In addition to providing a new understanding of this aspect of the energy balance systems, these factors provide potential new targets for therapeutic intervention in metabolic diseases, such as obesity and type 2 diabetes mellitus. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Cell Biol, Boston, MA 02115 USA. RP Wu, ZD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Cell Biol, 44 Binney St, Boston, MA 02115 USA. NR 53 TC 82 Z9 83 U1 1 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD DEC PY 1999 VL 11 IS 6 BP 689 EP 694 DI 10.1016/S0955-0674(99)00037-X PG 6 WC Cell Biology SC Cell Biology GA 261LE UT WOS:000084010000007 PM 10600710 ER PT J AU Jenkins, BG Kraft, E AF Jenkins, BG Kraft, E TI Magnetic resonance spectroscopy in toxic encephalopathy and neurodegeneration SO CURRENT OPINION IN NEUROLOGY LA English DT Article ID PROTON MR SPECTROSCOPY; SUBCLINICAL HEPATIC-ENCEPHALOPATHY; DEHYDROGENASE COMPLEX DEFICIENCY; IDIOPATHIC PARKINSONS-DISEASE; VIVO C-13 NMR; IN-VIVO; N-ACETYLASPARTATE; GLUTAMINE SYNTHESIS; MULTIPLE-SCLEROSIS; ALZHEIMERS-DISEASE AB Magnetic resonance spectroscopy allows neurochemistry to be probed noninvasively in vivo. Recent advances in our understanding of the biochemical significance of the various neurochemicals that are observable allow a variety of pathologic states of relevance to encephalopathies and neurodegenerative disorders to be observed, Measurements of brain glutamate and glutamine allow observation of neuronal/glial substrate cycling and ammonia detoxification. Myo-inositol allows changes in cerebral osmolarity and gliosis to be observed. N-acetylaspartate is a marker of neuronal health and number. Lactate allows nonoxidative glycolysis to be observed. These molecules are now being used to ask etiologic questions that are of relevance to encephalopathies and neurodegeneration, as well to probe longitudinally both natural history and therapeutic interventions in these conditions. Combined with recent advances in anatomic magnetic resonance imaging as well as perfusion magnetic resonance imaging, magnetic resonance spectroscopy has the potential to aid greatly in our understanding of neuronal dysfunction in a wide variety of neurologic pathologies, even in single patients. Curr Opin Neurol 12:753-760. (C) 1999 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Jenkins, BG (reprint author), Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 55 TC 13 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD DEC PY 1999 VL 12 IS 6 BP 753 EP 760 DI 10.1097/00019052-199912000-00016 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 418XV UT WOS:000167920600016 PM 10676760 ER PT J AU Amatruda, JF Zon, LI AF Amatruda, JF Zon, LI TI Dissecting hematopoiesis and disease using the zebrafish SO DEVELOPMENTAL BIOLOGY LA English DT Review DE zebrafish; hematopoiesis; genetics; disease model ID BONE MORPHOGENETIC PROTEIN-4; DORSOVENTRAL PATTERN-FORMATION; GERM-LINE TRANSMISSION; STEM-CELLS; VENTRAL MESODERM; HOMEOBOX GENE; DEFINITIVE HEMATOPOIESIS; VERTEBRATE DEVELOPMENT; VASCULAR DEVELOPMENT; XENOPUS DEVELOPMENT AB The study of blood has often defined paradigms that are relevant to the biology of other vertebrate organ systems. As examples, stem cell physiology and the structure of the membrane cytoskeleton were first described in hematopoietic cells. Much of the reason for these successes resides in the ease with which blood cells can be isolated and manipulated in vitro. The cell biology of hematopoiesis can also be illuminated by the study of human disease states such as anemia, immunodeficiency, and leukemia. The sequential development of the blood system in vertebrates is characterized by ventral mesoderm induction, hematopoietic stem cell specification, and subsequent cell lineage differentiation. Some of the key regulatory steps in this process have been uncovered by studies in mouse, chicken, and Xenopus. More recently, the genetics of the zebrafish (Danio rerio) have been employed to define novel points of regulation of the hematopoietic program. In this review, we describe the advantages of the zebrafish system for the study of blood cell development and the initial success of the system in this pursuit. The striking similarity of zebrafish mutant phenotypes and human diseases emphasizes the utility of this model system for elucidating pathophysiologic mechanisms. New screens for lineage-specific mutations are beginning, and the availability of transgenics promises a better understanding of lineage-specific gene expression. The infrastructure of the zebrafish system is growing with an NIH-directed genome initiative, providing a detailed map of the zebrafish genome and an increasing number of candidate genes for the mutations. The zebrafish is poised to contribute greatly to our understanding of normal and disease-related hematopoiesis. (C) 1999 Academic Press. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Boston Childrens Hosp, Dept Hematol Oncol, Boston, MA 02115 USA. RP Amatruda, JF (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL07623-13] NR 103 TC 111 Z9 114 U1 1 U2 10 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 DEC 1 PY 1999 VL 216 IS 1 BP 1 EP 15 DI 10.1006/dbio.1999.9462 PG 15 WC Developmental Biology SC Developmental Biology GA 264GD UT WOS:000084171500001 PM 10588859 ER PT J AU Maytin, EV Lin, JC Krishnamurthy, R Batchvarova, N Ron, D Mitchell, PJ Habener, JF AF Maytin, EV Lin, JC Krishnamurthy, R Batchvarova, N Ron, D Mitchell, PJ Habener, JF TI Keratin 10 gene expression during differentiation of mouse epidermis requires transcription factors C/EBP and AP-2 SO DEVELOPMENTAL BIOLOGY LA English DT Article DE keratinocytes; cell differentiation; transcription factors; skin ID ENHANCER-BINDING-PROTEIN; ACUTE-PHASE RESPONSE; DNA-BINDING; EPIDERMOLYTIC HYPERKERATOSIS; ADIPOCYTE DIFFERENTIATION; MURINE EMBRYOGENESIS; CYTOKERATIN GENE; MESSENGER-RNA; ALPHA-GENE; SPECIFICITY AB The epidermis forms a vital barrier composed of stratified keratinocytes and their differentiated products. One of these products, keratin K10, is critical to epidermal integrity, because mutations in k10 lend to abnormal blistering. For the normal expression of k10, differentiation-associated transcription factors C/EBP alpha, C/EBP beta, and AP-2 are well positioned to play an important role. Here, regulation of the k10 gene is examined in keratinocytes in the skin of normal mice and in transgenic mice carrying targeted deletions of c/ebp beta and ap-2 alpha. In cultured cells, C/EBP alpha and C/EBP beta are each capable of activating the k10 promoter via three binding sites, identified by site-directed mutagenesis. In a given epidermal cell in vivo, however, the selection of C/EBP alpha versus C/EBP beta for k10 regulation is determined via a third transcription factor, AP-2. This novel regulatory scheme involves: (1) unique gradients of expression for each transcription factor, i.e., C/EBP beta and AP-2 most abundant in the lower epidermis, C/EBP alpha in the upper; (2) C/EBP-binding sites in the ap-2 alpha gene promoter, through which C/EBP beta stimulates ap-2 alpha; and (3) AP-2 binding sites in the c/ebp alpha promoter, through which AP-2 represses c/ebp alpha. Promoter-analysis and gene-expression data presented herein support a regulatory model in which C/EBP beta activates and maintains AP-2 expression in basal keratinocytes, whereas AP-2 represses C/EBPa in those cells. In response to differentiation signals, loss of AP-2 expression leads to derepression of the c/ebp alpha promoter and activation of k10 as cells migrate upward. (C) 1999 Academic Press. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. NYU, Med Ctr, Howard Hughes Med Inst, New York, NY 10016 USA. NYU, Med Ctr, Skirball Inst Biomol Med, New York, NY 10016 USA. Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16302 USA. RP Maytin, EV (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. NR 68 TC 73 Z9 76 U1 0 U2 3 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 DEC 1 PY 1999 VL 216 IS 1 BP 164 EP 181 DI 10.1006/dbio.1999.9460 PG 18 WC Developmental Biology SC Developmental Biology GA 264GD UT WOS:000084171500012 PM 10588870 ER PT J AU Huang, XM Birk, DE Goetinck, PF AF Huang, XM Birk, DE Goetinck, PF TI Mice lacking matrilin-1 (cartilage matrix protein) have alterations in type II collagen fibrillogenesis and fibril organization SO DEVELOPMENTAL DYNAMICS LA English DT Article DE matrilin-1 (cartilage matrix protein); cartilage; collagen fibrillogenesis ID SKIN FRAGILITY; MOUSE; GENE; AGGRECAN; MORPHOGENESIS; MATURATION; MORPHOLOGY; SEQUENCE; SUBUNITS; ABSENCE AB Matrilin-1 (cartilage matrix protein) is a homotrimeric protein that forms collagen-dependent and collagen-independent fibrils in the extracelluar matrix of cartilage. In the growth plate of developing long bones, the gene for matrilin-1 is transcribed exclusively by the chondrocytes of the zone of maturation which is situated between the zones of proliferation and hypertrophy. When associated with the cartilage collagen fibril, which consists of collagens type II, IX, and SI, matrilin-1 displays a periodicity of 59.3 nm. Matrilin-1 also interacts with the proteoglycan, aggrecan. Because of its association with the collagen fibril, we tested the hypothesis that matrilin-1 may play a role in collagen fibril formation and cartilage matrix assembly by generating mice with targeted mutations in the matrilin-1 gene. Ultrastructural studies of the cartilage of growth plates of matrilin-1 null mice reveal an abnormal type II collagen fibrillogenesis and fibril organization in the matrix of the zone of maturation. These results represent the first report on the regulation of the heterotypic type II collagen fibril by a non-collagenous protein. The abnormal fibrillogenesis had no obvious effects on skeletal development, on the organization of chondrocytes in the growth plate and on the deposition of aggrecan and the hypertrophic-specific type X collagen in the cartilaginous matrix. (C) 1999 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. RP Goetinck, PF (reprint author), Massachusetts Gen Hosp E, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Birk, David/I-4072-2012 OI Birk, David/0000-0002-4865-9088 FU NEI NIH HHS [EY-5129]; NIAMS NIH HHS [AR-44745]; NICHD NIH HHS [HD-22016] NR 34 TC 45 Z9 45 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 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD DEC PY 1999 VL 216 IS 4-5 BP 434 EP 441 DI 10.1002/(SICI)1097-0177(199912)216:4/5<434::AID-DVDY11>3.0.CO;2-X PG 8 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 264GC UT WOS:000084171400011 PM 10633862 ER PT J AU Xu, G Stoffers, DA Habener, JF Bonner-Weir, S AF Xu, G Stoffers, DA Habener, JF Bonner-Weir, S TI Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats SO DIABETES LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; GLP-1 RECEPTOR; ENDOCRINE PANCREAS; INSULIN RELEASE; GENE-EXPRESSION; MELLITUS; GROWTH; MICE; TRANSPLANTATION; REGENERATION AB Diabetes is a disease of increasing prevalence in the general population and of unknown cause. Diabetes is manifested as hyperglycemia due to a relative deficiency of the production of insulin by the pancreatic beta-cells. one determinant in the development of diabetes is an inadequate mass of beta-cells, either absolute (type 1, juvenile diabetes) or relative (type 2, maturity-onset diabetes). Earlier, me reported that the intestinal hormone glucagon-like peptide I (GLP-I) effectively augments glucose-stimulated insulin secretion. Here me report that exendin-4, a long-acting GLP-I agonist, stimulates both the differentiation of beta-cells from ductal progenitor cells (neogenesis) and proliferation of beta-cells when administered to rats. In a partial pancreatectomy rat model of type 2 diabetes, the daily administration of exendin-4 for 10 days post-pancreatectomy attenuates the development of diabetes, We show that exendin-4 stimulates the regeneration of the pancreas and expansion of beta-cen mass by processes of both neogenesis and proliferation of beta-cells. Thus, GLP-I and analogs thereof hold promise as a novel therapy to stimulate beta-cell growth and differentiation when administered to diabetic individuals with reduced beta-cell mass. C1 Joslin Diabet Ctr, Elliott P Joslin Res Labs, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Massachusetts Gen Hosp,Labs Mol Endocrinol, Boston, MA 02115 USA. RP Bonner-Weir, S (reprint author), Joslin Diabet Ctr, Elliott P Joslin Res Labs, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. RI Stoffers, Doris/H-6157-2012 FU NIDDK NIH HHS [DK-36836, DK-30834, DK-44523] NR 31 TC 832 Z9 878 U1 5 U2 58 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 1999 VL 48 IS 12 BP 2270 EP 2276 DI 10.2337/diabetes.48.12.2270 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 259EE UT WOS:000083880900002 PM 10580413 ER PT J AU Friedman, T Smith, RN Colvin, RB Iacomini, J AF Friedman, T Smith, RN Colvin, RB Iacomini, J TI A critical role for human CD4(+) T-cells in rejection of porcine islet cell xenografts SO DIABETES LA English DT Article ID IMMUNODEFICIENT MOUSE; DIABETIC-PATIENTS; FETAL PANCREAS; NUDE-MICE; TRANSPLANTATION; PIG; ENGRAFTMENT; CLUSTERS; MODEL AB T-cell-mediated rejection is likely to present a significant barrier to porcine islet xenotransplantation. Little is known, however, about human anti-porcine islet rejection because no suitable model exists to study this process. To address this problem, we have developed an immunodeficient mouse model to study rejection of fetal porcine islet cell clusters (ICCs) by human lymphocytes. Transplantation of porcine ICCs into hyperglycemic recombinase activating gene-deficient (R-) mice restores normal blood glucose levels within 5 weeks. Adoptive transfer of in vitro-stimulated human peripheral blood mononuclear cells into R- mice before islet cell transplantation leads to acute cellular rejection of porcine ICCs, The first human cells observed to infiltrate rejecting grafts are CD4(+) T-cells, Although CD8(+) T-cells are observed within the grafts at later time points, CD4(+) T-cells predominate until the graft is destroyed. Adoptive transfer of purified human CD4(+) T-cells before ICC transplantation is sufficient to cause acute cellular rejection. These data demonstrate that human CD4(+) T-cells play a critical role in porcine ICC xenograft rejection. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Iacomini, J (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, 149 13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [F32 AI09882-02, R01 AI41081] NR 27 TC 42 Z9 47 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 1999 VL 48 IS 12 BP 2340 EP 2348 DI 10.2337/diabetes.48.12.2340 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 259EE UT WOS:000083880900011 PM 10580422 ER PT J AU Fine, EL Horal, M Chang, TI Fortin, G Loeken, MR AF Fine, EL Horal, M Chang, TI Fortin, G Loeken, MR TI Evidence that elevated glucose causes altered gene expression, apoptosis, and neural tube defects in a mouse model of diabetic pregnancy SO DIABETES LA English DT Article ID PROGRAMMED CELL-DEATH; PROTEIN-KINASE-C; PAX-3 GENE; CONGENITAL-MALFORMATIONS; OXIDATIVE STRESS; EMBRYONIC MALFORMATIONS; SUPEROXIDE-DISMUTASE; TRANSCRIPTION FACTOR; BIOCHEMICAL BASIS; GLYCEMIC CONTROL AB Congenital malformations, including neural tube defects (NTDs), are significantly increased in the offspring of diabetic mothers. We previously reported that in the embryos of a mouse model of diabetic pregnancy NTDs are associated with reduced expression of the gene Pax-3, which encodes a transcription factor that regulates neural tube development, and that reduced expression of Pax-3 leads to neuroepithelial apoptosis. In this study, me used three approaches to test whether glucose alone could be responsible for these adverse effects of diabetes on embryonic development. First, primary culture of embryo tissue in medium containing 15 mmol/l glucose inhibited Pax-3 expression compared with culture in medium containing 5 mmol/l glucose. Second, inducing hyperglycemia in pregnant mice by subcutaneous glucose administration significantly inhibited Pax-3 expression (P < 0.05), as demonstrated by quantitative reverse transcription-polymerase chain reaction assay of Pax-3 mRNA, and also increased neural tube apoptosis (P < 0.05). NTDs were significantly increased in glucose-injected pregnancies when blood glucose let els were >250 mg/dl (P < 0.002) but not in moderately hyperglycemic pregnancies (150-250 mg/dl, P = 0.37). Third, phlorizin administration to pregnant diabetic mice reduced blood glucose levels and the rate of NTDs. As seen with glucose-injected pregnancies, the rate of NTDs in phlorizin-treated diabetic pregnancies was related to the severity of hyperglycemia, since NTDs were significantly increased in severely hyperglycemic (>250 mg/dl) diabetic pregnancies (P < 0.001) but not in moderately hyperglycemic pregnancies (150-250 mg/dl, P = 0.35). These two findings, that elevated glucose alone can cause the changes in Pax-3 expression observed during diabetic pregnancy and that the NTD fate rises with significant increases in blood glucose levels, suggest that congenital malformations associated with diabetic pregnancy are caused by disruption of regulatory gene expression in the embryo in response to elevated glucose. C1 Joslin Diabet Ctr, Mol Biol Sect, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Loeken, MR (reprint author), Joslin Diabet Ctr, Mol Biol Sect, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK52865] NR 71 TC 134 Z9 138 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 1999 VL 48 IS 12 BP 2454 EP 2462 DI 10.2337/diabetes.48.12.2454 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 259EE UT WOS:000083880900025 PM 10580436 ER PT J AU Signoretti, S Murphy, M Puddu, P DeCoteau, JF Faraggiana, T Kadin, ME Loda, M AF Signoretti, S Murphy, M Puddu, P DeCoteau, JF Faraggiana, T Kadin, ME Loda, M TI Clonality of cutaneous B-cell infiltrates determined by microdissection and immunoglobulin gene rearrangement SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Article DE cutaneous B-cell lymphomas; microdissection; gene rearrangement; IgH ID POLYMERASE-CHAIN-REACTION; OPTIMAL PRIMER SELECTION; MARGINAL ZONE LYMPHOMA; LYMPHOPROLIFERATIVE DISORDERS; MALIGNANT-LYMPHOMA; DIAGNOSIS; TISSUE; SKIN; CLASSIFICATION; MONOCLONALITY AB Diagnosis of primary cutaneous B-cell lymphoma (PCBCL) is supported by the demonstration of a monoclonal B-cell population. Immunoglobulin heavy chain (IgH) gene-rearrangement analysis by polymerase chain reaction (PCR) is a reliable technique to detect B-cell monoclonality in paraffin-embedded tissue, but the presence of numerous reactive B lymphocytes in PCBCL may complicate the interpretation of clonality test results. To test this hypothesis, IgH gene-rearrangement analysis by PCR was performed on paraffin-embedded whole tissue sections of 19 cutaneous B-cell infiltrates diagnosed either as consistent with PCBCL (10 specimens) or unclassified lymphoid infiltrates (ULI) (9 specimens). In specimens that did not show monoclonal bands by IgH gene-rearrangement on DNA extracted from whole tissue sections, clonality assays were repeated on microdissected B-cell subpopulations suspicious for neoplastic cells. In the analysis of whole tissue sections, 4 (40%) of 10 specimens consistent with PCBCL showed one or two monoclonal bands, whereas 9 of 9 ULI specimens showed either a ladder or a smear. Clonality analysis of microdissected B-cell subpopulations showed 3 additional PCBCL specimens (total, 7 of 10) and 1 ULI specimen (total, 1 of 9) with unequivocal and reproducible monoclonal bands. Addition of microdissection increases the sensitivity of PCR-based B-cell clonality assay in PCBCL compared with analysis performed on the whole section (70% versus 40% monoclonal cases) and allows the recognition of a dominant clone in ULI specimens, possibly representing early PCBCL. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Ist Dermopat Immacolata, Rome, Italy. RP Loda, M (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 31 TC 8 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD DEC PY 1999 VL 8 IS 4 BP 176 EP 182 DI 10.1097/00019606-199912000-00002 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA 267FN UT WOS:000084347300002 PM 10617273 ER PT J AU Fausti, SA Henry, JA Helt, WJ Phillips, DS Frey, RH Noffsinger, D Larson, VD Fowler, CG AF Fausti, SA Henry, JA Helt, WJ Phillips, DS Frey, RH Noffsinger, D Larson, VD Fowler, CG TI An individualized, sensitive frequency range for early detection of ototoxicity SO EAR AND HEARING LA English DT Article ID CISPLATIN OTOTOXICITY; GUINEA-PIG AB Objective: The aim of this study was to identify auditory frequencies at which serial threshold testing would provide the greatest sensitivity for early detection of ototoxicity. The overall objective is to develop a more time-efficient ototoxicity monitoring protocol. Design: Threshold data were analyzed from 370 hospitalized patients treated with aminoglycoside antibiotics (AMGs) or cisplatin (CDDP) who received serial auditory monitoring before, during, and after treatment at conventional (0.25 to 8 kHz) and high (9 to 20 kHz) frequencies. Results: For patients showing hearing changes due to ototoxicity, a frequency range was identified for its apparent high sensitivity to initial ototoxicity. This sensitive range is identified according to an individual's hearing threshold configuration, and is, therefore, unique for each patient. The range consists of five frequencies, generally separated by 1/6 octave, e.g., 8, 9, 10, 11.2, and 12.5 kHz. To determine frequencies and combinations of frequencies that were most often involved in ototoxicity detection, threshold data in the sensitive range were analyzed in detail. This analysis suggests that patients receiving treatment with AMG or CDDP can be monitored for hearing thresholds at only five frequencies, resulting in an 84% detection rate for AMG and 94% for CDDP compared with monitoring at all conventional and high frequencies. Conclusions: This comprehensive analysis supports earlier observations that a sensitive, limited frequency range exists in which serial threshold monitoring will provide early warning of ototoxicity before effects in the speech frequency range. This finding is now being evaluated in a prospective investigation. C1 Natl Ctr Rehabil Auditory Res, Dept Vet Affairs Med Ctr, VA RR&D, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. George Washington Univ, Washington, DC USA. Univ Wisconsin, Madison, WI USA. RP Henry, JA (reprint author), Natl Ctr Rehabil Auditory Res, Dept Vet Affairs Med Ctr, VA RR&D, POB 1034,R&D NCAR, Portland, OR 97207 USA. NR 24 TC 56 Z9 60 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-0202 J9 EAR HEARING JI Ear Hear. PD DEC PY 1999 VL 20 IS 6 BP 497 EP 505 DI 10.1097/00003446-199912000-00005 PG 9 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 266UH UT WOS:000084318300005 PM 10613387 ER PT J AU Kieffer, TJ Habener, JL AF Kieffer, TJ Habener, JL TI The glucagon-like peptides SO ENDOCRINE REVIEWS LA English DT Review ID GASTRIC-INHIBITORY POLYPEPTIDE; PANCREATIC BETA-CELLS; DEPENDENT INSULINOTROPIC POLYPEPTIDE; AMINO-ACID-SEQUENCE; PROGLUCAGON-DERIVED PEPTIDES; MESSENGER-RIBONUCLEIC-ACID; PERFUSED RAT PANCREAS; TERMINAL EXTRACELLULAR DOMAIN; IMPROVED GLUCOSE-TOLERANCE; CYCLASE-ACTIVATING POLYPEPTIDE C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst,Lab Mol Endocrinol, Boston, MA 02114 USA. Univ Alberta, Dept Med, Edmonton, AB T6G 2S2, Canada. Univ Alberta, Dept Physiol, Edmonton, AB T6G 2S2, Canada. RP Habener, JL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst,Lab Mol Endocrinol, 55 Fruit St,WEL320, Boston, MA 02114 USA. EM jhabener@partners.org FU NIDDK NIH HHS [DK-30834, DK-25532, DK-30457] NR 583 TC 675 Z9 705 U1 3 U2 34 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD DEC PY 1999 VL 20 IS 6 BP 876 EP 913 DI 10.1210/er.20.6.876 PG 38 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 263PG UT WOS:000084134000004 PM 10605628 ER PT J AU Pete, G Fuller, CR Oldham, JM Smith, DR D'Ercole, AJ Kahn, CR Lund, PK AF Pete, G Fuller, CR Oldham, JM Smith, DR D'Ercole, AJ Kahn, CR Lund, PK TI Postnatal growth responses to insulin-like growth factor I in insulin receptor substrate-1-deficient mice SO ENDOCRINOLOGY LA English DT Article ID TRANSGENIC MICE; SOMATOMEDIN-C; SMALL-BOWEL; SUBSTRATE; ENHANCEMENT; HORMONE; PHOSPHORYLATION; DISRUPTION; EXPRESSION; TISSUES AB Organ weight was compared in adult mice with deletion of one (IRS-1(-/+)) or both (IRS-1(-/-)) copies of the insulin receptor substrate-1 (IRS-1) gene and IRS-1(+/+) Littermates. IRS-1(-/+) mice showed modest reductions in weight of most organs in proportion to a decrease in body weight. IRS-1(-/-) mice showed major reductions in weight of heart, liver, and spleen that were directly proportional to a decrease in body weight. In IRS-1(-/-) mice, kidney and particularly small intestine and brain exhibited proportionately smaller weight reductions, and gastrocnemius muscle showed a proportionately greater weight reduction than the decrease in body weight. Growth deficits in IRS-1(-/-) mice could reflect impaired actions of multiple hormones or cytokines that activate IRS-1. To assess the requirement for IRS-1 in insulin-like growth factor I(EGF-I)-dependent postnatal growth, IRS-1(-/+) mice were cross-bred with mice that widely overexpress a human IGF-I transgene (IGF+) to generate IGF+ and wild-type mice on an IRS-1(+/+), IRS-1(-/+), and IRS-1(-/-) background. IGF-I overexpression increased body weight and weight of brain, small intestine, kidney, spleen, heart, and gastrocnemius muscle in IRS-1(+/+) mice. EGF-I overexpression could not completely reverse the body growth retardation in IRS-1(-/-) mice. Absolute or partial IRS-1 deficiency impaired IGF-1-induced body overgrowth more in females than in males. In males and females, IGF-I stimulated similar overgrowth of brain regardless of IRS-1 status, and intestine and spleen showed dose dependence on IRS-1 for IGF-1-induced growth. IGF-1-induced growth of gastrocnemius muscle had an absolute requirement for IRS-1. IGF-1-induced growth of kidney and heart was impaired by IRS-1 deficiency only in females. In vivo, therefore, most organs do not require IRS-1 for IGF-1-induced growth and can use alternate signaling molecules to mediate IGF-1 action. Other organs, such as gastrocnemius muscle, require IRS-1 for IGF-1-induced growth in vivo. C1 Univ N Carolina, Dept Physiol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Pediat, Chapel Hill, NC 27599 USA. AgResearch, Ruakura Res Ctr, Hamilton, New Zealand. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Lund, PK (reprint author), Univ N Carolina, Dept Cell & Mol Physiol, CB 7545, Chapel Hill, NC 27599 USA. EM empk@med.unc.edu NR 30 TC 65 Z9 66 U1 0 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 DEC PY 1999 VL 140 IS 12 BP 5478 EP 5487 DI 10.1210/en.140.12.5478 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 257QF UT WOS:000083792500003 PM 10579310 ER PT J AU Mao, YL Ling, PR Fitzgibbons, TP McCowen, KC Frick, GP Bistrian, BR Smith, RJ AF Mao, YL Ling, PR Fitzgibbons, TP McCowen, KC Frick, GP Bistrian, BR Smith, RJ TI Endotoxin-induced inhibition of growth hormone receptor signaling in rat liver in vivo SO ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT 81st Annual Meeting of the Endocrine-Society CY JUN 12-16, 1999 CL SAN DIEGO, CA SP Endocrine Soc ID STIMULATES TYROSINE PHOSPHORYLATION; MESSENGER-RIBONUCLEIC-ACID; TUMOR-NECROSIS-FACTOR; INSULIN-RECEPTOR; SKELETAL-MUSCLE; GENE-EXPRESSION; JAK2; PROTEIN; KINASE; SUBSTRATE-1 AB The bacterial lipopolysaccharide endotoxin induces a catabolic response characterized by resistance to multiple anabolic hormones. The objective of this study was to determine the effects of endotoxin on the GH signaling pathway in rat liver in vivo. After the iv injection of Escherichia. coli endotoxin (1 mg/kg), there was a progressive decrease in liver STATE (signal transducer and activator of transcription-5) tyrosine phosphorylation in response to GH (40% decrease 6 h after endotoxin), which occurred in the absence of a change in abundance of the STAT5 protein. Endotoxin resulted in a rapid 40-fold increase in liver Janus family kinase-2 (JAK2) messenger RNA, followed by a 2-fold increase in JAK2 protein abundance. This was associated with a 50% decrease in phosphorylated/total JAK2 after GH stimulation. GH receptor abundance was unchanged, suggesting a postreceptor site of endotoxin-induced GH resistance. Rat complementary DNAs for three members of the suppressor of cytokine signaling gene family were cloned [cytobine-inducible sequence (CIS), suppressor of cytokine signaling-2 (SOCS-2), and SOCS-3] and, using these probes, messenger RNAs for SOCS-3 and CIS were shown to be increased 10- and 4-fold above control values, respectively, 2 h after endotoxin infusion. The finding of endotoxin inhibition of in vivo STAT5 tyrosine phosphorylation in response to a supramaximal dose of GH in the absence of a change in GH receptor abundance or total GH-stimulated JAK2 tyrosine phosphorylation provides the first demonstration of acquired postreceptor GH resistance. We hypothesize that this may occur through a specificity-spillover mechanism involving the induction of SOCS genes by cytokines released in response to endotoxin and subsequent SOCS inhibition of GH signaling. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Massachusetts, Sch Med, Dept Physiol, Worcester, MA 01655 USA. RP Smith, RJ (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM robert.smith@joslin.harvard.edu NR 49 TC 69 Z9 79 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1999 VL 140 IS 12 BP 5505 EP 5515 DI 10.1210/en.140.12.5505 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 257QF UT WOS:000083792500006 PM 10579313 ER PT J AU Figlewicz, DP AF Figlewicz, DP TI Endocrine regulation of neurotransmitter transporters SO EPILEPSY RESEARCH LA English DT Article; Proceedings Paper CT Workshop on the Ketogenic Diet - Mechanisms and Models CY SEP 18-19, 1998 CL SEATTLE, WASHINGTON SP Parke Davis, Ortho McNeil Pharmaceut Inc, Glaxo Wellcome Inc, Novartis Pharmaceut Corp DE insulin; glucocorticoids; transporters; dopamine ID HUMAN DOPAMINE TRANSPORTER; BRAIN GABA TRANSPORTER; MESSENGER-RNA; RAT-BRAIN; SEROTONIN TRANSPORTERS; NOREPINEPHRINE UPTAKE; FUNCTIONAL REGULATION; TYROSINE-HYDROXYLASE; EXPRESSION CLONING; NEURONAL CULTURES AB Aminergic signalling in the CNS is terminated by clearance of neurotransmitters from the synapse via high affinity transporter molecules in the presynaptic membrane. Relatively recent sequence identification of these molecules has now permitted the initiation of studies of regulation of transporter function at the cellular and systems levels. In vitro studies provide evidence that the transporters for dopamine, serotonin, and gamma-aminobutyric acid (GABA) may be substrates for regulation by protein kinase C and protein kinase A signalling. Changes in energy balance and metabolic status, such as starvation, result in major shifts in hormonal output. It is now recognized that metabolic hormones such as insulin or the adrenal steroids can have significant acute and chronic effects on several aspects of CNS function. Data from this laboratory and others now provide evidence that insulin and adrenal and gonadal steroid hormones may regulate the synthesis and activity of the transporters. Future studies should permit elucidation of the cellular basis for endocrine regulation of neurotransmitter clearance, and thus, the role of endocrines in the maintenance of normal CNS aminergic signalling. The potential relevance of transporter regulation for the ketogenic diet is discussed. (C) 1999 Published by Elsevier Science B.V. All rights reserved. C1 Univ Washington, Dept Psychol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Figlewicz, DP (reprint author), VA Puget Sound Hlth Care Syst, Dept Metab Endocrinol, 151,1660 So Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [R01-DK40963] NR 55 TC 36 Z9 36 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD DEC PY 1999 VL 37 IS 3 BP 203 EP 210 DI 10.1016/S0920-1211(99)00072-8 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 251YK UT WOS:000083473800005 PM 10584970 ER PT J AU Methia, N Denis, CV Wagner, DD AF Methia, N Denis, CV Wagner, DD TI Carboxypeptidase E does not mediate von Willebrand factor targeting to storage granules SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Article DE carboxypeptidase E (CPE); von Willebrand factor; endothelium; protein targeting; secretory granules ID HUMAN-ENDOTHELIAL CELLS; REGULATED SECRETORY PATHWAY; WEIBEL-PALADE BODIES; CPE(FAT)/CPE(FAT) MICE; SORTING RECEPTOR; SUBSTANCE-P; PROTEIN; EXPRESSION; PROINSULIN; DEFICIENT AB Sorting of von Willebrand factor precursor (pro-vWf) from the trans-Golgi network to secretory granules (Weibel-Palade bodies) is critical for its conversion to the biologically active highly multimeric form, as well as for regulated secretion by the endothelial cells, When expressed in hormone-secretory cells, vWf is also recognized as a stored protein and is directed to storage granules. Recently, carboxypeptidase E (CPE) was proposed as a granular sorting receptor for prohormones (Cool et al,, Cell 88: 73, 1997), To explore whether CPE is also involved in pro-vWf sorting, we initially examined its expression in human umbilical vein endothelial cells. A specific message for CPE and the protein itself were detected making it a plausible candidate as a targeting receptor for vWf in endothelium, To investigate this possibility we used mice lacking CPE, The highly multimeric forms, subunit composition and plasma levels of vWf in CPE-deficient mice were similar to those of their wild-type littermates. vWf was also found in alpha-granules of platelets and in Weibel-Palade bodies of endothelial cells obtained from the CPE-deficient mice. Furthermore, vWf was released from the cultured CPE-deficient endothelial cells after stimulation with a secretagogue, We conclude that CPE is not essential for sorting vWf to the regulated secretory pathway. Thus, a CPE-independent mechanism must exist for protein sorting to storage granules. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Denis , Cecile/A-7649-2011 OI Denis , Cecile/0000-0001-5152-9156 FU NHLBI NIH HHS [R01 HL 41002] NR 43 TC 4 Z9 4 U1 0 U2 0 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 DEC PY 1999 VL 78 IS 12 BP 884 EP 891 PG 8 WC Cell Biology SC Cell Biology GA 275PX UT WOS:000084829500005 PM 10669107 ER PT J AU Koya, D Dennis, JW Warren, CE Takahara, N Schoen, FJ Nishio, Y Nakajima, T Lipes, MA King, GL AF Koya, D Dennis, JW Warren, CE Takahara, N Schoen, FJ Nishio, Y Nakajima, T Lipes, MA King, GL TI Overexpression of core 2 N-acetylglycosaminyltransferase enhances cytokine actions and induces hypertrophic myocardium in transgenic mice SO FASEB JOURNAL LA English DT Article DE O-linked glycans; diabetes; cardiac hypertrophy; MAP kinase activation ID CARDIAC GENE-EXPRESSION; SELECTIN GLYCOPROTEIN LIGAND-1; P-SELECTIN; PROTEIN; SPECIFICITY; ACTIVATION; OLIGOSACCHARIDES; BIOSYNTHESIS; RECEPTORS; DISEASE AB Elevated levels of glycocojugates, commonly observed in the myocardium of diabetic animals and patients, are postulated to contribute to the myocardial dysfunction in diabetes. Previously, we reported that UDP-GlcNAc: Gal beta 1-3GalNAc alpha R beta 1-6-N-acetylglucosaminyltransferase (core 2 GlcNAc-T), a developmentally regulated enzyme of O-linked glycans biosynthesis pathway, is specifically increased in the heart of diabetic animals and Is regulated by hyperglycemia and insulin. In this study, transgenic mice overexpressing core 2 GlcNAc-T with severe increase in cardiac core 2 GlcNAc-T activities were normal at birth but showed progressive and significant cardiac hypertrophy at 6 months of age. The heart of transgenic mice showed elevation of sialylated O-glycan and increases of c-fos gene expression and AP-I activity, which are characteristics of cardiac stress. Furthermore, transfection of PC12 cells with core 2 GlcNAc-T also induced c-fos promoter activation, mitogen activated-protein kinase (MAPK) phosphorylation, Trk receptor glycosylation, and cell differentiation. These results suggested a novel role for core 2 GlcNAc-T in the development of diabetic cardiomyopathy and modulation of the MAP kinase pathway in the heart. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. RP King, GL (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. RI Dennis, James/E-7268-2013; Koya, Daisuke /J-3257-2014 FU NEI NIH HHS [EY05110]; NIDDK NIH HHS [DK 36836, DK53281] NR 34 TC 20 Z9 23 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD DEC PY 1999 VL 13 IS 15 BP 2329 EP 2337 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 266QN UT WOS:000084310800024 PM 10593880 ER PT J AU Lipsky, BA AF Lipsky, BA TI Evidence-based antibiotic therapy of diabetic foot infections SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE diabetes mellitus; foot infection; antibiotic therapy; evidence-based treatment ID LOWER-EXTREMITY INFECTIONS; PERIPHERAL VASCULAR-DISEASE; TISSUE CONCENTRATIONS; CIPROFLOXACIN; AMPICILLIN/SULBACTAM; CLINDAMYCIN; OFLOXACIN; MELLITUS; COST AB In addition to proper cleansing, debridement and local wound care, foot infections in diabetic patients require carefully selected antibiotic therapy. Serious infections necessitate hospitalization for initial parenteral broad-spectrum antibiotic therapy. Appropriately selected patients with mild infections can be treated as outpatients with oral (or even topical) therapy. Initial antibiotic selection is usually empirical, but definitive therapy may be modified based on culture results and the clinical response. Therapy should nearly always be active against staphylococci and streptococci, with broader-spectrum agents indicated if Gram-negative or anaerobic organisms are likely. In infected foot tissues levels of most antibiotics, except fluoroquinolones. ale often subtherapeutic. The duration of therapy ranges fi om a week (for mild soft tissue infections) to over 6 weeks (for osteomyelitis). Recent antibiotic trials have shown that several intravenously or orally administered agents are effective in treating these infections, with no one agent or combination emerging as optimal. Suggested regimens based on the severity of infection are provided. (C) 1999 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved. C1 Univ Washington, Sch Med, Dept Med, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Med Serv, Seattle, WA 98108 USA. RP Lipsky, BA (reprint author), Univ Washington, Sch Med, Dept Med, 1660 S Columbian Way, Seattle, WA 98108 USA. OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 40 TC 72 Z9 73 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD DEC PY 1999 VL 26 IS 3-4 BP 267 EP 276 DI 10.1016/S0928-8244(99)00143-1 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 260WQ UT WOS:000083976800012 PM 10575138 ER PT J AU Park, S Krebs, DE Mann, RW AF Park, S Krebs, DE Mann, RW TI Hip muscle co-contraction: evidence from concurrent in vivo pressure measurement and force estimation SO GAIT & POSTURE LA English DT Article DE hip muscle co-contraction; in vivo pressure measurement; force estimation ID GAIT AB The biomechanical literature over the past three decades reports direct measurements of human hip joint contact forces from instrumented implants which in general are guile different than estimates of contact forces based on external kinematic-ground reaction force data and inverse Newtonian analyses. Because direct physical measurement establishes veridical values in science, the higher analytical estimates may overestimate the balanced muscle force increments in agonist-antagonistic muscles about the joint (called co-contraction) which control joint impedance and contribute to joint stability. We studied the extent of muscle co-contraction by comparing in vivo endoprosthesis pressure measurements on hip articular cartilage and intersegmental force estimations from concurrent kinetic-kinematic data. Muscle co-contraction was evident from pressure magnitudes higher than those: consistent with external data, from pressure rises before foot-floor contact, and substantial differences in the locations on the acetabulum of the highest pressures compared with the corresponding force vectors estimated from external data. Therefore, joint force and pressure inferences from external kinematic and kinetic data, without corroborating direct, internal measurements, should be made with more caution than is evident in the current literature. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Biomot Lab, Boston, MA 02114 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Krebs, DE (reprint author), Massachusetts Gen Hosp, Biomot Lab, Boston, MA 02114 USA. FU NHLBI NIH HHS [REC-HI33E80024]; NIAMS NIH HHS [R01-AR40036]; NICHD NIH HHS [R01-HD30063] NR 32 TC 28 Z9 29 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0966-6362 J9 GAIT POSTURE JI Gait Posture PD DEC PY 1999 VL 10 IS 3 BP 211 EP 222 DI 10.1016/S0966-6362(99)00033-8 PG 12 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA 261AD UT WOS:000083984900005 PM 10567753 ER PT J AU Sands, BE Podolsky, DK AF Sands, BE Podolsky, DK TI New life in a sleeper: Thalidomide and Crohn's disease SO GASTROENTEROLOGY LA English DT Editorial Material ID NECROSIS-FACTOR-ALPHA; MONOCLONAL-ANTIBODY CA2; TRIAL; THERAPY; AIDS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. RP Sands, BE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, 55 Fruit St,GRJ825, Boston, MA 02114 USA. NR 32 TC 31 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 1999 VL 117 IS 6 BP 1485 EP 1488 DI 10.1016/S0016-5085(99)70299-4 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 260LQ UT WOS:000083952500030 PM 10579990 ER PT J AU Yeh, JJ Marsh, DJ Zedenius, J Dwight, T Delbridge, L Robinson, BG Eng, C AF Yeh, JJ Marsh, DJ Zedenius, J Dwight, T Delbridge, L Robinson, BG Eng, C TI Fine-structure deletion mapping of 10q22-24 identifies regions of loss of heterozygosity and suggests that sporadic follicular thyroid adenomas and follicular thyroid carcinomas develop along distinct neoplastic pathways SO GENES CHROMOSOMES & CANCER LA English DT Article ID TUMOR-SUPPRESSOR GENE; SOMATIC MUTATIONS; COWDEN-DISEASE; PTEN/MMAC1 MUTATIONS; ENDOMETRIAL CANCERS; PTEN MUTATIONS; CELL-LINES; BREAST; LOCUS; FREQUENT AB Previous studies have demonstrated frequent loss of heterozygosity (LOH) of markers on chromosome arm 10q in both follicular thyroid carcinomas (FTCs) and follicular thyroid adenomas (FAs). A novel tumor suppressor gene, PTEN, has been mapped to 10q23.3 and is the susceptibility gene for Cowden syndrome, an autosomal dominant disorder characterized by multiple hamartomas and a risk of benign and malignant tumors of the breast and thyroid. Studies examining the relationship of somatic PTEN status and follicular thyroid neoplasms have only demonstrated a variable subset of tumors that have somatic monoallelic deletions of PTEN, suggesting that other tumor suppressor genes may be present in this region. We therefore sought to conduct a detailed examination of LOH of 20 polymorphic markers in a 19-cM region spanning 10q22-24, including PTEN, in 44 FAs and 17 FTCs. Using this fine-structure somatic mapping approach, we defined at least two novel regions of LOH in follicular adenomas and follicular carcinomas, suggesting the presence of at least two distinct tumor suppressor genes that may play a role in thyroid neoplasia. Furthermore, the difference in patterns of LOH in adenomas versus carcinomas lends additional support to the hypothesis that adenomas and carcinomas can develop along two separate, nonserial pathways. (C) 1999 Wiley-Liss, Inc. C1 Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Med Res Facil 690C, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Clin Canc Genet Program, Columbus, OH 43210 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Charles A Dana Human Canc Genet Unit,Dept Med, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA. Huddinge Univ Hosp, Ctr Metab & Endocrinol, Dept Surg, Karolinska Inst, Stockholm, Sweden. Univ Sydney, Royal N Shore Hosp, Mol Genet Lab, Dept Med, St Leonards, NSW 2065, Australia. Royal N Shore Hosp, Dept Surg, Sydney, NSW, Australia. Univ Sydney, Sydney, NSW, Australia. Univ Cambridge, Canc Res Campaign, Human Canc Genet Res Grp, Cambridge, England. RP Eng, C (reprint author), Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Med Res Facil 690C, 420 W 12th Ave, Columbus, OH 43210 USA. RI Marsh, Deborah/I-1491-2014; OI Marsh, Deborah/0000-0001-5899-4931; Eng, Charis/0000-0002-3693-5145 FU NCI NIH HHS [P30CA16058] NR 40 TC 39 Z9 40 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD DEC PY 1999 VL 26 IS 4 BP 322 EP 328 DI 10.1002/(SICI)1098-2264(199912)26:4<322::AID-GCC6>3.0.CO;2-# PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 253QQ UT WOS:000083567600006 PM 10534767 ER PT J AU Kim, DR Dai, Y Mundy, CL Yang, W Oettinger, MA AF Kim, DR Dai, Y Mundy, CL Yang, W Oettinger, MA TI Mutations of acidic residues in RAG1 define the active site of the V(D)J recombinase SO GENES & DEVELOPMENT LA English DT Article DE RAG1; RAG2; V(D)J recombination; T-cell receptor; recombination signal sequence ID HIV-1 INTEGRASE; RESTRICTION ENDONUCLEASES; RETROVIRAL INTEGRASES; DIRECTED MUTAGENESIS; CATALYTIC DOMAIN; STRUCTURAL BASIS; DNA; CLEAVAGE; MECHANISM; PROTEIN AB The RAG1 and RAG2 proteins collaborate to initiate V(D)J recombination by binding recombination signal sequences (RSSs) and making a double-strand break between the RSS and adjacent coding DNA. Like the reactions of their biochemical cousins, the bacterial transposases and retroviral integrases, cleavage by the RAG proteins requires a divalent metal ion but does not involve a covalent protein/DNA intermediate. In the transposase/integrase family, a triplet of acidic residues, commonly called a DDE motif, is often found to coordinate the metal ion used for catalysis. We show here that mutations in each of three acidic residues in RAG1 result in mutant derivatives that can bind the RSS but whose ability to catalyze either of the two chemical steps of V(D)J cleavage (nicking and hairpin formation) is severely impaired. Because both chemical steps are affected by the same mutations, a single active site appears responsible for both reactions. Two independent lines of evidence demonstrate that at least two of these acidic residues are directly involved in coordinating a divalent metal ion: The substitution of Cys for Asp allows rescue of some catalytic function, whereas an alanine substitution is no longer subject to iron-induced hydroxyl radical cleavage. Our results support a model in which the RAG1 protein contains the active site of the V(D)J recombinase and are interpreted in light of predictions about the structure of RAG1. C1 Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Oettinger, MA (reprint author), Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. RI Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 FU NIGMS NIH HHS [GM58026] NR 49 TC 144 Z9 149 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD DEC 1 PY 1999 VL 13 IS 23 BP 3070 EP 3080 DI 10.1101/gad.13.23.3070 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 266EP UT WOS:000084287900004 PM 10601033 ER PT J AU Price, JA Brewer, CS Howard, TD Fossey, SC Sale, MM Li, LN Krolewski, AS Bowden, DW AF Price, JA Brewer, CS Howard, TD Fossey, SC Sale, MM Li, LN Krolewski, AS Bowden, DW TI A physical map of the 20q12-q13.1 region associated with Type 2 diabetes SO GENOMICS LA English DT Article ID HEPATOCYTE NUCLEAR FACTOR-4-ALPHA; HUMAN GENOME; SUSCEPTIBILITY LOCUS; MISSENSE MUTATION; GENE; MODY1; CHROMOSOME-20; SEQUENCE; MELLITUS; NIDDM AB Several recent genetic studies have suggested Linkage of Type 2 diabetes (non-insulin-dependent diabetes mellitus) susceptibility to a region of chromosome 20q12-q13.1, To facilitate the identification and cloning of a diabetes susceptibility gene(s) in this region, me have constructed correlated radiation hybrid and YAC/BAC contig physical maps of the region. A high-resolution radiation hybrid map encompassing 9.5 Mb between the PLC and the CEBPB genes was constructed using 68 markers: 25 polymorphic markers, 15 known genes, 21 ESTs, and 7 random genomic sequences. The physical order of the polymorphic markers within this radiation hybrid map is consistent with published genetic maps. A YAC/BAC contig that gives continuous coverage between PLC and CEBPB was also constructed. This contig was constructed from 24 YACs, 34 BACs, and 1 P1 phage clone onto which 71 markers were mapped: 23 polymorphic markers, 12 genes, 24 ESTs, and 12 random genomic sequences. The radiation hybrid map and YAC/BAC physical map enable precise mapping of newly identified transcribed sequences and polymorphic markers that will aid in linkage and Linkage disequilibrium studies and facilitate identification and cloning of candidate Type 2 diabetes susceptibility genes residing in 20q12-q13.1. (C) 1999 Academic Press. C1 Wake Forest Univ, Sch Med, Dept Biochem, Winston Salem, NC 27157 USA. Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Bowden, DW (reprint author), Wake Forest Univ, Sch Med, Dept Biochem, Med Ctr Blvd, Winston Salem, NC 27157 USA. FU NIDDK NIH HHS [R01 DK47475, R01 DK41269] NR 29 TC 9 Z9 10 U1 0 U2 0 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 DEC 1 PY 1999 VL 62 IS 2 BP 208 EP 215 DI 10.1006/geno.1999.6007 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 275MZ UT WOS:000084825100011 PM 10610714 ER PT J AU Caterina, J Shi, J Krakora, S Bartlett, JD Engler, JA Kozak, CA Birkedal-Hansen, H AF Caterina, J Shi, J Krakora, S Bartlett, JD Engler, JA Kozak, CA Birkedal-Hansen, H TI Isolation, characterization, and chromosomal location of the mouse enamelysin gene SO GENOMICS LA English DT Article ID MATRIX; METALLOPROTEINASE; TOOTH AB Mouse enamelysin (Mmp20), a member of the matrix metalloproteinase (MMP) family of extracellular matrix degrading enzymes, shows a high degree of homology with other MMPs, particularly those of the stromelysin/collagenase subfamilies. It is expressed exclusively in ameloblasts and odontoblasts. The mouse enamelysin gene (Mmp20) is made up of 10 exons spanning approximately 65 kb within the MMP gene cluster at the centromeric end of chromosome 9. (C) 1999 Academic Press. C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA. Univ Alabama, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA. RP Caterina, J (reprint author), Natl Inst Dent & Craniofacial Res, NIH, 30 Convent Dr,MSC 4380, Bethesda, MD 20892 USA. FU NIDCR NIH HHS [DE08228, DE12098, R29 DE012098, DE10631] NR 15 TC 12 Z9 13 U1 0 U2 0 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 DEC 1 PY 1999 VL 62 IS 2 BP 308 EP 311 DI 10.1006/geno.1999.5990 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 275MZ UT WOS:000084825100025 PM 10610728 ER PT J AU Sjak-Shie, NN Vescio, RA Berenson, JR AF Sjak-Shie, NN Vescio, RA Berenson, JR TI The role of human herpesvirus-8 in the pathogenesis of multiple myeloma SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; PROTEIN-COUPLED RECEPTOR; HIV-INFECTED INDIVIDUALS; KAPOSIS-SARCOMA; DENDRITIC CELLS; DNA-SEQUENCES; HUMAN-HERPESVIRUS-8; KSHV; GROWTH; HHV-8 AB Human herpesvirus-8 (HHV-8), a new gammaherpesvirus, was recently detected in long-term stromal cultures derived from fresh bone marrow aspirates from myeloma patients. The association between HHV-8 and multiple myeloma and the question whether HHV-8 is of pathophysiologic significance in myeloma, remains controversial. Evidence supporting an association between this virus and multiple myeloma is, however, accumulating. It seems that the strain of HHV-8 found in myeloma harbors sequence variations within ORF65 unique to myeloma. HHV-8 encodes several genes homologous to eukaryotic genes involved in cellular proliferation, apoptosis, cell migration, and intercellular signaling, through which it may induce abnormal cellular proliferation and tumor formation in its hosts. C1 Univ Calif Los Angeles, Sch Med, Div Hematol Oncol, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA. RP Berenson, JR (reprint author), Univ Calif Los Angeles, Sch Med, Div Hematol Oncol, Los Angeles, CA 90024 USA. NR 56 TC 6 Z9 7 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 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD DEC PY 1999 VL 13 IS 6 BP 1159 EP + DI 10.1016/S0889-8588(05)70118-0 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 270YH UT WOS:000084564400005 PM 10626142 ER PT J AU Awwad, JT Sayegh, RA Tao, XJ Hassan, T Awwad, ST Isaacson, K AF Awwad, JT Sayegh, RA Tao, XJ Hassan, T Awwad, ST Isaacson, K TI The SCID mouse: an experimental model for endometriosis SO HUMAN REPRODUCTION LA English DT Article DE animal model; complement C3; cytokeratin; endometriosis; SCID mouse ID NUDE-MICE; COMPLEMENT COMPONENT-3; STEROID-HORMONES; MENSTRUAL-CYCLE; HUMAN TUMORS; CYTOKERATIN; TISSUE; GROWTH; TRANSPLANTATION; SECRETION AB The purpose of this study was to validate the suitability of the severe combined immunodeficient (SCID) mouse as an experimental model for endometriosis, by defining the morphological and histological features of induced endometrial implants, and characterizing specific biochemical properties of these implants. Human secretory endometrial tissues were injected into the peritoneal cavity of SCID/SCID CB17 mature female mice. Successful peritoneal implantation was observed in 55 of 57 (96.5%) SCID mice and consisted of circumscribed elevated nodules, Haematoxylin-eosin staining of implanting lesions demonstrated the presence of endometrial glandular tissue in a mixed background of stromal and inflammatory cells, When progesterone was administered to mice, epithelial glands underwent well-defined secretory changes. Immunohistochemical analysis using polyclonal human pan-cytokeratin antibodies demonstrated selective positive staining in the glandular epithelium of the human implants with none in the surrounding stroma. In-situ hybridization analysis using complement component 3 cDNA radiolabelled riboprobes yielded significantly more intense signals in glands compared to stroma, As human endometrial implants in SCID mice were shown to retain specific histological, functional and biochemical properties, we conclude that the SCID mouse is an attractive animal model for the study of endometriosis. C1 Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Awwad, JT (reprint author), Amer Univ Beirut, Med Ctr, Dept Obstet & Gynecol, 850 3rd Ave,18th Floor, New York, NY 10022 USA. NR 28 TC 57 Z9 68 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD DEC PY 1999 VL 14 IS 12 BP 3107 EP 3111 DI 10.1093/humrep/14.12.3107 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 265VD UT WOS:000084265800034 PM 10601104 ER PT J AU Chen, AI McAdam, AJ Buhlmann, JE Scott, S Lupher, ML Greenfield, EA Baum, PR Fanslow, WC Calderhead, DM Freeman, GJ Sharpe, AH AF Chen, AI McAdam, AJ Buhlmann, JE Scott, S Lupher, ML Greenfield, EA Baum, PR Fanslow, WC Calderhead, DM Freeman, GJ Sharpe, AH TI Ox40-ligand has a critical costimulatory role in dendritic cell: T cell interactions SO IMMUNITY LA English DT Article ID DELAYED-TYPE HYPERSENSITIVITY; VASCULAR ENDOTHELIAL-CELLS; CONTACT HYPERSENSITIVITY; OX40 LIGAND; CYTOKINE PRODUCTION; IMMUNE-RESPONSES; INTERFERON-GAMMA; OX-40 LIGAND; MURINE; SENSITIVITY AB The tumor necrosis factor family molecule Ox40-ligand (Ox40L) has been identified as a potential costimulatory molecule and also has been implicated in T cell homing and B cell activation. To ascertain the essential functions of Ox40L, we generated and characterized Ox40L-deficient mice. Mice lacking Ox40L exhibit an impaired contact hypersensitivity response, a dendritic cell-dependent T cell-mediated response, due to defects in T cell priming and cytokine production. In contrast, Ox40L-deficient mice do not have defects in T cell homing or humoral immune responses. In vitro, Ox40L-deficient dendritic cells are defective in costimulating T cell cytokine production. Thus, Ox40L has a critical costimulatory function in vitro and in vivo for dendritic cell:T cell interactions. C1 Brigham & Womens Hosp, Dept Pathol, Div Immunol Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Adult Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Immunex Res & Dev Corp, Seattle, WA 98101 USA. Dartmouth Med Sch, Lebanon, NH 03756 USA. RP Sharpe, AH (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Immunol Res, 75 Francis St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI/GF41584]; NIAMS NIH HHS [AR42689] NR 45 TC 220 Z9 232 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 1999 VL 11 IS 6 BP 689 EP 698 DI 10.1016/S1074-7613(00)80143-0 PG 10 WC Immunology SC Immunology GA 271UX UT WOS:000084612900005 PM 10626891 ER PT J AU Pimentel-Muinos, FX Seed, B AF Pimentel-Muinos, FX Seed, B TI Regulated commitment of TNF receptor signaling: A molecular switch for death or activation SO IMMUNITY LA English DT Article ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; LYMPHOTOXIN-BETA-RECEPTOR; CELL-DEATH; INDUCED APOPTOSIS; T-CELLS; LYMPHOCYTES-T; MICE LACKING; FACTOR-ALPHA; KINASE RIP AB Tumor necrosis factor receptor (TNFR) superfamily members can induce a context-dependent apoptosis or cell activation. However, the mechanisms by which these opposing programs are selected remain unclear. We show that in T cells, TNFR2 (TNFRSF1B) signaling is dramatically affected by the intracellular mediator RIP, a protein Ser/Thr kinase required for NF-kappa B activation by TNFR1 (TNFRSF1A). In the presence of RIP, TNFRP triggers cell death, whereas in the absence of RIP, TNFR2 activates NF-kappa B. RIP is induced during IL2-driven T cell proliferation, and its inhibition reduces susceptibility to TNF-dependent apoptosis. Evidence that signaling outputs are shaped by intracellular constraints helps reconcile conflicting views of TNFR1 and TNFRP as apoptotic mediators. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Seed, B (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RI Pimentel-Muinos, Felipe/K-4557-2014 OI Pimentel-Muinos, Felipe/0000-0002-0258-2855 FU NIAID NIH HHS [AI27849]; NIDDK NIH HHS [DK43039] NR 70 TC 210 Z9 214 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 1999 VL 11 IS 6 BP 783 EP 793 DI 10.1016/S1074-7613(00)80152-1 PG 11 WC Immunology SC Immunology GA 271UX UT WOS:000084612900014 PM 10626900 ER PT J AU Jespersgaard, C Hajishengallis, G Huang, Y Russell, MW Smith, DJ Michalek, SM AF Jespersgaard, C Hajishengallis, G Huang, Y Russell, MW Smith, DJ Michalek, SM TI Protective immunity against Streptococcus mutans infection in mice after intranasal immunization with the glucan-binding region of S-mutans glucosyltransferase SO INFECTION AND IMMUNITY LA English DT Article ID DENTAL-CARIES; SUBSEQUENCE PEPTIDE; SEQUENCE-ANALYSIS; ESCHERICHIA-COLI; CHOLERA-TOXIN; GENE; DOMAIN; SOBRINUS; EXPRESSION; INHIBITION AB Here we present the construction and characterization of a chimeric vaccine protein combining the glucan-binding domain (GLU) of the gtfB-encoded water-insoluble glucan-synthesizing glucosyltransferase enzyme (GTF-I) from Streptococcus mutans and thioredoxin from Escherichia coli, which increases the solubility of coexpressed recombinant proteins and stimulates proliferation of murine T cells. The protective potential of intranasal (i.n.) immunization with this chimeric immunogen was compared to that of the GLU polgpeptide alone in a mouse infection model. Both immunogens were able to induce statistically significant mucosal (salivary and vaginal) and serum responses (P < 0.01) which were sustained to the end of the study (experimental day 100). Following infection with S. mutans, sham-immunized mice maintained high levels of this cariogenic organism (similar to 60% of the total oral streptococci) for at least 5 weeks. In contrast, animals immunized with the thioredoxin-GLU chimeric protein (Thio-GLU) showed significant reduction (>85%) in S. mutans colonization after 3 weeks (P < 0.05. The animals immunized with GLU alone required 5 weeks to demonstrate significant reduction (>50%) of S. mutans infection (P < 0.05). Evaluation of dental caries activity at the end of the study showed that mice immunized with either Thio-GLU or GLU had significantly fewer carious lesions in the buccal enamel or dentinal surfaces than the sham-immunized animals (P < 0.01). The protective effects against S. mutans colonization and caries activity following i.n. immunization with GLU or Thio-GLU are attributed to the induced salivary immunoglobulin A (IgA) anti-GLU responses. Although in general Thio GLU was not significantly better than GLU alone in stimulating salivary IgA responses and in protection against dental caries, the finding that the GLU polypeptide alone, in the absence of any inmunoenhancing agents, is protective against disease offers a promising and safe strategy for the development of a vaccine against caries. C1 Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. Univ Alabama Birmingham, Dept Oral Biol, Birmingham, AL 35294 USA. Forsyth Dent Ctr, Dept Immunol, Boston, MA 02115 USA. RP Michalek, SM (reprint author), Univ Alabama Birmingham, Dept Microbiol, 845 S 19th,BBRB 258, Birmingham, AL 35294 USA. EM suemich@uab.edu OI Russell, Michael/0000-0002-1303-4061 FU NIDCR NIH HHS [DE06746, DE08182, DE09081, R01 DE008182, R01 DE009081, R37 DE006746] NR 34 TC 38 Z9 42 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 1999 VL 67 IS 12 BP 6543 EP 6549 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 257DW UT WOS:000083768000043 PM 10569773 ER PT J AU Haake, DA Mazel, MK McCoy, AM Milward, F Chao, G Matsunaga, J Wagar, EA AF Haake, DA Mazel, MK McCoy, AM Milward, F Chao, G Matsunaga, J Wagar, EA TI Leptospiral outer membrane proteins OmpL1 and LipL41 exhibit synergistic immunoprotection SO INFECTION AND IMMUNITY LA English DT Article ID HARDJO-BOVIS INFECTION; BORRELIA-BURGDORFERI; TREPONEMA-PALLIDUM; PATHOGENIC LEPTOSPIRA; MOLECULAR-CLONING; SEQUENCE-ANALYSIS; NEISSERIA-MENINGITIDIS; PSEUDOMONAS-AERUGINOSA; PROTECTIVE CAPACITY; ESCHERICHIA-COLI AB New vaccine strategies are needed for prevention of leptospirosis. a widespread human and veterinary disease caused by invasive spirochetes belonging to the genus Leptospira, We have examined the immunoprotective capacity of the leptospiral porin OmpL1 and the leptospiral outer membrane Lipoprotein LipL41 in the Golden Syrian hamster model of leptospirosis, Specialized expression plasmids were developed to facilitate expression of leptospiral proteins in Escherichia coli as the membrane-associated proteins OmpL1-M and LipL41-M. Although OmpL1-M expression is highly toxic in E. coli, this was accomplished by using plasmid pMMB66-OmpL1, which has undetectable background expression without induction. LipL41-M expression and processing were enhanced by altering its lipoprotein signal peptidase cleavage site to mimic that of the murein lipoprotein. Active immunization of hamsters with E, coli membrane fractions containing a combination of OmpL1-M and LipL41-M was found to provide significant protection against homologous challenge with Leptospira kirschneri serovar grippotyphosa. At 28 days after intraperitoneal inoculation, survival in animals vaccinated dth both proteins was 71% (95% confidence interval [CI], 53 to 89%), compared with only 25% (95% CII 8 to 42%) in the control group (P < 0.001). On the basis of serological, histological, and microbiological assays, no evidence of infection was found in the vaccinated survivors. The protective effects of immunization with OmpL1-M and Lip41-M sere synergistic, since significant levels of protection Here not observed in animals immunized with either OmpL1-M or LipL41-M alone. In contrast to immunization with the membrane-associated farms of leptospiral proteins, hamsters immunized with His(6)-OmpL1 and His(6)-LipL41 fusion proteins, either alone or in combination, were not protected, These data indicate that the manner in which OmpL1 and LipL41 associates with membranes is an important determinant of immunoprotection. C1 VA Greater LA Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. Predev, Merial Biodiv, F-69342 Lyon 07, France. RP Haake, DA (reprint author), VA Greater LA Healthcare Syst, Div Infect Dis, 111F, Los Angeles, CA 90073 USA. EM dhaake@ucla.edu FU NIAID NIH HHS [AI34431, R01 AI034431, R21 AI034431, R29 AI034431, R29 AI034431-04] NR 56 TC 145 Z9 164 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 1999 VL 67 IS 12 BP 6572 EP 6582 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 257DW UT WOS:000083768000047 PM 10569777 ER PT J AU Ouellette, AJ Darmoul, D Tran, D Huttner, KM Yuan, J Selsted, ME AF Ouellette, AJ Darmoul, D Tran, D Huttner, KM Yuan, J Selsted, ME TI Peptide localization and gene structure of cryptdin 4, a differentially expressed mouse paneth cell alpha-defensin SO INFECTION AND IMMUNITY LA English DT Article ID TRANSCRIPTION FACTORS DATABASE; ANTIMICROBIAL PEPTIDE; SMALL-INTESTINE; MESSENGER-RNA; HOST-DEFENSE; PROTEIN; FAMILY; TFD AB Paneth cells in crypts of the small intestine express antimicrobial peptides, including ol defensins, termed cryptdins in mice. Of the known Paneth cell alpha-defensins, the cryptdin 4 gene is unique, because it is inactive in the duodenum and expressed at maximal levels in the distal small bowel (D. Darmoul and A. J. Ouellette, Am. J, Physiol, 271:G68-G74, 1996). With a cryptdin 4-specific antibody, immunohistochemical staining of ileal Paneth cells was strong and specific for cytoplasmic granules, demonstrating that this microbicidal peptide is a secretory product of Paneth cells in the distal small intestine. Consistent with the pattern of cryptdin 4 mRNA distribution along the length of the gut, the cryptdin 4 peptide was not detected in duodenum. Structurally, the cryptdin 4 gene resembles other Paneth cell alpha-defensin genes. Its two exons, transcriptional start site, intron, splice sites, and 3' flanking sequences are characteristic of the highly conserved mouse alpha-defensin genes. However, in the region upstream of the transcriptional initiation site, the cryptdin 4 gene contains a repeated 130-bp element that is unique to this alpha-defensin gene. Every independent cryptdin 4 genomic clone examined carries the repeated element, which contains putative recognition sequences for TF-IID-EIIA, cMyc-RS-1, and IgHC.2/CuE1.1; the repeat proximal to the start of transcription replaces DNA at the corresponding position in other mouse alpha-defensin genes. We speculate that this unique duplicated element may have a cis-acting regulatory role in the positional specificity of cryptdin 4 gene expression, C1 Univ Calif Irvine, Coll Med, Dept Pathol, Irvine, CA 92697 USA. Univ Calif Irvine, Coll Med, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA. INSERM U410, Fac Med Xavier Bichat, F-75018 Paris, France. Massachusetts Gen Hosp, Dept Pediat, Sect Neonatol, Boston, MA 02114 USA. RP Ouellette, AJ (reprint author), Univ Calif Irvine, Coll Med, Dept Pathol, Irvine, CA 92697 USA. FU NIAID NIH HHS [R01 AI022931, AI22931, R37 AI022931]; NIDDK NIH HHS [DK33506, DK44632, P01 DK033506, R01 DK044632] NR 33 TC 37 Z9 40 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 DEC PY 1999 VL 67 IS 12 BP 6643 EP 6651 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 257DW UT WOS:000083768000056 PM 10569786 ER PT J AU Athanasoulis, CA Athanasoulis, MA AF Athanasoulis, CA Athanasoulis, MA TI The Friday afternoon pulmonary angiogram: Temporal relationship between onset of symptoms and requests for angiography SO INTERNATIONAL ANGIOLOGY LA English DT Article DE pulmonary embolism radiography; angiography; pulmonary embolism epidemiology ID SEASONAL-VARIATION; NECROPSY INCIDENCE; THROMBOEMBOLISM; EMBOLISM AB Background. To determine if pulmonary embolism symptoms and pulmonary angiography have a proclivity for a particular day of the week, month or season (Part I) and to assess the length of time elapsing between the appearance of symptoms and requests for pulmonary angiography (Part II). Design: Prospective (in part) collection of data and retrospective review of clinical records. Setting: Large metropolitan, university affiliated hospital. Methods. Part I: 2,969 consecutive pulmonary angiograms performed over 17 years, were collected according to the day of the week, month and season of their performance, Relevant rates were calculated. Part II: A study of the time interval between the onset of pulmonary embolism symptoms and requests for and performance of angiography was conducted in 128 patients. Results. Part l. In the course of 17 years, more pulmonary angiograms were performed on Fridays (mean 37.2, SE 1.8), than on any other day of the week (p < .001). No proclivity for a particular month or season was observed. Part II. The mean time elapsed between the onset of symptoms and requests for angiography was 24 hours (range 0.2-162, SE 4.3) for inpatients, and 45 hours (range 3-358, SE 7.8) for outpatients. The angiogram was completed urgently, within two hours of the onset of symptoms, only in 2.4%. Conclusions. Pulmonary angiography has a proclivity for Fridays. Pulmonary embolism symptoms and consequent angiograms do not favour a specific day, month or season. In most cases the time elapsing between the onset of symptoms and requests for angiography is too long to be consistent with urgency. The frequent Friday pulmonary angiogram reflects a tendency to "mop up" unfinished business prior to the week's end. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. RP Athanasoulis, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, GRB-290, Boston, MA 02114 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0392-9590 J9 INT ANGIOL JI Int. Angiol. PD DEC PY 1999 VL 18 IS 4 BP 299 EP 305 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 294RT UT WOS:000085924700008 PM 10811518 ER PT J AU Duerinckx, AJ Laughrun, D Lewis, BS AF Duerinckx, AJ Laughrun, D Lewis, BS TI Usefulness of coronary MR angiography prior to angioplasty SO INTERNATIONAL JOURNAL OF CARDIAC IMAGING LA English DT Article DE coronary arteries; coronary stenosis; heart; MR angiography; PTCA ID ARTERIES AB The range of indications for percutaneous transluminal coronary angioplasty (PTCA) has increased greatly since the procedure was initially introduced. The success rate depends on the anatomy and length of the occlusion and on the state of the distal vessel. We present a case where the use of magnetic resonance angiography (MRA) allowed to evaluate the length of a subtotal occlusion prior to PTCA, and thus could have had an impact on therapeutic decisions. Coronary MR angiography is one of the many applications of breathhold MRI, where breathholding and segmented k-space acquisition are combined to provide anatomical images of coronary vessels. Coronary MR angiography allows reproducible visualization of coronary vessels. Even under adverse circumstances (poor cardiac triggering) the images are sometimes of sufficient quality to help make a diagnosis. This capability may increase the as yet limited clinical use of MR technology in the practice of cardiology. C1 VA Greater Los Angeles Healthcare Ctr, Serv Radiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Med Ctr, Dept Radiol, Los Angeles, CA 90053 USA. VA Greater Los Angeles Healthcare Ctr, Cardiol Sect, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Lady Davies Carmel Med Ctr, Dept Cardiol, IL-34362 Haifa, Israel. RP Duerinckx, AJ (reprint author), VA Greater Los Angeles Healthcare Ctr, Serv Radiol, Mail Route W114,MRI,Bld 507,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 18 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-9899 J9 INT J CARDIAC IMAG JI Int. J. Card. Imaging PD DEC PY 1999 VL 15 IS 6 BP 533 EP 540 DI 10.1023/A:1006331628682 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 288TF UT WOS:000085580000011 PM 10768747 ER PT J AU Asawanonda, P Oberlender, S Taylor, C AF Asawanonda, P Oberlender, S Taylor, C TI The use of dihydroxyacetone for photoprotection in variegate porphyria SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Article ID PROTECTION AB A 33-year-old woman presented with complaints of facial scarring. blisters on the dorsal hands, skin fragility, and increased hair growth on the temples. She reported that these "scratch marks" had appeared spontaneously for 3 years. She was otherwise healthy and not on any medication. On examination, the patient had several 3-4-mm erythematous papules, some with depressed centers, on the dorsal aspects of the hands (Fig. 1) and the face, but no observable milia. In the perioral region, there were numerous depressed pock-like scars. There was no obvious hypertrichosis. A punch biopsy specimen obtained from the left forearm revealed an ulcer with acute and chronic inflammation and periodic acid-Schiff (PAS)-positive material around the dermal blood Vessels and adnexae (Fig. 2). Direct immunofluorescence analysis revealed linear immunoglobulin G (IgG) (2+) along the epidermal and adnexal basement membrane zone and around the blood vessels (Fig. 3). C3 (2+) was also present at the epidermal basement membrane zone and around papillary dermal vessels. The patient had a positive hepatitis A antibody, but was negative for hepatitis B and C. Complete blood count and liver function tests were within normal limits. tron, ferritin, and total iron binding capacity levels were all within normal limits. Antinuclear antibody was positive at 1:160 with a speckled pattern, but anti-Re and anti-La were within normal limits. Total plasma porphyrins measured 4 (normal less than or equal to 1). A 24-h stool porphyrin collection showed diffuse elevations as follows: coproporphyrin 307.0 (0-50), uroprophyrin 5.00 (0-4), protoporphyrin 515.0 (0-105), total stool porphyrins 827.0 (0-159). A 24-h urine porphyrin collection also revealed elevations of all the metabolites as follows: porphobilinogen 22.4 (0-2.7), coproporphyrin 2211.0 (0-155), uroprophyrin 122.1 (3.3-29.5), heptacarboxylporphyrin 35.2 (0-6.8), hexacarboxylporphyrin 21.3 (0-0.9), pentacarboxylporphyrin 120.8 (0-4.7), total urine porphyrins 2510.4 (12-190). The patient's plasma was diluted with phosphate-buffered saline and scanned between 550 and 650 nm at an excitation wavelength of 405 nm. The emission maximum occurred at 630 nm. In spite of a clinical appearance suggestive of porphyria cutanea tarda (PCT), without any history of acute abdomen or neurologic crises, the clinical diagnosis was clearly variegate porphyria (VP), based on the extensive laboratory abnormalities. At the time of diagnosis, the patient was provided with a list of medications which may exacerbate the condition and was instructed to practice vigorous sun protection at all times. Later, she started using a self-tanning lotion. She reported an excellent response to the combination of sunscreen and dihydroxyacetone-containing preparation with far fewer eruptions and a markedly increased tolerance to ambient sun exposure. C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Taylor, C (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Bartlett Hall,Room 410,55 Fruit St, Boston, MA 02114 USA. NR 4 TC 10 Z9 10 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD DEC PY 1999 VL 38 IS 12 BP 916 EP 918 DI 10.1046/j.1365-4362.1999.00779.x PG 3 WC Dermatology SC Dermatology GA 276GP UT WOS:000084868300008 PM 10632771 ER PT J AU Frazer, A Gerhardt, GA Daws, LC AF Frazer, A Gerhardt, GA Daws, LC TI New views of biogenic amine transporter function: implications for neuropsychopharmacology SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Review DE dopamine transporter; norepinephrine transporter; serotonin transporter ID HUMAN NOREPINEPHRINE TRANSPORTER; HUMAN SEROTONIN TRANSPORTER; HUMAN DOPAMINE TRANSPORTER; RECEPTOR-LIKE IMMUNOREACTIVITY; VOLTAGE-DEPENDENT UPTAKE; CENTRAL-NERVOUS-SYSTEM; RAT NUCLEUS-ACCUMBENS; MESSENGER-RNA LEVELS; IN-VIVO; EXTRACELLULAR DOPAMINE AB Biogenic amine transporters, namely the dopamine (DA), norepinephrine (NE) and 5-hydroxytryptamine (serotonin 5-HT) transporters (DAT, NET and 5-HTT, respectively) appear to be the key elements in regulating biogenic amine neurotransmission. These proteins therefore represent a primary target for therapeutic intervention in the treatment of numerous psychiatric disorders, such as depression, anxiety and perhaps even schizophrenia as well as drug abuse. The cloning of DAT, NET and 5-HTT and development of selective radioligands for them over the last decade has dramatically increased our understanding of their location, structure and function. These breakthroughs have also enabled remarkable progress in determining how biogenic amine transporters are regulated under not only normal conditions but also when confronted with acute or chronic exposure to a variety of stimuli including psychotherapeutic drugs. Because of the important therapeutic consequences of a better understanding of these transporters, the present review discusses recent advances in defining their mechanism of action, location and regulation and the implications of the newer data for neurupsychopharmacology. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Mem Hosp Div, San Antonio, TX USA. Univ Kentucky, Dept Anat & Neurobiol, Lexington, KY 40536 USA. RP Daws, LC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, 7703 Floyd Curl Dr,Mail Code 7764, San Antonio, TX 78229 USA. EM daws@uthscsa.edu NR 126 TC 16 Z9 17 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD DEC PY 1999 VL 2 IS 4 BP 305 EP 320 DI 10.1017/S1461145799001625 PG 16 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 273VW UT WOS:000084729400008 PM 11285147 ER PT J AU Levy, RM Giannobile, WV Feres, M Haffajee, AD Smith, C Socransky, SS AF Levy, RM Giannobile, WV Feres, M Haffajee, AD Smith, C Socransky, SS TI The short-term effect of apically repositioned flap surgery on the composition of the subgingival microbiota SO INTERNATIONAL JOURNAL OF PERIODONTICS & RESTORATIVE DENTISTRY LA English DT Article ID NON-SURGICAL TREATMENT; PERIODONTAL THERAPY; ATTACHMENT LEVEL; POCKET DEPTH; DISEASE; MODALITIES; REDUCTION; CALCULUS; PLAQUE AB The purpose of this investigation was to examine the short-term effect of apically repositioned flap surgery on clinical and microbiologic parameters in patients with adult periodontitis. A total of 11 patients with moderate to advanced periodontitis received apically repositioned nap surgery. Subjects were monitored during a 3-month pretreatment phase, the baseline surgical phase, and for 3 months post surgery: Clinical assessments including plaque accumulation gingival redness, suppuration bleeding on probing, pocket depth, and attachment level were made at 6 sites per tooth. Subgingival plaque samples were taken from the mesial aspect of each tooth and the presence and levels of 29 subgingival taxa were determined using whole genomic DNA probes and checkerboard DNA-DNA hybridization. The mean levels and percentage of sites colonized by each species (prevalence) were computed for each subject at each visit After surgery there was a significant decrease in mean pocket depth and percentage of sites exhibiting gingival redness. Significant decreases were seen in the percentage of sites that had attachment levels < 4 mm, with a significant increase in the percentage of sites with attachment levels of 4 to 6 mm after therapy. The mean total DNA probe count for all bacterial species was significantly decreased by both scaling and roof planing and surgical therapy P gingivalis and B forsythus, 2 bacteria previously shown to be susceptible to mechanical therapy exhibited statistically significant decreases in mean total DNA probe count. Because surgical therapy decreased levels of the suspected periodontal pathogens C rectus, P nigrescens, and C gracilis. it may be speculated that there was a potential added beneficial effect of surgery on the periodontal microbiota. C1 Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. Univ Michigan, Sch Dent, Dept Periodont Prevent Geriatr, Ann Arbor, MI 48109 USA. RP Levy, RM (reprint author), Forsyth Inst, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. RI Feres, Magda/H-7964-2012; OI Giannobile, William/0000-0002-7102-9746 FU NIDCR NIH HHS [DE-04881, DE-10977] NR 30 TC 18 Z9 19 U1 0 U2 0 PU QUINTESSENCE PUBL CO INC PI CAROL STREAM PA 551 NORTH KIMBERLY DR, CAROL STREAM, IL 60188-1881 USA SN 0198-7569 J9 INT J PERIODONT REST JI Int. J. Periodontics Restor. Dent. PD DEC PY 1999 VL 19 IS 6 BP 555 EP 568 PG 14 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 271HD UT WOS:000084587400004 PM 10815594 ER PT J AU Willett, CG AF Willett, CG TI Technical advances in the treatment of patients with rectal cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material ID BOWEL C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Willett, CG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Blossom St, Boston, MA 02114 USA. NR 6 TC 14 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD DEC 1 PY 1999 VL 45 IS 5 BP 1107 EP 1108 DI 10.1016/S0360-3016(99)00329-6 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 264WY UT WOS:000084207000005 PM 10613301 ER PT J AU Galper, S Recht, A Silver, B Manola, J Gelman, R Schnitt, SJ Connolly, JL Harris, JR AF Galper, S Recht, A Silver, B Manola, J Gelman, R Schnitt, SJ Connolly, JL Harris, JR TI Factors associated with regional nodal failure in patients with early stage breast cancer with 0-3 positive axillary nodes following tangential irradiation alone SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE breast cancer; regional nodes; axillary dissection ID RADIATION-THERAPY; CONSERVATIVE SURGERY; PREMENOPAUSAL WOMEN; LUNG-CANCER; RADIOTHERAPY; RISK; CHEMOTHERAPY; MANAGEMENT; MORTALITY; TRIAL AB Purpose: Recent randomized trials have suggested that improved local-regional control after radiation therapy significantly increases survival for breast cancer patients with positive axillary nodes treated with adjuvant systemic therapy (1, 2). It has been our policy to use a third radiation field only in patients with 4 or more positive nodes. The purpose of this study was to assess whether there are any clinical or pathologic factors associated with an increased risk of regional nodal failure (RNF) in patients with 0-3 positive nodes treated with tangential radiotherapy (RT) alone with or without systemic therapy. Methods and Materials: We retrospectively analyzed the incidence of RNF for 691 patients with clinical Stage I or II invasive breast cancer treated with complete gross excision of the primary tumor and tangential RT alone between 1978-87; 12% also received systemic therapy. All had 03 positive nodes on axillary dissection that had histologic examination of greater than or equal to 6 nodes, and all had potential 8-year follow-up. The median number of axillary nodes removed was II (range 6-36). RNF was defined as any recurrence in ipsilateral axillary, internal mammary, supraclavicular, or infraclavicular nodes in the absence of recurrence in the breast,,vith or without simultaneous distant metastasis. Crude rates for first sites of failure within the first 8 years after treatment were calculated. A polychotomous logistic regression was used to identify factors prognostic for RNF and other sites of first failure. Results: Within 8 years, RNF was the first site of failure for 27 patients for a crude 8-year rate of 3.9%. Isolated axillary failure occurred in 8 patients (1.2%). Isolated supraclavicular and/or infraclavicular failure occurred in 5 (1.3%) and 3 (0.4%) patients, respectively. Isolated internal mammary node failure occurred in 2 patients (0.3%). A polychotomous logistic regression model of first site of failure (local failure, regional nodal, distant/opposite breast, dead without recurrence, no evidence of disease) within 8 years found age <50 years, moderate or marked necrosis, size greater than I cm, and presence of an extensive intraductal component (EIC) to be significantly correlated with site of first failure, but only the last two were associated with a significantly larger relative risk of RNF versus being no evidence of disease at 8 years. The incidence of RNF was 0.7% for patients with tumors less than or equal to 1 cm compared to 5.7% among-patients with larger tumors. Among patients with EIC-positive tumors the incidence of RNF was 7.6% compared to 3.1% among those whose tumors were EIC-negative. Conclusions: Although the incidence of RNF has been shown to be somewhat higher in patients with tumors measuring greater than 1 cm and those with an EIC, RNF is uncommon among all subsets of patients with negative or 1-3 positive lymph nodes treated with conservative surgery, axillary dissection, and only tangential RT fields. Therefore, giving only tangential RT (without a separate nodal field) appears generally acceptable for patients with 0-3 positive nodes. (C) 1999 Elsevier Science Inc. C1 Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. RP Galper, S (reprint author), Dana Farber Canc Inst, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. NR 21 TC 60 Z9 63 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD DEC 1 PY 1999 VL 45 IS 5 BP 1157 EP 1166 DI 10.1016/S0360-3016(99)00334-X PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 264WY UT WOS:000084207000012 PM 10613308 ER PT J AU Fidias, P Spiro, I Sobczak, ML Nielsen, GP Ruffolo, EF Mankin, H Suit, HD Harmon, DC AF Fidias, P Spiro, I Sobczak, ML Nielsen, GP Ruffolo, EF Mankin, H Suit, HD Harmon, DC TI Long-term results of combined modality therapy in primary bone lymphomas SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE bone neoplasms; lymphoma non-Hodgkin's; combined modality therapy ID LARGE-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMAS; RADIATION-THERAPY; MALIGNANT-LYMPHOMA; PROGNOSTIC FACTORS; EWINGS-SARCOMA; STAGE-I; CHEMOTHERAPY; CYCLOPHOSPHAMIDE; RADIOTHERAPY AB Purpose: To report the Massachusetts General Hospital experience in the management of patients with primary bone lymphoma (PBL) treated with combined modality therapy (CMT). Methods and Materials: Records from 37 eligible patients were reviewed. Two patients were treated with complete resection of the tumor, while 35 patients underwent radiation therapy with a median total dose of 54 Gy (range 38.35-66.5), All patients received combination chemotherapy, which contained doxorubicin in 33 cases. We compared the current data with our previous experience in patients treated with local measures only. Results: Actuarial disease-free survival (DFS) at 5 and 10 years is 78% and 73%, respectively, while overall survival (OS) is 91% and 87%, respectively. No local failures were seen. Pathologic fracture at presentation influenced DFS (p = 0.005) and OS (p = 0.017) adversely. OS was compromised in patients older than 60 years (p = 0.059) and DFS in patients with pelvic primaries (p = 0.015), CMT was associated with improved DFS (p = 0.0008) and OS (p = 0.0001) compared to our historical controls. Ten patients (27%) developed complications requiring orthopedic procedures following completion of therapy at a median of 25.5 months (range 4-228), Conclusion: Patients with PBL have a favorable outcome with CMT, which appears superior to radiation therapy alone. Late complications can be seen, especially in weight-bearing bones. (C) 1999 Elsevier Science Inc. C1 Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthoped Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fidias, P (reprint author), 100 Blossom St,Cox 201, Boston, MA 02114 USA. NR 24 TC 48 Z9 50 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD DEC 1 PY 1999 VL 45 IS 5 BP 1213 EP 1218 DI 10.1016/S0360-3016(99)00305-3 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 264WY UT WOS:000084207000019 PM 10613315 ER PT J AU Spear, MA Dupuy, DE Park, JJ Halpern, EF Spiro, IJ AF Spear, MA Dupuy, DE Park, JJ Halpern, EF Spiro, IJ TI Tolerance of autologous and allogeneic bone grafts to therapeutic radiation in humans SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 38th ASTRO Annual Meeting CY OCT 27-31, 1996 CL LOS ANGELES, CALIFORNIA SP Amer Soc Therapeut Radiol & Oncol DE radiation; bone graft ID IRRADIATION; RABBIT; TONGUE AB Purpose: To examine the effect of perioperative irradiation on bone graft healing and functional integrity. Methods and Materials: Fifty-five bone grafts (10 autologus and 45 allogeneic) performed between 1978 and 1995 were evaluated retrospectively. Sixteen received preoperative radiation, 11 received postoperative, and 13 were treated with a combination of pre- and postoperative radiation. Fifteen nonirradiated grafts were randomly selected to serve as controls, Twenty-three of the grafts were placed in patients who received chemotherapy in the perioperative period. Functional graft survival and radiographic healing quality were evaluated. Results: Overall rates of graft survival at 1 year were 89% for autografts and 79% for allografts. Graft survival rates were 86% and 68% at 1 and 5 years for the irradiated group, and 67% and 58% for the control group. No significant difference was seen in the Kaplan-Meier graft survival curves of the two groups. There was a nonsignificant trend toward improved radiographic healing quality in the control group. No significant differences in outcome based on treatment chronology were found with survival rates of 88% for preoperative treatment and 100% for postoperative treatment. No relation between outcome and bone dose (preoperative + postoperative dose), graft dose (postoperative dose), or mean dose/day was found. There was a trend (p = 0.0525) toward worse outcome seen in the Kaplan-Meier curves of patients who received chemotherapy, This difference, however, was not seen in the I-year survival rates or healing quality. Tobacco use tended toward predicting failure, with 63% graft survival compared to 85% in nonsmokers (p = 0.09), Healing quality was significantly lower in the smoking group. Conclusion: The low failure rate of grafts in irradiated sites, overall and compared to controls from this study and relevant literature, as well as the lack of dose and time effects, does not support significant deviation from the indicated treatment regimen for patients who have received or are expected to receive a graft. The trend toward decreased quality of radiographic bone healing, and data published in relevant literature indicating improved healing when radiation is withheld until 3-4 weeks postoperatively suggest this delay should be attempted when not expected to otherwise compromise patient outcome. A nonsignificant trend only for the effect of chemotherapy on bone grafts was seen, thus we do not recommend changes in its use as appropriate for disease management other than a preference against use during the immediate perioperative period. (C) 1999 Elsevier Science Inc. C1 Univ Calif San Diego, UCSD Canc Ctr, Dept Radiol, Div Radiat Oncol, San Diego, CA 92103 USA. Brown Univ, Rhode Isl Hosp, Sch Med, Dept Diagnost Imaging, Providence, RI 02903 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Connect Tissue Oncol Grp, Boston, MA USA. RP Spear, MA (reprint author), Univ Calif San Diego, UCSD Canc Ctr, Dept Radiol, Div Radiat Oncol, 200 W Arbor Dr,MC 8757, San Diego, CA 92103 USA. OI Dupuy, Damian/0000-0003-0524-5982 NR 27 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD DEC 1 PY 1999 VL 45 IS 5 BP 1275 EP 1280 DI 10.1016/S0360-3016(99)00339-9 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 264WY UT WOS:000084207000027 PM 10613323 ER PT J AU Hoffman, RS Power, WJ AF Hoffman, RS Power, WJ TI Current options in pterygium management SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID CONJUNCTIVAL AUTOGRAFT TRANSPLANTATION; POSTOPERATIVE BETA-RADIATION; TOPICAL MITOMYCIN-C; RECURRENT PTERYGIUM; EYE DROPS; INTRAOPERATIVE MITOMYCIN; RANDOMIZED TRIAL; IRRADIATION; EXCISION; COMPLICATIONS C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Hoffman, RS (reprint author), Doctors Eye Inst, POB 206068, Louisville, KY 40250 USA. NR 45 TC 15 Z9 17 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1999 VL 39 IS 1 BP 15 EP 26 DI 10.1097/00004397-199903910-00004 PG 12 WC Ophthalmology SC Ophthalmology GA 171TQ UT WOS:000078880500003 PM 10083903 ER PT J AU Jakobiec, FA Krzystolik, M AF Jakobiec, FA Krzystolik, M TI Surgical advances in ophthalmology - Preface SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Editorial Material C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1999 VL 39 IS 1 BP XXI EP XXI DI 10.1097/00004397-199903910-00002 PG 1 WC Ophthalmology SC Ophthalmology GA 171TQ UT WOS:000078880500001 ER PT J AU Yoo, SH Azar, DT AF Yoo, SH Azar, DT TI Laser in situ keratomileusis for the treatment of myopia SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID PHOTOREFRACTIVE KERATECTOMY; DIOPTERS C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Yoo, SH (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 24 TC 4 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1999 VL 39 IS 1 BP 37 EP 44 DI 10.1097/00004397-199903910-00006 PG 8 WC Ophthalmology SC Ophthalmology GA 171TQ UT WOS:000078880500005 PM 10083905 ER PT J AU Garrana, RMR Azar, DT AF Garrana, RMR Azar, DT TI Phakic intraocular lenses for correction of high myopia SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID LASER PHOTOREFRACTIVE KERATECTOMY; EXCIMER-LASER; RETINAL-DETACHMENT; SURGICAL-CORRECTION; FOLLOW-UP; EYES; KERATOMILEUSIS; EPIKERATOPLASTY; IMPLANTATION; EXTRACTION C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Garrana, RMR (reprint author), 5 Quincy Ave,Apt C, Long Beach, CA 90803 USA. NR 51 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1999 VL 39 IS 1 BP 45 EP 57 DI 10.1097/00004397-199903910-00007 PG 13 WC Ophthalmology SC Ophthalmology GA 171TQ UT WOS:000078880500006 PM 10083906 ER PT J AU Colby, K AF Colby, K TI Management of open globe injuries SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID OCULAR TRAUMA; ENDOPHTHALMITIS C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Emergency Eye Serv, Boston, MA 02114 USA. RP Colby, K (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Emergency Eye Serv, 243 Charles St, Boston, MA 02114 USA. NR 15 TC 9 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1999 VL 39 IS 1 BP 59 EP 69 DI 10.1097/00004397-199903910-00008 PG 11 WC Ophthalmology SC Ophthalmology GA 171TQ UT WOS:000078880500007 PM 10083907 ER PT J AU Akpek, EK Foster, CS AF Akpek, EK Foster, CS TI Limbal stem-cell transplantation SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID CORNEAL EPITHELIAL REGENERATION; OCULAR SURFACE DISORDERS; EPIDERMAL GROWTH-FACTOR; CONJUNCTIVAL TRANSDIFFERENTIATION; RABBIT CORNEAS; EXPRESSION; KERATIN; RECONSTRUCTION; PROLIFERATION; ALLOGRAFT C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Akpek, EK (reprint author), Wilmer Eye Inst, 600 N Wolfe St, Baltimore, MD 21287 USA. NR 66 TC 11 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1999 VL 39 IS 1 BP 71 EP 82 DI 10.1097/00004397-199903910-00009 PG 12 WC Ophthalmology SC Ophthalmology GA 171TQ UT WOS:000078880500008 PM 10083908 ER PT J AU Chan, RY Foster, CS AF Chan, RY Foster, CS TI A step-wise approach to ocular surface rehabilitation in patients with ocular inflammatory disease SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Review ID AMNIOTIC MEMBRANE TRANSPLANTATION; MEIBOMIAN GLAND DYSFUNCTION; TOPICAL RETINOID TREATMENT; STEVENS-JOHNSON SYNDROME; DRY-EYE DISORDERS; LIMBAL TRANSPLANTATION; ROSE-BENGAL; CONJUNCTIVAL TRANSPLANTATION; IMMUNOSUPPRESSIVE THERAPY; AUTOGRAFT TRANSPLANTATION C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Chan, RY (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 101 TC 4 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1999 VL 39 IS 1 BP 83 EP 108 DI 10.1097/00004397-199903910-00010 PG 26 WC Ophthalmology SC Ophthalmology GA 171TQ UT WOS:000078880500009 PM 10083909 ER PT J AU Nguyen, QD Foster, CS AF Nguyen, QD Foster, CS TI Scleral patch graft in the management of necrotizing scleritis SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID RHEUMATOID-ARTHRITIS; WEGENERS GRANULOMATOSIS; RELAPSING POLYCHONDRITIS; EPISCLERITIS; ANTIBODIES; DISEASE; AUTOANTIBODIES; CYCLOSPORINE; DIAGNOSIS; THERAPY C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Nguyen, QD (reprint author), 6800 Little River Turnpike, Annandale, VA 22003 USA. NR 48 TC 20 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1999 VL 39 IS 1 BP 109 EP 131 DI 10.1097/00004397-199903910-00011 PG 23 WC Ophthalmology SC Ophthalmology GA 171TQ UT WOS:000078880500010 PM 10083910 ER PT J AU Wang, WQ Bellows, AR Guedes, V Hutchinson, BT AF Wang, WQ Bellows, AR Guedes, V Hutchinson, BT TI Long-term evaluation of initial filtration surgery SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID FOLLOW-UP; TRABECULECTOMY; GLAUCOMA C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Wang, WQ (reprint author), 4155 13th Ave S, Seattle, WA 98108 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1999 VL 39 IS 1 BP 133 EP 138 DI 10.1097/00004397-199903910-00012 PG 6 WC Ophthalmology SC Ophthalmology GA 171TQ UT WOS:000078880500011 PM 10083911 ER PT J AU Leuenberger, EU Grosskreutz, CL Walton, DS Pasquale, LR AF Leuenberger, EU Grosskreutz, CL Walton, DS Pasquale, LR TI Advances in aqueous shunting procedures SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID AHMED GLAUCOMA VALVE; INITIAL CLINICAL-EXPERIENCE; CHAMBER TUBE SHUNT; DRAINAGE IMPLANT-SURGERY; PLATE MOLTENO IMPLANT; COMPLICATED GLAUCOMAS; SINGLE-PLATE; REFRACTORY GLAUCOMA; LONG-TERM; ENCIRCLING BAND C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Leuenberger, EU (reprint author), 12 Flame Tree Rd,S Forbes Pk, Makati City, Philippines. NR 79 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1999 VL 39 IS 1 BP 139 EP 153 DI 10.1097/00004397-199903910-00013 PG 15 WC Ophthalmology SC Ophthalmology GA 171TQ UT WOS:000078880500012 PM 10083912 ER PT J AU Da Mata, AP Foster, CS AF Da Mata, AP Foster, CS TI Ahmed valve and uveitic glaucoma SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID ARGON-LASER TRABECULOPLASTY; OPEN-ANGLE GLAUCOMA; INFLAMMATORY GLAUCOMA; TRABECULECTOMY; 5-FLUOROURACIL C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Da Mata, AP (reprint author), R Tome de Souza 10,Apt 402,30140139-BH-MG, Rio De Janeiro, Brazil. NR 26 TC 10 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1999 VL 39 IS 1 BP 155 EP 167 DI 10.1097/00004397-199903910-00014 PG 13 WC Ophthalmology SC Ophthalmology GA 171TQ UT WOS:000078880500013 PM 10083913 ER PT J AU Chen, TC Pasquale, LR Walton, DS Grosskreutz, CL AF Chen, TC Pasquale, LR Walton, DS Grosskreutz, CL TI Diode laser transscleral cyclophotocoagulation SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID CONTINUOUS WAVE NEODYMIUM; YTTRIUM-ALUMINUM-GARNET; CILIARY BODY; CADAVER EYES; REFRACTORY GLAUCOMA; ND-YAG; CONTACT; ABLATION C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Glaucoma Serv, Boston, MA 02114 USA. RP Chen, TC (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Glaucoma Serv, 243 Charles St, Boston, MA 02114 USA. NR 32 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1999 VL 39 IS 1 BP 169 EP 176 DI 10.1097/00004397-199903910-00015 PG 8 WC Ophthalmology SC Ophthalmology GA 171TQ UT WOS:000078880500014 PM 10083914 ER PT J AU Fay, AM Michalos, P Rubin, PAD AF Fay, AM Michalos, P Rubin, PAD TI Endocanalicular Nd : YAG laser dacryocystorhinostomy SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID ASSISTED DACRYOCYSTORHINOSTOMY C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Eye Plast & Orbit Surg Serv, Boston, MA 02114 USA. RP Fay, AM (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Eye Plast & Orbit Surg Serv, 243 Charles St, Boston, MA 02114 USA. NR 18 TC 9 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1999 VL 39 IS 1 BP 177 EP 184 DI 10.1097/00004397-199903910-00016 PG 8 WC Ophthalmology SC Ophthalmology GA 171TQ UT WOS:000078880500015 PM 10083915 ER PT J AU Pomeranz, HD Rizzo, JF Lessell, S AF Pomeranz, HD Rizzo, JF Lessell, S TI Treatment of traumatic optic neuropathy SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID SPINAL-CORD INJURY; CANAL DECOMPRESSION; NERVE; METHYLPREDNISOLONE; FRACTURES; RECOVERY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Pomeranz, HD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 49 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1999 VL 39 IS 1 BP 185 EP 194 DI 10.1097/00004397-199903910-00017 PG 10 WC Ophthalmology SC Ophthalmology GA 171TQ UT WOS:000078880500016 PM 10083916 ER PT J AU Polcharoen, W Pilch, BZ Jakobiec, FA AF Polcharoen, W Pilch, BZ Jakobiec, FA TI Frozen-section diagnosis in ophthalmic surgery SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID SQUAMOUS-CELL CARCINOMA; MICROSCOPICALLY CONTROLLED EXCISION; MOHS MICROGRAPHIC SURGERY; BASAL-CELL; SEBACEOUS CARCINOMA; TELEPATHOLOGY; CONJUNCTIVAL; EYELIDS; EXPERIENCE; MANAGEMENT C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Polcharoen, W (reprint author), 71 Paholyothin Soi 41, Bangkok 10900, Thailand. NR 50 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1999 VL 39 IS 1 BP 195 EP 211 DI 10.1097/00004397-199903910-00018 PG 17 WC Ophthalmology SC Ophthalmology GA 171TQ UT WOS:000078880500017 PM 10083917 ER PT J AU Arbour, JD Mukai, S AF Arbour, JD Mukai, S TI Biopsy of the retina and the choroid SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID POLYMERASE CHAIN-REACTION; NEEDLE ASPIRATION BIOPSY; SOLID INTRAOCULAR TUMORS; RETINOCHOROIDAL BIOPSY; OCULAR TOXOPLASMOSIS; ENDORETINAL BIOPSY; DIAGNOSIS; VIRUS; HYBRIDIZATION; UVEITIS C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Arbour, JD (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 48 TC 3 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1999 VL 39 IS 1 BP 213 EP 222 DI 10.1097/00004397-199903910-00019 PG 10 WC Ophthalmology SC Ophthalmology GA 171TQ UT WOS:000078880500018 PM 10083918 ER PT J AU Uy, HS Foster, CS AF Uy, HS Foster, CS TI Diagnostic vitrectomy and uveitis SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID POLYMERASE CHAIN-REACTION; PRIMARY INTRAOCULAR LYMPHOMA; INFLAMMATORY EYE DISEASES; PARS-PLANA VITRECTOMY; VITREOUS-HUMOR; ENDOPHTHALMITIS; IDENTIFICATION; SYSTEM; FLUID; INTERLEUKIN-10 C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Uy, HS (reprint author), 9 Gladiola St,AVF, Malabar 01476, Philippines. NR 49 TC 12 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1999 VL 39 IS 1 BP 223 EP 235 DI 10.1097/00004397-199903910-00020 PG 13 WC Ophthalmology SC Ophthalmology GA 171TQ UT WOS:000078880500019 PM 10083919 ER PT J AU You, TT Arroyo, JG AF You, TT Arroyo, JG TI Surgical approaches for the removal of posteriorly dislocated crystalline lenses SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID CATARACT-SURGERY; FRAGMENTS; PHACOEMULSIFICATION; MANAGEMENT; NUCLEUS; LIQUID C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP You, TT (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 27 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1999 VL 39 IS 1 BP 249 EP 259 DI 10.1097/00004397-199903910-00022 PG 11 WC Ophthalmology SC Ophthalmology GA 171TQ UT WOS:000078880500021 PM 10083921 ER PT J AU Miller, DG Lou, PL Kroll, AJ Ryan, EA AF Miller, DG Lou, PL Kroll, AJ Ryan, EA TI Surgical management of macular hole SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID FLUORESCEIN ANGIOGRAPHIC CHARACTERISTICS; VITREOUS SURGERY; TRANSFORMING GROWTH-FACTOR-BETA-2; ULTRASTRUCTURAL FEATURES; AUTOLOGOUS SERUM; VITRECTOMY; COMPLICATIONS; PSEUDOHOLES; TAMPONADE; OUTCOMES C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Miller, DG (reprint author), Retina Associates Cleveland, 26900 Cedar Rd,Ste 303, Beachwood, OH 44122 USA. NR 55 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1999 VL 39 IS 1 BP 261 EP 274 DI 10.1097/00004397-199903910-00023 PG 14 WC Ophthalmology SC Ophthalmology GA 171TQ UT WOS:000078880500022 PM 10083922 ER PT J AU Khadem, J Veloso, AA Tolentino, F Hasan, T Hamblin, MR AF Khadem, J Veloso, AA Tolentino, F Hasan, T Hamblin, MR TI Photodynamic tissue adhesion with chlorin(e6) protein conjugates SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID FIBRIN SEALANT; CLINICAL-APPLICATIONS; CROSS-LINKING; CELLS; GLUE; ANASTOMOSES; CLOSURE; THERAPY; CHARGE; TUMORS AB PURPOSE. To test the hypothesis that a photodynamic laser-activated tissue solder would perform better in sealing scleral incisions when the photosensitizer was covalently linked to the protein than when it was noncovalently mixed. METHODS. Conjugates and mixtures were prepared between the photosensitizer chlorin(e6) and various proteins (albumin, fibrinogen, and gelatin) in different ratios and used to weld penetrating scleral incisions made in human cadaveric eyes. A blue-green (488-514 nm) argon laser activated the adhesive, and the strength of the closure was measured by increasing the intraocular pressure until the wound showed leakage. RESULTS. Both covalent conjugates and noncovalent mixtures showed a light close-dependent increase in leaking pressure. A preparation of albumin chlorin(e6) conjugate with additional albumin added (2.5 protein to chlorin(e6) molar ratio) showed significantly higher weld strength than other protein conjugates and mixtures. CONCLUSIONS. This is the first report of dye-protein conjugates as tissue solders. These conjugates may have applications in ophthalmology. C1 Harvard Univ, Sch Med, Retina Specialists Boston, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. RP Khadem, J (reprint author), Harvard Univ, Sch Med, Retina Specialists Boston, 100 Charles River Plaza,4th Floor, Boston, MA 02114 USA. OI Hamblin, Michael/0000-0001-6431-4605 NR 45 TC 10 Z9 11 U1 0 U2 2 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 DEC PY 1999 VL 40 IS 13 BP 3132 EP 3137 PG 6 WC Ophthalmology SC Ophthalmology GA 260FU UT WOS:000083939500011 PM 10586934 ER PT J AU Lu, M Amano, S Miyamoto, K Garland, R Keough, K Qin, WY Adamis, AP AF Lu, M Amano, S Miyamoto, K Garland, R Keough, K Qin, WY Adamis, AP TI Insulin-induced vascular endothelial growth factor expression in retina 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 09-14, 1999 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol, Natl Hlth Public Serv Award, Childern Hosp Res Fdn ID DEPENDENT DIABETES-MELLITUS; PROTEIN-KINASE-C; ELEVATED GLUCOSE-LEVELS; FACTOR MESSENGER-RNA; IRIS NEOVASCULARIZATION; PERMEABILITY FACTOR; NONHUMAN PRIMATE; GLYCEMIC CONTROL; IN-VITRO; RETINOPATHY AB PURPOSE. Clinical studies have demonstrated that intensive insulin therapy causes a transient worsening of retinopathy. The mechanisms underlying the initial insulin-induced deterioration of retinal status in patients with diabetes remain unknown. Vascular endothelial growth factor (VEGF) is known to be operative in the pathogenesis of diabetic retinopathy. The current study was conducted to characterize the effect of insulin on retinal VEGF gene expression in vitro and in vivo. METHODS. The effect of insulin on VEGF expression in vivo was examined by in situ hybridization studies of rat retinal VEGF transcripts. To examine the mechanisms by which insulin regulates VEGF expression, human retinal pigment epithelial (RPE) cells were exposed to insulin, and VEGF mRNA levels were quantified wish RNase protection assays (RPAs). Conditioned media from insulin-treated RPE cells were assayed for VEGF protein and capillary endothelial cell proliferation. The capacity of insulin to stimulate the VEGF promoter linked to a luciferase reporter gene was characterized in transient transfection assays. RESULTS. Insulin increased VEGF mRNA levels in the ganglion, inner nuclear, and RPE cell layers. In vitro, insulin increased VEGF mRNA levels in human RPE cells and enhanced VEGF promoter activity without affecting transcript stability. Insulin treatment also increased VEGF protein levels in conditioned RPE cell media in a dose-dependent manner with a median effective concentration of 5 nM. The insulin-conditioned RPE cell media stimulated capillary endothelial cell proliferation, an effect that was completely blocked by anti-VEGF neutralizing antibody. CONCLUSIONS. Insulin increases VEGF mRNA and secreted protein levels in RPE cells through enhanced transcription of the VEGF gene. Intensive insulin therapy may cause a transient worsening of retinopathy in patients with diabetes through increased retinal VEGF gene expression. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Childrens Hosp, Sch Med, Surg Res Lab, Boston, MA 02114 USA. Univ Tokyo, Sch Med, Dept Ophthalmol, Tokyo 113, Japan. RP Adamis, AP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. FU NEI NIH HHS [EY11622, EY12611] NR 50 TC 68 Z9 75 U1 1 U2 5 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 DEC PY 1999 VL 40 IS 13 BP 3281 EP 3286 PG 6 WC Ophthalmology SC Ophthalmology GA 260FU UT WOS:000083939500031 PM 10586954 ER PT J AU Gill, TJ Sledge, JB Orler, R Ganz, R AF Gill, TJ Sledge, JB Orler, R Ganz, R TI Lateral insufficiency fractures of the femur caused by osteopenia and varus angulation - A complication of total hip arthroplasty SO JOURNAL OF ARTHROPLASTY LA English DT Article DE osteopenia; femur fracture; arthroplasty; stress fracture; revision; complication AB Lateral femoral insufficiency fractures in total hip arthroplasty occur due to osteopenia and varus positioning of the femoral component, the femur itself, or both. The presentation of these fractures can be unclear but usually involves the insidious onset of unexplained thigh or groin pain. The patients are likely to have significant comorbidities as well. Characteristic radiographic findings may be present, depending on when the patient presents. The insufficiency fractures generally occur at the level of the femoral stem tip on the lateral cortex of the femur. If left untreated, pain and loss of function continue. Eventually an insufficiency fracture can progress to a displaced periprosthetic fracture. Nonsurgical treatment is not successful. Recommended treatment involves revision to a long-stem femoral component. The risk of postoperative complications is significant. C1 Massachusetts Gen Hosp, Dept Orthoped, Boston, MA 02114 USA. RP Gill, TJ (reprint author), Massachusetts Gen Hosp, Dept Orthoped, WACC-514,15 Parkman St, Boston, MA 02114 USA. NR 26 TC 21 Z9 22 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD DEC PY 1999 VL 14 IS 8 BP 982 EP 987 DI 10.1016/S0883-5403(99)90014-1 PG 6 WC Orthopedics SC Orthopedics GA 266FU UT WOS:000084290600015 PM 10614891 ER PT J AU Wrobel, C Schmidt, EV Polymenis, M AF Wrobel, C Schmidt, EV Polymenis, M TI CDC64 encodes cytoplasmic alanyl-tRNA synthetase, Ala1p, of Saccharomyces cerevisiae SO JOURNAL OF BACTERIOLOGY LA English DT Article ID TRANSFER-RNA-SYNTHETASE; TRANSLATIONAL CONTROL; CELL-DIVISION; YEAST; MUTATIONS; GENE; ARREST; GROWTH AB The cdc64-1 mutation causes G(1) arrest in Saccharomyces cerevisiae corresponding to a type II Start phenotype. We report that CDC64 encodes Ala1p, an alanyl-tRNA synthetase. Thus, cdc64-1 might affect charging of tRNA(Ala) and thereby initiation of cell division. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Tumor Biol,MGH Canc Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Serv Pediat, Boston, MA 02114 USA. RP Schmidt, EV (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Tumor Biol,MGH Canc Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [R01-CA69009, R01-CA63117, R01 CA063117, R01 CA069069] NR 17 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 1999 VL 181 IS 24 BP 7618 EP 7620 PG 3 WC Microbiology SC Microbiology GA 263QZ UT WOS:000084137900029 PM 10601222 ER PT J AU Czeisler, CA Brown, EN AF Czeisler, CA Brown, EN TI Commentary: Models of the effect of light on the human circadian system: Current state of the art SO JOURNAL OF BIOLOGICAL RHYTHMS LA English DT Editorial Material ID MORNING BRIGHT LIGHT; CORE BODY-TEMPERATURE; CONSTANT CONDITIONS; MELATONIN RHYTHM; PHASE-SHIFTS; YOUNG-ADULTS; PACEMAKER; EXPOSURE; SLEEP; ENTRAINMENT C1 Harvard Univ, Brigham & Womens Hosp,Sch Med,Dept Med, MIT Div Hlth Sci & Technol,Div Endocrinol, Circadian Neuroendocrine & Sleep Disorders Sect, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,MIT Div Hlth Sci & Technol, Stat Res Lab,Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Czeisler, CA (reprint author), Harvard Univ, Brigham & Womens Hosp,Sch Med,Dept Med, MIT Div Hlth Sci & Technol,Div Endocrinol, Circadian Neuroendocrine & Sleep Disorders Sect, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM53559] NR 72 TC 10 Z9 10 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0748-7304 J9 J BIOL RHYTHM JI J. Biol. Rhythms PD DEC PY 1999 VL 14 IS 6 BP 538 EP 543 DI 10.1177/074873099129000876 PG 6 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 270PL UT WOS:000084544600013 PM 10643751 ER PT J AU Brown, EN Luithardt, H AF Brown, EN Luithardt, H TI Statistical model building and model criticism for human circadian data SO JOURNAL OF BIOLOGICAL RHYTHMS LA English DT Article; Proceedings Paper CT Workshop on Biomathematical Models of Circadian Rhythmicity - Sleep Regulation and Neurobehavioral Function in Humans CY MAY 18-21, 1999 CL DEDHAM, MASSACHUSETTS SP Natl Space Biomed Res Inst, NASA Ames Res Ctr, Air Force Off Sci Res DE box iterative model-building paradigm; core temperature; direct problem; harmonic regression model; inverse problem; van der Pol equation ID PARAMETER AB Mathematical models have played an important role in the analysis of circadian systems. The models include simulation of differential equation systems to assess the dynamic properties of a circadian system and the use of statistical models, primarily harmonic regression methods, to assess the static properties of the system. The dynamical behaviors characterized by the simulation studies are the response of the circadian pacemaker to Light, its rate of decay to its limit cycle, and its response to the rest-activity cycle. The static properties are phase, amplitude, and period of the intrinsic oscillator. Formal statistical methods are not routinely employed in simulation studies, and therefore the uncertainty in inferences based on the differential equation models and their sensitivity to model specification and parameter estimation error cannot be evaluated. The harmonic regression models allow formal statistical analysis of static but not dynamical features of the circadian pacemaker. The authors present a paradigm for analyzing circadian data based on the Box iterative scheme for statistical model building. The paradigm unifies the differential equation-based simulations (direct problem) and the model fitting approach using harmonic regression techniques (inverse problem) under a single schema. The framework is illustrated with the analysis of a core-temperature data series collected under a forced desynchrony protocol. The Box iterative paradigm provides a framework for systematically constructing and analyzing models of circadian data. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Anesthesia & Crit Care, MIT Div Hlth Sci & Technol,Stat Res Lab, Boston, MA 02114 USA. RP Brown, EN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Anesthesia & Crit Care, MIT Div Hlth Sci & Technol,Stat Res Lab, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM53559] NR 15 TC 15 Z9 15 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0748-7304 J9 J BIOL RHYTHM JI J. Biol. Rhythms PD DEC PY 1999 VL 14 IS 6 BP 609 EP 616 DI 10.1177/074873099129000975 PG 8 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 270PL UT WOS:000084544600022 PM 10643759 ER PT J AU Dai, GH Gertler, JP Kamm, RD AF Dai, GH Gertler, JP Kamm, RD TI The effects of external compression on venous blood flow and tissue deformation in the lower leg SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article ID TOTAL HIP-REPLACEMENT; DEEP-VEIN THROMBOSIS; PNEUMATIC CALF COMPRESSION; HUMAN-ENDOTHELIAL-CELLS; PLASMINOGEN-ACTIVATOR; FIBRINOLYTIC-ACTIVITY; PREVENTION; THROMBOEMBOLISM; OPTIMIZATION; PROPHYLAXIS AB External pneumatic compression of the lower legs is effective as prophylaxis against deep vein thrombosis. In a typical application, inflatable cliffs are wrapped around the patient's legs and periodically inflated to pr-event stasis, accelerate venous blood flow, and enhance fibrinolysis. The purpose of this study was to examine the stress distribution within the tissues, and the corresponding venous blood flow and intravascular shear stress with different external compression modalities. A two-dimensional finite element analysis (FEA) was used to determine venous collapse as a function of internal (venous) pressure and the magnitude and spatial distribution of external (surface) pressure. Using the one-dimensional equations governing pow in a collapsible tube and the relations for venous collapse from the FEA, blood pow resulting from external compression was simulated. Tests were conducted to compare circumferentially symmetric (C) and asymmetric (A) compression and to examine distributions of pressure along the limb. Results show that A compression produces greater vessel collapse and generates larger blood flow velocities and shear stresses than C compression. The differences between axially uniform and graded-sequential compression are less marked than previously found, with uniform compression providing slightly greater peak pow velocities and shear stresses. The major advantage of graded-sequential compression is found at midcalf Strains at the lumenal border are approximately 20 percent at art external pressure of 50 mmHg (6650 Pa) with all compression modalities. C1 MIT, Ctr Biomed Engn, Cambridge, MA 02139 USA. MIT, Dept Engn Mech, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vasc Res Lab, Boston, MA 02114 USA. RP Dai, GH (reprint author), MIT, Ctr Biomed Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. OI Dai, Guohao/0000-0001-7346-2685 NR 29 TC 45 Z9 47 U1 0 U2 8 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD DEC PY 1999 VL 121 IS 6 BP 557 EP 564 DI 10.1115/1.2800853 PG 8 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 271KN UT WOS:000084592900001 PM 10633254 ER PT J AU Li, G Gil, J Kanamori, A Woo, SLY AF Li, G Gil, J Kanamori, A Woo, SLY TI A validated three-dimensional computational model of a human knee joint SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article ID ANTERIOR CRUCIATE LIGAMENT; IN-SITU FORCES; 3-DIMENSIONAL MODEL; MATHEMATICAL-MODEL; CONTRACTIONS AB This paper presents a three-dimensional finite element tibio-femoral joint model of a human knee that was validated using experimental data. The geometry, of the joint model was obtained from magnetic resonance (MR) images of a cadaveric knee specimen. The same specimen was biomechanically tested using a robotic/univevsal force-moment sensor (UFS) system and knee kinematic data under anterior-posterior tibial loads (up to 100 N) were obtained. In the finite element model (FEM), cartilage was modeled as an elastic material, ligaments were represented as nonlinear elastic springs, and menisci were simulated by equivalent-resistance springs. Reference lengths (zero-load lengths) of the ligaments and stiffness of the meniscus springs were estimated using an optimization procedure that involved the minimization of the differences between the kinematics predicted by the model and those obtained experimentally. The joint kinematics and in-situ forces in the ligaments in response to axial tibial moments of up to 10 Nm were calculated using the model and were compared with published experimental data on knee specimens. It was also demonstrated that the equivalent-resistance springs representing the menisci are important for accurate calculation of knee kinematics. Thus, the methodology developed in this study can be a valuable tool for further analysis of knee joint function and could serve as a step toward the development of more advanced computational knee models. C1 Univ Pittsburgh, Dept Orthopaed Surg, Musculoskeletal Res Ctr, Pittsburgh, PA 15213 USA. Harvard Univ, Sch Med, Orthoped Biomech Lab, MGH,BIDMC, Boston, MA 02215 USA. RP Li, G (reprint author), Univ Pittsburgh, Dept Orthopaed Surg, Musculoskeletal Res Ctr, Pittsburgh, PA 15213 USA. FU NIAMS NIH HHS [AR39683] NR 26 TC 139 Z9 146 U1 0 U2 14 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD DEC PY 1999 VL 121 IS 6 BP 657 EP 662 DI 10.1115/1.2800871 PG 6 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 271KN UT WOS:000084592900015 PM 10633268 ER PT J AU Swartz, MA Kaipainen, A Netti, PA Brekken, C Boucher, Y Grodzinsky, AJ Jain, RK AF Swartz, MA Kaipainen, A Netti, PA Brekken, C Boucher, Y Grodzinsky, AJ Jain, RK TI Mechanics of interstitial-lymphatic fluid transport: theoretical foundation and experimental validation SO JOURNAL OF BIOMECHANICS LA English DT Article DE tissue compliance; hydraulic conductivity; lymphatic conductance; poroelastic; edema ID SOLID TUMORS; FLOW; TISSUE; CARTILAGE AB Interstitial fluid movement is intrinsically linked to lymphatic drainage. However, their relationship is poorly understood. and associated pathologies are mostly untreatable. In this work we test the hypothesis that bulk tissue fluid movement can be evaluated in situ and described by a linear biphasic theory which integrates the regulatory function of the lymphatics with the mechanical stresses of the tissue. To accomplish this, we develop a novel experimental and theoretical model using the skin of the mouse tail. We then use the model to demonstrate how interstitial-lymphatic fluid movement depends on a balance between the elasticity, hydraulic conductivity, and lymphatic conductance as well as to demonstrate how chronic swelling (edema) alters the equipoise between tissue fluid balance parameters. Specifically, tissue fluid equilibrium is perturbed with a continuous interstitial infusion of saline into the tip of the tail. The resulting gradients in tissue stress are measured in terms of interstitial fluid pressure using a servo-null system. These measurements are then fit to the theory to provide in vivo estimates of the tissue hydraulic conductivity, elastic modulus, and overall resistance to lymphatic drainage. Additional experiments are performed on edematous tails to show that although chronic swelling causes an increase in the hydraulic conductivity, its greatly increased distensibility (due to matrix remodeling) dampens the driving forces for fluid movement and leads to fluid stagnation. This model is useful for examining potential treatments for edema and lymphatic disorders as well as substances which may alter tissue fluid balance and/or lymphatic drainage. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. MIT, Dept Elect Engn, Cambridge, MA 02139 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RI Swartz, Melody/B-7633-2009; Swartz, Melody/F-9563-2011; OI NETTI, PAOLO/0000-0002-2435-7181 FU NCI NIH HHS [CA-56591] NR 19 TC 63 Z9 70 U1 0 U2 15 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD DEC PY 1999 VL 32 IS 12 BP 1297 EP 1307 DI 10.1016/S0021-9290(99)00125-6 PG 11 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 254AW UT WOS:000083590200005 PM 10569708 ER PT J AU Bal, BS Maurer, T Harris, WH AF Bal, BS Maurer, T Harris, WH TI Revision of the acetabular component without cement after a previous acetabular reconstruction with use of a bulk femoral head graft in patients who had congenital dislocation or dysplasia - A follow-up note SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article AB Background: Revision of an acetabular component that has failed after a total hip arthroplasty in which a bulk femoral head autogenous graft or allograft was used as a structural graft for acetabular reconstruction is an uncommon but complex and challenging procedure. We previously reported the results for seventy hips at an average of 16.5 years after a total hip arthroplasty in which an acetabular reconstruction had been performed with a femoral head graft. In the present study, we evaluated a subset of nine hips from that series that had a subsequent revision of the acetabular component without cement. The purpose of the current study was to assess the usefulness of the bone graft in this revision, Methods: The nine patients (nine hips) were followed clinically and radiographically for an average of seventy-six months (range, sixty-one to 114 months) after the index revision. In six hips the autogenous femoral head graft previously had been bolted to the lateral side of the ilium, and in one hip the femoral head allograft had been affixed in this manner. In the two remaining hips, the allograft had been placed within the acetabulum, The hips were classified according to the extent of acetabular bone loss, with use of criteria described previously. Three hips had stage-I bone loss; four, stage-II; and two, stage-IIIB. A porous-coated hemispherical acetabular component was inserted without cement and fixed with screws in each hip. At least 70 percent of the porous coating was in contact with viable bone. Results: At the time of the latest follow-up after the index revision, all nine acetabular components were functioning well without loosening or osteolysis and none had been revised. The average Harris hip score was 77 points (range, 61 to 98 points) compared with 49 points (range, 27 to 96 points) preoperatively, One hip had had revision of the femoral stem, and another had had exchange of the acetabular liner because of recurrent dislocations. There was no additional resorption of the residual bulk graft that was in contact,vith the metal shell in any hip. Conclusions: In this small series of complex acetabular revisions, the healed bulk graft provided valuable additional bone stock for the support of an acetabular component that was inserted without cement, Insertion of the acetabular component into the available bone, which consisted in major part of host bone and in minor part of united revascularized bulk graft, resulted in a well functioning hip after an intermediate duration of follow-up. In all except two hips, the enlarged bone stock allowed insertion of a larger acetabular component than had been used previously. C1 Massachusetts Gen Hosp, Orthopaed Biomech Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Hip & Implant Unit, Boston, MA 02114 USA. RP Bal, BS (reprint author), Jackson Cty Orthopaed Inc, 801 NW St Marys Dr,Suite 101, Blue Springs, MO 64104 USA. OI Bal, B. Sonny/0000-0002-9615-8632 NR 5 TC 15 Z9 16 U1 0 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD DEC PY 1999 VL 81A IS 12 BP 1703 EP 1706 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 264WM UT WOS:000084206000007 PM 10608381 ER PT J AU Heckman, JD Ehler, W Brooks, BP Aufdemorte, TB Lohmann, CH Morgan, T Boyan, BD AF Heckman, JD Ehler, W Brooks, BP Aufdemorte, TB Lohmann, CH Morgan, T Boyan, BD TI Bone morphogenetic protein but not transforming growth factor-beta enhances bone formation in canine diaphyseal nonunions implanted with a biodegradable composite polymer SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID SKULL DEFECTS; CARTILAGE; TISSUE; REPAIR; CHROMATOGRAPHY; OSTEOGENESIS; INVITRO; MUSCLE; DOGS AB Background: The purpose of the present study was to create an effective bone-graft substitute for the treatment of a diaphyseal nonunion. Methods: A standardized nonunion was established in the midportion of the radial diaphysis in thirty mongrel dogs by creating a three-millimeter segmental bone defect (at least 2 percent of the total length of the bone). The nonunion was treated with implantation of a carrier comprised of poly(DL-lactic acid) and polyglycolic acid copolymer (50:50 polglactic acid-polyglycolic acid [PLG50]) containing canine purified bone morphogenetic protein (BMP) or recombinant human transforming growth factor-beta (TGF-beta 1), or both, or the carrier without BMP or TGF-beta 1, Five groups, consisting of sis dogs each, were treated with implantation of the carrier alone, implantation of the carrier with fifteen milligrams of BR IP, implantation of the carrier with 1.5 milligrams of BR IP, implantation of the carrier with fifteen milligrams of BMP and ten nanograms of TGF-beta 1, or implantation of the carrier,vith ten nanograms of TGF-beta 1, At twelve weeks after implantation, the radii were examined radiographically and the sites of nonunion were examined histomorphometrically. Results: We found that implantation of the polylactic acid-polyglycolic acid carrier alone or in combination with ten nanograms of TGF-beta 1 failed to induce significant radiographic or histomorphometric evidence of healing at the site of the nonunion. The radii treated with the carrier enriched,vith either 1.5 or fifteen milligrams of BMP showed significantly increased periosteal and endosteal bone formation on histomorphometric (p < 0.05) and radiographic (p < 0.02) analysis. Conclusions: Bone formation in a persistent osseous defect that is similar to an ununited diaphyseal fracture is increased when species-specific BMP incorporated into a polylactic acid-polyglycolic acid carrier is implanted at the site of the nonunion. TGF-beta 1 at a dose of ten nanograms per implant did not induce a similar degree of bone formation or potentiate the effect of BMP in this model. Clinical Relevance: The biodegradable implant containing BMP that was used in the present study to treat diaphyseal nonunion is an effective bone-graft substitute. C1 Univ Texas, Hlth Sci Ctr, Dept Orthopaed, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Adm Hosp, San Antonio, TX 78284 USA. Wilford Hall USAF Med Ctr, Lackland AFB, TX USA. RP Heckman, JD (reprint author), Univ Texas, Hlth Sci Ctr, Dept Orthopaed, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIDCR NIH HHS [DE08603] NR 60 TC 77 Z9 87 U1 0 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD DEC PY 1999 VL 81A IS 12 BP 1717 EP 1729 PG 13 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 264WM UT WOS:000084206000009 PM 10608383 ER PT J AU Mueller, SM Mizuno, S Gerstenfeld, LC Glowacki, J AF Mueller, SM Mizuno, S Gerstenfeld, LC Glowacki, J TI Medium perfusion enhances osteogenesis by murine osteosarcoma cells in three-dimensional collagen sponges SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the Orthopaedic-Research-Society CY FEB, 1999 CL ANATHEIM, CALIFORNIA SP Orthopaed Res Soc ID HUMAN DERMAL FIBROBLASTS; OSTEOBLAST-LIKE CELLS; MARROW STROMAL CELLS; BONE-FORMATION; IN-VITRO; 3-DIMENSIONAL CULTURE; DEMINERALIZED BONE; MATRIX; GENE; MINERALIZATION AB In this study, we examined in vitro histogenesis by murine K8 osteosarcoma cells maintained in three-dimensional (3D) collagen sponges. We tested the hypothesis that perfusion of medium enhances cell viability and their biosynthetic activity as assessed by expression of the osteoblastic phenotype and mineral deposition. At intervals, samples were harvested and analyzed histologically, biochemically, and by Northern hybridization for type I collagen, osteopontin (OPN), osteocalcin (OC), and core binding factor alpha 1 (Cbfa1), Histologic evaluation showed greater viability, more alkaline phosphatase (ALP)-positive cells, and more mineralized tissue in the perfused sponges after 21 days. Immunohistological assessment of proliferating cell nuclear antigen revealed 5-fold more proliferating cells in the perfused sponges compared with the controls (p = 0.0201), There was 3-fold more ALP activity in the perfused sponges than the controls at 6 days and 14 days (p = 0.0053). The perfused sponges contained twice the DNA and eight times more calcium than the nonperfused controls after 21 days (p < 0.0001 for both). Northern hybridization analysis revealed more mRNA for collagen type I (2-fold) and 50% more for OC at 14 days and 21 days, whereas OPN and Cbfa1 mRNA expression remained unaffected by the medium perfusion. These results show that medium perfusion had beneficial effects on the proliferation and biosynthetic activity of this osteosarcoma cell line. This system mimics the 3D geometry of bone tissue and has the potential for revealing mechanisms of regulation of osteogenesis. C1 Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Med Ctr, Dept Orthoped Surg, Musculoskeletal Res Lab, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Skeletal Biol Res Ctr, Boston, MA USA. RP Glowacki, J (reprint author), Brigham & Womens Hosp, Dept Orthoped Surg, 75 Francis St, Boston, MA 02115 USA. OI /0000-0002-0477-1211 FU NIAMS NIH HHS [AR43434] NR 44 TC 74 Z9 76 U1 1 U2 3 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD DEC PY 1999 VL 14 IS 12 BP 2118 EP 2126 DI 10.1359/jbmr.1999.14.12.2118 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 270DT UT WOS:000084520700016 PM 10620071 ER PT J AU Chen, YM Lee, WH Chew, HK AF Chen, YM Lee, WH Chew, HK TI Emerging roles of BRCA1 in transcriptional regulation and DNA repair SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Review ID CANCER SUSCEPTIBILITY GENE; EARLY EMBRYONIC LETHALITY; POLYMERASE-II HOLOENZYME; C-TERMINAL REGION; BREAST-CANCER; CELL-CYCLE; FAMILIAL BREAST; OVARIAN-CANCER; PROTEIN; DAMAGE AB BRCA1 was the first breast cancer susceptibility gene to be identified and cloned. In individuals from high-risk families, mutations in BRCA1 increase the lifetime risk of developing breast cancer eight to tenfold, compared to the general population. How the BRCA1 protein product normally functions to suppress tumor formation and how defects in the gene can ultimately lead to breast cancer have been the focus of intense scrutiny by the scientific and medical communities. BRCA1 has intrinsic transactivation activity and is able to activate the p21 promoter. In addition, BRCA1 is linked to a number of genes involved in transcriptional regulation, including CtlP, c-Myc, the RNA holoenzyme complex, and the histone deacetylase complex. Moreover, BRCA1 is essential for cellular response to DNA damage repair. Inactivation of Brca1 in mouse embryonic stem and fibroblast cells results in increased cell sensitivity to DNA-damaging agents. In human cells, BRCA1 binds to both Rad50 and Rad51 and colocalizes with these proteins at repair foci. Part of BRCA1's response to DNA damage may in fact be corroborated through transcriptional regulation. The expression of GADD45, a DNA damage-responsive gene, is increased immediately after induction of BRCA1. Recently, BRCA1 was shown to repress estradiol (E2)-responsive ER-alpha-mediated transcriptional activity, potentially linking the multiple functions of BRCA1 to specific tissue targets. These recent developments in BRCA1 function are an encouraging step toward understanding the role of BRCA1 in breast cancer formation. (C) 1999 Wiley-Liss, Inc. C1 Univ Texas, Hlth Sci Ctr, Dept Internal Med, Div Med Oncol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Mol Med, Inst Biotechnol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Div Med Res, San Antonio, TX USA. RP Chew, HK (reprint author), Univ Texas, Hlth Sci Ctr, Dept Internal Med, Div Med Oncol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 49 TC 54 Z9 56 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD DEC PY 1999 VL 181 IS 3 BP 385 EP 392 DI 10.1002/(SICI)1097-4652(199912)181:3<385::AID-JCP2>3.0.CO;2-4 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 252UT UT WOS:000083521200002 PM 10528224 ER PT J AU Kitten, AM Kreisberg, JI Olson, MS AF Kitten, AM Kreisberg, JI Olson, MS TI Expression of osteogenic protein-1 mRNA in cultured kidney cells SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID BONE MORPHOGENETIC PROTEIN-7; MESSENGER-RNA; I RECEPTORS; RAT; ACTIVIN; REGULATORS; INDUCTION; INJURY; BMP-7; EYE AB Osteogenic protein-1 (OP-1 or BMP-7) is a multifunctional cytokine that regulates the development of several tissues during embryogenesis, including the skeleton, eye, and kidney. In postnatal life, OP-1 expression is most abundant in the kidney, although the cellular localization of this expression has not been described. In this study, we utilized a cell culture approach to localize OP-1 mRNA expression in various renal cell types and to determine potential target cells for OP-1 effects. OP-1 mRNA expression was demonstrated in several glomerular cell types, such as mesangial, epithelial, and endothelial cells. Distal tubule MDCK cells also expressed OP-1 mRNA but human proximal tubule HK-2 cells did not. Multiple OP-1 transcripts, which ranged in size from 1.6 to 3.8 kb, were observed in both glomerular and tubule cells. Interestingly, the pattern of expression varied among the different cell types, suggesting cell-specific expression of OP-1 mRNA. Analysis of OP-1 receptor expression revealed transcripts for BMP receptors type IA and IB in HK-2 cells and transcripts for BMPR-IA and ALK-2 in mesangial cells. Treatment of HK-2 cells with OP-1 (300 ng/ml) for 24-48 hr increased cellular proliferation whereas treatment of cells with transforming growth factor-beta had no effect. Mesangial cell proliferation was not affected by OP-1. The results suggest that OP-1 is produced in the renal glomerulus and then travels to the proximal tubule to regulate the proliferation of cells in this region of the nephron. (C) 1999 Wiley-Liss, Inc. C1 Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, Res & Dev Serv, San Antonio, TX 78284 USA. RP Olson, MS (reprint author), Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA. OI Kitten, Allison/0000-0002-6047-1379 FU NIA NIH HHS [AG-14384]; NIDDK NIH HHS [DK-19473] NR 33 TC 24 Z9 29 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD DEC PY 1999 VL 181 IS 3 BP 410 EP 415 DI 10.1002/(SICI)1097-4652(199912)181:3<410::AID-JCP4>3.0.CO;2-H PG 6 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 252UT UT WOS:000083521200004 PM 10528226 ER PT J AU Farokhzad, OC Sagar, GDV Mun, EC Sicklick, JK Lotz, M Smith, JA Song, JKC O'Brien, TC Sharma, CP Kinane, TB Hodin, RA Matthews, JB AF Farokhzad, OC Sagar, GDV Mun, EC Sicklick, JK Lotz, M Smith, JA Song, JKC O'Brien, TC Sharma, CP Kinane, TB Hodin, RA Matthews, JB TI Protein kinase C activation downregulates the expression and function of the basolateral Na+/K+/2Cl(-) cotransporter SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID INTESTINAL EPITHELIAL-CELLS; PHORBOL ESTER; NA-K-2CL COTRANSPORTER; BUMETANIDE BINDING; DOWN-REGULATION; HUMAN COLON; CHLORIDE SECRETION; MOLECULAR-CLONING; MESSENGER-RNA; T84 CELLS AB The basolateral Na+/K+/2Cl(-) cotransporter (NKCC1) has been shown to be an independent regulatory site for electrogenic Cl- secretion. The proinflammatory phorbol ester, phorbol 12-myristate 13-acetate (PMA), which activates protein kinase C (PKC), inhibits basal and cyclic adenosine monophosphate (cAMP)-stimulated NKCC1 activity in T84 intestinal epithelial cells and decreases the steady state levels of NKCC1 mRNA in a time- and dose-dependent manner. The levels of NKCC1 protein also fall in accordance with the NKCC1 mRNA transcript and these levels are unaffected by 4 alpha-phorbol, which does not activate PKC. Inhibition of maximal (cAMP-stimulated) NKCC1 functional activity by PMA was first detected by 1 h, whereas decreases in the steady stale levels of NKCC1 mRNA were not detectable until 4 h. NKCC1 mRNA expression recovers toward control levels with extended treatment of cells with PMA suggesting that the PMA effects on NKCC1 expression are mediated through activation of PKC. Although NKCC1 mRNA and protein levels return to control values after extended PMA exposure, NKCC1 functional activity does not recover. Immunofluorescence imaging suggest that the absence of functional recovery is due to failure of newly synthesized NKKC1 protein to reach the cell surface. We conclude that NKCC1 has the capacity to be regulated at the level of de novo expression by PKC, although decreased NKCC1 expression alone cannot account for either early or late loss of NKCC1 function. (C) 1999 Wiley-Liss, Inc. C1 Beth Israel Deaconess Med Ctr, Dept Surg, Div Gen & Gastrointestinal Surg, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med, Renal Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Matthews, JB (reprint author), Beth Israel Deaconess Med Ctr, Dept Surg, Div Gen & Gastrointestinal Surg, East Campus,330 Brookline Ave, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK48010] NR 53 TC 19 Z9 19 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD DEC PY 1999 VL 181 IS 3 BP 489 EP 498 DI 10.1002/(SICI)1097-4652(199912)181:3<489::AID-JCP13>3.3.CO;2-Z PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 252UT UT WOS:000083521200013 PM 10528235 ER PT J AU Meng, W Wang, XY Asahi, M Kano, T Asahi, K Ackerman, RH Lo, EH AF Meng, W Wang, XY Asahi, M Kano, T Asahi, K Ackerman, RH Lo, EH TI Effects of tissue type plasminogen activator in embolic versus mechanical models of focal cerebral ischemia in rats SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE cerebral ischemia; excitotoxicity; hemorrhage; neuroprotection; reperfusion injury; thrombolysis ID ARTERY OCCLUSION; NEURONAL DEATH; HEMODYNAMIC PENUMBRA; MAGNETIC-RESONANCE; BLOOD; DEGENERATION; REPERFUSION; HIPPOCAMPUS; DEFICIENT; STROKE AB Tissue type plasminogen activator (tPA) can be effective therapy for embolic stroke by restoring cerebral perfusion. However, a recent experimental study showed that tPA increased infarct size in a mouse model of transient focal ischemia, suggesting a possible adverse effect of tPA on ischemic tissue per se. In this report. the effects of tPA in two rat models of cerebral ischemia were compared. In experiment 1, rats were subjected to focal ischemia via injection of autologous clots into the middle cerebral artery territory. Two hours after clot injection, rats were treated with 10 mg/kg tPA or normal saline. Perfusion-sensitive computed tomography scanning showed that tPA restored cerebral perfusion in this thromboembolic model. Treatment with tPA significantly reduced ischemic lesion volumes measured at 24 hours by >60%. In experiment 2, three groups of rats were subjected to focal ischemia via a mechanical approach in which a silicon-coated filament was used intraluminally to occlude the origin of the middle cerebral artery. In two groups, the filament was withdrawn after 2 hours to allow for reperfusion, and then rats were randomly treated with 10 mg/kg tPA or normal saline. in the third group. rats were not treated and the filament was not withdrawn so that permanent focal ischemia was present. In this experiment, tPA did not significantly alter lesion volumes after 2 hours of transient focal ischemia. In contrast, permanent ischemia significantly increased lesion volumes by 55% compared with transient ischemia. These results indicate that in these rat models of focal cerebral ischemia, tPA did not have detectable negative effects. Other potentially negative effects of tPA may be dependent on choice of animal species and model systems. C1 Harvard Univ, Sch Med, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Neuroprotect Res Lab, Boston, MA USA. Harvard Univ, Sch Med, Neurovasc Lab, Dept Neurol, Boston, MA USA. Harvard Univ, Sch Med, Neurovasc Lab, Dept Radiol, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Nihon Univ, Sch Med, Dept Neurosurg, Tokyo, Japan. RP Lo, EH (reprint author), Harvard Univ, Sch Med, Neuroprotect Res Lab, Dept Neurol, MGH E Bldg 149,Rm 2322, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS37074, NS32806] NR 31 TC 49 Z9 51 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD DEC PY 1999 VL 19 IS 12 BP 1316 EP 1321 PG 6 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 276NL UT WOS:000084884200004 PM 10598935 ER PT J AU Burke, JF AF Burke, JF TI New advances in preventing and treating serious surgical infection: Introduction SO JOURNAL OF CHEMOTHERAPY LA English DT Editorial Material ID VIRULENCE FACTORS; TRAUMA C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Trauma Serv, Boston, MA 02114 USA. RP Burke, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Trauma Serv, 55 Fruit St,Warren 941, Boston, MA 02114 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU E I F T SRL PI FLORENCE PA VIA XX SETTEMBRE 102, 50129 FLORENCE, ITALY SN 1120-009X J9 J CHEMOTHERAPY JI J. Chemother. PD DEC PY 1999 VL 11 IS 6 BP 423 EP 425 PG 3 WC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy SC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy GA 270DX UT WOS:000084521100002 PM 10678783 ER PT J AU Biederman, J Spencer, T AF Biederman, J Spencer, T TI Depressive disorders in childhood and adolescence: A clinical perspective SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Editorial Material ID MAJOR DEPRESSION; PSYCHIATRIC-DISORDERS; CO-MORBIDITY; CHILDREN; COMORBIDITY; RISK; RELATIVES; PROBANDS; ADHD C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, WACC 725,15 Parkman St, Boston, MA 02114 USA. NR 31 TC 11 Z9 11 U1 1 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD WIN PY 1999 VL 9 IS 4 BP 233 EP 237 DI 10.1089/cap.1999.9.233 PG 5 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 267WF UT WOS:000084381700001 PM 10630452 ER PT J AU Biederman, J Mick, E Prince, J Bostic, JQ Wilens, TE Spencer, T Wozniak, J Faraone, SV AF Biederman, J Mick, E Prince, J Bostic, JQ Wilens, TE Spencer, T Wozniak, J Faraone, SV TI Systematic chart review of the pharmacologic treatment of comorbid attention deficit hyperactivity disorder in youth with bipolar disorder SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID JUVENILE MANIA; DOUBLE-BLIND; ONSET MANIA; CHILDREN; ADHD; METHYLPHENIDATE; DESIPRAMINE; SYMPTOMS; PLACEBO; MODELS AB The objective of this study was to evaluate pharmacological approaches for attention deficit hyperactivity disorder (ADHD) in children with bipolar disorder and comorbid ADHD. The medical charts of 38 patients with diagnoses of both Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised ADHD and bipolar disorder were reviewed over multiple visits to assess improvement and prescription patterns. Logistic regression was used to model the probability of improvement at each visit, and robust standard errors were estimated in order to account for correlation among individuals using Huber's correction for clustered data. The proportion of visits at which ADHD symptoms were rated as improved following initial improvement in manic symptoms was 7.5 times greater than before initial improvement of manic symptoms. The recurrence of manic symptoms following their initial stabilization significantly inhibited ADHD response to medication. Although tricyclic antidepressants (TCAs) significantly increased the probability of ADHD improvement following mood stabilization, there was also a significant association between treatment with TCAs and relapse of manic symptoms. Our results support the hypothesis that mood stabilization is a prerequisite for the successful pharmacologic treatment of ADHD in children with both ADHD and manic symptoms. Although TCAs can be helpful in the management of ADHD children with manic symptoms, these drugs should be used with caution since they can also have a destabilizing effect on manic symptoms. C1 Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Commonwealth Res Ctr, Boston, MA USA. RP Biederman, J (reprint author), Pediat Psychopharmacol Unit, ACC 725,15 Parkman St, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 NR 24 TC 74 Z9 76 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD WIN PY 1999 VL 9 IS 4 BP 247 EP 256 DI 10.1089/cap.1999.9.247 PG 10 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 267WF UT WOS:000084381700003 PM 10630454 ER PT J AU Palmert, MR Mansfield, MJ Crowley, WF Crigler, JF Crawford, JD Boepple, PA AF Palmert, MR Mansfield, MJ Crowley, WF Crigler, JF Crawford, JD Boepple, PA TI Is obesity an outcome of gonadotropin-releasing hormone agonist administration? Analysis of growth and body composition in 110 patients with central precocious puberty SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID X-RAY ABSORPTIOMETRY; LONG-TERM TREATMENT; MASS INDEX; FINAL HEIGHT; ACTING ANALOG; SOMATOMEDIN-C; ADULT HEIGHT; SKELETAL MATURATION; EXPERT COMMITTEE; FOLLOW-UP AB Concern has been raised that children with central precocious puberty (CPP) are prone to the development of obesity. Here we report longitudinal height, weight, and body mass index (BMI)) data from 96 girls and 14 boys with CPP before, during and after GnRH agonist (GnRHa) administration. Skinfold thickness (n = 46) and percent body fat by dual energy x-ray absorptiometry (n = 21) were determined in subsets for more accurate assessment of body composition and to validate the use of the BMI so score as an index of body fatness in our subjects. Before the initiation of therapy (PRE), the girls with CPP had a mean BMI SD score for chronological age (CA) of 1.1 +/- 0.1 and for bone age (BA) of 0.1 +/- 0.1. By the end of the study, 12-24 months after the discontinuation of GnRHa, the mean BMT so score was 0.9 +/- 0.1 for CA and 0.6 +/- 0.1 for BA. At the visit when GnRHa was discontinued, 41% and 22% of the girls had a BMT so score for GA more than the 85th and 95th percentiles, respectively, indicating that obesity was present at a high rate among our subjects; the BMI so score for CA at the PRE visit was its strongest predictor. Indeed, 86% of the girls with BMI so store for CA shove the 85th percentile when GnRHa was discontinued also had BMI so score for CA above the 85th percentile at the PRE visit. The proportion of boys with elevated BMI so score for CA was also high. Fifty-four percent and 31% of the so scores were greater than the 85th and 95th percentiles after 36 months of GnRHa therapy; the BMI sn score for CA PRE had been above the 85th percentile in 71% of these overweight subjects. Obesity occurs at a high rate among children with CPP, hut does not appear to be related to long term pituitary-gonadal suppression induced by GnRHa administration. Children with CPP should have a baseline BMI so score calculated, and those at risk for obesity should be counseled appropriately. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. Harvard Mit Div Hlth Sci & Technol, Beth Israel Deaconess Med Ctr, Clin Investigator Training Program, Pfizer Inc, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Div Adolescent Med, Boston, MA 02115 USA. RP Boepple, PA (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Bartlett Hall Extens 5,Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [RR-01066, RR-02172]; NICHD NIH HHS [HD-18169] NR 55 TC 61 Z9 69 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1999 VL 84 IS 12 BP 4480 EP 4488 DI 10.1210/jc.84.12.4480 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 263PH UT WOS:000084134100029 PM 10599706 ER PT J AU Soyka, LA Grinspoon, S Levitsky, LL Herzog, DB Klibanski, A AF Soyka, LA Grinspoon, S Levitsky, LL Herzog, DB Klibanski, A TI Tbe effects of anorexia nervosa on bone metabolism in female adolescents SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID X-RAY ABSORPTIOMETRY; GROWTH-HORMONE-SECRETION; SOFT-TISSUE COMPOSITION; MINERAL DENSITY; BODY-COMPOSITION; CALCIUM SUPPLEMENTATION; BIOCHEMICAL MARKERS; HEALTHY-CHILDREN; MENSTRUAL-CYCLE; FACTOR-I AB Osteopenia is a frequent, often persistent, complication of anorexia nervosa (AN) in adolescent girls and occurs during a critical time in bone development. Little is known about bone metabolism in this patient population. Therefore, we measured bone density (BMD) and body composition by dual energy x-ray absorptiometry, nutritional status, bane turnover, calcium; and hormonal status in 19 adolescent girls with AN (mean +/- SEM, 16.0 +/- 0.4 yr) and 19 bone age-matched controls. The mean duration of AN was 19 +/- 5 months. Spinal (L1-L4) osteopenia was common in AN. Lumbar anterioposterior BMD was more than 1 sn below the mean in 42% of patients, and lateral spine BMD was more than 1 SD below in 63% of patients compared with controls. Lean body mass significantly predicted lumbar bone mineral content (r = 0.75; P < 0.0001) in controls only. In AN, duration of illness was the most significant predictor of spinal BMD (lumbar: r = -0.44; P = 0.06; lateral: r = -0.59; P = 0.008). AN adolescents with mature BA (15 yr and greater) were hypogonadal [estradiol, 16.2 +/- 1.9 vs. 23.3 +/- 1.6 pg/mL (P = 0.01); free testosterone, 0.70 +/- 0.17 us. 1.36 +/- 0.14 pg/mL (P = 0.01)1 although dehydroepiandrosterone sulfate and urinary free cortisol levels did not differ. Leptin levels were reduced in AN (2.9 +/- 2.1 vs. 16.5 +/- 1.8 ng/mL; P < 0.0001). Insulin like growth factor I (IGF-I) was reduced in AN to 50% of control levels (219 +/- 41 vs. 511 +/- 35 ng/mL; P < 0.0001) and correlated with all measures of nutritional status, particularly leptin (r = 0.80; P < 0.0001). Surrogate markers of bone formation, serum osteocalcin (OC) and bone-specific alkaline phosphatase (BSAP), were significantly (P = 0.02) reduced in AN vs. controls (OC, 39.1 r 6.4 vs. 59.2 +/- 5.2 ng/mL; BSAP, 27.9 +/- 4.0 vs. 40.6 +/- 3.4 U/L). The majority of the variation in bone formation in AN was due to IGF-I levels (OC: r(2) = 0.72: P = 0.002; BSAP: r(2) = 0.53; P = 0.01) in stepwise regression analyses. Bone resorption was comparable in patients and controls. These data demonstrate that bone formation is reduced and uncoupled to bone resorption in mature adolescents with AN in association with low bone density. Lean body mass was a significant predictor of BMD in controls, but not AN patients. The major correlate of bone formation in AN was the nutritionally dependent bone trophic factor, IGF-I. Reduced IGF-I during the critical period of bone mineral accumulation may be an important factor in the development of osteopenia in adolescents with AN. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Eating Disorders Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR-01066]; NIDDK NIH HHS [R01-DK-52625]; PHS HHS [R01-3833] NR 48 TC 199 Z9 205 U1 1 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1999 VL 84 IS 12 BP 4489 EP 4496 DI 10.1210/jc.84.12.4489 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 263PH UT WOS:000084134100030 PM 10599707 ER PT J AU Achermann, JC Gu, WX Kotlar, TJ Meeks, JJ Sabacan, LP Seminara, SB Habiby, RL Hindmarsh, PC Bick, DP Sherins, RJ Crowley, WF Layman, LC Jameson, JL AF Achermann, JC Gu, WX Kotlar, TJ Meeks, JJ Sabacan, LP Seminara, SB Habiby, RL Hindmarsh, PC Bick, DP Sherins, RJ Crowley, WF Layman, LC Jameson, JL TI Mutational analysis of DAX1 in patients with hypogonadotropic hypogonadism or pubertal delay SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ADRENAL HYPOPLASIA CONGENITA; PITUITARY-GONADAL AXIS; HORMONE DEFICIENCY; GENE-MUTATIONS; KALLMANNS-SYNDROME; JAPANESE PATIENTS; RECEPTOR; HETEROGENEITY; INFERTILITY; EXPRESSION AB Although delayed puberty is relatively common and often familial, its molecular and pathophysiologic basis is poorly understood. In contrast, the molecular mechanisms underlying some forms of hypogonadotropic hypogonadism (HH) are clearer, following the description of mutations in the genes KAL, GNRHR, and PROP1. Mutations in another gene, DAX1 (AHC), cause X-linked adrenal hypoplasia congenita and HH. Affected boys usually present with primary adrenal failure in infancy or childhood and HH at the expected time of puberty. DAX1 mutations have also been reported to occur with a wider spectrum of clinical presentations. These cases include female carriers of DAX1 mutations with marked pubertal delay and a male with incomplete BH and mild adrenal insufficiency in adulthood. Given this emerging phenotypic spectrum of clinical presentation in men and women with DAX1 mutations, we hypothesized that DAX1 might be a candidate gene for mutation in patients with idiopathic sporadic or familial HH or constitutional delay of puberty. Direct sequencing of DAX1 was performed in 106 patients, including 85 (80 men and 5 women) with sporadic HH or constitutional delay of puberty and patients from 21 kindreds with familial forms of these disorders. No DAX1 mutations were found in these groups of patients, although silent single nucleotide polymorphisms were identified (T114C, G498A). This study suggests that mutations in DAX1 are unlikely to be a common cause of HH or pubertal delay in the absence of a concomitant history of adrenal insufficiency. C1 Northwestern Univ, Sch Med, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. UCL, London Ctr Paediat Endocrinol, London W1N 8AA, England. Genet & IVF Inst, Fairfax, VA 22031 USA. Univ Chicago, Sect Reprod Endocrinol & Infertil, Chicago, IL 60637 USA. RP Jameson, JL (reprint author), Northwestern Univ, Sch Med, Div Endocrinol Metab & Mol Med, 303 E Chicago Ave,Tarry Bldg 15-709, Chicago, IL 60611 USA. RI Hindmarsh, Peter/C-4964-2008; Achermann, John/C-5476-2008; OI Achermann, John/0000-0001-8787-6272; Jameson, James/0000-0001-9538-4059 FU NCRR NIH HHS [MO1-RR-00048]; NICHD NIH HHS [P01-HD-21921, R01 HD015788, U54 HD028138, U54 HD029164, U54-HD-29164] NR 45 TC 49 Z9 51 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1999 VL 84 IS 12 BP 4497 EP 4500 DI 10.1210/jc.84.12.4497 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 263PH UT WOS:000084134100031 PM 10599708 ER PT J AU Seminara, SB Achermann, JC Genel, M Jameson, JL Crowley, WF AF Seminara, SB Achermann, JC Genel, M Jameson, JL Crowley, WF TI X-linked adrenal hypoplasia congenita: A mutation in DAX1 expands the phenotypic spectrum in males and females SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; ORNITHINE TRANSCARBAMYLASE DEFICIENCY; DUCHENNE MUSCULAR-DYSTROPHY; HYPOGONADOTROPIC HYPOGONADISM; HEMOPHILIA-B; GENE; CARRIER; MEN; TESTOSTERONE; INACTIVATION AB X-linked adrenal hypoplasia congenita (AHC) is a disorder associated with primary adrenal insufficiency and hypogonadotropic hypogonadism (HH). The gene responsible for X-linked AHC, DAX1, encodes a member of the nuclear hormone receptor superfamily. We studied an extended kindred with AHC and HH in which two males (the proband and his nephew) were affected with a nucleotide deletion (501delA). The proband's mother, sister, and niece were heterozygous for this frameshift mutation. At age 27 yr, after 7 yr of low dose hCG therapy, the proband underwent a testicular biopsy revealing rare spermatogonia and Leydig cell hyperplasia. Despite steadily progressive doses of hCG and Pergonal administered over a 3-yr period, the proband remained azoospermic. The proband's mother, sister (obligate carrier), and niece all had a history of delayed puberty, with menarche occurring at ages 17-18 yr. Baseline patterns of pulsatile gonadotropin secretion and gonad otropin responsiveness to exogenous pulsatile GnRH were examined in the affected males. LH, FSK, and free alpha-subunit were determined during 12.5-24 h of frequent blood sampling (every 10 min). Both patients then received pulsatile GnRH (25 ng/kg) sc every 2 h for 6-7 days. Gonadotropin responses to a single GnRH pulse iv were monitored daily to assess the pituitary responsiveness to exogenous GnRH. In the proband, FSH and LH levels demonstrated a subtle, but significant, response to GnRH over the week of pulsatile GnRH therapy. Free alpha-subunit levels demonstrated an erratic pattern of secretion at baseline and no significant response to pulsatile GnRH. We conclude that 1) affected males with AHC/HH may have an intrinsic defect in spermatogenesis that is not responsive to gonadotropin therapy; 2) female carriers of DAX1 mutations may express the phenotype of delayed puberty; and 3) although affected individuals display minimal responses to pulsatile GnRH, as observed in other AHC kindreds, subtle differences in gonadotropin patterns may nevertheless exist between affected individuals within a kindred. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Northwestern Univ, Div Endocrinol Metab & Mol Med, Sch Med, Chicago, IL 60611 USA. Yale Univ, Sch Med, Sect Pediat Endocrinol, New Haven, CT 06520 USA. RP Seminara, SB (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Bartlett Hall Extens 505,Fruit St, Boston, MA 02114 USA. EM seminara.stephanie@mgh.harvard.edu RI Achermann, John/C-5476-2008; OI Achermann, John/0000-0001-8787-6272; Jameson, James/0000-0001-9538-4059 FU NICHD NIH HHS [U54 HD028138, P30-HD-28138, R01 HD015788, U54 HD029164, U54-HD-29164] NR 36 TC 119 Z9 126 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1999 VL 84 IS 12 BP 4501 EP 4509 DI 10.1210/jc.84.12.4501 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 263PH UT WOS:000084134100032 PM 10599709 ER PT J AU Zhang, X Danila, DC Katai, M Swearingen, B Klibanski, A AF Zhang, X Danila, DC Katai, M Swearingen, B Klibanski, A TI Expression of prolactin-releasing peptide and its receptor messenger ribonucleic acid in normal human pituitary and pituitary adenomas SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HORMONE RECEPTOR; HYPOGONADOTROPIC HYPOGONADISM; ACTIVIN; GENE; MUTATIONS; INHIBIN; DISEASE AB The recently identified PRL-releasing peptide (PrRP) is the first hypothalamic peptide hormone that specifically stimulates PRL production from the pituitary gland. Similar to other hypothalamic regulatory hormones, it acts through its specific seven-transmembrane domain, G protein-coupled receptor. Using RT-PCR, we examined messenger ribonucleic acid (mRNA) expression of PrRP and its receptor in normal human pituitary tissue and in pituitary tumors. PrRP mRNA was expressed in all five normal pituitary glands examined In contrast, PrRP mRNA was detected in only 5 of 11 of the human prolactinomas. All 5 prolactinomas expressing PrRP were responsive to dopamine agonist treatment, whereas PrRP-negative prolactinomas were non- or partially responsive. PrRP mRNA was also detected in 6 of 18 GH-secreting tumors and 5 of 10 clinically nonfunctioning tumors investigated. PrRP receptor mRNA was found in all the normal and neoplastic human pituitary samples studied. The production of PrRP and its receptor by normal and neoplastic pituitary tissue raises the question of whether it may regulate PRL production in an autocrine/paracrine manner in pituitary tissue. Further investigation of PrRP and its receptor expression and function will be needed to clarify its potential role in regulating PRL secretion in normal human lactotrophs and pituitary tumors. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Med, BUL 457B,55 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [R01-DK-40947]; NIMH NIH HHS [MH/NS 31862] NR 21 TC 22 Z9 24 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 DEC PY 1999 VL 84 IS 12 BP 4652 EP 4655 DI 10.1210/jc.84.12.4652 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 263PH UT WOS:000084134100059 PM 10599733 ER PT J AU Ahmed, SF Marsh, DJ Weremowicz, S Morton, CC Williams, DM Eng, C AF Ahmed, SF Marsh, DJ Weremowicz, S Morton, CC Williams, DM Eng, C TI Balanced translocation of 10q and 13q, including the PTEN gene, in a boy with a human chorionic gonadotropin-secreting tumor and the Bannayan-Riley-Ruvalcaba syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID COWDEN-DISEASE; GERMLINE MUTATIONS; JUVENILE POLYPOSIS; ZONANA-SYNDROME; CELL-SURVIVAL; SUPPRESSOR; PHOSPHATASE; DELETION; PTEN/MMAC1; PHENOTYPE C1 Univ Cambridge, Dept Pediat, Cambridge CB2 2QQ, England. Univ Cambridge, CRC, Human Canc Genet Res Grp, Cambridge CB2 2QQ, England. Ohio State Univ, Ctr Comprehens Canc, Clin Canc Genet Program, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Charles A Dana Human Canc Genet Unit, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Cytogenet Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ahmed, SF (reprint author), Univ Cambridge, Addenbrookes Hosp, Sch Clin, Dept Pediat, Box 116,Hills Rd, Cambridge CB2 2QQ, England. EM sfa21@cam.ac.uk RI Marsh, Deborah/I-1491-2014; OI Marsh, Deborah/0000-0001-5899-4931; Eng, Charis/0000-0002-3693-5145 NR 43 TC 9 Z9 9 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1999 VL 84 IS 12 BP 4665 EP 4670 DI 10.1210/jc.84.12.4665 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 263PH UT WOS:000084134100061 ER PT J AU Simon, JA Hudes, ES AF Simon, JA Hudes, ES TI Serum ascorbic acid and other correlates of self-reported cataract among older Americans SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE age-related; antioxidants; ascorbic acid; cataract; vitamin C ID AGE-RELATED CATARACTS; BEAVER DAM EYE; CIGARETTE-SMOKING; LENS OPACITIES; RISK-FACTORS; VITAMIN-C; NUCLEAR; ANTIOXIDANTS; SUNLIGHT; WOMEN AB The purpose of this study was to examine the correlates of self-reported cataract among older Americans, and specifically, to determine whether serum ascorbic acid levels are associated with a decreased prevalence of cataract. A national probability survey of Americans, the Second National Health and Nutrition Examination Survey (NHANES II), was conducted between 1976 and 1980. A total of 4001 participants were included between the ages of 60 and 74 years with data on serum ascorbic acid level and other variables of interest. A total of 252 women (12%) and 164 men (9%) reported a history of cataract. Serum ascorbic acid level was inversely associated with prevalence of cataract in multiple logistic regression analyses; each 1 mg/dl increase was independently associated with a 26% decrease in cataract (P = 0.03). Other independent correlates of cataract included increasing age, female sex, smoking, and diabetes mellitus (all P < 0.01). We identified four correlates of cataract among older Americans: serum ascorbic acid level, increasing age, smoking, and diabetes mellitus. Ascorbic acid, a water-soluble antioxidant found in high concentrations in the lens, may be of importance for the prevention of cataract among older Americans. Published by Elsevier Science Inc. C1 San Francisco VA Med Ctr, Gen Internal Med Sect 111A1, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Biostat & Epidemiol, San Francisco, CA 94143 USA. RP San Francisco VA Med Ctr, Gen Internal Med Sect 111A1, 4150 Clement St, San Francisco, CA 94121 USA. EM jasimon@itsa.ucsf.edu FU NHLBI NIH HHS [HL53479] NR 36 TC 38 Z9 39 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-4356 EI 1878-5921 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD DEC PY 1999 VL 52 IS 12 BP 1207 EP 1211 DI 10.1016/S0895-4356(99)00110-9 PG 5 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 258AZ UT WOS:000083817000011 PM 10580784 ER PT J AU Rosenthal, N Harvey, RP AF Rosenthal, N Harvey, RP TI Single allele mutations at the heart of congenital disease SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material C1 Massachusetts Gen Hosp E, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Victor Chang Cardiac Res Inst, Darlinghurst, NSW 2010, Australia. Univ New S Wales, Fac Med, Sydney, NSW 2052, Australia. Univ New S Wales, Fac Life Sci, Sydney, NSW 2052, Australia. RP Rosenthal, N (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. NR 10 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1999 VL 104 IS 11 BP 1483 EP 1484 DI 10.1172/JCI8825 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 263FG UT WOS:000084114200001 PM 10587507 ER PT J AU Kaelin, WG AF Kaelin, WG TI Taking aim at novel molecular targets in cancer therapy SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, 44 Binney St,Mayer 457, Boston, MA 02115 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1999 VL 104 IS 11 BP 1495 EP 1495 DI 10.1172/JCI2 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 263FG UT WOS:000084114200005 PM 10587511 ER PT J AU Kaelin, WG AF Kaelin, WG TI Choosing anticancer drug targets in the postgenomic era SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HUMAN CANCER; CELL-CYCLE; TUMOR-SUPPRESSOR; RETINOBLASTOMA PROTEIN; GENE; P53; MDM2 C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, 44 Binney St,Mayer 457, Boston, MA 02115 USA. NR 21 TC 46 Z9 46 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1999 VL 104 IS 11 BP 1503 EP 1506 DI 10.1172/JCI8888 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 263FG UT WOS:000084114200007 PM 10587513 ER PT J AU Itoh, H Beck, PL Inoue, N Xavier, R Podolsky, DK AF Itoh, H Beck, PL Inoue, N Xavier, R Podolsky, DK TI A paradoxical reduction in susceptibility to colonic injury upon targeted transgenic ablation of goblet cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID INTESTINAL TREFOIL FACTOR; INFLAMMATORY BOWEL-DISEASE; EPIDERMAL-GROWTH-FACTOR; HAPTEN-INDUCED MODEL; MUC3 MESSENGER-RNA; ULCERATIVE-COLITIS; GENETIC ABLATION; LINEAGE ABLATION; FACTOR-ALPHA; TOXIN GENE AB Goblet cells are the major mucus-producing cells of the intestine and are presumed to play an important role in mucosal protection. However, their functional role has not been directly assessed in vivo. In initial studies, a 5' flanking sequence of the murine intestinal trefoil factor (ITF) gene was found to confer goblet cell-specific expression of a transgene. To assess the role of globlet cells in the intestine, we generated transgenic mice in which similar to 60% of goblet cells were ablated by the expression of an attenuated diphtheria toxin (DT) gene driven by the ITF promoter; other cell lineages were unaffected. We administered 2 exogenous agents, dextran sodium sulfate (DSS) and acetic acid, to assess the susceptibility of mITF/DT-A transgenic mice to colonic injury. After oral administration of DSS, 55% of control mice died, whereas DT transgenic mice retained their body weight and less than 5% died. Similarly, 30% of the wild-type mice died after mucosal administration of acetic acid, compared with 3.2% of the transgenic mice. Despite the reduction in goblet-cell number, the total amount of ITF was increased in the mITF/DT-A transgenic mice, indicating inducible compensatory mechanisms. These results suggest that goblet cells contribute to mucosal protection and repair predominantly through production of trefoil peptides. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Inflammatory Bowel Dis, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ-719, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-46906, DKJ-43351, R01 DK046906, P30 DK043351] NR 42 TC 45 Z9 45 U1 1 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1999 VL 104 IS 11 BP 1539 EP 1547 DI 10.1172/JCI6211 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 263FG UT WOS:000084114200011 PM 10587517 ER PT J AU Ohh, M Takagi, Y Aso, T Stebbins, CE Pavletich, NP Zbar, B Conaway, RC Conaway, JW Kaelin, WG AF Ohh, M Takagi, Y Aso, T Stebbins, CE Pavletich, NP Zbar, B Conaway, RC Conaway, JW Kaelin, WG TI Synthetic peptides define critical contacts between elongin C, elongin B, and the von Hippel-Lindau protein SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TUMOR-SUPPRESSOR GENE; GERMLINE MUTATIONS; CELLULAR PROTEINS; PRODUCT; DISEASE; VHL; BINDING; IDENTIFICATION; ELONGATION; CARCINOMA AB The von Hippel-Lindau tumor suppressor protein (pVHL) negatively regulates hypoxia-inducible mRNAs such as the mRNA encoding vascular endothelial growth factor (VEGF). This activity has been linked to its ability to form multimeric complexes that contain elongin C, elongin B, and Cul2. To understand this process in greater detail, we performed a series of in vitro binding assays using pVHL, elongin B, and elongin C variants as well as synthetic peptide competitors derived from pVHL or elongin C. A subdomain of elongin C (residues 17-50) was necessary and sufficient for detectable binding to elongin B. In contrast, elongin B residues required for binding to elongin C were not confined to a discrete colinear domain. We found that the pVHL (residues 157-171) is necessary and sufficient for binding to elongin C in vitro and is frequently mutated in families with VHL disease. These mutations preferentially involve residues that directly bind to elongin C and/or alter the conformation of pVHL such that binding to elongin C is at least partially diminished. These results are consistent with the view that diminished binding of pVHL to the elongins plays a causal role in VHL disease. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Oklahoma Med Res Fdn, Program Mol & Cell Biol, Oklahoma City, OK 73104 USA. Cornell Univ, Joan & Sanford I Weill Grad Sch Med Sci, Dept Biochem & Struct Biol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Cellular Biochem & Biophys Program, New York, NY 10021 USA. NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73190 USA. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. OI Conaway, Joan/0000-0002-2786-0663 NR 31 TC 69 Z9 72 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1999 VL 104 IS 11 BP 1583 EP 1591 DI 10.1172/JCI8161 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 263FG UT WOS:000084114200016 PM 10587522 ER PT J AU Shapiro, GI Harper, JW AF Shapiro, GI Harper, JW TI Anticancer drug targets: cell cycle and checkpoint control SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID DEPENDENT KINASE INHIBITOR; BREAST-CARCINOMA CELLS; CHEMICAL INHIBITORS; GROWTH-INHIBITION; CANCER CELLS; DNA-DAMAGE; S-PHASE; FLAVOPIRIDOL; ARREST; UCN-01 C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Baylor Coll Med, Verna & Marrs Mclean Dept Biochem & Mol Biol, Houston, TX 77030 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Adult Oncol, Boston, MA 02115 USA. RP Shapiro, GI (reprint author), Dana Farber Canc Inst, Mayer 422,44 Binney St, Boston, MA 02115 USA. NR 44 TC 238 Z9 250 U1 2 U2 8 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1999 VL 104 IS 12 BP 1645 EP 1653 DI 10.1172/JCI9054 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 268EE UT WOS:000084400700002 PM 10606615 ER PT J AU Sellers, WR Fisher, DE AF Sellers, WR Fisher, DE TI Apoptosis and cancer drug targeting SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NF-KAPPA-B; TRANSFORMATION; ACTIVATION; INDUCTION; CELLS; P53; PROTEIN; PATHWAY; KINASE; GENE C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Adult Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. RP Sellers, WR (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 21 TC 147 Z9 155 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1999 VL 104 IS 12 BP 1655 EP 1661 DI 10.1172/JCI9053 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 268EE UT WOS:000084400700003 PM 10606616 ER PT J AU Abel, ED Kaulbach, HC Tian, R Hopkins, JCA Duffy, J Doetschman, T Minnemann, T Boers, ME Hadro, E Oberste-Berghaus, C Quist, W Lowell, BB Ingwall, JS Kahn, BB AF Abel, ED Kaulbach, HC Tian, R Hopkins, JCA Duffy, J Doetschman, T Minnemann, T Boers, ME Hadro, E Oberste-Berghaus, C Quist, W Lowell, BB Ingwall, JS Kahn, BB TI Cardiac hypertrophy with preserved contractile function after selective deletion of GLUT4 from the heart SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TISSUE-SPECIFIC REGULATION; GLUCOSE-TRANSPORTER GLUT4; SKELETAL-MUSCLE; DIABETIC RATS; IN-VIVO; MYOCARDIAL-ISCHEMIA; INSULIN-RESISTANCE; GENE-EXPRESSION; TRANSLOCATION; MYOCYTES AB Glucose enters the heart via GLUT1 and GLUT4 glucose transporters. GLUT4-deficient mice develop striking cardiac hypertrophy and die prematurely. Whether their cardiac changes are caused primarily by GLUT4 deficiency in cardiomyocytes or by metabolic changes resulting from the absence of GLUT4 in skeletal muscle and adipose tissue is unclear. To determine the role of GLUT4 in the heart we used cre-loxP recombination to generate G4H(-/-) mice in which GLUT4 expression is abolished in the heart but is present in skeletal muscle and adipose tissue. Life span and serum concentrations of insulin, glucose, FFAs, lactate, and beta-hydroxybutyrate were normal. Basal cardiac glucose transport and GLUT1 expression were both increased approximately 3-fold in G4H(-/-) mice, but insulin-stimulated glucose uptake was abolished. G4H(-/-) mice develop modest cardiac hypertrophy associated with increased myocyte size and induction of atrial natriuretic and brain natriuretic peptide gene expression in the ventricles. Myocardial fibrosis did not occur. Basal and isoproterenol-stimulated isovolumic contractile performance was preserved. Thus, selective ablation of GLUT4 in the heart initiates a series of events that results in compensated cardiac hypertrophy. C1 Beth Deaconedd Med Ctr, Div Endocrinol & Metab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Nucl Magnet Resonance Lab Physiol Chem, Boston, MA 02115 USA. Univ Cincinnati, Dept Mol Genet, Cincinnati, OH 45267 USA. Beth Deaconedd Med Ctr, Dept Pathol, Boston, MA 02215 USA. Childrens Hosp, Dept Cardiac Surg, Boston, MA 02115 USA. RP Abel, ED (reprint author), Beth Deaconedd Med Ctr, Div Endocrinol & Metab, Res N BIDMC,POB 15707, Boston, MA 02215 USA. OI Tian, Rong/0000-0002-3676-3830 FU NHLBI NIH HHS [HL-59246, HL-62886, P50 HL052320, R01 HL059246]; NIDDK NIH HHS [DK-02495, P30 DK046200, R37 DK043051, R01 DK043051] NR 57 TC 194 Z9 200 U1 0 U2 7 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1999 VL 104 IS 12 BP 1703 EP 1714 DI 10.1172/JCI7605 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 268EE UT WOS:000084400700011 PM 10606624 ER PT J AU Kulkarni, RN Winnay, JN Daniels, M Bruning, JC Flier, SN Hanahan, D Kahn, CR AF Kulkarni, RN Winnay, JN Daniels, M Bruning, JC Flier, SN Hanahan, D Kahn, CR TI Altered function of insulin receptor substrate-1-deficient mouse islets and cultured beta-cell lines SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID DEPENDENT DIABETES-MELLITUS; SIGNAL-TRANSDUCTION PATHWAYS; PHOSPHATIDYLINOSITOL 3-KINASE; CYTOKINE ACTION; KNOCKOUT MICE; S6 KINASE; GLUCOSE; GROWTH; IRS-1; GENE AB Insulin receptor substrate-1 (IRS-1) is pivotal in mediating the actions of insulin and growth factors in most tissues of the body, but its role in insulin-producing beta islet cells is unclear. Freshly isolated islets from IRS-I knockout mice and SV40-transformed IRS-l-deficient beta-cell lines exhibit marked insulin secretory defects in response to glucose and arginine. Furthermore, insulin expression is reduced by about 2-fold in the IRS-l-null islets and beta-cell lines, and this defect can be partially restored by transfecting the cells with IRS-1. These data provide evidence for an important role of IRS-1 in islet function and provide a novel functional link between the insulin signaling and insulin secretion pathways. C1 Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr,Div Cellular & Mol Physiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Univ Calif San Francisco, Hormone Res Inst, Dept Biochem & Biophys, San Francisco, CA 94143 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr,Div Cellular & Mol Physiol, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu FU NIDDK NIH HHS [P30 DK-36836, DK-09825-02, DK-31036, F32 DK009825, P30 DK036836, R01 DK031036, R37 DK031036] NR 48 TC 196 Z9 201 U1 1 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1999 VL 104 IS 12 BP R69 EP R75 DI 10.1172/JCI8339 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 268EE UT WOS:000084400700019 PM 10606633 ER PT J AU Barker, JH Musher, DM Silberman, R Phan, HM Watson, DA AF Barker, JH Musher, DM Silberman, R Phan, HM Watson, DA TI Genetic relatedness among nontypeable pneumococci implicated in sporadic cases of conjunctivitis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID STREPTOCOCCUS-PNEUMONIAE; PHASE VARIATION; SEROTYPES; VIRULENCE AB Nontypeable Streptococcus pneumoniae is a common cause of epidemic conjunctivitis, A previous molecular fingerprinting study identified a clone of nontypeable pneumococcus that was responsible for a recent outbreak of conjunctivitis. In the present study, we examined the extent to which pneumococci that cause sporadic cases of conjunctivitis are related to this epidemic strain, Using arbitrarily primed BOX-PCR, we have determined that, of 10 nontypeable pneumococci causing sporadic conjunctivitis, 5 were clonal and closely related to a previous outbreak strain, whereas 5 others were genetically diverse. C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Vet Affairs Med Ctr, Infect Dis Labs, Houston, TX 77030 USA. Louisiana State Univ, Med Ctr, Dept Pathol, Shreveport, LA USA. Informat Dynam Inc, Washington, DC USA. RP Musher, DM (reprint author), Infect Dis Sect, Dept Vet Affairs Med Ctr, 2002 Holcombe Blvd,Room 4B-370, Houston, TX 77030 USA. NR 16 TC 18 Z9 18 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 1999 VL 37 IS 12 BP 4039 EP 4041 PG 3 WC Microbiology SC Microbiology GA 259CY UT WOS:000083877400042 PM 10565927 ER PT J AU Grier, HE AF Grier, HE TI Soft tissue sarcoma: Apples, oranges, and passion fruit SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID CYTOGENETIC ANALYSIS; GENE FUSION; TUMORS C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Grier, HE (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 16 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC PY 1999 VL 17 IS 12 BP 3695 EP 3696 PG 2 WC Oncology SC Oncology GA 262AJ UT WOS:000084043300001 PM 10577840 ER PT J AU Byrd, JC Dodge, RK Carroll, A Baer, MR Edwards, C Stamberg, J Qumsiyeh, M Moore, JO Mayer, RJ Davey, F Schiffer, CA Bloomfield, CD AF Byrd, JC Dodge, RK Carroll, A Baer, MR Edwards, C Stamberg, J Qumsiyeh, M Moore, JO Mayer, RJ Davey, F Schiffer, CA Bloomfield, CD TI Patients with t(8;21)(q22;q22) and acute myeloid leukemia have superior failure-free and overall survival when repetitive cycles of high-dose cytarabine are administered SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE NONLYMPHOCYTIC LEUKEMIA; BONE-MARROW TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; INTENSIVE POSTREMISSION CHEMOTHERAPY; PROGNOSTIC-SIGNIFICANCE; CYTOSINE-ARABINOSIDE; REMISSION DURATION; FOLLOW-UP; TRANSLOCATION; THERAPY AB Purpose: To examine the effect of single compared with repetitive (at least three) cycles of high-dose cytarabine after induction therapy for patients with acute myeloid leukemia (AML) who have the t(8;21)(q22;q22) karyotype. Patients and Methods: Patients entered onto the study had AML and t(8;21) and attained a complete remission on four successive Cancer and Leukemia Group B studies. In these studies, either greater than or equal to three cycles of high-dose cytarabine or one cycle of high-dose cytarabine was administered, followed by sequential cyclophosphamide/etoposide and mitoxantrone/diaziquone with or without filgrastim support. Outcomes of these two groups of t(8;21) patients were compared. Results: A total of 50 patients with centrally reviewed AML and t(8;21) were assigned to receive one (n = 29) or greater than or equal to three cycles (9 = 21) of high-dose cytarabine as postinduction therapy. The clinical features of these two groups of patients were similar. Initial remission duration for t(8;21) patients assigned to one cycle of high-dose cytarabine was significantly inferior (P =.03), with 62% of patients experiencing relapse with a median failure-free survival of 10.5 months, compared with the group of patients who received greater than or equal to three cycles, in which only 19% experienced relapse and failure-free survival is estimated to be greater than 35 months. furthermore, overall survival was also significantly compromised (P =.04) in patients assigned to one cycle of high-dose cytarabine, with 59% having died as a consequence of AML, compared with 24% of those who received greater than or equal to three cycles of high-dose cytarabine. Conclusion: These data demonstrate that failure-free survival and overall survival of patients with t(8; 21)(q22;q22) may be compromised by treatment approaches that do not include sequential high-dose cytarabine therapy. J Clin Oncol 17:3767-3775. (C) 1999 by American Society of Clinical Oncology. C1 Walter Reed Army Med Ctr, Hematol Oncol Serv, Washington, DC 20307 USA. Leukemia Grp B Stat Off, Durham, NC USA. Univ Alabama, Birmingham, AL USA. Roswell Pk Canc Inst, Buffalo, NY USA. Univ Maryland, Ctr Canc, Baltimore, MD 21201 USA. Duke Univ, Med Ctr, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. SUNY Hlth Sci Ctr, Syracuse, NY 13210 USA. Ohio State Univ, Columbus, OH 43210 USA. RP Byrd, JC (reprint author), Walter Reed Army Med Ctr, Hematol Oncol Serv, Ward 78, Washington, DC 20307 USA. FU NCI NIH HHS [CA26806, CA33601, CA47545] NR 38 TC 195 Z9 206 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 DEC PY 1999 VL 17 IS 12 BP 3767 EP 3775 PG 9 WC Oncology SC Oncology GA 262AJ UT WOS:000084043300009 PM 10577848 ER PT J AU Sparano, JA Hu, P Rao, RM Falkson, CI Wolff, AC Wood, WC AF Sparano, JA Hu, P Rao, RM Falkson, CI Wolff, AC Wood, WC TI Phase II trial of doxorubicin and paclitaxel plus granulocyte colony-stimulating factor in metastatic breast cancer: An eastern cooperative oncology group study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 20th Annual San Antonio Breast Cancer Symposium CY DEC 03-06, 1997 CL SAN ANTONIO, TEXAS ID CONTAINING THERAPY; DEXRAZOXANE; PHARMACOKINETICS; CARDIOPROTECTION; CARDIOTOXICITY; COMBINATION; WOMEN AB Purpose: Several groups have reported that the combination of doxorubicin plus paclitaxel given as a 3-hour intravenous (IV) infusion for up to eight cycles produces a high response rate (> 80%) and complete response rate (> 20%) in metastatic breast cancer, but is also complicated by a 20% incidence of congestive heart failure [CHF). The purpose of this phase Il trial was to evaluate the antineoplastic activity of the regimen in a multi-institutional setting and to reduce the incidence of cardiotoxicity by limiting treatment to a maximum of six cycles. Patients and Methods: Fifty-two patients with advanced breast cancer received doxorubicin (60 mg/m(2) by IV injection) followed 15 minutes later by paclitaxel (200 mg/m(2) by IV infusion over 3 hours) every 3 weeks for four to six cycles. Results: Objective responses occurred in 25 of 48 assessable patients (52%; 95% confidence interval [CI], 38% to 66%), including four complete responses (8%; 95% CI, 0% to 16%), The median cumulative doxorubicin dose given was 240 mg/m(2) (range, 132 to 360 mg/m(2)). Eleven patients (21%) were documented as having a decrease in the LVEF below normal, including three patients (6%; 95% CI, 0% to 12%) who developed CHF, Conclusion: The doxorubicin/paclitaxel regimen that we used is unlikely to produce an objective response rate of more than 70% and a complete response rate of more than 20% in patients with metastatic breast cancer, and proved to be excessively cardiotoxic for use in the adjuvant setting. J Clin Oncol 11:3828-3834, (C) 1999 by American Society of Clinical Oncology. C1 Montefiore Med Ctr, Albert Einstein Comprehens Canc Ctr, Dept Oncol, Bronx, NY 10461 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Siouxland Hematol Oncol Associat, Sioux City, IA USA. Univ Pretoria, ZA-0002 Pretoria, South Africa. Emory Univ, Sch Med, Atlanta, GA USA. RP Sparano, JA (reprint author), Montefiore Med Ctr, Albert Einstein Comprehens Canc Ctr, Dept Oncol, 2 South,Room 52,1825 Eastchester Rd, Bronx, NY 10461 USA. OI Wolff, Antonio/0000-0003-3734-1063 FU NCI NIH HHS [CA23318, CA21076, CA21692] NR 30 TC 49 Z9 49 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC PY 1999 VL 17 IS 12 BP 3828 EP 3834 PG 7 WC Oncology SC Oncology GA 262AJ UT WOS:000084043300017 PM 10577856 ER PT J AU Harris, NL Jaffe, ES Diebold, J Flandrin, G Muller-Hermelink, HK Vardiman, J Lister, TA Bloomfield, CD AF Harris, NL Jaffe, ES Diebold, J Flandrin, G Muller-Hermelink, HK Vardiman, J Lister, TA Bloomfield, CD TI World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: Report of the Clinical Advisory Committee Meeting - Airlie House, Virginia, November 1997 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID AMERICAN AB Purpose: The European Association of Hematopathologists and the Society for Hematopathology have developed a new World Health Organization (WHO) classification of hematologic malignancies, including lymphoid, myeloid, histiocytic, and mast cell neoplasms, Design: Ten committees of pathologists developed lists and definitions of disease entities. A clinical advisory committee (CAC) of international hematologists and oncologists was formed to ensure that the classification would be useful to clinicians, The CAC met in November 1997 to discuss clinical issues related to the classification. Results: The WHO uses the Revised European-American Lymphoma (REAL) classification, published in 1994 by the International Lymphoma Study Group, to categorize lymphoid neoplasms. The REAL classification is based on the principle that a classification is a list of "real" disease entities, which are defined by a combination of morphology, immunophenotype, genetic features, and clinical features. The relative importance of each of these features varies among diseases, and there is no one gold standard, The WHO classification applies the principles of the REAL classification to myeloid and histiocytic neoplasms. The classification of myeloid neoplasms recognizes distinct entities defined by a combination of morphology and cytogenetic abnormalities. At the CAC meeting, which was organized around a series of clinical questions, participants reached a consensus on most of the questions posed. They concluded that clinical groupings of lymphoid neoplasms were neither necessary nor desirable. Patient treatment is determined by the specific type of lymphoma, with the addition of grade within the tumor type, if applicable, and clinical prognostic factors, such as the International Prognostic Index. Conclusion: The WHO classification has produced a new and exciting degree of cooperation and communication between oncologists and pathologists from around the world, which should facilitate progress in the understanding and treatment of hematologic malignancies, J Clin Oncol 17:3835-3849, (C) 1999 by American Society of Clinical Oncology. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. Hotel Dieu, Paris, France. Hop Necker Enfants Malad, Paris, France. Univ Wurzburg, Wurzburg, Germany. Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. St Bartholomews Hosp, Dept Med Oncol, London, England. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. RP Harris, NL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2,Fruit St, Boston, MA 02114 USA. NR 4 TC 1896 Z9 1993 U1 1 U2 57 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC PY 1999 VL 17 IS 12 BP 3835 EP 3849 PG 15 WC Oncology SC Oncology GA 262AJ UT WOS:000084043300018 PM 10577857 ER PT J AU Feres, M Haffajee, AD Goncalves, C Allard, KA Som, S Smith, C Goodson, JM Socransky, SS AF Feres, M Haffajee, AD Goncalves, C Allard, KA Som, S Smith, C Goodson, JM Socransky, SS TI Systemic doxycycline administration in the treatment of periodontal infections - (I) - Effect on the subgingival microbiota SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE microbiology; bacteria; subgingival plaque; doxycycline; periodontal diseases; periodontitis; antibiotic ID LOCALIZED JUVENILE PERIODONTITIS; ACTINOMYCETEMCOMITANS-ASSOCIATED PERIODONTITIS; MUCOID PSEUDOMONAS-AERUGINOSA; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; REFRACTORY PERIODONTITIS; TOBRAMYCIN RESISTANCE; TETRACYCLINE THERAPY; ADULT PERIODONTITIS; IMMUNOLOGICAL FEATURES; TET(Q) GENE AB Systemic doxycycline is one of the more common antimicrobial agents used in the treatment of periodontal infections and yet little is known of its effect on subgingival plaque composition during and after its administration. The purpose of the present investigation was to evaluate changes in subgingival plaque composition during and after 14 days of doxycycline administration. 20 subjects with adult periodontitis were randomly assigned to test (n=10) and control (n=10) groups. The subjects received full mouth clinical assessment of pocket depth, attachment level, BOP, gingival redness, suppuration and plaque accumulation at baseline and 90 days. All subjects received full mouth SRP at baseline and, additionally, the test group received 100 mg doxycycline daily for 14 days. Subgingival plaque samples were taken from the mesial surface of up to 28 teeth in each subject at baseline and 90 days. In addition, plaque samples were taken from 2 randomly selected teeth at 3, 7 and 14 days during and after antibiotic administration. Control subjects were sampled at the same time points. Counts of 40 subgingival species were determined using checkerboard DNA-DNA hybridization and fluorescent detection. Significance of differences between test and control groups was determined at each time point using the Mann Whitney test. Significance of changes over time within test and control groups was determined using the Quade test. A modest but significant reduction in mean pocket depth from baseline to 90 days occurred in both test and control groups. A significant decrease in the % of sites with gingival redness occurred in the test group. There were no significant differences in proportions between test and control groups for 33 of the test species at any time point. Test subjects exhibited lower proportions of 4 Actinomyces species and an increase in 3 Streptococcus species during antibiotic administration. After cessation of doxycycline, Actinomyces sp. increased while Streptococcus sp. returned to baseline proportions. The relationship between these 2 genera appeared to be reciprocal; an increase in one was accompanied by a decrease in the other. Periodontal pathogens including B. forsythus, P. gingivalis, T. denticola and A. actinomycetemcomitans were not significantly altered by oral administration of doxycycline using conventional therapeutic dosage. C1 Forsyth Dent Ctr, Dept Periodontol, Boston, MA 02115 USA. RP Haffajee, AD (reprint author), Forsyth Dent Ctr, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. RI Feres, Magda/H-7964-2012 FU NIDCR NIH HHS [DE-04881, DE-09513, DE-10977] NR 65 TC 41 Z9 42 U1 1 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD DEC PY 1999 VL 26 IS 12 BP 775 EP 783 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 259ZF UT WOS:000083923300001 PM 10599904 ER PT J AU Feres, M Haffajee, AD Goncalves, C Allard, KA Som, S Smith, C Goodson, JM Socransky, SS AF Feres, M Haffajee, AD Goncalves, C Allard, KA Som, S Smith, C Goodson, JM Socransky, SS TI Systemic doxycycline administration in the treatment of periodontal infections - (II). Effect on antibiotic resistance of subgingival species SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE antibiotic resistance; microbiology; bacteria; subgingival plaque; doxycycline; periodontal diseases; periodontitis; antibiotic ID TETRACYCLINE RESISTANCE; ADULT PERIODONTITIS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; MINOCYCLINE-HCL; TET(Q) GENE; DISEASE; MICROFLORA; BACTERIA; THERAPY; MICROBIOTA AB The purpose of this investigation was to determine the proportion and prevalence of doxycycline resistant species in subgingival plaque samples taken during and after doxycycline administration. 20 subjects with adult periodontitis were randomly assigned to test (n=10) or control groups (n=10). Saliva samples as well as subgingival plaque samples taken from the distal surface of 6 posterior teeth were collected at baseline. All subjects received full mouth SRP and the test group systemic doxycycline at the dosage of 100 mg/day for 14 days. Saliva samples and plaque samples from the distal surface of 2 randomly selected teeth were taken at 3, 7 and 14 days during and after antibiotic administration. Control subjects were sampled at the same time points. Samples were anaerobically dispersed and serially diluted in PRAS Ringer's solution and plated on enriched Trypticase soy blood agar plates with or without 4 mu g/ml doxycycline. After 7 days of anaerobic incubation, colonies were counted on both sets of plates. Microbial growth was washed from the doxycycline-containing media and the species identified using 40 DNA probes and checkerboard DNA-DNA hybridization. Differences in proportions of resistant species between test and control groups were tested for significance at each time point using the Mann Whitney test and over time within each group using the Quads test. The mean % (+/-SEM) of isolates resistant to 4 mu g/ml doxycycline in the plaque samples of the test subjects increased from 6+/-2 to 48+/-9% during doxycycline administration, decreasing to 25+/-6% 2 weeks later and 9+/-2% at 90 days. In saliva, the % of resistant isolates rose from 13+/-1% to 81+/-10% during doxycycline administration falling to 46+/-8% 2 weeks later and 22+/-5% at 90 days. The % of resistant isolates did not change significantly in plaque or saliva samples of the control subjects at the same time points. For all subject visits combined, the most prevalent resistant species were: Streptococcus anginosus, Streptococcus oralis, Streptococcus intermedius, Streptococcus sanguis, Streptococcus mitis, Veillonella parvula, Actinomyces gerencseriae, Streptococcus constellatus, Actinomyces naeslundii genospecies 2, Streptococcus gordonii, Eikenella corrodens and Actinomyces naeslundii genospecies 1. Doxycycline resistant strains of these species were detected in both plaque and saliva samples prior to therapy and in the control group. Despite the finding of increased resistance, approximately 50% of the organisms present at periodontal sites at the end of 14 days of doxycycline administration tested sensitive to the agent. C1 Forsyth Dent Ctr, Dept Periodontol, Boston, MA 02115 USA. RP Haffajee, AD (reprint author), Forsyth Dent Ctr, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. RI Feres, Magda/H-7964-2012 FU NIDCR NIH HHS [DE-11814, DE-04881, DE-10977] NR 49 TC 35 Z9 37 U1 0 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD DEC PY 1999 VL 26 IS 12 BP 784 EP 792 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 259ZF UT WOS:000083923300002 PM 10599905 ER PT J AU Lee, KH Tanner, ACR Maiden, MFJ Weber, HP AF Lee, KH Tanner, ACR Maiden, MFJ Weber, HP TI Pre- and post-implantation microbiota of the tongue, teeth, and newly-placed implants SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE microbiology; dental implants; tongue; subgingival species ID ORAL MUCOUS-MEMBRANES; PUTATIVE PERIODONTAL PATHOGENS; BLACK-PIGMENTED BACTEROIDES; DENTAL IMPLANTS; EDENTULOUS PATIENTS; GINGIVITIS; BACTERIA; DISEASE; SITES; DNA AB Objectives: This investigation sought intra-oral sources of species colonizing dental implants. Materials and Methods: Plaque samples were taken pre- and post-successful osseointegration from implants, teeth, and from tongues of 10 edentulous and 11 partially-dentate subjects. Samples were assayed using whole genomic DNA probes in a checkerboard assay to 42 subgingival species. Results: Similar prevalences and mean levels (10(3) to 10(4)) Of micro-organisms colonized implants and teeth. Species levels from tongue samples were higher than those of teeth and implants, although species prevalence was similar, suggesting that larger samples were obtained from the tongue. No significant differences were observed between the microbiota from the tongue of edentulous and partially dentate subjects. Most implant species were detected on tongue pre-implantation. In individual edentulous subjects, there were positive associations between Capnocytophaga ochracea and Campylobacter rectus from tongue and implant samples. In individual partially dentate subjects, there were positive associations between Fusobacterium nucleatum subsp. vincentii from tongue and implant samples, and Treponema denticola from implant and tooth samples taken at the same visit. Conclusion: This study indicated that the tongue, in addition to teeth, can be a source for species colonizing new implants. C1 Forsyth Dent Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Tanner, ACR (reprint author), Forsyth Dent Ctr, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE 10160] NR 49 TC 40 Z9 42 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD DEC PY 1999 VL 26 IS 12 BP 822 EP 832 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 259ZF UT WOS:000083923300008 PM 10599911 ER PT J AU Safren, SA Heimberg, RG AF Safren, SA Heimberg, RG TI Depression, hopelessness, suicidality, and related factors in sexual minority and heterosexual adolescents SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID THEORETICALLY BASED APPROACH; SOCIAL SUPPORT; BISEXUAL YOUTHS; RISK-FACTORS; COMMUNITY SETTINGS; MENTAL-HEALTH; GAY; ORIENTATION; VICTIMIZATION; SCALE AB In the present study, the researchers examined factors related to depression, hopelessness, and suicidality in gay, lesbian, and bisexual adolescents, compared with demographically similar heterosexual adolescents. Sexual minority adolescents reported greater depression, hopelessness, and past and present suicidality than did heterosexual adolescents. However, when controlling for other psychosocial predictors of present distress, significant differences between the 2 samples disappeared. For past suicidality scores, the effects of sexual orientation were reduced, but still significant, when accounting for the other predictor variables. These results suggest that environmental factors associated with sexual orientation, which can be targeted and changed through prevention and intervention efforts, play a major role in predicting distress in this population. C1 Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. RP Heimberg, RG (reprint author), Temple Univ, Dept Psychol, Weiss Hall 657,1701 N 13th St, Philadelphia, PA 19122 USA. NR 39 TC 158 Z9 158 U1 1 U2 10 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD DEC PY 1999 VL 67 IS 6 BP 859 EP 866 DI 10.1037//0022-006X.67.6.859 PG 8 WC Psychology, Clinical SC Psychology GA 260XP UT WOS:000083979000005 PM 10596508 ER PT J AU Peters, AS Clark-Chiarelli, N Block, SD AF Peters, AS Clark-Chiarelli, N Block, SD TI Comparison of osteopathic and allopathic medical schools' support for primary care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE osteopaths; allopaths; medical school; primary care ID PHYSICIANS; CULTURE AB OBJECTIVE:To contrast prevailing behaviors and attitudes relative to primary care education and practice in osteopathic and allopathic medical schools. DESIGN:Descriptive study using confidential telephone interviews conducted in 1993-94, Analyses compared responses of osteopaths and allopaths, controlling for primary care orientation. SETTING:United States academic health centers, PARTICIPANTS: National stratified probability samples of first-year and fourth-year medical students, postgraduate year 2 residents, and clinical faculty in osteopathic and allopathic medical schools, a sample of allopathic deans, and a census of deans of osteopathic schools (n = 457 osteopaths; n = 2,045 allopaths), MEASUREMENTS: Survey items assessed personal characteristics, students' reasons for entering medicine, learners' primary care educational experiences, community support for primary care, and attitudes toward the clinical and academic competence of primary care physicians. MAIN RESULTS:Primary care physicians composed a larger fraction of the faculty in osteopathic schools than in allopathic schools. Members of the osteopathic community were significantly more likely than their allopathic peers to describe themselves as socioemotionally oriented rather than technoscientifically oriented. Osteopathic learners were more likely than allopathic learners to have educational experiences in primary care venues and with primary care faculty, and to receive encouragement from faculty, including specialists, to enter primary care. Attitudes toward the clinical and academic competence of primary care physicians were consistently negative in both communities. Differences between communities were sustained after controlling for primary care orientation. CONCLUSIONS:In comparison with allopathic schools, the cultural practices and educational structures in osteopathic medical schools better support the production of primary care physicians. However, there is a lack of alignment between attitudes and practices in the osteopathic community. C1 Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. Harvard Univ, Sch Med, Off Educ Dev, Boston, MA USA. Harvard Univ, Sch Med, Off Educ Dev, Boston, MA USA. Dana Farber Canc Inst, Adult Psychosocial Oncol Program, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Psychiat, Boston, MA 02115 USA. RP Peters, AS (reprint author), Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, 126 Brookline Ave, Boston, MA 02215 USA. NR 19 TC 6 Z9 6 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 1999 VL 14 IS 12 BP 730 EP 739 DI 10.1046/j.1525-1497.1999.03179.x PG 10 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 267LG UT WOS:000084359000003 PM 10632817 ER PT J AU Lutz, GK Butzlaff, ME Atlas, SJ Keller, RB Singer, DE Deyo, RA AF Lutz, GK Butzlaff, ME Atlas, SJ Keller, RB Singer, DE Deyo, RA TI The relation between expectations and outcomes in surgery for sciatica SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE patient expectations; physician expectations; sciatica; diskectomy ID LOW-BACK-PAIN; MAINE LUMBAR SPINE; DISK AB OBJECTIVE: To describe the expectations that patients and their physicians have for outcomes after surgical treatment for sciatica and to examine the associations between expectations and outcomes. DESIGN:Prospective cohort study. SETTING/PATIENTS: We recruited 273 patients, from the offices of orthopedic surgeons, neurosurgeons, and occupational medicine physicians in Maine, who had diskectomy for sciatica, MEASUREMENTS AND MAIN RESULTS: Patients' and physicians' expectations were measured before surgery. Satisfaction with care and changes in symptoms and functional status were measured 12 months after surgery, More patients who expected a shorter recovery time after surgery were "delighted," "pleased," or "mostly satisfied" with their outcomes 12 months after surgery than patients who expected a longer recovery time (odds ratio [OR] 2.2; 95% confidence interval [CI] 1.1, 4.4). Also, more patients who preferred surgery after learning that sciatica could get better without surgery had good symptom scores 12 months after surgery than patients who did not prefer surgery (OR 2.9; 95% CI 1.2, 7.0). When physicians predicted a "great deal of improvement" after surgery, 39% of patients were not satisfied with their outcomes and 25% said their symptoms had not improved, CONCLUSIONS: More patients with favorable expectations about surgery had good outcomes than patients with unfavorable expectations. Physicians' expectations were overly optimistic. Patient expectations appear to be important predictors of outcomes, and eliciting them may help physicians identify patients more likely to benefit from diskectomy for sciatica. C1 Univ Washington, Ctr Cost & Outcomes Res, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, NW Hlth Serv Field Program, Vet Adm Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Div Gen Internal Med, Seattle, WA 98195 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Practices Evaluat Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA. RP Butzlaff, ME (reprint author), Univ Washington, Ctr Cost & Outcomes Res, POB 358853, Seattle, WA 98195 USA. FU AHRQ HHS [HS08194, HS06344, HS06813-04] NR 15 TC 71 Z9 72 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 1999 VL 14 IS 12 BP 740 EP 744 DI 10.1046/j.1525-1497.1999.10417.x PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 267LG UT WOS:000084359000004 PM 10632818 ER PT J AU Saha, S Saint, S Christakis, DA Simon, SR Fihn, SD AF Saha, S Saint, S Christakis, DA Simon, SR Fihn, SD TI A survival guide for generalist physicians in academic fellowships - Part 2: Preparing for the transition to junior faculty SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article ID INTERNAL-MEDICINE; RESEARCH CAREER C1 Oregon Hlth Sci Univ, Vet Affairs Med Ctr, Gen Internal Med Sect, Dept Med,Med Serv P3MED, Portland, OR 97207 USA. Univ Michigan, Div Gen Med, Ann Arbor, MI 48109 USA. Univ Washington, Dept Pediat, Seattle, WA 98195 USA. Univ Washington, Inst Child Hlth, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Univ Washington, NW Hlth Serv Res & Dev Field Program, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Saha, S (reprint author), Oregon Hlth Sci Univ, Vet Affairs Med Ctr, Gen Internal Med Sect, Dept Med,Med Serv P3MED, 3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. NR 12 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 1999 VL 14 IS 12 BP 750 EP 755 DI 10.1046/j.1525-1497.1999.12148.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 267LG UT WOS:000084359000006 PM 10632820 ER PT J AU Helander, KG AF Helander, KG TI Formaldehyde binding in brain and kidney: A kinetic study of fixation SO JOURNAL OF HISTOTECHNOLOGY LA English DT Article DE C-14-formaldehyde; lipids; proteins; rats AB The aim of the study was to estimate the time needed for fixation of tissues with formaldehyde. For this purpose, rat brains and kidneys were cut in half and put into 4% buffered formaldehyde containing C-14-formaldehyde. The specimens measured about 1.5 cm(3) in size, and the distance from the surface to the center was about 4 mm. At regular intervals, specimens were removed from the fixative for determination of bound C-14-formaldehyde. Maximal binding was reached after about 50 hr; half-maximal binding was reached after 3 hr in kidney and 5 hr in brain. Maximal binding was slightly higher in kidney than in brain, possibly because of a higher protein content in the kidney than in the brain. It is concluded that formaldehyde fixation is complete only after prolonged immersion of the tissues: in this study, the rate of fixation was about 80 mu m/hr. C1 Univ Calif Los Angeles, Lab Membrane Biol, Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. Univ Gothenburg, Dept med Lab Sci, Gothenburg, Sweden. RP Helander, KG (reprint author), Sahlgrens Univ Hosp, Dept Pathol, S-41345 Gothenburg, Sweden. NR 5 TC 8 Z9 8 U1 1 U2 3 PU NATL SOC HISTOTECHNOLOGY PI BOWIE PA 4201 NORTHVIEW DR, STE 502, BOWIE, MD 20716-1073 USA SN 0147-8885 J9 J HISTOTECHNOL JI J. Histotechnol. PD DEC PY 1999 VL 22 IS 4 BP 317 EP 318 PG 2 WC Cell Biology SC Cell Biology GA 264ND UT WOS:000084187600008 ER PT J AU Geng, LP Raab, M Rudd, CE AF Geng, LP Raab, M Rudd, CE TI Cutting edge: SLP-76 cooperativity with FYB/FYN-T in the up-regulation of TCR-Driven IL-2 transcription requires SLP-76 binding to EYE at Tyr(595) and Tyr(651) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TYROSINE KINASE SUBSTRATE; ADAPTER PROTEIN SLP-76; CELL RECEPTOR; INTERLEUKIN-2 PRODUCTION; MOLECULAR-CLONING; PHOSPHORYLATION; ACTIVATION; LAT AB SLP-76 (Src homology (SH) 2-domain-containing leukocyte protein of 76 kDa) and FYB/SLAP (FYN-T-binding protein/ SLP-76-associated protein) are two hemopoietic cell-specific adaptor proteins downstream of TCR-activated protein ty, rosine kinases, SLP-76 has been implicated as an essential component in T cell signaling. FYB is selectively phosphorylated by FYN-T, providing a template for the recruitment of FYN-T and SLP-76 SH2 domains. Coexpression of FYN-T, FYB, and SLP-76 can synergistically up-regulate IL-2 production in T cells upon TCR ligation, In this report, we show that two tyrosines, Tyr(595) and Tyr(651), Of FYB are major sites of phosphorylation by FYN-T and mediate binding to SLP-76 in jurkat T cells. Furthermore, the synergistic up-regulation of IL-2 promoter activity in the FYN-T-FYB-SLP-76 pathway is contingent upon the interaction between FYB and SLP-76, but not the interaction between FYB and FYN-T, These observations define a pathway by which SLP-76 interacts with downstream components in the up-regulation of T cell cytokine production. C1 Dana Farber Canc Inst, Div Tumor Immunol, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Rudd, CE (reprint author), Dana Farber Canc Inst, Div Tumor Immunol, Dept Canc Immunol & AIDS, 44 Binney St,D520, Boston, MA 02115 USA. NR 22 TC 58 Z9 59 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1999 VL 163 IS 11 BP 5753 EP 5757 PG 5 WC Immunology SC Immunology GA 258MT UT WOS:000083843500001 PM 10570256 ER PT J AU Yankee, TM Keshvara, LM Sawasdikosol, S Harrison, ML Geahlen, RL AF Yankee, TM Keshvara, LM Sawasdikosol, S Harrison, ML Geahlen, RL TI Inhibition of signaling through the B cell antigen receptor by the protooncogene product, c-Cbl, requires Syk tyrosine 317 and the c-Cbl phosphotyrosine-binding domain SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NEGATIVE REGULATOR; PHOSPHORYLATION; KINASES; ACTIVATION; INTERACTS; ZAP-70; MOTIF; SITE; FYN; LYN AB The Syk protein-tyrosine kinase couples the B cell Ag receptor (BCR) to intracellular biochemical pathways. Syk becomes phosphorylated on multiple tyrosine residues upon receptor cross-linking. Tyrosine 317 is a site of phosphorylation located within the linker region of Syk that separates the amino-terminal, tandem pair of SH2 domains from the carboxyl-terminal catalytic domain. The amino acid sequence surrounding phosphotyrosine 317 matches the consensus sequence for recognition by the phosphotyrosine-binding (PTB) domain of the protooncogene product, c-Cbl. The overexpression of c-Cbl in DT40 B cells inhibits Ag receptor-mediated activation of the NF-AT transcription factor. The ability of overexpressed c-Cbl to inhibit signaling requires both Syk tyrosine 317 and a functional c-Cbl PTB domain. Mutant forms of Syk lacking tyrosine 317 exhibit an enhanced ability to couple the BCR to pathways leading to the activation of both NF-AT and Elk-l. Coimmunoprecipitation experiments indicate that Syk phosphotyrosine 317 and the c-Cbl PTB domain enhance, but are not required for, all interactions between these two proteins. In unstimulated cells, c-Cbl and Syk can be isolated in a complex that also contains tubulin, A mutant form of Syk lacking tyrosine at position 317 exhibits an enhanced ability to interact with a diphosphopeptide modeled on the immunoreceptor tyrosine-based activation motif of the CD79a component of the Ag receptor, These studies indicate that c-Cbl may contribute to the regulation of BCR signaling by modulating the ability of Syk to associate with the BCR and couple the receptor to intracellular signaling pathways. C1 Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. RP Geahlen, RL (reprint author), Purdue Univ, Dept Med Chem & Mol Pharmacol, Hansen Life Sci Res Bldg, W Lafayette, IN 47907 USA. OI Yankee, Thomas/0000-0002-3907-4838; Geahlen, Robert/0000-0001-8400-2924 FU NCI NIH HHS [CA09634, CA37372] NR 32 TC 56 Z9 56 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1999 VL 163 IS 11 BP 5827 EP 5835 PG 9 WC Immunology SC Immunology GA 258MT UT WOS:000083843500011 PM 10570266 ER PT J AU Castro, AG Hauser, TM Cocks, BG Abrams, J Zurawski, S Churakova, T Zonin, F Robinson, D Tangye, SG Aversa, G Nichols, KE de Vries, JE Lanier, LL O'Garra, A AF Castro, AG Hauser, TM Cocks, BG Abrams, J Zurawski, S Churakova, T Zonin, F Robinson, D Tangye, SG Aversa, G Nichols, KE de Vries, JE Lanier, LL O'Garra, A TI Molecular and functional characterization of mouse signaling lymphocytic activation molecule (SLAM): Differential expression and responsiveness in Th1 and Th2 cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IFN-GAMMA PRODUCTION; LINKED LYMPHOPROLIFERATIVE SYNDROME; PLACENTAL ALKALINE-PHOSPHATASE; HUMAN B-LYMPHOCYTES; HUMAN T-CELLS; INTERFERON-GAMMA; CYTOKINE PRODUCTION; LYMPHOKINE PRODUCTION; MONOCLONAL-ANTIBODY; IL-18 RECEPTOR AB Optimal T cell activation and expansion require engagement of the TCR plus costimulatory signals delivered through accessory molecules, SLAM (signaling lymphocytic activation molecule), a 70-kDa costimulatory molecule belonging to the Ig superfamily, was defined as a human cell surface molecule that mediated CD28-independent proliferation of human T cells and IFN-gamma production by human Th1 and Th2 clones. In this study, we describe the cloning of mouse SLAM and the production of mAb against it which reveal its expression on primary mouse T and B cells, Mouse SLAM is expressed on highly polarized Th1 and Th2 populations, and is maintained on Th1, but not on Th2 clones. Anti-mouse SLAM mAb augmented IFN-gamma production by Th1 cells and Th1 clones stimulated through the TCR, but did not induce IFN-gamma production by Th2 cells, nor their production of IL-4 or their proliferation, Mouse SLAM is a 75-kDa glycoprotein that upon tyrosine phosphorylation associates with the spe homology 2-domain-containing protein tyrosine phosphatase SHP-2; but not SHP-1. Mouse SLAM also associates with the recently described human SLAM-associated protein. These studies may provide new insights into the regulation of Th1 responses. C1 DNAX Res Inst Mol & Cellular Biol Inc, Dept Immunobiol, Palo Alto, CA 94304 USA. Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. RP O'Garra, A (reprint author), DNAX Res Inst Mol & Cellular Biol Inc, Dept Immunobiol, 901 Calif Ave, Palo Alto, CA 94304 USA. RI Castro, Antonio/F-5863-2011; Tangye, Stuart/H-4023-2014; OI Castro, Antonio/0000-0002-4684-4183; O'Garra, Anne/0000-0001-9845-6134 NR 76 TC 105 Z9 107 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1999 VL 163 IS 11 BP 5860 EP 5870 PG 11 WC Immunology SC Immunology GA 258MT UT WOS:000083843500015 PM 10570270 ER PT J AU Crawford, K Gabuzda, D Pantazopoulos, V Xu, JH Clement, C Reinherz, E Alper, CA AF Crawford, K Gabuzda, D Pantazopoulos, V Xu, JH Clement, C Reinherz, E Alper, CA TI Circulating CD2(+) monocytes are dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; PERIPHERAL-BLOOD MONOCYTES; T-CELLS; LYMPHOID ORGANS; ANTIGEN; DIFFERENTIATION; INTERLEUKIN-4; PROTEIN; POPULATIONS; MACROPHAGES AB Low levels of CD2 have been described on subsets of monocytes, macrophages, and dendritic cells. CD2 is expressed an about one-third of circulating monocytes, at levels one-half log lower than on T or NK cells, representing 2-4% of PBMC. FAGS analysis of CD2(+) and CD2(-) monocytes revealed no significant difference in the expression of adhesion molecules (CD11a/b/c), class II Ags (HLA-DR, -DQ, -DP), myeloid Ags (CD13, CD14, CD33), or costimulatory molecules (CD80, CD86). Freshly isolated CD2(+) and CD2- monocytes were morphologically indistinguishable by phase contrast microscopy. However, scanning electron microscopy revealed large prominent ruffles on CD2(+) monocytes in contrast to small knob-like projections on CD2(-) monocytes. After 2 days of culture, the CD2(+) monocytes largely lost CD14 expression and developed distinct dendrites, where as the CD2(-) monocytes retained surface CD14 and remained round or oval. Freshly isolated CD2(+) monocytes were more potent inducers of the allogeneic MLR and more efficiently induced proliferation of naive T cells in the presence of HIV-1 gp120 than did CD2(-) monocytes. After culture in the presence of GM/CSF and IL-4, CD2(+) monocytes were up to 40-fold more potent than monocyte-derived dendritic cells or CD2- monocytes at inducing allogeneic T cell proliferation. These findings suggest that circulating CD2(+) and CD2(-) monocytes are dendritic cells and the precursors of macrophages, respectively. Thus, dendritic cells are far more abundant in the blood than previously thought, and they and precursors of macrophages exist in the circulation as phenotypically, morphologically, and functionally distinct monocyte populations. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Alper, CA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA09141]; NHLBI NIH HHS [HL29583]; NIAID NIH HHS [AI35630] NR 43 TC 47 Z9 47 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1999 VL 163 IS 11 BP 5920 EP 5928 PG 9 WC Immunology SC Immunology GA 258MT UT WOS:000083843500023 PM 10570278 ER PT J AU Fabbi, M Geginat, J Tiso, M Ramarli, D Parent, D Bargellesi, A Remold-O'Donnell, E AF Fabbi, M Geginat, J Tiso, M Ramarli, D Parent, D Bargellesi, A Remold-O'Donnell, E TI 8B4/20, a private CD43 epitope on developing human thymocytes, is involved in thymocyte maturation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID WISKOTT-ALDRICH SYNDROME; LYMPHOCYTE SURFACE SIALOGLYCOPROTEIN; THYMIC EPITHELIAL-CELLS; T-CELLS; ENDOGENOUS LECTIN; PEANUT AGGLUTININ; SIALOPHORIN CD43; HUMAN-LEUKOCYTES; LEUKEMIA CELLS; O-GLYCANS AB The 8B4/20 Ag is a 120-kDa molecule whose expression on human thymocytes varies according to the differentiation stage: high density on immature CD3(-)/(low) thymocytes, reduced density on CD3(medium) and double-positive thymocytes, and absent on CD3(high) and single-positive thymocytes and on circulating T cells, In this paper are present immunological and biochemical evidence demonstrating that 8B4/20 Ag is a variant of CD43, We show that 8B4/20-expressing molecules, which are a subset of the CD43 molecules on thymocytes, are heterogeneous in charge, suggesting varying sialylation levels. The 8B4/20 epitope was mapped to the peripherally exposed N-terminal region of CD43, and the 8B4/20 antigenic determinant was characterized by requirement for the sialic acid exocyclic polyhydroxyl side chain, a feature shared with ligands of CD22, Altogether, 8B4/20-CD43 expression pattern and biochemical characteristics suggest its participation in carbohydrate-based interactions in the thymus, We therefore used specific Ab to mimic putative 8B4/20 interactions with natural Ligand and examined the effect on isolated thymocytes, Treatment with 8B4/20 had no effect on in vitro apoptosis of isolated thymocytes, In contrast, 8B4/20 ligation enhanced the conversion of isolated thymocytes to differentiated phenotypes, Increased numbers were found in 8B4/20-treated cultures of CD3(high) and single-positive thymocytes and decreased numbers of CD3(-/low) and double-positive thymocytes, strongly suggesting that engagement of 8B4/20 delivers a positive signal that favors completion of the thymocyte maturation program. The ability of 8B4/20 mAb to drive thymocyte maturation in vitro suggests that CD43 molecules bearing the 8B4/20 epitope participate in early events of thymic selection. C1 Ist Nazl Ric Canc, I-16132 Genoa, Italy. FU Berlin, FB Biol Chem Pharm, Berlin, Germany. Univ Genoa, Dipartimento Med Sperimentale, Sez Biochim, Genoa, Italy. Azienda Osped, Verona, Italy. Univ Verona, Policlin Borgo Roma, I-37134 Verona, Italy. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Fabbi, M (reprint author), Ctr Biotecnol Avanzate, Largo R Benzi 10, I-16132 Genoa, Italy. RI Fabbi, Marina/I-1290-2012; OI Geginat, Jens/0000-0003-4813-0384 FU NIAID NIH HHS [AI29880, AI39574, R01 AI039574] NR 53 TC 7 Z9 7 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1999 VL 163 IS 11 BP 5964 EP 5970 PG 7 WC Immunology SC Immunology GA 258MT UT WOS:000083843500028 PM 10570283 ER PT J AU Biancone, L Cantaluppi, V Boccellino, M Del Sorbo, L Russo, S Albini, A Stamenkovic, I Camussi, G AF Biancone, L Cantaluppi, V Boccellino, M Del Sorbo, L Russo, S Albini, A Stamenkovic, I Camussi, G TI Activation of CD40 favors the growth and vascularization of Kaposi's sarcoma SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ENDOTHELIAL-CELLS; EXTRACELLULAR-MATRIX; BASEMENT-MEMBRANE; FUNCTIONAL CD40; SOLUBLE FORM; TUMOR-GROWTH; IN-VITRO; B-CELLS; EXPRESSION; ANGIOGENESIS AB Although CD40 is expressed by several tumor lines and is up-regulated in tumor vascular endothelium, its role in tumor biology is still unclear. In the present study, we investigated the role of CD40 in the growth and vascularization of Kaposi's sarcoma (KS), In vitro, stimulation of CD40 induced migration of KS cells and inhibited vincristine-induced apoptosis, Similarly, the CD40 engagement on endothelial cells resulted in cell contraction, migration, and prevention of serum withdrawal-apoptosis. To understand the biological relevance of CD40 in vivo, KS cells were engineered to express and release a soluble form of CD40 (KS-sCD40) able to disrupt CD40-CD154 interaction. SCID mice s.c. injected with KS-sCD40 cells developed tumors that were significantly smaller than those induced by control cells (KS-neo), In addition, KS-sCD40 tumors showed several areas of necrosis, diffuse presence of apoptotic cells, and poor vascularization. In contrast, KS-neo tumors showed few or absent areas of necrosis and apoptosis and intense vascularization: Moreover, anti-CD40 Abs stimulated neo-angiogenesis in a murine model in which s.c, implantation of Matrigel was used as a vehicle for the delivery of mediators. These observations provide demonstration that CD40 supports tumor cell survival, growth, and neo-vascularization of KS. C1 Univ Turin, Dipartimento Med Interna, Cattedra Nefrol, Chair Nephrol, I-10126 Turin, Italy. Ist Nazl Ric Canc, I-16132 Genoa, Italy. Harvard Univ, Sch Med, Dept Pathol, Mol Pathol Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Camussi, G (reprint author), Univ Turin, Dipartimento Med Interna, Cattedra Nefrol, Chair Nephrol, Corso Dogliotti 14, I-10126 Turin, Italy. RI Camussi, Giovanni/J-7624-2016; OI Camussi, Giovanni/0000-0003-2795-232X; Del Sorbo, Lorenzo/0000-0003-3294-9838 FU NCI NIH HHS [CA55735]; NIGMS NIH HHS [GM48614] NR 32 TC 35 Z9 38 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1999 VL 163 IS 11 BP 6201 EP 6208 PG 8 WC Immunology SC Immunology GA 258MT UT WOS:000083843500057 PM 10570312 ER PT J AU Scherbina, A Rosen, FS Remold-O'Donnell, E AF Scherbina, A Rosen, FS Remold-O'Donnell, E TI WASP levels in platelets and lymphocytes of Wiskott-Aldrich syndrome patients correlate with cell dysfunction SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYNDROME PROTEIN; ACTIN POLYMERIZATION; BLOOD-CELLS; T-CELLS; GENE; MUTATIONS; THROMBOCYTOPENIA; EXPRESSION; DIFFERENTIATION; IDENTIFICATION AB Wiskott-Aldrich syndrome, an inherited blood cell disorder due to mutations of the X-chromosome gene WASP (Wiskott-Aldrich syndrome protein), was characterized originally by thrombocytopenia, immunodeficiency, and eczema. Whereas platelet dysfunction is severe and consistent, immune defects are clinically variable, ranging from negligible to life threatening, To understand this heterogeneity, we quantified WASP in PBMC and platelets, and also in neutrophils, of patients with diverse mutations. A surprisingly complex pattern of WASP expression found for lymphoid cells formed the basis for dividing the patient mutations into four groups, Group A have low WASP levels in PBMC and higher levels in EBV cell lines, as wed as near normal WASP RNA levels (7 patients, most with mild disease), suggesting that group A WASP molecules are hypersusceptible to proteolysis, Group B have low WASP levels in PBMC and EBV cells and similar low RNA levels (2 patients, moderate disease). Group C have discordant expression: WASP-positive peripheral T cells and WASP-negative peripheral B cells and EBV cell lines (9 patients, variable disease severity). Noteworthy among group C kindred are several instances of B cell lymphomas, In group D, PBMC and EBV cell lines are WASP negative (7 patients, severe disease), In contrast to the complex lymphoid cell expression patterns, all patient platelets examined were WASP negative (18 diverse patients). WASP absence in platelets provides an apparent molecular explanation for the universally severe platelet dysfunction in this disease, and the cumulative lymphoid cell findings suggest that WASP levels play a substantial role in determining immune outcome. 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. NR 39 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1999 VL 163 IS 11 BP 6314 EP 6320 PG 7 WC Immunology SC Immunology GA 258MT UT WOS:000083843500071 ER PT J AU Gauthier, J Bourne, EJ Lutz, MW Crowther, LM Dienstag, JL Brown, NA Condreay, LD AF Gauthier, J Bourne, EJ Lutz, MW Crowther, LM Dienstag, JL Brown, NA Condreay, LD TI Quantitation of hepatitis B viremia and emergence of YMDD variants in patients with chronic hepatitis B treated with lamivudine SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 38th Interscience Conference on Antimicrobial Agents and Chemotherapy CY SEP 24-28, 1998 CL SAN DIEGO, CALIFORNIA ID POLYMERASE CHAIN-REACTION; VIRUS POLYMERASE; REACTION ASSAY; INFECTION; THERAPY; DNA; IDENTIFICATION; RESISTANCE; MUTATIONS; TRIAL AB Hepatitis B viremia and emergence of hepatitis B virus (HBV) YMDD variants with reduced susceptibility to lamivudine were analyzed in patient sera from a phase II study of extended lamivudine therapy. Within 12 weeks, all patients exhibited a marked virologic response to lamivudine: >99% reduction (median 5 log decrease) in serum HBV DNA levels. Virus remained at >10(4) genomes/mL in ii patients and decreased to <10(4) genomes/mL in the remaining 12 patients. In 10 patients, detectable YMDD variants emerged during the course of treatment. Six patients, including 3 with YMDD variants, experienced hepatitis B e antigen seroconversion while on lamivudine therapy or soon after its discontinuation. No patients with HBV DNA levels >10(4) genomes/mL seroconverted, Thus, patients who respond to lamivudine therapy with dramatic reductions in viral DNA level (to <10(4) genomes/ml) appear more likely to seroconvert than patients who do not achieve this level of HBV clearance. C1 Glaxo Wellcome Inc, Dept Virol, Res Triangle Pk, NC 27709 USA. Glaxo Wellcome Inc, Dept Infect Dis & Hepatitis, Res Triangle Pk, NC 27709 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Gauthier, J (reprint author), Glaxo Wellcome Inc, Dept Virol, 5 Moore Dr, Res Triangle Pk, NC 27709 USA. OI Lutz, Michael/0000-0001-8809-5574 NR 16 TC 99 Z9 111 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 DEC PY 1999 VL 180 IS 6 BP 1757 EP 1762 DI 10.1086/315147 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 263QW UT WOS:000084137600001 PM 10558928 ER PT J AU Lori, F Jessen, H Lieberman, J Finzi, D Rosenberg, E Tinelli, C Walker, B Siliciano, RF Lisziewicz, J AF Lori, F Jessen, H Lieberman, J Finzi, D Rosenberg, E Tinelli, C Walker, B Siliciano, RF Lisziewicz, J TI Treatment of human immunodeficiency virus infection with hydroxyurea, didanosine, and a protease inhibitor before seroconversion is associated with normalized immune parameters and limited viral reservoir 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 ACTIVE ANTIRETROVIRAL THERAPY; HIV-1 INFECTION; T-CELLS; MACROPHAGE; REPLICATION; LYMPHOCYTES; SUPPRESSION; DISEASE; VIREMIA AB Current treatments for human immunodeficiency virus (HIV) require uninterrupted drug administration because they are unable to reconstitute the immune response and do not affect the viral reservoir. Ten patients were treated during acute HIV infection before complete Western blot (WB) seroconversion with the combination of hydroxyurea, didanosine, and indinavir, This treatment was associated with the normalization of some immune parameters and functions. No loss of naive CD4 T lymphocytes was observed, and recovery of up to 35% of naive CD8 T lymphocytes occurred in several weeks. A vigorous HIV-specific T helper response (stimulation index >8) was observed in 7 of 8 patients treated before complete WB seroconversion but in only 1 of 5 controls treated after seroconversion, In addition, a limited latent viral reservoir (<0.02-0.5 infectious units/10(6) cells) was documented in quiescent peripheral blood lymphocytes after treatment initiated before complete WE seroconversion. C1 RIGHT, Washington, DC 20007 USA. Policlin San Matteo, Ist Ricovero & Cura & Carattere Sci, I-27100 Pavia, Italy. Jessen Praxis, Berlin, Germany. Massachusetts Gen Hosp, Ctr Blood Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. RP Lori, F (reprint author), RIGHT, Med Dent Bldg,SW307,3900 Reservoir Rd NW, Washington, DC 20007 USA. NR 33 TC 78 Z9 78 U1 0 U2 3 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 DEC PY 1999 VL 180 IS 6 BP 1827 EP 1832 DI 10.1086/315113 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 263QW UT WOS:000084137600010 PM 10558937 ER PT J AU Quackenbush, EJ Kraemer, KH Gahl, WA Schirch, V Whiteman, DAH Levine, K Levy, HL AF Quackenbush, EJ Kraemer, KH Gahl, WA Schirch, V Whiteman, DAH Levine, K Levy, HL TI Hypoglycinaemia and psychomotor delay in a child with xeroderma pigmentosum SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID 3-PHOSPHOGLYCERATE DEHYDROGENASE-DEFICIENCY; SERINE HYDROXYMETHYLTRANSFERASE; DISORDERS; GLYCINE AB Glycine is a nonessential amino acid that serves as both an inhibitory and an excitatory neurotransmitter. Hyperglycinaemia occurs in nonketotic hyperglycinaemia, a primary defect in the glycine cleavage pathway, and as a secondary feature of several inborn errors of organic acid metabolism. However, specifically low levels of glycine have never been reported. Here we report a child with complementation group C xeroderma pigmentosum (XP) characterized by a splice donor mutation in the XPC gene, multiple skin cancers and specific and persistent hypoglycinaemia. He has cognitive delay, lack of speech, autistic features, hyperactivity and hypotonia, all unexplained by the diagnosis of XP group C, a non-neurological form of the disease. Treatment with oral glycine has improved his hyperactivity. Specific hypoglycinaemia could indicate a metabolic disorder producing neurological dysfunction. Whether it is related to or coincidental with the XP is unclear. C1 Childrens Hosp, Div Genet, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. NCI, Mol Carcinogenesis Lab, Bethesda, MD 20892 USA. NICHHD, Heritable Disorders Branch, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Richmond, VA USA. Maine Med Ctr, Portland, OR USA. RP Levy, HL (reprint author), Childrens Hosp, Div Genet & Metab, IC Smith Bldg,300 Longwood Ave, Boston, MA 02115 USA. FU Intramural NIH HHS [Z01 BC004517-31] NR 23 TC 5 Z9 5 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD DEC PY 1999 VL 22 IS 8 BP 915 EP 924 DI 10.1023/A:1005691424004 PG 10 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 256GA UT WOS:000083716500006 PM 10604143 ER PT J AU Murray, GB AF Murray, GB TI Last resort: Psychosurgery an the limits of medicine. SO JOURNAL OF INTERDISCIPLINARY HISTORY LA English DT Book Review C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Murray, GB (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0022-1953 J9 J INTERDISCIPL HIST JI J. Interdiscip. Hist. PD WIN PY 1999 VL 30 IS 3 BP 489 EP 490 DI 10.1162/jinh.1999.30.3.489 PG 2 WC History SC History GA 276TD UT WOS:000084892700009 ER PT J AU Brancaleon, L Lin, G Kollias, N AF Brancaleon, L Lin, G Kollias, N TI The in vivo fluorescence of tryptophan moieties in human skin increases with UV exposure and is a marker for epidermal proliferation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE collagen fluorescence; optical spectroscopy ID THYMINE DIMERS; IN-VIVO; MELANOMAS AB We have investigated the in vivo fluorescence of human skin with UV excitation and the effect of UV irradiation on the UV fluorescence. A particular chromophore was found to be very sensitive to suberythemogenic UV radiation. This chromophore has the spectral characteristics of tryptophan residues in proteins and is characterized by a fluorescence excitation maximum at 295 nm. The fluorescence of this chromophore in human epidermis has an excitation maximum that is coincident with the maximum of the action spectrum of most UV-induced photobiologic responses to human skin. The fluorescence of the chromophore was found to increase with UV exposure. The action spectrum was determined by following the increase of the emission at 345 nm with excitation at 295 nm as a function of skin exposure to a number of wavelengths in the UV region of the spectrum. The results show that irradiation in the UVB (290-320 nm) is more effective in producing the change in the fluorescence of tryptophan. Irradiation in the UVA (320-380 nm) was found to be capable of producing the increase but to a smaller extent. Whereas tryptophan fluorescence is found in both the epidermis and the dermis, it is only the epidermal component that increases with UV exposure. The change in 295 nm fluorescence with UV exposure was determined to be oxygen dependent. The fluorescence of tryptophan moieties measured in situ was found to increase when epidermal proliferation increases. This was verified by inducing epidermal repair after mechanical insult (tape stripping). The results suggest two possible scenarios for the UV-induced increase of the fluorescence: a prompt photooxidation of tryptophan moieties or a fast proliferation response to the insult created by UV irradiation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. RP Kollias, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, MGH BHX 630,55 Fruit St, Boston, MA 02114 USA. RI Brancaleon, Lorenzo/B-5625-2009 NR 38 TC 51 Z9 51 U1 0 U2 4 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 1999 VL 113 IS 6 BP 977 EP 982 DI 10.1046/j.1523-1747.1999.00799.x PG 6 WC Dermatology SC Dermatology GA 268VE UT WOS:000084436600018 PM 10594740 ER PT J AU Bales, ES Dietrich, C Bandyopadhyay, D Schwahn, DJ Xu, WD Didenko, V Leiss, P Conrad, N Pereira-Smith, O Orengo, I Medrano, EE AF Bales, ES Dietrich, C Bandyopadhyay, D Schwahn, DJ Xu, WD Didenko, V Leiss, P Conrad, N Pereira-Smith, O Orengo, I Medrano, EE TI High levels of expression of p27(KIP1) and cyclin E in invasive primary malignant melanomas SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; INHIBITOR P27(KIP1); FREE SURVIVAL; PROTEIN; P21(WAF1/CIP1); PROGRESSION; DIFFERENTIATION; GENE; P53; P21 AB Cancer cells have abnormal cell cycle regulation which favors accelerated proliferation, chromosomal instability, and resistance to the senescence response. Although the p16(INK5n) locus is the most prominent susceptibility locus for familial melanomas, the low frequency of p16 mutations in sporadic melanomas suggests additional alterations in other cell cycle regulatory genes. Here we used primary melanoma tumors to reveal early cell cycle alterations that could be masked in advanced metastatic lesions due to their inherently high genetic instability. Unexpectedly, the cyclin-dependent kinase inhibitors p27(KIP1) and/or p21(Waf-1/SDI-1) were found to be expressed in 13 of 18 (72%) of the primary melanomas with a Breslow thickness greater than 0.076 mm, In general, p27 and/or p21 staining in the primary tumors correlated with low Ki-67 index, Importantly, most of the p21- and p27-positive tumors expressed high levels of cyclin D1 and cyclin E, In proliferating cells p27 is predominantly associated with cyclin D-CDK4 complexes, but does not inhibit the kinase activity, whereas in quiescent cells p27 is found associated with inactive CDK2 complexes, p27 was also expressed at high levels in proliferating primary melanomas in culture, and found to be associated with active cyclin E-CDK2 complexes containing high levels of cyclin E, It is thus Likely that accumulation of cyclin E overcomes the potent inhibitory activity of p27 and p21 in CDK2 complexes. Of the primary melanomas with no indication of invasiveness, only three of 15 (20%) were positive for p27 and/or p21, We propose that high levels of p27 and p21 may confer upon melanoma tumors their characteristic resistance to conventional therapies. In turn, high levels of cyclins E and D1 may contribute to unlimited proliferation in primary melanomas that express the tumor suppressor p16(INK4). C1 Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA. Baylor Coll Med, Div Mol Virol, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Dermatol, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurosurg, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. RP Medrano, EE (reprint author), Baylor Coll Med, VAMC, Res Serv, Bld 110, Houston, TX 77030 USA. FU NIA NIH HHS [AG00594, AG3663] NR 45 TC 56 Z9 58 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 1999 VL 113 IS 6 BP 1039 EP 1046 DI 10.1046/j.1523-1747.1999.00812.x PG 8 WC Dermatology SC Dermatology GA 268VE UT WOS:000084436600027 PM 10594749 ER PT J AU Skobe, M Brown, LF Tognazzi, K Ganju, RK Dezube, BJ Alitalo, K Detmar, M AF Skobe, M Brown, LF Tognazzi, K Ganju, RK Dezube, BJ Alitalo, K Detmar, M TI Vascular endothelial growth factor-C (VEGF-C) and its receptors KDR and flt-4 are expressed in AIDS-associated Kaposi's sarcoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE angiogenesis; HIV; lymphatics; VEGF ID PERMEABILITY FACTOR; TYROSINE KINASE; LYMPHATIC ENDOTHELIUM; SPINDLE CELLS; ANGIOGENESIS; ULTRASTRUCTURE; INDUCTION; MITOGEN; CULTURE; LIGAND AB Kaposi's sarcoma is characterized by clusters of spindle-shaped cells that are considered to be tumor cells and by prominent vasculature. Whereas spindle cells are most likely endothelial in origin, it remains controversial whether they are of lymphatic or blood vascular derivation. To test the hypothesis that the lymphangiogenesis factor vascular endothelial growth factor-C and its receptors, KDR and flt-4, are involved in the pathogenesis of Kaposi's sarcoma, we performed in situ hybridizations and immunofluorescent stainings on human immunodeficiency virus-associated Kaposi's sarcoma, Spindle-shaped tumor cells strongly expressed KDR and flt-4 mRNA, Immunofluorescent staining confirmed expression of the flt-4 receptor in Kaposi's sarcoma cells, and double labeling revealed its colocalization with the endothelial cell marker CD31. Vascular endothelial growth factor-C was strongly expressed in blood vessels associated with Kaposi's sarcoma. In vitro, human dermal microvascular endothelial cells also expressed vascular endothelial growth factor-C mRNA that was further upregulated by vascular permeability factor/vascular endothelial growth factor. Vascular endothelial growth factor-C potently stimulated the proliferation of Kaposi's sarcoma tumor cells in vitro. These results demonstrate important paracrine functions of vascular endothelial growth factor-C, produced by blood vessels, in the pathogenesis of cutaneous Kaposi's sarcoma, and suggest a lymphatic origin and/or differentiation of Kaposi's sarcoma tumor cells. C1 Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Med Sch, Charlestown, MA USA. Beth Israel Deaconess Med Ctr, Div Expt Med & Hematol Oncol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. Univ Helsinki, Haartman Inst, FIN-00014 Helsinki, Finland. RP Detmar, M (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Alitalo, Kari/J-5013-2014 OI Alitalo, Kari/0000-0002-7331-0902 FU NCI NIH HHS [CA69184] NR 42 TC 87 Z9 92 U1 0 U2 3 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 1999 VL 113 IS 6 BP 1047 EP 1053 DI 10.1046/j.1523-1747.1999.00798.x PG 7 WC Dermatology SC Dermatology GA 268VE UT WOS:000084436600028 PM 10594750 ER PT J AU Tager, AM Luster, AD Leary, CP Sakamoto, H Zhao, LH Preffer, F Kradin, RL AF Tager, AM Luster, AD Leary, CP Sakamoto, H Zhao, LH Preffer, F Kradin, RL TI Accessory cells with immunophenotypic and functional features of monocyte-derived dendritic cells are recruited to the lung during pulmonary inflammation SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE macrophages; bleomycin ID CD34(+) HEMATOPOIETIC PROGENITORS; COLONY-STIMULATING-FACTOR; CORD-BLOOD DIFFERENTIATE; ALVEOLAR MACROPHAGES; BLEOMYCIN; FIBROSIS; MICE; ANTIGEN; SURFACE; ALPHA AB Pulmonary macrophages (M phi) increase in tissue and bronchoalveolar lavage (BAL) fluid during inflammation caused by bleomycin (BLM). This study demonstrates that increasing numbers of exudate M phi in BLM lung injury exhibit dendritic cell(DC) features. After the intratracheal administration of BLM (0.075 U), adherent mononuclear cells front the bronchoalveolar lavage fluid (BAMC) of C57BL/6 mice were characterized for morphology, immunophenotype, and accessory cell activities. At day 7 post-BLM, 48% of CD11b(+) BAMC displayed features of DC differentiation, as judged by dendritic morphology, expression of class II MHC, 33D1, Factor XIIIa, CD80, and CD86 antigens, and the ability to support a primary allogeneic lymphocyte response (MLR). After BLM treatment, CD11b(+) peripheral blood monocytes also showed increased expression of 33D1, Factor XIIIa, CD86? and the ability to stimulate an MLR. We conclude that inflammatory DC with immunophenotypic features of monocyte-derived DC increase in the peripheral blood and lung after an inflammatory stimulus. C1 Massachusetts Gen Hosp, Dept Med, Immunopathol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kradin, RL (reprint author), Massachusetts Gen Hosp, Dept Med, Immunopathol Unit, 100 Blossom St,Cox 5, Boston, MA 02114 USA. FU NIAID NIH HHS [R01 AI39054] NR 48 TC 14 Z9 14 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD DEC PY 1999 VL 66 IS 6 BP 901 EP 908 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 266UA UT WOS:000084317600004 PM 10614770 ER PT J AU Wong, GP Tseng, CH Pomeroy, VR Mair, RW Hinton, DP Hoffmann, D Stoner, RE Hersman, FW Cory, DG Walsworth, RL AF Wong, GP Tseng, CH Pomeroy, VR Mair, RW Hinton, DP Hoffmann, D Stoner, RE Hersman, FW Cory, DG Walsworth, RL TI A system for low field imaging of laser-polarized noble gas SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE laser-polarized noble gas; low magnetic field; magnetic resonance imaging; lung imaging; radiation damping ID HYPERPOLARIZED HE-3; RESONANCE; DIFFUSION; XE-129; MRI AB We describe a device for performing MRI: with laser-polarized noble gas at low magnetic fields (<50 G). The system is robust, portable, inexpensive, and provides gas-phase imaging resolution comparable to that of high field clinical instruments. At 20.6 G, we have imaged laser-polarized He-3 (Larmor frequency of 67 kHz) in both sealed glass cells and excised rat lungs, using similar to 0.1 G/cm gradients to achieve similar to 1 mm(2) resolution. In addition, we measured He-3 T-2(*) times greater than 100 ms in excised rat lungs, which is roughly 20 times longer than typical values observed at high (similar to 2 T) fields. We include a discussion of the practical considerations for working at low magnetic fields and conclude with evidence of radiation damping in this system. (C) 1999 academic Press. C1 Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA. MIT, Dept Nucl Engn, Cambridge, MA 02138 USA. Univ New Hampshire, Dept Phys, Durham, NH 03824 USA. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. RP Wong, GP (reprint author), Harvard Smithsonian Ctr Astrophys, 60 Garden St, Cambridge, MA 02138 USA. OI Stoner, Richard/0000-0001-7949-6747 NR 25 TC 40 Z9 40 U1 0 U2 8 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD DEC PY 1999 VL 141 IS 2 BP 217 EP 227 DI 10.1006/jmre.1999.1904 PG 11 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 263RZ UT WOS:000084140200003 PM 10579945 ER PT J AU Cariski, D Rosenbek, J AF Cariski, D Rosenbek, J TI The effectiveness of the Speech Enhancer (TM) SO JOURNAL OF MEDICAL SPEECH-LANGUAGE PATHOLOGY LA English DT Article ID PARKINSONS-DISEASE AB The influence of the Speech Enhancer(TM) on sentence intelligibility was measured for two males with severe hypokinetic dysarthria under a variety of environmental settings. Comparisons of speech intelligibility were made between sentences read aloud with and without the Speech Enhancer. Additional measures of speech intelligibility were made for one of the subjects, including a comparison between the Speech Enhancer and another amplifier and the combined effect of treatment with the Speech Enhancer. The treatment effects on speech intelligibility were appreciable. Clinical implications are discussed. C1 William S Middleton Mem Vet Hosp, Speech Pathol Serv, Madison, WI 53705 USA. RP Cariski, D (reprint author), William S Middleton Mem Vet Hosp, Audiol & Speech Pathol Serv, 2500 Overlook Terrace, Madison, WI 53705 USA. NR 16 TC 7 Z9 7 U1 1 U2 3 PU SINGULAR PUBLISHING GROUP INC PI SAN DIEGO PA 401 WEST A ST, STE 325, SAN DIEGO, CA 92101-7904 USA SN 1065-1438 J9 J MED SPEECH-LANG PA JI J. Med. Speech-Lang. Pathol. PD DEC PY 1999 VL 7 IS 4 BP 315 EP 322 PG 8 WC Audiology & Speech-Language Pathology; Clinical Neurology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology GA 264LL UT WOS:000084183700007 ER PT J AU Prabhu, SD Azimi, A Frosto, T AF Prabhu, SD Azimi, A Frosto, T TI Nitric oxide effects on myocardial function and force-interval relations: Regulation of twitch duration SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE nitric oxide; myocardial contraction; force-interval relaion; systole e-c coupling; sarcoplasmic reticulum; rat ID RAT VENTRICULAR MYOCYTES; CARDIAC-MUSCLE; FREQUENCY-RELATIONSHIP; CONTRACTILE RESPONSE; ACTIVATION; SYNTHASE; RELEASE; HUMANS; FERRET; CGMP AB As the precise role of nitric oxide (NO) as a modulator of myocardial contraction and the force-interval relationship remains unclear, the objective of this study was to examine the effect of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) on baseline myocardial contraction, and the impact of both SNAP and the NO synthase (NOS) inhibitor N-G-nitro-L-arginine methyl ester (L-NAME) on the force interval relation, Studies were performed using isolated rat papillary muscles. In the presence of baseline NOS blockade, nanomolar to micromolar concentrations of SNAP exerted a modest positive inotropic effect with a small but significant increase in twitch isometric tension (P<0.007). Nanomolar concentrations of SNAP also reduced overall twitch duration (P<0.007). These effects were not seen in control experiments using N-acetyl-penicillamine instead of SNAP The force-frequency response (FFR) and post-rest contractile potentiation, mechanical correlates of sarcoplasmic reticulum ISR) Ca2+ handling, were also examined. Neither L-NAME, nor SNAP had any effect on post-rest potentiation following rest intervals as long as 6 min, or on the negative FFR at stimulation frequencies between 0.3 to 1.7 Hz, However, L-NAME significantly blunted the net reduction in twitch duration between 0.3 Hz and 1.7 Wt compared to control (P = 0.006), an effect reversed by 100 nM SNAP. These results indicate that low concentrations of NO can modulate myocardial function by influencing myocardial inotropy and the time course of myofilament interaction, but do not impact significantly on the force interval relation and, by inference, SR Ca2+ handling. Moreover, modulation of twitch duration occurs over a of stimulation frequencies, suggesting a mechanistic role for NO in the changes range ol simulation frequencies. suggesting a mechanist: relaxation time intervals seen during changes in heart rate. (C) in contraction and (C) 1399 Academic Press. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX 78284 USA. RP Prabhu, SD (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med Cardiol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM Prabhu@uthscsa.edu RI Prabhu, Sumanth/D-5223-2009 NR 28 TC 19 Z9 20 U1 3 U2 5 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD DEC PY 1999 VL 31 IS 12 BP 2077 EP 2085 DI 10.1006/jmcc.1999.1038 PG 9 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 274UB UT WOS:000084782500001 PM 10640437 ER PT J AU Chin, MT Pellacani, A Hsieh, CM Lin, SSJ Jain, MK Patel, A Huggins, GS Reeves, R Perrella, MA Lee, ME AF Chin, MT Pellacani, A Hsieh, CM Lin, SSJ Jain, MK Patel, A Huggins, GS Reeves, R Perrella, MA Lee, ME TI Induction of high mobility group I architectural transcription factors in proliferating vascular smooth muscle in vivo and in vitro SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE restenosis; vascular injury; arteriosclerosis ID RAT-THYROID CELLS; FACTOR HMGI-C; DNA-BINDING; CHROMOSOMAL-PROTEINS; NEOPLASTIC TRANSFORMATION; CELLULAR PROLIFERATION; GENE-EXPRESSION; HMG-I(Y); GROWTH; CDNA AB Proliferation of vascular smooth muscle cells (VSMCs) is a hallmark of arteriosclerosis. Architectural transcription factors of the high mobility group (HMG)-I family have been implicated in the control of cell proliferation and gene expression. We studied the pattern of HMG-I mRNA and protein expression in proliferating VSMCs. HMG-I(Y) and HMGI-C mRNAs were barely detectable by Northern analysis in samples prepared from uninjured rat carotid arteries. In contrast, these mRNAs were induced dramatically in carotid arteries 2 and 5-6 days after balloon injury. By in situ hybridization at 6 days after injury, the induced mRNAs localized to smooth muscle cells of the developing neointima, and immunocytochemical analysis showed that HMG-I(Y) protein was expressed in the nuclei of these cells. To confirm this association between HMG-I protein induction and cell growth, we assessed HMG-I(Y) and HMGI-C mRNA expression in rat aortic smooth muscle cells (RASMCs) in primary culture. The HMG-I mRNAs were barely detectable in quiescent RASMCs but were induced markedly by serum stimulation. This induction of mRNA by serum was time dependent and peaked at 9 h, Western blot analysis confirmed that HMG-I(Y) protein induction also occurred in vitro. To our knowledge, this is the first demonstration of induction of HMG-I protein expression in proliferating RASMCs in vivo and in vitro. This demonstration suggests that the HMG-I proteins may play an important role in smooth muscle cell proliferation. (C) 1999 Academic Press. C1 Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Brigham & Womens Hosp, Div Pulm & Crit Care, Boston, MA 02115 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Washington State Univ, Dept Biochem & Biophys, Pullman, WA 99164 USA. RP Lee, ME (reprint author), Brigham & Womens Hosp, Div Cardiovasc, Thorn 12,75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL03194, HL03745]; NIGMS NIH HHS [GM53249] NR 32 TC 12 Z9 12 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD DEC PY 1999 VL 31 IS 12 BP 2199 EP 2205 DI 10.1006/jmcc.1999.1054 PG 7 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 274UB UT WOS:000084782500011 PM 10640447 ER PT J AU Scott, EL Pollack, MH Otto, MW Simon, NM Worthington, JJ AF Scott, EL Pollack, MH Otto, MW Simon, NM Worthington, JJ TI Clinician response to treatment refractory panic disorder: A survey of psychiatrists SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID THERAPY; ANXIETY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA 02114 USA. Temple Univ, Adult Anxiety Clin, Philadelphia, PA 19122 USA. RP Scott, EL (reprint author), Massachusetts Gen Hosp, 15 Parkman St,WACC 815, Boston, MA 02114 USA. NR 13 TC 5 Z9 5 U1 1 U2 1 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 DEC PY 1999 VL 187 IS 12 BP 755 EP 757 DI 10.1097/00005053-199912000-00009 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 271EE UT WOS:000084580600009 PM 10665472 ER PT J AU Holtzman, D Khait, I Mulkern, R Allred, E Rand, T Jensen, F Kraft, R AF Holtzman, D Khait, I Mulkern, R Allred, E Rand, T Jensen, F Kraft, R TI In vivo development of brain phosphocreatine in normal and creatine-treated rabbit pups SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE creatine; development; seizures; brain phosphocreatine; hypoxia; nuclear magnetic resonance spectroscopy ID MAGNETIC-RESONANCE SPECTROSCOPY; CEREBRAL GRAY; WHITE-MATTER; RAT-BRAIN; PHOSPHORUS METABOLITES; INTRACELLULAR PH; IN-VIVO; SEIZURES; KINASE; ATP AB To study the effects; of creatine (Cr) on brain energy metabolism and on hypoxia-induced seizures, 5-to 30-day-old rabbit pups were given subcutaneous Cr (3 g/kg) for 3 days before exposure to 4% O-2 for 8 min. In saline-treated controls, hypoxic seizures were most frequent at 15 days (80% of pups) and 20 days (60%) of age. Seizures were prevented at 15 days and reduced 60% at 20 days in Cr-treated pups. In surface coil-localized brain P-31 nuclear magnetic resonance spectra, with signal from both cerebral gray (GM) and white (WM) matter, the phosphocreatine (PCr)/nucleoside triphosphate (NTP) ratio doubled between 5 and 30 days of age in controls. In all Cr-injected pups;, brain PCr/NTP increased to values seen in 30-day-old controls. When spectra were acquired in predominantly GM and WM slices in vivo, the PCr/NTP ratio was very low in GM at 5 days but reached adult levels by 15 days in controls. In WM, the ratio increased steadily from 5 to 30 days of age. In Cr-injected pups, PCr/NTP increased to mature levels in WM and in GM at all ages. In conclusion, hypoxic seizures occur midway in the time course of brain PCr/NTP increase in rabbit pups as previously described in rat pups. In both altricial pups, systemic Cr increases brain PCr/NTP ratio and prevents hypoxic seizures. These results suggest that mature levels of PCr and/or Cr in brain limit EEG activation either directly or indirectly by preventing hypoxic metabolic changes. C1 Brigham & Womens Hosp, LMRC, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Childrens Hosp, Dept Neurol Epidemiol, Boston, MA 02115 USA. MIT, Dept Nucl Engn, Cambridge, MA 02139 USA. Childrens Hosp, Dept Radiol, Cambridge, MA USA. RP Holtzman, D (reprint author), Brigham & Womens Hosp, LMRC, Dept Radiol, 221 Longwood Ave, Boston, MA 02115 USA. FU NINDS NIH HHS [NS 26371] NR 42 TC 26 Z9 28 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 1999 VL 73 IS 6 BP 2477 EP 2484 DI 10.1046/j.1471-4159.1999.0732477.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 256JX UT WOS:000083723100029 PM 10582608 ER PT J AU Newell, KL Boyer, P Gomez-Tortosa, E Hobbs, W Hedley-Whyte, ET Vonsattel, JP Hyman, BT AF Newell, KL Boyer, P Gomez-Tortosa, E Hobbs, W Hedley-Whyte, ET Vonsattel, JP Hyman, BT TI alpha-synuclein immunoreactivity is present in axonal swellings in neuroaxonal dystrophy and acute traumatic brain injury SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE alpha-synuclein; axonal spheroids; axonal swellings; diffuse axonal injury; Hallervorden-Spatz syndrome; Lewy body; neuroaxonal dystrophy ID AMYLOID PRECURSOR PROTEIN; MULTIPLE SYSTEM ATROPHY; HALLERVORDEN-SPATZ SYNDROME; LEWY BODY DISEASE; GLIAL CYTOPLASMIC INCLUSIONS; PARKINSONS-DISEASE; NEURODEGENERATIVE DISORDERS; ALZHEIMERS-DISEASE; BODIES; DEMENTIA AB The primary neuroaxonal dystrophies (NAD), which include infantile NAD and Hallervorden-Spatz syndrome (HSS), an characterized by dystrophic terminal axons and axonal swellings. Lewy bodies have been found in some cases. In Parkinson disease (PD) and dementia with Lewy bodies (DLB), Lewy bodies and neurites display prominent alpha-synuclein immunoreactivity. We examined 2 cases of HSS and 4 cases of infantile NAD with alpha-synuclein immunohistochemistry to test the hypothesis that these disorders with similar morphological findings might share a biochemical phenotype. Furthermore, we compared them to 8 cases of secondary or physiologic NAD of various causes and 2 cases of recent traumatic head injury. alpha-Synuclein positive neuronal cytoplasmic inclusions, including Lewy bodies, and neurites were numerous in 1 HSS and 1 infantile NAD case. In addition, axonal spheroids were immunostained in all 6 cases of primary NAD, 5 cases of secondary NAD, and 2 cases of recent head injury. Axonal spheroids were faintly stained in the 3 physiologic NAD cases. alpha-Synuclein positive axonal swellings may suggest a mechanism, such as axonal injury, leading to the neuronal cytoplasmic accumulation of alpha-synuclein in NAD and other disorders. C1 Harvard Univ, Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. RP Newell, KL (reprint author), Massachusetts Gen Hosp E, Alzheimers Dis Res Unit, 149 13th St,Room 6604B, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG05134] NR 35 TC 82 Z9 82 U1 0 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD DEC PY 1999 VL 58 IS 12 BP 1263 EP 1268 DI 10.1097/00005072-199912000-00007 PG 6 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 267JU UT WOS:000084355500007 PM 10604751 ER PT J AU Yoshida, N Liberman, MC Brown, MC Sewell, WF AF Yoshida, N Liberman, MC Brown, MC Sewell, WF TI Gentamicin blocks both fast and slow effects of olivocochlear activation in anesthetized guinea pigs SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID OUTER HAIR-CELLS; PRODUCT OTOACOUSTIC EMISSIONS; AMINOGLYCOSIDE ANTIBIOTICS; CONTRALATERAL SOUND; NEUROMUSCULAR-TRANSMISSION; COCHLEAR POTENTIALS; NERVE-TERMINALS; CALCIUM; ACETYLCHOLINE; STIMULATION AB The medial olivocochlear (MOC) efferent system, which innervates cochlear outer hair cells, suppresses cochlear responses. MOC-mediated suppression includes both slow and fast components, with time courses differing by three orders of magnitude. Pharmacological studies in anesthetized guinea pigs suggest that both slow and fast effects on cochlear responses require an initial acetylcholine activation of alpha-9 nicotinic receptors on outer hair cells and that slow effects require additional intracellular events downstream from those mediating fast effects. Gentamicin, an aminoglycoside antibiotic, has been reported to block fast effects of sound-evoked OC activation following intramuscular injection in unanesthetized guinea pigs, without changing slow effects. In the present study, we show that electrically evoked fast and slow effects in the anesthetized guinea pig are both blocked by either intramuscular or intracochlear gentamicin, with similar time courses and/or dose-response curves. We suggest that sound-evoked slow effects in unanesthetized animals are fundamentally different from electrically evoked slow effects in anesthetized animals, and that the former may arise from effects of the lateral OC system. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Tohoku Univ, Grad Sch Med, Dept Otolaryngol, Sendai, Miyagi 9808574, Japan. RP Sewell, WF (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [P01 DC-0119] NR 46 TC 31 Z9 31 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 1999 VL 82 IS 6 BP 3168 EP 3174 PG 7 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 268NH UT WOS:000084422100028 PM 10601450 ER PT J AU Fitten, LJ Ortiz, F Siembieda, DW O'Neill, J Halgren, E Fisher, A AF Fitten, LJ Ortiz, F Siembieda, DW O'Neill, J Halgren, E Fisher, A TI Reduction of motoric agitation and restlessness by AF102B and tacrine in the macaque SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID ALZHEIMERS-DISEASE; AGED MONKEYS; DOUBLE-BLIND; CHOLINESTERASE-INHIBITORS; CHOLINERGIC HYPOTHESIS; PRIMATE MODELS; DEMENTIA; PATIENT; MEMORY; TETRAHYDROAMINOACRIDINE AB The cholinesterase inhibitor tacrine (THA) and the M(1) muscarinic agonist AF102B (cevimeline), both reported to enhance cognition in animals and humans, were tested in 5 macaques for reduction of spontaneous, random movements. Monkeys were videotaped 1 hour after administration of normal saline vehicle, after low- and high-dose intramuscular AF102B, and after low- and high-dose oral THA. Two independent blind judges counted numbers of spontaneous movements made by each monkey over 12 consecutive 15-second segments for each drug condition. Both THA and AF102B reduced movement significantly at high doses without overt side effects, warranting further research on the agitation-reducing potential of cognition-enhancing cholinomimetic drugs. C1 US Dept Vet Affairs, Supulveda Med Ctr, Los Angeles, CA USA. RP Fitten, LJ (reprint author), Vet Adm Med Ctr, 116A-9,16111 Plummer St, Sepulveda, CA 91343 USA. NR 47 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD WIN PY 1999 VL 11 IS 1 BP 79 EP 85 PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 162PC UT WOS:000078354800012 PM 9990560 ER PT J AU Takahashi, T Goto, T Miyama, S Nowakowski, RS Caviness, VS AF Takahashi, T Goto, T Miyama, S Nowakowski, RS Caviness, VS TI Sequence of neuron origin and neocortical laminar fate: Relation to cell cycle of origin in the developing murine cerebral wall SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neocortical histogenesis; neuronogenesis; pseudostratified ventricular epithelium (PVE); cell cycle; neuronogenetic sequence; transverse neuronogenetic gradient ID PRIMARY VISUAL-CORTEX; PROLIFERATIVE EPITHELIUM; SOMATOSENSORY CORTEX; CORTICAL-NEURONS; REELER MICE; MOUSE; MIGRATION; DEATH; AREAS; HISTOGENESIS AB Neurons destined for each region of the neocortex are known to arise approximately in an "inside-to-outside" sequence from a pseudostratified ventricular epithelium (PVE). This sequence is initiated rostrolaterally and propagates caudomedially. Moreover, independently of location in the PVE, the neuronogenetic sequence in mouse is divisible into 11 cell cycles that occur over a 6 d period. Here we use a novel "birth hour" method that identifies small cohorts of neurons born during a single 2 hr period, i.e., 10-20% of a single cell cycle, which corresponds to similar to 1.5% of the 6 d neuronogenetic period. This method shows that neurons arising with the same cycle of the 11 cycle sequence in mouse have common laminar fates even if they arise from widely separated positions on the PVE (neurons of fields 1 and 40) and therefore arise at different embryonic times. Even at this high level of temporal resolution, simultaneously arising cells occupy more than one cortical layer, and there is substantial overlap in the distributions of cells arising with successive cycles. We demonstrate additionally that the laminar representation of cells arising with a given cycle is little if at all modified over the early postnatal interval of histogenetic cell death. We infer from these findings that cell cycle is a neuronogenetic counting mechanism and that this counting mechanism is integral to subsequent processes that determine cortical laminar fate. C1 Keio Univ, Sch Med, Dept Pediat, Tokyo 160, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA. RP Takahashi, T (reprint author), Keio Univ, Sch Med, Dept Pediat, Tokyo 160, Japan. RI Nowakowski, Richard/C-3217-2016; OI Nowakowski, Richard/0000-0002-5006-3670 FU NINDS NIH HHS [NS12005, NS33433] NR 71 TC 205 Z9 207 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 1 PY 1999 VL 19 IS 23 BP 10357 EP 10371 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 258YN UT WOS:000083867400018 PM 10575033 ER PT J AU Park, JK Williams, BP Alberta, JA Stiles, CD AF Park, JK Williams, BP Alberta, JA Stiles, CD TI Bipotent cortical progenitor cells process conflicting cues for neurons and glia in a hierarchical manner SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neurons; astrocytes; CNTF; PDGF; cortical development; neuroepithelial cells; signal transduction ID CENTRAL-NERVOUS-SYSTEM; FIBROBLAST GROWTH-FACTOR; STEM-CELLS; PRECURSOR CELL; DIFFERENTIATION; PROLIFERATION; RAT; BRAIN; EGF; NEUROTROPHINS AB Neurons and glia of the cerebral cortex are thought to arise from a common, multipotent progenitor cell that is instructed toward alternate fates by extracellular cues. How do these cells behave when confronted with conflicting cues? We show here that nestin-positive neuroepithelial (NE) cells from embryonic day 14 rat cortex coexpress surface receptor proteins for ciliary neurotrophic factor (CNTF) and platelet-derived growth factor (PDGF). Both sets of these receptor proteins are functional in NE cells, as shown by ligand-dependent activation of downstream signal-generating proteins. Transient (30') exposure to CNTF instructs NE cells toward an astrocyte fate. Brief exposure to PDGF initiates neuronal differentiation. However, when challenged with conflicting cues, PDGF is dominant to CNTF. Moreover, CNTF-treated NE cells can be "redirected" by a subsequent exposure to PDGF to form neurons instead of astrocytes, whereas the converse is not true. The asymmetric relationship between CNTF and PDGF indicates that these two growth factors act on a common progenitor cell that has, at a minimum, two fates available to it rather than separate populations of precommitted neuroblasts and astroblasts. This bi-potent progenitor cell processes conflicting cues for neurons and glia in a hierarchical manner. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Neurosurg, Boston, MA 02115 USA. UCL, Sch Med, Windeyer Inst Med Sci, Dept Mol Pathol, London W1P 6DB, England. RP Stiles, CD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Microbiol & Mol Genet, 44 Binney St, Boston, MA 02115 USA. EM charles_stiles@dfci.harvard.edu FU NICHD NIH HHS [P01 HD24826-10] NR 32 TC 53 Z9 56 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 1 PY 1999 VL 19 IS 23 BP 10383 EP 10389 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 258YN UT WOS:000083867400020 PM 10575035 ER PT J AU Benmansour, S Cecchi, M Morilak, DA Gerhardt, GA Javors, MA Gould, GG Frazer, A AF Benmansour, S Cecchi, M Morilak, DA Gerhardt, GA Javors, MA Gould, GG Frazer, A TI Effects of chronic antidepressant treatments on serotonin transporter function, density, and mRNA level SO JOURNAL OF NEUROSCIENCE LA English DT Article DE serotonin transporter; antidepressants; in vivo electrochemistry; [H-3]CN-IMI binding; mRNA for the SERT; dorsal hippocampus ID DORSAL RAPHE NUCLEUS; MESSENGER-RNA LEVELS; LONG-TERM TREATMENT; RAT-BRAIN; 5-HT UPTAKE; QUANTITATIVE AUTORADIOGRAPHY; UPTAKE SITES; FLUOXETINE TREATMENT; IN-VIVO; PAROXETINE AB To investigate functional changes in the brain serotonin transporter (SERT) after chronic antidepressant treatment, several techniques were used to assess SERT activity, density, or its mRNA content. Rats were treated by osmotic minipump for 21 d with the selective serotonin reuptake inhibitors (SSRIs) paroxetine or sertraline, the selective norepinephrine reuptake inhibitor desipramine (DMI), or the monoamine oxidase inhibitor phenelzine. High-speed in vivo electrochemical recordings were used to assess the ability of the SSRI fluvoxamine to modulate the clearance of locally applied serotonin in the CA3 region of hippocampus in drug- or vehicle-treated rats. Fluvoxamine decreased the clearance of serotonin in rats treated with vehicle, DMI, or phenelzine but had no effect on the clearance of serotonin in SSRI-treated rats. SERT density in the CA3 region of the hippocampus of the same rats, assessed by quantitative autoradiography with tritiated cyanoimipramine ([H-3]CN-IMI), was decreased by 80-90% in SSRI-treated rats but not in those treated with phenelzine or DMI. The serotonin content of the hippocampus was unaffected by paroxetine or sertraline treatment, ruling out neurotoxicity as a possible explanation for the SSRI-induced decrease in SERT binding and alteration in 5-HT clearance. Levels of mRNA for the SERT in the raphe nucleus were also unaltered by chronic paroxetine treatment. Based on these results, it appears that the SERT is downregulated by chronic administration of SSRIs but not other types of antidepressants; furthermore, the downregulation is not caused by decreases in SERT gene expression. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. Univ Kentucky, Dept Anat, Lexington, KY 40536 USA. Univ Kentucky, Dept Neurobiol, Lexington, KY 40536 USA. RP Benmansour, S (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. OI Gould, Georgianna/0000-0002-5470-8763 FU NIMH NIH HHS [MH53851, MH01245, MH57001] NR 42 TC 202 Z9 204 U1 1 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 1 PY 1999 VL 19 IS 23 BP 10494 EP 10501 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 258YN UT WOS:000083867400030 PM 10575045 ER PT J AU Gabuzda, D Wang, JB AF Gabuzda, D Wang, JB TI Chemokine receptors and virus entry in the central nervous system SO JOURNAL OF NEUROVIROLOGY LA English DT Review DE HIV-1; SIV; chemokine receptor; coreceptor; microglia; brain ID HUMAN-IMMUNODEFICIENCY-VIRUS; BLOOD-BRAIN-BARRIER; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MONOCYTE CHEMOTACTIC PROTEIN-1; CAPILLARY ENDOTHELIAL-CELLS; HIV-1 DISEASE PROGRESSION; IN-VIVO DISTRIBUTION; CD8(+) T-CELLS; CEREBROSPINAL-FLUID; CD4-INDEPENDENT INFECTION AB Several members of the chemokine receptor family are used as coreceptors together with CD4 for HIV and SIV entry in the central nervous system (CNS). CCR5 is the major coreceptor for HIV-1 infection of macrophages and microglia, the major target cells for HIV-1 infection in the CNS. CXCR4 and CCR3 are also expressed on microglia and can mediate infection by certain HIV-1 isolates but at lower efficiency than CCR5. Additional chemokine receptors that can function as HIV-1 and SIV coreceptors for a subset of viruses are expressed in the brain (i.e. Apj, CX3CR1, STRL33/BONZO, and gpr1), but their role in CNS infection has not been defined. The expression of CXCR4, and possibly other chemokine receptors, on subpopulations of neurons and glial cells may contribute to mechanisms of CNS injury that are independent of viral infection. Understanding the role of chemokine receptors and their chemokine ligands in HIV-1 and SIV infection of the CNS will elucidate mechanisms of viral tropism and pathogenesis and advance the development of new therapeutic strategies. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, JF 712,44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI 28691]; NINDS NIH HHS [NS35734, NS37277] NR 171 TC 49 Z9 50 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD DEC PY 1999 VL 5 IS 6 BP 643 EP 658 DI 10.3109/13550289909021293 PG 16 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 268ZN UT WOS:000084451300011 PM 10602405 ER PT J AU Seldin, EB Troulis, MJ Kaban, LB AF Seldin, EB Troulis, MJ Kaban, LB TI Evaluation of a semiburied, fixed-trajectory, curvilinear, distraction device in an animal model SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Association-of-Oral-and-Maxillofacial-Surgeons CY SEP 19, 1997 CL SEATTLE, WASHINGTON SP Amer Assoc Oral & Maxillofacial Surgeons ID OSTEOGENESIS AB Purpose: This study evaluated a new small, buried distracter, capable of curvilinear movement while following a fixed trajectory. The geometrical basis for such devices and the 3-dimensional treatment planning system required to make buried distracters practical are discussed. Materials and Methods: A curved rack and worm-gear device, based on the design of a hose clamp, was constructed to produce a curved distraction path, and this distractor was tested in 2 minipigs using a protocol with zero latency and 1 mm/d X 7 days of distraction. Serial standardized lateral cephalograms were used to verify distracter function and path. Results: Curvilinear distraction was documented by clinical examination and serial cephalometric analysis in the 2 minipigs. Observed angulation of the margins of the wedge-shaped distraction gap conformed to the calculated angulation based an the fixed radius of curvature of the distracter. Conclusion: Distraction along a curved trajectory using a small, semiburied, curvilinear device of novel design is feasible in the minipig mandible. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Skeletal Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Seldin, EB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Skeletal Biol Res Ctr, Warren 1201, Boston, MA 02114 USA. NR 8 TC 28 Z9 28 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD DEC PY 1999 VL 57 IS 12 BP 1442 EP 1446 DI 10.1016/S0278-2391(99)90729-2 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 261TL UT WOS:000084025200015 PM 10596666 ER PT J AU Blais, MA Lenderking, WR Baer, L deLorell, A Peets, K Leahy, L Burns, C AF Blais, MA Lenderking, WR Baer, L deLorell, A Peets, K Leahy, L Burns, C TI Development and initial validation of a brief mental health outcome measure SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID RELIABILITY; SCALE; VALIDITY AB Using a combination of classical test theory and Rasch item analysis, we developed a short scale designed to measure the effectiveness of mental health treatment across a wide range of mental health services and populations. Item development for the scale was guided by literature review and interviews with senior clinicians and with patients. Using 3 different samples consisting of inpatients, outpatients, and nonpatients, we reduced our initial item pool from 81 to 10 items. The 10-item scale had an alpha of .96 and showed strong correlations with commonly used measures of psychological well-being and distress. Our results suggest that the scale appears to measure a broad domain of psychological health. The scale appeared to lack ceiling and floor effects, and it discriminated between inpatients, outpatients, and nonpatients, suggesting the scale has excellent potential to be broadly responsive to a variety of treatment effects. In addition, the new scale proved to be sensitive to treatment changes in a sample of 20 psychiatric inpatients. Overall, the initial data suggest that we have developed a brief, sensitive outcome measure designed to have wide application across psychiatric and psychological treatments and populations. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. RP Blais, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Blake 11,55 Fruit St, Boston, MA 02114 USA. NR 44 TC 92 Z9 92 U1 0 U2 4 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD DEC PY 1999 VL 73 IS 3 BP 359 EP 373 DI 10.1207/S15327752JPA7303_5 PG 15 WC Psychology, Clinical; Psychology, Social SC Psychology GA 271KD UT WOS:000084592000005 PM 10689649 ER PT J AU Supko, JG Nair, RV Seiden, MV Lu, H AF Supko, JG Nair, RV Seiden, MV Lu, H TI Adaptation of solid phase extraction to an automated column switching method for online sample cleanup as the basis of a facile and sensitive high-performance liquid chromatographic assay for paclitaxel in human plasma SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE paclitaxel; high-performance liquid chromatography; column switching; analysis; plasma; pharmacokinetics; human, anticancer agents ID METASTATIC BREAST-CANCER; LUNG-CANCER; CLINICAL PHARMACOKINETICS; ULTRAVIOLET DETECTION; BIOLOGICAL-FLUIDS; 96-HOUR INFUSION; OVARIAN-CANCER; MOUSE PLASMA; CELL-LINES; I TRIAL AB An improved method for assaying paclitaxel in human plasma by high-performance liquid chromatography (HPLC) with UV detection at 227 nm has been developed by adapting previously reported sample preparation methods and chromatographic conditions to facilitate semi-automated sample cleanup using a column switching technique. Manual sample manipulations were limited to isolating the drug and internal standard from plasma (1.0 mi) by liquid-liquid extraction using tert-butyl methyl ether. The sample extract was initially loaded onto a short cartridge column containing a cyanopropyl stationary phase. During the predetermined time interval that the drug and internal standard eluted from the cartridge, 1.50-2.20 min, a fully automated 6-position switching valve was used to direct the effluent onto an octylsilica analytical column. The same mobile phase, composed of acetonitrile-methanol- ammonium acetate buffer (pH 5.0;20 mM) (76:19:105, v/v/v) and delivered at flow rate of 1.0 ml/min, was used for both separations. The overall retention times of paclitaxel and the internal standard were 10.9 and 18.1 min, respectively. The analytical method was thoroughly validated for quantitating paclitaxel in plasma at concentrations ranging from 6 to 586 nM (5-500 ng/ml). The lowest concentration of paclitaxel measured with acceptable day-to-day accuracy (100.2%) and precision (RSD 11.7%, n = 21, 5 months) was 6 nM (5 ng/ml). The sensitivity and selectivity of the assay proved to be more than adequate for monitoring steady-state plasma concentrations of the drug when administered to cancer patients as a 96 h continuous intravenous infusion in combination with other anticancer agents, such as doxorubicin and topotecan. Moreover, the heart-cutting procedure prevented the problematic introduction of interfering nonpolar plasma components onto the analytical column, thereby enhancing sample throughput while decreasing the technical demands of the assay. The method was found to be extremely reproducible and robust during extended use for the routine analysis of plasma specimens acquired from several clinical trials. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Clin Pharmacol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Supko, JG (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Clin Pharmacol Lab, 55 Fruit St,GRJ1025, Boston, MA 02114 USA. NR 28 TC 23 Z9 23 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD DEC PY 1999 VL 21 IS 5 BP 1025 EP 1036 DI 10.1016/S0731-7085(99)00229-0 PG 12 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 268XT UT WOS:000084445500016 PM 10703971 ER PT J AU Zinckgraf, JW Winchell, JM Silbart, LK AF Zinckgraf, JW Winchell, JM Silbart, LK TI Antibody responses to a mucosally delivered HIV-1 gp120-derived C4/V3 peptide SO JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE HIV; mucosa; peptide immunization; secretory IgA; vagina ID HUMAN-IMMUNODEFICIENCY-VIRUS; FEMALE REPRODUCTIVE-TRACT; TOXIN-B-SUBUNIT; VAGINAL IMMUNIZATION; NEUTRALIZING ANTIBODIES; INTRANASAL IMMUNIZATION; IMMUNE-RESPONSES; IMMUNOGLOBULIN-G; ENVELOPE GLYCOPROTEIN; SYNTHETIC PEPTIDES AB T1-SP10MN(A) is a synthetic peptide containing a T-helper (Th), cytotoxic T cell (CTL) and a B-cell epitope derived from the HIV-1 gp120 envelope protein. This peptide can elicit both systemic and mucosal antibody responses following nasal immunization in various species. In the present study, three different mucosal immunization strategies were performed in rabbits to determine which induced a more vigorous antibody response to T1-SP10MN(A). Nasal immunization followed by nasal boosting was found to be superior at inducing both serum IgG and vaginal secretory IgA (S-IgA): when compared to nasal followed by vaginal boosting. Conversely, vaginal priming followed by vaginal boosting elicited minimal serum IgG and vaginal S-IgA responses to T1-SP10MN(A), but moderate levels of vaginal IgG were detected. This study further demonstrates that vaginal immune responses can be elicited by immunization at distant and local mucosal sites. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Connecticut, Dept Mol & Cell Biol, Storrs, CT 06269 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Connecticut, Ctr Environm Hlth, Dept Anim Sci, Storrs, CT 06269 USA. RP Silbart, LK (reprint author), Univ Connecticut, Dept Mol & Cell Biol, Storrs, CT 06269 USA. FU NIAID NIH HHS [AI35351] NR 44 TC 7 Z9 8 U1 0 U2 0 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 DEC PY 1999 VL 45 IS 2 BP 99 EP 112 PG 14 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA 277YL UT WOS:000084961100001 PM 10674979 ER PT J AU Biller, BMK Luciano, A Crosignani, PG Molitch, M Olive, D Rebar, R Sanfilippo, J Webster, J Zacur, H AF Biller, BMK Luciano, A Crosignani, PG Molitch, M Olive, D Rebar, R Sanfilippo, J Webster, J Zacur, H TI Guidelines for the diagnosis and treatment of hyperprolactinemia SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE prolactinemia; dopamine agonists; bromocriptine; cabergoline ID CABERGOLINE; PROLACTIN; MULTICENTER; INHIBITION; AMENORRHEA AB Hyperprolactinemia is the most common endocrine disorder of the hypothalamic-pituitary axis. While if can occur in men, it occurs more commonly in women. The prevalence of hyperprolactinemia ranges from 0.4% in an unselected normal adult population to as high as 9-17% in women with reproductive disorders. There are many possible muses of hyperprolactinemia, falling into three general categories: physiologic, pharmacologic and pathologic. When specific treatable underlying causes have been eliminated and in cases Of severe hyperprolactinemia, the most likely cause is a prolactin (PRL)-secreting pituitary adenoma. Microadenomas should be treated medically, with a dopamine agonist, if there is an indication for therapy (such as amenorrhea, infertility or bothersome galactorrhea). If there is no indication for therapy, microadenomas may be followed conservatively, as growth is uncommon. Macroadenomas may grow larger; medical therapy is recommended initially, with neurosurgical evaluation reserved for specific clinical situations, such as failure of medical therapy and evidence of mass effect despite medical therapy. In the United States, the dopamine agonists indicated for treatment of hyperprolactinemia are bromocriptine and cabergoline. Bromocriptine is usually given once or twice daily, while cabergoline has a long duration of action and is given once or twice weekly. Results of comparative studies indicate that cabergoline is clearly superior to bromocriptine in efficacy (PRL suppression, restoration of gonadal function) and tolerability. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. New Britain Gen Hosp, Ctr Fertil & Reprod Endocrinol, New Britain, CT USA. RP Biller, BMK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroendocrine Unit, Bullfinch 45B, Boston, MA 02114 USA. NR 13 TC 74 Z9 86 U1 0 U2 2 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 DEC PY 1999 VL 44 IS 12 SU S BP 1075 EP 1084 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 271BZ UT WOS:000084574400001 PM 10649814 ER PT J AU Biller, BMK AF Biller, BMK TI Diagnostic evaluation of hyperprolactinemia SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE hyperprolactinemia; prolactin; amenorrhea; galactorrhea; dopamine agonists AB A serum prolactin (PRL) level is obtained in response to a specific clinical presentation, including symptoms of hyperprolactinemia (such as amenorrhea and galactorrhea); serum PRL measurement may also be performed as part of an infertility evaluation. An initial level above the normal range should be followed by a repeat level from a blood sample drawn in the morning with the patient in a fasting state. The medical history and a few laboratory tests can eliminate the most common physiologic and pharmacologic causes of hyperprolactinemia, including pregnancy, primary hypothyroidism and treatment with drugs (such as neuroleptics) that reduce dopaminergic effects on the pituitary. In the absence of such causes, radiologic imaging of the sella turcica is necessary to establish whether a PRL-secreting pituitary adenoma or other lesion is present. The vast majority of patients are treated medically, with dopamine agonist drugs. Surgery is reserved for the patient with the uncommon tumor that does not respond to medical therapy or has a large cystic component or for the occasional patient who cannot tolerate dopamine agonists or who experiences pituitary apoplexy. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Clin Endocrine Fellowship Training Program, Cambridge, MA 02138 USA. RP Biller, BMK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bullfinch 45B, Boston, MA 02114 USA. NR 0 TC 13 Z9 13 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 DEC PY 1999 VL 44 IS 12 SU S BP 1095 EP 1099 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 271BZ UT WOS:000084574400004 PM 10649817 ER PT J AU Wong, AL Wong, WK Harker, J Sterz, M Bulpitt, K Park, G Ramos, B Clements, P Paulus, H AF Wong, AL Wong, WK Harker, J Sterz, M Bulpitt, K Park, G Ramos, B Clements, P Paulus, H CA Western Consortium Practicing Rheu TI Patient self-report tender and swollen joint counts in early rheumatoid arthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE rheumatoid arthritis; self-report articular scores; joint count ID DISEASE-ACTIVITY MEASURES; REPORT ARTICULAR INDEX; VALIDITY; QUESTIONNAIRE; RELIABILITY; SENSITIVITY; SCORES; MOOD AB Objective. To determine the correlation between patient self-report joint counts and standard physician joint counts, and to compare pictorial (Mannequin) and text (Rapid Assessment of Disease Activity in Rheumatology, RADAR) formats for obtaining patient self-reports, Methods. Baseline patient self-report joint counts were mailed and completed by 60 patients with early rheumatoid arthritis (RA) one day before and one day after being examined by a physician. Twenty-seven were randomized to the Mannequin tender and Mannequin swollen joint counts; 33 were randomized to the RADAR tender and swollen joint counts. Agreement between patient and physician self-report joint counts, diagnostic characteristics, and lest-retest reliability of patient self-report joint counts was computed. Stepwise regression analyses were performed to identify predictors of patient-physician differences in total joint count. Results, Means and standard deviations of paired patient and physician total joint counts were not different for Mannequin or RADAR forms. Spearman correlations were moderate (0.58 to 0.69 for Mannequin, 0.37 to 0.58 for RADAR). Agreement (intraclass correlations) was 0.65 for the Mannequin and 0.56 for the RADAR forms. Patient test-retest reproducibility was moderate for RADAR tenderness (0.58) and high (r > 0.90) for RADAR swollen and both Mannequin forms, Level of patient education predicted patient-physician differences on the RADAR swollen joint counts (p = 0,003), but was not significant in Mannequin forms, suggesting that education was not a factor in accurate completion of Mannequin forms, Conclusion, Both pictorial and text format patient self-report joint counts are significantly correlated with physician joint counts, In addition to moderately high patient test-retest reproducibility, this suggests that patient self-reports in both formats may yield accurate measures of improvement in disease activity. C1 Olive View UCLA Med Ctr, Dept Rheumatol, Sylmar, CA 91326 USA. Vet Adm Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Med, Dept Rheumatol, Los Angeles, CA USA. RP Wong, AL (reprint author), Olive View UCLA Med Ctr, Dept Rheumatol, 14445 Olive view Dr,2B182, Sylmar, CA 91326 USA. NR 30 TC 40 Z9 41 U1 1 U2 2 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD DEC PY 1999 VL 26 IS 12 BP 2551 EP 2561 PG 11 WC Rheumatology SC Rheumatology GA 262ZP UT WOS:000084098400011 PM 10606362 ER PT J AU Pawlik, TM Platteborze, N Souba, WW AF Pawlik, TM Platteborze, N Souba, WW TI Ethics and surgical research: What should guide our behavior? SO JOURNAL OF SURGICAL RESEARCH LA English DT Article C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Divin, Boston, MA 02114 USA. RP Pawlik, TM (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 15 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD DEC PY 1999 VL 87 IS 2 BP 263 EP 269 DI 10.1006/jsre.1999.5772 PG 7 WC Surgery SC Surgery GA 263ZU UT WOS:000084155800017 PM 10600359 ER PT J AU Maslow, AD Regan, MM Haering, JM Johnson, RG Levine, RA AF Maslow, AD Regan, MM Haering, JM Johnson, RG Levine, RA TI Echocardiographic predictors of left ventricular outflow tract obstruction and systolic anterior motion of the mitral valve after mitral valve reconstruction for myxomatous valve disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID HYPERTROPHIC CARDIOMYOPATHY; SUBAORTIC OBSTRUCTION; REPAIR; MECHANISM; VALVULOPLASTY; VALIDATION; MYECTOMY; PROLAPSE; INSIGHTS; INVITRO AB OBJECTIVE To determine predictors of systolic anterior motion and left ventricular outflow tract obstruction (SAM/LVOTO) after mitral valve repair (MVRep) in patients with myxomatous mitral valve disease. BACKGROUND Mechanisms for the development of SAM/LVOTO after MVRep have been described; however, predictors of this complication have not been explored. We hypothesize that pre-MVRep transesophageal echocardiography (TEE) can predict postrepair SAM/LVOTO. METHODS Using TEE, the lengths of the coapted anterior (AL) and posterior (PL) leaflets and the distance from the coaptation point to the septum (C-Sept) were measured before and after MVRep in 33 patients, including 11 who developed SAM/LVOTO (Group 1) and 22 who did not (Group 2). RESULTS Group 1 patients had smaller AL/PL ratios (0.99 vs. 1.95, p < 0.0001) and C-Sept distances (2.53 vs. 3.01 cm, p = 0.012) prior to MVRep than those in Group 2. Resolution of SAM/LVOTO was associated with increases in AL/PL ratio and C-Sept distance. This reflects a more anterior position of the coaptation point in those who developed SAM/LVOTO. CONCLUSIONS These data suggest that TEE analysis of the mitral apparatus can identify patients likely to develop SAM/LVOTO after MVRep for myxomatous valve disease. The findings are consistent with the concept that SAM of mitral leaflets is due to anterior malposition of slack mitral leaflet portions into the LVOT. The position of the coaptation point of the mitral leaflets is dynamic and a potential target and end point for surgical designs to prevent SAM/LVOTO post MVRep. (C) 1999 by the American College of Cardiology. C1 Rhode Isl Hosp, Dept Anesthesia, Providence, RI 02903 USA. Beth Israel Deaconess Med Ctr, Dept Anesthesia & Crit Care, Boston, MA USA. Beth Israel Deaconess Med Ctr, Biomet Ctr, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Surg, Div Cardiothorac Surg, Boston, MA USA. Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Maslow, AD (reprint author), Rhode Isl Hosp, Dept Anesthesia, 593 Eddy St,Davol 129, Providence, RI 02903 USA. FU NHLBI NIH HHS [HL38176] NR 26 TC 100 Z9 104 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC PY 1999 VL 34 IS 7 BP 2096 EP 2104 DI 10.1016/S0735-1097(99)00464-7 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 260NH UT WOS:000083956400040 PM 10588230 ER PT J AU Mertens, PR Alfonso-Jaume, MA Steinmann, K Lovett, DH AF Mertens, PR Alfonso-Jaume, MA Steinmann, K Lovett, DH TI YB-1 regulation of the human and rat gelatinase A genes via similar enhancer elements SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID MATRIX METALLOPROTEINASE-2; CELL-PROLIFERATION; IV COLLAGENASE; EXPRESSION; TRANSCRIPTION; PROMOTER; GLOMERULONEPHRITIS; DIFFERENTIATION; IDENTIFICATION; PROTEIN AB Experimental and clinical studies strongly suggest that gelatinase a plays a central role in the evolution of glomerular injury and sclerosis. The sequences of the 5' flanking regions of the human and rat gelatinase A genes do not share similarities with other members of the matrix metalloproteinase gene family and are regulated in a distinctive manner. The human and rat gelatinase A genes include regions of significant homology (r2 human; RE-1 rat), which have been shown to act as potent cis-activators of transcription. The rat RE-1 sequence interacts specifically with the developmentally regulated transcription factors AP2 and YB-1, resulting in a synergistic activation of gelatinase A transcription. Although the human r2 sequence specifically interacts with AP2 (Mol Cell Biol 10: 6524-6532, 1990), there is no clear evidence for the presence of a canonical YB-1 binding site (Y-box) within this sequence. This study demonstrates, despite the absence of a canonical Y-box sequence in the r2 element, that YB-1 and AP2. specifically interact with r2, yielding synergistic transactivation of the human gelatinase A gene. It is concluded that the r2 element is the conserved functional analog of the RE-1 element, and that interactions of AP2 and YB-1 govern human gelatinase A gene expression. C1 Rhein Westfal TH Aachen, Med Klin 2, D-52057 Aachen, Germany. Univ Calif San Francisco, San Francisco VAMC, Dept Med, San Francisco, CA 94143 USA. RP Mertens, PR (reprint author), Rhein Westfal TH Aachen, Med Klin 2, Pauwelsstr 30, D-52057 Aachen, Germany. FU NIDDK NIH HHS [DK 39776] NR 18 TC 38 Z9 38 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 1999 VL 10 IS 12 BP 2480 EP 2487 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 259CH UT WOS:000083876000003 PM 10589685 ER PT J AU Bonetti, M Cole, BF Gelber, RD AF Bonetti, M Cole, BF Gelber, RD TI A method-of-moments estimation procedure for categorical quality-of-life data with nonignorable missingness SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE identifiability; multinomial model; nonignorable missingness; quality of life ID CANCER CLINICAL-TRIALS; OUTCOME SUBJECT; NONRESPONSE; MODELS; REGRESSION; THERAPY AB Quality-of-life outcomes collected during clinical trials often have considerable amounts of missing data, which, if not appropriately accounted for, may lead to bias in inferences. We introduce a method-of-moments (MM) estimating procedure for a model designed to handle nonignorable missingness arising in categorical data measured on independent populations. The missingness mechanism is assumed to be the same across the populations. We derive necessary and sufficient conditions for the identifiability of the model and fit the model to quality-of-life data collected as part of a breast cancer clinical trial. We compare the MM estimator to the maximum likelihood estimator in a simulation study. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Dartmouth Med Sch, Epidemiol & Biostat Sect, Lebanon, NH 03756 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Bonetti, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. OI Bonetti, Marco/0000-0003-2304-4180 NR 25 TC 8 Z9 8 U1 0 U2 2 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD DEC PY 1999 VL 94 IS 448 BP 1025 EP 1034 DI 10.2307/2669916 PG 10 WC Statistics & Probability SC Mathematics GA 259DU UT WOS:000083879800004 ER PT J AU Laird, NM Pauler, DK AF Laird, NM Pauler, DK TI Adjusting for nonignorable drop-out using semiparametric nonresponse models - Comment SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Editorial Material ID INCOMPLETE-DATA; MIXTURE-MODELS; SAMPLE-SURVEYS C1 Harvard Univ, Sch Med, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Laird, NM (reprint author), Harvard Univ, Sch Med, Dept Biostat, Boston, MA 02115 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD DEC PY 1999 VL 94 IS 448 BP 1133 EP 1135 PG 3 WC Statistics & Probability SC Mathematics GA 259DU UT WOS:000083879800017 ER PT J AU Lipsitz, SR Ibrahim, JG Zhao, LP AF Lipsitz, SR Ibrahim, JG Zhao, LP TI A weighted estimating equation for missing covariate data with properties similar to maximum likelihood SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE generalized linear model; missing at random; missing completely at random; missing-data mechanism ID EM ALGORITHM; INCOMPLETE DATA; MODELS AB In regression analysis, missing covariate data occurs often. A recent approach to analyzing such data is weighted estimating equations. With weighted estimating equations, the contribution to the estimating equation from a complete observation is weighted by the inverse probability of being observed. In this article we propose a weighted estimating equation that is almost identical to the maximum likelihood estimating equations. As such, we propose an EM-type algorithm to solve these weighted estimating equations. Although the weighted estimating equations are a special case of those proposed earlier by Robins et al., our EM-type algorithm to solve them is new. Similar to Robins and Ritov, we give the result that to obtain a consistent estimate of the regression parameters, either the missing-data mechanism or the distribution of thr missing data given the observed data must be correctly specified. We compare the weighted estimating equations to maximum likelihood via two examples, a simulation and an asymptotic study. C1 Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. RP Lipsitz, SR (reprint author), Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. NR 17 TC 63 Z9 65 U1 2 U2 7 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD DEC PY 1999 VL 94 IS 448 BP 1147 EP 1160 DI 10.2307/2669931 PG 14 WC Statistics & Probability SC Mathematics GA 259DU UT WOS:000083879800019 ER PT J AU Nelson, HH Christiani, DC Mark, EJ Wiencke, JK Wain, JC Kelsey, KT AF Nelson, HH Christiani, DC Mark, EJ Wiencke, JK Wain, JC Kelsey, KT TI Implications and prognostic value of K-ras mutation for early-stage lung cancer in women SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ONCOGENE ACTIVATION; CIGARETTE-SMOKING; GENE-MUTATIONS; ADENOCARCINOMA; RISK; TRANSFORMATION; EXPRESSION; MARKER; P53; CARCINOMAS AB Background: Because there is no clear consensus as to the predictive value of K-ras gene mutation for survival in patients with lung cancer, we examined the occurrence of K-ras mutations in a large, prospective case series of nonsmall-cell lung cancer (NSCLC). Our goals mere to define the patient characteristics associated with K-ras mutation and to determine whether mutation of this gene might be a biomarker of patient prognosis. Methods: Consecutive, newly diagnosed patients with lung cancer treated with potentially curative resection over a 4-year period were recruited for study. The mutation status of K-ras codon 12 in each patient's tumor DNA was determined by means of polymerase chain reaction-restriction fragment length polymorphism analysis of archived pathology specimens, Analyses were restricted to adenocarcinoma, Results: There was a statistically significant association between female sex and K-ras mutation after adjustment for carcinogen exposures (odds ratio = 3.3; 95% confidence interval [CI] = 1.3-7.9); mutations were found only in smokers. Comparison of Kaplan-Meier curves indicated a strong association between K-ras mutation and decreased patient survival (two-sided P = .009); analysis stratified by pathologic staging groups revealed that this association was statistically significant only for stage I tumors (two-sided P = .002), Cox proportional hazards modeling indicated that K-ras codon 12 mutation was a statistically significant predictor of patient survival, after adjustment for the effects of age, sex, and stage (risk ratio = 1.8; 95% Cf = 1.1-3.1), Conclusions: After adjustment for environmental exposures, non-small-cell lung tumors in women appear to be more likely than those in men to harbor K-ras mutations, suggesting a possible role of estrogen exposure in either the initiation or the selection of K-ras mutant clones in adenocarcinoma. In addition, our data suggest that K-ras codon 12 mutation is a marker of aggressive NSCLC, as evidenced by its association with decreased patient survival, particularly for early-stage disease. C1 Harvard Univ, Sch Publ Hlth, Dept Canc Cell Biol, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Sch Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Thorac Surg Unit, Sch Med,Dept Surg, Boston, MA USA. Univ Calif San Francisco, Lab Mol Epidemiol, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Kelsey, KT (reprint author), Harvard Univ, Sch Publ Hlth, Dept Canc Cell Biol, Occupat Hlth Program, 665 Huntington Ave,Bldg 1,Rm 207, Boston, MA 02115 USA. RI Kelsey, Karl/I-1252-2014 FU NIEHS NIH HHS [ES04705, ES08357, ES00002] NR 54 TC 148 Z9 156 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 DEC 1 PY 1999 VL 91 IS 23 BP 2032 EP 2038 DI 10.1093/jnci/91.23.2032 PG 7 WC Oncology SC Oncology GA 266ER UT WOS:000084288100015 PM 10580029 ER PT J AU Singhal, AB Buonanno, F Rordorf, G AF Singhal, AB Buonanno, F Rordorf, G TI Cerebral venous sinus thrombosis associated with hepatic cirrhosis SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE cerebral venous sinus thrombosis; cirrhosis; protein C; protein S; antithrombin III; spinal puncture; low molecular weight heparin ID DEFICIENCY AB Cerebral venous sinus thrombosis is not a recognized complication of end-stage liver disease. A case of sagittal sinus thrombosis in a 44-year-old male with end-stage hepatic cirrhosis is described. Recurrent seizures were the only manifestation. Work-up revealed severe deficiency of protein C, protein S, and antithrombin III. He was treated with low molecular weight heparin and underwent an orthotopic liver transplant after three months. Follow-up helical CT venogram showed resolution of the sinus thrombosis. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Singhal, AB (reprint author), Massachusetts Gen Hosp, Dept Neurol, VBK 802,55 Fruit St, Boston, MA 02114 USA. NR 10 TC 2 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD DEC 1 PY 1999 VL 171 IS 1 BP 65 EP 68 DI 10.1016/S0022-510X(99)00233-6 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 269PX UT WOS:000084487700012 PM 10567052 ER PT J AU Sheridan, RL Uberti, E Frank, KT DelMonico, FL AF Sheridan, RL Uberti, E Frank, KT DelMonico, FL TI Solid organ procurement from burned children SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the American-Burn-Association CY MAR 23-27, 1999 CL ORLANDO, FLORIDA SP Amer Burn Assoc DE transplantation; burns; brain death criteria ID THERMAL-INJURY; UNITED-STATES; TRANSPLANTATION; AVAILABILITY; BACTEREMIA; DISEASE; DONORS AB Background: Burns have constituted a traditional contraindication to solid organ procurement because of concerns that such organs may be damaged by bun shock associated splanchnic ischemia and contaminated by burn wound manipulation associated bacteremia. Methods: Over a 5-year period, me attempted solid organ procurement from five burned children who had suffered concurrent anoxic brain injury. Results: These four boys and one girl had an average age of 8.1 years (range, 2.5-12 years) and burn size of 29% (range, 4-70%), All were injured in house fires and four of five (80%) required prehospital external cardiac compressions. Brain death was declared an average of 35 hours (range, 2.75-77 hours) after injury. Solid organs procured and successfully transplanted from this group were 4 livers, 10 kidneys, and 2 hearts. Two of the livers and one heart mere placed into pediatric recipients. Procured tissues included three sets of cardiac valves, and two corneas, All solid organs transplanted were functional at 6 months, although longer follow-up is not available. Conclusion: Early identification and diagnosis of brain death during resuscitation of burn patients with anoxic brain injury, combined with careful resuscitation and support of the brain dead potential organ donor, can result in the recovery of suitable solid organs and tissues for transplantation. C1 Shriners Burn Hosp, Dept Surg, Div Trauma & Burns, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Div Transplantat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. New England Organ Bank, Boston, MA USA. RP Sheridan, RL (reprint author), Shriners Burn Hosp, Dept Surg, Div Trauma & Burns, 51 Blossom St, Boston, MA 02114 USA. NR 22 TC 3 Z9 3 U1 1 U2 1 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 DEC PY 1999 VL 47 IS 6 BP 1060 EP 1062 DI 10.1097/00005373-199912000-00011 PG 3 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 266JD UT WOS:000084296100016 PM 10608533 ER PT J AU Accola, MA Bukovsky, AA Jones, MS Gottlinger, HG AF Accola, MA Bukovsky, AA Jones, MS Gottlinger, HG TI A conserved dileucine-containing motif in p6(gag) governs the particle association of Vpx and Vpr of simian immunodeficiency viruses SIVmac and SIVagm SO JOURNAL OF VIROLOGY LA English DT Article ID CELL-CYCLE ARREST; VIRION-ASSOCIATED PROTEIN; AFRICAN-GREEN MONKEYS; TYPE-1 VPR; MUTATIONAL ANALYSIS; NUCLEAR-LOCALIZATION; PRODUCTIVE INFECTION; VIRAL EXPRESSION; HIV-1 VIRIONS; T-CELLS AB Vpr is a small accessory protein of human and simian immunodeficiency viruses (HIV and SIV) that is specifically incorporated into virions. Members of the HIV-2/SIVsm/SIVmac lineage of primate lentiviruses also incorporate a related protein designated Vpx. We previously identified a highly conserved L-X-X-L-F sequence near the C terminus of the p6 domain of the Gag precursor as the major virion association motif for HIV-1 Vpr. In the present study, we show that a different leucine-containing motif CD-X-A-X-X-L-LI in the N-terminal half of p6(gag) is required for the incorporation of SIVmac Vpx. Similarly, the uptake of SIVmac Vpr depended primarily on the D-X-A-X-X-L-L motif. SIVmac Vpr was unstable when expressed alone, but its intracellular steady-state levels increased significantly in the presence of wild-type Gag or of the proteasome inhibitor lactacystin. Collectively, our results indicate that the interaction with the Gag precursor via the D-IC-A-X-XL-L motif diverts SIVmac Vpr away from the proteasome-degradative pathway. While absent from HIV-1 p6(gag), the D-X-A-X-X-L-L motif is conserved in both the HIV-2/SIVsm/SIVmac and SIVagm lineages of primate lentiviruses. We found that the incorporation of SIVagm Vpr, like that of SIVmac Vpx, is absolutely dependent on the D-X-A-X-X-L-L motif, while the L-X-X-L-F motif used by HIV-1 Vpr is dispensable. The similar requirements for the incorporation of SIVmac Vpx and SIVagm Vpr provide support for their proposed common ancestry. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Gottlinger, HG (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [T32 CA009141, T32 CA09141]; NIAID NIH HHS [AI28691, R01 AI029873, P30 AI028691, R37 AI029873, AI29873] NR 63 TC 72 Z9 72 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1999 VL 73 IS 12 BP 9992 EP 9999 PG 8 WC Virology SC Virology GA 255ZD UT WOS:000083699300036 PM 10559313 ER PT J AU Hofmann, W Schubert, D LaBonte, J Munson, L Gibson, S Scammell, J Ferrigno, P Sodroski, J AF Hofmann, W Schubert, D LaBonte, J Munson, L Gibson, S Scammell, J Ferrigno, P Sodroski, J TI Species-specific, postentry barriers to primate immunodeficiency virus infection SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 ENVELOPE GLYCOPROTEINS; CYCLOPHILIN-A; T-CELL; TYPE-1 REPLICATION; HUMAN-LYMPHOCYTES; VIF PROTEIN; USE CCR5; AIDS; RETROVIRUS; RECEPTOR AB By using replication defective vectors derived from human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus (SIVmac), and murine leukemia virus (MuLV), all of which were pseudotyped,vith the vesicular stomatitis virus (VSV) G glycoprotein, the efficiency of postentry, early infection events was examined in target cells of several mammalian species. Titers of HIV-1 vectors were significantly lower than those of SIVmac and MuLV vectors in most cell lines and primary cells from Old World monkeys. By contrast, most New World monkey cells exhibited much lower titers for the SIVmac vector compared with those of the HTV-1 vector. Prosimian cells were resistant to both HIV-1 and SIVmac vectors, although the MuLV vector was able to infect these cells. Cells from other mammalian species were roughly equivalent in susceptibility to the three vectors, with, the exception of rabbit cells, which were specifically resistant to the HIV-1 vector. The level of HIV-1 vector expression was very low in transduced cells of rodent, rabbit, cow, and pig origin. Early postentry restriction of primate immunodeficiency virus infection exhibits patterns largely coincident with species borders and applies to diverse cell types within an individual host, suggesting the involvement of species-specific, widely expressed cellular factors. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Univ Calif Davis, Dept Vet Med, PMI, Davis, CA 95616 USA. Univ S Alabama, Coll Med, Mobile, AL 36688 USA. Univ S Alabama, Dept Pharmacol, Mobile, AL 36688 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. FU NHLBI NIH HHS [P50 HL054785, HL54785] NR 62 TC 201 Z9 209 U1 1 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1999 VL 73 IS 12 BP 10020 EP 10028 PG 9 WC Virology SC Virology GA 255ZD UT WOS:000083699300039 PM 10559316 ER PT J AU Brander, C Yang, OO Jones, NG Lee, Y Goulder, P Johnson, RP Trocha, A Colbert, D Hay, C Buchbinder, S Bergmann, CC Zweerink, HJ Wolinsky, S Blattner, WA Kalams, SA Walker, BD AF Brander, C Yang, OO Jones, NG Lee, Y Goulder, P Johnson, RP Trocha, A Colbert, D Hay, C Buchbinder, S Bergmann, CC Zweerink, HJ Wolinsky, S Blattner, WA Kalams, SA Walker, BD TI Efficient processing of the immunodominant, HLA-A*0201-restricted human immunodeficiency virus type 1 cytotoxic T-lymphocyte epitope despite multiple variations in the epitope flanking sequences SO JOURNAL OF VIROLOGY LA English DT Article ID CELL RESPONSES; ANTIGEN PRESENTATION; LABORATORY WORKERS; VIRAL REPLICATION; PRIMARY INFECTION; CD8(+) CELLS; IN-VITRO; HIV-1; SELECTION; PEPTIDES AB Immune escape from cytotoxic T-lymphocyte (CTL) responses has been shown to occur not only by changes within the targeted epitope but also by changes in the flanking sequences which interfere with the processing of the immunogenic peptide. However, the frequency of such an escape mechanism has not been determined. To investigate whether naturally occurring variations in the flanking sequences of an immunodominant human immunodeficiency virus type 1 (HIV-1) Gag CTL epitope prevent antigen processing, cells infected with HIV-1 or vaccinia virus constructs encoding different patient-derived Gag sequences were tested for recognition by HLA-A*0201-restricted, p17-specific CTL. We found that the immunodominant p17 epitope (SL9) and its variants were efficiently processed from minigene expressing vectors and from sis HIV-1 Gag variants expressed by recombinant vaccinia virus constructs. Furthermore, SL9-specific CTL clones derived from multiple donors efficiently inhibited virus replication when added to HLA-*0201-bearing cells infected with primary or laboratory-adapted strains of virus, despite the variability in the SL9 flanking sequences. These data suggest that escape from this immunodominant CTL response is not frequently accomplished by changes in the epitope flanking sequences. C1 Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. Dept Publ Hlth, HIV Res Sect, San Francisco, CA 94102 USA. Univ So Calif, Sch Med, Los Angeles, CA 90033 USA. Merck Res Labs, Dept Inflammat & Rheumatol, Rahway, NJ 07065 USA. Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. Univ Maryland, Div Geog Med, Baltimore, MD 21201 USA. RP Brander, C (reprint author), Massachusetts Gen Hosp E, AIDS Res Ctr, 149 13th St, Charlestown, MA 02129 USA. RI Wolinsky, Steven/B-2893-2012; OI Wolinsky, Steven/0000-0002-9625-6697 FU NIAID NIH HHS [AI33314, R01 AI028568, R01 AI030914, R01 AI039966, R37 AI028568, AI33327]; NICHD NIH HHS [HD31756] NR 54 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 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1999 VL 73 IS 12 BP 10191 EP 10198 PG 8 WC Virology SC Virology GA 255ZD UT WOS:000083699300058 PM 10559335 ER PT J AU Crawford, JM Earl, PL Moss, B Reimann, KA Wyand, MS Manson, KH Bilska, M Zhou, JT Pauza, CD Parren, PWHI Burton, DR Sodroski, JG Letvin, NL Montefiori, DC AF Crawford, JM Earl, PL Moss, B Reimann, KA Wyand, MS Manson, KH Bilska, M Zhou, JT Pauza, CD Parren, PWHI Burton, DR Sodroski, JG Letvin, NL Montefiori, DC TI Characterization of primary isolate-like variants of simian-human immunodeficiency virus SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; N-LINKED OLIGOSACCHARIDE; NEUTRALIZING ANTIBODIES; ENVELOPE GLYCOPROTEIN; PERSISTENT INFECTION; RHESUS MACAQUES; V3 LOOP; LYMPHOCYTE DEPLETION; SOLUBLE CD4; HIV TYPE-1 AB Several different strains of simian-human immunodeficiency virus (SHIV) that contain the envelope glycoproteins of either T-cell-line-adapted (TCLA) strains or primary isolates of human immunodeficiency virus type 1 (HIV-1) are now available. One of the advantages of these chimeric viruses is their application to studies of HIV-1-specific neutralizing antibodies in preclinical AIDS vaccine studies in nonhuman primates. In this regard, an important consideration is the spectrum of antigenic properties exhibited by the different envelope glycoproteins used for SHIV construction. The antigenic properties of six SHIV variants were characterized here in neutralization assays with recombinant soluble CD4 (rsCD4), monoclonal antibodies, and serum samples from SHIV-infected macaques and HIV-1-infected individuals, Neutralization of SHIV variants HXBc2, KU2, 89.6, and 89.6P by autologous and heterologous sera from SHIV-infected macaques was restricted to an extent that these viruses may be considered heterologous to one another in their major neutralization determinants. Little or no variation was seen in the neutralization determinants on SHIV variants 89.6P, 89.6PD, and SHIV-KB9, Neutralization of SHIV HXBc2 by sera from HXBc2-infected macaques could be blocked with autologous V3-loop peptide; this was less true in the case of SHIV 89.6 and sera from SHIV 89.6-infected macaques, The poorly immunogenic but highly conserved epitope for monoclonal antibody 1gG1b12 was a target for neutralization on SHIV variants HXBc2, KU2, and 89.6 but not on 89.6P and KB9, The 2G12 epitope was a target for neutralization on all five SHIV variants. SHIV variants KU2, 89.6, 89.6P, 89.6PD, and KB9 exhibited antigenic properties characteristic of primary isolates by being relatively insensitive to neutralization in peripheral blood mononuclear cells with serum samples from HIV-1-infected individuals and 12 fold to 38-fold less sensitive to inhibition with recombinant soluble CD4 than TCLA strains of HIV-1. The utility of nonhuman primate models in AIDS vaccine development is strengthened by the availability of SHIV variants that are heterologous in their neutralization determinants and exhibit antigenic properties shared with primary isolates. C1 Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. Primedica Corp, Worcester, MA 01608 USA. Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. RP Montefiori, DC (reprint author), Duke Univ, Med Ctr, Dept Surg, Box 2926, Durham, NC 27710 USA. OI Parren, Paul/0000-0002-4365-3859 FU NIAID NIH HHS [R37 AI033292, AI-85345, AI36643, AI65303, R01 AI033292, R01 AI065303] NR 75 TC 65 Z9 65 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1999 VL 73 IS 12 BP 10199 EP 10207 PG 9 WC Virology SC Virology GA 255ZD UT WOS:000083699300059 PM 10559336 ER PT J AU Sena-Esteves, M Saeki, Y Camp, SM Chiocca, EA Breakefield, XO AF Sena-Esteves, M Saeki, Y Camp, SM Chiocca, EA Breakefield, XO TI Single-step conversion of cells to retrovirus vector producers with herpes simplex virus-Epstein-Barr virus hybrid amplicons SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN GLIOMA-CELLS; MEDIATED GENE-TRANSFER; HIGH-TITER; HELPER-FREE; RECOMBINANT RETROVIRUSES; CYSTIC-FIBROSIS; HUMAN SERUM; IN-VIVO; TRANSGENE EXPRESSION; DEFECTIVE RETROVIRUS AB We report here on the development and characterization of a novel herpes simplex virus type 1 (HSV-1) amplicon-based vector system which takes advantage of the host range and retention properties of HSV-Epstein-Barr virus (EBV) hybrid amplicons to efficiently convert tells to retrovirus sector producer cells after single-step transduction, The retrovirus genes gag-pol and env (GPE) and retroviral vector sequences were modified to minimize sequence overlap and cloned into an HSV-EBV hybrid amplicon, Retrovirus expression cassettes were used to generate the HSV-EBV-retrovirus hybrid vectors, HERE and HERA, which code for the ecotropic and the amphotropic envelopes, respectively. Retrovirus vector sequences encoding lacZ were cloned downstream from the GPE expression unit. Transfection of 293T/17 cells with amplicon plasmids yielded retrovirus titers between 10(6) and 10(7) transducing units/ml, while infection of the same cells with amplicon vectors generated maximum titers I order of magnitude lower, Retrovirus titers were dependent on the extent of transduction by amplicon vectors for the same cell line, but different cell lines displayed varying capacities to produce retrovirus vectors even at the same transduction efficiencies. Infection of human and dog primary gliomas with this system resulted in the production of retrovirus vectors for more than 1 week and the longterm retention and increase in transgene activity over time in these cell populations. Although the efficiency of this system still has to be determined in vivo, many applications are foreseeable for this approach to gene delivery. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Mol Neurogenet Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Charlestown, MA 02129 USA. RP Breakefield, XO (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Mol Neurogenet Unit, CNY 6205,Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA-69246, P01 CA069246]; NINDS NIH HHS [NS-24279, P01 NS024279] NR 69 TC 68 Z9 70 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1999 VL 73 IS 12 BP 10426 EP 10439 PG 14 WC Virology SC Virology GA 255ZD UT WOS:000083699300084 PM 10559361 ER PT J AU Kennefick, TM Al-Nimri, MA Oyama, TT Thompson, MM Kelly, FJ Chapman, JG Anderson, S AF Kennefick, TM Al-Nimri, MA Oyama, TT Thompson, MM Kelly, FJ Chapman, JG Anderson, S TI Hypertension and renal injury in experimental polycystic kidney disease SO KIDNEY INTERNATIONAL LA English DT Article DE angiotensin; hydralazine; interstitial fibrosis; progressive renal disease ID CONVERTING-ENZYME-INHIBITION; EPIDERMAL GROWTH-FACTOR; RENIN-ANGIOTENSIN SYSTEM; CYCLOSPORINE NEPHROPATHY; FAMILY MEMBERS; ACE-INHIBITION; II BLOCKADE; RAT; ENDOTHELIN; SODIUM AB Background. Hypertension accelerates renal failure in autosomal dominant polycystic kidney disease (ADPKD), and evidence suggests a role for the renin-angiotensin system (RAS) in the functional and structural changes. To explore the hypothesis that RAS adaptations contribute to disease progression, we examined RAS activity and the long-term consequences of antihypertensive drugs, which suppress (enalapril) or stimulate (hydralazine) the RAS, in experimental polycystic kidney disease. Methods. Studies were conducted in male heterozygous cystic Han:SPRD rats (Cy/+) and in unaffected littermates (controls). In protocol 1, either angiotensin II (Ang II), enalaprilat, or saline vehicle was acutely infused into cystic and control rats, which were aged 10 to 12 weeks. The mean arterial pressure (MAP), glomerular filtration rate (GFR), and renal plasma flow (RPF) were measured at baseline and after an infusion of test substances. In protocol 2, cystic rats received chronic therapy with either enalapril, hydralazine, or no therapy for 10 to 12 weeks of age and then underwent renal function and RAS studies. In protocol 3, similar cohorts were followed for 40 weeks to assess the effects of therapy on blood pressure, proteinuria, serum creatinine, RAS parameters, and renal morphology. Results. In protocol 1, cystic rats had massive kidneys, slightly elevated blood pressure, and profound renal vasoconstriction and reduced GFR. Ang II induced similar changes in MAP and renal function in control and cystic rats. Enalaprilat induced little effect on MAP but more striking increases in GFR and RPF in cystic rats. In protocol 2, at 10 weeks of age, enalapril was superior in preserving renal function, but neither drug limited the expansion of the tubulointerstitium. In protocol 3, at 40 weeks of age, both drugs ameliorated the increase in serum creatinine, although only enalapril reduced proteinuria and kidney size. Conclusions. In polycystic rats, acute RAS suppression markedly ameliorates renal dysfunction. However, although chronic enalapril and hydralazine protect against the loss of renal function, only enalapril limits renal growth and proteinuria, and neither significantly limits tubulointerstitial fibrosis. The long-term studies give clear support to the importance of blood pressure control, per se, but only partial support to the importance of the particular agent used. As in clinical studies, angiotensin-converting enzyme inhibition may be less beneficial in ADPKD than in renal diseases characterized by predominant glomerular injury. C1 Oregon Hlth Sci Univ, Dept Med, Div Nephrol & Hypertens, Portland, OR 97201 USA. Portland VA Med Ctr, Med Serv, Portland, OR USA. RP Anderson, S (reprint author), Oregon Hlth Sci Univ, Div Nephrol, PP262,3314 SW US Vet Hosp Rd, Portland, OR 97201 USA. NR 51 TC 28 Z9 31 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 1999 VL 56 IS 6 BP 2181 EP 2190 DI 10.1046/j.1523-1755.1999.00783.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 263CK UT WOS:000084104900019 PM 10594794 ER PT J AU Nash, K Chang, Q Watts, A Treter, S Oravec, G Ferrara, V Buhler, L Basker, M Gojo, S Sachs, DH White-Scharf, M Down, JD Cooper, DKC AF Nash, K Chang, Q Watts, A Treter, S Oravec, G Ferrara, V Buhler, L Basker, M Gojo, S Sachs, DH White-Scharf, M Down, JD Cooper, DKC TI Peripheral blood progenitor cell mobilization and leukapheresis in pigs SO LABORATORY ANIMAL SCIENCE LA English DT Article ID COLONY-STIMULATING FACTOR; NONLETHAL PREPARATIVE REGIMEN; BONE-MARROW TRANSPLANTATION; MIXED CHIMERISM; CYNOMOLGUS MONKEYS; TOLERANCE; ENGRAFTMENT; CHEMOTHERAPY; CLONING; DONOR AB Background and Purpose: The pig is being investigated as an organ donor for humans. Induction of immunologic tolerance to pig tissues in primates would overcome the major immunologic barriers to xenotransplantation. A proven method of inducing tolerance to allografts is by the induction of mixed hematopoietic chimerism by bone marrow transplantation. We are therefore investigating induction of mixed hematopoietic chimerism in the pig-to-baboon model. Methods: To obtain large numbers of pig hematopoietic cells, leukapheresis was used to collect blood cell products in miniature swine (n = 5) after progenitor cell mobilization by use of a course of hematopoietic growth factors (cytokines), consisting of porcine interleukin 3, porcine stem cell factor, and human granulocyte colony-stimulating factor. Results: Cytokine therapy and leukapheresis were well tolerated. Cytokine therapy increased the total white blood cell count and allowed large numbers of leukocytes (60 x 10(10)) to be obtained by apheresis, of which approximately 0.1% were granulocyte-erythrocyte-monocyte-megakaryocyte colony-forming units (CFU-GEMMs), which are considered to be representative of hematopoietic progenitors with multi-lineage potential. Conclusions: The combination of cytokine therapy and leukapheresis enables hematopoietic progenitor cells to be obtained safely from miniature swine. C1 Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. Biotransplant Inc, Charlestown, MA USA. RP Cooper, DKC (reprint author), Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Sch Med, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. NR 31 TC 31 Z9 33 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD DEC PY 1999 VL 49 IS 6 BP 645 EP 649 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 273JN UT WOS:000084704300011 PM 10638501 ER PT J AU Menghini, VV Savcenko, V Olson, LJ Tazelaar, HD Dec, GW Kao, A Cooper, LT AF Menghini, VV Savcenko, V Olson, LJ Tazelaar, HD Dec, GW Kao, A Cooper, LT TI Combined immunosuppression for the treatment of idiopathic giant cell myocarditis SO MAYO CLINIC PROCEEDINGS LA English DT Article ID EXPERIMENTAL AUTOIMMUNE MYOCARDITIS; HEART-TRANSPLANTATION; ULCERATIVE-COLITIS; CYTOKINE; FAILURE; ENTITY; RATS AB Giant cell myocarditis (GCM) is a rare and frequently fatal disorder with no proven treatment. Case reports and data from a rat model of GCM suggest that immunosuppressive therapy directed against T lymphocytes may have clinical benefit. We describe a 47-year-old man with severe acute heart failure due to GCM in whom the left ventricular ejection fraction normalized and the myocardial inflammatory infiltrate resolved rapidly after treatment with muromonab-CD3, cyclosporine, azathioprine, and corticosteroids, Three previously published cases with less impressive responses to treatment including muromonab-CD3 and a critical review of the published data on immunosuppressive therapy are included in this report. The response to immunosuppressive therapy is highly variable, and direct comparisons between immunosuppressive regimens do not exist. Therefore, despite individual reports of dramatic improvement after immunosuppressive treatment, firm conclusions cannot be made about the benefit of immunosuppression for GCM. The benefits of immunosuppressive therapy must be confirmed in a prospective, randomized trial. C1 Mayo Clin & Mayo Fdn, Dept Internal Med, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Diagnost Radiol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Div Cardiovasc Dis & Internal Med, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. Univ Penn, Div Cardiol, Philadelphia, PA 19104 USA. RP Cooper, LT (reprint author), Mayo Clin & Mayo Fdn, Div Cardiovasc Dis, 200 1st St SW, Rochester, MN 55905 USA. NR 46 TC 29 Z9 31 U1 0 U2 0 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD DEC PY 1999 VL 74 IS 12 BP 1221 EP 1226 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 261QC UT WOS:000084019100005 PM 10593350 ER PT J AU Ayanian, JZ Weissman, JS Chasan-Taber, S Epstein, AM AF Ayanian, JZ Weissman, JS Chasan-Taber, S Epstein, AM TI Quality of care by race and gender for congestive heart failure and pneumonia SO MEDICAL CARE LA English DT Article DE race; sex differences; socioeconomic status; quality of care; congestive heart failure; pneumonia, Medicare ID CORONARY-ARTERY DISEASE; BLACK-WHITE DIFFERENCES; RENAL-TRANSPLANTATION; REVASCULARIZATION PROCEDURES; RACIAL-DIFFERENCES; SEX-DIFFERENCES; HEALTH-CARE; MEDICARE; AGE; INEQUALITIES AB BACKGROUND. Variations in the rates of major procedures by race and gender are well described, but few studies have assessed the quality of care by race and gender for basic hospital services. OBJECTIVE. To assess quality of care by race and gender. RESEARCH DESIGN. Retrospective review of medical records. SUBJECTS. Stratified random sample of 2,175 Medicare beneficiaries hospitalized for congestive heart failure or pneumonia in Illinois, New York, and Pennsylvania during 1991 and 1992. MEASURES. Explicit process criteria and implicit review by physicians. RESULTS. In adjusted analyses, black patients with congestive heart failure or pneumonia received lower quality of care overall than other patients with these conditions by both explicit process criteria and implicit review (P < 0.05), On explicit measures, overall quality of care did not differ by gender for either condition, but significant differences were noted on explicit subscales. Women received worse cognitive care than men from physicians for both conditions, better cognitive care from nurses for pneumonia, and better therapeutic care for congestive heart failure (P < 0.05). Women received worse quality of care than men by implicit, review (P = 0.03) for congestive heart failure but not pneumonia. CONCLUSIONS. Consistent racial differences in quality of care persist in basic hospital services for two common medical conditions. Physicians, nurses, and policy makers should strive to eliminate these differences. Gender differences in quality of care are less pronounced and may vary by condition and type of provider or service. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gen Med, Sect Hlth Serv & Policy Res, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA USA. Boston Bioistat Inc, Framingham, MA USA. Harvard Univ, Sch Med, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Ayanian, JZ (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. FU AHRQ HHS [HS 06631] NR 39 TC 145 Z9 146 U1 2 U2 8 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 DEC PY 1999 VL 37 IS 12 BP 1260 EP 1269 DI 10.1097/00005650-199912000-00009 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 261PQ UT WOS:000084017900009 PM 10599607 ER PT J AU Biggs, PJ Beatty, J Yasuda, T AF Biggs, PJ Beatty, J Yasuda, T TI Distance-dose curve for a miniature x-ray tube for stereotactic radiosurgery using an optimized aperture with a parallel-plate ionization chamber SO MEDICAL PHYSICS LA English DT Article DE low energy x rays; ion chambers; calibration; apertures; percent depth dose ID INTERSTITIAL RADIOSURGERY; DEVICE AB A recently developed miniature x-ray tube operating at 40 kV has been used in a randomized trial for the treatment of small intracranial lesions. The diameter of these lesions ranges from 10 to 30 mm. A thin window parallel-plate ionization chamber was used to calibrate the output of the x-ray tube, modified by the addition of a thin platinum aperture to reduce the charge collecting area of the chamber. The effect of such an aperture on the measurement of dose versus distance from the x-ray tube in a phantom has been examined as a function of aperture diameter. Aperture diameters were varied between 0 and 5 mm and dose measurements were made for distances between the x-ray source and the front surface of the chamber of 5-30 mm in water. The ratio of doses measured with and without an aperture, when normalized to unity at a distance of 10 mm, differs significantly from unity, for distances between 7.5 and 15 mm, for aperture diameters <1.5 mm and differs from unity, but less significantly, for apertures greater than or equal to 3 mm. For intermediate diameters, however, this dose dependence is minimized, indicating an aperture diameter that provides a similar distance-dose curve as the measurement taken without an aperture over this range of distances. This diameter was found to be between 2 and 2.5 mm with a dose variation of less than +/-1%. For distances <7.5 mm, measurements made with a 1.5-mm-diam aperture agree better with those taken with a 1.7-mm-diamm chamber compared with a 5.2-mm-diam chamber. (C) 1999 American Association of Physicists in Medicine. [S0094-2405(99)01412-1]. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Div Radiat Biophys, Boston, MA 02114 USA. Northeastern Univ, Dept Phys, Boston, MA 02115 USA. RP Biggs, PJ (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Div Radiat Biophys, Boston, MA 02114 USA. NR 6 TC 3 Z9 4 U1 0 U2 2 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD DEC PY 1999 VL 26 IS 12 BP 2550 EP 2554 DI 10.1118/1.598792 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 267LJ UT WOS:000084359200007 PM 10619238 ER PT J AU Gottschalk, B Platais, R Paganetti, H AF Gottschalk, B Platais, R Paganetti, H TI Nuclear interactions of 160 MeV protons stopping in copper: A test of Monte Carlo nuclear models SO MEDICAL PHYSICS LA English DT Article DE nuclear interactions; 160 MeV; stopping protons; nuclear models; Monte Carlo ID RELATIVE BIOLOGICAL EFFECTIVENESS; RADIATION-THERAPY; BEAMS AB To estimate the influence of nuclear interactions on dose or biological effect one uses Monte Carlo programs which include nuclear models. We introduce an experimental method to check these models at proton therapy energies. We have measured the distribution of charge deposited by 160 MeV protons stopping in a stack of insulated copper plates. A buildup region ahead of the main peak contains approximate to 20% of the total charge and is entirely due to charged secondaries from inelastic nuclear interactions. The acceptance for charged secondaries is 100%. Therefore the data are a good benchmark for nuclear models. We have simulated the stack using GEANT with two nuclear models. FLUKA agrees fairly well with the measurement but GHEISHA, designed for much higher energies, does not. The experimental method will work for many other materials, including insulators. Therefore it can also be used for light nuclei. (C) 1999 American Association of Physicists in Medicine. [S0094-2405(99)00312-0]. C1 Harvard Univ, Cyclotron Lab, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Gottschalk, B (reprint author), Harvard Univ, Cyclotron Lab, 44 Oxford St, Cambridge, MA 02138 USA. NR 20 TC 28 Z9 29 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 DEC PY 1999 VL 26 IS 12 BP 2597 EP 2601 DI 10.1118/1.598799 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 267LJ UT WOS:000084359200014 PM 10619245 ER PT J AU Chen, WY Colditz, G AF Chen, WY Colditz, G TI Hormone replacement therapy, selective estrogen receptor modulators, and breast cancer risk SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID POSTMENOPAUSAL WOMEN; FAMILY HISTORY; TAMOXIFEN; MORTALITY C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Chen, WY (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 NR 14 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD WIN PY 1999 VL 6 IS 4 BP 279 EP 281 DI 10.1097/00042192-199906040-00002 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 266KN UT WOS:000084299300002 PM 10614673 ER PT J AU Sayegh, RA Kelly, L Wurtman, J Deitch, A Chelmow, D AF Sayegh, RA Kelly, L Wurtman, J Deitch, A Chelmow, D TI Impact of hormone replacement therapy on the body mass and fat compositions of menopausal women: A cross-sectional study SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE hormone replacement; body mass composition; impedance ID EARLY POSTMENOPAUSAL WOMEN; WEIGHT; ESTROGEN AB Objective: The purpose of the study was to compare the body mass and fat compositions of menopausal women who were taking conventional doses of hormone replacement therapy (HRT) with that of menopausal women who were not taking any hormones. Design: The body fat composition of 169 healthy postmenopausal women was measured using a noninvasive handheld machine, the Electrolipograph (BioAnalogics ELG, Beaverton, OR, USA). Impedance to electrical flow in tissues is lower with increasing water content of the tissue. Information on HRT, lifestyle, diet, smoking, and alcohol was obtained from the medical record and by a telephone interview before women were invited to participate. HRT and non-HRT groups were compared. Multivariate linear regression, which included age, years since menopause, type of menopause, and use of HRT, was performed for each of the two major outcomes: body mass index (BMI) and percentage of body fat. Results: Comparisons between subgroups showed a large number of significant differences reflecting differences in age since menopause, baseline BMIs, and baseline waist to hip ratios. In the regression model, however, the only factor significantly associated with lower fat and BMI was the use of HRT. Women who were taking HRT had significantly lower percentages of body fat (-4.8%; p < 0.001) and BMI (-2.6 kg/m(2); p < 0.001) compared with nonusers. Age and duration and type of menopause were not significant predictors of weight and BMI in this group of postmenopausal women. Conclusions: In this study, HRT seems to be associated with a significant reduction in postmenopausal weight and fat mass gains. This may be an important mechanism by which HRT exerts its beneficial long-term effects on cardiovascular health. (Menopause 1999;6:312-315. (C) 1999, The North American Menopause Society.). C1 Boston Med Ctr, Dept Obstet & Gynecol, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. New England Med Ctr, Dept Obstet & Gynecol, Boston, MA 02111 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. MIT, Dept Nutr, Cambridge, MA 02139 USA. RP Sayegh, RA (reprint author), Boston Med Ctr, Dept Obstet & Gynecol, 720 Harrison Ave,DOB,Suite 1105, Boston, MA 02118 USA. NR 13 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD WIN PY 1999 VL 6 IS 4 BP 312 EP 315 DI 10.1097/00042192-199906040-00007 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 266KN UT WOS:000084299300007 PM 10614678 ER PT J AU Keel, SB Bacha, E Mark, EJ Nielsen, GP Rosenberg, AE AF Keel, SB Bacha, E Mark, EJ Nielsen, GP Rosenberg, AE TI Primary pulmonary sarcoma: A clinicopathologic study of 26 cases SO MODERN PATHOLOGY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 28-MAR 06, 1998 CL BOSTON, MASSACHUSETTS SP US & Canadian Acad Pathol DE lung; malignancy; pulmonary; sarcoma ID MALIGNANT FIBROUS HISTIOCYTOMA; MONOPHASIC SYNOVIAL SARCOMA; LUNG; FEATURES; LEIOMYOSARCOMA AB The clinical and pathologic features of 26 primary pulmonary sarcomas were analyzed. Fourteen patients were male and 12 were female; ranging in age from 18 to 75 years (mean, 48 yr). The tumors measured from 0.9 cm in greatest diameter to filling the entire hemithorax. Thirteen tumors were in the left lung and nine in the right lung; one was bilateral, two were in the pulmonary artery, and the location of one tumor was not available. The histologic diagnoses were malignant fibrous histiocytoma (7), synovial sarcoma (6), malignant peripheral nerve sheath tumor (3), leiomyosarcoma (3), angiosarcoma (2), intimal sarcoma (2), fibrosarcoma (2), and one case of epithelioid hemangioendothelioma. Immunohistochemical and ultrastructural examination supported these diagnoses. Morphologically, the differential diagnosis often included sarcomatoid carcinoma or desmoplastic malignant mesothelioma. Patients were treated with surgery, chemotherapy, radiation therapy, or a combination of these. Follow-up was available for 22 patients and ranged from 2 to 183 months (mean, 45 mo). Fourteen patients are free of disease, four died of disease, three are alive with disease, and one died of surgical complications. A variety of sarcomas, especially malignant fibrous histiocytoma and synovial sarcoma, arise within the pulmonary parenchyma. These tumors have the potential to behave aggressively but can be cured by resection, with or without adjuvant therapy. Immunohistochemistry and electron microscopy can be helpful in distinguishing primary pulmonary sarcoma from other tumors in the differential diagnosis. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Keel, SB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,James Homer Wright Pathol Labs, 32 Fruit St, Boston, MA 02114 USA. NR 24 TC 57 Z9 61 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD DEC PY 1999 VL 12 IS 12 BP 1124 EP 1131 PG 8 WC Pathology SC Pathology GA 270WA UT WOS:000084559100007 PM 10619264 ER PT J AU Asahara, H Dutta, S Kao, HY Evans, RM Montminy, M AF Asahara, H Dutta, S Kao, HY Evans, RM Montminy, M TI Pbx-hox heterodimers recruit coactivator-corepressor complexes in an isoform-specific manner SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GENE-TRANSCRIPTION FACTOR; PANCREATIC-ISLET CELLS; RNA-POLYMERASE-II; HISTONE DEACETYLASE; INSULIN GENE; DNA-BINDING; COOPERATIVE INTERACTIONS; HOMEODOMAIN PROTEIN; HOMEOBOX FACTOR; FACTOR STF-1 AB Homeobox (hox) proteins have been shown to regulate cell fate and segment identity by promoting the expression of specific genetic programs. In contrast to their restricted biological action in vivo, however, most homeodomain factors exhibit promiscuous DNA binding properties in vitro, suggesting a requirement for additional cofactors that enhance target site selectivity. In this regard, the pbx family of homeobox genes has been found to heterodimerize with and thereby augment the DNA binding activity of certain hox proteins on a subset of potential target sites, Here we examine the transcriptional properties of a forced hox-pbx heterodimer containing the pancreas-specific orphan homeobox factor pdx fused to pbx-1a. Compared to the pdx monomer, the forced pdx-pbx1a dimer, displayed 10- to 20-fold-higher affinity for a consensus hox-pbx binding site but was completely unable to bind a hox monomer recognition site. The pdx-pbx dimer stimulated target gene expression via an N-terminal trans-activation domain in pdr that interacts with the coactivator CREB binding protein. The pdx-pbx dimer was also found to repress transcription via a C-terminal domain in pbx-1a that associates with the corepressors SMRT and NCoR The transcriptional properties of the pdx-pbx1 complex appear to be regulated at the level of alternative splicing; a pdx-pbx polypeptide containing the pbx1b isoform, which lacks the C-terminal extension in pbx1a, was unable to repress target gene expression via NCoR-SMRT, Since pbx1a and pbx1b are differentially expressed in endocrine versus exocrine compartments of the adult pancreas, our results illustrate a novel mechanism by which pbn proteins may modulate the expression of specific genetic programs, either positively or negatively, during development. C1 Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA. RP Montminy, M (reprint author), Salk Inst Biol Studies, Howard Hughes Med Inst, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. FU NIDDK NIH HHS [R01 DK049777, R0IDK49777]; PHS HHS [P0I54418] NR 36 TC 115 Z9 116 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 DEC PY 1999 VL 19 IS 12 BP 8219 EP 8225 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 257KP UT WOS:000083781300032 PM 10567547 ER PT J AU Campanero, MR Armstrong, M Flemington, E AF Campanero, MR Armstrong, M Flemington, E TI Distinct cellular factors regulate the c-myb promoter through its E2F element SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; TRANSCRIPTION FACTOR E2F; HISTONE DEACETYLASE; S-PHASE; REPRESS TRANSCRIPTION; CYCLE PROGRESSION; COMPLEX-FORMATION; FACTOR DRTF1/E2F; COLON-CARCINOMA; MAMMALIAN-CELLS AB Most E2F-driven promoters are transiently activated around the G(1)/S transition. Although the promoter for the c-myb proto-oncogene harbors an E2F element, it is induced early in G(1) following entry into the cell cycle. Furthermore, this promoter remains active throughout subsequent cell cycles. Since E2F sites function as repressor elements during G(1) (due to the association of pRb with E2F factors), we investigated whether the E2F element in the c-myb promoter is regulated differently than E2F elements in promoters that are repressed during G(1). By gel shia analysis, the E2F element from the c-myb promoter was found to farm a unique complex, referred to as E2Fmyb-sp, which was not observed with E2F elements from several other promoters. Antibodies to DP-1, E2F1 to -5, p107, or pRb failed to either supershift or block E2Fmyb-sp complex formation. Methylation interference experiments indicate that the DNA contact residues for the E2Fmyb-sp complex are distinct from but overlapping with residues required for the binding of E2F proteins. In addition to the identification of E2Fmyb-sp, we have found that SP-1 binds to the c-myb E2F element. Functional studies revealed that E2Fmyb-sp and/or SP-1 are required to achieve full activation of the c-myb promoter in different cell types and to maintain elevated expression of the c-myb promoter during G(1) in NIH 3T3 cells. These studies demonstrate that E2F elements can be regulated differently through the binding of unique sets of proteins. C1 Harvard Univ, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Flemington, E (reprint author), Harvard Univ, 44 Binney St, Boston, MA 02115 USA. RI Campanero, Miguel/A-4052-2013 OI Campanero, Miguel/0000-0003-1410-8621 FU NIGMS NIH HHS [R01 GM048045, R01GM48045] NR 75 TC 30 Z9 31 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 DEC PY 1999 VL 19 IS 12 BP 8442 EP 8450 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 257KP UT WOS:000083781300054 PM 10567569 ER PT J AU Yamamoto, K Ichijo, H Korsmeyer, SJ AF Yamamoto, K Ichijo, H Korsmeyer, SJ TI BCL-2 is phosphorylated and inactivated by an ASK1/Jun N-terminal protein kinase pathway normally activated at G(2)/M SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CELL-CYCLE PROGRESSION; SIGNAL-TRANSDUCTION; FOLLICULAR LYMPHOMA; CYTOCHROME-C; CANCER-CELLS; X-L; APOPTOSIS; DEATH; SURVIVAL; BAD AB Multiple signal transduction pathways are capable of modifying BCL-2 family members to reset susceptibility to apoptosis. We used two-dimensional peptide mapping and sequencing to identify three residues (Ser70, Ser87, and Thr69) within the unstructured loop of BCL-2 that were phosphorylated in response to microtubule-damaging agents, which also arrest cells at G(2)/M. Changing these sites to alanine conferred more antiapoptotic activity on BCL-2 following physiologic death signals as well as paclitaxel, indicating that phosphorylation is inactivating. An examination of cycling cells enriched by elutriation for distinct phases of the cell cycle revealed that BCL-2 was phosphorylated at the G2/M phase of the cell cycle. G(2)/M-phase cells proved more susceptible to death signals, and phosphorylation of BCL-2 appeared to be responsible, as a Ser70Ala substitution restored resistance to apoptosis, We noted that ASK1 and JNK1 were normally activated at G(2)/M phase, and JNK was capable of phosphorylating BCL-2. Expression of a series of wild-type and dominant-negative kinases indicated an ASK1/Jun N-terminal protein kinase 1 (JNK1) pathway phosphorylated BCL-2 in vivo. Moreover, the combination of dominant negative ASK1, (dnASK1), dnMKK7, and dnJNK1 inhibited paclitaxel-induced BCL-2 phosphorylation. Thus, stress response kinases phosphorylate BCL-2 during cell cycle progression as a normal physiologic process to inactivate BCL-2 at G(2)/M. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Korsmeyer, SJ (reprint author), Harvard Univ, Sch Med, Dept Pathol, 1 Jimmy Fund Way, Boston, MA 02115 USA. NR 71 TC 755 Z9 771 U1 2 U2 18 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1999 VL 19 IS 12 BP 8469 EP 8478 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 257KP UT WOS:000083781300057 PM 10567572 ER PT J AU Thomas, MK Yao, KM Tenser, MS Wong, GG Habener, JF AF Thomas, MK Yao, KM Tenser, MS Wong, GG Habener, JF TI Bridge-1, a novel PDZ-domain coactivator of E2A-mediated regulation of insulin gene transcription SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID UBIQUITIN-CONJUGATING ENZYME; LOOP-HELIX PROTEINS; E2A PROTEINS; CDNA CLONING; CELL-LINES; FACTOR E47; EXPRESSION; DIFFERENTIATION; INHIBITION; SEQUENCES AB Proteins in the E2A family of basic helix-loop-helix transcription factors are important in a wide spectrum of physiologic processes as diverse as neurogenesis, myogenesis, lymphopoeisis, and sex determination. In the pancreatic beta cell, E2A proteins, in combination with tissue-specific transcription factors, regulate expression of the insulin gene and other genes critical for beta-cell function. By yeast two-hybrid screening of a cDNA library prepared from rat insulinoma (INS-I) cells, we identified a novel protein, Bridge-1, that interacts with E2A proteins and functions as a coactivator of gene transcription mediated by E12 and E47. Bridge-1 contains a PDZ-like domain, a domain known to be involved in protein-protein interactions. Bridge-1 is highly expressed in pancreatic islets and islet cell lines and the expression pattern is primarily nuclear. The interaction of Bridge-1 with E2A proteins is further demonstrated by coimmunoprecipitation of in vitro-translated Bridge-1 with E12 or E47 and by mammalian two-hybrid studies. The PDZ-like domain of Bridge-1 is required for interaction with the carboxy terminus of E12. In both yeast and mammalian two-hybrid interaction studies, Bridge-1 mutants lacking an intact PDZ-like domain interact poorly with E12. An E12 mutant (E12 Delta C) lacking the carboxy-terminal nine amino acids shows impaired interaction with Bridge-1. Bridge-1 has direct transactivational activity, since a Gal4 DNA-binding domain-Bridge-1 fusion protein transactivates a Gal4CAT reporter. Bridge-1 also functions as a coactivator by enhancing E12- or E47-mediated activation of a rat insulin I gene minienhancer promoter-reporter construct in transient-transfection experiments. Substitution of the mutant E12 Delta C for E12 reduces the coactivation of the rat insulin I minienhancer by Bridge-1. Inactivation of endogenous Bridge-1 in insulinoma (INS-1) cells by expression of a Bridge-1 antisense RNA diminishes rat insulin I promoter activity. Bridge-1, by utilizing its PDZ-like domain to interact with E12, may pro vide a new mechanism for the coactivation and regulation of transcription of the insulin gene. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Endocrinol Lab, Boston, MA 02114 USA. Howard Hughes Med Inst, Boston, MA 02114 USA. Genet Inst, Cambridge, MA 02140 USA. Univ Hong Kong, Fac Med, Dept Biochem, Hong Kong, Peoples R China. RP Habener, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Endocrinol Lab, 55 Fruit St,WEL320, Boston, MA 02114 USA. RI Yao, Kwok Ming/C-4457-2009 NR 49 TC 56 Z9 57 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1999 VL 19 IS 12 BP 8492 EP 8504 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 257KP UT WOS:000083781300059 PM 10567574 ER PT J AU Bastepe, M Pincus, JE Juppner, H AF Bastepe, M Pincus, JE Juppner, H TI Two frequent tetra-nucleotide repeat polymorphisms between VAPB and STX16 on chromosome 20q13 SO MOLECULAR AND CELLULAR PROBES LA English DT Article ID SYNTAXIN-16; SNARE C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,WEL 5, Boston, MA 02114 USA. FU PHS HHS [R0146718-06] NR 5 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD DEC PY 1999 VL 13 IS 6 BP 449 EP 451 DI 10.1006/mcpr.1999.0271 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 282JU UT WOS:000085215500008 PM 10657150 ER PT J AU Scully, R Ganesan, S Vlasakova, K Chen, JJ Socolovsky, M Livingston, DM AF Scully, R Ganesan, S Vlasakova, K Chen, JJ Socolovsky, M Livingston, DM TI Genetic analysis of BRCA1 function in a defined tumor cell line SO MOLECULAR CELL LA English DT Article ID DOUBLE-STRAND BREAKS; INTERACT IN-VIVO; ATAXIA-TELANGIECTASIA; DNA-DAMAGE; TRANSCRIPTIONAL ACTIVATION; EMBRYONIC LETHALITY; MEIOTIC CELLS; INDUCTION; REPAIR; RADIOSENSITIVITY AB Retrovirally expressed, wild-type BRCA1 decreased the gamma radiation (IR) sensitivity and increased the efficiency of double-strand DNA break repair (DSBR) of the BRCA1(-/-) human breast cancer line, HCC1937. It also reduced its susceptibility to DSB generation by IR. By contrast, multiple, clinically validated, missense mutant BRCA1 products were nonfunctional in these assays. These data constitute the basis for a BRCA1 functional assay and suggest that efficient repair of double-strand DNA breaks is linked to BRCA1 tumor suppression function. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Whitehead Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02138 USA. RP Livingston, DM (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. RI Scully, Ralph/F-5008-2013 FU NCI NIH HHS [K01 CA079576]; NHLBI NIH HHS [HL 32262] NR 41 TC 270 Z9 278 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD DEC PY 1999 VL 4 IS 6 BP 1093 EP 1099 DI 10.1016/S1097-2765(00)80238-5 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 269PC UT WOS:000084485900021 PM 10635334 ER PT J AU Roy, P Roth, CM Margolies, MN Yarmush, ML AF Roy, P Roth, CM Margolies, MN Yarmush, ML TI Effect of pressure on antigen-antibody complexes: modulation by temperature and ionic strength SO MOLECULAR IMMUNOLOGY LA English DT Article DE immunoadsorption; hydrostatic pressure; thermodynamics; salt bridges ID HEN EGG LYSOZYME; MONOCLONAL-ANTIBODIES; DISSOCIATION KINETICS; WHITE LYSOZYME; ASSOCIATION; HYHEL-5; SPECIFICITY; PROTEINS; AFFINITY; BINDING AB Changes in the equilibrium binding affinity of antigen-antibody complexes subjected to hydrostatic pressures of about 2000 bar provide a potential means for the separation and recovery under mild conditions of biological molecules from immunoadsorbents or immunosensors, We have investigated the ability of temperature and ionic strength to modulate the pressure sensitivity of several antigen-antibody complexes in solution. For two different protein:monoclonal antibody complexes (BSA,9.1 and HEWL,HyHEL-10) exhibiting pressure-induced dissociation (positive association volume), we find little temperature dependence to the association volume, For another complex (digoxigenin:26-10) exhibiting pressure-induced association, the association volume increases with temperature, which, via a Maxwell relation, indicates that enthalpic changes drive the pressure effect. An increase in ionic strength decreases the affinity of binding the HEWL:HyHEL-5 complex, which contains several salt bridges. At low ionic strengths (< 0.3 M), no pressure dependence of the free energy of association is observed, but at higher ionic strengths, significant pressure-induced association is observed, suggesting that positive contributions to the association volume provided by the salt bridges are counterbalanced by other (e.g., aromatic stacking) interactions that lead to negative association volumes. These results suggest that ionic strength may be used to modulate the pressure sensitivity of antigen-antibody complexes, which may be useful in designing processes that exploit this phenomenon for immunoseparations. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Shriners Burns Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Yarmush, ML (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. OI Roth, Charles/0000-0002-4924-0721 FU NHLBI NIH HHS [R01 HL47415] NR 38 TC 7 Z9 7 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD DEC PY 1999 VL 36 IS 17 BP 1149 EP 1158 DI 10.1016/S0161-5890(99)00133-9 PG 10 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 283VT UT WOS:000085297300003 PM 10698317 ER PT J AU Berger, O Gan, XH Gujuluva, C Burns, AR Sulur, G Stins, M Way, D Witte, M Weinand, M Said, J Kim, KS Taub, D Graves, MC Fiala, M AF Berger, O Gan, XH Gujuluva, C Burns, AR Sulur, G Stins, M Way, D Witte, M Weinand, M Said, J Kim, KS Taub, D Graves, MC Fiala, M TI CXC and CC chemokine receptors on coronary and brain endothelia SO MOLECULAR MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LOW-DENSITY-LIPOPROTEIN; INFLAMMATORY CYTOKINES; HIV-1 INFECTION; CO-RECEPTORS; TNF-ALPHA; CELLS; EXPRESSION; CORECEPTORS; BETA AB Background: Chemokine receptors on leukocytes play a key role in inflammation and HIV-1 infection. Chemokine receptors on endothelia may serve an important role in HIV-1 tissue invasion and angiogenesis. Materials and Methods: The expression of chemokine receptors in human brain microvascular endothelial cells (BMVEC) and coronary artery endothelial cells (CAEC) in vitro and cryostat sections of the heart tissue was determined by light and confocal microscopy and now cytometry with monodonal antibodies. Chemotaxis of endothelia by CC chemokines was evaluated in a transmigration assay. Results: In BMVEC, the chemokine receptors CCR3 and CXCR4 showed the strongest expression. CXCR4 was localized by confocal microscopy to both the cytoplasm and the plasma membrane of BMVEC. In CAEC, CXCR4 demonstrated a strong expression with predominantly periplasmic localization. CCR5 expression was detected both in BMVEC and CAEC but at a lower level. Human strongly CXCR4 but only weakly CCR3 and CCRS5. Two additional CC chemokines, CCR2A and CCR4, were detected in BMVEC and CAEC by immunostaining. Immunocytochemistry of the heart tissues with monoclonal antibodies revealed a high expression of CXCR4 and CCR2A and a low expression of CCR3 and CCR5 on coronary vessel endothelia. Coronary endothelia showed in vitro a strong chemotactic response to the CC chemokines RANTEs, MIP-1 alpha, and MIP-1 beta. Conclusions: The endothelia isolated from the brain display strongly both the CCR3 and CXCR4 HIV-1 coreceptors, whereas the coronary endothelia express strongly only the CXCR4 coreceptor. CCR5 is expressed at a lower level in both endothelia. The differential display of CCR3 on the brain and coronary endothelia could be significant with respect to the differential susceptibility of the heart and the brain to HIV-1 invasion. In addition, CCR2A is strongly expressed in the heart endothelium. All of the above chemokine receptors could play a role in endothelial migration and repair. C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Microbiol & Immunol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. Baylor Coll Med, Dept Med, Sect Cardiovasc Sci & Leukocyte Biol, Houston, TX 77030 USA. Childrens Hosp Los Angeles, Div Infect Dis, Los Angeles, CA 90027 USA. Univ Arizona, Dept Surg, Tucson, AZ USA. NIA, Baltimore, MD 21224 USA. W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. RP Fiala, M (reprint author), Univ Calif Los Angeles, Sch Med, Dept Neurol, 710 Westwood Plaza, Los Angeles, CA 90095 USA. FU NHLBI NIH HHS [HL 48493]; NIDA NIH HHS [DA10442]; NINDS NIH HHS [NS 26126] NR 45 TC 89 Z9 98 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD DEC PY 1999 VL 5 IS 12 BP 795 EP 805 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 280CF UT WOS:000085084100003 PM 10666479 ER PT J AU McDonough, MA Butterton, JR AF McDonough, MA Butterton, JR TI Spontaneous tandem amplification and deletion of the Shiga toxin operon in Shigella dysenteriae 1 SO MOLECULAR MICROBIOLOGY LA English DT Article ID NUCLEOTIDE-SEQUENCE ANALYSIS; ENTEROHEMORRHAGIC ESCHERICHIA-COLI; VIBRIO-CHOLERAE; PATHOGENICITY ISLANDS; CONVERTING PHAGES; STRUCTURAL GENES; EDEMA DISEASE; B-SUBUNIT; STRAINS; EXPRESSION AB Only one species of Shigella, Shigella dysenteriae 1, has been demonstrated to produce Shiga toxin (Stx). Stx is closely related Po the toxins produced by Shiga toxin-producing Escherichia coli (STEC). In STEC, these toxins are often encoded on lambdoid bacteriophages and are major virulence factors for these organisms. Although the bacteriophage-encoded stx genes of STEC are highly mobile, the stx genes in S. dysenteriae 1 have been believed to be chromosomally encoded and not transmissible. We have located the toxin genes of S. dysenteriae 1 to a region homologous to minute 30 of the E. coli chromosome, within a 22.4 kbp putative composite transposon bracketed by IS600 insertion sequences. This region is present In all the a dysenteriae 1 strains examined. Tandem amplification occurs via the flanking insertion sequences, leading to increased toxin production. The global regulatory gene, fnr, is located within the stx region, allowing deletions of the toxin genes to be created by anaerobic growth on chlorate-containing medium. Deletions occur by recombination between the flanking IS600 elements. Lambdoid bacteriophage genes are found both upstream and within the region, and we demonstrate the lysogeny of Shigella species with STEC bacteriophages. These observations suggest that S. dysenteriae 1 originally carried a Stx-encoding lambdoid prophage, which became defective due to loss of bacteriophage sequences after IS element insertions and rearrangements. These insertion sequences have subsequently allowed the amplification and deletion of the stx region. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Butterton, JR (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. FU NIAID NIH HHS [AI01386] NR 59 TC 64 Z9 69 U1 2 U2 7 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD DEC PY 1999 VL 34 IS 5 BP 1058 EP 1069 DI 10.1046/j.1365-2958.1999.01669.x PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 268UL UT WOS:000084433900017 PM 10594830 ER PT J AU Morimura, H Saindelle-Ribeaudeau, F Berson, EL Dryja, TP AF Morimura, H Saindelle-Ribeaudeau, F Berson, EL Dryja, TP TI Mutations in RGR, encoding a light-sensitive opsin homologue, in patients with retinitis pigmentosa SO NATURE GENETICS LA English DT Article ID LOCALIZATION; EPITHELIUM; GENE C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Oncol 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. Le Mans Hosp, Dept Ophthalmol, F-72037 Le Mans, France. RP Morimura, H (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Oncol Mol Genet Inst, Boston, MA 02114 USA. FU NEI NIH HHS [EY00169, EY08683] NR 11 TC 82 Z9 84 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 DEC PY 1999 VL 23 IS 4 BP 393 EP 394 DI 10.1038/70496 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 261RZ UT WOS:000084023900012 PM 10581022 ER PT J AU Li, YP Chen, W Liang, YQ Li, E Stashenko, P AF Li, YP Chen, W Liang, YQ Li, E Stashenko, P TI Atp6i-deficient mice exhibit severe osteopetrosis due to loss of osteoclast-mediated extracellular acidification SO NATURE GENETICS LA English DT Article ID PROTON PUMP; RESORPTION; CELLS; PH AB Solubilization of bone mineral by osteoclasts depends on the formation of an acidic extracellular compartment through the action of a V-proton pump that has not yet been characterized at the molecular level(1-3). We previously cloned a gene (Atp6i, for V-proton pump, H+ transporting (vacuolar proton pump) member I) encoding a putative osteoclast-specific proton pump subunit, termed OC-116kD (ref, 4), Here we show that targeted disruption of Atp6i in mice results in severe osteopetrosis. Atp6i(-/-) osteoclast-like cells (OCLs) lose the function of extracellular acidification, but retain intracellular lysosomal proton pump activity. The pH in Atp6i(-/-) liver lysosomes and proton transport in microsomes of Atp6i(-/-) kidney are identical to that in wild-type mice. Atp6i(-/-) mice exhibit a normal acid-base balance in blood and urine. Our results demonstrate that Atp6i is unique and necessary for osteoclast-mediated extracellular acidification. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. Harvard Univ, Forsyth Inst, Forsyth Dept Oral Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr,Dept Med, Charlestown, MA USA. RP Li, YP (reprint author), Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. FU NIAMS NIH HHS [AR44741]; NIDCR NIH HHS [DE-07378] NR 20 TC 322 Z9 332 U1 1 U2 8 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 1999 VL 23 IS 4 BP 447 EP 451 DI 10.1038/70563 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 261RZ UT WOS:000084023900022 PM 10581033 ER PT J AU Furukawa, T Morrow, EM Li, TS Davis, FC Cepko, CL AF Furukawa, T Morrow, EM Li, TS Davis, FC Cepko, CL TI Retinopathy and attenuated circadian entrainment in Crx-deficient mice SO NATURE GENETICS LA English DT Article ID CONE-ROD DYSTROPHY; RDS MUTANT MICE; HOMEOBOX GENE; RETINITIS-PIGMENTOSA; TRANSGENIC MICE; OUTER SEGMENTS; MUTATIONS; PHOTORECEPTOR; EXPRESSION; DIFFERENTIATION AB Crx, an Otx-like homeobox gene, is expressed specifically in the photoreceptors of the retina and the pinealocytes of the pineal gland(1,2). Crx has been proposed to have a role in the regulation of photoreceptor-specific genes in the eye and of pineal-specific genes in the pineal gland. Mutations in human CRX are associated with the retinal diseases, cone-rod dystrophy-2 (adCRD2; refs 3-5), retinitis pigmentosa(5) (RP) and Leber congenital amaurosis(5,6) (LCA), which all lead to loss of vision. We generated mice carrying a targeted disruption of Crx. Crx(-/-) mice do not elaborate photoreceptor outer segments and lacked rod and cone activity as assayed by electroretinogram (ERG). Expression of several photoreceptor- and pineal-specific genes was reduced in Crx mutants. Circadian entrainment was also affected in Crx(-/-) mice. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. Northeastern Univ, Dept Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Furukawa, T (reprint author), Univ Texas, SW Med Ctr, Ctr Dev Biol, 5323 Harry Hines Blvd, Dallas, TX USA. RI Morrow, Eric/J-2767-2013 NR 27 TC 347 Z9 351 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 DEC PY 1999 VL 23 IS 4 BP 466 EP 470 DI 10.1038/70591 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 261RZ UT WOS:000084023900026 PM 10581037 ER PT J AU Passafaro, M Sala, C Niethammer, M Sheng, M AF Passafaro, M Sala, C Niethammer, M Sheng, M TI Microtubule binding by CRIPT and its potential role in the synaptic clustering of PSD-95 SO NATURE NEUROSCIENCE LA English DT Article ID NMDA RECEPTOR SUBUNITS; POSTSYNAPTIC DENSITY; NEUROMUSCULAR-JUNCTION; HIPPOCAMPAL-NEURONS; GUANYLATE KINASES; PDZ DOMAIN; PROTEIN; CHANNEL; LOCALIZATION; MEMBRANE AB CRIPT is a postsynaptic protein that binds selectively to the third PDZ domain (PDZ3) of PSD-95. Here we show that CRIPT also binds directly to microtubules, thereby linking PSD-95 to the microtubule cytoskeleton. Disrupting the CRIPT-PSD-95 interaction in cultured hippocampal neurons with a PDZ3-specific peptide prevented the association of PSD-95 with microtubules and inhibited the synaptic clustering of PSD-95, chapsyn-110/PSD-93 and GKAP (a PSD-95-binding protein). However, the number of synapses and the synaptic clustering of NMDA receptors were unaffected, suggesting that PSD-95-family proteins are not essential for the maintenance of synapses and the synaptic localization of NMDA receptors. C1 Massachusetts Gen Hosp, 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 Sheng, M (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, HHMI Wellman 423,50 Blossom St, Boston, MA 02114 USA. RI Sala, Carlo/A-2493-2009 OI Sala, Carlo/0000-0003-0662-9523 FU NINDS NIH HHS [NS35050] NR 39 TC 87 Z9 89 U1 2 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD DEC PY 1999 VL 2 IS 12 BP 1063 EP 1069 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 292TA UT WOS:000085810100009 PM 10570482 ER PT J AU Ji, RR Baba, H Brenner, GJ Woolf, CJ AF Ji, RR Baba, H Brenner, GJ Woolf, CJ TI Nociceptive-specific activation of ERK in spinal neurons contributes to pain hypersensitivity SO NATURE NEUROSCIENCE LA English DT Article ID DORSAL HORN NEURONS; FORMALIN-INDUCED ACTIVITY; LONG-TERM POTENTIATION; RECEPTOR MESSENGER-RNA; PROTEIN-KINASE; CENTRAL SENSITIZATION; TISSUE-INJURY; IN-VIVO; RAT; STIMULATION AB We investigated the involvement of extracellular signal-regulated protein kinases (ERK) within spinal neurons in producing pain hypersensitivity. Within a minute of an intense noxious peripheral or C-fiber electrical stimulus, many phosphoERK-positive neurons were observed, most predominantly in lamina I and IIo of the ipsilateral dorsal horn. This staining was intensity and NMDA receptor dependent. Low-intensity stimuli or A-fiber input had no effect. Inhibition of ERK phosphorylation by a MEK inhibitor reduced the second phase of formalin-induced pain behavior, a measure of spinal neuron sensitization. ERK signaling within the spinal cord is therefore involved in generating pain hypersensitivity. Because of its rapid activation, this effect probably involves regulation of neuronal excitability without changes in transcription. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Ji, RR (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, 149 13th St,Rm 4309, Boston, MA 02129 USA. OI Ji, Ru-Rong/0000-0002-9355-3688 FU NINDS NIH HHS [NS 38253-01] NR 50 TC 474 Z9 514 U1 0 U2 13 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD DEC PY 1999 VL 2 IS 12 BP 1114 EP 1119 DI 10.1038/16040 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 292TA UT WOS:000085810100016 PM 10570489 ER PT J AU Gotter, AL Levine, JD Reppert, SM AF Gotter, AL Levine, JD Reppert, SM TI Sex-linked period genes in the silkmoth, Antheraea pernyi: Implications for circadian clock regulation and the evolution of sex chromosomes SO NEURON LA English DT Article ID DROSOPHILA CLOCK; DOSAGE COMPENSATION; ANTISENSE RNA; PROTEIN; TIMELESS; RHYTHMS; TRANSCRIPTION; MELANOGASTER; MUTATION; TIM AB Regulation of the period (per) gene is a critical feature of circadian clock function in insects. Here, we show that per is sex-linked in the silkmoth, Antheraea pernyi. The previously described silkmoth per gene is found on the Z chromosome. Silkmoth per is not dosage compensated at either the RNA or the protein level. Although earlier studies showed the presence of an oscillating endogenous antisense per transcript, we show that this transcript comes from a locus on the female-specific W chromosome. We further demonstrate the presence of a homolog of per on W that encodes a truncated protein. Rhythmicity of male (ZZ) moths demonstrates that neither of the W-linked per-like genes is essential for clock function. The presence of a per allele with duplications on W provides insight into the evolution of the sex chromosomes. C1 Massachusetts Gen Hosp, Lab Dev Chronobiol, Serv Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Reppert, SM (reprint author), Massachusetts Gen Hosp, Lab Dev Chronobiol, Serv Pediat, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM55820]; NIMH NIH HHS [MH12117] NR 62 TC 43 Z9 44 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD DEC PY 1999 VL 24 IS 4 BP 953 EP 965 DI 10.1016/S0896-6273(00)81042-9 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 269UE UT WOS:000084495300023 PM 10624958 ER PT J AU Marder, SR AF Marder, SR TI Limitations of dopamine-D-2 antagonists and the search for novel antipsychotic strategies SO NEUROPSYCHOPHARMACOLOGY LA English DT Article ID SCHIZOPHRENIA; CLOZAPINE C1 W Los Angeles Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. RP Marder, SR (reprint author), W Los Angeles Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Mental Illness Res Educ & Clin Ctr, MIRECC 210 A,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 6 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 1999 VL 21 IS 6 SU S BP S117 EP S121 DI 10.1016/S0893-133X(99)00105-0 PG 5 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 268AJ UT WOS:000084391200001 ER PT J AU Weber, GF AF Weber, GF TI Final common pathways in neurodegenerative diseases: regulatory role of the glutathione cycle SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE neurodegenerative diseases; homeostasis; glutathione cycle ID AMYOTROPHIC-LATERAL-SCLEROSIS; HYDROXYL RADICAL PRODUCTION; LONG-TERM POTENTIATION; TUMOR-NECROSIS-FACTOR; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; ARACHIDONIC-ACID; CELL-DEATH; SUPEROXIDE-DISMUTASE; GLUTAMATE TOXICITY AB Attempts to unify diverse mechanisms of neurotoxicity have led to the concept of final common pathways which characterize frequently occurring cellular responses to disruption of homeostasis. The clinical presentation and common patho-biochemistry of reactive oxygen intermediates of Guam's disease have suggested that such pathways may be operative in three major neurodegenerative disorders: Alzheimer's dementia, amyotrophic lateral sclerosis and Parkinson's disease. A candidate-signaling pathway in this regard is characterized by the cascade arachidonic acid/HPETE/(OH)-O-./cGMP followed by activation of cGMP-dependent kinase and phosphorylation of NF-kB proteins and possibly CREB. This sequence may lead to apoptosis as well as long-term potentiation and memory and constitutes a biochemical correlate to excitotoxicity. The predominant control of (OH)-O-. release from HPETE, a checkpoint in this pathway, is exerted by the glutathione cycle, a central biochemical process that is also intimately associated with the synthesis of the neurotransmitters glutamate and GABA and is connected to energy metabolism. Modifications in the activity of the glutathione cycle may provide treatment options. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Weber, GF (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, 44 Binney St,Room SM 718, Boston, MA 02115 USA. NR 50 TC 45 Z9 49 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD DEC PY 1999 VL 23 IS 8 BP 1079 EP 1086 DI 10.1016/S0149-7634(99)00041-X PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 273VL UT WOS:000084728500002 PM 10643818 ER PT J AU Bromley, B Shipp, TD Benacerraf, BR AF Bromley, B Shipp, TD Benacerraf, BR TI Amnion-chorion separation after 17 weeks' gestation SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID AMNIOCENTESIS; BAND AB Objective: To evaluate the cause of and perinatal outcomes of amnion-chorion separation that is apparent sonographically after 17 weeks' gestation. Methods: We searched our ultrasound database over 7 years for information on pregnant women who had live fetuses and complete separation between amnion and chorion that persisted beyond 17 weeks' gestation. For inclusion in the study, the women had to have amnion separated from chorion on at least three sides of the gestational sac. Medical records were reviewed for whether women had amniocenteses, results of the amniocenteses, and outcomes of the pregnancies. Results: Of 15 pregnant women with live fetuses, ten had amniocenteses before identification of amnion-chorion separation and five did not. Three had fetuses with Down syndrome, two of whom had amnion-chorion separation evident before amniocentesis, and all three had other sonographic findings suggestive of aneuploidy. Three fetuses died. The other pregnancies were complicated by one or more adverse events, including two fetuses with growth restriction, five preterm deliveries, two with oligohydramnios, and one with abruptio placentae. Five infants were delivered at term and are alive and well. Overall ten of 15 pregnancies resulted in live newborns, one of whom had Down syndrome. Conclusion: Complete amnion-chorion separation that persisted after 17 weeks' gestation is associated with a variety of adverse perinatal outcomes, including aneuploidy. (Obstet Gynecol 1999;94:1024-6. (C) 1999 by The American College of Obstetricians and Gynecologists.). C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Bromley, B (reprint author), Diagnost Ultrasound Associates, 333 Longwood Ave, Boston, MA 02115 USA. NR 6 TC 18 Z9 18 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 1999 VL 94 IS 6 BP 1024 EP 1026 DI 10.1016/S0029-7844(99)00457-3 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 257QJ UT WOS:000083792800022 PM 10576194 ER PT J AU Akpek, EK Maca, SM Christen, WG Foster, CS AF Akpek, EK Maca, SM Christen, WG Foster, CS TI Elevated vitreous interrleukin-10 level is not diagnostic of intraocular-central nervous system lymphoma SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Uveitis-Society CY NOV, 1998 CL NEW ORLEANS, LOUISIANA SP Amer Uveitis Soc ID POLYMERASE-CHAIN-REACTION; RETICULUM-CELL SARCOMA; EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; INTERLEUKIN-10; CYTOKINES; UVEITIS; TRANSLOCATION; EXPRESSION; UTILITY; TISSUES AB Objective: Diagnosis of intraocular-central nervous system (CNS) lymphoma is commonly made by identifying malignant lymphocytes in the vitreous. However, such cells are in the minority in the vitreous cellular infiltrate (most are reactive lymphocytes), and therefore lack of cytologic support from biopsied vitreous samples in patients suspected of having intraocular-CNS lymphoma may occur. Recent data suggest that interleukin-10 (IL-10) levels are elevated in the serum and vitreous of patients with non-Hodgkin's lymphoma, whereas IL-12 and IL-6 levels are elevated in patients with uveitis of non-neoplastic etiology. The authors evaluated the usefulness of measuring vitreous levels of IL-6, -10, and -12 in the diagnosis of intraocular-CNS lymphoma. Design: Prospective case series. Participants: Seventeen patients with intraocular inflammation who underwent a diagnostic or therapeutic vitrectomy: 4 patients with intraocular-CNS lymphoma and 13 patients with uveitis unrelated to a neoplasm, Intervention: Eighteen vitreous specimens were obtained prospectively. Concentrations of IL-6, -10, and -12 were measured by enzyme immunosorbent assay, and relative ratios of the interleukins were calculated. Cytopathologic examination and flow cytometry of vitreous cells were also performed. Main Outcome Measures: The ratio of IL-10/IL-12 and IL-10/IL-6 was calculated to assess any association of intraocular-CNS lymphoma and high vitreous IL-10 relative to IL-6 and IL-12 levels, Results: The IL-10/IL-6 and IL-10/IL-12 ratio was greater than 1 in 8 of 14 vitreous specimens obtained from 13 patients with non-neoplastic uveitis, One of the four specimens from patients with cytologically proven intraocular-CNS lymphoma had vitreous IL-10/IL-6 and IL-10/IL-12 ratios of less than 1. Conclusion: Although a helpful diagnostic tool, an elevated vitreous IL-10 to IL-6 or IL-12 ratio is not always associated with intraocular-CNS lymphoma. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Prevent Med, Boston, MA USA. RP Foster, CS (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. NR 31 TC 34 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 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD DEC PY 1999 VL 106 IS 12 BP 2291 EP 2295 PG 5 WC Ophthalmology SC Ophthalmology GA 261BC UT WOS:000083987100026 PM 10599659 ER PT J AU Neto, JFL Burns, AG Lu, L Mombach, R Saffer, M AF Neto, JFL Burns, AG Lu, L Mombach, R Saffer, M TI Passive smoking and nonrecurrent acute otitis media in children SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID MIDDLE-EAR EFFUSION; RISK-FACTORS; LIFE; EPIDEMIOLOGY; CARE AB INTRODUCTION: It remains uncertain whether passive smoking is a risk factor (RF) for nonrecurrent acute otitis media (AOM). The aim of this study was to evaluate whether exposure to second-hand smoke at home increased the prevalence of an isolated single episode of nonrecurrent AOM in children. METHODS AND MATERIAL: We performed a cross-sectional study with 192 children younger than 3 years who were seen at a general pediatric clinic. A questionnaire was used to quantify the exposure to cigarette smoke at home and to assess other RFs for AOM. The diagnosis of AOM was made by pediatricians using otoscopy. The results of the associations were reported by prevalence ratios with 95% confidence intervals. Multiple logistic regression was used to investigate the role of confounding variables among other potential RFs and passive smoking. RESULTS: The prevalence ratio of an isolated single episode of nonrecurrent AOM between patients exposed and those not exposed to passive smoking was 0.82 (0.67 to 1.02). In logistic regression, any RF changed the main association significantly. CONCLUSION: Exposure to passive smoking did not change the prevalence of an isolated single episode of nonrecurrent AOM in children. C1 Fed Fdn Med Sci, Dept Ophthalmootorhinolaryngol, Porto Alegre, RS, Brazil. Hosp Ciranca Santo Antonio, Div Pediat Otolaryngol, Porto Alegre, RS, Brazil. Univ Fed Rio Grande Sul, Hosp Clin Porto Alegre, Dept Pediat, Porto Alegre, RS, Brazil. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Neto, JFL (reprint author), Rua Cel Corte Real 122,Apt 603, BR-90630080 Porto Alegre, RS, Brazil. NR 25 TC 3 Z9 4 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD DEC PY 1999 VL 121 IS 6 BP 805 EP 808 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 262MX UT WOS:000084072000023 ER PT J AU Grabowski, EF Carter, CA Ingelfinger, JR Tsukurov, O Conroy, N Abbott, WM Orkin, RW AF Grabowski, EF Carter, CA Ingelfinger, JR Tsukurov, O Conroy, N Abbott, WM Orkin, RW TI Comparison of tissue factor pathway in human umbilical vein and adult saphenous vein endothelial cells: Implications for newborn hemostasis and for laboratory models of endothelial cell function SO PEDIATRIC RESEARCH LA English DT Article ID BLOOD-COAGULATION; VASCULAR ENDOTHELIUM; EXPRESSION; INHIBITOR; HETEROGENEITY; ACTIVATION; PLATELETS; CULTURE; ANTIGEN; TFPI AB In this work we have undertaken a comparative study of human umbilical vein endothelial cells (HUVECs) and human saphenous vein endothelial cells (HSVECs) with respect to functional and antigenic tissue factor (TF), tissue factor pathway inhibitor (TFPI), and TF mRNA. Monolayers of each cell type (passage 2, except where specified) were grown to confluence and then activated for 4 h with either 50 U/mL IL-1-alpha or 10 mu g/mL tumor necrosis factor-alpha. Activated factor X appearing in supernatant was measured using a chromogenic assay, and both Northern blots and quantitative RT-PCR were performed to assess concentrations of TF mRNA accompanying activation. The role of TFPI was separately determined by ELISA for supernatant TFPI antigen, and by measurements of production of activated factor X in the presence of 0, 5, 15, or 50 mu g/mL of an antibody directed against TFPI. To address a non-TF pathway endothelial cell function, antigenic concentrations of tissue plasminogen activator for both cell types was also determined by ELISA. HUVECs were found to produce 2.4- to 3.5-fold more functional TF. No significant HUVEC-HSVEC differences were detected in TF antigen, supernatant TFPI, anti-TFPI affinity for endothelial cell-associated TFPI, TF mRNA or its amplification products, and tissue plasminogen activator. Immunostaining for TF antigen, however, may have failed to detect a modest HUVEC-HSVEC difference. Our finding with respect to functional TF indicates that HUVECs and HSVECs are not equivalent in terms of models for endothelial cell function in small children versus adults. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Grabowski, EF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Blake 255,Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL 33095, HL52183] NR 26 TC 12 Z9 12 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD DEC PY 1999 VL 46 IS 6 BP 742 EP 747 DI 10.1203/00006450-199912000-00017 PG 6 WC Pediatrics SC Pediatrics GA 258ZU UT WOS:000083870200017 PM 10590033 ER PT J AU Marcotti, W Geleoc, GSG Lennan, GWT Kros, CJ AF Marcotti, W Geleoc, GSG Lennan, GWT Kros, CJ TI Transient expression of an inwardly rectifying potassium conductance in developing inner and outer hair cells along the mouse cochlea SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE cochlea; development; hair cell; inward rectification; mouse; potassium current ID GUINEA-PIG COCHLEA; ANOMALOUS RECTIFICATION; IONIC CURRENTS; DIFFERENTIAL EXPRESSION; POSTNATAL-DEVELOPMENT; SUPPORTING CELLS; NEONATAL MICE; CHICK; MEMBRANE; CHANNEL AB Inwardly rectifying K+ currents in inner and outer hair cells (IHCs, OHCs) were studied during post natal development of the mouse cochlea. Hyperpolarizing steps: from a holding potential of -64 mV induced a rapidly activating current in both cell types. This current showed strong inward rectification around the Kt equilibrium potential and, at potentials negative to -130 mV, partial inactivation. The activation range varied with extracellular K+ concentration. External application of Ba2+ and Cs+ reversibly blocked the elicited current. The results are consistent with the presence of an I-K1-type inwardly rectifying potassium conductance in these cells. The maximum current was 60% larger in IHCs than in OHCs; In OHCs, but not IHCs, the amplitude of I-K1 varied significantly with the cells' position along the cochlea. I-K1 was maximal in cells located in the most basal region of the cochlea and its amplitude decreased in the apical coil. I-K1 disappeared upon functional maturation: in OHCs at the end of the first postnatal week, and in IHCs at the onset of auditory function 12 days after birth. The current is active at the resting potential of the cells and plays a role in regulating the spiking behaviour characteristic of developing hair cells. C1 Univ Bristol, Sch Med Sci, Dept Physiol, Bristol BS8 1TD, Avon, England. Univ Sussex, Sch Biol Sci, Brighton BN1 9QG, E Sussex, England. Massachusetts Gen Hosp, HHMI, Boston, MA 02114 USA. Univ Montpellier 2, Lab Neurobiol & Dev Syst Vestibulaire, F-34095 Montpellier, France. RP Kros, CJ (reprint author), Univ Bristol, Sch Med Sci, Dept Physiol, Univ Walk, Bristol BS8 1TD, Avon, England. NR 38 TC 57 Z9 57 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD DEC PY 1999 VL 439 IS 1-2 BP 113 EP 122 DI 10.1007/s004240051134 PG 10 WC Physiology SC Physiology GA 261JX UT WOS:000084007000014 PM 10651007 ER PT J AU Kolesar, JM Johnson, CL Freeberg, BL Berlin, JD Schiller, JH AF Kolesar, JM Johnson, CL Freeberg, BL Berlin, JD Schiller, JH TI Warfarin-5-FU interaction - A consecutive case series SO PHARMACOTHERAPY LA English DT Article ID 5-FLUOROURACIL; LEVAMISOLE AB Five patients from a single institution received concomitant warfarin and 5-fluorouracil (5-FU) during a 3-year period. The mean weekly warfarin dose before starting chemotherapy was 40.66 mg and during chemotherapy it was 24 mg (p=0.0026). All patients required a warfarin dosage reduction (range 18-74%, mean 44%). Two patients were hospitalized, one with a major retroperitoneal bleed, the other for fresh-frozen plasma administration and observation. Maximum international normalized ratios (INRs) ranged from 3.66-23.7. This series confirms a common, clinically significant interaction between warfarin and 5-FU. An interaction between capecitabine, the orally available prodrug of S-FU, and warfarin also has been reported. We recommend weekly monitoring of prothrombin time and INR for all patients receiving concomitant warfarin and 5-FU or capecitabine. C1 Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA. Univ Wisconsin, Sch Med, Madison, WI USA. William S Middleton Mem Vet Hosp, Nursing Serv, Madison, WI 53705 USA. Univ Cincinnati, Adjunct Ambulatory Care Fac, Cincinnati, OH USA. Vanderbilt Univ, Med Ctr, Div Hematol Oncol, Nashville, TN USA. RP Kolesar, JM (reprint author), Univ Wisconsin, Sch Pharm, 425 N Charter St, Madison, WI 53706 USA. NR 18 TC 37 Z9 37 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD DEC PY 1999 VL 19 IS 12 BP 1445 EP 1449 DI 10.1592/phco.19.18.1445.30897 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 262HZ UT WOS:000084062400015 PM 10600095 ER PT J AU Krebs, DE McGibbon, CA Fagerson, TL AF Krebs, DE McGibbon, CA Fagerson, TL TI An electromyographic study of the hip abductor muscles as subjects with a hip prosthesis walked with different methods of using a cane and carrying a load - Invited commentary SO PHYSICAL THERAPY LA English DT Article C1 Massachusetts Gen Hosp, Biomot Lab, Boston, MA 02114 USA. MGH Inst Hlth Profess, Boston, MA 02114 USA. Orthopaed PT Serv Inc, Wellesley, MA 02481 USA. RP Krebs, DE (reprint author), Massachusetts Gen Hosp, Biomot Lab, Boston, MA 02114 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU AMER PHYSICAL THERAPY ASSOC PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD DEC PY 1999 VL 79 IS 12 BP 1174 EP 1175 PG 2 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA 264GR UT WOS:000084172700007 ER PT J AU May, JW Silverman, RP Kaufman, JA AF May, JW Silverman, RP Kaufman, JA TI Flap perfusion mapping: TRAM flap after abdominal suction-assisted lipectomy SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID METHYLENE-BLUE; BREAST RECONSTRUCTION; ISLAND FLAP C1 Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Vasc Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. RP May, JW (reprint author), Massachusetts Gen Hosp, Div Plast Surg, 15 Parkman St, Boston, MA 02114 USA. NR 12 TC 8 Z9 8 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 DEC PY 1999 VL 104 IS 7 BP 2278 EP 2281 DI 10.1097/00006534-199912000-00055 PG 4 WC Surgery SC Surgery GA 258TH UT WOS:000083854900056 PM 11149798 ER PT J AU Lawrence, VA De Moor, C Glenn, ME AF Lawrence, VA De Moor, C Glenn, ME TI Systematic differences in validity of self-reported mammography behavior: A problem for intergroup comparisons? SO PREVENTIVE MEDICINE LA English DT Article DE mammography; screening.tw; validity; sensitivity; specificity ID PAP SMEAR; WOMEN; ACCURACY; POPULATION; BREAST; AUDIT AB Background Prior studies of recall accuracy for screening mammogram behavior have examined relatively homogeneous groups. Data are limited on possible systematic group differences, so we evaluated women's recall accuracy in two separate care systems in one city. Methods. Women 50 to 70 years old with and without screening mammograms 10 to 14 months prior were identified from fiscal, clinic, and radiology records at a military care system (MCS) and a county-funded system (CFS) for indigents. Mammogram status was verified through radiology records. Women were excluded if mammograms were diagnostic, done for other than annual screening, or had abnormal results. Interviewers blinded to mammogram status surveyed randomly selected eligible women. Results. For 62 screened/31 unscreened MCS women and 78 screened/61 unscreened CFS women, specificity was similar, at 65 and 62%, respectively. In contrast, sensitivity varied significantly: 95% versus 79% (P = 0.011). Primary ethonocultural groups were Euro-American (MCS-60%) and Mexican American (CFS-85%)Although not different in specificity of recall (67% versus 61%), these major subgroups significantly differed insensitivity (97% versus 80%, P = 0.017), proportion of true negatives due to never having a mammogram (35% versus 57%, P = 0.003), and proportion with greater than or equal to high school education (78% versus 19%, P < 0.00001). Conclusion. Systematic differences in recall validity may exist and compromise the accuracy of intergroup comparisons. (C) 1999 American Health Foundation and Academic Press. C1 S Texas Vet Hlth Care Syst, Audie L Murphy Div, Div Gen Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Med Oncol, San Antonio, TX 78284 USA. Brooke Army Med Ctr, Dept Radiol, Ft Sam Houston, TX 78234 USA. RP Lawrence, VA (reprint author), S Texas Vet Hlth Care Syst, Audie L Murphy Div, Div Gen Med, San Antonio, TX 78284 USA. FU NCI NIH HHS [P30CA54174, P50CA58183] NR 13 TC 26 Z9 26 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD DEC PY 1999 VL 29 IS 6 BP 577 EP 580 DI 10.1006/pmed.1999.0575 PN 1 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 268CU UT WOS:000084397400019 PM 10600440 ER PT J AU Karel, MJ Molinari, V Gallagher-Thomson, D Hillman, SL AF Karel, MJ Molinari, V Gallagher-Thomson, D Hillman, SL TI Postdoctoral training in professional geropsychology: A survey of fellowship graduates SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article AB Have psychologists who have pursued postdoctoral training in geropsychology viewed such training as a worthwhile professional investment? As the population is aging, psychologists are increasingly working with older adults. For many psychologists, competent practice with the elderly will require some continuing education, whereas other psychologists may choose to secure specialty-level training in the field. A survey of psychologists who completed such specialized postdoctoral training found a high level of satisfaction with the training and a sense of professional competence in most of the geropsychology competency areas set forth by the American Psychological Association. The need for increased opportunities for both proficiency and specialty-level training in applied geropsychology is discussed. C1 Dept Vet Affairs Med Ctr, Brockton, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Dept Vet Affairs Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Palo Alto Hlth Care Syst, Dept Vet Affairs, Palo Alto, CA USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Karel, MJ (reprint author), Vet Adm Med Ctr, Psychol Serv, 940 Belmont st, Brockton, MA 02401 USA. NR 11 TC 12 Z9 12 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7028 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD DEC PY 1999 VL 30 IS 6 BP 617 EP 622 DI 10.1037/0735-7028.30.6.617 PG 6 WC Psychology, Multidisciplinary SC Psychology GA 259LF UT WOS:000083894800013 ER PT J AU Planz, B Aretz, HT Wang, QF Tabatabaei, S Kirley, SD Lin, CW McDougal, WS AF Planz, B Aretz, HT Wang, QF Tabatabaei, S Kirley, SD Lin, CW McDougal, WS TI Immunolocalization of the keratinocyte growth factor in benign and neoplastic human prostate and its relation to androgen receptor SO PROSTATE LA English DT Article DE keratinocyte growth factor; androgen receptor; prostate; cancer ID MESSENGER-RNA; FACTOR EXPRESSION; HORMONAL-THERAPY; EPITHELIAL-CELLS; STROMAL CELLS; CANCER; HYPERPLASIA; KGF; IMMUNOHISTOCHEMISTRY; INDUCTION AB BACKGROUND. Growth and development of the prostate are androgen-dependent. Keratinocyte growth factor (KGF), widely expressed by mesenchymal cells, is thought to act like an andromedin between stroma and epithelium of the prostate. Since KGF has recently emerged as an autocrine mediator in prostate cancer, we investigated the role KGF plays in the human prostate and its relationship to androgen receptor (AR). METHODS. Normal (n = 13), benign hyperplastic (n = 5), and neoplastic (n = 14) human prostate tissues as well as cultured epithelial and stromal cells were analyzed using polymerase chain reaction (PCR), Western blot analysis, and immunohistochemistry. RESULTS. Reverse transcriptase polymerase chain reaction and Western blotting showed KGF expression in stromal cultured cells of the normal prostate but not in epithelial cells. Using immunohistochemistry, KGF was found to be Localized in fibroblasts and smooth muscle cells, independent of prostate disease. There was KGF expression in epithelial cells of BPH and prostate cancer. Human androgen receptor was uniformly expressed in the same secretory glandular cells that were positive for KGF in BPH and prostate cancer. CONCLUSIONS. Our results provide evidence that KGF is a stromal-derived mediator, recently shown to act in a paracrine manner in normal prostate but now detected in epithelial cells in prostate cancer and BPH. These findings support the hypothesis that KGF might act as an autocrine factor in prostate cancer and BPH. (C) 1999 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Reprod Endocrinol, Boston, MA 02114 USA. RP Planz, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. FU NICHD NIH HHS [HD29164] NR 46 TC 42 Z9 44 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 0270-4137 J9 PROSTATE JI Prostate PD DEC 1 PY 1999 VL 41 IS 4 BP 233 EP 242 PG 10 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 258DW UT WOS:000083823700003 PM 10544296 ER PT J AU Fertig, D Winer, E Silver, C AF Fertig, D Winer, E Silver, C TI Informed consent and psychological impact of tumor markers in metastatic breast cancer patients: A pilot study SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD DEC PY 1999 VL 8 IS 6 SU S MA 200 BP 52 EP 52 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 270JG UT WOS:000084531700198 ER PT J AU Mahmood, U Tung, CH Bogdanov, A Weissleder, R AF Mahmood, U Tung, CH Bogdanov, A Weissleder, R TI Near-infrared optical imaging of protease activity for tumor detection SO RADIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting and Scientific Assembly of the Radiological-Society-of-North-America (RSNA) CY NOV 29-DEC 06, 1998 CL CHICAGO, ILLINOIS SP Radiol Soc N Amer DE animals; breast neoplasms, experimental studies; contrast media, experimental studies; enzymes; neoplasms, diagnosis; neoplasms, experimental studies ID CELL LUNG-CARCINOMA; MATRIX METALLOPROTEINASES; TURBID MEDIA; EXPRESSION; INHIBITORS; BLOOD; PHASE; LIGHT AB PURPOSE: To build and test an optical imaging system that is sensitive to near-infrared fluorescent molecular probes activated by specific enzymes in tumor tissues in mice. MATERIALS AND METHODS: The imaging system consisted of a source that delivered 610-650-nm excitation light within a lighttight chamber, a 700-nm longpass filter for selecting near-infrared fluorescence emission photons from tissues, and a charge-coupled device (CCD) for recording images. The molecular probe was a biocompatible autoquenched near-infrared fluorescent compound that was activated by tumor-associated proteases for cathepsins B and H. Imaging experiments were performed 0-72 hours after intravenous injection of the probe in nude mice that bore human breast carcinoma (BT-20). RESULTS: The imaging system had a maximal spatial resolution of 60 mu m, with a field of view of 14 cm(2). The detection threshold of the nonquenched near-infrared fluorescent dye was subpicomolar in the imaging phantom experiments. In tissue, 250 pmol of fluorochrome was easily detected during the 10-second image acquisition. After intravenous injection of the probe into the tumor-bearing animals, tumors as small as 1 mm became detectable because of tumor-associated enzymatic activation of the quenched compound. CONCLUSION: Tumor proteases can be used as molecular targets, allowing visualization of millimeter-sized tumors. The development of this technology, probe design, and optical imaging systems hold promise for molecular imaging, cancer detection, and evaluation of treatment. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Boston, MA 02125 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, CNY149-5403,13th St, Boston, MA 02125 USA. OI Tung, Ching-Hsuan/0000-0001-6648-6195 NR 28 TC 230 Z9 234 U1 4 U2 28 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 1999 VL 213 IS 3 BP 866 EP 870 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 258EM UT WOS:000083825200036 PM 10580968 ER PT J AU Rahbar, G Sie, AC Hansen, GC Prince, JS Melany, ML Reynolds, HE Jackson, VP Sayre, JW Bassett, LW AF Rahbar, G Sie, AC Hansen, GC Prince, JS Melany, ML Reynolds, HE Jackson, VP Sayre, JW Bassett, LW TI Benign versus malignant solid breast masses: US differentiation SO RADIOLOGY LA English DT Article; Proceedings Paper CT 82nd Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY DEC 01-06, 1996 CL CHICAGO, ILLINOIS SP Radiol Soc N Amer DE breast, US; breast neoplasms, diagnosis; breast neoplasms, radiography; breast neoplasms, US; breast radiography, comparative studies ID SONOGRAPHY; MAMMOGRAPHY; CANCER; WOMEN; FIBROADENOMA; MANAGEMENT; LESIONS; NODULES; BIOPSY AB PURPOSE: To investigate the general applicability and interobserver variability of ultrasonographic (US) features in differentiating benign from malignant solid breast masses. MATERIALS AND METHODS: One hundred sixty-two consecutive solid masses with a tissue diagnosis were reviewed. Three radiologists reviewed the masses without knowledge of clinical history or histologic examination results. RESULTS: US features that most reliably characterize masses as benign were a round or oval shape (67 of 71 [94%] were benign), circumscribed margins (95 of 104 [91%] were benign), and a width-to-anteroposterior (AP) dimension ratio greater than 1.4 (82 of 92 [89%] were benign). Features that characterize masses as malignant included irregular shape (19 of 31 [61%] were malignant), microlobulated (four of six [67%] were malignant) or spiculated (two of three [67%] were malignant;) margins, and width-to-AP dimension ratio of 1.4 or less (28 of 70 [40%] were malignant). If the three most reliable criteria had been strictly applied by each radiologist, the overall cancer biopsy yield would have increased (from 23% to 39%) by 16%. When US images and mammograms were available, the increase in biopsy yield contributed by US was not statistically significant (2%, P = .73). However, in independent reviews, one to three reviewers interpreted four carcinomas as benign at US. CONCLUSION: The data confirm that certain US features can help differentiate benign from malignant masses. However, practice and interpreter variability should be further explored before these criteria are generally applied to defer biopsy of solid masses. C1 Univ Calif Los Angeles, Sch Med, Dept Radiol Sci, Iris Cantor Ctr Breast Imaging, Los Angeles, CA 90095 USA. Olive View UCLA Med Ctr, Dept Radiol, Sylmar, CA 91342 USA. W Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. Indiana Univ, Sch Med, Dept Radiol, Indianapolis, IN 46202 USA. RP Bassett, LW (reprint author), Univ Calif Los Angeles, Sch Med, Dept Radiol Sci, Iris Cantor Ctr Breast Imaging, 200 UCLA Med Plaza,Rm 165-49, Los Angeles, CA 90095 USA. NR 23 TC 210 Z9 233 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 1999 VL 213 IS 3 BP 889 EP 894 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 258EM UT WOS:000083825200039 PM 10580971 ER PT J AU Stone, ME AF Stone, ME TI Modern American literature, 5th edition. SO REFERENCE & USER SERVICES QUARTERLY LA English DT Book Review C1 Massachusetts Gen Hosp, Treadwell Lib, Reference Serv, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp, Treadwell Lib, Reference Serv, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER LIBRARY ASSOC PI CHICAGO PA 50 E HURON ST, CHICAGO, IL 60611 USA SN 1094-9054 J9 REF USER SERV Q JI Ref. User Serv. Q. PD WIN PY 1999 VL 39 IS 2 BP 195 EP 196 PG 2 WC Information Science & Library Science SC Information Science & Library Science GA 302JU UT WOS:000086362600028 ER PT J AU Hoop, B Beagle, JL Maher, TJ Kazemi, H AF Hoop, B Beagle, JL Maher, TJ Kazemi, H TI Brainstem amino acid neurotransmitters and hypoxic ventilatory response SO RESPIRATION PHYSIOLOGY LA English DT Article DE control of breathing, hypoxia, neurotransmitters; hypoxia, biphasic response, neurotransmitters; mammals, rat; mediators, glutamate; neurotransmitters, hypoxia, taurine, GABA ID ROSTRAL VENTROLATERAL MEDULLA; NUCLEUS-TRACTUS-SOLITARII; METHYL-D-ASPARTATE; SUSTAINED HYPOXIA; RAT; GLUTAMATE; MICRODIALYSIS; RELEASE; PIGLETS; CATS AB The ventilatory response to acute hypoxia in mammalian species is biphasic, an initial hyperventilatory response is followed by a reduction in ventilation within 2-3 min below the peak level (roll-off). Brain amino acid neurotransmitters also change during hypoxia. This study explores the role of neurotransmitters in anesthetized adult Sprague-Dawley rats mechanically ventilated during 20 min of 10% O(2) breathing. Phrenic nerve activity was recorded, and microdialysate concentrations of selected amino acids were determined at 3- to 5-min intervals in respiratory chemosensitive areas of the ventrolateral medulla (VMS) 1.25-2.00 mm below the surface. Phonic nerve output was biphasic during hypoxia, concurrent with a rapid glutamate and gradual GABA increase. Taurine first decreased, then increased. In both intact and chemodenervated animals, time-dependent change in phrenic nerve activity during hypoxia was associated with corresponding changes in glutamate, GABA, and taurine concentrations, suggesting that cumulative effects of changes in the concentration of these three amino acids could account for response of the phrenic nerve to hypoxia. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv,Pulm & Crit Care Unit, Boston, MA 02114 USA. Massachusetts Coll Pharm & Allied Hlth Sci, Div Pharmaceut Sci, Boston, MA 02115 USA. RP Kazemi, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv,Pulm & Crit Care Unit, Bulfinch 148, Boston, MA 02114 USA. EM kazemi.homayoun@mgh.harvard.edu NR 37 TC 36 Z9 36 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0034-5687 J9 RESP PHYSIOL JI Respir. Physiol. PD DEC 1 PY 1999 VL 118 IS 2-3 BP 117 EP 129 DI 10.1016/S0034-5687(99)00072-9 PG 13 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 270UP UT WOS:000084555800005 PM 10647857 ER PT J AU Vonsattel, JPG Louis, DN De Girolami, U AF Vonsattel, JPG Louis, DN De Girolami, U TI Hommage to Edward Peirson Richardson Jr. SO REVUE NEUROLOGIQUE LA French DT Biographical-Item C1 Brigham & Womens Hosp, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Vonsattel, JPG (reprint author), Brigham & Womens Hosp, Massachusetts Gen Hosp, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSON EDITEUR PI PARIS 06 PA 120 BLVD SAINT-GERMAIN, 75280 PARIS 06, FRANCE SN 0035-3787 J9 REV NEUROL JI Rev. Neurol. PD DEC PY 1999 VL 155 IS 12 BP 1088 EP 1089 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 269KW UT WOS:000084477000012 ER PT J AU Winer, E Berry, D Duggan, D Henderson, IC Cirrincione, C Cooper, MR Norton, L AF Winer, E Berry, D Duggan, D Henderson, IC Cirrincione, C Cooper, MR Norton, L CA Canc Leukemia Grp B TI CALGB 9342: A randomized trial of three doses of paclitaxel in patients with metastatic breast cancer SO SEMINARS IN ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC USA. Syracuse Univ, Syracuse, NY USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 1999 VL 26 IS 6 SU 18 BP 9 EP 9 PG 1 WC Oncology SC Oncology GA 268AK UT WOS:000084391300007 ER PT J AU Monga, TN Monga, U Tan, G Grabois, M AF Monga, TN Monga, U Tan, G Grabois, M TI Coital positions and sexual functioning in patients with chronic pain SO SEXUALITY AND DISABILITY LA English DT Article DE sexuality; chronic pain; coital positions AB The objectives of this study were to describe (1) coital positions adopted by chronic back pain patients, (2) and to describe sexual function as assessed by Derogatis Inventory of Sexual Functioning (DISF), In addition, patients were asked questions regarding effects of sexual intercourse on severity of pain, influence of pain over sexual functioning, and perceived factors causing sexual problems. This is a subset (45 patients) of a larger study (70 patients) describing sexual functioning. These 45 patients responded to additional questions as described above. Mean age of the patients was 55.7 years (range 36-74 years). There were 40 male patients. Twenty-five patients (56%) were married. Mean duration of pain was 145.2 months. Thirty-two patients (27 male and 5 female) were sexually active. Eighty-one percent of male and 100% of female patients, who were sexually active, preferred "male superior" position. Of those sexually active, 41% performed sexual intercourse while sitting on a chair. A majority of patients were experiencing problems in all domains of sexual functioning except for fantasy. Thirty-nine patients (87%) reported that pain extremely interfered in performing sexual intercourse. Twenty-nine patients (64%) reported worsening of pain due to sexual intercourse. Majority (n = 34) of the patients (76%) had fear of failure to perform and 25 patients (56%) reported fear of aggravating pain due to sexual activity. There is need for further research in this area. C1 Houston VA Med Ctr, Dept Phys Med & Rehabil, Houston, TX 77030 USA. Houston VA Med Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. Houston VA Med Ctr, Dept Psychol, Houston, TX 77030 USA. RP Monga, TN (reprint author), Houston VA Med Ctr, Dept Phys Med & Rehabil, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 18 TC 6 Z9 6 U1 1 U2 2 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0146-1044 J9 SEX DISABIL JI Sex. Disabil. PD WIN PY 1999 VL 17 IS 4 BP 287 EP 297 DI 10.1023/A:1021373428492 PG 11 WC Rehabilitation SC Rehabilitation GA 271HQ UT WOS:000084588500002 ER PT J AU Ay, H Oliveira, J Buonanno, FS Ezzeddine, M Schaefer, PW Rordorf, G Schwamm, LH Gonzalez, RG Koroshetz, WJ AF Ay, H Oliveira, J Buonanno, FS Ezzeddine, M Schaefer, PW Rordorf, G Schwamm, LH Gonzalez, RG Koroshetz, WJ TI Diffusion-weighted imaging identifies a subset of lacunar infarction associated with embolic source SO STROKE LA English DT Article DE embolism; lacunar infarction; magnetic resonance imaging, diffusion-weighted ID CEREBRAL-ISCHEMIA; SUBCORTICAL INFARCTION; COEFFICIENT ADC; STROKE PATIENTS; TIME-COURSE; OCCLUSION; BRAIN; WATER; ANGIOGRAPHY; PREVALENCE AB Background and Purpose-Small infarcts in the territory of penetrator arteries were described as causing a number of distinct clinical syndromes. The vascular pathophysiology underlying such infarcts is difficult to ascertain without careful pathological study. However, the occurrence of multiple, small infarcts, linked closely in time but dispersed widely in the brain, raises the possibility of an embolic mechanism. The current study determines the frequency and clinical characteristics of patients with well-defined lacunar syndromes and the diffusion-weighted imaging (DWI) evidence of multiple acute lesions. Methods-Sixty-two consecutive patients who presented to the emergency room with a clinically well-defined lacunar syndrome were studied by DWI within the first 3 days of admission. Results-DWI showed multiple regions of increased signal intensity in 10 patients (16%). A hemispheric or brain stem Index lesion") was found in all. lesion in a penetrator territory that accounted for the clinical syndrome (" DWI-hyperintense lesions other than the index lesion ("subsidiary infarctions") were punctate and lay within leptomeningeal artery territories in the majority. As opposed to patients with a single lacunar infarction, patients with a subsidiary infarction more frequently (P<0.05) harbored an identifiable cause of stroke. Conclusions-Almost 1 of every 6 patients presenting with a classic lacunar syndrome has multiple infarctions demonstrated on DWI, This DWT finding usually indicates an identifiable cause of stroke and therefore may influence clinical decisions regarding the extent of etiologic investigations and treatment for secondary prevention. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol Stroke Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroradiol Div, Boston, MA 02114 USA. RP Koroshetz, WJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol Stroke Serv, VBK-915, Boston, MA 02114 USA. OI Schwamm, Lee/0000-0003-0592-9145 FU NINDS NIH HHS [5 P50 NS108288-22, 5RO1 NS35284, R01-NS28371] NR 44 TC 84 Z9 90 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 1999 VL 30 IS 12 BP 2644 EP 2650 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 259JL UT WOS:000083890700022 PM 10582991 ER PT J AU Kvedar, JC Menn, ER Baradagunta, S Smulders-Meyer, O Gonzalez, E AF Kvedar, JC Menn, ER Baradagunta, S Smulders-Meyer, O Gonzalez, E TI Teledermatology in a capitated delivery system using distributed information architecture: Design and development SO TELEMEDICINE JOURNAL LA English DT Article ID PRIMARY CARE PHYSICIANS; QUALITY-OF-LIFE; WORLD-WIDE-WEB; MANAGED CARE; SKIN-DISEASE; PATIENT; COMMUNICATION; DERMATOLOGY; AGREEMENT; ABILITY AB Objective: This report describes the design, development, and technical evaluation of a teledermatology system utilizing digital images and electronic forms captured through, stored on, and viewed through a common web server in an urban capitated delivery system. Materials and Methods: The authors designed a system whereby a primary care physician was able to seek a dermatologic consultation electronically, provide the specialist with digital images acquired according to a standardized protocol, and review the specialist response within 2 business days of the request. The settings were two primary care practices in eastern Massachusetts that were affiliated with a large integrated delivery system. Technical evaluation of the effectiveness of the system involved 18 patients. Main outcome measures included physician and patient satisfaction and comfort and efficiency of care delivery. Results: In 15 cases, the consultant dermatologist was comfortable in providing definitive diagnosis and treatment recommendations. In 3 cases, additional information (laboratory studies or more history) was requested. There were no instances where the dermatologist felt that a face-to-face visit was necessary. Conclusions: This novel approach shows promise for the delivery of specialist expertise via the internet. Cost-effectiveness studies may be necessary for more widespread implementation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. Partners HealthCare Syst Inc, Boston, MA USA. RP Kvedar, JC (reprint author), Partners Telemed, 1 Longfellow Pl,Suite 216, Boston, MA 02114 USA. NR 28 TC 21 Z9 21 U1 2 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1078-3024 J9 TELEMED J JI Telemed. J. PD WIN PY 1999 VL 5 IS 4 BP 357 EP 366 DI 10.1089/107830299311925 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 288CR UT WOS:000085544700005 PM 10908451 ER PT J AU Lin, AE AF Lin, AE TI Using birth defects epidemiology to take CHARGE SO TERATOLOGY LA English DT Editorial Material ID CLINICAL GENETICS; CHOANAL ATRESIA; ASSOCIATION; ANOMALIES C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. RP Lin, AE (reprint author), Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0040-3709 J9 TERATOLOGY JI Teratology PD DEC PY 1999 VL 60 IS 6 BP 332 EP 333 DI 10.1002/(SICI)1096-9926(199912)60:6<332::AID-TERA4>3.0.CO;2-X PG 2 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 262DQ UT WOS:000084050700004 PM 10590393 ER PT J AU Morin, BJ Owen, MH Ramamurthy, GV Holmes, LB AF Morin, BJ Owen, MH Ramamurthy, GV Holmes, LB TI Pattern of skeletal malformations produced by Dominant hemimelia (Dh) SO TERATOLOGY LA English DT Article ID GROWTH-FACTOR-I; LIMB DEVELOPMENT; VERTEBRATE LIMB; ORTHODENTICLE GENE; DROSOPHILA EMBRYO; ADDITIONAL LIMB; LATERAL PLATE; CHICK-EMBRYO; IGF-I; OUTGROWTH AB The hindlimb malformations in adult mice heterozygous for the dominant gene Dominant hemimelia (Dh) and +/+ littermates were characterized in skeletons that had been fixed, stained, and cleared. When the tibia was shortened, the deficiency was always an absence of the distal portion, and never the proximal portion. Although tibial hemimelia has been well documented in Dh mice, this study demonstrated a distinctive pattern of shortening of the tibia. Measurements of the length of the tibia (relative to the length of the humerus) showed only three patterns of shortening of the tibia (i.e., mild, moderate, and severe), rather than a continuous spectrum of shortening from mild to complete absence. The hindlimb malformation of Dh/+ mice occurred in association with a reduced number (five) of lumbar vertebrae. The interrelationship of the hindlimb malformations and the reduction in the vertebral number suggests a relationship between the development of the axial skeleton and the abnormal limb. (C) 1999 Wiley-Liss, Inc. C1 Simmons Coll, Dept Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Owen, MH (reprint author), Simmons Coll, Dept Biol, 300 The Fenway, Boston, MA 02115 USA. EM owen@simmons.edu FU PHS HHS [2-T32-6M07748] NR 53 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0040-3709 J9 TERATOLOGY JI Teratology PD DEC PY 1999 VL 60 IS 6 BP 348 EP 355 DI 10.1002/(SICI)1096-9926(199912)60:6<348::AID-TERA7>3.0.CO;2-F PG 8 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 262DQ UT WOS:000084050700007 PM 10590396 ER PT J AU Berthiaume, F Aparicio, CL Eungdamrong, J Yarmush, ML AF Berthiaume, F Aparicio, CL Eungdamrong, J Yarmush, ML TI Age- and disease-related decline in immune function: An opportunity for "thymus-boosting" therapies SO TISSUE ENGINEERING LA English DT Review ID T-CELL DEVELOPMENT; TUMOR-NECROSIS-FACTOR; BONE-MARROW TRANSPLANTATION; ADULT-MOUSE THYMUS; THYMOCYTE DEVELOPMENT; PRECURSOR CELLS; STEM-CELLS; ALPHA-BETA; IN-VIVO; TNF-ALPHA AB The thymus is the site of production of mature T lymphocytes and thus is indispensable for the development and maintenance of the T cell-mediated arm of the immune system. Thymic production of mature T cells is critically dependent on an influx of bone marrow-derived progenitor T cells that undergo replication and selection within the thymus. Thymus cellularity and thymic hormone secretion reach a peak during the first year of life and then decline gradually until the age of 50-60 years, a process known as "thymic involution." A rapid reduction of thymus cellularity occurs in young patients following injuries, chemotherapy, and other forms of stress. The mechanisms underlying the involution process appear to be dependent on factors intrinsic to the thymic tissue, such as the local production of cytokines and chemoattractants, promoting the recruitment, growth, and differentiation of bone marrow-derived T cell progenitors in the thymus, as well as extrinsic factors, such as systemic levels of endocrine hormones and mediators released by intrathymic nerves of the autonomous nervous system. Knowledge of these factors, provides a rational basis for the development of an approach based on tissue engineering that could be used to provide either temporary or permanent reconstitution of thymic function. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Shriners Burns Hosp, Boston, MA USA. NR 156 TC 19 Z9 21 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD DEC PY 1999 VL 5 IS 6 BP 499 EP 514 DI 10.1089/ten.1999.5.499 PG 16 WC Cell & Tissue Engineering SC Cell Biology GA 271LL UT WOS:000084595000001 PM 10611542 ER PT J AU Cefalu, WT Wagner, JD Bell-Farrow, AD Edwards, IJ Terry, JG Weindruch, R Kemnitz, JW AF Cefalu, WT Wagner, JD Bell-Farrow, AD Edwards, IJ Terry, JG Weindruch, R Kemnitz, JW TI Influence of caloric restriction on the development of atherosclerosis in nonhuman primates: Progress to date SO TOXICOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT Society-of-Toxicology Symposium on Contemporary Concepts in Toxicology CY OCT 26-28, 1998 CL RESTON, VIRGINIA SP Soc Toxicol DE atherosclerosis; insulin; glucose; obesity; lipids ID MONKEYS MACACA-FASCICULARIS; CARDIOVASCULAR RISK-FACTORS; BODY-FAT DISTRIBUTION; LOW-DENSITY LIPOPROTEINS; INTRA-ABDOMINAL FAT; DIETARY RESTRICTION; RHESUS-MONKEYS; CYNOMOLGUS MONKEYS; HEART-DISEASE; MYOCARDIAL-INFARCTION AB Caloric restriction (CR) has been observed to retard aging processes and extend the maximum life span in rodents. In an effort to evaluate the effect of this nutritional intervention on physiologic variables in higher species, several nonhuman primate trials are ongoing. In particular, a study evaluating the independent effect of CR on the extent of atherosclerosis was initiated in 1993 in 32 adult cynomolgus monkeys. Therefore, the trial was designed to achieve identical cholesterol intake after animals were randomized to a control group or a calorie-restricted group (30% reduction from baseline caloric intake). The animals were routinely evaluated for glycated proteins, plasma insulin and glucose levels, insulin sensitivity, and specific measures for abdominal fat distribution by CT scans over a 4-year interval. The results from 4 years of intervention demonstrate that CR improves cardiovascular risk factors (such as visceral fat accumulation) and improves insulin sensitivity. In contrast to other primate studies with normolipidemic animals, CR had no independent effects on plasma lipid levels and composition in the presence of equivalent amounts of dietary cholesterol intake. Preliminary analysis of atherosclerotic lesion extent in the abdominal aorta has failed to demonstrate differences between control animals and CR animals. Follow-up studies are being conducted to determine the effect of CR on atherosclerosis extent in coronary and carotid arteries. C1 Univ Vermont, Coll Med, Dept Med, Endocrine Unit, Burlington, VT 05405 USA. Wake Forest Univ, Sch Med, Dept Med & Comparat Med, Winston Salem, NC 27109 USA. Univ Wisconsin, Dept Med, Madison, WI USA. Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI USA. William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI 53705 USA. RP Cefalu, WT (reprint author), Univ Vermont, Coll Med, Dept Med, Endocrine Unit, Given C331, Burlington, VT 05405 USA. FU NIA NIH HHS [AG00578, AG11915, AG10816] NR 47 TC 30 Z9 30 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 DEC PY 1999 VL 52 IS 2 SU S BP 49 EP 55 DI 10.1093/toxsci/52.suppl_1.49 PG 7 WC Toxicology SC Toxicology GA 268VX UT WOS:000084438400008 PM 10630590 ER PT J AU Morgan, MB Goldstein, NB Scadden, D Lacy, J Curiel, DT Curiel, TJ AF Morgan, MB Goldstein, NB Scadden, D Lacy, J Curiel, DT Curiel, TJ TI Treatment of EBV transformed tumors with antisense oligodeoxynucleotides against EBNA-1 enhances tumor chemosensitivity SO TUMOR TARGETING LA English DT Article DE Epstein-Barr virus; EBNA-1; chemotherapy; antisense oligodeoxynucleotide; transforming gene, lymphoma; AIDS-related malignancy; tumor transformation; viral tumorigenesis ID EPSTEIN-BARR-VIRUS; NON-HODGKINS-LYMPHOMA; SMOOTH-MUSCLE TUMORS; IMMORTALIZED B-CELLS; NUCLEAR ANTIGEN-1; GENE-THERAPY; LYMPHOPROLIFERATIVE DISORDERS; BCL-2 EXPRESSION; AIDS; CHEMOTHERAPY AB Epstein - Barr virus infection is associated with certain non-Hodgkin's lymphomas, including AIDS-related lymphomas, Neoplastic transformation of B cells is related to expression of a subset of Epstein-Barr virus-derived genes, affording a potential site of therapeutic attack. Using antisense oligodeoxynucleotides, we now demonstrate that inhibition of Epstein-Barr virus-encoded EBNA-1, a gene product required to maintain the transformed phenotype, enhances the cytotoxicity of doxorubicin and etoposide (two commonly used lymphoma chemotherapy agents) for Epstein - Barr virus transformed B cell tumor cells. Primary AIDS-related lymphoma lines were also susceptible to the chemosensitizing effects of deoxyoligonucleotide-mediated EBNA-1 inhibition, suggesting that the wild type EBNA-1 sequences were targeted. B cell tumor cells not transformed with Epstein-Barr virus, and non-B cell tumor cells, were not specifically affected by anti-EBNA-1 oligodeoxynucleotide antisense treatment, although non-specific cytotoxicity was apparent. Thus, inhibition of Epstein-Barr virus transforming genes may represent a novel strategy to augment certain anti-non-Hodgkin's lymphoma chemotherapies, although the mechanism of chemosensitization remains undefined. These studies will also afford insights into mechanisms of Epstein - Barr virus-related tumorigenesis. C1 Univ Colorado, Hlth Sci Ctr, Dept Med, Div Infect Dis, Denver, CO 80262 USA. Massachusetts Gen Hosp, AIDS Res Unit, Boston, MA 02114 USA. Yale Univ, Sch Med, Dept Med, Div Med Oncol, New Haven, CT 06510 USA. Univ Alabama, Gene Therapy Program, Birmingham, AL USA. RP Curiel, TJ (reprint author), Baylor Inst Immunol Res, 3434 Live Oak St,Suite 205, Dallas, TX 75204 USA. NR 48 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1351-8488 J9 TUMOR TARGET JI Tumor Target. PD DEC PY 1999 VL 4 IS 4 BP 278 EP 286 PG 9 WC Materials Science, Multidisciplinary; Medicine, Research & Experimental SC Materials Science; Research & Experimental Medicine GA 324AP UT WOS:000087598400010 ER PT J AU Nelson, JB Chen, RN Bishoff, JT Oh, WK Kantoff, PW Donehower, RC Kavoussi, LR AF Nelson, JB Chen, RN Bishoff, JT Oh, WK Kantoff, PW Donehower, RC Kavoussi, LR TI Laparoscopic retroperitoneal lymph node dissection for clinical stage I nonseminomatous germ cell testicular tumors SO UROLOGY LA English DT Article ID MULTIINSTITUTIONAL ANALYSIS; TESTIS CANCER; LYMPHADENECTOMY; RELAPSE; TERATOMA AB Objectives. To assess retrospectively whether laparoscopic retroperitoneal lymph node dissection (RPLND) in patients with clinical Stage I nonseminomatous germ cell testicular tumor (NSGCT) provides useful pathologic staging information on which subsequent management can be based. Approximately 30% of patients with clinical Stage I NSGCT will have pathologic Stage II disease. Methods. A retrospective review of 29 patients with clinical Stage I NSGCT who underwent transperitoneal laparoscopic RPLND by a single surgeon was performed. Selection criteria included the presence of embryonal carcinoma in the primary tumor or vascular invasion. A modified left: (n = 18) or right (n = 11) template was used. Results, Positive retroperitoneal nodes were detected in 12 (41%) of 29 patients. Ten of these patients received immediate adjuvant platinum-based chemotherapy, and 2 patients refused chemotherapy. The nodes were negative in 17 (59%) of 29 patients; all but 2 patients (one with recurrence in the chest, the other with biochemical recurrence) have undergone observation, No evidence of disease recurrence has been found in the retroperitoneum of any patient (follow-up range 1 to 65 months). Prospectively, the dissection was limited if grossly positive nodes were encountered; therefore, the total number of nodes removed was significantly different if the nodes were positive or negative (14 +/- 2 and 25 +/- 3, respectively; P <0.004). Two patients required an open conversion because of hemorrhage. Complications included lymphocele (n = 1) and flank compartment syndrome (n = 1). Conclusions. Laparoscopic RPLND is a feasible, minimally invasive surgical alternative to observation or open RPLND for Stage I NSGCT. Disease outcomes are favorable to date. Longer follow-up in a larger series is necessary to determine therapeutic efficacy. (C) 1999, Elsevier Science Inc. C1 Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Div Med Oncol, Baltimore, MD 21205 USA. Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Adult Oncol, Boston, MA 02115 USA. RP Kavoussi, LR (reprint author), Johns Hopkins Bayview Med Ctr, Brady Urol Inst, 4940 Eastern Ave, Baltimore, MD 21224 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 20 TC 64 Z9 67 U1 1 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 DEC PY 1999 VL 54 IS 6 BP 1064 EP 1067 DI 10.1016/S0090-4295(99)00289-7 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 264GT UT WOS:000084172800027 PM 10604709 ER PT J AU Olsen, BR AF Olsen, BR TI Life without perlecan has its problems SO JOURNAL OF CELL BIOLOGY LA English DT Review ID HEPARAN-SULFATE PROTEOGLYCAN; GROWTH; ANGIOGENESIS; MITOGENESIS; BINDING; PROTEIN; GENE; EXT1 C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Harvard Univ, Forsyth Dept Oral Biol, Boston, MA 02115 USA. RP Olsen, BR (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. NR 18 TC 40 Z9 43 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV 29 PY 1999 VL 147 IS 5 BP 909 EP 911 DI 10.1083/jcb.147.5.909 PG 3 WC Cell Biology SC Cell Biology GA 261EK UT WOS:000083995800004 PM 10579711 ER PT J AU Fite, KV Janusonis, S Foote, W Bengston, L AF Fite, KV Janusonis, S Foote, W Bengston, L TI Retinal afferents to the dorsal raphe nucleus in rats and Mongolian gerbils SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE subcortical vision; rodent visual system; environmental light stimulation; periaqueductal gray; retinal ganglion cells; serotonin ID LATERAL GENICULATE-NUCLEUS; SUPRACHIASMATIC CIRCADIAN PACEMAKER; GANGLION-CELLS; INTERGENICULATE LEAFLET; MERIONES-UNGUICULATUS; SUPERIOR COLLICULUS; VISUAL-SYSTEM; LIGHT THERAPY; SEROTONERGIC PROJECTION; HORSERADISH-PEROXIDASE AB A direct pathway from the retina to the dorsal raphe nucleus (DRN) has been demonstrated in both albino rats and Mongolian gerbils. Following intraocular injection of cholera toxin subunit B (CTB), a diffuse stream of CTB-positive, fine-caliber optic axons emerged from the optic tract at the level of the pretectum/anterior mesencephalon. In gerbils, CTB-positive axons descended ventromedially into the periaqueductal gray, moving caudally and arborizing extensively throughout the DRN. In rats, the retinal-DRN projection comprised fewer, but larger caliber, axons, which arborized in a relatively restricted region of the lateral and ventral DRN. Following injection of CTB into the lateral DRN, retrogradely labeled ganglion cells (GCs) were observed in whole-mount retinas of both species. In gerbils, CTB-positive GCs were distributed over the entire retina, and a nearest-neighbor analysis of CTB-positive GCs showed significant regularity (nonrandomness) in their distribution. The overall distribution of gerbil GC soma diameters ranged from 8 to 22 mu m and was skewed slightly towards the larger soma diameters. Based on an adaptive mixtures model statistical analysis, two Gaussian distributions appeared to comprise the total GC distribution, with mean soma diameters of 13 (SEM +/-1.7) mu m, and 17 (SEM +/-1.5) mu m, respectively. In rats, many fewer CTB-positive GCs were labeled following CTB injections into the lateral DRN, and nearly all occurred in the inferior retina. The total distribution of rat GC soma diameters was similar to that in gerbils and also was skewed towards the larger soma diameters. Major differences observed in the extent and configuration of the retinal-DRN pathway may be related to the diurnal/crepuscular vs. nocturnal habits of these two species. (C) 1999 Wiley-Liss, Inc. C1 Univ Massachusetts, Neurosci & Behav Program, Amherst, MA 01003 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Fite, KV (reprint author), Univ Massachusetts, Neurosci & Behav Program, Tobin Hall, Amherst, MA 01003 USA. EM kfite@psych.umass.edu NR 93 TC 67 Z9 69 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD NOV 29 PY 1999 VL 414 IS 4 BP 469 EP 484 DI 10.1002/(SICI)1096-9861(19991129)414:4<469::AID-CNE4>3.0.CO;2-P PG 16 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 249VW UT WOS:000083354800004 PM 10531540 ER PT J AU Nathoo, A Moeller, R Hart, A AF Nathoo, A Moeller, R Hart, A TI Identification and analysis of novel C-elegans neuropeptide genes SO BRAIN RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. Harvard Univ, Boston, MA 02129 USA. Sch Med, Dept Pathol, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 27 PY 1999 VL 848 IS 1-2 MA P14 BP A21 EP A22 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 268MN UT WOS:000084420300036 ER PT J AU Jernstrom, H Lerman, C Ghadirian, P Lynch, HT Weber, B Garber, J Daly, M Olopade, OI Foulkes, WD Warner, E Brunet, JS Narod, SA AF Jernstrom, H Lerman, C Ghadirian, P Lynch, HT Weber, B Garber, J Daly, M Olopade, OI Foulkes, WD Warner, E Brunet, JS Narod, SA TI Pregnancy and risk of early breast cancer in carriers of BRCA1 and BRCA2 SO LANCET LA English DT Article ID FAMILY HISTORY; MUTATION CARRIERS; AGE; DIFFERENTIATION; PATTERN; PARITY; WOMEN AB Background Early age at first full-term pregnancy and increasing parity are associated with a reduced risk of breast cancer. However, whether pregnancy decreases the risk of early-onset hereditary breast cancer is unknown. There is concern that pregnancy may increase breast-cancer risk in carriers of BRCA1 and BRCA2 germline mutations. We aimed to establish whether pregnancy is a risk factor for hereditary breast cancer. Methods We did a matched case-control study of breast cancer in women who carry deleterious BRCA1 or BRCA2 mutations. Cases were carriers who developed breast cancer by age 40 years, and controls were carriers of the same age without breast cancer, or who were diagnosed with breast cancer after age 40 years. Women who had undergone preventive mastectomy, hysterectomy, or oophorectomy, or who were diagnosed with ovarian cancer before the age at which breast cancer was diagnosed in the matched case were excluded. Information about pregnancies and pregnancy outcome was derived from a questionnaire completed by women in the course of genetic counselling. Findings A higher proportion of cases than controls had had a full term pregnancy (173/236 vs 146/236; odds ratio 1.71 [95% CI 1.13-2.62], p=0.01). The mean number of births was also greater for cases than for controls (1.62 vs 1.38, p=0.04). The risk increased with the number of births and did not diminish with time since last pregnancy. There were no significant differences in age at first birth or age at last birth between cases and controls. Interpretation Carriers of the BRCA1 and BRCA2 mutations who have children are significantly more likely to develop breast cancer by age 40 than carriers who are nulliparous. Each pregnancy is associated with an increased cancer risk. An early first pregnancy does not confer protection for carriers of BRCA1 or BRCA2 mutations. C1 Univ Toronto, Womens Coll Hosp, Ctr Res Womens Hlth, Toronto, ON M5G 1N8, Canada. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Ctr Hosp Univ Montreal, Epidemiol Res Unit, Res Ctr, Montreal, PQ, Canada. Creighton Univ, Sch Med, Dept Prevent Med & Publ Hlth, Omaha, NE USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Div Canc Epidemiol & Control, Boston, MA 02115 USA. Fox Chase Canc Ctr, Div Basic Sci & Populat Sci, Philadelphia, PA 19111 USA. Univ Chicago, Med Ctr, Canc Risk Clin, Sect Hematol & Oncol, Chicago, IL 60637 USA. McGill Univ, Dept Med, Montreal, PQ, Canada. McGill Univ, Dept Human Genet, Montreal, PQ, Canada. McGill Univ, Dept Oncol, Montreal, PQ, Canada. Toronto Sunnybrook Reg Canc Ctr, Div Med Oncol, Toronto, ON, Canada. Univ Lund Hosp, Dept Oncol, Jubileum Inst, S-22185 Lund, Sweden. RP Narod, SA (reprint author), Univ Toronto, Womens Coll Hosp, Ctr Res Womens Hlth, 790 Bay St,Room 750, Toronto, ON M5G 1N8, Canada. EM steven.narod@swchsc.on.ca FU NCI NIH HHS [CA63678, CA57601, R01 CA63682] NR 30 TC 136 Z9 141 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD NOV 27 PY 1999 VL 354 IS 9193 BP 1846 EP 1850 DI 10.1016/S0140-6736(99)04336-6 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 259TF UT WOS:000083909100009 PM 10584720 ER PT J AU Gonzalez-Agosti, C Wiederhold, T Herndon, ME Gusella, J Ramesh, V AF Gonzalez-Agosti, C Wiederhold, T Herndon, ME Gusella, J Ramesh, V TI Interdomain interaction of merlin isoforms and its influence on intermolecular binding to NHE-RF SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NEUROFIBROMATOSIS-2 TUMOR-SUPPRESSOR; EZRIN/RADIXIN/MOESIN ERM PROTEINS; TERMINAL REGION; NF2 GENE; EZRIN; MEMBRANE; ACTIN; MOESIN; ASSOCIATION; DOMAIN AB Merlin, the neurofibromatosis 2 tumor suppressor protein, has two major isoforms with alternate C termini and is related to the ERM (ezrin, radixin, moesin) proteins. Regulation of the ERMs involves intramolecular and/or intermolecular head-to-tail associations between family members. We have determined whether merlin undergoes similar interactions, and our findings indicate that the C terminus of merlin isoform 1 is able to associate with its N-terminal domain in a head-to-tail fashion. However, the C terminus of isoform 2 lacks this property. Similarly, the N terminus of merlin can also associate with C terminus of moesin, We have also explored the effect of merlin self-association on binding to the regulatory cofactor of Na+-H+ exchanger (NHE-RF), an interacting protein for merlin and the ERMs, Merlin isoform 2 captures more NHE-RF than merlin isoform 1 in affinity binding assays, suggesting that in full-length merlin isoform 1, the NHE-RF binding site is masked because of the self-interactions of merlin. Treatment with a phospholipid known to decrease self-association of ERMs enhances the binding of merlin isoform 1 to NHE-RF, Thus, although isoform 1 resembles the ERM proteins, which transition between inactive (closed) and active (open) states, isoform 2 is distinct, existing only in the active (open) state and presumably constitutively more available for interaction with other protein partners. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Ramesh, V (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS24279] NR 37 TC 70 Z9 70 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 26 PY 1999 VL 274 IS 48 BP 34438 EP 34442 DI 10.1074/jbc.274.48.34438 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 258UL UT WOS:000083857500089 PM 10567424 ER PT J AU Isotani, S Hara, K Tokunaga, C Inoue, H Avruch, J Yonezawa, K AF Isotani, S Hara, K Tokunaga, C Inoue, H Avruch, J Yonezawa, K TI Immunopurified mammalian target of rapamycin phosphorylates and activates p70 S6 kinase alpha in vitro SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE; EIF-4E BP1; IN-VIVO; SITE; P70(S6K); MTOR; ANTIBODIES AB p70 S6 kinase alpha (p70 alpha) is activated in vivo through a multisite phosphorylation in response to mitogens if a sufficient supply of amino acids is available or to high concentrations of amino acids per se. The immunosuppressant drug rapamycin inhibits p70 alpha activation in a manner that can be overcome by coexpression of p70 alpha with a rapamycin-resistant mutant of the mammalian target of rapamycin (mTOR) but only if the mTOR kinase domain is intact. We report here that a mammalian recombinant p70 alpha polypeptide, extracted in an inactive form from rapamycin-treated cells, can be directly phosphorylated by the mTOR kinase in vitro predominantly at the rapamycin-sensitive site Thr-412. mTOR-catalyzed p70 alpha phosphorylation in vitro is accompanied by a substantial restoration in p70 alpha kinase activity toward its physiologic substrate, the 40 S ribosomal protein S6. Moreover, sequential phosphorylation of p70 alpha by mTOR and 3-phosphoinositide-dependent protein kinase 1 in vitro resulted in a synergistic stimulation of p70 alpha activity to levels similar to that attained by serum stimulation in vivo. These results indicate that mTOR is likely to function as a direct activator of p70 in vivo, although the relative contribution of mTOR-catalyzed p70 phosphorylation in each of the many circumstances that engender p70 activation remains to be defined. C1 Kobe Univ, Biosignal Res Ctr, Nada Ku, Kobe, Hyogo 6518501, Japan. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02129 USA. Massachusetts Gen Hosp, Med Serv, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Yonezawa, K (reprint author), Kobe Univ, Biosignal Res Ctr, Nada Ku, 1-1 Rokkodai Cho, Kobe, Hyogo 6518501, Japan. EM yonezawa@kobe-u.ac.jp FU NCI NIH HHS [CA73818]; NIDDK NIH HHS [DK17776] NR 23 TC 225 Z9 232 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 26 PY 1999 VL 274 IS 48 BP 34493 EP 34498 DI 10.1074/jbc.274.48.34493 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 258UL UT WOS:000083857500096 PM 10567431 ER PT J AU Matsumoto, I Staub, A Benoist, C Mathis, D AF Matsumoto, I Staub, A Benoist, C Mathis, D TI Arthritis provoked by linked T and B cell recognition of a glycolytic enzyme SO SCIENCE LA English DT Article ID RHEUMATOID-ARTHRITIS; AUTOIMMUNITY; COLLAGEN; MODEL AB The hallmark of rheumatoid arthritis (RA) is specific destruction of the synovial joints. In a mouse line that spontaneously develops a disorder with many of the features of human RA, disease is initiated by T cell recognition of a ubiquitously expressed self-antigen; once initiated, pathology is driven almost entirely by immunoglobulins. In this study, the target of both the initiating T cells and pathogenic immunoglobulins was identified as glucose-6-phosphate isomerase, a glycolytic enzyme, Thus, some forms of RA or related arthritides may develop by a mechanism fundamentally different from the currently popular paradigm of a joint-specific T cell response. C1 ULP, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch, CU Strasbourg, France. RP Benoist, C (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. NR 20 TC 395 Z9 410 U1 1 U2 10 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD NOV 26 PY 1999 VL 286 IS 5445 BP 1732 EP 1735 DI 10.1126/science.286.5445.1732 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 259UK UT WOS:000083912200037 PM 10576739 ER PT J AU Ayanian, JZ Cleary, PD Weissman, JS Epstein, AM AF Ayanian, JZ Cleary, PD Weissman, JS Epstein, AM TI The effect of patients' preferences on racial differences in access to renal transplantation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID REVASCULARIZATION PROCEDURES; SURGICAL-PROCEDURES; HEART-DISEASE; RACE; WOMEN; ENDARTERECTOMY; ANGIOGRAPHY; DIALYSIS; QUALITY; SURGERY AB Background: In the United States, black patients undergo renal transplantation less often than white patients, but few studies have directly assessed the association between race and patients' preferences with respect to transplantation. Methods: To assess preferences with respect to transplantation and experiences with medical care, we interviewed 1392 (82.9 percent) of 1679 eligible patients with end-stage renal disease (age range, 18 to 54 years) approximately 10 months after they had begun maintenance treatment with dialysis. Participants were selected from a stratified random sample of patients undergoing dialysis in four regions of the United States (Alabama, southern California, Michigan, and the mid-Atlantic region of Maryland, Virginia, and the District of Columbia) in 1996 and 1997. Patients were followed until March 1999. Results: The interviews were conducted with 384 black women, 354 white women, 337 black men, and 317 white men. Black patients were less likely than white patients to want a transplant (76.3 percent of black women reported such a preference, vs. 79.3 percent of white women, and 80.7 percent of black men vs. 85.5 percent of white men), and they were less likely to be very certain about this preference (58.3 percent vs. 65.3 percent and 64.1 percent vs. 75.7 percent, respectively; P<0.01 for each comparison with both sexes combined). However, much larger differences were evident in rates of referral for evaluation at a transplantation center (50.4 percent for black women vs. 70.5 percent for white women, and 53.9 percent for black men vs. 76.2 percent for white men; P<0.001 for each comparison) and placement on a waiting list or transplantation within 18 months after the start of dialysis therapy (31.3 percent for black women vs. 56.5 percent for white women, and 35.3 percent for black men vs. 60.6 percent for white men; P<0.001). These racial differences remained significant after adjustment for patients' preferences and expectations about transplantation, sociodemographic characteristics, the type of dialysis facility, perceptions of care, health status, the cause of renal failure, and the presence or absence of coexisting illnesses. Conclusions: In the United States, the preferences and expectations with respect to renal transplantation among patients with end-stage renal disease differ according to race. These differences, however, explain only a small fraction of the substantial racial differences in access to transplantation. Physicians should ensure that black patients who desire renal transplantation are fully informed about it and are referred for evaluation. (N Engl J Med 1999;341:1661-9.) (C) 1999, Massachusetts Medical Society. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Gen Med & Primary Care, Sect Hlth Serv & Policy Res, Boston, MA 02115 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Ayanian, JZ (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. NR 41 TC 402 Z9 402 U1 1 U2 6 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 25 PY 1999 VL 341 IS 22 BP 1661 EP 1669 DI 10.1056/NEJM199911253412206 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 258PL UT WOS:000083847500006 PM 10572155 ER PT J AU Hendren, WH Connolly, SA Shannon, DC Mark, EJ Doody, DP AF Hendren, WH Connolly, SA Shannon, DC Mark, EJ Doody, DP TI A 32-day-old girl with a retroperitoneal mass - Subdiaphragmatic extralobar sequestration of the lung with congenital cystic adenomatoid malformation. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID INTRAABDOMINAL PULMONARY SEQUESTRATION; BRONCHIOLOALVEOLAR CARCINOMA; BRONCHOGENIC CYST; LESIONS C1 Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hendren, WH (reprint author), Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. NR 28 TC 2 Z9 2 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 NOV 25 PY 1999 VL 341 IS 22 BP 1680 EP 1685 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 258PL UT WOS:000083847500008 ER PT J AU Yoon, Y Ao, ZH Cheng, Y Schlossman, SF Prasad, KVS AF Yoon, Y Ao, ZH Cheng, Y Schlossman, SF Prasad, KVS TI Murine Siva-1 and Siva-2, alternate splice forms of the mouse Siva gene, both bind to CD27 but differentially transduce apoptosis SO ONCOGENE LA English DT Article DE Siva; CD27; apoptosis; alternate splice forms; murine Siva gene; TNFR family ID NECROSIS-FACTOR RECEPTOR; NF-KAPPA-B; DOMAIN-CONTAINING RECEPTOR; T-CELL ACTIVATION; RING FINGER PROTEIN; DEATH-DOMAIN; CYTOPLASMIC DOMAIN; SIGNAL-TRANSDUCTION; KINASE RIP; FAMILY AB CD27, a member of the TNFR family known to provide essential co-stimulatory signals for T cell growth and B cell Ig synthesis, can also mediate cell death. Using the CD27 cytoplasmic tail as the bait in yeast two hybrid assay, me previously cloned human Siva, a pro-apoptotic molecule. Here me report the characterization of the mouse Siva gene as a 4 kb sequence containing 4 exons and 3 introns. RT-PCR has revealed the presence of two forms of mouse Siva mRNA, the longer full length form Siva-1 and the shorter Siva-2 lacking the sequence coded by exon 2. Immunoblotting with anti-Siva (human) antibodies clearly demonstrate the presence of both Siva-1 and Siva-2. Cotransfection experiments in 293T cells reveal that mouse CD27 receptor can interact with both forms of Siva. Although mouse Siva-1 can trigger apoptosis in Rat-1 cells and in some of the mouse cell lines in transient transfection experiments, similar to the observation made with human Siva, intriguingly its alternate splice form, Siva-2 appears to be much less toxic. It is therefore likely that Siva-2 could regulate the function of Siva-1. C1 Dana Farber Canc Inst, Div Tumor Immunol, Dept Canc Immunol & Aids, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Prasad, KVS (reprint author), Dana Farber Canc Inst, Div Tumor Immunol, Dept Canc Immunol & Aids, M552,44 Binney St, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM56706] NR 49 TC 36 Z9 40 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 25 PY 1999 VL 18 IS 50 BP 7174 EP 7179 DI 10.1038/sj.onc.1203144 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 259PH UT WOS:000083901900025 PM 10597319 ER PT J AU Garber, J AF Garber, J TI A 40-year-old woman with a strong family history of breast cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID OVARIAN-CANCER; PROPHYLACTIC OOPHORECTOMY; SUSCEPTIBILITY GENES; HEREDITARY BREAST; BRCA1 MUTATIONS; RISK; WOMEN; RECOMMENDATIONS; PROBABILITIES; EPIDEMIOLOGY C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Garber, J (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 52 TC 14 Z9 14 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 24 PY 1999 VL 282 IS 20 BP 1953 EP 1960 DI 10.1001/jama.282.20.1953 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 257BZ UT WOS:000083763400031 PM 10580462 ER PT J AU Teixeira, J Kehas, DJ Antun, R Donahoe, PK AF Teixeira, J Kehas, DJ Antun, R Donahoe, PK TI Transcriptional regulation of the rat Mullerian inhibiting substance type II receptor in rodent Leydig cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ORPHAN NUCLEAR RECEPTOR; STEROIDOGENIC FACTOR-I; GROWTH-FACTOR-BETA; SEXUAL-DIFFERENTIATION; GONADAL DEVELOPMENT; HORMONE-RECEPTOR; TRANSGENIC MICE; GENE-EXPRESSION; PROMOTER; SP1 AB Mullerian inhibiting substance (MIS) causes regression of the fetal Mullerian duct on binding a heteromeric complex of types I and II cell-surface receptors in the fetal urogenital ridge. The MIS type II receptor (MISRII), which provides specificity for MIS, is also expressed in the adult testis, ovary, and uterus. The rat MISRII promoter was cloned to study the molecular mechanisms underlying its temporal and cell-specific expression. The 7.6-kilobase (kb) promoter contained no recognizable TATA or CAAT box, but there was a consensus Spl site upstream of the transcription initiation site. Two binding sites for the orphan nuclear receptor steroidogenic factor-1 (SF-1) are occupied in vitro by using nuclear extracts from R2C cells, an MIS-responsive rat Leydig cell line that expresses endogenous MISRII, with differing affinities, indicating that the distal SF-l site is bound more avidly than is the proximal SF-l site. R2C cells transfected with MISRII promoter/luciferase reporter constructs show a 12-fold induction with the 1.6-kb fragment and deletion of sequences upstream of -282-bp lowered luciferase expression to one-third. Mutation of both SF-l sites greatly inhibited luciferase expression, whereas mutation of either site atone resulted in continuing activation by endogenous SF-1, indicating redundancy. In vitro binding and transcriptional analyses suggest that a proximal potential Smad-responsive element and an uncharacterized element also contribute to activation of the MISRII gene. R2C cells and MISRII promoter regulation can now be used to uncover endogenous transcription factors responsible for receptor expression or repression. C1 Massachusetts Gen Hosp, Pediat Surg Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Teixeira, J (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Lab, WRN1151,37 Fruit St, Boston, MA 02114 USA. EM teixeira@helix.mgh.harvard.edu FU NCI NIH HHS [R29-CA79459]; NICHD NIH HHS [F32 HD007954-03, R01 HD032112, F32 HD007954, R01-HD32112, F32-HD07954] NR 44 TC 30 Z9 33 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 23 PY 1999 VL 96 IS 24 BP 13831 EP 13838 DI 10.1073/pnas.96.24.13831 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 259AY UT WOS:000083872900044 PM 10570158 ER PT J AU Manjunath, N Shankar, P Stockton, B Dubey, PD Lieberman, J von Andrian, UH AF Manjunath, N Shankar, P Stockton, B Dubey, PD Lieberman, J von Andrian, UH TI A transgenic mouse model to analyze CD8(+) effector T cell differentiation in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LYMPHOCYTES-T; ANTIGENIC-STIMULATION; IN-VITRO; ACTIVATION; MEMORY; NAIVE; TUMOR; CYTOTOXICITY; EXPRESSION; INFECTION AB Antigen-specific effector T cells are prerequisite to immune protection, but because of the lack of effector cell-specific markers, their generation and differentiation has been difficult to study. We report that effector cells are highly enriched in a T cell subset that can be specifically identified in transgenic (T-GFP) mice expressing green fluorescent protein (GFP) under control of the murine CD4 promoter and proximal enhancer. Consistent with previous studies of these transcriptional control elements, GFP was strongly and specifically expressed in nearly all resting and short-term activated CD4(+) and CD8(+) T cells. However, when T-GFP mice were challenged with vaccinia virus, allogeneic tumor cells, or staphylococcal enterotoxin A, the cytotoxic and IFN-gamma-producing T cells lost GFP expression. Upon T cell receptor (TCR) ligation by alpha CD3, sorted GFP(+) cells fluxed calcium and proliferated vigorously. In contrast, GFP(-) effector cells showed a diminished calcium flux and did not proliferate, instead, they underwent apoptosis unless supplied with exogenous IL-2. By reverse transcription-PCR analysis, the GFP(-) cells up-regulated the pro-apoptotic molecule, Fas-L, and down-regulated gene expression of the proximal TCR signaling molecule, CD3 zeta, and c-jun, a component of the AP-1 transcription factor. Thus, differential regulation of TCR signaling may explain the divergent responses of naive and effector T cells to antigen stimulation. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Tufts Univ, Dept Med, Boston, MA 02111 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; Lieberman, Judy/A-2717-2015 FU NHLBI NIH HHS [HL56949, HL02881, HL54936, P01 HL029583, P01 HL056949] NR 32 TC 68 Z9 68 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 23 PY 1999 VL 96 IS 24 BP 13932 EP 13937 DI 10.1073/pnas.96.24.13932 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 259AY UT WOS:000083872900062 PM 10570176 ER PT J AU Freedman, SD Katz, MH Parker, EM Laposata, M Urman, MY Alvarez, JG AF Freedman, SD Katz, MH Parker, EM Laposata, M Urman, MY Alvarez, JG TI A membrane lipid imbalance plays a role in the phenotypic expression of cystic fibrosis in cftr(-/-) mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE docosahexaenoic acid; arachidonic acid; fish oil pancreas; lung ID TRANSMEMBRANE CONDUCTANCE REGULATOR; POLYUNSATURATED FATTY-ACIDS; DOCOSAHEXAENOIC ACID; ARACHIDONIC-ACID; CHANNELS; GENE; SUPPLEMENTATION; PHOSPHOLIPIDS; MODEL; OMEGA-3-FATTY-ACIDS AB A deficiency in essential fatty acid metabolism has been reported in plasma from patients with cystic: fibrosis (CF), However, its etiology and role in the expression of disease is unknown. The objective of this study was to determine whether alterations in fatty acid metabolism are specific to CF-regulated organs and whether they play a role in the expression of disease. A membrane lipid imbalance was found in ileum, pancreas, and lung from cftr(-/-) mice characterized by an increase in phospholipid-bound arachidonic acid and a decrease in phospholipid-bound docosahexaenoic acid (DHA). This lipid imbalance was observed in organs pathologically affected by CF including lung, pancreas, and ileum and was not secondary to impaired intestinal absorption or hepatic biosynthesis of DHA. As proof of concept, oral administration of DHA to cftr(-/-) mice corrected this lipid imbalance and reversed the observed pathological manifestations. These results strongly suggest that certain phenotypic manifestations of CF may result from remediable alterations in phospholipid-bound arachidonic acid and DHA levels. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Obstet & Gynecol, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Lab Med, Boston, MA 02215 USA. RP Alvarez, JG (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Dana 501,330 Brookline Ave, Boston, MA 02215 USA. FU NIDDK NIH HHS [R01 DK-52765, R01 DK052765] NR 48 TC 196 Z9 198 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 23 PY 1999 VL 96 IS 24 BP 13995 EP 14000 DI 10.1073/pnas.96.24.13995 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 259AY UT WOS:000083872900073 PM 10570187 ER PT J AU Gauduin, MC Glickman, RL Ahmad, S Yilma, T Johnson, RP AF Gauduin, MC Glickman, RL Ahmad, S Yilma, T Johnson, RP TI Immunization with live attenuated simian immunodeficiency virus induces strong type 1 T helper responses and beta-chemokine production SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RHESUS MACAQUES; IMMUNE-RESPONSE; DELETION MUTANT; CELL RESPONSES; NEF GENE; INFECTION; VACCINE; IDENTIFICATION; PROTECTION; EXPRESSION AB Immunization with live attenuated simian immunodeficiency virus (SIV) strains has proved to be one of the most effective strategies to induce protective immunity in the SIV/macaque model. To better understand the role that CD4(+) T helper responses may play in mediating protection in this model, we characterized SIV-specific proliferative and cytokine responses in macaques immunized with live attenuated SIV strains. Macaques chronically infected with live attenuated SIV had strong proliferative responses to SIV proteins, with stimulation indices of up to 74, The magnitude of the proliferative response to SIV Gag varied inversely with the degree of attenuation; Gag-specific but not envelope-specific responses were lower in animals infected with more highly attenuated SIV strains, SIV-specific stimulation of lymphocytes from vaccinated macaques resulted in secretion of interferon-gamma, IL-2, regulated-upon-activation, normal T cells expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1 alpha, and MIP-1 beta but not IL-4 or IL-10. Intracellular flow cytometric analysis documented that, in macaques vaccinated with SIVmac239 Delta nef, up to 2% of all CD4(+) T cells were specific for SIV p55, The ability of live attenuated SIV to induce a strong, sustained type 1 T helper response may play a role in the success of this Vaccination approach to generate protection against challenge with wild-type SIV. C1 New England Reg Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA. Harvard Univ, Sch Med, Southborough, MA 01772 USA. Univ Calif Davis, Int Lab Mol Biol Trop Dis Agents, Davis, CA 95616 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02115 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. RP Johnson, RP (reprint author), New England Reg Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA. FU NCRR NIH HHS [RR00168]; NIAID NIH HHS [AI43044, AI45314] NR 39 TC 66 Z9 66 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 23 PY 1999 VL 96 IS 24 BP 14031 EP 14036 DI 10.1073/pnas.96.24.14031 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 259AY UT WOS:000083872900079 PM 10570193 ER PT J AU Bates, DW Miller, EB Cullen, DJ Burdick, L Williams, L Laird, N Petersen, LA Small, SD Sweitzer, BJ Vander Vliet, M Leape, LL AF Bates, DW Miller, EB Cullen, DJ Burdick, L Williams, L Laird, N Petersen, LA Small, SD Sweitzer, BJ Vander Vliet, M Leape, LL CA ADE Prevention Study Grp TI Patient risk factors for adverse drug events in hospitalized patients SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID POLYPHARMACY; OUTPATIENTS; FEEDBACK; THERAPY; ADULTS; ERRORS AB Background: Adverse drug events (ADEs) are common in hospitalized patients, but few empirical data are available regarding the strength of patient risk factors for ADEs. Methods: We performed a nested case-control study within a cohort that included 4108 admissions to a stratified random sample of 11 medical and surgical units in 2 tertiary care hospitals during a B-month period. Analyses were conducted on 2 levels: (1) using a limited set of variables available for all patients using computerized data available from 1 hospital and (2) using a larger set of variables for the case patients and matched controls from both hospitals. Case patients were patients with an ADE, and the matched control for each case patient was the patient on the same unit as the case patient with the most similar preevent length of stay. Main outcome measures were presence of an ADE, preventable ADE, or severe ADE. Results: In the cohort analysis, electrolyte concentrates (odds ratio [OR], 1.7), diuretics (OR, 1.7), and medical admission (OR, 1.6) were independent correlates of ADEs. Independent correlates of preventable ADEs in the cohort analysis were low platelet count (OR, 4.5), antidepressants (OR, 3.3), antihypertensive agents (OR, 2.9), medical admission (OR, 2.2), and electrolyte concentrates (OR, 2.1). In the case-control analysis, exposure to psychoactive drugs (OR, 2.1) was an independent correlate of an ADE, and use of cardiovascular drugs (OR, 2.4) was independently correlated with severe ADEs. For preventable ADEs, no independent predictors were retained after multivariate analysis. Conclusions: Adverse drug events occurred more frequently in sicker patients who stayed in the hospital longer. However, after controlling for level of care and preevent length of stay, few risk factors emerged. These results suggest that, rather than targeting ADE-prone individuals, prevention strategies should focus on improving medication systems. C1 Harvard Univ, Sch Med, Dept Anaesthesia, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Vet Affairs Med Ctr, Houstan Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Brigham & Womens Hosp, Dept Med, Div Gen Med, Boston, MA 02115 USA. RP Bates, DW (reprint author), Brigham & Womens Hosp, Div Gen Med & Primary Care, 75 Francis St, Boston, MA 02115 USA. FU AHRQ HHS [R01-HS07107-01] NR 52 TC 176 Z9 189 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 22 PY 1999 VL 159 IS 21 BP 2553 EP 2560 DI 10.1001/archinte.159.21.2553 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 257DJ UT WOS:000083766800007 PM 10573045 ER PT J AU Camargo, CA Weiss, ST Zhang, SM Willett, WC Speizer, FE AF Camargo, CA Weiss, ST Zhang, SM Willett, WC Speizer, FE TI Prospective study of body mass index, weight change, and risk of adult-onset asthma in women SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID NUTRITION-EXAMINATION-SURVEY; PULMONARY-FUNCTION; VITAL CAPACITY; MORBIDLY OBESE; UNITED-STATES; PROSPECTIVE COHORT; FAT DISTRIBUTION; NATIONAL-HEALTH; LUNG-FUNCTION; CHILDREN AB Background: Obesity and asthma are common disorders, and their prevalence rates continue to rise. Although individuals with asthma ma) gain weight as a result of activity limitations, the relationship between body mass index (BMI), which is calculated as weight in kilograms divided by the square of height in meters, and risk of developing asthma is not known. Methods: We performed a prospective cohort study of female US registered nurses in the Nurses' Health Study 11. In 1991, after excluding women who died with probable asthma or with incomplete data, there were 85 911 participants, aged 26 to 46 years. The main outcome measure was self-report of physician-diagnosed asthma with recent use of an asthma medication. Results: From 1991 to 1995, we identified 1596 incident cases of asthma. In a multivariate model controlling for 9 potential confounding factors (including age, race, smoking, physical activity, and energy intake), the relative risks of asthma for 6 increasing categories of BMI in 1991 were 0.9, 1.0 (reference), 1.1, 1.6, 1.7, and 2.7 (P for trend <.001). Stronger associations were found using stricter definitions for asthma, and the finding was present in a variety of subgroups. In analyses controlling for the same variables, as well as BMI at age 18, women who gained weight after age 18 were at significantly increased risk of developing asthma during the 4-year follow-up period (P for trend <.001). Conclusions: The BMI has a strong, independent, and positive association with risk of adult-onset asthma. The increasing prevalence of obesity in developed nations may help explain concomitant increases in asthma prevalence. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Camargo, CA (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA-50385]; NHLBI NIH HHS [HL-03533] NR 58 TC 456 Z9 467 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 22 PY 1999 VL 159 IS 21 BP 2582 EP 2588 DI 10.1001/archinte.159.21.2582 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 257DJ UT WOS:000083766800010 PM 10573048 ER PT J AU Arystarkhova, E Wetzel, RK Asinovski, NK Sweadner, KJ AF Arystarkhova, E Wetzel, RK Asinovski, NK Sweadner, KJ TI The gamma subunit modulates Na+ and K+ affinity of the renal Na,K-ATPase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALPHA-SUBUNIT; PUMP ACTIVITY; ATPASE; ISOFORMS; NA+,K+-ATPASE; POLYPEPTIDE; EXPRESSION; COMPONENT; INSULIN; OUABAIN AB The Na+,K+F-ATPase catalyzes the active transport of ions. It has two necessary subunits, alpha and beta, but in kidney it is also associated with a 7.4-kDa protein, the gamma subunit. Stable transfection was used to determine the effect of gamma on Na,K-ATPase properties. When isolated from either kidney or transfected cells, alpha beta gamma had lower affinities for both Na+ and K-_ than alpha beta. A post-translational modification of gamma selectively eliminated the effect on Naf affinity, suggesting three configurations (alpha beta, alpha beta gamma, and alpha beta gamma*) conferring different stable properties to Na,H-ATPase, In the nephron, segment-specific differences in Na+ affinity have been reported that cannot be explained by the known alpha and beta subunit isoforms of Na,K-ATPase, Immunofluorescence was used to detect gamma in rat renal cortex. Cortical ascending limb and same cortical collecting tubules lacked gamma, correlating with higher Na+ affinities in those segments reported in the literature. Selective expression in different segments of the nephron is consistent with a modulatory role for the gamma subunit in renal physiology. C1 Massachusetts Gen Hosp, Ctr Neurosci, Lab Membrane Biol, Charlestown, MA 02129 USA. RP Sweadner, KJ (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Lab Membrane Biol, 149-6118,149 13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL36271]; NINDS NIH HHS [NS27653] NR 29 TC 157 Z9 162 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 19 PY 1999 VL 274 IS 47 BP 33183 EP 33185 DI 10.1074/jbc.274.47.33183 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 256UQ UT WOS:000083745200002 PM 10559186 ER PT J AU Lien, E Sellati, TJ Yoshimura, A Flo, TH Rawadi, G Finberg, RW Carroll, JD Espevik, T Ingalls, RR Radolf, JD Golenbock, DT AF Lien, E Sellati, TJ Yoshimura, A Flo, TH Rawadi, G Finberg, RW Carroll, JD Espevik, T Ingalls, RR Radolf, JD Golenbock, DT TI Toll-like receptor 2 functions as a pattern recognition receptor for diverse bacterial products SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BORRELIA-BURGDORFERI LIPOPROTEINS; TUMOR-NECROSIS-FACTOR; FACTOR-KAPPA-B; JARISCH-HERXHEIMER REACTION; OUTER SURFACE LIPOPROTEINS; LYME-DISEASE SPIROCHETE; PROTEIN-KINASE PATHWAYS; TREPONEMA-PALLIDUM; DROSOPHILA TOLL; MEMBRANE LIPOPROTEINS AB Toll-like receptors (TLRs) 2 and 4 are signal transducers for lipopolysaccharide, the major proinflammatory constituent in the outer membrane of Gram-negative bacteria. We observed that membrane lipoproteins/lipopeptides from Borrelia burgdorferi, Treponema pallidum, and Mycoplasma fermentans activated cells heterologously expressing TLR2 but not those expressing TLR1 or TLR4. These TLR2-expressing cells were also stimulated by living motile B. burgdorferi, suggesting that TLR2 recognition of lipoproteins is relevant to natural Borrelia infection, Importantly, a TLR2 antibody inhibited bacterial lipoprotein/lipopeptide-induced tumor necrosis factor release from human peripheral blood mononuclear cells, and TLR2-null Chinese hamster macrophages were insensitive to lipoprotein/lipopeptide challenge. The data suggest a role for the native protein in cellular activation by these ligands, In addition, TLR2-dependent responses were seen using whole Mycobacterium avium and Staphylococcus aureus, demonstrating that this receptor can function as a signal transducer for a wide spectrum of bacterial products. We conclude that diverse pathogens activate cells through TLR2 and propose that this molecule is a central pattern recognition receptor in host immune responses to microbial invasion. C1 Boston Univ, Sch Med, Boston Med Ctr, Maxwell Finland Lab Infect Dis, Boston, MA 02118 USA. Norwegian Univ Sci & Technol, Inst Canc Res & Mol Biol, N-7489 Trondheim, Norway. Inst Pasteur, Dept Bacteriol, F-75724 Paris, France. Boston Univ, Sch Med, Dept Med, Boston Vet Affairs Med Ctr, Boston, MA 02130 USA. Dana Farber Canc Inst, Infect Dis Lab, Boston, MA 02115 USA. RP Golenbock, DT (reprint author), Boston Univ, Sch Med, Boston Med Ctr, Maxwell Finland Lab Infect Dis, 774 Albany St, Boston, MA 02118 USA. RI Finberg, Robert/E-3323-2010; Flo, Trude/E-1311-2013 FU NIAID NIH HHS [AI01476, AI38515, F32 AI009973]; NIGMS NIH HHS [GM54060] NR 61 TC 685 Z9 720 U1 2 U2 17 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 19 PY 1999 VL 274 IS 47 BP 33419 EP 33425 DI 10.1074/jbc.274.47.33419 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 256UQ UT WOS:000083745200039 PM 10559223 ER PT J AU Sun, YP Zhang, JY Kraeft, SK Auclair, D Chang, MS Liu, Y Sutherland, R Salgia, R Griffin, JD Ferland, LH Chen, LB AF Sun, YP Zhang, JY Kraeft, SK Auclair, D Chang, MS Liu, Y Sutherland, R Salgia, R Griffin, JD Ferland, LH Chen, LB TI Molecular cloning and characterization of human trabeculin-alpha a giant protein defining a new family of actin-binding proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BULLOUS PEMPHIGOID ANTIGEN; INTERMEDIATE FILAMENTS; STRUCTURAL-ANALYSIS; MEMBRANE SKELETON; FOCAL ADHESIONS; STRESS FIBERS; SPECTRIN; PHOSPHORYLATION; CYTOSKELETON; DROSOPHILA AB We describe the molecular cloning and characterization of a novel giant human cytoplasmic protein, trabeculin-alpha (M-r = 614,000), Analysis of the deduced amino acid sequence reveals homologies with several putative functional domains, including a pair of alpha-actinin-like actin binding domains; regions of homology to plakins at either end of the giant polypeptide; 29 copies of a spectrin-like motif in the central region of the protein; two potential Ca2+-binding EF-hand motifs; and a Ser-rich region containing a repeated GSRX motif, With similarities to both plakins and spectrins, trabeculin-alpha appears to have evolved as a hybrid of these two families of proteins. The functionality of the actin binding domains located near the N terminus was confirmed with an F-actin binding assay using glutathione S-transferase fusion proteins comprising amino acids 9-486 of the deduced peptide. Northern and Western blotting and immunofluorescence studies suggest that trabeculin is ubiquitously expressed and is distributed throughout the cytoplasm, though the protein was found to be greatly up-regulated upon differentiation of myoblasts into myotubes. Finally, the presence of cDNAs similar to, yet distinct from, trabeculin-alpha in both human and mouse suggests that trabeculins may form a new subfamily of giant actin-binding/cytoskeletal cross-linking proteins. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Chen, LB (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 45 TC 29 Z9 32 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 19 PY 1999 VL 274 IS 47 BP 33522 EP 33530 DI 10.1074/jbc.274.47.33522 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 256UQ UT WOS:000083745200053 PM 10559237 ER PT J AU Rosowsky, A Cody, V Galitsky, N Fu, HN Papoulis, AT Queener, SF AF Rosowsky, A Cody, V Galitsky, N Fu, HN Papoulis, AT Queener, SF TI Structure-based design of selective inhibitors of dihydrofolate reductase: Synthesis and antiparasitic activity of 2,4-diaminopteridine analogues with a bridged diarylamine side chain SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; TOXOPLASMA-GONDII; TRIMETHOPRIM-SULFAMETHOXAZOLE; OPPORTUNISTIC INFECTIONS; BIOLOGICAL-ACTIVITIES; MYCOBACTERIUM-AVIUM; POTENTIAL ANTITUMOR; TRIMETREXATE; AGENTS AB As part of a larger search for potent as well as selective inhibitors of dihydrofolate reductase (DHFR) enzymes from opportunistic pathogens found in patients with AIDS and other immune disorders, N-[(2,4-diaminopteridin-6-yl)methyl] dibenz [b,f]azepine (4a) and the corresponding dihydrodibenz[b,f]azepine, dihydroacridine, phenoxazine, phenothiazine, carbazole, and diphenylamine analogues were synthesized from 2,4-diamino-6-(bromomethyl)pteridine in 50-75% yield by reaction with the sodium salts of the amines in dry tetrahydrofuran at room temperature. The products were tested for the ability to inhibit DHFR from Pneumocystis carinii (pcDHFR), Toxoplasma gondii (tgDHFR), Mycobacterium avium (maDHFR), and rat liver (rlDHFR). The member of the series with the best combination of potency and species selectivity was 4a, with IC50 values against the four enzymes of 0.21, 0.043, 0.012, and 4.4 mu M, respectively. The dihydroacridine, phenothiazine, and carbazole analogues were also potent, but nonselective. Of the compounds tested, 4a was the only one to successfully combine the potency of trimetrexate with the selectivity of trimethoprim. Molecular docking simulations using published 3D structural coordinates for the crystalline ternary complexes of pcDHFR and hDHFR suggested a possible structural interpretation for the binding selectivity of 4a and the lack of selectivity of the other compounds. According to this model, 4a is selective because of a unique propensity of the seven-membered ring in the dibenz[b,f]azepine moiety to adopt a puckered orientation that allows it to fit more comfortably into the active site of the P. carinii enzyme than into the active site of the human enzyme. Compound 4a was also evaluated for the ability to be taken up into, and retard the growth of, P. carinii and T. gondii in culture. The IC50 of 4a against P. carinii trophozoites after 7 days of continuous drug treatment was 1.9 mu M as compared with previously observed IC50 values of >340 mu M for trimethoprim and 0.27 mu M for trimetrexate. In an assay involving [H-3]uracil incorporation into the nuclear DNA of T. gondii tachyzoites as the surrogate endpoint for growth, the IC50 Of 4a after 5 h of drug exposure was 0.077 mu M. The favorable combination of potency and enzyme selectivity shown by 4a suggests that this novel structure may be an interesting lead for structure-activity optimization. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Hauptman Woodward, Med Res, Buffalo, NY 14203 USA. Indiana Univ, Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA. RP Rosowsky, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [R01-AI35171, N01-AI35171]; NIGMS NIH HHS [R01-GM51670] NR 54 TC 51 Z9 52 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 18 PY 1999 VL 42 IS 23 BP 4853 EP 4860 DI 10.1021/jm990331q PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 258BY UT WOS:000083819300012 PM 10579848 ER PT J AU Raje, N Anderson, K AF Raje, N Anderson, K TI Thalidomide - A revival story. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MULTIPLE-MYELOMA C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Raje, N (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 17 TC 143 Z9 145 U1 1 U2 7 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 18 PY 1999 VL 341 IS 21 BP 1606 EP 1609 DI 10.1056/NEJM199911183412110 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 256GF UT WOS:000083717000010 PM 10564693 ER PT J AU Chauhan, D Hideshima, T Pandey, P Treon, S Teoh, G Raje, N Rosen, S Krett, N Husson, H Avraham, S Kharbanda, S Anderson, KC AF Chauhan, D Hideshima, T Pandey, P Treon, S Teoh, G Raje, N Rosen, S Krett, N Husson, H Avraham, S Kharbanda, S Anderson, KC TI RAFTK/PYK2-dependent and -independent apoptosis in multiple myeloma cells SO ONCOGENE LA English DT Article DE multiple myeloma; irradiation; dexamethasone; apoptosis ID FOCAL TYROSINE KINASE; HEMATOPOIETIC-CELLS; ACTIVATION; INTERLEUKIN-6; ASSOCIATION; PYK2; PHOSPHORYLATION; MEGAKARYOCYTES; STIMULATION; PAXILLIN AB Related Adhesion Focal Tyrosine Kinase (RAFTK; also known as Pyk2), is a member of the Focal Adhesion Kinase (FAK) subfamily and is activated by TNF alpha, UV light and increases in intracellular calcium levels. However, the function of RAFTK remains largely unknown. Our previous studies demonstrated that treatment with dexamethasone (Dex), ionizing radiation (IR), and anti-Fas mAb induces apoptosis in multiple myeloma (MM) cells. In the present study, we examined the potential role of RAFTK during induction of apoptosis in human MM cells triggered by these three stimuli. Dex-induced apoptosis, in contrast to apoptosis triggered by anti-Fas mAb or IR, is associated with activation of RAFTK. Transient overexpression of RAFTK wild type (RAFTK WT) induces apoptosis, whereas transient overexpression of Kinase inactive RAFTK (RAFTK K-M) blocks Dex-induced apoptosis. In contrast, transient overexpression of RAFTK K-M has no effect on apoptosis triggered by IR or Fas. In Dex-resistant cells, Dex does not trigger either RAFTK activation or apoptosis. Finally, interleukin-6 (IL-6), a known survival factor for MM cells, inhibits both activation of RAFTK and apoptosis of MM.1S cells triggered by Dex. Our studies therefore demonstrate Dex-induced RAFTK-dependent, and IR or Fas induced RAFTK-independent apoptotic signaling cascades in MM cells. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Inst Med, Beth Israel Deaconess Med Ctr, Div Expt Med & Hematol Oncol, Boston, MA 02115 USA. Northwestern Univ, Sch Med, Robert H Lurie Canc Ctr, Chicago, IL 60611 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02215 USA. FU NCI NIH HHS [CA50947, CA75216]; NHLBI NIH HHS [HL55445] NR 31 TC 84 Z9 85 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 18 PY 1999 VL 18 IS 48 BP 6733 EP 6740 DI 10.1038/sj.onc.1203082 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 257QA UT WOS:000083792000015 PM 10597281 ER PT J AU Michaels, AD Maynard, C Every, NR Barron, HV AF Michaels, AD Maynard, C Every, NR Barron, HV CA Natl Registry Myocardial Infarctio TI Early use of ACE inhibitors in the treatment of acute myocardial infarction in the United States: Experience from the National Registry of Myocardial Infarction 2 SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CONVERTING ENZYME-INHIBITORS; DIABETIC NEPHROPATHY; THERAPY; MORTALITY; GUIDELINES; ENALAPRIL; CAPTOPRIL; SURVIVAL; AGE AB This study was undertaken to examine recent trends in the use of angiotensin-converting enzyme (ACE) inhibitors within 24 hours of admission in patients hospitalized for acute myocardial infarction (AMI) and to identify clinical factors associated with ACE inhibitor-prescribing patterns, Demographic, procedural, and acute medication use from 202,438 patients with AMI were collected at 1,470 US hospitals participating in the National Registry of Myocardial Infarction 2 from June 1994 through June 1996, Acute ACE inhibitor use increased from 14.0% in 1994 to 17.3% in 1996, After controlling for all important clinical variables, we found that there was a significant increase in the odds of acute ACE inhibitor treatment over time (odds ratio [OR]1.07 for each 180-day period; 95% confidence intervals [CI] 1.06 to 1.08; p < 0.0001), Univariate data suggested that patients treated acutely with ACE inhibitors tended to be older (70.9 vs 67.2 years) and had lower rates of in-hospital mortality (8.8% vs 11.0%). Independent predictors of receiving an ACE inhibitor acutely included anterior wall infarction (OR 1.36; 95% CI 1.32 to 1.40), Killip class 2 or 3 (OR 1.77; 95% CI 1.72 to 1.83), prior myocardial infarction (OR 1.33; 95% CI 1.30 to 1.37), prior history of congestive heart failure (OR 1.88; 95% CI 1.82 to 1.95), and diabetes mellitus (OR 1.34; 95% CI 1.30 to 1.38). Physicians are prescribing ACE inhibitors acutely in patients with AMI with increasing frequency. patients with evidence of congestive heart failure and those with anterior myocardial infarction have the greatest expected benefit from such therapy, and these persons receive such treatment most often. However, most patients hospitalized with AAAI do not receive this potentially life-saving therapy. (C) 1999 by Excerpta Medico, Inc. C1 Univ Calif San Francisco, Med Ctr, Div Cardiol, Moffitt Hosp, San Francisco, CA 94143 USA. VA Puget Sound Healthcare Syst, Seattle, WA USA. Genentech Inc, S San Francisco, CA 94080 USA. RP Michaels, AD (reprint author), Univ Calif San Francisco, Med Ctr, Div Cardiol, Moffitt Hosp, 505 Parnassus Ave,11th Floor,Box 0124, San Francisco, CA 94143 USA. RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 28 TC 9 Z9 9 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 15 PY 1999 VL 84 IS 10 BP 1176 EP 1181 DI 10.1016/S0002-9149(99)00530-5 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 253AP UT WOS:000083534700006 PM 10569326 ER PT J AU Garg, HG Joseph, PAM Thompson, BT Hales, CA Toida, T Imanari, T Capila, I Linhardt, RJ AF Garg, HG Joseph, PAM Thompson, BT Hales, CA Toida, T Imanari, T Capila, I Linhardt, RJ TI Effect of fully sulfated glycosaminoglycans on pulmonary artery smooth muscle cell proliferation SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE chemical sulfonation; glycosaminoglycans; smooth muscle cell; proliferation ID CHONDROITIN SULFATE; STRUCTURAL DETERMINANTS; ANTICOAGULANT ACTIVITY; MOLECULAR-WEIGHT; DERMATAN SULFATE; MAST-CELLS; HEPARIN; HYPERTENSION; PROTEOGLYCANS; FIBROBLASTS AB Fully sulfated heparin and other glycosaminogly-cans, namely heparan, chondroitin, and dermatan sulfates, and hyaluronan have been prepared by using sulfur trioxide under mild chemical conditions. All these derivatives were assayed for antiproliferative activity on cultured bovine pulmonary artery smooth muscle cells (BPASMCs). No appreciable difference was found between heparin and fully sulfated heparin, Chondroitin and dermatan sulfates actually stimulated BPASMCs growth but full sulfonation made them strongly antiproliferative. Native hyaluronan was not antiproliferative but became strongly so after sulfonation. Neither acharan sulfate nor N-sulfoacharan sulfate had any antiproliferative activity. This suggests that O-sulfonation of the polysaccharide is critical for antiproliferative activity, whereas N-sulfonation of glucosamine residues is not. (C) 1999 Academic Press. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm Crit Care Unit, Boston, MA 02114 USA. Chiba Univ, Fac Pharmaceut Sci, Chiba 263, Japan. Univ Iowa, Dept Chem, Div Med & Nat Prod Chem, Iowa City, IA 52242 USA. Univ Iowa, Dept Chem & Biochem Engn, Iowa City, IA 52242 USA. RP Garg, HG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm Res Labs, 13th St,Bldg 149, Charlestown, MA 02129 USA. NR 34 TC 28 Z9 28 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD NOV 15 PY 1999 VL 371 IS 2 BP 228 EP 233 DI 10.1006/abbi.1999.1456 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 256LC UT WOS:000083725900011 PM 10545209 ER PT J AU Grader-Beck, T Berezovskaya, A Nadler, LM Boussiotis, VA AF Grader-Beck, T Berezovskaya, A Nadler, LM Boussiotis, VA TI Downregulation of intracellular cyclic-amp is responsible for activation of p70s6 kinase by CD28 costimulation. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4 BP 4A EP 5A PN 1 PG 2 WC Hematology SC Hematology GA 257PH UT WOS:000083790300053 ER PT J AU Ghia, P Trasidico, P Veiga, JP Stroia, G Mantovani, A Caligaris-Cappio, F Nadler, LM Cardoso, AA AF Ghia, P Trasidico, P Veiga, JP Stroia, G Mantovani, A Caligaris-Cappio, F Nadler, LM Cardoso, AA TI Expression of the chemokines MDC and TARC by B-cells deciphers mechanisms of T-cell attraction in B-cell/T-cell cross-talk. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Turin, Turin, Italy. Ist Mario Negri, Milan, Italy. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 9 BP 6A EP 6A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300058 ER PT J AU von Bergwelt-Baildon, MS Maecker, B Bedor, MM Schnipper, DR Vonderheide, RH Nadler, LM Schultze, JL AF von Bergwelt-Baildon, MS Maecker, B Bedor, MM Schnipper, DR Vonderheide, RH Nadler, LM Schultze, JL TI Visualization of MHC/peptide complexes on primary antigen presenting cells: Implications for cellular immunotherapy. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 20 BP 8A EP 8A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300069 ER PT J AU van den Brink, MRM Pratt, JC Igras, VE Walk, SF Ravichandran, KS Burakoff, SJ AF van den Brink, MRM Pratt, JC Igras, VE Walk, SF Ravichandran, KS Burakoff, SJ TI Requirement for SHC in T cell antigen receptor-mediated activation of a T cell hybridoma. SO BLOOD LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Virginia, Charlottesville, VA 22903 USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 23 BP 9A EP 9A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300072 ER PT J AU Wang, F Wu, E Wiederschain, D Anderson, I Moses, M Shipp, M AF Wang, F Wu, E Wiederschain, D Anderson, I Moses, M Shipp, M TI The coculture of diffuse large B-cell lymphomas with normal stromal cells augments the release of bioactive bFGF: Implications for tumor angiogenesis. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 37 BP 12A EP 12A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300086 ER PT J AU Goepfert, C Buhler, L Alwayn, I Basker, M Imai, M Tsai, HM Sachs, DH Cooper, DKC Sackstein, R Robson, SC AF Goepfert, C Buhler, L Alwayn, I Basker, M Imai, M Tsai, HM Sachs, DH Cooper, DKC Sackstein, R Robson, SC TI Thrombotic thrombocytopenic purpura following peripheral blood progenitor cell xenotransplantation occurs independently of aberrant vWF multimer proteolysis. SO BLOOD LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, TBRC, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, IRC, Boston, MA USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 42 BP 13A EP 13A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300091 ER PT J AU Glaspy, J Demetri, G Cremieux, P AF Glaspy, J Demetri, G Cremieux, P TI Does baseline endogenous erythropoietin level impact hemoglobin (Hb) response to r-HuEPO in cancer patients? SO BLOOD LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Anal Grp Econ, Cambridge, MA USA. Univ Quebec, Montreal, PQ H3C 3P8, Canada. NR 0 TC 1 Z9 1 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3210 BP 15B EP 15B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790700054 ER PT J AU Nisbet-Brown, E AF Nisbet-Brown, E CA Thalassemia Clinical Res Grp TI Thalassemia syndromes in North America: Demographic and selected clinical characteristics. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3301 BP 34B EP 34B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790700145 ER PT J AU Schultz, S Harris, KW AF Schultz, S Harris, KW TI The erythropoietin receptor WSXWS motif regulates correct receptor folding and secretion in yeast by stabilization of the second cytokine receptor module. SO BLOOD LA English DT Meeting Abstract C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Div Hematol, San Antonio, TX USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 190 BP 45A EP 45A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300239 ER PT J AU Kussick, SJ Chinery, R Tkachuk, DC AF Kussick, SJ Chinery, R Tkachuk, DC TI Leukemia-associated HRX fusion proteins inhibit p53-dependent apoptosis transcriptional activity. SO BLOOD LA English DT Meeting Abstract C1 Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Sch Med, Dept Lab Med, Seattle, WA 98195 USA. Vanderbilt Univ, Med Ctr, Dept Cell Biol, Nashville, TN USA. Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 219 BP 52A EP 52A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300268 ER PT J AU Wu, DY Krumm, A Schubach, WH AF Wu, DY Krumm, A Schubach, WH TI In vivo promoter targeting of the human SWI/SNF complex by Epstein-Barr nuclear protein EBNA2. SO BLOOD LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 235 BP 55A EP 55A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300284 ER PT J AU Grandori, C Coller, H Tamayo, P Lander, ES Eisenman, R Golub, TR AF Grandori, C Coller, H Tamayo, P Lander, ES Eisenman, R Golub, TR TI Identifying MYC target genes using oligonucleotide microarrays. SO BLOOD LA English DT Meeting Abstract C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Whitehead Inst, Cambridge, MA 02142 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 253 BP 59A EP 59A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300302 ER PT J AU Johansen, LM Iwama, A Golub, TR Tenen, DG AF Johansen, LM Iwama, A Golub, TR Tenen, DG TI c-myc is a critical target for C/EBP alpha in granulopoiesis. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. Harvard Univ, Inst Med, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 1 Z9 1 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 252 BP 59A EP 59A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300301 ER PT J AU Dessain, SK Peters, DG Yu, HY Weinberg, RA Daley, GQ AF Dessain, SK Peters, DG Yu, HY Weinberg, RA Daley, GQ TI Cooperation of the c-myc oncogene with bcr/abl in the transformation of a murine embryonic hematopoietic stem cell line. SO BLOOD LA English DT Meeting Abstract C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 256 BP 60A EP 60A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300305 ER PT J AU Heinrich, M Zigler, A Griffith, D Druker, B Wait, C Ott, K AF Heinrich, M Zigler, A Griffith, D Druker, B Wait, C Ott, K TI Selective pharmacological inhibition of wild type and mutant c-kit receptor tyrosine kinase activity in hematopoietic cells. SO BLOOD LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Div Hematol Med Oncol, Portland, OR 97201 USA. Portland VA Med Ctr, Div Hematol, Portland, OR USA. RI zigler, arie/C-2667-2012 NR 0 TC 1 Z9 1 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 265 BP 62A EP 62A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300314 ER PT J AU Vonderheide, RH Dutcher, J Eckhardt, G Gribben, JG Perry, V Caron, D Ghalie, R AF Vonderheide, RH Dutcher, J Eckhardt, G Gribben, JG Perry, V Caron, D Ghalie, R TI Phase I study of RhuCD40 ligand (RhuCD40L) in cancer patients. SO BLOOD LA English DT Meeting Abstract C1 Our Lady Mercy Canc Ctr, Bronx, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. Immunex Res & Dev Corp, Seattle, WA 98101 USA. NR 0 TC 1 Z9 1 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 270 BP 63A EP 63A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300319 ER PT J AU Armitage, R Ulrich, D Macduff, B Vonderheide, RH Dutcher, J Eckhardt, G Gribben, JG Perry, V Bell, A Caron, D Ghalie, R Fanslow, W AF Armitage, R Ulrich, D Macduff, B Vonderheide, RH Dutcher, J Eckhardt, G Gribben, JG Perry, V Bell, A Caron, D Ghalie, R Fanslow, W TI Analysis of circulating mononuclear cell, antibody and cytokine levels in phase I cancer patients treated with recombinant human CD40 ligand (AVREND (TM)). SO BLOOD LA English DT Meeting Abstract C1 Immunex Res & Dev Corp, Seattle, WA 98101 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Our Lady Mercy Canc Ctr, Bronx, NY USA. Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 284 BP 66A EP 66A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300333 ER PT J AU Lin, CW Manshouri, T Neuberg, D Patel, K Gidel, C Kantarjian, H Andreeff, M Estrov, Z Beran, M Keating, M Estey, E Albitar, M AF Lin, CW Manshouri, T Neuberg, D Patel, K Gidel, C Kantarjian, H Andreeff, M Estrov, Z Beran, M Keating, M Estey, E Albitar, M TI Proliferation and apoptosis in leukemias and myelodysplasia as measured by PCNA level and caspase-3 activity. SO BLOOD LA English DT Meeting Abstract C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 296 BP 69A EP 69A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300345 ER PT J AU Barata, JT Cardoso, AA Donovan, J Nadler, LM Boussiotis, VA AF Barata, JT Cardoso, AA Donovan, J Nadler, LM Boussiotis, VA TI Identification of molecular targets regulating growth of childhood T cell leukemia by IL-4 and IL-7. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 304 BP 70A EP 70A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300353 ER PT J AU Durante, W Liao, L Reyna, SV Peyton, KJ Schafer, AI AF Durante, W Liao, L Reyna, SV Peyton, KJ Schafer, AI TI Transforming growth factor-beta 1 stimulates L-arginine transport and metabolism in vascular smooth muscle cells: Role in arterial remodeling. SO BLOOD LA English DT Meeting Abstract C1 Houston VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3478 BP 72B EP 72B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790700322 ER PT J AU Price, TH Kuter, DJ AF Price, TH Kuter, DJ TI Stimulation of platelet production - Clinical experience SO BLOOD LA English DT Meeting Abstract C1 Puget Sound Blood Ctr, Seattle, WA 98104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 BP 75 EP 76 PN 1 PG 2 WC Hematology SC Hematology GA 257PH UT WOS:000083790300043 ER PT J AU Cardoso, AA Alves, P Veiga, P Haininh, WN Afonso, H Sallan, SE Golub, T Nadler, LM AF Cardoso, AA Alves, P Veiga, P Haininh, WN Afonso, H Sallan, SE Golub, T Nadler, LM TI Immunity to the fusion gene TEL-AML1 represents only a part of the overall anti-leukemia T-cell mediated immunity generated in TEL-AML1(+) patients. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 332 BP 76A EP 76A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300381 ER PT J AU Sackstein, R Fuhlbrigge, R AF Sackstein, R Fuhlbrigge, R TI A novel method for investigation of cellular adhesive interactions with immobilized ligands under flow conditions. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Skin Dis Res Ctr,Dept Med, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3496 BP 76B EP 76B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790700340 ER PT J AU Galardy, PJ McMahon, LE Reininger, AJ Grabowski, EF AF Galardy, PJ McMahon, LE Reininger, AJ Grabowski, EF TI Adherent sickle erythrocytes augment tissue factor production by IL-1-stimulated endothelial cells. SO BLOOD LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Pediat Hematol Oncol Unit, Boston, MA 02114 USA. Boston Med Ctr, Div Pediat Hematol Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3554 BP 88B EP 88B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790700398 ER PT J AU Vose, JM Link, BK Grossbard, ML Fisher, RI Czuczman, M Grillo-Lopez, A Gilman, P Lowe, A Kunkel, LA AF Vose, JM Link, BK Grossbard, ML Fisher, RI Czuczman, M Grillo-Lopez, A Gilman, P Lowe, A Kunkel, LA TI Phase II study of rituximab in combination with CHOP chemotherapy in patients with previously untreated intermediate- or high-grade non-Hodgkin's lymphoma (NHL). SO BLOOD LA English DT Meeting Abstract C1 Univ Nebraska, Omaha, NE 68182 USA. Univ Iowa, Iowa City, IA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Loyola Univ, Maywood, IL 60153 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Idec Pharmaceut Corp, San Diego, CA USA. Genentech Inc, S San Francisco, CA USA. NR 0 TC 17 Z9 17 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 388 BP 89A EP 89A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300437 ER PT J AU Grossbard, ML Blankenberg, F Beaulieu, CF Stagg, R Chang, J Tidmarsh, G Kroll, S Swinnen, L AF Grossbard, ML Blankenberg, F Beaulieu, CF Stagg, R Chang, J Tidmarsh, G Kroll, S Swinnen, L TI Masked independent randomized radiology and oncology (MIRROR) review panel assessment of response in phase III trial of iodine I 131 tositumomab. SO BLOOD LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Stanford Univ, Palo Alto, CA 94304 USA. Coulter Pharmaceut Inc, S San Francisco, CA USA. Loyola Univ, Maywood, IL 60153 USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 398 BP 91A EP 91A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300447 ER PT J AU Suzuki, S Hanada, S Ishitsuka, K Uozumi, K Utsunomiya, A Ohno, N Arima, T Takahashi, H AF Suzuki, S Hanada, S Ishitsuka, K Uozumi, K Utsunomiya, A Ohno, N Arima, T Takahashi, H TI Peripheral blood lymphocytes from patients with adult T-cell leukemia in remission induce apoptosis to HTLV-1 infected T-cell line by activation with chimeric SF-25 monoclonal antibody. SO BLOOD LA English DT Meeting Abstract C1 Kagoshima Univ, Dept Internal Med 2, Kagoshima 890, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, GI Unit, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 430 BP 98A EP 98A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300479 ER PT J AU Smith, KM Van Etten, RA AF Smith, KM Van Etten, RA TI A novel conditional mutant of the Bcr/Abl tyrosine kinase using a chemical inducer of dimerization. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 446 BP 102A EP 102A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300495 ER PT J AU Treon, SP Shima, Y Raje, N Tai, YT Hideshima, T Chauhan, D Grossbard, ML Preffer, FI Doss, S Schlossman, R Szczepek, R Belch, AR Pilarski, LM Anderson, KC AF Treon, SP Shima, Y Raje, N Tai, YT Hideshima, T Chauhan, D Grossbard, ML Preffer, FI Doss, S Schlossman, R Szczepek, R Belch, AR Pilarski, LM Anderson, KC TI Interferon-gamma induces CD20 expression on multiple myeloma cells via induction of Pu.1 and augments rituximab binding to myeloma cells. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Alberta, Cross Canc Ctr, Edmonton, AB, Canada. NR 0 TC 9 Z9 9 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 521 BP 119A EP 119A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300570 ER PT J AU Treon, SP Raje, N Tai, YT Hideshima, T Shima, Y Davies, FE Hilgers, J Hoffman, P Anderson, KC AF Treon, SP Raje, N Tai, YT Hideshima, T Shima, Y Davies, FE Hilgers, J Hoffman, P Anderson, KC TI Expression of MUC-1 core protein on multiple myeloma plasma cells permits binding to ICAM-1. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Vrije Univ Amsterdam, NL-1081 HV Amsterdam, Netherlands. ICOS Pharmaceut, Bothell, WA USA. NR 0 TC 1 Z9 1 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 533 BP 121A EP 121A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300582 ER PT J AU Raje, N Hideshima, T Teoh, G Shima, Y Davies, FE Chauhan, D Treon, SP Tai, YT Schlossman, RL Avigan, D Gong, J Kufe, DW Anderson, KC AF Raje, N Hideshima, T Teoh, G Shima, Y Davies, FE Chauhan, D Treon, SP Tai, YT Schlossman, RL Avigan, D Gong, J Kufe, DW Anderson, KC TI Multiple Myeloma/Dendritic cell fusions as a vaccination strategy for myeloma. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 538 BP 123A EP 123A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300587 ER PT J AU Shima, Y Treon, SP Yoshizaki, K Tai, YT Hideshima, T Raje, N Chauhan, D Davies, F Schlossman, R Anderson, KC AF Shima, Y Treon, SP Yoshizaki, K Tai, YT Hideshima, T Raje, N Chauhan, D Davies, F Schlossman, R Anderson, KC TI Clinical and biological activity of thalidomide (Thal) in multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Osaka Univ, Sch Hlth & Sports Sci, Osaka, Japan. NR 0 TC 11 Z9 11 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 549 BP 125A EP 125A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300598 ER PT J AU Rebel, VI Hartnett, S Hill, GR Lazo-Kallanian, SB Ferrara, JLM Sieff, CA AF Rebel, VI Hartnett, S Hill, GR Lazo-Kallanian, SB Ferrara, JLM Sieff, CA TI Signaling through the p55-TNF receptor is essential in regulating hematopoiesis at a stem cell level. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3759 BP 133B EP 133B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790700603 ER PT J AU Webb, IJ Weller, E Gribben, JG Freedman, A Soiffer, RJ Antin, JH Ritz, J AF Webb, IJ Weller, E Gribben, JG Freedman, A Soiffer, RJ Antin, JH Ritz, J TI CD34+cell, CFU-GM and nucleated cell dose predict engraftment but not survival following autologous purged bone marrow transplantation (BMT), yet do not predict outcomes following CD6+T cell depleted allogeneic BMT. SO BLOOD LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 647 BP 147A EP 147A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300696 ER PT J AU Tsai, TW Patterson, JE Przykucki, J Callander, N Anderson, J Alsina, M Cruz, J Baltathakis, I Freytes, CO AF Tsai, TW Patterson, JE Przykucki, J Callander, N Anderson, J Alsina, M Cruz, J Baltathakis, I Freytes, CO TI Prospective study evaluating the incidence and clinical outcome of vancomycin-resistant enterococcus (VRE) colonization and infection in stem cell transplant patients. SO BLOOD LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 659 BP 150A EP 150A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300708 ER PT J AU Antin, JH Weisdorf, D Neuberg, D Bressler, S Nicklow, R Lee, SJ Alyea, E McGarigle, C Soiffer, R Ferrara, J AF Antin, JH Weisdorf, D Neuberg, D Bressler, S Nicklow, R Lee, SJ Alyea, E McGarigle, C Soiffer, R Ferrara, J TI Interleukin-1 block ide does not prevent acute graft versus host disease (GVHD). Results of a randomized, double blind, placebo-controlled trial of interleukin 1 receptor antagonist (IL-1RA). SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Minnesota, Minneapolis, MN USA. NR 0 TC 4 Z9 4 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 664 BP 152A EP 152A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300713 ER PT J AU Kwiatkowski, BA Zielinska-Kwiatkowska, AG Hickstein, DD AF Kwiatkowski, BA Zielinska-Kwiatkowska, AG Hickstein, DD TI Transfer of Tel into the acute lymphoblastic leukemia cell line REH results in increased expression of Bax and decreased cell survival. SO BLOOD LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Sch Med, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3876 BP 157B EP 157B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790700720 ER PT J AU Shimamura, A Ballif, BA Richards, SA Blenis, J AF Shimamura, A Ballif, BA Richards, SA Blenis, J TI The MAP kinase target RSK1 promotes cell survival and phosphorylates bad. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3890 BP 160B EP 160B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790700734 ER PT J AU Alyea, EP Canning, CM Houde, H Soiffer, RJ Giralt, S Webb, IJ Donovan, J Gee, A Gribben, J Champlin, R Atkinson, K AF Alyea, EP Canning, CM Houde, H Soiffer, RJ Giralt, S Webb, IJ Donovan, J Gee, A Gribben, J Champlin, R Atkinson, K TI A pilot study of CD8+cell depletion of donor lymphocyte infusions (DLI) using CD8 monoclonal antibody coated high density microparticles (HDM). SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Eligix Inc, Medford, MA USA. NR 0 TC 1 Z9 1 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 707 BP 161A EP 161A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300756 ER PT J AU Orsini, E Chillemi, A McLaughlin, S Alyea, EP Schlossman, R Anderson, KC Ritz, J AF Orsini, E Chillemi, A McLaughlin, S Alyea, EP Schlossman, R Anderson, KC Ritz, J TI Conversion to full donor chimerism is associated with disease response in patients with multiple myeloma following donor lymphocyte infusion. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 709 BP 162A EP 162A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300758 ER PT J AU Goff, JP Shields, DS Meuller, S Glowacki, J Greenberger, JS AF Goff, JP Shields, DS Meuller, S Glowacki, J Greenberger, JS TI Matrix and growth factors promote adherence, proliferation, and osteoblastic differentiation of single STRO-1+cells. SO BLOOD LA English DT Meeting Abstract C1 Univ Pittsburgh, Dept Radiat Oncol, Pittsburgh, PA USA. Brigham & Womens Hosp, Dept Orthoped, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3908 BP 164B EP 164B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790700752 ER PT J AU Hamada, M Yakushijin, Y Shipp, MA Yasukawa, M Fujita, S AF Hamada, M Yakushijin, Y Shipp, MA Yasukawa, M Fujita, S TI Chromosome checkpoint gene BTAK/STK15 is associated with transformation and clinical outcome in B-cell non-Hodgkin's lymphoma. SO BLOOD LA English DT Meeting Abstract C1 Ehime Univ, Sch Med, Dept Internal Med 1, Matsuyama, Ehime 790, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3998 BP 183B EP 183B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790700842 ER PT J AU Cremieux, P Barrett, B Anderson, K AF Cremieux, P Barrett, B Anderson, K TI Cost of outpatient blood transfusion in cancer patients. SO BLOOD LA English DT Meeting Abstract C1 Anal Grp Econ, Cambridge, MA USA. Univ Quebec, Montreal, PQ H3C 3P8, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 803 BP 184A EP 184A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300852 ER PT J AU Moller, MB Kania, PW Ino, Y Gerdes, AM Neilsen, O Louis, DN Skjodt, K Pedersen, NT AF Moller, MB Kania, PW Ino, Y Gerdes, AM Neilsen, O Louis, DN Skjodt, K Pedersen, NT TI Disruption of RB1 and/or p53 pathways in the majority of diffuse large B-cell lymphomas: Cyclin D3 and p16(INK4A) alterations are mutually exclusive. SO BLOOD LA English DT Meeting Abstract C1 Odense Univ, Univ So Denmark, Dept Pathol, DK-5230 Odense M, Denmark. Odense Univ, Univ So Denmark, Dept Clin Genet, DK-5230 Odense, Denmark. Odense Univ, Univ So Denmark, Dept Immunol & Microbiol, DK-5230 Odense M, Denmark. Massachusetts Gen Hosp, Mol Neurooncol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RI Moller, Michael/G-8340-2016 OI Moller, Michael/0000-0003-2041-3630 NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4003 BP 184B EP 184B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790700847 ER PT J AU Earle, C Menzin, J Lang, K Berger, M Mallick, R AF Earle, C Menzin, J Lang, K Berger, M Mallick, R TI Validating the use of administrative claims data for assessing cancer relapse: The case of acute myeloid leukemia (AML). SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Boston Hlth Econ, Billerica, MA USA. Wyeth Ayerst Res, Radnor, PA USA. NR 0 TC 2 Z9 2 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 807 BP 185A EP 185A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300856 ER PT J AU McCarthy, P Hahn, T Kulikov, S Paltiel, O Drozdova, V Tichonova, L Shmatina, N Moysich, K Weinstein, H AF McCarthy, P Hahn, T Kulikov, S Paltiel, O Drozdova, V Tichonova, L Shmatina, N Moysich, K Weinstein, H TI International leukemia diagnostic working group (LDWG) verification of acute leukemia (AL) cases in Belarus, Russia and Ukraine. SO BLOOD LA English DT Meeting Abstract C1 Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Natl Hematol Res Ctr, Moscow, Russia. Hadassah Med Ctr, IL-91120 Jerusalem, Israel. Pediat Hematol Ctr, Kiev, Ukraine. Hosp 9, Minsk, Byelarus. Massachusetts Gen Hosp, Boston, MA 02114 USA. Int Consortium Res Hlth Effects Radiat, Annapolis, MD USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4190 BP 221B EP 221B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701034 ER PT J AU Grabowski, EF Reininger, AJ Tsukarov, O Petteruti, PG Orkin, R AF Grabowski, EF Reininger, AJ Tsukarov, O Petteruti, PG Orkin, R TI Shear stress diminishes the functional, but not the antigenic, expression of tissue factor by cultured vascular endothelial cells while augmenting the production of tissue factor pathway inhibitor. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 990 BP 224A EP 224A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301039 ER PT J AU Tallman, MS Lee, S Oken, MM Cassileth, PA Bennett, JM Wiernik, PH Rowe, JM AF Tallman, MS Lee, S Oken, MM Cassileth, PA Bennett, JM Wiernik, PH Rowe, JM TI Duration of second complete remission compared with first complete remission in patients with acute myeloid leukemia. SO BLOOD LA English DT Meeting Abstract C1 Northwestern Univ, Sch Med, Chicago, IL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Virginia Piper Canc Inst, Minneapolis, MN USA. Univ Miami, Sch Med, Miami, FL USA. Univ Rochester, Ctr Canc, Rochester, NY USA. New York Med Coll, OLM Canc Ctr, Bronx, NY USA. Rambam Med Ctr, Haifa, Israel. ECOG, Brookline, MA USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4205 BP 224B EP 224B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701049 ER PT J AU Lee, BC Cheng, T Olszak, I Hancock, J Garcia-Zepeda, EA Luster, AD Scadden, DT AF Lee, BC Cheng, T Olszak, I Hancock, J Garcia-Zepeda, EA Luster, AD Scadden, DT TI SC-GPR1, a functional G protein-coupled receptor expressed on quiescent hematopoietic stem cells. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr AIDS Res, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Infect Dis Unit, Charlestown, MA USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1110 BP 251A EP 251A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301159 ER PT J AU Cheng, T Rodrigues, N Shen, H Yang, YG Dombkowski, D Sykes, M Scadden, DT AF Cheng, T Rodrigues, N Shen, H Yang, YG Dombkowski, D Sykes, M Scadden, DT TI Hematopoietic stem cell quiescence in vivo is maintained by p21(clp1/waf1) and is critical for preventing premature exhaustion of hematopoiesis. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc,AIDS Res Ctr, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1119 BP 253A EP 253A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301168 ER PT J AU Dimitroff, CJ Schor, K Grove, G Lee, J Watts, J Sackstein, R AF Dimitroff, CJ Schor, K Grove, G Lee, J Watts, J Sackstein, R TI Novel L-selectin ligand activity with unique biophysical characteristics on hematopoietic progenitor cells. SO BLOOD LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Med Sch, Harvard Skin Dis Res Ctr, Boston, MA USA. NR 0 TC 1 Z9 1 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1132 BP 255A EP 255A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301181 ER PT J AU Kwiatkowski, BA Zielinska-Kwiatkowska, AG Hickstein, DD AF Kwiatkowski, BA Zielinska-Kwiatkowska, AG Hickstein, DD TI The ETS factor Tel inhibits proliferation of K562 cells by downregulation of the cyclin D3. SO BLOOD LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1155 BP 260A EP 260A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301204 ER PT J AU Duarte, RF Frank, DA AF Duarte, RF Frank, DA TI SCF and G-CSF lead to the synergistic induction of gene expression through the activation of STATs and complementary signaling pathways. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1170 BP 263A EP 263A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301219 ER PT J AU Shaun, N Thomas, B Glassford, J Banerji, L van der Sman, J Scinsinski, P Klaus, GGB Lam, EWF AF Shaun, N Thomas, B Glassford, J Banerji, L van der Sman, J Scinsinski, P Klaus, GGB Lam, EWF TI Cyclin D3 is induced and compensates for loss of cyclin D2 in mouse primary B-lymphocytes following stimulation via antigen receptor and CD40. SO BLOOD LA English DT Meeting Abstract C1 Royal Free & UC Med Sch, Dept Haematol, London NW3 2QG, England. Univ London Imperial Coll Sci Technol & Med, Virol & Cell Biol Sect, London, England. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NIMR, London, England. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1197 BP 269A EP 269A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301246 ER PT J AU Inukai, T Inaba, T Goi, K Sugita, K Look, T Nakazawa, S AF Inukai, T Inaba, T Goi, K Sugita, K Look, T Nakazawa, S TI Thyrotroph embryonic factor (TEF) is a possible regulatory factor maintaining the quiescent hematopoietic progenitors. SO BLOOD LA English DT Meeting Abstract C1 Yamanashi Med Univ, Dept Pediat, Yamanashi, Japan. Jichi Med Sch, Dept Biol Mol, Tochigi, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1208 BP 271A EP 271A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301257 ER PT J AU Silverman, LB Dalton, VMK Zou, GY Su, JT Gelber, RD Schorin, M Moghrabi, A Asselin, B Sallan, SE AF Silverman, LB Dalton, VMK Zou, GY Su, JT Gelber, RD Schorin, M Moghrabi, A Asselin, B Sallan, SE TI Erwinia asparaginase is less toxic than E.coli asparaginase in children with acute lymphoblastic leukemia (ALL): Results from the Dana-Farber cancer institute ALL consortium. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Alton Ochsner Med Fdn & Ochsner Clin, New Orleans, LA 70121 USA. Hop St Justine, Montreal, PQ H3T 1C5, Canada. Univ Rochester, Rochester, NY USA. RI Zou, Guangyong/K-6408-2013 NR 0 TC 2 Z9 2 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1296 BP 290A EP 290A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301345 ER PT J AU Berenson, JR Webb, IJ Anderson, K Schlossman, R Vescio, R Doss, D Goon, B Swift, R VonTeichert, J Kowalski, M Seaman, J AF Berenson, JR Webb, IJ Anderson, K Schlossman, R Vescio, R Doss, D Goon, B Swift, R VonTeichert, J Kowalski, M Seaman, J TI Single-agent Aredia for relapsed/refractory multiple myeloma. SO BLOOD LA English DT Meeting Abstract C1 W LA VA Med Ctr, Los Angeles, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Novartis Pharmaceut Corp, Clin Res, E Hanover, NJ USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4601 BP 307B EP 307B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701445 ER PT J AU Liou, R Stone, RM AF Liou, R Stone, RM TI The histone deacetylase inhibitor trichostatin A (TSA) potentiates 1,25 dihydroxy vitamin D3 (1,25 D3)-induced monocytic differentiation in human leukemic cells. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1377 BP 308A EP 308A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301426 ER PT J AU Flinn, IW Lee, S Bennett, JM Falkson, CI Flynn, P Pundaleeka, S Stadtmauer, E Schnell, F Tallman, M Rowe, JM AF Flinn, IW Lee, S Bennett, JM Falkson, CI Flynn, P Pundaleeka, S Stadtmauer, E Schnell, F Tallman, M Rowe, JM TI Phase II trial of fludarabine and cyclophosphamide (Flu/Cy) in patients with previously untreated chronic lymphocytic leukemia: An eastern cooperative oncology group study (E1997). SO BLOOD LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Rochester, Ctr Canc, Rochester, NY USA. Univ Pretoria, ZA-0002 Pretoria, South Africa. Metro Minnesota CCOP, St Louis Pk, MN USA. Joilet Oncol Hematol Associates, Joliet, IL USA. Univ Penn, Philadelphia, PA 19104 USA. Med Ctr Cent Georgia, Macon, GA USA. Northwestern Univ, Chicago, IL 60611 USA. Rambam Med Ctr, Haifa, Israel. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4610 BP 309B EP 309B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701454 ER PT J AU Treon, SP Grossbard, ML Doss, DS Schlossman, RL Ellman, L Preffer, FI Belch, AR Pilarski, LM Anderson, KC AF Treon, SP Grossbard, ML Doss, DS Schlossman, RL Ellman, L Preffer, FI Belch, AR Pilarski, LM Anderson, KC TI Phase II study of Rituximab in previously treated patients with multiple myeloma (MM): Progress report. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dana Farber Canc Inst, Boston, MA USA. Univ Alberta, Cross Canc Ctr, Edmonton, AB, Canada. NR 0 TC 4 Z9 4 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1398 BP 312A EP 313A PN 1 PG 2 WC Hematology SC Hematology GA 257PH UT WOS:000083790301447 ER PT J AU Andrews, D Sackstein, R Saidman, S Weymouth, D Preffer, F Colby, C Macfee, S Spitzer, T Sykes, M AF Andrews, D Sackstein, R Saidman, S Weymouth, D Preffer, F Colby, C Macfee, S Spitzer, T Sykes, M TI Analysis of donor erythropoiesis and recipient RBC isohemagglutinins in major ABO blood group mismatched recipients of a non-myeloablative bone marrow transplant regimen. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Blood Transfus Serv, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4639 BP 316B EP 316B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701483 ER PT J AU Gokmen, E Callander, N Alexander, J Morris, A Tsai, TW Rosen, DM Anderson, J Alsina, M Craig, F Holle, L Cruz, J Baltathakis, I Hilsenbeck, S Valley, A West, L Egorin, MJ Freytes, CO AF Gokmen, E Callander, N Alexander, J Morris, A Tsai, TW Rosen, DM Anderson, J Alsina, M Craig, F Holle, L Cruz, J Baltathakis, I Hilsenbeck, S Valley, A West, L Egorin, MJ Freytes, CO TI A phase I and pharmacokinetic study of paclitaxel incorporated into the "augmented" high-dose cyclophosphamide, carmustine and etoposide (CBV) as conditioning chemotherapy for autologous stem cell transplantation in patients with Hodgkin's and non-Hodgkin's lymphoma. SO BLOOD LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Maryland, Ctr Canc, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4656 BP 320B EP 320B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701500 ER PT J AU van den Brink, MRM Horndasch, KJ Teshima, T Ferrara, JLM Burakoff, SJ AF van den Brink, MRM Horndasch, KJ Teshima, T Ferrara, JLM Burakoff, SJ TI Differential use of Fas ligand and perforin effector pathways by donor T cells in graft-versus-host disease and graft-versus-leukemia. SO BLOOD LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Michigan, Ctr Canc, Bone Marrow Transplant Program, Ann Arbor, MI 48109 USA. RI teshima, takanori/G-1671-2012 NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1447 BP 324A EP 324A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301495 ER PT J AU Down, JD Chang, Q Sciortino, T Treter, S Harper, D Gray, HK Abraham, S Sachs, DH Cooper, DKC White-Scharf, ME AF Down, JD Chang, Q Sciortino, T Treter, S Harper, D Gray, HK Abraham, S Sachs, DH Cooper, DKC White-Scharf, ME TI Increase in primitive hematopoietic cell subsets in the blood of miniature swine mobilized by extended courses of porcine recombinant cytokines. SO BLOOD LA English DT Meeting Abstract C1 BioTransplant Inc, Charlestown, MA USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Charlestown, MA USA. NR 0 TC 1 Z9 1 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1471 BP 329A EP 329A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301519 ER PT J AU Cruz, JC Tsai, TW Callander, N Anderson, JE Alsina, M Holle, L Craig, F Baltathakis, I Freytes, CO AF Cruz, JC Tsai, TW Callander, N Anderson, JE Alsina, M Holle, L Craig, F Baltathakis, I Freytes, CO TI Paclitaxel is an effective agent for peripheral blood stem cell (PBSC) mobilization in patients (PTS) with hematologic malignancies. SO BLOOD LA English DT Meeting Abstract C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4729 BP 336B EP 337B PN 2 PG 2 WC Hematology SC Hematology GA 257PM UT WOS:000083790701573 ER PT J AU Gazitt, Y Callander, N Freytes, CO Shaughnessy, P Tsai, TW Alsina, M Anderson, JE Devore, P AF Gazitt, Y Callander, N Freytes, CO Shaughnessy, P Tsai, TW Alsina, M Anderson, JE Devore, P TI A randomized prospective study of peripheral blood stem cell (PBSC) mobilization with cyclophosphamide (CTX) in combination with G-CSF, GM-CSF, or sequential GM-CSF followed by G-CSF, in non-Hodgkin's lymphoma (NHL) patients. SO BLOOD LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Audie L Murphy Vet Adm Hosp, San Antonio, TX USA. Wilford Hall USAF Med Ctr, San Antonio, TX 78236 USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4736 BP 338B EP 338B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701580 ER PT J AU Lehmann, LE Whyte, EA Russell, JD Spencer, S McIntosh, K Guinan, EC AF Lehmann, LE Whyte, EA Russell, JD Spencer, S McIntosh, K Guinan, EC TI Cytomegalovirus antigen (CMV AG) screening to direct therapy for pediatric allogeneic stem cell transplant(alloSCT) patients at risk for CMV infection. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1521 BP 340A EP 340A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301569 ER PT J AU Tsai, TW Callander, N Anderson, JE Alsina, M Holle, L Craig, F Cruz, J Baltathakis, I Freytes, CO AF Tsai, TW Callander, N Anderson, JE Alsina, M Holle, L Craig, F Cruz, J Baltathakis, I Freytes, CO TI Prospective controlled study using paclitaxel for peripheral blood stem cell (PBSC) mobilization in patients with hematologic malignancies and solid tumors. SO BLOOD LA English DT Meeting Abstract C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. NR 0 TC 1 Z9 1 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4757 BP 342B EP 343B PN 2 PG 2 WC Hematology SC Hematology GA 257PM UT WOS:000083790701601 ER PT J AU LaCasce, A Neuberg, D Janosova, A Friedberg, J Freedman, A Nadler, L Stone, R AF LaCasce, A Neuberg, D Janosova, A Friedberg, J Freedman, A Nadler, L Stone, R TI Clonal karyotypic abnormalities after autologous bone marrow transplantation (ABMT) for non-Hodgkin's lymphoma (NHL) are common and not always associated with myelodysplastic syndrome (MDS). SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1538 BP 344A EP 344A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301586 ER PT J AU Chang, Q Sciortino, T Harper, D Gray, HK Fuchimoto, Y Huang, C Ferrera, V Hope, J Sachs, DH White-Scharf, ME Down, JD AF Chang, Q Sciortino, T Harper, D Gray, HK Fuchimoto, Y Huang, C Ferrera, V Hope, J Sachs, DH White-Scharf, ME Down, JD TI Enrichment of cytokine mobilized hematopoietic long-term repopulating cells by dendreon buoyant density separation in miniature swine. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Charlestown, MA USA. BioTransplant Inc, Charlestown, MA USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4770 BP 345B EP 345B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701614 ER PT J AU Desikan, R Salmon, S Anderson, K Kyle, R Crowley, J Barlogie, B AF Desikan, R Salmon, S Anderson, K Kyle, R Crowley, J Barlogie, B TI Planned melphalan-total body irradiation (MEL-TBI)-based allogeneic transplantation for multiple myeloma (MM) up to age 55: An intergroup experience (CALGB, ECOG and SWOG) under the auspices of the southwest oncology group (SWOG 9321). SO BLOOD LA English DT Meeting Abstract C1 Univ Arkansas Med Sci, Myeloma & Transplantat Res Ctr, Little Rock, AR 72205 USA. Arizona Canc Ctr, Tucson, AZ USA. Dana Farber, Boston, MA USA. Mayo Clin, Rochester, MN USA. SW Oncol Grp, Seattle, WA USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1546 BP 346A EP 346A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301594 ER PT J AU Kraus, A Spitzer, TR McAfee, S Sackstein, R Toh, H Multani, P Colby, C Preffer, F Saidman, S Dombkowski, D Weymouth, D Youssef, N Takedatsu, H Cox, B Evans, T Gribben, J Sykes, M AF Kraus, A Spitzer, TR McAfee, S Sackstein, R Toh, H Multani, P Colby, C Preffer, F Saidman, S Dombkowski, D Weymouth, D Youssef, N Takedatsu, H Cox, B Evans, T Gribben, J Sykes, M TI Graft-versus-leukemia effects, mixed chimerism and early T-cell reconstitution in two patients with advanced stage chronic lymphocytic leukemia after pone marrow transplantation with a novel nonmyeloablative conditioning regimen. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 1 Z9 1 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1558 BP 349A EP 349A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301606 ER PT J AU Kraus, A Spitzer, TR McAfee, S Sackstein, R Toh, H Multani, P Colby, C Saidman, S Weymouth, D Cox, B Youssef, N Takedatsu, H Sachs, DH Cosimi, AB Sykes, M AF Kraus, A Spitzer, TR McAfee, S Sackstein, R Toh, H Multani, P Colby, C Saidman, S Weymouth, D Cox, B Youssef, N Takedatsu, H Sachs, DH Cosimi, AB Sykes, M TI Association of anti-donor reactive cytotoxic T lymphocyte responses with marrow graft rejection following bone marrow transplantation (BMT) with a novel non-myeloablative conditioning regimen: Evidence for split tolerance in a patient with combined kidney and BMT. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1557 BP 349A EP 349A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301605 ER PT J AU Nisbet-Brown, E Denham, J Guinan, E Gribben, J Wagner, J Mulligan, R Sieff, C D'Andrea, A AF Nisbet-Brown, E Denham, J Guinan, E Gribben, J Wagner, J Mulligan, R Sieff, C D'Andrea, A TI Gene therapy of Fanconi Anemia: Correction of mitomycin C sensitivity in human bone marrow progenitor colonies using a VSV-G pseudotyped retrovirus vector. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Univ Minnesota, Dept Pediat, Minneapolis, MN USA. Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1624 BP 365A EP 365A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301673 ER PT J AU Weilbaecher, KN Motyckova, G Takemoto, C Horstmann, M Ding, HF Fisher, DE AF Weilbaecher, KN Motyckova, G Takemoto, C Horstmann, M Ding, HF Fisher, DE TI A helix-loop-helix transcription factor family links M-CSF signaling to osteoclast development. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1641 BP 369A EP 369A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301690 ER EF