FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Nguyen, QE Foster, CS AF Nguyen, QE Foster, CS TI Saving the vision of children with juvenile rheumatoid arthritis-associated uveitis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID THERAPY; IRIDOCYCLITIS; METHOTREXATE C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. NR 20 TC 17 Z9 19 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 7 PY 1998 VL 280 IS 13 BP 1133 EP 1134 DI 10.1001/jama.280.13.1133 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 124YR UT WOS:000076210800011 PM 9777803 ER PT J AU Cairncross, JG Ueki, K Zlatescu, MC Lisle, DK Finkelstein, DM Hammond, RR Silver, JS Stark, PC Macdonald, DR Ino, Y Ramsay, DA Louis, DN AF Cairncross, JG Ueki, K Zlatescu, MC Lisle, DK Finkelstein, DM Hammond, RR Silver, JS Stark, PC Macdonald, DR Ino, Y Ramsay, DA Louis, DN TI Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID TUMOR-SUPPRESSOR GENE; RECURRENT MALIGNANT GLIOMA; HUMAN BRAIN-TUMORS; HUMAN ASTROCYTOMAS; PCV CHEMOTHERAPY; ALLELIC LOSS; P53 GENE; 19Q; 1P; PROTEIN AB Background/Methods: Gliomas are common malignant neoplasms of the central nervous system, Among the major subtypes of gliomas, oligodendrogliomas are distinguished by their remarkable sensitivity to chemotherapy, with approximately two thirds of anaplastic (malignant) oligodendrogliomas responding dramatically to combination treatment with procarbazine, lomustine, and vincristine (termed PCV). Unfortunately, no clinical or pathologic feature of these tumors allows accurate prediction of their response to chemotherapy. Anaplastic oligodendrogliomas also are distinguished by a unique constellation of molecular genetic alterations, including coincident loss of chromosomal arms 1p and 19q in 50%-70% of tumors. We have hypothesized that these or other specific genetic changes might predict the response to chemotherapy and prognosis in patients with anaplastic oligodendrogliomas, Therefore, we have analyzed molecular genetic alterations involving chromosomes 1p, 10q, and 19q and the TP53 (on chromosome 17p) and CDKN2A (on chromosome 9p) genes, in addition to clinicopathologic features in 39 patients with anaplastic oligodendrogliomas for whom chemotherapeutic response and survival could be assessed. Results/Conclusions: Allelic loss (or loss of heterozygosity) of chromosome 1p is a statistically significant predictor of chemosensitivity, and combined loss involving chromosomes 1p and 19q is statistically significantly associated with both chemosensitivity and longer recurrence-free survival after chemotherapy. Moreover, in both univariate and multivariate analyses, losses involving both chromosomes 1p and 19q were strongly associated with longer overall survival, whereas CDKN2A gene deletions and ring enhancement (i.e., contrast enhancement forming a rim around the tumor) on neuroimaging were associated with a significantly worse prognosis. The inverse relationship between CDKN2A gene deletions and losses of chromosomes Ip and 19q further implies that these differential clinical behaviors reflect two independent genetic subtypes of anaplastic oligodendroglioma. These results suggest that molecular genetic analysis may aid therapeutic decisions and predict outcome in patients with anaplastic oligodendrogliomas. C1 London Reg Canc Ctr, Dept Med Oncol, London, ON N6A 4L6, Canada. London Reg Canc Ctr, Dept Expt Oncol, London, ON N6A 4L6, Canada. Massachusetts Gen Hosp, Mol Neurooncol Lab, Dept Pathol & Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Biostat Grp, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Western Ontario, Dept Clin Neurol Sci, London, ON, Canada. Univ Western Ontario, Dept Pathol, London, ON, Canada. London Hlth Sci Ctr, London, ON, Canada. RP Louis, DN (reprint author), Massachusetts Gen Hosp, Mol Neurooncol Lab, CNY6,149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA57683, CA69285] NR 33 TC 970 Z9 998 U1 2 U2 26 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 OCT 7 PY 1998 VL 90 IS 19 BP 1473 EP 1479 DI 10.1093/jnci/90.19.1473 PG 7 WC Oncology SC Oncology GA 127QV UT WOS:000076362800013 PM 9776413 ER PT J AU Neri, G Gurrieri, F Zanni, G Lin, A AF Neri, G Gurrieri, F Zanni, G Lin, A TI Clinical and molecular aspects of the Simpson-Golabi-Behmel syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article; Proceedings Paper CT 7th Robert J Gorlin Conference on Dysmorphology CY OCT 25-26, 1997 CL MINNEAPOLIS, MINNESOTA SP Guilan Norouzi, Hassan Norouzi DE Simpson-Golabi-Behmel syndrome; SGBS; overgrowth; Wilms tumor; X-linkage ID OVERGROWTH SYNDROME; ROSEN SYNDROME; GENE; DYSPLASIA; GIGANTISM; FAMILIES; PERLMAN; GPC3 AB The Simpson-Golabi-Behmel syndrome (SGBS) is an overgrowth/multiple congenital anomalies/dysplasia syndrome caused by a mutant X-linked gene. The spectrum of its clinical manifestations is broad, varying from very mild forms in carrier females to infantile lethal forms in affected males. A typically affected male will show tall stature, "coarse" face, supernumerary nipples, congenital heart defect, and generalized muscular hypotonia, Mental development is normal in most cases. There is an increased risk of neoplasia in infancy, especially Wilms tumor. The SC;BS gene spans 500 kilobases in the Xq26 region and contains eight exons, It encodes an extracellular proteoglycan, designated glypican 3 (GPC3), capable of interacting with the insulin-like growth factor IGF2, At present, only deletions of various sizes have been found in at number of affected families. (C) 1998 Wiley-Liss, Inc. C1 Univ Cattolica, Ist Genet Med, Fac Med A Gemelli, I-00168 Rome, Italy. Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. RP Neri, G (reprint author), Univ Cattolica, Ist Genet Med, Fac Med A Gemelli, Largo F Vito 1, I-00168 Rome, Italy. RI Zanni, Ginevra/L-2869-2015; Gurrieri, Fiorella/K-3214-2016 OI Zanni, Ginevra/0000-0002-6367-1843; Gurrieri, Fiorella/0000-0002-6775-5972 NR 27 TC 115 Z9 118 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 2 PY 1998 VL 79 IS 4 BP 279 EP 283 DI 10.1002/(SICI)1096-8628(19981002)79:4<279::AID-AJMG9>3.0.CO;2-H PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 123KL UT WOS:000076124300009 PM 9781908 ER PT J AU Kumar, S Pandey, P Bharti, A Jin, SF Weichselbaum, R Weavers, D Kufe, D Kharbanda, S AF Kumar, S Pandey, P Bharti, A Jin, SF Weichselbaum, R Weavers, D Kufe, D Kharbanda, S TI Regulation of DNA-dependent protein kinase by the Lyn tyrosine kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STRAND-BREAK REPAIR; C-ABL; IONIZING-RADIATION; PHOSPHATIDYLINOSITOL 3-KINASE; CATALYTIC SUBUNIT; CELLULAR-RESPONSE; STRESS-RESPONSE; ACTIVATION; CELLS; PHOSPHORYLATION AB The Src-like protein-tyrosine kinase Lyn is activated by ionizing radiation and certain other DNA-damaging agents, whereas the DNA-dependent protein kinase (DNA-PK), consisting of the catalytic subunits (DNA-PKcs) and Ku DNA-binding components, requires DNA double-stranded breaks for activation. Here me demonstrate that Lyn associates constitutively with DNA-PKcs. The SH3 domain of Lyn interacts directly with DNA-PKcs near a leucine zipper homology domain. We also show that Lyn phosphorylates DNA-PKcs but not Ku in vitro. The interaction between Lyn and DNA-PKcs inhibits DNA-PKcs activity and the ability of DNA-PKcs to form a complex with Ku/DNA. These results support the hypothesis that there are functional interactions between Lyn and DNA-PKcs in the response to DNA damage. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Univ Chicago, Dept Radiat & Cellular Biol, Chicago, IL 60637 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Kharbanda, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA75216, CA55241] NR 34 TC 29 Z9 29 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 OCT 2 PY 1998 VL 273 IS 40 BP 25654 EP 25658 DI 10.1074/jbc.273.40.25654 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 125XU UT WOS:000076263100022 PM 9748231 ER PT J AU Krainc, D Bai, G Okamoto, S Carles, M Kusiak, JW Brent, RN Lipton, SA AF Krainc, D Bai, G Okamoto, S Carles, M Kusiak, JW Brent, RN Lipton, SA TI Synergistic activation of the N-methyl-D-aspartate receptor subunit 1 promoter by myocyte enhancer factor 2C and Sp1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID UPSTREAM REGULATORY ELEMENTS; NEURON-SPECIFIC EXPRESSION; TRANSCRIPTION FACTOR SP1; SODIUM-CHANNEL GENE; NMDA RECEPTOR; DNA-BINDING; RAT-BRAIN; EMBRYONIC-DEVELOPMENT; CORTICAL-NEURONS; NERVOUS-SYSTEM AB The N-methyl-D-aspartate (NMDA) subtype of glutamate receptor plays important roles in neuronal development, plasticity, and cell death. NMDA receptor subunit 1 (NR1) is an essential subunit of the NMDA receptor and is developmentally expressed in postnatal neurons of the central nervous system. Here we identify on the NR1 promoter a binding site for myocyte enhancer factor 2C (MEF2C), a developmentally expressed neuron/muscle transcription factor found in cerebrocortical neurons, and study its regulation of the NR1 gene. Co-expression of MEF2C and Sp1 cDNAs in primary neurons or cell lines synergistically activates the NR1 promoter. Disruption of the MEF2 site or the MEF2C DNA binding domain moderately reduces this synergism. Mutation of the Sp1 sites or the activation domains of Sp1 protein strongly reduces the synergism. Results of yeast two-hybrid and co-immunoprecipitation experiments reveal a physical interaction between MEF2C and Sp1 proteins. The MEF2C DNA binding domain is sufficient for this interaction. Dominant-negative MEF2C interferes with expression of NR1 mRNA in neuronally differentiated P19 cells. Growth factors, including epidermal growth factor and basic fibroblast growth factor, can up-regulate NR1 promoter activity in stably transfected PC12 cells, even in the absence of the MEF2 site, but the Sp1 sites are necessary for this growth factor regulation, suggesting that Spl sites may mediate these effects. C1 Brigham & Womens Hosp, CNS Res Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. NIA, Mol Neurobiol Unit, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Lipton, SA (reprint author), Brigham & Womens Hosp, CNS Res Inst, 221 Longwood Ave,LMRC 1st Floor, Boston, MA 02115 USA. FU NEI NIH HHS [R01 EY05477, R01 EY06087]; NICHD NIH HHS [P01 HD29587] NR 71 TC 71 Z9 73 U1 2 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 2 PY 1998 VL 273 IS 40 BP 26218 EP 26224 DI 10.1074/jbc.273.40.26218 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 125XU UT WOS:000076263100096 PM 9748305 ER PT J AU Tsang, SH Burns, ME Calvert, PD Gouras, P Baylor, DA Goff, SP Arshavsky, VY AF Tsang, SH Burns, ME Calvert, PD Gouras, P Baylor, DA Goff, SP Arshavsky, VY TI Role for the target enzyme in deactivation of photoreceptor G protein in vivo SO SCIENCE LA English DT Article ID CYCLIC-GMP PHOSPHODIESTERASE; ROD OUTER SEGMENTS; TRANSDUCIN GTPASE ACTIVITY; CGMP PHOSPHODIESTERASE; RETINAL RODS; VISUAL TRANSDUCTION; ACTIVATION STEPS; GAMMA-SUBUNIT; RGS PROTEINS; FAMILY AB Heterotrimeric guanosine 5'-triphosphate (GTP)-binding proteins (C proteins) are deactivated by hydrolysis of the CTP that they bind when activated by transmembrane receptors. Transducin, the C protein that relays visual excitation from rhodopsin to the cyclic guanosine 3',5'-monophosphate phosphodiesterase (PDE) in retinal photoreceptors, must be deactivated for the light response to recover. A point mutation in the gamma subunit of PDE impaired transducin-PDE interactions and slowed the recovery rate of the flash response in transgenic mouse rods. These results indicate that the normal deactivation of transducin in vivo requires the G protein to interact with its target enzyme. C1 Harvard Univ, Sch Med, Howe Lab Ophthalmol, Boston, MA 02114 USA. Columbia Univ Coll Phys & Surg, Edward S Harkness Eye Inst, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Biochem & Mol Biophys, New York, NY 10032 USA. Stanford Univ, Sch Med, Dept Neurobiol, Stanford, CA 94305 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Columbia Univ Coll Phys & Surg, Howard Hughes Med Inst, New York, NY 10032 USA. RP Arshavsky, VY (reprint author), Harvard Univ, Sch Med, Howe Lab Ophthalmol, Boston, MA 02114 USA. RI Goff, Stephen/K-6337-2014 OI Goff, Stephen/0000-0003-0693-5547 FU NEI NIH HHS [EY05750, EY10336, T32 EY07105] NR 47 TC 145 Z9 146 U1 0 U2 3 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 OCT 2 PY 1998 VL 282 IS 5386 BP 117 EP 121 DI 10.1126/science.282.5386.117 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 126LM UT WOS:000076294900052 PM 9756475 ER PT J AU Adler, JN Hughes, LA Vivilecchia, R Camargo, CA AF Adler, JN Hughes, LA Vivilecchia, R Camargo, CA TI Effect of skin pigmentation on pulse oximetry accuracy in the emergency department SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE pulse oximeter; oxygen saturation; skin pigmentation ID EAR OXIMETRY; RELIABILITY; METHEMOGLOBINEMIA; AGREEMENT; EXERCISE AB Objective: To determine whether pulse oximeter (PO) accuracy and signal quality are affected by level of skin pigmentation. Methods: Observational study in a community hospital ED. Consecutive adult patients undergoing arterial blood gas determination were enrolled into the study. Skin pigmentation was determined by comparison with standardized color swatches under controlled lighting; assigned values were used to stratify patients into 3 groups (light, intermediate, and dark) using predetermined criteria. Simultaneous with arterial blood sampling, staff recorded PO reading of O-2 saturation using the Nellcor D-25 oximeter. PO values were compared with criterion standard values measured using a 4-wavelength spectrophotometer or co-oximeter. PO signal quality also was recorded. Bias (the mean difference between PO and co-oximeter-measured values of hemoglobin saturation) and precision (the standard deviation of the bias) were calculated. Groups were compared using one-way ANOVA, Bartlett's test for variances, and chi(2) test. Results: O-2 saturation data were obtained for 284 patients. Bias values did not differ between the 3 skin pigment groups (p = 0.79). Precision was of borderline significance (p = 0.05), but there was no dose-response relation between skin pigmentation and precision. Study personnel reported suboptimal PO function most often among patients in the dark group (p = 0.003), but this finding was of no clinical significance. PO signal failure was rare (<1% of all patients). Conclusions: Although several prior studies suggest the contrary, this study found that skin pigmentation does not affect the bias or precision of pulse oximetry. Furthermore, skin pigmentation has no clinically significant effect on PO signal quality. C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp, Boston, MA 02115 USA. Lowell Gen Hosp, Clin Labs Dept, Lowell, MA USA. Lowell Gen Hosp, Dept Emergency Med, Lowell, MA USA. RP Adler, JN (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Founders Bldg 150, Boston, MA 02114 USA. EM adler.jonathan@mgh.harvard.edu FU NHLBI NIH HHS [HL-03533] NR 25 TC 16 Z9 17 U1 0 U2 3 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD OCT PY 1998 VL 5 IS 10 BP 965 EP 970 PG 6 WC Emergency Medicine SC Emergency Medicine GA 128PL UT WOS:000076415000006 PM 9862586 ER PT J AU Silverman, SG Khorasani, R Adams, DF Phillips, MD Sica, GT Mayer, RJ AF Silverman, SG Khorasani, R Adams, DF Phillips, MD Sica, GT Mayer, RJ TI Multidisciplinary gastrointestinal cancer clinic: Abdominal radiologist as active participant SO ACADEMIC RADIOLOGY LA English DT Article DE gastrointestinal tract; radiology and radiologists AB ,;Rationale and Objectives. Abdominal radiologist actively participated and provided subspecialty radiologic expertise in a multidisciplinary gastrointestinal cancer clinic that served a tertiary referral center. The purpose of this study was to evaluate the feasibility and nonradiologists' opinions of this new approach to radiologic consultation. Materials and Methods. One Of four subspecialty-trained abdominal radiologists joined physicians from four other subspecialties in staffing weekly 4-hour clinic sessions. Images were reviewed, opinions on test selection and interventional options rendered, and patients met with en interventional options were considered. Radiologists were compensated a fixed SLIM for each session. A survey of nonradiologists' opinions about the radiologists' active participation was conducted after 15 months (61 clinic sessions). Results. Abdominal radiologists' active participation was feasible and highly regarded by nonradiologist physicians. Specific benefits cited in the survey included improved interpretation, more efficient use of nonradiologist physician time, and improved rapport between radiologists and nonradiologists. Nonradiologist physicians believed that patient care was improved and that the radiologists' participation should continue, Conclusion. The active participation of abdominal radiologists in a multidisciplinary gastrointestinal cancer clinic is feasible and highly regarded by non-radiologists. C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Silverman, SG (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. NR 10 TC 2 Z9 2 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD OCT PY 1998 VL 5 IS 10 BP 694 EP 697 DI 10.1016/S1076-6332(98)80564-3 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V3314 UT WOS:000175068200006 PM 9787840 ER PT J AU Lieber, CS AF Lieber, CS TI Gastritis in the alcoholic: relationship to gastric alcohol metabolism and Helicobacter pylori SO ADDICTION BIOLOGY LA English DT Article ID FIRST-PASS METABOLISM; PLACEBO-CONTROLLED TRIAL; NON-ULCER DYSPEPSIA; UREA BREATH TEST; CAMPYLOBACTER-PYLORIDIS; BLOOD-ALCOHOL; DEHYDROGENASE-ACTIVITY; 1ST-PASS METABOLISM; ADH7 GENE; MOLECULAR-CLONING AB Chronic gastritis is common in the alcoholic. It is characterized by histological inflammation of the gastric mucosa and is associated with variable symptomatology. its etiology is still the subject of debate. Recently, a new alcohol dehydrogenase isoenzyme, called sigma ADH, absent from the liver but predominant in the upper GI tract, has been fully characterized its gene cloned, and it appears to play a major role in gastric ethanol metabolism. Indeed, it has now been established, both in vivo in experimental animals and in vitro in cultured human gastric cells, that alcohol is metabolized in the gastric mucosa, resulting in the production of acetaldehyde, a toxic metabolite. In addition, Helicobacter pylori infection is common in the alcoholic, resulting in the breakdown of urea to ammonia, another toxic product. A number of studies carried out over the last 40 years revealed that antibiotic treatment eradicates ammonia production and results in histological and symptomatic improvement in the majority of patients with alcoholic gastritis. Non-invasive tests for the detection of H. pylori are now available which will facilitate the large scale studies needed to confirm whether, in H. pylori-positive patients, antibiotics should become routine treatment for alcoholic gastritis. C1 Bronx Vet Affairs Med Ctr, Sect Liver Dis & Nutr, Ctr Alcohol Res & Treatment, Bronx, NY 10468 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. RP Lieber, CS (reprint author), Bronx Vet Affairs Med Ctr, Sect Liver Dis & Nutr, Ctr Alcohol Res & Treatment, 151-2,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM liebercs@aol.com NR 94 TC 3 Z9 5 U1 0 U2 4 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 1355-6215 J9 ADDICT BIOL JI Addict. Biol. PD OCT PY 1998 VL 3 IS 4 BP 423 EP 433 DI 10.1080/13556219871967 PG 11 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA 126HE UT WOS:000076287200005 PM 26735117 ER PT J AU Pahlavani, MA AF Pahlavani, MA TI Intervention in the aging immune system: Influence of dietary restriction, dehydroepiandrosterone, melatonin, and exercise SO AGE LA English DT Review ID PINEAL HORMONE MELATONIN; LOW-DOSE INTERLEUKIN-2; INDUCED LYMPHOCYTE-PROLIFERATION; AGE-ASSOCIATED DECLINE; HEAT-SHOCK PROTEINS; CELL LUNG-CANCER; FOOD RESTRICTION; SUBCUTANEOUS INTERLEUKIN-2; PHYSICAL EXERCISE; NEUROHORMONE MELATONIN AB The decline in immunologic function with age is associated with an increase in susceptibility to infections and the occurrence of autoimmune diseases and cancers, Hence, the restoration of immunologic function is expected to have a beneficial effect in reducing pathology and maintaining a healthy condition in advanced age. A number of therapeutic strategies have been employed to intervene in the aging immune system, This article reviews the effect of dietary restriction (DR), dehydroepiandrosterone (DHEA) treatment, melatonin (MLT) therapy, and exercise on modulating the immune responses and retarding/reducing immunosenescence, DR has been subject to intensive research and is known to be the most efficacious means of increasing longevity, reducing pathology and enhancing immune function. The circulatory levels of the androgen ic hormone DHEA and the pineal hormone MLT decrease with increasing age, and this decrease has been correlated with the age-related decline in the immune system, Therefore, the observation that immunosenescence is associated with low levels of DHEA and MLT has provided a rationale for therapeutic intervention. DH EA treatment and MLT therapy both exhibit immune-stimulatory actions and preliminary reports indicate that hormonal (DHEA or MLT) substitution therapy reverses immunosenescence in mice, Similarly, exercise in some studies has been shown to enhance the immune response, However, these findings have not been confirmed by other laboratories, Thus, at the present time, it is difficult to draw any definitive conclusions on the efficacy of DHEA, MLT, and exercise on reversing or restoring the aging immune system. C1 S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. RP Pahlavani, MA (reprint author), Audie L Murphy Mem Vet Adm Med Ctr, GRECC 182, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. EM Pahlavani@uthscsa.edu NR 173 TC 5 Z9 6 U1 2 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0161-9152 J9 AGE JI Age PD OCT PY 1998 VL 21 IS 4 BP 153 EP 173 DI 10.1007/s11357-998-0025-5 PG 21 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 179PW UT WOS:000079338700002 PM 23604377 ER PT J AU Kiesz, RS Rozek, MM Sepeda, JM Chang, CW Patel, V Sako, EY Miller, OL AF Kiesz, RS Rozek, MM Sepeda, JM Chang, CW Patel, V Sako, EY Miller, OL TI Comparison of multivessel, multidevice unstaged intervention with coronary artery bypass surgery: A single-center experience. SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Syst, Audie Murphy Div, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT PY 1998 VL 82 IS 7A SI SI BP 58S EP 58S PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 128LR UT WOS:000076408200151 ER PT J AU El-Khoury, AE Basile, A Beaumier, L Wang, SY Al-Amiri, HA Selvaraj, A Wong, S Atkinson, A Ajami, AM Young, VR AF El-Khoury, AE Basile, A Beaumier, L Wang, SY Al-Amiri, HA Selvaraj, A Wong, S Atkinson, A Ajami, AM Young, VR TI Twenty-four-hour intravenous and oral tracer studies with L-[1-C-13]-2-aminoadipic acid and L-[1-C-13]lysine as tracers at generous nitrogen and lysine intakes in healthy adults SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE tracer balance; lysine oxidation; lysine balance; diurnal pattern; indispensable amino acid requirements; healthy adults; lysine kinetics; aminoadipic acid kinetics ID DIETARY-PROTEIN INTAKE; YOUNG MEN; LEUCINE OXIDATION; AMINO-ACIDS; PHENYLALANINE INTAKE; 24-H PATTERN; KINETICS; REQUIREMENTS; HUMANS; L-<1-C-13>PHENYLALANINE AB Background: This is a continuation of investigations of the relations between amino acid kinetics and amino acid dietary requirements in healthy adults. Objective: The aim was to investigate the 24-h pattern and rate of the metabolism of an L-[1-C-13]-2-aminoadipic acid ([C-13]AAA) tracer and of whole-body L-[1-C-13]lysine ([C-13]lysine) oxidation and balance in healthy, young adults receiving a generous intake of lysine. Design: Thirteen healthy adults were given an adequate, L-amino acid-based diet supplying 77 mg lysine.kg(-1).d(-1) for 6 d before the tracer studies. Two subjects received [C-13]AAA intravenously and 2 received it orally; 3 subjects received [C-13]lysine intravenously and 6 received it orally. We measured (CO2)-C-13 output, plasma [C-13]AAA and [C-13]lysine enrichment, and urinary [C-13]AAA. Results: [C-13]AAA oxidation was estimated to be higher after the orally administered than after the intravenously administer tracer; plasma [C-13]AAA was similar to urinary [C-13]AAA. Whole-body lysine oxidation showed a rhythm that was induced by meal feeding. The intravenous [C-13]lysine tracer gave mean estimates of lysine balances (lysine intake minus oxidation) that apparently were too low (-15.7 mg.kg(-1).d(-1)) or too high (16.6 mg.kg(-1).d(-1), P < 0.05 from zero balance) on the basis of urinary [C-13]AAA or plasma [C-13]lysine estimates of oxidation, respectively. For the orally administered tracer and plasma [C-13]lysine enrichment, the mean balance was slightly positive (8.7 mg.kg(-1).d(-1), P < 0.05 from zero). Conclusions: Use of urinary [C-13]AAA as an index of the enrichment of the precursor pool did not appear to significantly improve the estimate of the fasting and feeding components of daily lysine balance. For estimates of daily, whole-body lysine oxidation, we propose use of plasma [C-13]lysine with a 24-h, orally administered tracer protocol. C1 MIT, Human Nutr Lab, Cambridge, MA 02139 USA. MIT, Clin Res Ctr, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Shriners Burns Inst, Boston, MA 02114 USA. MassTrace Inc, Woburn, MA USA. RP El-Khoury, AE (reprint author), MIT, Human Nutr Lab, Room E17-434,77 Massachusetts Ave, Cambridge, MA 02139 USA. FU NCRR NIH HHS [RR88 DK 42101]; NIDDK NIH HHS [P-30-DK-40561] NR 46 TC 26 Z9 26 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 1998 VL 68 IS 4 BP 827 EP 839 PG 13 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 124QE UT WOS:000076192600011 PM 9771859 ER PT J AU Colevas, AD Posner, MR AF Colevas, AD Posner, MR TI Docetaxel in head and neck cancer - A review SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Review DE docetaxel; Taxotere; squamous cell carcinoma of the head and neck ID HIGH-DOSE LEUCOVORIN; SQUAMOUS-CELL CARCINOMA; PHASE-I; INTRAVENOUS-INFUSION; TAXOTERE RP-56976; INDUCTION CHEMOTHERAPY; CISPLATIN; FLUOROURACIL; TRIAL; TAXOL AB Docetaxel has been shown to have significant antitumor activity. The mechanism of action is through stabilization of tubulin, arresting cells in the G(2)M phase of the cell cycle. The maximum tolerated dose of docetaxel is 100 mg/m(2) every 21 days. Short-lasting neutropenia is the dose-limiting toxicity. Other significant toxicities include alopecia, mucositis, fatigue, sensory neuropathy, fluid retention, rash, and hypersensitivity reactions. Phase II studies of docetaxel as a single agent in patients with squamous cell carcinoma of the head and neck (SCCHN) have documented response rates of 27% to 43%. Studies of docetaxel combined with cisplatin, and docetaxel, cisplatin, and 5-fluorouracil (TPF) as induction therapy for patients with SCCHN demonstrate that these regimens are highly active. An early trial of induction TPF with leucovorin (TPFL) has yielded an overall response rate of 100% and complete response rate of 61%. In vitro studies have shown docetaxel to be a potent radiation sensitizer for squamous cell carcinoma cell Lines, and phase I trials using concurrent docetaxel and radiotherapy are ongoing. C1 Dana Farber Canc Inst, Div Med Oncol, Head & Neck Oncol Program, Boston, MA 02115 USA. RP Colevas, AD (reprint author), Dana Farber Canc Inst, Div Med Oncol, Head & Neck Oncol Program, Boston, MA 02115 USA. NR 27 TC 28 Z9 28 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD OCT PY 1998 VL 21 IS 5 BP 482 EP 486 DI 10.1097/00000421-199810000-00013 PG 5 WC Oncology SC Oncology GA 127FE UT WOS:000076339300013 PM 9781605 ER PT J AU Fong, GCY Shah, PU Gee, MN Serratosa, JM Castroviejo, IP Khan, S Ravat, SH Mani, J Huang, Y Zhao, HZ Medina, MT Treiman, LJ Pineda, G Delgado-Escueta, AV AF Fong, GCY Shah, PU Gee, MN Serratosa, JM Castroviejo, IP Khan, S Ravat, SH Mani, J Huang, Y Zhao, HZ Medina, MT Treiman, LJ Pineda, G Delgado-Escueta, AV TI Childhood absence epilepsy with tonic-clonic seizures and electroencephalogram 3-4-Hz spike and multispike-slow wave complexes: Linkage to chromosome 8q24 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID JUVENILE MYOCLONIC EPILEPSY; IDIOPATHIC GENERALIZED EPILEPSY; HUMAN GENOME; LOCALIZATION; FAMILIES; PEDIGREE; GENES; LOCUS; MAP AB Childhood absence epilepsy (CAE), a common form of idiopathic generalized epilepsy, accounts for 5%-15% of childhood epilepsies. To map the chromosomal locus of persisting CAE, we studied the clinical and electroencephalographic traits of 78 members of a five-generation family from Bombay, India. The model-free affected-pedigree member method was used during initial screening with chromosome Gp, 8q, and Ip microsatellites, and only individuals with absence seizures and/or electroencephalogram 3-4-Hz spike- and multi-spike-slow wave complexes were considered to be affected. Significant P values of .00000-.02 for several markers on 8q were obtained. Two-point linkage analysis, assuming autosomal dominant inheritance with 50% penetrance, yielded a maximum LOD score (Z(max)) of 3.6 for D8S502. No other locus in the genome achieved a significant Z(max). For five smaller multiplex families, summed Z(max) was 2.4 for D8S537 and 1.7 for D8S1761. Haplotypes composed of the same 8q24 microsatellites segregated with affected members of the large family from India and with all five smaller families. Recombinations positioned the CAE gene in a 3.2-cM interval. C1 W Los Angeles Vet Affairs Med Ctr, Serv Neurol, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Calif Comprehens Epilepsy Program, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Inst Brain Res, Los Angeles, CA USA. KEM Hosp, Bombay, Maharashtra, India. Seth GS Med Coll, Bombay, Maharashtra, India. Fdn Jimenez Diaz, Serv Neurol, Epilepsy Unit, E-28040 Madrid, Spain. Univ Hosp La Paz, Madrid, Spain. Riyadh Armed Forces Hosp, Dept Neurosci, Riyadh, Saudi Arabia. Natl Univ Honduras, Tegucigalpa, Honduras. RP Delgado-Escueta, AV (reprint author), W Los Angeles Vet Affairs Med Ctr, Serv Neurol, Room 3405 127B,Bldg 500,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NINDS NIH HHS [NS21908] NR 38 TC 88 Z9 99 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1998 VL 63 IS 4 BP 1117 EP 1129 DI 10.1086/302066 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 131LP UT WOS:000076577800026 PM 9758624 ER PT J AU Hanson, RL Ehm, MG Pettitt, DJ Prochazka, M Thompson, DB Timberlake, D Foroud, T Kobes, S Baler, L Burns, DK Almasy, L Blangero, J Garvey, WT Bennett, PH Knowler, WC AF Hanson, RL Ehm, MG Pettitt, DJ Prochazka, M Thompson, DB Timberlake, D Foroud, T Kobes, S Baler, L Burns, DK Almasy, L Blangero, J Garvey, WT Bennett, PH Knowler, WC TI An autosomal genomic scan for loci linked to type II diabetes mellitus and body-mass index in Pima Indians SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID ASSESSING GENETIC-LINKAGE; QUANTITATIVE TRAIT LOCI; SIB-PAIR ANALYSIS; COMPONENTS MODELS; PEDIGREE ANALYSIS; WIDE SEARCH; SUSCEPTIBILITY; OBESITY; NIDDM; EXTENSIONS AB Genetic factors influence the development of type II diabetes mellitus, but genetic loci for the most common forms of diabetes have not been identified. A genomic scan was conducted to identify loci linked to diabetes and body-mass index (BMI) in Pima Indians, a Native American population with a high prevalence of type II diabetes. Among 264 nuclear families containing 966 siblings, 516 autosomal markers with a median distance between adjacent markers of 6.4 cM were genotyped. Variance-components methods were used to test for linkage with an age-adjusted diabetes score and with BMI. In multipoint analyses, the strongest evidence for linkage with age-adjusted diabetes (LOD = 1.7) was on chromosome 11q, in the region that was also linked most strongly with BMI (LOD = 3.6). Bivariate linkage analyses strongly rejected both the null hypothesis of no linkage with either trait and the null hypothesis of no contribution of the locus to the covariation among the two traits. Sib-pair analyses suggest additional potential diabetes-susceptibility loci on chromosomes Iq and 7q. C1 NIDDKD, Diabet & Arthritis Epidemiol Sect, NIH, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ 85014 USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. Sequana Therapeut Inc, Dept Stat Genet, La Jolla, CA USA. Indiana Univ, Sch Med, Dept Med Genet, Indianapolis, IN USA. SW Fdn Biomed Res, Dept Genet, San Antonio, TX USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Hanson, RL (reprint author), NIDDKD, Diabet & Arthritis Epidemiol Sect, NIH, Phoenix Epidemiol & Clin Res Branch, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. RI Baier, Leslie/F-9008-2013; Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU NCRR NIH HHS [1P41 RR03655]; NIDDK NIH HHS [DK-47461]; NIGMS NIH HHS [GM-18897] NR 55 TC 357 Z9 368 U1 0 U2 10 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1998 VL 63 IS 4 BP 1130 EP 1138 DI 10.1086/302061 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 131LP UT WOS:000076577800027 PM 9758619 ER PT J AU Stehman-Breen, CO Emerson, S Gretch, D Johnson, RJ AF Stehman-Breen, CO Emerson, S Gretch, D Johnson, RJ TI Risk of death among chronic dialysis patients infected with hepatitis C virus SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE hepatitis C virus; dialysis; survival ID HEMODIALYSIS-PATIENTS; HEPATOCELLULAR-CARCINOMA; UNITED-STATES; ANTI-HCV; PREVALENCE; ANTIBODIES; RNA; TAIWAN; STAFF AB Hepatitis C virus (HCV) infection is highly prevalent among chronic dialysis patients (10% to 40%) and is the most common cause of chronic liver disease. However, there are no studies estimating the risk for death among dialysis patients infected with HCV compared with those not infected. We conducted a prospective cohort study to estimate the risk for death among chronic dialysis patients infected with HCV compared with those not infected. In 1992, 200 patients (91%) who had been underging dialysis therapy for at least 6 months consented to be screened for HCV infection by enzyme immunoblot assay and polymerase chain reaction (PCR). Information about potential confounders and potential risk factors for death and HCV infection was obtained from the dialysis center database, Patient outcomes collected included death, transplantation, and loss to follow-up. The Cox proportional hazards model was used to estimate the odds of death among dialysis patients who were positive for the HCV antibody and HCV RNA compared with negative patients. Forty-four patients (22%) were HCV antibody positive. Thirty-four patients (17%) were HCV RNA positive. Patients in the HCV RNA-positive group were more likely to be younger (51.8 +/- 12.6 v 57.2 +/- 17.3 years of age), men (77% v 54%), and black (65% v 37%). None of the home hemodialysis or peritoneal dialysis patients were HCV RNA positive, whereas one of the home hemodialysis and one of the peritoneal dialysis patients were HCV antibody positive. Two patients became infected with HCV during the follow-up period, Patients who were HCV RNA positive and those who were HCV antibody positive were at increased risk for death compared with patients who were negative (adjusted relative risk [aRR] = 1.78; 95% confidence interval [CI], 1.01 to 3.14; P = 0.045; and aRR = 1.97; 95% CI, 1.16 to 3.33; P = 0.012, respectively), after adjusting for time on dialysis, race, transplantation, and age. We conclude that HCV infection increased the risk for death during the study period compared with those not infected. Further studies should assess the measures used to prevent and treat HCV infection. (C) 1998 by the National Kidney Foundation, Inc. C1 Univ Washington, Dept Med, Div Nephrol, Seattle, WA USA. Univ Washington, Dept Biostat, Div Nephrol, Seattle, WA USA. Univ Washington, Dept Lab Med, Div Nephrol, Seattle, WA USA. RP Stehman-Breen, CO (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way,Mailstop 111A, Seattle, WA 98108 USA. NR 26 TC 123 Z9 125 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD OCT PY 1998 VL 32 IS 4 BP 629 EP 634 DI 10.1016/S0272-6386(98)70027-7 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 125GF UT WOS:000076228500015 PM 9774125 ER PT J AU Muder, RR AF Muder, RR TI Pneumonia in residents of long-term care facilities: Epidemiology, etiology, management, and prevention SO AMERICAN JOURNAL OF MEDICINE LA English DT Review ID NURSING-HOME RESIDENTS; COMMUNITY-ACQUIRED PNEUMONIA; RESPIRATORY SYNCYTIAL VIRUS; INFLUENZAE TYPE-B; NOSOCOMIAL INFECTIONS; PNEUMOCOCCAL VACCINE; RISK-FACTORS; STREPTOCOCCUS-PNEUMONIAE; TRACT INFECTIONS; UNITED-STATES AB Pneumonia is a leading cause of morbidity and mortality among patients in long-term care facilities; the median reported incidence is 1 per 1,000 patient-days. Risk factors include functional dependency, chronic pulmonary disease, and conditions causing aspiration. The frequency of etiologic agents varies widely among reports; for example; Streptococcus pneumoniae ranges from 0% to 39% of cases, and gram negative bacilli ranges from 0% to 51% of reported cases. Viral respiratory infections, particularly influenza and respiratory syncytial virus, typically occur in outbreaks. Mortality varies from 5% to 40%; functional status is the major determinant of survival. Many patients receive inadequate initial evaluations, and as many as 40% receive no physician visit during the episode. Although transfer to an acute care facility occurs in 9% to 51% of cases, most transferred patients could be managed in the nursing home with minimal additional support. Appropriate evaluation includes examination by a practitioner, recording of vital signs, chest radiograph, and examination of an adequate sputum sample, if available. Patients without contraindications to oral therapy or severe abnormalities of vital signs (pulse >120 beats per minute, respirations >30 per minute, systolic blood pressure <90) may initially receive oral therapy. Appropriate oral agents include amoxicillin/clavulanate, second generation cephalosporins, quinolones active against S pneumoniae, or trimethoprim/sulfamethoxazole. Appropriate parenteral agents include beta-lactam/beta-lactamase inhibitor combinations, second or third generation cephalosporins, or quinolones. Pneumococcal and influenza vaccines should be administered to all residents. Future studies should focus on identifying risk factors for pneumonia that are amenable to intervention and to identifying highly effective, preferably oral, antimicrobial regimens in randomized trials. (C) 1998 by Excerpta Medica, Inc. C1 VA Pittsburgh Healthcare Syst, Infect Dis Sect, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. RP Muder, RR (reprint author), VA Pittsburgh Healthcare Syst, Infect Dis Sect, Univ Dr C, Pittsburgh, PA 15240 USA. NR 133 TC 170 Z9 174 U1 0 U2 3 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT PY 1998 VL 105 IS 4 BP 319 EP 330 DI 10.1016/S0002-9343(98)00262-9 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 133NF UT WOS:000076692100011 PM 9809694 ER PT J AU Hunter, SJ Garvey, WT AF Hunter, SJ Garvey, WT TI Insulin action and insulin resistance: Diseases involving defects in insulin receptors, signal transduction, and the glucose transport effector system SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID POLYCYSTIC-OVARY-SYNDROME; DEPENDENT DIABETES-MELLITUS; HUMAN SKELETAL-MUSCLE; KINASE-ACTIVITY; PROTEIN-KINASE; TYROSINE PHOSPHORYLATION; PHOSPHOTYROSINE PROTEIN; ESSENTIAL-HYPERTENSION; ACANTHOSIS NIGRICANS; 3T3-L1 ADIPOCYTES C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Garvey, WT (reprint author), Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. FU NHLBI NIH HHS [P01 HL-55782]; NIDDK NIH HHS [DK-38763, DK-42469] NR 100 TC 82 Z9 84 U1 0 U2 6 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT PY 1998 VL 105 IS 4 BP 331 EP 345 DI 10.1016/S0002-9343(98)00300-3 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 133NF UT WOS:000076692100012 PM 9809695 ER PT J AU Braddock, CH AF Braddock, CH TI Advancing the cause of informed consent: Moving from disclosure to understanding SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Div Gen Internal Med, Seattle, WA 98195 USA. RP Braddock, CH (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 5 TC 10 Z9 10 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT PY 1998 VL 105 IS 4 BP 354 EP 355 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 133NF UT WOS:000076692100016 PM 9809699 ER PT J AU Harris, GJ Lewis, RF Satlin, A English, CD Scott, TM Yurgelun-Todd, DA Renshaw, PF AF Harris, GJ Lewis, RF Satlin, A English, CD Scott, TM Yurgelun-Todd, DA Renshaw, PF TI Dynamic susceptibility contrast MR imaging of regional cerebral blood volume in Alzheimer disease: A promising alternative to nuclear medicine SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT 82nd Annual Meeting of the Radiological-Society-of-North-America CY DEC 01-06, 1996 CL CHICAGO, ILLINOIS SP Radiol Soc N Amer ID POSITRON EMISSION TOMOGRAPHY; SPECT; DEMENTIA; BRAIN; NEUROPSYCHIATRY; QUANTIFICATION; PERFUSION; FLOW AB BACKGROUND AND PURPOSE: The goal of our study was to evaluate the sensitivity and specificity for Alzheimer disease of semiquantitative dynamic susceptibility contrast (DSC) MR imaging as compared with results of qualitative single-photon emission computed tomography (SPECT) in the same patients and with previously published semiquantitative SPECT results. METHODS: Fifty subjects were studied: 19 patients with probable Alzheimer disease with moderate cognitive impairment, eight mildly impaired patients with possible or probable Alzheimer disease, 18 group-matched elderly healthy comparison subjects, and five elderly comparison patients with psychiatric diagnoses. Relative values of temporoparietal regional cerebral blood volume (rCBV) were measured as a percentage of cerebellar rCBV, and group classification was assessed with logistic regression. The DSC MR imaging results were compared with SPECT scans in these same subjects and with previously published semiquantitative SPECT data. RESULTS: Temporoparietal rCBV ratios were reduced 20% bilaterally in the patients with Alzheimer disease. Using left and right temporoparietal rCBV as index measures, sensitivity mas 95% in moderately affected patients with Alzheimer disease and 88% in patients with mild cases. Specificity was 96% in healthy comparison subjects and in psychiatric comparison subjects. Sensitivity with DSC MR imaging was considerably better than with visual clinical readings of SPECT scans (74% in moderate and 50% in mild Alzheimer disease cases), and was similar to previous published SPECT temporoparietal measurements (90%). Specificity with SPECT was 100% visually and 87% based on previous temporoparietal measurements. CONCLUSIONS: DSC MR imaging of rCBV is promising as a safe, potentially lower-cost alternative to nuclear medicine imaging for the evaluation of patients with dementia. C1 Massachusetts Gen Hosp, Radiol Comp Aided Diagnost Lab, Boston, MA 02114 USA. McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. McLean Hosp, Memory Diagnost Clin, Belmont, MA 02178 USA. New England Med Ctr, Dept Psychiat, Boston, MA 02111 USA. RP Harris, GJ (reprint author), Massachusetts Gen Hosp, Radiol Comp Aided Diagnost Lab, Gray 2-B285,55 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [RR00054] NR 29 TC 93 Z9 98 U1 1 U2 2 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD OCT PY 1998 VL 19 IS 9 BP 1727 EP 1732 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 129FF UT WOS:000076452600024 PM 9802497 ER PT J AU Caughey, AA Shipp, TD Repke, JT Zelop, C Cohen, A Lieherman, E AF Caughey, AA Shipp, TD Repke, JT Zelop, C Cohen, A Lieherman, E TI Trial of labor after cesarean delivery: The effect of previous vaginal delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the Society-of-Perinatal-Obstetricians CY FEB 02-07, 1998 CL MIAMI, FLORIDA SP Soc Perinatal Obstetricians DE cesarean delivery; duration of labor; trial of labor; vaginal birth after cesarean birth ID SCORING SYSTEM; BIRTH; SECTION; SUCCESS; PREDICTORS AB OBJECTIVE: This study examined the effects of order of previous modes of delivery on the rate of cesarean delivery and duration of a trial of labor among women with a history of 1 previous cesarean delivery and 1 previous vaginal delivery. STUDY DESIGN: The medical records of 4393 women at our institution who were seen June 1984-JuIy 1996 for a trial of labor after a previous cesarean delivery were abstracted. The 800 women with a history of 1 previous cesarean and 1 previous vaginal delivery were included in this analysis. They were split into 2 groups by obstetric history: (1) 1 cesarean delivery followed by 1 vaginal delivery (vaginal last) and (2) 1 vaginal delivery followed by 1 cesarean delivery (cesarean last). Patient characteristics, durations of labor, and rates of cesarean delivery were compared with chi(2) analysis, the Student f test, and the Wilcoxon rank sum test. Possible confounding variables were controlled for with multivariate logistic regression. RESULTS: The rates of cesarean delivery for the vaginal last and cesarean last groups were 7.2% and 14.7%, respectively (P = .002). The median durations of labor for the vaginal last and cesarean last groups were 5.6 and 7.0 hours, respectively (P = .01). The differences in cesarean rates and durations of labor were seen regardless of the indication for the previous cesarean delivery. CONCLUSIONS: Among women with 1 previous cesarean and 1 previous Vaginal delivery, those whose most recent delivery was vaginal had a lower rate of cesarean delivery and shorter duration of labor than did those whose most recent delivery was cesarean. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02115 USA. Univ Nebraska, Med Ctr, Dept Obstet & Gynecol, Lincoln, NE 68583 USA. Univ Chicago, Chicago Lying Hosp, Dept Obstet & Gynecol, Chicago, IL 60637 USA. RP Shipp, TD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Founders 430, Boston, MA 02115 USA. NR 11 TC 38 Z9 39 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 1998 VL 179 IS 4 BP 938 EP 941 DI 10.1016/S0002-9378(98)70192-9 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 129RC UT WOS:000076475900019 PM 9790374 ER PT J AU Livir-Rallatos, C El-Shabrawi, Y Zatirakis, P Pellett, PE Stamey, FR Foster, CS AF Livir-Rallatos, C El-Shabrawi, Y Zatirakis, P Pellett, PE Stamey, FR Foster, CS TI Recurrent nodular scleritis associated with varicella zoster virus SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID HERPES-ZOSTER AB PURPOSE: To describe a case of recurrent nodular scleritis that was apparently caused by reactivation of a varicella tester virus infection. METHODS: Case report. Immunohistochemistry and polymerase chain reaction were used to detect viral antigen and DNA in the biopsy specimen of inflamed sclera of a patient with a history of recurrent nodular scleritis. RESULTS: Immunohistochemistry and polymerase chain reaction disclosed varicella tester virus protein and DNA in the biopsy specimen of inflamed sclera from the patient. The scleritis resolved with oral famciclovir therapy. CONCLUSION: Reactivation of latent varicella zoster virus and direct viral invasion of sclera apparently caused the recurrent anti-inflammatory resistant scleritis in our patient. (Am J Ophthalmol 1998;126:594-597. (C) 1998 by Elsevier Science Inc. All rights reserved.). C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Uveitis & Immunol Serv, Boston, MA 02114 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Uveitis & Immunol Serv, 243 Charles St, Boston, MA 02114 USA. NR 5 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD OCT PY 1998 VL 126 IS 4 BP 594 EP 597 DI 10.1016/S0002-9394(98)00120-2 PG 4 WC Ophthalmology SC Ophthalmology GA 126WA UT WOS:000076316500017 PM 9780109 ER PT J AU Pomeranz, HD Henson, JW Lessell, S AF Pomeranz, HD Henson, JW Lessell, S TI Radiation-associated cerebral blindness SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID THERAPY AB PURPOSE: To report a case of blindness caused by a white-matter injury after whole brain irradiation for metastatic renal cell carcinoma. METHODS: Case report, We performed comprehensive serial neuro-ophthalmologic examinations. RESULTS: Four to 5 months after resection of renal cell metastasis in the left occipital cortex, interleukin-2 therapy, and whole brain irradiation with 3,000 cGy plus a 1,500-cGy boost to the posterior third of the brain, the patient developed a progressive decline in visual acuity in both eyes to hand motions. Magnetic resonance imaging disclosed signal abnormalities without mass effect in the white matter of the parietal and occipital lobes bilaterally, including the optic radiations. CONCLUSION: This case is a unique example of cortical blindness secondary to radiation injury in the occipital lobes and optic radiations, (Am J Ophthalmol 1998;126:609-611, (C) 1998 by Elsevier Science Inc. All rights reserved.). C1 Massachusetts Eye & Ear Infirm, Neuroophthalmol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. RP Pomeranz, HD (reprint author), Massachusetts Eye & Ear Infirm, Neuroophthalmol Unit, 243 Charles St, Boston, MA 02114 USA. NR 6 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD OCT PY 1998 VL 126 IS 4 BP 609 EP 611 DI 10.1016/S0002-9394(98)00132-9 PG 3 WC Ophthalmology SC Ophthalmology GA 126WA UT WOS:000076316500023 PM 9780115 ER PT J AU Breton, S Hammar, K Smith, PJS Brown, D AF Breton, S Hammar, K Smith, PJS Brown, D TI Proton secretion in the male reproductive tract: involvement of Cl--independent HCO3- transport SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE carbonic anhydrase II; self-referencing proton-selective electrode; immunocytochemistry; hydrogen-adenosine 5 '-triphosphatase ID CARBONIC-ANHYDRASE; MITOCHONDRIA-RICH; CYSTIC-FIBROSIS; RAT EPIDIDYMIS; ANION CHANNEL; CELLS; ACIDIFICATION; BICARBONATE; MOTILITY; PH AB The lumen of the epididymis is the site where spermatozoa undergo their final maturation and acquire the capacity to become motile. An acidic luminal fluid is required for the maintenance of sperm quiescence and for the prevention of premature activation of acrosomal enzymes during their storage in the cauda epididymis and vas deferens. We have previously demonstrated that a vacuolar H+-ATPase [proton pump (PP)] is present in the apical pole of apical and narrow cells in the caput epididymis and of clear cells in the corpus and cauda epididymis and that this PP is responsible for the majority of proton secretion in the proximal vas deferens. We now show that PP-rich cells in the vas deferens express a high level of carbonic anhydrase type II (CAII) and that acetazolamide markedly inhibits the rate of proton secretion by 46.2 +/- 6.1%. The rate of acidification was independent of Cl- and was strongly inhibited by SITS under both normal and Cl--free conditions (50.6 +/- 5.0 and 57.5 +/- 6.0%, respectively). In the presence of Cl-, diphenylamine-2-carboxylate (DPC) had no effect, whereas SITS inhibited proton secretion by 63.7 +/- 11.3% when applied together with DPC. In Cl- free solution, DPC markedly inhibited proton efflux by 45.1 +/- 7.6%, SITS produced an additional inhibition of 18.2 +/- 6.6%, and bafilomycin had no additive effect. In conclusion, we propose that CAII plays a major role in proton secretion by the proximal vas deferens. Acidification does not require the presence of Cl-, but DPC-sensitive Cl- channels might contribute to basolateral extrusion of HCO, under Cl--free conditions. The inhibition by SITS observed under both normal and Cl--free conditions indicates that a Cl-/HCO3- exchanger is not involved and that an alternative HCO3- transporter participates in proton secretion in the proximal vas deferens. C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Marine Biol Lab, Biocurrents Res Ctr, Woods Hole, MA 02543 USA. RP Breton, S (reprint author), Massachusetts Gen Hosp, Renal Unit, 149 13th St,8th Floor, Charlestown, MA 02129 USA. FU NCRR NIH HHS [P41-RR-O1395]; NIDDK NIH HHS [DK-38452] NR 38 TC 29 Z9 29 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 OCT PY 1998 VL 275 IS 4 BP C1134 EP C1142 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 125ZE UT WOS:000076267000026 PM 9755067 ER PT J AU Zhang, Z Yang, XY Cohen, DM AF Zhang, Z Yang, XY Cohen, DM TI Hypotonicity activates transcription through ERK-dependent and -independent pathways in renal cells SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE urea; kidney; signal transduction; p38; stress-activated protein kinase; c-Jun amino-terminal kinase ID MEDULLARY COLLECTING DUCT; SIGNAL-TRANSDUCTION PATHWAY; PAPILLARY EPITHELIAL-CELLS; ORGANIC OSMOLYTE EFFLUX; PROTEIN-KINASE; MAP KINASE; INTRACELLULAR CALCIUM; SORBITOL PERMEASE; TYROSINE KINASE; MAMMALIAN-CELLS AB Acute hypotonic shock (50% dilution of medium with sterile water, but not with isotonic NaCl) activated the extracellular signal response kinase (ERK) mitogen-activated protein (MAP) kinases in renal medullary cells, as measured by Western analysis with a phospho-ERK-specific antibody and by in vitro kinase assay of epitope-tagged ERKs immunoprecipitated from stable HA-ERK transfectants. Hypotonicity also activated the transcription factor and ERK substrate Elk-l in a partially PD-98059-sensitive fashion, as assessed by chimeric reporter gene assay. Consistent with these data, hypotonic stress activated transcription of the immediate-early gene transcription factor Egr-1 in a partially PD-98059-sensitive fashion. Hypotonicity-inducible Egr-1 transcription was mediated in part through 5'-flanking regions containing serum response elements and in part through the minimal Egr-1 promoter. Elimination of the Ets motifs adjacent to key regulatory serum response elements in the Egr-1 promoter diminished the effect of hypotonicity but failed to abolish it. Interestingly, hypotonicity also transiently activated p38 and c-Jun NH2-terminal kinase 1, as determined by immunoblotting with anti-phospho-MAP kinase antibodies. Taken together, these data strongly suggest that hypotonicity activates immediate-early gene transcription in renal medullary cells via MAP kinase kinase-dependent and -independent mechanisms. C1 Oregon Hlth Sci Univ, Div Nephrol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Div Mol Med, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. RP Cohen, DM (reprint author), PP262,3314 SW US Vet Hosp Rd, Portland, OR 97201 USA. RI Zhang, Zheng/J-2388-2014 OI Zhang, Zheng/0000-0003-2497-0362 FU NIDDK NIH HHS [DK-52494] NR 65 TC 22 Z9 22 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 OCT PY 1998 VL 275 IS 4 BP C1104 EP C1112 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 125ZE UT WOS:000076267000023 PM 9755064 ER PT J AU Ohning, GV Song, M Wong, HC Wu, SV Walsh, JH AF Ohning, GV Song, M Wong, HC Wu, SV Walsh, JH TI Immunolocalization of gastrin-dependent histidine decarboxylase activity in rat gastric mucosa during feeding SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE enterochromaffin-like cells; histamine ID ENTEROCHROMAFFIN-LIKE CELLS; MONOCLONAL-ANTIBODY; ACID-SECRETION; MAST-CELLS; HISTAMINE; RELEASE; MESSENGER; COMMON; PHASE AB The localization of histidine decarboxylase (HDC) activity; in the enterochromaffin-like (ECL) cells of the oxyntic mucosa was studied during fasting and refeeding using monoclonal (CURE no. 44178) and polyclonal (CURE no. 94211) antibodies directed against the COOH terminus of HDC (HDC-CT). Changes in HDC immunostaining were correlated with mucosal HDC enzyme activity. Immunoneutralization of circulating gastrin and atropine treatment during refeeding were used to determine the relative importance of gastrin and cholinergic mechanisms in the regulation of HDC activity and immunostaining. Fasting caused a rapid reduction in the number of ECL cells immunostaining for HDC that was correlated with an almost complete loss of mucosal HDC enzyme activity Refeeding restored both HDC immunostaining and enzyme activity within 2-4 h, and this response was inhibited by gastrin immunoneutralization but not by atropine treatment. Immunostaining was uniformly decreased and restored in the lower half of the oxyntic mucosa, which corresponds to the predominant area of ECL cells in the gastric gland. Histamine immunostaining and mucosal histamine content were not significantly changed during fasting and refeeding or by gastrin antibody and/or atropine treatment during refeeding These findings indicate that HDC activity correlates with HDC-CT immunostaining and that both HDC activity and HDC-CT immunostaining are regulated by gastrin during refeeding. C1 Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Digest Dis Res Ctr, Res Serv,CURE, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Med Serv, CURE,Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. RP Ohning, GV (reprint author), Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Digest Dis Res Ctr, Res Serv,CURE, Bld 115,Rm 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-41301, DK-17294] NR 24 TC 12 Z9 12 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD OCT PY 1998 VL 275 IS 4 BP G660 EP G667 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 126VX UT WOS:000076316100008 PM 9756494 ER PT J AU Meyer, JH Hlinka, M Khatibi, A Raybould, HE Tso, P AF Meyer, JH Hlinka, M Khatibi, A Raybould, HE Tso, P TI Role of small intestine in caloric compensations to oil premeals in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE caloric adjustments; temporality ID APOLIPOPROTEIN-A-IV; FOOD-INTAKE; PANCREATIC INSUFFICIENCY; FAT DIGESTION; SATIETY; CHOLECYSTOKININ; HUMANS; TRIGLYCERIDE; CARBOHYDRATE; INHIBITION AB We postulated that dose-responsive satiety after oil premeals varies with the number of gut sensors stimulated by lipolytic products along intestine. These experiments in fasted rats on satiety after oil premeals were performed to 1) determine whether satiety was induced by lipolytic products but not triglycerides; 2) confirm that oil empties from the stomach at rates that vary with oil loads; 3) ascertain that increasing rates of oil entry into duodenum extend the length of gut contacted by lipolytic products; and 4)judge whether length of gut contacted correlated with dose-responsive satieties to dietary oils. 5) Using specific antagonists, we attempted to define how satiety was signalled by gut sensors. Timing and degrees of satiety did not correlate with timing and extent of gastric distensions but, rather, with the timing and extent of spread of lipolytic products along small bowel. Satiety after the highest premeal load of oil was blocked by Pluronic L-81, an inhibitor of intestinal secretion of apolipoprotein A-IV, but was unaffected by MK-329 (a specific antagonist of cholecystokinin) or by capsaicin blockade of chemosensory nerves. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Sepulveda Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA USA. Louisiana State Med Sch, Dept Physiol, Shreveport, LA 71103 USA. RP Meyer, JH (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,Rm 105,Bldg 115, Los Angeles, CA 90073 USA. NR 32 TC 37 Z9 37 U1 0 U2 2 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 OCT PY 1998 VL 275 IS 4 BP R1320 EP R1333 PG 14 WC Physiology SC Physiology GA 125KB UT WOS:000076235800046 PM 9756565 ER PT J AU Meyer, JH Hlinka, M Tabrizi, Y DiMaso, N Raybould, HE AF Meyer, JH Hlinka, M Tabrizi, Y DiMaso, N Raybould, HE TI Chemical specificities and intestinal distributions of nutrient-driven satiety SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE chemospecificities; sensory distributions; caloric reduction ratios ID FOOD-INTAKE; CARBOHYDRATE; COMPENSATION; HUNGER; HUMANS; ILEAL; RAT; FAT AB We measured intakes of sham- and naturally feeding rats during gut perfusions of nutrients. Our objectives were to determine 1) which nutrient products in gut lumen suppressed intakes; 2) how suppression by various nutrients is distributed along gut; and 3) whether time courses of suppression were similar among different nutrients. We found that satiating nutrients consisted of fatty acids only longer than 10 carbons, of monomeric carbohydrates only with affinity for the glucose transporter, and, among several amino acids, of only phenylalanine and tryptophan. Dimeric maltose had about the same potency as an isocaloric mixture of longer glucose polymers; since responses to either were blocked by a glucosidase inhibitor, each probably acted after hydrolysis to free glucose. Effective nutrients suppressed intakes about equally on infusion into duodenum vs, midgut, and the same nutrients also suppressed intakes when infused into colon. Food intakes were suppressed only while maltose was infused, not after it was stopped, but suppression persisted for 2 h after stopping perfusions with fatty or amino acids. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Sepulveda Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. RP Meyer, JH (reprint author), W Los Angeles Vet Affairs Med Ctr, Rm 105,Bldg 115,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 41 TC 68 Z9 69 U1 1 U2 5 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 OCT PY 1998 VL 275 IS 4 BP R1293 EP R1307 PG 15 WC Physiology SC Physiology GA 125KB UT WOS:000076235800044 PM 9756563 ER PT J AU Meyer, JH Tabrizi, Y DiMaso, N Hlinka, M Raybould, HE AF Meyer, JH Tabrizi, Y DiMaso, N Hlinka, M Raybould, HE TI Length of intestinal contact on nutrient-driven satiety SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE length of contact; load dependence; caloric equivalencies; intestinal integration ID PANCREATIC INSUFFICIENCY; FAT DIGESTION; TRIGLYCERIDE; TRANSPORT; INHIBITION; ABSORPTION; RESPONSES; PRODUCTS; GLUCOSE; DEPENDS AB Chemosensors throughout small bowel and colon inhibit food intakes when contacted by monomeric nutrients. We postulated that calorie-dependent inhibition of food intakes depended on additions of feedbacks from sensors in proximal and distal bowel contacted after high intakes of nutrients. Therefore, we determined how feedback from sensors in proximal gut interacted with feedback from simultaneously contacted sensors in distal bowel and whether suppression of nutrient intakes by intestinally perfused nutrients depended on length of g-ut contacted. Suppression of food intakes by maltose simply added to that from dodecanoate when both were present together either in proximal or distal small bowel. When dodecanoate was infused into proximal gut while maltose was infused distally, suppression of intake was threefold higher and was thus potentiated. Limiting contact of slowly absorbed lactose or oleate to 35 cm of jejunum nearly abolished the satiating potencies each exhibited during access to whole gut. The observations were consistent with our hypothesis. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. RP Meyer, JH (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,Rm 105,Bldg 115, Los Angeles, CA 90073 USA. NR 33 TC 45 Z9 46 U1 0 U2 2 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 OCT PY 1998 VL 275 IS 4 BP R1308 EP R1319 PG 12 WC Physiology SC Physiology GA 125KB UT WOS:000076235800045 PM 9756564 ER PT J AU Tondo, L Baldessarini, RJ AF Tondo, L Baldessarini, RJ TI Rapid cycling in women and men with bipolar manic-depressive disorders SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID FAMILY HISTORY; ILLNESS; VALIDITY AB Objective: This study investigated risks for rapid cycling, as defined by DSM-IV, in women and men with bipolar disorders. Method: The results of 10 studies with a total of 2,057 bipolar patients were meta-analyzed by pooled contingency methods. Results: The proportions of women and men among rapid-cycling cases averaged 72% and 28%, respectively, but the risk of rapid cycling was inconsistently more frequent among women (29.6%) than among men (16.5%). The mean number of episodes per year was much higher in rapid-cycling patients before and during lithium treatment but was similar in rapid-cycling men and women. Conclusions: Rapid cycling was only moderately, and inconsistently, more common in bipolar women than men. C1 Harvard Univ, Sch Med, Dept Psychiat, Int Consortium Bipolar Disorder Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Mailman Res Ctr, McLean Div, Boston, MA 02114 USA. Stanley Fdn European Psychiat Res Ctr, Ctr Lucio Bini, Sardinia, Italy. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02178 USA. FU NIMH NIH HHS [MH-47370] NR 20 TC 88 Z9 90 U1 1 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD OCT PY 1998 VL 155 IS 10 BP 1434 EP 1436 PG 3 WC Psychiatry SC Psychiatry GA 125HY UT WOS:000076233200020 PM 9766777 ER PT J AU Lee, BW Wain, JC Kelsey, KT Wiencke, JK Christiani, DC AF Lee, BW Wain, JC Kelsey, KT Wiencke, JK Christiani, DC TI Association between diet and lung cancer location SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID VITAMIN-A; BETA-CAROTENE; ASBESTOS-EXPOSURE; CARDIOVASCULAR-DISEASE; RISK; SMOKING; PREVENTION; PATHOLOGY; MORTALITY; CARCINOMA AB Lung cancers occur more commonly in the upper lobes than in the lower lobes, but its pathophysiologic basis is not well understood. Because numerous studies have reported a consistent inverse relationship between lung cancer risk and intake of certain vegetables and fruits, we hypothesized that the balance between diet-derived protective substances delivered via the circulation and cigarette-derived carcinogenic substances delivered via the airways would be less favorable in the upper lobes compared with the lower lobes, hence accounting for the upper lobe predominance of tumors among smokers. Thus, we examined the association between diet and tumor location in 328 patients with lung cancer. The ratio of upper to lower robe tumors was 2.5:1.0. In univariate analysis, age, height, weight, sex, race, family history of cancer, education level, tumor histology, calories consumed per day, and intake of animal fat did not differ significantly between patients with upper versus lower lobe tumors. Predictors of tumor location in univariate analysis were family history of lung cancer; smoking history; history of asbestos exposure; and intakes of yellow-orange vegetables, cr-carotene, p-carotene, and vitamins A, C, and E. In multivariable logistic regression analysis, the independent predictors of upper lobe tumor location were family history of lung cancer (p = 0.03), history of asbestos exposure (p = 0.02), less intake of yellow-orange vegetables (p < 0.04), and less intake of vitamin E (p = 0.05). Our results show a strong inverse association between upper lobe location of lung cancer and intake of yellow-orange vegetables and vitamin E. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Thorac Surg Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Canc Biol, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. RI Kelsey, Karl/I-1252-2014 FU NCI NIH HHS [CA-74386]; NIEHS NIH HHS [ES-06707, ES/CA-06409] NR 35 TC 7 Z9 8 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 OCT PY 1998 VL 158 IS 4 BP 1197 EP 1203 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 129FN UT WOS:000076453300030 PM 9769282 ER PT J AU Conhaim, RL Cooler, SD McGrath, AM DeAngeles, DA Myers, GA Harms, BA AF Conhaim, RL Cooler, SD McGrath, AM DeAngeles, DA Myers, GA Harms, BA TI Filtration of diaspirin crosslinked hemoglobin into lung and soft tissue lymph SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID CROSS-LINKED HEMOGLOBIN; PULMONARY-HYPERTENSION; BLOOD SUBSTITUTE; ALPHA-CHAINS; NITRIC-OXIDE; SHEEP; RESUSCITATION; EXCHANGE; PRODUCT; PRESSOR AB Diaspirin crosslinked hemoglobin (DCHb) is a new blood substitute manufactured from human blood. To evaluate its microvascular filtration properties, we infused DCLHb into unanesthetized sheep (10%, 20 ml/kg) and measured the flow and composition of lung and soft tissue lymph. For comparison, we also infused human serum albumin (HSA; 10%, 20 ml/kg). DCLHb raised systemic and pulmonary arterial pressures from baseline values of 83 +/- 7 and 13 +/- 2 mm Hg, respectively, to peak values of 113 +/- 9 and 26 +/- 3 mm Hg (p < 0.05 versus baseline). These increases were significantly greater than those associated with HSA, which raised systemic and pulmonary arterial pressures from baseline values of 86 +/- 4 and 13 +/- 2 mm Hg, respectively, to peak values of 97 +/- 3 and 21 +/- 7 mm Hg (p less than or equal to 0.05 versus baseline and versus DCLHb). These differences reflect the known presser properties of DCLHb. Accordingly, DCLHb raised lung and soft tissue lymph flows to peak values of 12.2 +/- 3.8 and 1.6 +/- 0.7 ml/30 min, respectively, while HSA raised lung and soft tissue lymph flows to peak values of 7.5 +/- 4.8 and 4.6 +/- 1.9 ml/30 min, respectively (p less than or equal to 0.05 versus DCLHb). The half-times of DCLHb equilibration from plasma into lung and soft tissue lymph of 1.0 +/- 0.3 and 2.1 +/- 1.1 h, respectively, were significantly faster than HSA equilibration half-times of 3.1 +/- 0.2 and 3.8 +/- 0.9 h. Filtration differences between DCLHb and HSA appear to be due to the presser properties DCLHb. C1 William S Middleton Mem Vet Hosp, Dept Surg, Madison, WI 53705 USA. Univ Wisconsin, Dept Surg, Madison, WI USA. RP Conhaim, RL (reprint author), William S Middleton Mem Vet Hosp, Dept Surg, B-7112A,2500 Overlook Terrace, Madison, WI 53705 USA. FU NHLBI NIH HHS [HL46236] NR 31 TC 7 Z9 7 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 OCT PY 1998 VL 158 IS 4 BP 1204 EP 1212 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 129FN UT WOS:000076453300031 PM 9769283 ER PT J AU Powell, PP Wang, CC Horinouchi, H Shepherd, K Jacobson, M Lipson, M Jones, R AF Powell, PP Wang, CC Horinouchi, H Shepherd, K Jacobson, M Lipson, M Jones, R TI Differential expression of fibroblast growth factor receptors 1 to 4 and ligand genes in late fetal and early postnatal rat lung SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID MESSENGER-RNA; FGF; FAMILY; MOUSE; HEPARIN; MEMBER; ORGANOGENESIS; SPECIFICITY; PATTERNS; LOCALIZE AB To characterize fibroblast growth factor (FGF) gene expression in the late fetal (days E18 to E22) and early postnatal lung (days P0 to P28), when the alveolar region undergoes extensive growth and reorganization, we analyzed the expression of four FGF receptors and six ligands. FGF receptor 1 (FGFR1) RNA levels were first low (E18) before rising late in the postnatal period (P28). FGFR2 RNA levels were detected early (at E18) and then increased (E20-P0) before falling (P2) to below later postnatal levels (P6 to P28). FGFR3 RNA levels were low at first (E18) and then increased, with peak levels in the days after birth (P2 to P10). FGFR4 RNA levels, barely detected in fetal lung (E18 to E22), increased at birth (PO) and remained high postnatally (P2 to P28). In fetal lung, FGF2 (basic FGF) RNA expression levels were low and FGF1 (acidic FGF) RNA levels were not detected: low RNA levels of each ligand were detected postnatally (P7 to P28). FGF3 to 5 and FGF7 RNA were not detected in fetal or postnatal lung. With in situ hybridization, predominantly the smooth muscle cells of large vessels expressed FGFR1 and 4 mRNA; the epithelial cells of large airways expressed FGFR1, 2, and 4; and alveolar cells expressed FGFR2, 3, and 4. Analysis of protein expression first identified FGF2 localized to the basement membrane of large airways and branching epithelial buds, to mesenchymal cells associated with buds, to the putative smooth muscle cells of large airways and vessels, and to pleural- and mesenchymal-associated cells (E18). Immediately before birth, this pattern of expression persisted (E20 to E22), with FGF2 also being expressed by putative smooth muscle cells of smaller airways and vessels (E22). After birth (P0 to P28), FGF2 expression remained relatively high in the smooth muscle cells of large and small vessels and in pleural cells; in airway smooth muscle cells and in most cells in the alveolar region, however, although FGF2 expression persisted in some cells, its intensity decreased with time. C1 Massachusetts Gen Hosp East, Dept Anaesthesia & Crit Care Med, Mol & Cell Biol Lab, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. BBSRC Inst Anim Hlth, Dept Pathol & Immunol, Surrey, England. Keio Univ, Sch Med, Dept Surg, Div Thorac Surg,Shinjuku Ku, Tokyo 160, Japan. RP Jones, R (reprint author), Massachusetts Gen Hosp East, Dept Anaesthesia & Crit Care Med, Mol & Cell Biol Lab, 149 23rd St, Boston, MA 02129 USA. EM Ljones@etherdome.mgh.harvard.edu NR 37 TC 44 Z9 44 U1 0 U2 2 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD OCT PY 1998 VL 19 IS 4 BP 563 EP 572 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 130RY UT WOS:000076535200005 PM 9761752 ER PT J AU Tager, AM Wu, JY Vermeulen, MW AF Tager, AM Wu, JY Vermeulen, MW TI The effect of chloride concentration on human neutrophil functions: Potential relevance to cystic fibrosis SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID AIRWAY SURFACE FLUID; BRONCHOALVEOLAR LAVAGE; PSEUDOMONAS-AERUGINOSA; AGING NEUTROPHILS; INTERLEUKIN-8; IDENTIFICATION; LUNG; GENE; INFLAMMATION; EPITHELIA AB Recently, some investigators have observed elevated concentrations of chloride in the airway surface fluid (ASF) overlying respiratory epithelia from cystic fibrosis (CF) patients compared with ASF overlying non-CF epithelia. Others have shown that this elevated ASF salt concentration can inactivate human beta-defensin-1, an antimicrobial peptide secreted by respiratory epithelia. This could impair the primary epithelial defense against bacteria in the CF airway, thereby forcing a greater reliance on polymorphonuclear leukocyte (PMN)-mediated defenses. Pseudomonas aeruginosa (Psa) flourishes in the CF airway despite the presence of abundant PMN. We therefore investigated whether elevated ASF chloride concentration in CF might also compromise PMN function. We employed a cell-culture model in which halide concentrations and osmolarity were varied independently. We examined the effects of chloride concentration on three aspects of PMN function: recruitment of PMN to the airway (production of interleukin-8 [IL-8]), PMN antimicrobial activity (killing of Psa), and PMN clearance from the airways (apoptosis and lysis). We found that exposure to elevated chloride concentration increased PMN synthesis of IL-8, decreased PMN killing of Psa, and accelerated PMN apoptosis and lysis. In CF airways, elevated chloride therefore could contribute to the increased number of PMN recruited into the airways, the increased survival of Psa, and the increased quantity of toxic mediators released by PMN into the airways. These effects of elevated chloride on PMN function may provide another causal link between loss of cystic fibrosis transmembrane conductance regulator function and CF lung disease. C1 Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Vermeulen, MW (reprint author), Eisai Res Inst, 4 Corp Dr, Andover, MA 01810 USA. EM mary_vermeulen@eisai.com NR 40 TC 22 Z9 22 U1 1 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD OCT PY 1998 VL 19 IS 4 BP 643 EP 652 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 130RY UT WOS:000076535200015 PM 9761762 ER PT J AU Noh, HM Chew, FS AF Noh, HM Chew, FS TI Small-bowel perforation by a foreign body SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Chew, FS (reprint author), Wake Forest Univ, Sch Med, Dept Radiol, Med Ctr Blvd, Winston Salem, NC 27157 USA. NR 4 TC 10 Z9 11 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 OCT PY 1998 VL 171 IS 4 BP 1002 EP 1002 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 123GK UT WOS:000076117300018 PM 9762984 ER PT J AU Ryan, JM Hahn, PF Mueller, PR AF Ryan, JM Hahn, PF Mueller, PR TI Performing radiologic gastrostomy or gastrojejunostomy in patients with malignant ascites SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID PERCUTANEOUS FEEDING GASTROSTOMY; SMALL-BOWEL OBSTRUCTION; CANCER-PATIENTS; T-FASTENER; EXPERIENCE; GASTROPEXY; CARCINOMA; DRAINAGE AB OBJECTIVE. We describe our protocol for performing decompression radiologic gastrostomy and gastrojejunostomy in patients with ascites and small-bowel obstruction. We also assess the technical success rate, the complications, and the morbidity and mortality in 45 patients who underwent radiologic gastrostomy. MATERIALS AND METHODS. Forty-five consecutive patients with ascites associated with metastatic ovarian cancer underwent a radiologic gastrostomy or gastrojejunostomy with gastropexy. Six patients underwent gastrostomy, and 39 patients underwent gastrojejunostomy. Locking catheters were placed using the Seldinger technique after gastropexy in all patients. Paracentesis was performed before gastrostomy or gastrojejunostomy. Additional serial paracenteses were performed after the procedure when reaccumulation of ascites close to the site of gastropexy was detected on follow-up sonography. RESULTS. Forty-five procedures were attempted. The technical success rate was 97.8%. The complication rate was 15.6%. Three major complications (6.7%) and four minor complications (8.9%) occurred. One procedure-related death (2.2%) occurred 16 days after gastrojejunostomy. CONCLUSION. Radiologic gastrostomy and gastrojejunostomy can be performed safely in patients with ascites if the patients undergo paracentesis first and if the reaccumulation of ascites is prevented after tube placement. In patients with ascites, gastropexy plays an important role in preventing pericatheter leakage. Ascites and peritoneal carcinomatosis should not be considered contraindications for radiologic gastrostomy or gastrojejunostomy. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal & Intervent Radiol, Boston, MA 02114 USA. Duke Univ, Med Ctr, Dept Radiol, Div Angiointervent Radiol, Durham, NC 27710 USA. RP Ryan, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal & Intervent Radiol, Boston, MA 02114 USA. NR 21 TC 17 Z9 18 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 OCT PY 1998 VL 171 IS 4 BP 1003 EP 1006 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 123GK UT WOS:000076117300019 PM 9762985 ER PT J AU Nielsen, GP O'Connell, JX Rosenberg, AE AF Nielsen, GP O'Connell, JX Rosenberg, AE TI Intramuscular myxoma - A clinicopathologic study of 51 cases with emphasis on hypercellular and hypervascular variants SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE myxoma; soft tissue ID GRADE FIBROMYXOID SARCOMA; FIBROUS DYSPLASIA AB Intramuscular myxoma (IM) is a benign soft-tissue tumor that presents as a deeply seated mass confined to skeletal muscle. Surgical excision is virtually always curative. Recurrence, even after incomplete resection, is exceptional. Intramuscular myxoma is classically described as hypocellular and hypovascular, and is composed of cytologically bland stellate and bipolar fibroblasts separated by abundant extracellular myxoid matrix. What is underemphasized, however, is that IMs often show areas of increased cellularity and vascularity that can lead to a mistaken diagnosis of sarcoma, especially myxofibrosarcoma, low-grade fibromyxoid sarcoma, and myxoid liposarcoma. In this report, we describe the clinicopathologic features of 51 IMs with special emphasis on those that exhibit these "hypercellular regions." The patients included 35 women and 16 men who ranged in age from 27 to 89 (mean 52) years. The tumors measured from 2 to 15 (average 5.6) cm and all had a gelatinous, lobulated cut surface. Histologically, they all demonstrated classic hypocellular, hypovascular regions. Thirty eight tumors contained areas of relative increased cellularity that occupied from 10 to 80% of the tumor. These foci had increased numbers of cells, more prominent vascularity, and often increased collagen content. The hypercellular regions were not associated with cytologic atypia of the constituent cells, mitotic activity, or necrosis. Follow-up information was available for 32 patients and ranged from 3 to 108 (average 30) months. No tumor recurred or metastasized. Areas of hypercellularity are common in IMs. Their recognition is important to avoid an erroneous diagnosis of sarcoma. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,James Homer Wright Pathol Labs, Boston, MA 02114 USA. Vancouver Hosp & Hlth Sci Ctr, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. RP Nielsen, GP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,James Homer Wright Pathol Labs, Fruit St, Boston, MA 02114 USA. NR 14 TC 46 Z9 53 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 1998 VL 22 IS 10 BP 1222 EP 1227 DI 10.1097/00000478-199810000-00007 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 127RJ UT WOS:000076364100007 PM 9777984 ER PT J AU Carr, PL Ash, AS Friedman, RH Scaramucci, A Barnett, RC Szalacha, L Palepu, A Moskowitz, MA AF Carr, PL Ash, AS Friedman, RH Scaramucci, A Barnett, RC Szalacha, L Palepu, A Moskowitz, MA TI Relation of family responsibilities and gender to the productivity and career satisfaction of medical faculty SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE job satisfaction; faculty, medical; career mobility; sex factors; child rearing ID ACADEMIC MEDICINE; INTERNAL-MEDICINE; WOMEN PHYSICIANS; SEX-DIFFERENCES; MEN FACULTY; DEPARTMENTS AB Background: Studies have found that female faculty publish less, have slower career progress, and generally have a more difficult time in academic careers than male faculty. The relation of family (dependent) responsibilities to gender and academic productivity is unclear. Objective: To describe dependent responsibilities by gender and to identify their relation to the aspirations, goals, rate of progress, academic productivity, and career satisfaction of male and female medical school faculty. Design: 177-item survey questionnaire. Setting: 24 randomly selected medical schools in the contiguous United States. Participants: 1979 respondents from a probability sample of full-time academic medical school faculty. Measurements: The main end point for measuring academic productivity was the total number of publications in refereed journals. Perceived career progress and career satisfaction were assessed by using Likert scales. Results: For both male and female faculty, more than 90% of time devoted to family responsibilities was spent on child care. Among faculty with children, women had greater obstacles to academic careers and less institutional support, including research funding from their institutions (46% compared with 57%; P < 0.001) and secretarial sup port (0.68 full-time equivalents compared with 0.83 full-time equivalents; P = 0.003), than men. Compared with men with children, women with children had fewer publications (18.3 compared with 29.3; P < 0.001), slower self-perceived career progress (2.6 compared with 3.1; P < 0.001), and lower career satisfaction (5.9 compared with 6.6; P < 0.001). However, no significant differences between the sexes were seen for faculty without children. Conclusions: Compared with female faculty without children and compared with men, female faculty with children face major obstacles in academic careers. Some of these obstacles can be easily modified (for example, by eliminating after-hours meetings and creating part-time career tracks). Medical schools should address these obstacles and provide support for faculty with children. C1 Massachusetts Gen Hosp, Boston Med Ctr, Boston, MA 02114 USA. Radcliffe Coll, Murray Res Ctr, Cambridge, MA USA. Harvard Univ, Grad Sch Educ, Boston, MA 02115 USA. RP Carr, PL (reprint author), Massachusetts Gen Hosp, Womens Hlth Associates, Blake 10,55 Fruit St, Boston, MA 02114 USA. OI Palepu, Anita/0000-0002-7881-4800 NR 22 TC 185 Z9 186 U1 1 U2 14 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 OCT 1 PY 1998 VL 129 IS 7 BP 532 EP + PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 123KN UT WOS:000076124500003 PM 9758572 ER PT J AU Bhattacharyya, N Nadol, JB Curtin, HD Montgomery, WW AF Bhattacharyya, N Nadol, JB Curtin, HD Montgomery, WW TI Vertigo produced by petrous extension of a radiation induced fibrosarcoma of the anterior skull base SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article ID POSTIRRADIATION SARCOMA; INVERTED PAPILLOMA; PARANASAL SINUSES; NASAL CAVITY; THERAPY; HEAD; NECK C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Bhattacharyya, N (reprint author), Joint Ctr Otolaryngol, 333 Longwood Ave 3rd Floor, Boston, MA 02115 USA. NR 10 TC 3 Z9 3 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD OCT PY 1998 VL 107 IS 10 BP 898 EP 900 PN 1 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA 129QG UT WOS:000076474000015 PM 9794622 ER PT J AU Khuri, SF Daley, J Henderson, W Hur, K Demakis, J Aust, JB Chong, V Fabri, PJ Gibbs, JO Grover, F Hammermeister, K Irvin, G McDonald, G Passaro, E Phillips, L Scamman, F Spencer, J Stemple, JF AF Khuri, SF Daley, J Henderson, W Hur, K Demakis, J Aust, JB Chong, V Fabri, PJ Gibbs, JO Grover, F Hammermeister, K Irvin, G McDonald, G Passaro, E Phillips, L Scamman, F Spencer, J Stemple, JF CA Natl VA Surgical Quality Improvement Program TI The Department of Veterans Affairs' NSQIP - The first national, validated, outcome-based, risk-adjusted, and peer-controlled program for the measurement and enhancement of the quality of surgical care SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 118th Annual Meeting of the American-Surgical-Association CY APR 03, 1998 CL PALM BEACH, FLORIDA SP Amer Surgical Assoc ID CARDIAC-SURGERY; HEALTH-CARE; CONTINUOUS IMPROVEMENT AB Objective To provide reliable risk-adjusted morbidity and mortality rates after major surgery to the 123 Veterans Affairs Medical Centers (VAMCs) performing major surgery, and to use risk-adjusted outcomes in the monitoring and improvement of the quality of surgical care to all veterans. Summary Background Data Outcome-based comparative measures of the quality of surgical care among surgical services and surgical subspecialties have been elusive. Methods This study included prospective assessment of presurgical risk factors, process of care during surgery, and outcomes 30 days after surgery on veterans undergoing major surgery in 123 medical centers; development of multivariable risk-adjustment models; identification of high and low outlier facilities by observed-to-expected outcome ratios; and generation of annual reports of comparative outcomes to all surgical services in the Veterans Health Administration (VHA). Results The National VA Surgical Quality Improvement Program (NS-QIP) data base includes 417,944 major surgical procedures performed between October 1, 1991, and September 30, 1997. In FY97, 11 VAMCs were low outliers for risk-adjusted observed-to-expected mortality ratios; 13 VAMCs were high outliers for risk-adjusted observed-to-expected mortality ratios. Identification of high and low outliers by unadjusted mortality rates would have ascribed an outlier status incorrectly to 25 of 39 hospitals, an error rate of 64%. Since 1994, the 30-day mortality and morbidity rates for major surgery have fallen 9% and 30%, respectively. Conclusions Reliable, valid information on patient presurgical risk factors, process of care during surgery, and 30-day morbidity and mortality rates is available for all major surgical procedures in the 123 VAMCs performing surgery in the VHA. With;this information, the VHA has established the first prospective out come-based program for comparative assessment and enhancement of the quality of surgical care among multiple institutions for several surgical subspecialties. Key features to the success of the NSQIP are the support of the surgeons who practice in the VHA, consistent clinical definitions and data collection by dedicated nurses, a uniform nationwide informatics system, and the support of VHA administration and managerial staff. C1 Brockton W Roxbury Vet Affairs Med Ctr, W Roxbury, MA 02132 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA USA. Hines VA Ctr Cooperat Studies Hlth Serv, Hines, IL USA. Univ Texas, Hlth Sci Ctr, Dept Surg, San Antonio, TX 78284 USA. Vet Integrated Serv Network 17, Grand Prairie, TX USA. Vet Adm Med Ctr, Tampa, FL 33607 USA. Univ S Florida, Coll Med, Tampa, FL USA. Vet Adm Med Ctr, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Miami, Dept Surg, Miami, FL 33152 USA. Univ Miami, Sch Med, Miami, FL USA. Vet Adm Med Ctr, Miami, FL 33125 USA. Dept Vet Affairs Headquarters, Dept Surg, Washington, DC USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Vet Integrated Serv Network 11, Ann Arbor, MI USA. Natl Anesthesia Serv, Dept Anesthesia, Iowa City, IA USA. Vet Adm Med Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Khuri, SF (reprint author), Brockton W Roxbury Vet Affairs Med Ctr, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. NR 19 TC 868 Z9 874 U1 6 U2 26 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD OCT PY 1998 VL 228 IS 4 BP 491 EP 504 DI 10.1097/00000658-199810000-00006 PG 14 WC Surgery SC Surgery GA 129QK UT WOS:000076474300011 PM 9790339 ER PT J AU Akins, CW AF Akins, CW TI Full sternotomy through a minimally invasive incision: A cardiac surgeon's true comfort zone SO ANNALS OF THORACIC SURGERY LA English DT Article AB Increasing attention is being paid by cardiac surgeons to performing cardiac surgical procedures through less invasive approaches, including the use of limited incisions. A limited incisional approach is described that achieves full sternotomy, allows the use of standard operative instruments and techniques, permits rapid, easy conversion to normal sternotomy exposure, and is easy to learn. (Ann Thorac Surg 1998;66:1429-30) (C) 1998 by The Society of Thoracic Surgeons. C1 Massachusetts Gen Hosp, Dept Surg, Cardiac Surg Unit, Boston, MA 02114 USA. RP Akins, CW (reprint author), Massachusetts Gen Hosp, Dept Surg, Cardiac Surg Unit, White 503, Boston, MA 02114 USA. NR 5 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD OCT PY 1998 VL 66 IS 4 BP 1429 EP 1430 DI 10.1016/S0003-4975(98)00650-X PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 133NP UT WOS:000076692900085 PM 9800857 ER PT J AU Akins, CW AF Akins, CW TI Combined carotid endarterectomy and coronary revascularization operation SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT Outcomes 98 - the Key West Meeting CY MAY 27-31, 1998 CL KEY WEST, FLORIDA SP Bayer Pharmaceut, Medtron Bio Medicus, Sangtec Med AB, Somanet Corp ID ARTERY BYPASS-SURGERY; HIGH-GRADE; STENOSIS; EFFICACY; DISEASE; STROKE; BRUITS C1 Massachusetts Gen Hosp, Dept Surg, Cardiac Surg Unit, Boston, MA 02114 USA. RP Akins, CW (reprint author), Massachusetts Gen Hosp, Dept Surg, Cardiac Surg Unit, White 503,55 Fruit St, Boston, MA 02114 USA. NR 15 TC 7 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD OCT PY 1998 VL 66 IS 4 BP 1483 EP 1484 DI 10.1016/S0003-4975(98)00844-3 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 133NP UT WOS:000076692900110 PM 9800874 ER PT J AU Graybill, JR Bocanegra, R Najvar, LK Loebenberg, D Luther, MF AF Graybill, JR Bocanegra, R Najvar, LK Loebenberg, D Luther, MF TI Granulocyte colony-stimulating factor and azole antifungal therapy in murine aspergillosis: Role of immune suppression SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID INVASIVE PULMONARY ASPERGILLOSIS; AMPHOTERICIN-B; RESISTANCE; FUMIGATUS; LEUKEMIA; INVITRO; DAMAGE; HYPHAE; FLUCONAZOLE; NEUTROPHILS AB Outbred ICR mice were immune suppressed either with hydrocortisone or with 5-fluorouracil and were infected intranasally with Aspergillus fumigatus. Beginning 3 days before infection some groups of mice were given recombinant human granulocyte colony-stimulating factor (IG-CSF), SCH56592 (an antifungal triazole), or both. Corticosteroid-pretreated mice responded to SCH56592 and had reduced counts in lung tissue and prolonged survival. In these mice, G-CSF strongly antagonized the antifungal activity of SCH56592. Animals treated with both agents developed large lung abscesses with polymorphonuclear leukocytes and large amounts of Aspergillus. In contrast, mice made neutropenic with 5-fluorouracil and then infected with A. fumigatus conidia benefited from either G-CSF or triazoles, and the effect of the combination was additive rather than antagonistic. Host predisposing factors contribute in different ways to the outcome of growth factor therapy in aspergillosis. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Schering Plough Corp, Res Inst, Kenilworth, NJ USA. Audie L Murphy Mem Vet Adm Med Ctr, Infect Dis Sect 111F, San Antonio, TX 78284 USA. RP Graybill, JR (reprint author), Audie L Murphy Mem Vet Adm Med Ctr, Infect Dis Sect 111F, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. EM GRAYBILL@UTHSCSA.EDU NR 41 TC 65 Z9 68 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 OCT PY 1998 VL 42 IS 10 BP 2467 EP 2473 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 126MH UT WOS:000076296900001 PM 9756743 ER PT J AU Al-Abdely, HM Graybill, JR Bocanegra, R Najvar, L Montalbo, E Regen, SL Melby, PC AF Al-Abdely, HM Graybill, JR Bocanegra, R Najvar, L Montalbo, E Regen, SL Melby, PC TI Efficacies of KY62 against Leishmania amazonensis and Leishmania donovani in experimental murine cutaneous leishmaniasis and visceral leishmaniasis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID LIPOSOMAL AMPHOTERICIN-B; KALA-AZAR; KETOCONAZOLE; AMBISOME AB Current therapy for leishmaniasis is unsatisfactory because parenteral antimonial salts and pentamidine are associated with significant toxicity and failure rates, We examined the efficacy of KY62, a new, water-soluble, polyene antifungal, against cutaneous infection with Leishmania amazonensis and against visceral infection with Leishmania donovani in susceptible BALB/c mice. Mice were infected with I,, amazonensis promastigotes in the ear pinna and in the tail and were treated with KY62 or amphotericin B. The cutaneous Lesions showed a remarkable response to therapy with KY62 at a dose of 30 mg per kg of body weight per day, At this dose, the efficacy of KY62 was equivalent to or better than that of amphotericin B at 1 to 5 mg/kg/day, Mice infected intravenously with 10(7) L, donovani promastigotes and treated with KY62 showed a 4-log reduction in the parasite burden in the liver and spleen compared to untreated mice. These studies indicate potent activity of KY62 against experimental cutaneous leishmaniasis caused by L, amazoniensis and against experimental visceral leishmaniasis caused by L. donovani. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, San Antonio, TX 78284 USA. Audie Murphy Vet Adm Hosp, San Antonio, TX 78284 USA. Lehigh Univ, Dept Chem, Bethlehem, PA 18015 USA. RP Al-Abdely, HM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIAID NIH HHS [AI28220] NR 23 TC 14 Z9 14 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 OCT PY 1998 VL 42 IS 10 BP 2542 EP 2548 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 126MH UT WOS:000076296900011 PM 9756753 ER PT J AU Soukos, NS Ximenez-Fyvie, LA Hamblin, MR Socransky, SS Hasan, T AF Soukos, NS Ximenez-Fyvie, LA Hamblin, MR Socransky, SS Hasan, T TI Targeted antimicrobial photochemotherapy SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID GRAM-NEGATIVE BACTERIA; LOW-POWER LASER; MESOSUBSTITUTED CATIONIC PORPHYRINS; POSITIVE BACTERIA; ORAL BACTERIA; LETHAL PHOTOSENSITIZATION; OUTER-MEMBRANE; IN-VITRO; PHOTOINACTIVATION; CELLS AB This study explores a new approach for antimicrobial therapy with light activation of targeted poly-L-lysine (pL)-chlorin e6 (c(e6)) conjugates, The goal was to test the hypothesis that these conjugates between pL and c(e6) would efficiently target photodestruction towards gram-positive (Actinomyces viscosus) and gram-negative (Porphyromonas gingivalis) oral species while sparing an oral epithelial cell line (HCPC-1). Conjugates of c(e6) with pL (average molecular a eight, 2,000) having a positive, neutral, or negative charge were prepared. Illumination with red light (lambda(max) = 671 nm) from a diode array produced a dose-dependent loss of CFU from the bacteria, under conditions that did not affect the viability of the epithelial cells. For P, gingivalis, the cationic conjugate produced 99% killing, while the neutral conjugate killed 91% and the anionic conjugate killed 76% after I min of incubation and exposure to red light for 10 min. For A. viscosus, the cationic conjugate produced >99.99% killing while HCPC-1 cells remained intact. The importance of the positive charge was shown by the effectiveness of c(e6)-monoethylenediamine monoamide (a monocationic derivative of c(e6)) in killing both bacteria, The clinically employed benzoporphyrin derivative under the same conditions killed epithelial cells while leaving P, gingivalis relatively unharmed. A mixture of c(e6) with pi, did not show phototoxicity comparable with that of the cationic conjugate. These results were explained by the selective uptake of the conjugates by bacteria (20- to 100-fold) compared to that by mammalian cells, while free c(e6) showed much less selectivity for bacteria (5- to 20-fold), The data suggest that the cationic pL-c(e6) conjugate may have an application for the photodynamic therapy of periodontal disease. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Dermatol, Sch Med,Wellman Labs Photomed, Boston, MA 02114 USA. Forsyth Dent Ctr, Dept Periodontol, Boston, MA 02115 USA. RP Hasan, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Dermatol, Sch Med,Wellman Labs Photomed, 50 Blossom St,WEL 224, Boston, MA 02114 USA. EM hasan@helix.mgh.halvard.edu OI Hamblin, Michael/0000-0001-6431-4605 NR 35 TC 178 Z9 183 U1 3 U2 31 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 OCT PY 1998 VL 42 IS 10 BP 2595 EP 2601 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 126MH UT WOS:000076296900019 PM 9756761 ER PT J AU Narula, J Chandrasekhar, Y Dec, GW AF Narula, J Chandrasekhar, Y Dec, GW TI Apoptosis in heart failure: a tale of heightened expectations, unfulfilled promises and broken hearts ... SO APOPTOSIS LA English DT Article DE cardiomyopathy; caspases; cytochrome c; heart transplantation; ischemic heart disease; myocardial contractility; myocardium ID UNNATURAL GROWTH-RESPONSE; PROGRAMMED CELL-DEATH; TUMOR-NECROSIS-FACTOR; FAILING HUMAN HEART; CARDIAC MYOCYTES; ANGIOTENSIN-II; SOLUBLE FAS; CARDIOMYOPATHY; HYPERTROPHY; EXPRESSION AB Although apoptosis contributes significantly to remodeling of the fetal heart during evolution of cardiac chambers and correct routing of the great vessels, it has been believed that apoptosis does not occur in terminally differentiated adult cardiac muscle cells. However, apoptosis has recently been demonstrated in animal models of heart failure as well as in explanted hearts from patients with end-stage heart failure undergoing cardiac transplantation. Ventricular dilatation and neurohormonal activation, the hall-marks of heart failure, lead to upregulation of transctription factors, induce muscle cell hypertrophy and prepare cells for entry into the cell-division cycle. However, since terminally differentiated myocytes cannot divide, they die by apoptosis. It has been proposed that low-grade apoptosis in failing heart may be responsible for inexorable decline in left ventricular function. Better understanding of the molecular and cellular basis of apoptosis in the failing myocardium may lead to development of strategies aimed at preventing progressive myocyte loss and deterioration in left ventricular function. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Med Coll Penn & Hahnemann Univ, Sch Med, Philadelphia, PA 19102 USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. RP Narula, J (reprint author), Hahnemann Univ Hosp, Broad & Vine St,Mail Stop 471, Philadelphia, PA 19102 USA. NR 27 TC 4 Z9 4 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1360-8185 J9 APOPTOSIS JI Apoptosis PD OCT PY 1998 VL 3 IS 5 BP 309 EP 315 DI 10.1023/A:1009673501809 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 215WU UT WOS:000081407100001 PM 14646478 ER PT J AU Maurer, M Peters, EMJ Botchkarev, VA Paus, R AF Maurer, M Peters, EMJ Botchkarev, VA Paus, R TI Intact hair follicle innervation is not essential for anagen induction and development SO ARCHIVES OF DERMATOLOGICAL RESEARCH LA English DT Article DE hair growth; C57BL/6 mice; denervation ID GROWTH-FACTOR; MURINE SKIN; MAST-CELLS; MOUSE SKIN; INHIBITION; MODULATION; EXPRESSION; CATAGEN; CYCLE AB Neuropeptides produced, stored and secreted by the unusually dense sensory and autonomic innervation of hair follicles (HFs) can induce hair growth (anagen) and may be involved in hair growth control, To test the role of follicle innervation of HF cycling in vivo, we generated innervation-deficient HFs by unilateral surgical denervation of a defined region of back skin in C57BL/6 mice and assessed its effect on spontaneous and induced anagen development, Successful denervation was demonstrated by the absence of PGP 9.5+ or tyrosine hydroxylase+ nerves and nerve-associated neuropeptides (substance P, CGRP). By quantitative histomorphometry, no significant difference in spontaneous or cyclosporin A-induced anagen development could be detected between sham-operated control skin and denervated skin. Only after hair growth induction by depilation, a discrete, marginally significant retardation of anagen development was apparent in denervated HFs, Thus, even though cutaneous nerves may exert a minor modulatory role in depilation-induced hair growth, they are not essential for normal murine anagen development. C1 Charite Humboldt Univ Berlin, Dept Dermatol, D-10117 Berlin, Germany. RP Maurer, M (reprint author), Beth Israel Deaconess Med Ctr Sch, Dept Pathol, Div Expt Pathol, Res N,POB 15707, Boston, MA 02215 USA. NR 23 TC 18 Z9 19 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-3696 J9 ARCH DERMATOL RES JI Arch. Dermatol. Res. PD OCT PY 1998 VL 290 IS 10 BP 574 EP 578 DI 10.1007/s004030050354 PG 5 WC Dermatology SC Dermatology GA 137LH UT WOS:000076915900009 PM 9836509 ER PT J AU Duke, D Khatri, K Grevelink, JM Anderson, RR AF Duke, D Khatri, K Grevelink, JM Anderson, RR TI Comparative clinical trial of 2 carbon dioxide resurfacing lasers with varying pulse durations - 100 microseconds vs 1 millisecond SO ARCHIVES OF DERMATOLOGY LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the American-Society-of-Laser-Medicine-and-Surgery CY APR 04-06, 1997 CL PHOENIX, ARIZONA SP Amer Soc Laser Med & Surg ID HIGH-ENERGY; HUMAN-SKIN; WRINKLES; RHYTIDES AB Objectives: To compare the clinical and histological effects of 2 carbon dioxide lasers with different pulse durations and to evaluate the effect of carbon dioxide laser pulse duration on postprocedure erythema, wound healing, and efficacy of wrinkle treatment. Design: Prospective, randomized, comparative clinical, trial. Setting: A university-affiliated hospital-based laser center. Patients: Thirty-five patients with facial wrinkles were enrolled in the study. Treatment sites included 15 perioral, 14 periorbital areas, and 6 full face. Intervention: A 2-sided comparison was performed. One side of the study site was treated with. the TruPulse laser (Tissue Technologies, Palomar Medical Products Inc, Lexington, Mass). The other side of the study site was treated with the UltraPulse 5000 laser (Coherent Medical Inc, Pale Alto, Calif). The 2 sides were treated to equivalent tissue effects rather than maintaining the number of passes. Main Outcome Measures: Photographs of the treatment areas at baseline, week 1, week 2, month 2, and month 6 were evaluated by a 5-member panel for degree of erythema, amount of edema, and percentage of wrinkle improvement. Silicon skin casts for profilometry measurements before and after the treatment were compared. To evaluate skin shrinkage, surface area before and after treatment of square tattoos on both cheeks of the full-face patients were computed using a digital imaging system. Histological sections before and after the procedure were analyzed. Results: At week 1, 75% of the patients had more erythema on the UltraPulse than TruPulse sides. The difference in erythema (TruPulse less than UltraPulse) between the 2 treatment sides was clinically mild yet statistically significant for weeks I (P = .05) and 2 (P = .05). Although observed results favored the UltraPulse over the TruPulse, the difference in efficacy between the 2 lasers did not reach statistical significance. Conclusions: Compared with the longer pulse-duration carbon dioxide laser, the shorter pulse-duration carbon dioxide laser, used with higher energy and more passes, caused slightly less erythema while maintaining efficacy. The longer pulse-duration laser required lower energy and fewer number of passes to achieve an equivalent depth of ablation, level of residual thermal damage, and degree of efficacy. The shorter TruPulse allows for more superficial tissue damage per pass and therefore is best suited for situations requiring superficial or more controlled ablation. The longer UltraPulse achieves a desirable depth of tissue damage with fewer passes. The data did not support the long-term presence of tissue collagen shrinkage in the treated areas. C1 Massachusetts Gen Hosp, Dermatol Laser Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Wellman Labs Photomed, Boston, MA USA. RP Grevelink, JM (reprint author), Massachusetts Gen Hosp, Dermatol Laser Ctr, POB 503,275 Cambridge St, Boston, MA 02114 USA. NR 20 TC 11 Z9 11 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD OCT PY 1998 VL 134 IS 10 BP 1240 EP 1246 DI 10.1001/archderm.134.10.1240 PG 7 WC Dermatology SC Dermatology GA 129QH UT WOS:000076474100008 PM 9801679 ER PT J AU Hadlock, T Elisseeff, J Langer, R Vacanti, J Cheney, M AF Hadlock, T Elisseeff, J Langer, R Vacanti, J Cheney, M TI A tissue-engineered conduit for peripheral nerve repair SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID SCIATIC-NERVE; SCHWANN-CELLS; GUIDANCE CHANNELS; REGENERATION; RAT; INCREASES; TRAUMA; INVIVO; ACID; GAP AB Background: Peripheral nerve repair using autograft material has several shortcomings, including donor site morbidity, inadequate return of function, and aberrant regeneration. Recently, peripheral nerve research has focused on the generation of synthetic nerve guidance conduits that might overcome these phenomena to improve regeneration. In our laboratory, we use the unique chemical and physical properties of synthetic polymers in conjunction with the biological properties of Schwann cells to create a superior prosthesis for the repair of multiply branched peripheral nerves, such as the facial nerve. Objectives: To create a polymeric facial nerve analog approximating the fascicular architecture of the extratemporal facial nerve, to introduce a population of Schwann cells into the analog, and to implant the prosthesis into an animal model for assessment of regeneration. Results: Tubes of poly-L-lactic acid (molecular weight, 100000) or polylactic-co-glycolic acid copolymer were formed using a dip-molding technique. They were created containing 1, 2, 4, or 5 sublumina, or "fascicular analogs." Populations of Schwann cells were isolated, expanded in culture, and plated onto these polymer films, where they demonstrated excellent adherence to the polymer surfaces. Regeneration was demonstrated through several constructs. Conclusions: A tubular nerve guidance conduit possessing the macroarchitecture of a polyfascicular peripheral nerve was created. The establishment of resident Schwann cells onto poly-L-lactic acid and polylactic-co-glycolic acid surfaces was demonstrated, and the feasibility of in vivo regeneration through the conduit was shown. It is hypothesized that these tissue-engineered devices, composed of widely used biocompatible, biodegradable polymer materials and adherent Schwann cells, will be useful in promoting both more robust and more precisely directed peripheral nerve regeneration. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Childrens Hosp, Lab Transplantat & Tissue Engn, Boston, MA 02115 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hadlock, T (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 32 TC 113 Z9 123 U1 0 U2 15 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD OCT PY 1998 VL 124 IS 10 BP 1081 EP 1086 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 127QY UT WOS:000076363100001 PM 9776185 ER PT J AU Milberger, S Faraone, SV Biederman, J Chu, MP Wilens, T AF Milberger, S Faraone, SV Biederman, J Chu, MP Wilens, T TI Familial risk analysis of the association between attention-deficit/hyperactivity disorder and psychoactive substance use disorders SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; NATIONAL-COMORBIDITY-SURVEY; PSYCHIATRIC-DISORDERS; FOLLOW-UP; UNITED-STATES; CHILDREN; SELECTION; ADULTS; PREVALENCE; DEPENDENCE AB Objective: To test hypotheses about patterns of familial association between attention-deficit/hyperactivity disorder (ADHD) and psychoactive substance use disorders (PSUDs) by using the family study method. Design: The first-degree relatives of clinically referred children and adolescents with ADHD (131 probands, 413 relatives) and healthy control probands (106 probands, 323 relatives) were assessed by blind raters. Results: After stratifying the probands with ADHD and the control probands into those with PSUD (group 1 and group 3, respectively) and those without PSUD (group 2 and group 4, respectively), familial risk analyses revealed the following: (1) the risk for ADHD was not significantly different between relatives of group 2 and group 1 probands (19.6% vs 18.0%; P = .88), but these 2 risks were significantly greater than the risk to relatives of group 3 probands (1.0%; P = .01 and P = .02, respectively) and group 4 probands (7.0%; P = .001 and P = .01, respectively); (2) there were no significant differences in the risk for PSUD between relatives of group 1 (47.5%) and group 3 probands (39.7%; P = .40), but these risks were greater than the risk to relatives of group 2 (30.0%; P = .32) and group 4 probands (20.9%; P < .001); and (3) there was no evidence for nonrandom mating. Conclusions: These findings are consistent with the hypothesis that ADHD and PSUD are transmitted independently in families. Because the probands were young adolescents, many have not lived through the age at risk for PSUD. Thus, the hypothesis stating that ADHD and PSUD represent variable expressions of a common underlying risk factor cannot be ruled out. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, ACC-725,15 Parkman St, Boston, MA 02114 USA. EM biederman@helix.mgh.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NIDA NIH HHS [1 K01 DA00294-01]; NIMH NIH HHS [R01 MH41314-07] NR 47 TC 21 Z9 21 U1 4 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD OCT PY 1998 VL 152 IS 10 BP 945 EP 951 PG 7 WC Pediatrics SC Pediatrics GA 126LN UT WOS:000076295000002 PM 9790603 ER PT J AU Cooper, RA Dvorznak, MJ O'Connor, TJ Boninger, ML Jones, DK AF Cooper, RA Dvorznak, MJ O'Connor, TJ Boninger, ML Jones, DK TI Braking electric-powered wheelchairs: Effect of braking method, seatbelt, and legrests SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article ID OCCUPIED WHEELCHAIRS; UNITED-STATES; ACCIDENTS; STABILITY; DESIGN AB Objective: To examine the influence of three electric-powered wheelchair braking conditions and four wheelchair seating conditions on electric-powered wheelchair motion and Hybrid II test dummy motion. This study provides quantitative information related to assessing the safety of electric-powered wheelchair driving. Design: Rehabilitation engineering comparison and ANSI/ RESNA. standards testing. Convenience sample of eight different electric-powered wheelchairs. Within-chair comparisons were conducted. Intervention: Electric-powered wheelchairs were compared under three braking scenarios (joystick release, joystick reverse, power-oft? and four searing conditions (seatbelt and legrests, seatbelt and no legrests, no seatbelt but legrests, no seatbelt and no legrests), Setting: A rehabilitation engineering center. Main Outcome Measures: The braking distance, braking time, and braking accelerations for electric-powered wheelchairs during three braking scenarios; trunk motion, head motion, and trunk angular acceleration during three braking scenarios and four seating conditions; and number of fails from the wheelchairs for three braking scenarios and four seating conditions. Results: Significant differences (p <.05) were found in braking distance, braking time, and braking acceleration when comparing the joystick release and joystick reverse scenarios with the power-off scenario, The mean braking distance was shortest with the power-off braking scenario (.89m), whereas it was longest when the joystick was released (1.66m), Significant differences (p <.05) in head displacement and trunk angular displacement were observed among braking conditions and between seating conditions. There were also significant differences (p =.0011) among braking conditions for maximum trunk angular acceleration, The Hybrid II test dummy fell from the wheelchairs with highest frequency when there were no legrests and no seatbelt used. Conclusion: The results of this study indicate that use of a seatbelt when driving an electric-powered wheelchair reduces the risk of failing from a wheelchair, Furthermore, the use of legrests can reduce the risk of injury to the wheelchair driver. This study shows that the most abrupt braking occurs when deactivating the power switch. (C) 1998 by the American Congress of Rehabilitation Medicine and thr American Academy of Physical Medicine and Rehabilitation. C1 Univ Pittsburgh, Sch Hlth & Rehabil Sci, Dept Rehabil Sci & Technol, Human Engn Res Labs, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr Hlth Syst, Dept Orthopaed Surg, Div Phys Med & Rehabil, Pittsburgh, PA USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151R1, Res Serv, 7180 Highland Dr, Pittsburgh, PA 15206 USA. OI Boninger, Michael/0000-0001-6966-919X NR 20 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD OCT PY 1998 VL 79 IS 10 BP 1244 EP 1249 DI 10.1016/S0003-9993(98)90269-6 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 128CC UT WOS:000076386800009 PM 9779678 ER PT J AU Moore, KJ Fabunmi, RP Andersson, LP Freeman, MW AF Moore, KJ Fabunmi, RP Andersson, LP Freeman, MW TI In vitro differentiated embryonic stem cell macrophages - A model system for studying atherosclerosis-associated macrophage functions SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE atherosclerosis; macrophage; scavenger receptor; foam cell ID LOW-DENSITY-LIPOPROTEIN; SCAVENGER RECEPTOR; FOAM CELLS; EXPRESSION; MACROSIALIN; CYTOKINES; STABILITY; LESIONS; PLAQUE; LINES AB Monocytes/macrophages (Mo) appear to play a critical role in the initiation and progression of atherosclerotic lesions. In this study, we characterized in vitro-differentiated embryonic stem (ES) cell macrophages as a model system for studying atherosclerosis-associated Mo functions. Using immunofluorescence staining and Western analysis, we demonstrate that ES Mo express typical macrophage cell surface markers, as well as the known receptors for modified forms of low density lipoprotein (LDL), including the Mo scavenger receptors (SR-A type I and type II), CD36, and CD68. Differentiated ES Mo specifically bind and degrade I-125-labeled acetylated LDL with high affinity, and their incubation with acetylated LDL (15 mu g/mL) for 48 hours produces characteristic "foamy" Mo, as visualized by oil red O staining. ES Mo also express matrix-degrading metalloproteinases (MMP-3, MMP-9), which have been implicated in collagen breakdown in the fibrous cap of atherosclerotic plaques, and secrete cytokines (tumor necrosis factor-ct, interleukin-6) in response to inflammatory stimuli. Transfection experiments, using a green fluorescent protein reporter gene, driven by the myeloid-specific promoter, CD11b, demonstrated that ES Mo can also be used to study macrophage-restricted gene expression in vitro. Taken together, these data demonstrate that ES Mo exhibit many properties typical of arterial lesion macrophages. Its ease of genetic manipulation makes it an attractive system for investigations of macrophage functions in vitro. C1 Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. RP Freeman, MW (reprint author), Massachusetts Gen Hosp, Lipid Metab Unit, GRJ 1328,55 Fruit St, Boston, MA 02114 USA. EM freeman@frodo.mgh.harvard.edu FU NHLBI NIH HHS [5 R01 HL 45098-7]; PHS HHS [P01 50305-8] NR 26 TC 26 Z9 27 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD OCT PY 1998 VL 18 IS 10 BP 1647 EP 1654 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 128PP UT WOS:000076415300020 PM 9763539 ER PT J AU Cooper, GS Dooley, MA Treadwell, EL St Clair, EW Parks, CG Gilkeson, GS AF Cooper, GS Dooley, MA Treadwell, EL St Clair, EW Parks, CG Gilkeson, GS TI Hormonal, environmental, and infectious risk factors for developing systemic lupus erythematosus SO ARTHRITIS AND RHEUMATISM LA English DT Review ID AUTOIMMUNE-DISEASE; ANTINUCLEAR ANTIBODIES; RHEUMATOID-ARTHRITIS; ESTROGEN METABOLISM; ORAL-CONTRACEPTIVES; OCCASIONAL SERIES; AFRICAN-AMERICANS; CELL ACTIVATION; BETA-CAROTENE; SEX-HORMONES C1 NIEHS, Epidemiol Branch A3 05, Durham, NC 27709 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. E Carolina Univ, Sch Med, Greenville, NC 27858 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Cooper, GS (reprint author), NIEHS, Epidemiol Branch A3 05, POB 12233, Durham, NC 27709 USA. OI Parks, Christine/0000-0002-5734-3456 NR 99 TC 122 Z9 128 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD OCT PY 1998 VL 41 IS 10 BP 1714 EP 1724 DI 10.1002/1529-0131(199810)41:10<1714::AID-ART3>3.0.CO;2-U PG 11 WC Rheumatology SC Rheumatology GA 127FZ UT WOS:000076341300002 PM 9778212 ER PT J AU Warner, JJP Dirksmeier, P AF Warner, JJP Dirksmeier, P TI Glenoid fracture nonunion presenting as instability in a young athlete SO ARTHROSCOPY LA English DT Article DE fracture; instability; nonunion; glenoid ID SHOULDER AB A case of a teenage athlete with a 4-year history of shoulder pain caused by glenoid fracture nonunion is presented. This individual had findings consistent with traumatic anterior shoulder instability as well as normal radiographs. Arthroscopy showed a nondisplaced glenoid fracture that was stabilized successfully through a deltopectoral approach. C1 Univ Pittsburgh, Ctr Sports Med, Dept Orthopaed Surg, Shoulder Serv, Pittsburgh, PA 15261 USA. RP Warner, JJP (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St,GRB-624, Boston, MA 02114 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD OCT PY 1998 VL 14 IS 7 BP 738 EP 740 DI 10.1016/S0749-8063(98)70100-8 PG 3 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 127VY UT WOS:000076372300010 PM 9788369 ER PT J AU Katznelson, L AF Katznelson, L TI Therapeutic role of androgens in the treatment of osteoporosis in men SO BAILLIERES CLINICAL ENDOCRINOLOGY AND METABOLISM LA English DT Article DE testosterone; osteoporosis; hypogonadism ID BONE-MINERAL DENSITY; GROWTH-FACTOR-I; IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; ADOLESCENT MALE HYPOGONADISM; CLINICAL RESEARCH-CENTER; LEAN BODY-MASS; ELDERLY MEN; TESTOSTERONE REPLACEMENT; ESTROGEN-RECEPTOR; CONTROLLED TRIAL AB There has been much recent interest in the relationship between androgens and bone mineralization in men. Increases in serum androgens during puberty allow for skeletal maturation and the attainment of peak bone mass, and the persistence of normal testosterone secretion during adulthood is important for the maintenance of bone density. Testosterone deficiency is associated with heightened bone turnover and is a major risk factor for osteoporosis in men. The administration of testosterone to androgen-deficient men leads to an increase in bone mass, particularly in the trabecular bone compartment, and a reduction in levels of surrogate markers of bone turnover, suggesting that androgens have a dampening effect on bone remodelling. In addition, the administration of androgens to eugonadal men with idiopathic osteoporosis, with resulting supraphysiological testosterone concentrations, may lead to increases in bone mineral density. The risk of osteopenia due to androgen deficiency and the benefits of testosterone substitution therapy or supraphysiological administration on bone will be reviewed. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Unit, Boston, MA 02114 USA. RP Katznelson, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Unit, Boston, MA 02114 USA. NR 74 TC 11 Z9 11 U1 1 U2 2 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0950-351X J9 BAILLIERE CLIN ENDOC JI Baillieres Clin. Endocrinol. Metab. PD OCT PY 1998 VL 12 IS 3 BP 453 EP 470 DI 10.1016/S0950-351X(98)80210-3 PG 18 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 178MV UT WOS:000079270500009 PM 10332566 ER PT J AU Hooper, DC AF Hooper, DC TI Clinical applications of quinolones SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Review DE quinolone; infection; resistance; pharmacology; DNA gyrase; topoisomerase IV ID URINARY-TRACT INFECTIONS; RESISTANT ESCHERICHIA-COLI; COMMUNITY-ACQUIRED PNEUMONIA; FLUOROQUINOLONE ANTIMICROBIAL AGENTS; PSEUDOMONAS-AERUGINOSA INFECTION; MULTIPLE-ANTIBIOTIC-RESISTANCE; CHRONIC BACTERIAL PROSTATITIS; SHIGELLA-DYSENTERIAE TYPE-1; MAMMALIAN TOPOISOMERASE-II; LEVOFLOXACIN L-OFLOXACIN AB The quinolone antimicrobials are the class of inhibitors of bacterial topoisomerases that has been developed most fully for clinical use in human medicine. Initial members of the class had their greatest potency against Gram-negative bacteria, but newly developed members have exhibited increased potency against Gram-positive bacteria and soon agents will be available with additional activity against anaerobic bacteria, providing a broad spectrum of potency. After nalidixic acid, the earliest member of the class which was used for treatment of urinary tract infections, the later fluoroquinolone congeners have had sufficient potency, absorption, and distribution into tissue for additional uses in treatment of sexually transmitted diseases, infections of the gastrointestinal tract, respiratory tract, skin, and bones and joints. Tolerability of these agents in usual doses has been good. Acquired bacterial resistance resulting from clinical uses has occurred in particular among staphylococci and Pseudomonas aeruginosa. Intense drug use and ability of resistant pathogens to spread have also contributed to development of resistance in initially more susceptible pathogens such as Escherichia coli and Neisseria gonorrhoeae in certain settings. Preservation of the considerable clinical utility of the quinolone class for the long term will be affected by the extent to which their use is judicious. 0167-4781/98/$ - see front matter (C) 1998 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. RP Hooper, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. EM hooper.david@mgh.harvard.edu NR 187 TC 105 Z9 107 U1 2 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD OCT 1 PY 1998 VL 1400 IS 1-3 BP 45 EP 61 DI 10.1016/S0167-4781(98)00127-4 PG 17 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 129AH UT WOS:000076440500005 PM 9748496 ER PT J AU Vio, CP Oestreicher, E Olavarria, V Velarde, V Mayfield, RK Jaffa, AA AF Vio, CP Oestreicher, E Olavarria, V Velarde, V Mayfield, RK Jaffa, AA TI Cellular distribution of exogenous aprotinin in the rat kidney SO BIOLOGICAL CHEMISTRY LA English DT Article DE collecting ducts; connecting tubules; immunohistochemistry; kidney; proximal tubules ID KALLIKREIN-KININ SYSTEM; RENAL KALLIKREIN; RENIN RELEASE; INHIBITOR; HYPERFILTRATION; LOCALIZATION; RESPONSES; EXCRETION; INSULIN AB Aprotinin, an inhibitor of the enzymatic activity of kallikrein in vitro, has been used to study the possible contributions of the kallikrein-kinin systems to physiological and pathological conditions. Pharmacokinetic studies indicate that aprotinin is concentrated in the kidney; however, there is little information with regard to its cellular distribution. The purpose of the present work was to study the cellular distribution of aprotinin, which would be valuable for a better understanding of its intrarenal effects. Sprague-Dawley rats (200-250 g, n = 36) received aprotinin (50 000 KIU/rat) and were killed at different intervals after its administration. The kidneys were examined histologically and the cellular distribution of aprotinin was studied by immunohistochemistry. Aprotinin was localized at 30 min concentrated within vesicles in the apical border of the proximal tubule cells. Later (2 h) it was observed distributed over the cytoplasm, where it remained for the 24 h studied. Aprotinin was also detected in connecting tubule cells colocalized with kallikrein, and in the basal portion of collecting tubule cells. No evidence of endogenous aprotinin was observed. The binding of aprotinin to the connecting tubule cells and collecting ducts offers a partial explanation of its renal effects. C1 Pontificia Univ Catolica Chile, Fac Ciencias Biol, Dept Ciencias Fisiol, Santiago, Chile. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pharmacol, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Vio, CP (reprint author), Pontificia Univ Catolica Chile, Fac Ciencias Biol, Dept Ciencias Fisiol, Alameda 340, Santiago, Chile. OI Vio, Carlos/0000-0003-1850-5958 FU NIDDK NIH HHS [DK-46543] NR 39 TC 13 Z9 13 U1 0 U2 0 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1431-6730 J9 BIOL CHEM JI Biol. Chem. PD OCT PY 1998 VL 379 IS 10 BP 1271 EP 1277 DI 10.1515/bchm.1998.379.10.1271 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 131DP UT WOS:000076560700008 PM 9820588 ER PT J AU Sidis, Y Fujiwara, T Leykin, L Isaacson, K Toth, T Schneyer, AL AF Sidis, Y Fujiwara, T Leykin, L Isaacson, K Toth, T Schneyer, AL TI Characterization of inhibin/activin subunit, activin receptor, and follistatin messenger ribonucleic acid in human and mouse oocytes: Evidence for activin's paracrine signaling from granulosa cells to oocytes SO BIOLOGY OF REPRODUCTION LA English DT Article ID DIFFERENTIATION FACTOR-IX; IN-VITRO; ZONA-PELLUCIDA; OVARIAN FOLLICULOGENESIS; DEVELOPMENTAL EXPRESSION; MEIOTIC MATURATION; BINDING PROTEIN; INHIBIN-A; RNA; EMBRYOS AB Inhibin, activin, and follistatin (FS) are gonadal proteins that appear to have a role in regulating folliculogenesis through possible paracrine and/or autocrine interactions. To further examine the potential role of activin in oocyte-granulosa cell communication, we developed a sensitive reverse transcription-polymerase chain reaction protocol to analyze mRNA for the alpha, beta(A), and beta(B) inhibin/activin subunits, FS, and the four activin receptor subtypes in individual human and mouse oocytes. The resulting expression pattern was further compared to that in human cumulus granulosa cells. Our results indicate that neither beta(A) nor beta(B) mRNA was detectable in any human or mouse oocyte, that cu subunit was marginally present in some of the human oocytes, and that FS mRNA was detectable in human but not mouse oocytes. On the other hand, inhibin/activin subunit and FS mRNAs were abundantly expressed in cumulus cells. In addition, mRNAs for all four activin receptor subtypes (ActRIA, ActRIB, ActRIIA, and ActRIIB) were easily detectable in both oocytes and granulosa cells and appeared to be differentially expressed in oocytes during nuclear maturation. Finally, RNAs for both zona pellucida 3 and growth-differentiation factor-9, which were originally used as oocyte-specific markers, were detected in human but not mouse cumulus cells, although at lower levels than observed in oocytes. Taken together with previous studies, these results indicate that oocytes may be capable of responding to, but not synthesizing, activin. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, In Vitro Fertilizat Unit, Boston, MA 02114 USA. RP Sidis, Y (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, BHX-5, Boston, MA 02114 USA. FU NICHD NIH HHS [P30HD23138, R01HD31894, U54HD29164] NR 42 TC 82 Z9 85 U1 0 U2 3 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD OCT PY 1998 VL 59 IS 4 BP 807 EP 812 DI 10.1095/biolreprod59.4.807 PG 6 WC Reproductive Biology SC Reproductive Biology GA 124NF UT WOS:000076188100012 PM 9746729 ER PT J AU Goodman, SB Kugu, K Chen, SH Preutthipan, S Tilly, KI Tilly, JL Dharmarajan, AM AF Goodman, SB Kugu, K Chen, SH Preutthipan, S Tilly, KI Tilly, JL Dharmarajan, AM TI Estradiol-mediated suppression of apoptosis in the rabbit corpus luteum is associated with a shift in expression of bcl-2 family members favoring cellular survival SO BIOLOGY OF REPRODUCTION LA English DT Article ID RIBONUCLEIC-ACID LEVELS; CORPORA-LUTEA; PSEUDOPREGNANT RABBITS; DNA FRAGMENTATION; CHORIONIC-GONADOTROPIN; SUPEROXIDE-DISMUTASE; FOLLICULAR ATRESIA; OXIDATIVE STRESS; BLOOD-FLOW; REGRESSION AB In the rabbit, estradiol is the primary luteotropic hormone. Estradiol withdrawal results in a rapid decline in serum progesterone and eventually in corpus luteum (CL) regression. The objective of this study was to determine whether estradiol modulates luteal cell apoptosis. In the first experiment, rabbits were randomly assigned to one of five experimental groups. An empty capsule (control) or estradiol-filled Silastic capsule was inserted s.c. on Day 0 of pseudopregnancy (day of hCG administration). On Day 11 of pseudopregnancy, some of the group I (control) and group II (estradiol capsule) rabbits were subjected to laparotomy, and one ovary from each rabbit was perfused in vitro to determine progesterone secretion rates. The CL from the contralateral ovary were dissected, snap-frozen, and stored at -70 degrees C until analyzed for internucleosomal DNA cleavage (apoptosis), Estradiol-containing capsules were removed from some of the remaining rabbits on Days 8, 9, and 10 to initiate estradiol deprivation. Rabbits were then subjected to laparotomy 24, 48, or 72 h after capsule removal (groups III, IV, and V, respectively), and ovaries or CL were processed as described above. Deprivation of estradiol for 24 (group III), 48 (group IV), or 72 (group V) h in vivo reduced in vitro progesterone secretion rates by more than 90% as compared to that in ovaries collected from estradiol capsule-intact animals. After in vivo endogenous estradiol suppression, withdrawal of exogenous estradiol resulted in luteal cell apoptosis, which increased in a time-dependent manner. Northern blot analysis revealed an increase in bar mRNA levels and a decrease in bcl-x mRNA levels coincident with luteal cell apoptosis induced by estradiol withdrawal. These data demonstrate that changes in progesterone production caused by estradiol exposure and deprivation are in part related to luteal cell apoptosis, and alterations in the expression of bcl-2 gene family members may be one of the mechanisms by which estradiol exerts its luteotropic effect in the rabbit CL. C1 Johns Hopkins Univ, Sch Med, Dept On Gyn, Baltimore, MD 21201 USA. Johns Hopkins Univ, Dept Populat Dynam, Div Reprod Biol, Baltimore, MD 21201 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Ob Gyn,Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Univ Western Australia, Dept Anat & Human Biol, Perth, WA 6009, Australia. RP Dharmarajan, AM (reprint author), Johns Hopkins Univ, Sch Med, Dept On Gyn, Baltimore, MD 21201 USA. FU NIA NIH HHS [R01-AG12279]; NICHD NIH HHS [R01-HD19430, R01-HD34226] NR 43 TC 49 Z9 52 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD OCT PY 1998 VL 59 IS 4 BP 820 EP 827 DI 10.1095/biolreprod59.4.820 PG 8 WC Reproductive Biology SC Reproductive Biology GA 124NF UT WOS:000076188100014 PM 9746731 ER PT J AU Dhanda, RK van Orsouw, NJ Sigalas, I Eng, C Vijg, J AF Dhanda, RK van Orsouw, NJ Sigalas, I Eng, C Vijg, J TI Critical factors in the performance and cost of two-dimensional gene scanning: RB1 as a model SO BIOTECHNIQUES LA English DT Article ID STRAND CONFORMATION POLYMORPHISM; GRADIENT GEL-ELECTROPHORESIS; 2-DIMENSIONAL DNA ELECTROPHORESIS; DENSITY OLIGONUCLEOTIDE ARRAYS; MUTATIONS; CANCER; PCR; RETINOBLASTOMA; SEGMENTS; BREAST AB Two-dimensional (2-D) gene scanning (TDGS) is a method for mutation detection based on the electrophoretic separation of PCR-amplified DNA fragments according to size and base pair sequence. The use of denaturing gradient gel electrophoresis (DGGE) as the second separation step provides virtually 100% sensitivity, while the 2-D format allows the inspection of multiple gene fragments simultaneously. Analysis of many exons in parallel is greatly facilitated by extensive PCR multiplexing based on preamplification by long-distance PCR. Recently, TDGS has been applied to detect mutations in the retinoblastoma tumor suppressor gene RB1. Using RB1 as a model, we have now analyzed each step of the protocol, presenting overall improvements and a detailed cost analysis, where the total cost of the assay is found to be about $40 (US). An overall picture of TDGS cost-performance, as compared to direct sequencing, is provided as a function of the number of target fragments. C1 Beth Israel Deaconess Med Ctr, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Vijg, J (reprint author), Harvard Inst Med, Suite 921,77 Ave Louis Pasteur, Boston, MA 02115 USA. OI Eng, Charis/0000-0002-3693-5145 NR 34 TC 9 Z9 9 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD OCT PY 1998 VL 25 IS 4 BP 664 EP + PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 128RL UT WOS:000076420100023 PM 9793651 ER PT J AU Homeister, JW Zhang, MK Frenette, PS Hynes, RO Wagner, DD Lowe, JB Marks, RM AF Homeister, JW Zhang, MK Frenette, PS Hynes, RO Wagner, DD Lowe, JB Marks, RM TI Overlapping functions of E- and P-selectin in neutrophil recruitment during acute inflammation SO BLOOD LA English DT Article ID TUMOR-NECROSIS-FACTOR; DEFICIENT MICE; FACTOR-ALPHA; ENDOTHELIAL SELECTINS; IN-VIVO; ADHESION MOLECULE-1; LEUKOCYTE ADHESION; EXPRESSION; CELLS; MEMBRANE AB Selectin adhesion molecules mediate leukocyte rolling on activated endothelium, a prerequisite to leukocyte accumulation at sites of inflammation. The precise role of each selectin (E-, P-, and L-) in this process is unclear and may vary depending on the particular inflammatory stimulus, vascular bed, leukocyte subset, and species; most data suggest discrete functional roles for each selectin. To define the relative roles of E- and P-selectin in mediating neutrophil accumulation in acute dermal inflammation, mice genetically deficient in E-selectin, P-selectin, or both E- and P-selectin were injected intradermally with zymosan, Luminal endothelial expression of E- and P-selectin in response to zymosan was documented in wild-type mice by intravenous administration of fluorochrome-labeled anti-E- and anti-P-selectin antibodies, In mice deficient in E- or P-selectin, neutrophil accumulation was unchanged or only subtly reduced relative to wild-type control mice. In mice deficient in both E- and P-selectin, neutrophil accumulation was significantly reduced (87% at 4 hours and 79% at 8 hours). These data demonstrate that, in this model of acute inflammation, there is considerable overlap in the functions of E- and P-selectin; loss of both selectins was required to impair neutrophil accumulation. (C) 1998 by The American Society of Hematology. C1 Univ Michigan, Dept Internal Med, Med Ctr, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Pathol, Med Ctr, Ann Arbor, MI 48109 USA. Univ Michigan, Howard Hughes Med Inst, Med Ctr, Ann Arbor, MI 48109 USA. MIT, Ctr Canc Res, Dept Biol, Cambridge, MA 02139 USA. MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Marks, RM (reprint author), Univ Michigan, Dept Internal Med, Med Ctr, 5520 MSRB 1, Ann Arbor, MI 48109 USA. RI Frenette, Paul/J-8272-2012 FU NHLBI NIH HHS [HL53756, HL41484]; NIAID NIH HHS [AI33189] NR 37 TC 52 Z9 53 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 1998 VL 92 IS 7 BP 2345 EP 2352 PG 8 WC Hematology SC Hematology GA 123FN UT WOS:000076115300018 PM 9746773 ER PT J AU Cooke, KR Krenger, W Hill, G Martin, TR Kobzik, L Brewer, J Simmons, R Crawford, JM van den Brink, MRM Ferrara, JLM AF Cooke, KR Krenger, W Hill, G Martin, TR Kobzik, L Brewer, J Simmons, R Crawford, JM van den Brink, MRM Ferrara, JLM TI Host reactive donor T cells are associated with lung injury after experimental allogeneic bone marrow transplantation SO BLOOD LA English DT Article ID IDIOPATHIC-PNEUMONIA-SYNDROME; TOTAL-BODY IRRADIATION; AIR-FLOW OBSTRUCTION; INTERSTITIAL PNEUMONITIS; DENDRITIC CELLS; LETHAL GRAFT; IMMUNOSTIMULATORY ACTIVITY; BRONCHIOLITIS OBLITERANS; MEDIATED CYTOTOXICITY; PULMONARY SYNDROME AB Noninfectious lung injury is common after allogeneic bone marrow transplantation (BMT), but its association with acute graft-versus-host disease (GVHD) is unclear, Using a murine BMT system where donor and host differ by multiple minor histocompatibility (H) antigens, we investigated the nature of lung injury and its relationship both to systemic GVHD and host-reactive donor T cells. Lethally irradiated CBA hosts received syngeneic BMT or allogeneic (B10.BR) T-cell-depleted (TCD) bone marrow (BM) with and without the addition of T cells. Six weeks after BMT, significant pulmonary histopathology was observed in animals receiving allogeneic BMT compared with syngeneic controls. Lung damage was greater in mice that received allogeneic T cells and developed GVHD, but it was also detectable after TCD BMT when signs of clinical and histologic acute GVHD were absent. In each setting, lung injury was associated with significant alterations in pulmonary function. Mature, donor (V beta 6(+) and V beta 3(+))T cells were significantly increased in the broncho-alveolar lavage (BAL) fluid of all allogeneic BMT recipients compared with syngeneic controls, and these cells proliferated and produced interferon-gamma (IFN-gamma) to host antigens in vitro. These in vitro responses correlated with increased IFN-gamma and tumor necrosis factor-alpha (TNF-alpha) in the BAL fluid. We conclude that alloreactive donor lymphocytes are associated with lung injury in this allogeneic BMT model. The expansion of these cells in the BAL fluid and their ability to respond to host antigens even when systemic tolerance has been established (ie, the absence of clinical GVHD) suggest that the lung may serve as a sanctuary site for these host reactive donor T cells. These findings may have important implications with regard to the evaluation and treatment of pulmonary dysfunction after allogeneic BMT even when clinical GVHD is absent. (C) 1998 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Div Pediat Pulm, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. RP Cooke, KR (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, D1420,44 Binney St, Boston, MA 02115 USA. EM kenneth_cooke@dfci.harvard.edu RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NCI NIH HHS [CA39542]; NHLBI NIH HHS [HL55162]; NIDDK NIH HHS [DK39512] NR 59 TC 90 Z9 96 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 1998 VL 92 IS 7 BP 2571 EP 2580 PG 10 WC Hematology SC Hematology GA 123FN UT WOS:000076115300044 PM 9746799 ER PT J AU Adler, H Beland, JL Kozlow, W Del-Pan, NC Kobzik, L Rimm, IJ AF Adler, H Beland, JL Kozlow, W Del-Pan, NC Kobzik, L Rimm, IJ TI A role for transforming growth factor-beta 1 in the increased pneumonitis in murine allogeneic bone marrow transplant recipients with graft-versus-host disease after pulmonary herpes simplex virus type 1 infection SO BLOOD LA English DT Article ID MINOR HISTOCOMPATIBILITY BARRIERS; NITRIC-OXIDE SYNTHASE; NATURAL-KILLER-CELL; FACTOR-BETA; INTERSTITIAL PNEUMONITIS; VIRAL REPLICATION; TGF-BETA; INDUCTION; MICE; INHIBITION AB To gain further insights in the pathogenesis of herpesvirus pneumonia in allogeneic bone marrow transplant recipients, transplanted mice (B10,BR --> CBA) with graft-versus-host disease (GVHD) and control mice (transplanted mice without GVHD and normal CBA mice) were infected intranasally with herpes simplex virus type 1 (HSV-1). When compared with infected control mice, infected allogeneic transplant recipients with GVHD showed increased periluminal mononuclear cell infiltrates. However, infected allogeneic transplant recipients with GVHD showed lower virus content in the lung tissue than infected control mice. High concentrations of transforming growth factor-beta 1 (TGF-beta 1) were detected in the bronchoalveolar lavage (BAL) fluid of mock-infected allogeneic transplant recipients with GVHD, which increased slightly after infection. Anti-TGF-beta treatment of allogeneic transplant recipients with GVHD significantly decreased the histological evidence of pneumonitis at day 4 after HSV-1 infection. We conclude that allogeneic transplant recipients with GVHD have (1) increased pneumonia, (2) highly elevated levels of TGF-beta 1 in the BAL fluid, and (3) reduced pulmonary virus content after HSV-1 infection. Our data suggest that the newly recognized dysregulation of cytokine (TGF-beta 1) production may be more important than the viral load for the increased severity of HSV-1 pneumonia in allogeneic transplant recipients with GVHD, (C) 1998 by The American Society of Hematology. C1 Harvard Univ, Childrens Hosp, Sch Med,Div Pediat Hematol Oncol, Dept Pediat,Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Physiol Program, Boston, MA 02115 USA. RP Rimm, IJ (reprint author), Genet Inst, 87 Cambridge Pk Dr, Cambridge, MA 02140 USA. EM irimm@genetics.com NR 46 TC 15 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 1998 VL 92 IS 7 BP 2581 EP 2589 PG 9 WC Hematology SC Hematology GA 123FN UT WOS:000076115300045 PM 9746800 ER PT J AU Parsons, SK Neault, MW Lehmann, LE Brennan, LL Eickhoff, CE Kretschmar, CS Diller, LR AF Parsons, SK Neault, MW Lehmann, LE Brennan, LL Eickhoff, CE Kretschmar, CS Diller, LR TI Severe ototoxicity following carboplatin-containing conditioning regimen for autologous marrow transplantation for neuroblastoma SO BONE MARROW TRANSPLANTATION LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the ASCO CY MAY 20-23, 1995 CL LOS ANGELES, CALIFORNIA SP ASCO DE ototoxicity; neuroblastoma; carboplatin ID PRIOR CRANIAL IRRADIATION; CIS-PLATINUM OTOTOXICITY; PHASE-I; CISPLATIN OTOTOXICITY; RENAL-FUNCTION; BRAIN-TUMORS; HEARING-LOSS; CHILDREN; TOXICITY; CANCER AB Children with neuroblastoma receiving high-dose carboplatin as part of their conditioning regimen for autologous marrow transplantation have a high incidence of speech frequency hearing loss. We evaluated hearing loss in 11 children with advanced stage neuroblastoma who underwent autologous marrow transplantation, following a conditioning regimen containing high-dose carboplatin (2 g/m(2), total dose). Audiometric evaluations were obtained at diagnosis, prior to and following transplant. Exposure to other known ototoxins also was assessed. All patients sustained worsening of hearing following high-dose carboplatin. Nine of the 11 children (82%) had evidence of speech frequency hearing loss post transplant for which hearing aids were recommended (grades 3-4), Three of the nine children had speech frequency loss prior to transplant which progressed following transplant. The entire group was heavily pre-treated with platinum-containing chemotherapy pre-BMT and had extensive exposure to other ototoxins, including aminoglycoside antibiotics, diuretics, and noise exposure - all of which could have exacerbated the effects of carboplatin. High-dose carboplatin is ototoxic, particularly in patients who have been primed with previous platinum therapy or other ototoxic agents. We conclude that further efforts are needed to monitor and minimize this complication. In cases where hearing loss is inevitable due to cumulative ototoxic exposures, families need to be adequately prepared for the tradeoffs of potentially curable therapy. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Dept Otolaryngol & Commun Disorders, Boston, MA 02115 USA. New England Med Ctr, Floating Hosp, Div Hematol Oncol, Boston, MA 02111 USA. RP Parsons, SK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [KO7-CA01648-04, 5K12-CA01730] NR 27 TC 51 Z9 52 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD OCT PY 1998 VL 22 IS 7 BP 669 EP 674 DI 10.1038/sj.bmt.1701391 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 130ZW UT WOS:000076551700008 PM 9818694 ER PT J AU Vance, E George, S Guinan, EC Wheeler, C Antin, JH Ambrosino, DM Molrine, DC AF Vance, E George, S Guinan, EC Wheeler, C Antin, JH Ambrosino, DM Molrine, DC TI Comparison of multiple immunization schedules for Haemophilus influenzae type b conjugate and tetanus toxoid vaccines following bone marrow transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article DE immunizations, active; vaccines, conjugate; vaccines, protein; bone marrow transplantation ID ACUTE LYMPHOBLASTIC-LEUKEMIA; HOST-DISEASE; PNEUMOCOCCAL INFECTIONS; LATE VACCINATION; ALLOGENEIC BMT; CHRONIC GRAFT; POLYSACCHARIDE; RECIPIENTS; ANTIBODY; CHILDREN AB Antibody concentrations to vaccine-preventable diseases decline following BMT and an optimal schedule for vaccination after transplant has not been established. We examined antibody responses to tetanus toroid (TT) and Haemophilus influenzae type b-conjugate (HIB) vaccines of BMT patients immunized at 6, 12 and 24 months (6 month group, n = 21) and compared them to those previously reported for patients immunized at 3, 6, 12 and 24 months (3 month group, n = 74) or at 12 and 24 months (12 month group, n = 17) following transplantation. Geometric mean total anti-HIB and IgG anti-TT concentrations were significantly higher after the 12 month dose in the 3 and 6 month immunization groups compared to the group who received their first dose at 12 months. Although HIB antibody concentrations were higher in the 3 month and 6 month groups 12 to 24 months after BMT, the proportion of patients with protective levels was not significantly different from the proportion protected in the 12 month group, Following the 24 month immunizations, geometric mean antibody concentrations to HIB and TT were similar for all three immunization groups. The proportion of patients in each group with protective levels of HIB antibody after the 24 month dose was greater than or equal to 80%. A two dose schedule of HIB and TT vaccines at 12 and 24 months after BMT should afford protection. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Clin Invest Training Program, Boston, MA 02115 USA. Pfizer Inc, Beth Israel Deaconess Med Ctr, MIT Hlth Sci & Technol, Boston, MA USA. Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA USA. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. RP Molrine, DC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CAO1730]; PHS HHS [A129623] NR 29 TC 33 Z9 35 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD OCT PY 1998 VL 22 IS 8 BP 735 EP 741 DI 10.1038/sj.bmt.1701424 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 133NJ UT WOS:000076692400001 PM 9827969 ER PT J AU Pastore, C Gaidano, G Ghia, P Fassone, L Cilia, AM Gloghini, A Capello, D Buonaiuto, D Gonella, S Roncella, S Carbone, A Saglio, G AF Pastore, C Gaidano, G Ghia, P Fassone, L Cilia, AM Gloghini, A Capello, D Buonaiuto, D Gonella, S Roncella, S Carbone, A Saglio, G TI Patterns of cytokine expression in AIDS-related non-Hodgkin's lymphoma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE cytokines; lymphoma; AIDS; HHV-8; pathogenesis ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; EPSTEIN-BARR-VIRUS; IN-VITRO ESTABLISHMENT; B-CELL LYMPHOMA; BURKITTS-LYMPHOMA; IMMUNOPATHOGENIC MECHANISMS; TRANSGENIC MICE; LYMPHOCYTES-B; DNA-SEQUENCES; HIV-INFECTION AB The pathogenesis of AIDS-related non-Hodgkin's lymphomas (AIDS-NHL) involves accumulation of genetic lesions, stimulation and selection by antigen, as well as infection by viruses. Deregulation of cytokine loops has also been proposed to contribute to AIDS-NHL development, although data are available only for a limited number of cytokines. In this study we have utilized a panel of AIDS-NHL cell lines to investigate in detail the pattern of tumour expression and production of a wide spectrum of cytokines, The cytokines investigated included interleukin (IL)-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, TNF alpha, TNF beta, IFN gamma, TGF beta(2), G-CSF, GM-CSF and SCF. The AIDS-NHL cell lines utilized were representative of both AIDS-related Burkitt lymphoma (AIDS-BL) and AIDS-related body cavity-based lymphoma (AIDS-BCBL). Overall, AIDS-NHL were found to produce IL-6, IL-10 and TNF beta, although with different patterns depending upon the biological features of the tumour. Production of high levels of IL-10 preferentially associated with Epstein-Barr virus (EBV) positive AIDS-BL and AIDS-BCBL, although lower levels of the cytokine were also detectable among EBV-negative AIDS-BL. Production of IL-6 was restricted to EBV-positive AIDS-BL and AIDS-BCBL, whereas it was absent among EBV-negative AIDS-BL. Production of TNF beta clustered with AIDS-BL, whereas this was absent among AIDS-BCBL. These results define that the pattern of cytokine expression of AIDS-NHL depends upon the biological features of the tumour and may have implications for the pathogenesis of these disorders. C1 Univ Turin, Osped San Luigi Gonzaga, Dipartimento Sci Clin & Biol, Lab Med & Oncol Mol, I-10043 Orbassano Torino, Italy. Univ Turin, Dept Med Sci, Div Internal Med, Novara, Italy. Basel Inst Immunol, Basel, Switzerland. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. INRCC, Ctr Riferimento Oncol, Div Pathol, Aviano, Italy. Osped San Luigi, Lab Anal, I-10043 Orbassano Torino, Italy. Ist Nazl Ric Canc, IST, Serv Immunol Clin, I-16132 Genoa, Italy. Osped Sant Andrea, Div Pathol, La Spezia, Italy. RP Saglio, G (reprint author), Univ Turin, Osped San Luigi Gonzaga, Dipartimento Sci Clin & Biol, Lab Med & Oncol Mol, Med Interna 5A,Reg Gonzole 10, I-10043 Orbassano Torino, Italy. RI Capello, Daniela/J-4110-2012; Ghia, Paolo/K-7138-2016; Gloghini, Annunziata/C-1992-2017 OI Capello, Daniela/0000-0001-9157-8753; Ghia, Paolo/0000-0003-3750-7342; Gloghini, Annunziata/0000-0002-7226-1942 NR 54 TC 17 Z9 17 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 OCT PY 1998 VL 103 IS 1 BP 143 EP 149 DI 10.1046/j.1365-2141.1998.00927.x PG 7 WC Hematology SC Hematology GA 131KM UT WOS:000076575200021 PM 9792301 ER PT J AU Warmuth, MA Bowen, G Prosnitz, LR Chu, L Broadwater, G Peterson, B Leight, G Winer, EP AF Warmuth, MA Bowen, G Prosnitz, LR Chu, L Broadwater, G Peterson, B Leight, G Winer, EP TI Complications of axillary lymph node dissection for carcinoma of the breast - A report based on a patient survey SO CANCER LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 18-21, 1996 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Clin Oncol DE breast neoplasm; lymph node excision; cross-sectional study; survey; complications ID CANCER PATIENTS; RADIOTHERAPY; MASTECTOMY; MORBIDITY; ARM; THERAPY; SURGERY AB BACKGROUND. Axillary lymph node dissection is commonly performed as part of the primary management of breast carcinoma. Its value in patient management, however, has recently been questioned. Few studies exist that document long term complications. METHODS. Four hundred thirty-two patients with Stage I or II breast carcinoma who were free of recurrence 2-5 years after surgery were identified. A cross-sectional survey was conducted to determine the prevalence of long term symptoms and complications as perceived by the patient, and patient and treatment factors that may have predicted complications were determined. Three hundred thirty of the 432 (76%) completed a mailed, self-administered questionnaire. In addition, the medical records of the 330 patients were reviewed. Patient and treatment factors were analyzed with logistic regression. RESULTS. Numbness was reported by 35% of patients at the time of the survey. Pain was noted in 30%, arm swelling in 15%, and limitation of arm movement in 8%. Eight percent reported episodes of infection or inflammation at some point since the diagnosis of breast carcinoma. The majority of symptoms were mild and interfered minimally with daily activities. Younger age (P = 0.001) was associated with more frequent reporting of pain. Numbness was more common in younger patients (P = 0.004) as well as in those with a history of smoking (P = 0.012). There was a positive association of limitation of arm motion with adjuvant tamoxifen therapy (P = 0.016). Arm swelling was associated with both younger age (P = 0.004) and greater body surface area (P = 0.008). Radiation therapy was associated with a higher frequency of infection or inflammation in the arm andlor breast (P = 0.001). CONCLUSIONS. Mild symptoms, especially pain and numbness, are common 2-5 years after axillary lymph node dissection. The frequency of inflammation or infection in patients treated with radiation to the breast or chest wall after an axillary lymph node dissection may be greater than previously appreciated. Severe complications or symptoms that have a major impact on daily activities are uncommon. These findings should help health care providers and their patients with breast carcinoma weigh the pros and cons of axillary lymph node dissection. Cancer 1998;83:1362-8. (C) 1998 American Cancer Society. C1 Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. RP Winer, EP (reprint author), Dana Farber Canc Inst, Breast Canc Program, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [P50 CA68438] NR 26 TC 141 Z9 147 U1 2 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 1 PY 1998 VL 83 IS 7 BP 1362 EP 1368 DI 10.1002/(SICI)1097-0142(19981001)83:7<1362::AID-CNCR13>3.0.CO;2-2 PG 7 WC Oncology SC Oncology GA 122KF UT WOS:000076070200013 PM 9762937 ER PT J AU Chabner, BA Boral, AL Multani, P AF Chabner, BA Boral, AL Multani, P TI Translational research: Walking the bridge between idea and cure - Seventeenth Bruce F. Cain Memorial Award Lecture SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT 89th Annual Meeting of the American-Association-for-Cancer-Research CY MAR 27-APR 01, 1998 CL NEW ORLEANS, LOUISIANA SP Amer Assoc Canc Res ID SOUTHWEST-ONCOLOGY-GROUP; GROWTH-FACTOR RECEPTOR; ACUTE MYELOID-LEUKEMIA; I CLINICAL-TRIALS; CANCER CELL-LINES; C-RAF KINASE; MULTIDRUG-RESISTANCE; PHASE-I; DRUG-RESISTANCE; P-GLYCOPROTEIN AB Advances in the understanding of normal and malignant cell biology are allowing the development of biologically targeted drugs directed at specific differences between host and tumor. The array of potential new targets is vast, but drugs currently in development are targeted at cell-cycle regulators, growth factors and their receptors, signal transduction intermediates, angiogenesis, and the mechanisms that mediate apoptosis and DNA repair. Recent results raise the possibility that novel biologically targeted agents, perhaps in combination with traditional cytotoxic agents, may finally cure cancer. However, the development of a biologically targeted drug raises unique challenges in the design of clinical trials to demonstrate its efficacy, and despite the promising preclinical data that exist for most of the agents in development, the clinical trial remains the critical, final step across the bridge from basic research to clinical application. In this review, we discuss some of the challenges in the clinical development of biologically targeted agents and the implications for clinical trial design. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Chabner, BA (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Cox 640,100 Blossom St, Boston, MA 02114 USA. NR 66 TC 37 Z9 37 U1 0 U2 6 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 OCT 1 PY 1998 VL 58 IS 19 BP 4211 EP 4216 PG 6 WC Oncology SC Oncology GA 125CD UT WOS:000076219100002 PM 9766639 ER PT J AU Kornmann, M Maruyama, H Bergmann, U Tangvoranuntakul, P Beger, HG White, MF Korc, M AF Kornmann, M Maruyama, H Bergmann, U Tangvoranuntakul, P Beger, HG White, MF Korc, M TI Enhanced expression of the insulin receptor substrate-2 docking protein in human pancreatic cancer SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-I; SIGNALING SYSTEM; CYTOKINE ACTION; IRS-1; CELLS; OVEREXPRESSION; AUTOCRINE; ROLES AB Insulin receptor substrate-2 (IRS-2) is a multisite docking protein implicated in mitogenic signaling after activation of the insulin and insulin-like growth factor (IGF)-I receptors, In the present study, we characterized IRS-2 expression and function in human pancreatic cancer. IRS-2 mRNA and protein were expressed in ASPC-1 and COLO-357 human pancreatic cancer cell lines, Insulin, IGF-I, and IGF-II enhanced the growth of both cell lines, stimulated tyrosine phosphorylation of IRS-2, and increased IRS-2-associated phosphatidylinositol (PI) 3-kinase activity. The mitogenic effects of insulin, IGF-I, and IGF-II were markedly attenuated by the PI 3-kinase inhibitor LY 294002, Northern blot analysis of total RNA extracted from normal and cancerous tissues revealed that IRS-2 mRNA levels were increased in the cancer tissues (P = 0.032), In the normal pancreas, IRS-2 immunoreactivity was present at low levels in some ductal and acinar cells and at moderate levels in a heterogeneous pattern in all of the endocrine islets. In the pancreatic cancers, IRS-2 was abundant in the ductal-like cancer cells, These findings indicate that IRS-2 is overexpressed in human pancreatic cancer and suggest that it may contribute to enhanced mitogenic signaling via the PI 3-kinase pathway, thereby leading to excessive growth stimulation in this malignancy. C1 Univ Calif Irvine, Div Endocrinol Diabet & Metab, Dept Med, Irvine, CA 92697 USA. Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92717 USA. Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92697 USA. Univ Ulm, Dept Gen Surg, D-89075 Ulm, Germany. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Korc, M (reprint author), Univ Calif Irvine, Div Endocrinol Diabet & Metab, Dept Med, C240, Irvine, CA 92697 USA. FU NCI NIH HHS [CA-40162] NR 23 TC 60 Z9 61 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1998 VL 58 IS 19 BP 4250 EP 4254 PG 5 WC Oncology SC Oncology GA 125CD UT WOS:000076219100009 PM 9766646 ER PT J AU Wang, EH Ebrahimi, SA Wu, AY Kashefi, C Passaro, E Sawicki, MP AF Wang, EH Ebrahimi, SA Wu, AY Kashefi, C Passaro, E Sawicki, MP TI Mutation of the MENIN gene in sporadic pancreatic endocrine tumors SO CANCER RESEARCH LA English DT Article ID CPG ISLAND METHYLATION; NEOPLASIA TYPE-1; SUPPRESSOR GENE; CHROMOSOME 11Q13; ALLELIC DELETIONS; DNA METHYLATION; LONG-TERM; HETEROZYGOSITY; GASTRINOMAS; IDENTIFICATION AB Pancreatic endocrine tumors occur both sporadically and as part of the multiple endocrine neoplasia type 1 (MEN1) syndrome. MEN1 is an autosomal dominant disease characterized by parathyroid hyperplasia, pancreatic endocrine tumors, and pituitary adenomas, The MEN1 gene called MENIN maps to chromosome 11q13 and is thought to function as a tumor suppressor gene. We previously demonstrated loss of heterozygosity (LOH) at 11q13 in similar to 40% of sporadic pancreatic endocrine tumors and hypothesize that MENIN is involved in the development of these tumors. Thirty-one sporadic pancreatic endocrine tumors were analyzed for mutation of MENIN by nonradioactive single-stranded conformation polymorphism. Twelve mutations were detected in 31 sporadic pancreatic endocrine tumors (34%), Twelve of these 31 tumors previously demonstrated loss of heterozygosity at 11q13, Of the tumors with LOH, seven contained mutations of the MENIN gene (58%), The majority of the MENIN mutations occurred within exon 2, Two independent mutations in MENIN were detected in a gastrinoma that also revealed LOH, leading to the possibility of another tumor suppressor gene locus at 11q13, Mutations were present in both benign and malignant pancreatic endocrine tumors, suggesting that a MENIN gene mutation is a frequent and early event in the tumorigenesis, The high incidence of truncating mutations in tumors with LOH at 11q13 support the hypothesis that MENIN is a tumor suppressor gene. C1 W Los Angeles Vet Affairs Med Ctr, Dept Surg, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90073 USA. RP Sawicki, MP (reprint author), Dept Surg W112, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 30 TC 101 Z9 102 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1998 VL 58 IS 19 BP 4417 EP 4420 PG 4 WC Oncology SC Oncology GA 125CD UT WOS:000076219100035 PM 9766672 ER PT J AU Kiesz, RS Rozek, MM Mego, DM Patel, V Ebersole, DG Chilton, RJ AF Kiesz, RS Rozek, MM Mego, DM Patel, V Ebersole, DG Chilton, RJ TI Acute directional coronary atherectomy prior to stenting in complex coronary lesions: ADAPTS study SO CATHETERIZATION AND CARDIOVASCULAR DIAGNOSIS LA English DT Article DE atherectomy; stents; restenosis; complex lesions ID CONVENTIONAL BALLOON ANGIOPLASTY; MUSCLE CELL-PROLIFERATION; PALMAZ-SCHATZ STENTS; INTRAVASCULAR ULTRASOUND; INTRACORONARY IMPLANTATION; QUANTITATIVE-ANALYSIS; THREATENED CLOSURE; LUMEN ENLARGEMENT; ARTERIAL INJURY; PORCINE MODEL AB The purpose of this study was to determine the results of directional coronary atherectomy (DCA) combined with stenting in a high-risk patient population. The use of stenting or DCA alone for aorto-ostial lesions, total chronic occlusions, long lesions, and lesions containing thrombus is associated with lowered success and a relatively high restenosis rate. Between July 1993 and October 1996, we treated 89 lesions with the combined approach of DCA and stenting in 60 consecutive patients. Thirty-one (51.7%) patients were treated because of unstable angina, 11 (18.3%) for post-myocardial infarction (MI) angina, 3 (5.0%) for acute MI, and 15 (25.0%) patients for stable angina. A total of 43 (71.7%) patients had multivessel disease, 19 (31.7%) had undergone previous coronary artery bypass graft (CABG), and 17 (28.3%) patients had undergone multivessel revascularization. The procedure was successful in all patients; and no postprocedural deaths or emergent CABG occurred. Two patients (3.3%) had non-Q-wave MI after the procedure and 1 patient(1.7%) experienced Q-wave MI due to subacute stent closure 7 days after the procedure. During follow-up ranging from 6 months to 3 years, 2 (3.3%) patients died, 2 (3.3%) required CABG surgery, 1 (1.7%) patient had an MI, and 6 patients (10.0%) required target vessel revascularization. By the quantitative coronary angiography, the initial minimal luminal diameter (MLD) averaged 0.91 +/- 0.45 mm(74.7 +/- 11.8% stenosis) increasing to 3.80 +/- 0.44 mm (-6.7 +/- 12.1%) after the combined approach procedure. Thirty patients (50.0%) met criteria for late (greater than or equal to 6 months) angiographic follow-up. Late MLD loss averaged 1.13 +/- 1.07 mm, for a mean net gain of 1.61 +/- 1.23 mm. Available angiographic follow-up evaluation showed a restenosis rate of 13.3%, A combined approach, defined as the use of both DCA and stenting, is safe and yields a low restenosis rate in high-risk patients who have lesions known to respond less favorably to stenting or DCA alone. (C) 1998 Wiley-Liss, Inc. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Cardiol, San Antonio, TX 78284 USA. S Texas Vet Hlth Syst, Audie Murphy Div, San Antonio, TX USA. Brooke Army Med Ctr, San Antonio, TX USA. RP Kiesz, RS (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Cardiol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM kiesz@uthscsa.edu NR 56 TC 11 Z9 11 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0098-6569 J9 CATHETER CARDIO DIAG JI Catheter. Cardiovasc. Diagn. PD OCT PY 1998 VL 45 IS 2 BP 105 EP 112 DI 10.1002/(SICI)1097-0304(199810)45:2<105::AID-CCD1>3.0.CO;2-G PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 125NH UT WOS:000076243300001 PM 9786384 ER PT J AU Lehmann, KG Oomen, JA Slager, CJ DeFeyter, PJ Serruys, PW AF Lehmann, KG Oomen, JA Slager, CJ DeFeyter, PJ Serruys, PW TI Chromatic distortion during angioscopy: Assessment and correction by quantitative colorimetric angioscopic analysis SO CATHETERIZATION AND CARDIOVASCULAR DIAGNOSIS LA English DT Article DE angioscopy; vascular imaging; colorimetry ID HUMAN CORONARY-ARTERIES; PERIPHERAL VASCULAR-DISEASE; PERCUTANEOUS ANGIOSCOPY; ANGIOGRAPHIC DETECTION; VIDEO IMAGES; ANGIOPLASTY; THROMBUS; ANGINA; THROMBOLYSIS; ATHERECTOMY AB Angioscopy represents a diagnostic tool with the unique ability of assessing the true color of intravascular structures, Current angioscopic interpretation is entirely subjective, however, and the visual interpretation of color has been shown to be marginal at best. The quantitative colorimetric angioscopic analysis system permits the full characterization of angioscopic color using two parameters (C1 and C2), derived from a custom color coordinate system, that are independent of illuminating light intensity. Measurement variability was found to be low (coefficient of variation = 0.06-0.64%), and relatively stable colorimetric values were obtained even at the extremes of illumination power. Variability between different angioscopic catheters was good (maximum difference for C1, 0.022; for C2, 0.015), Catheter flexion did not significantly distort color transmission. Although the fiber optic illumination bundle was found to impart a slight yellow tint to objects in view (Delta C1 = 0.020, Delta C2 = 0.024, P < 0.0001) and the imaging bundle in isolation imparted a slight red tint(Delta C1 = 0.043, Delta C2 = -0.027, P < 0.0001), both of these artifacts could be corrected by proper white balancing. Finally, evaluation of regional chromatic characteristics revealed a radially symmetric and progressive blue shift in measured color when moving from the periphery to the center of an angioscopic image. An algorithm was developed that could automatically correct 93.0-94.3% of this error and provide accurate colorimetric measurements independent of spatial location within the angioscopic field. In summary, quantitative colorimetric angioscopic analysis provides objective and highly reproducible measurements of angioscopic color. This technique can correct for important chromatic distortions present in modern angioscopic systems. It can also help overcome current limitations in angioscopy research and clinical use imposed by the reliance on visual perception of color. (C) 1998 Wiley-Liss, Inc. C1 VA Puget Sound Hlth Care Syst, Sect Cardiol 111C, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Erasmus Univ, Thoraxctr, NL-3000 DR Rotterdam, Netherlands. RP Lehmann, KG (reprint author), VA Puget Sound Hlth Care Syst, Sect Cardiol 111C, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 40 TC 4 Z9 4 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0098-6569 J9 CATHETER CARDIO DIAG JI Catheter. Cardiovasc. Diagn. PD OCT PY 1998 VL 45 IS 2 BP 191 EP 201 DI 10.1002/(SICI)1097-0304(199810)45:2<191::AID-CCD19>3.0.CO;2-O PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 125NH UT WOS:000076243300019 PM 9786402 ER PT J AU Friedlander, RM Yuan, JY AF Friedlander, RM Yuan, JY TI ICE, neuronal apoptosis and neurodegeneration SO CELL DEATH AND DIFFERENTIATION LA English DT Review DE apoptosis; ICE; caspase; pathological cell death ID INTERLEUKIN-1-BETA CONVERTING-ENZYME; AMYOTROPHIC-LATERAL-SCLEROSIS; FAMILIAL ALZHEIMERS-DISEASE; DEATH GENE CED-3; TROPHIC FACTOR WITHDRAWAL; PROGRAMMED CELL-DEATH; NECROSIS-FACTOR-ALPHA; CYSTEINE PROTEASE; IL-1-BETA-CONVERTING ENZYME; TRANSGENIC MICE AB Significant progress has recently occurred in the understanding of the molecular mechanisms mediating vertebrate programmed cell death, or apoptosis. New advances in this field have stemmed from the identification of ICE (caspase-1) as the founding member of the mammalian caspase cell death family. Apoptotic cell death plays an important role in neuronal cell death. Both in vitro and in vivo evidence implicates ICE as an important factor in neuronal apoptosis, especially under pathological conditions. In addition, other caspases, such as caspase-3, have also been shown to be activated and may play a role in pathological neuronal loss. Understanding the basic mechanisms mediating cell death in neurodegenerative disease may lead to the development of novel approaches for the treatment of diseases featuring apoptosis. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Neurosurg Serv, Boston, MA 02114 USA. RP Yuan, JY (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. EM jyuan@hms.harvard.edu RI Friedlander, Robert/A-2845-2016 OI Friedlander, Robert/0000-0003-4423-9219 NR 83 TC 88 Z9 95 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD OCT PY 1998 VL 5 IS 10 BP 823 EP 831 DI 10.1038/sj.cdd.4400433 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 127PD UT WOS:000076359000004 PM 10203693 ER PT J AU Schulz, JB Weller, M Matthews, RT Heneka, MT Groscurth, P Martinou, JC Lommatzsch, J von Coelln, R Wullner, U Loschmann, PA Beal, MF Dichgans, J Klockgether, T AF Schulz, JB Weller, M Matthews, RT Heneka, MT Groscurth, P Martinou, JC Lommatzsch, J von Coelln, R Wullner, U Loschmann, PA Beal, MF Dichgans, J Klockgether, T TI Extended therapeutic window for caspase inhibition and synergy with MK-801 in the treatment of cerebral histotoxic hypoxia SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE caspases; malonate; apoptosis; excitotoxicity; therapeutic window; Nedd2 ID INTERLEUKIN-1-BETA CONVERTING-ENZYME; EXCITOTOXIC NEURONAL DAMAGE; TROPHIC FACTOR WITHDRAWAL; CELL-DEATH; FAMILY PROTEASES; IN-VIVO; ARTERY OCCLUSION; NEURAL CELLS; APOPTOSIS; BCL-2 AB In rats, striatal histotoxic hypoxic lesions produced by the mitochondrial toxin malonate resemble those of focal cerebral ischemia, Intrastriatal injections of malonate induced cleavage of caspase-2 beginning at 6 h, and caspase-3-like activity as identified by DEVD biotin affinity-labeling within 12 h. DEVD affinity-labeling was prevented and lesion volume reduced in transgenic mice overexpressing BCL-2 in neuronal cells. Intrastriatal injection of the tripeptide, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD-fmk), a caspase inhibitor, at 3 h, 6 h, or 9 h after malonate injections reduced the lesion volume produced by malonate, A combination of pretreatment with the NMDA antagonist, dizocilpine (MK-801), and delayed treatment with zVAD-fmk provided synergistic protection compared with either treatment alone and extended the therapeutic window for caspase inhibition to 12 h, Treatment with cycloheximide and zVAD-fmk, but not with MK-801, blocked the malonate-induced cleavage of caspase-2. NMDA injections alone resulted in a weak caspase-2 cleavage, These results suggest that malonate toxicity induces neuronal death by more than one pathway. They strongly implicate early excitotoxicity and delayed caspase activation in neuronal loss after focal ischemic lesions and offer a new strategy for the treatment of stroke. C1 Univ Tubingen, Dept Neurol, Expt Neuropharmacol Lab, D-72076 Tubingen, Germany. Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Glaxo Inst Mol Biol SA, CH-1228 Plan Les Ouates, Geneve, Switzerland. Univ Zurich, Div Cell Biol, Inst Anat, CH-8057 Zurich, Switzerland. RP Schulz, JB (reprint author), Univ Tubingen, Dept Neurol, Expt Neuropharmacol Lab, Hoppe Seyler Str 3, D-72076 Tubingen, Germany. RI Schulz, Jorg/D-9786-2012; OI Schulz, Jorg/0000-0002-8903-0593; von Coelln, Rainer/0000-0001-7651-2780 NR 36 TC 74 Z9 76 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD OCT PY 1998 VL 5 IS 10 BP 847 EP 857 DI 10.1038/sj.cdd.4400420 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 127PD UT WOS:000076359000007 PM 10203688 ER PT J AU Hughes, MP Carlson, TH McLaughlin, MK Bankson, DD AF Hughes, MP Carlson, TH McLaughlin, MK Bankson, DD TI Addition of sodium fluoride to whole blood does not stabilize plasma homocysteine but produces dilution effects on plasma constituents and hematocrit SO CLINICAL CHEMISTRY LA English DT Article ID SAMPLE C1 Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Hughes, MP (reprint author), Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. FU NIDDK NIH HHS [DK35816] NR 11 TC 18 Z9 18 U1 0 U2 0 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 OCT PY 1998 VL 44 IS 10 BP 2204 EP 2206 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 124RT UT WOS:000076196200025 PM 9761260 ER PT J AU Simms, V Musher, DM AF Simms, V Musher, DM TI Psoas muscle abscess due to Mycobacterium kansasii in an apparently immunocompetent adult SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID AIDS C1 Vet Affairs Med Ctr, Med Serv, Infect Dis Sect, Houston, TX 77030 USA. RP Musher, DM (reprint author), Dept Vet Affairs Med Ctr, Infect Dis Sect 111G, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 9 TC 5 Z9 6 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT PY 1998 VL 27 IS 4 BP 893 EP 894 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 129ZF UT WOS:000076493400039 PM 9798051 ER PT J AU Kawate, K Maloney, WJ Bragdon, CR Biggs, SA Jasty, M Harris, WH AF Kawate, K Maloney, WJ Bragdon, CR Biggs, SA Jasty, M Harris, WH TI Importance of a thin cement mantle - Autopsy studies of eight hips SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT 26th Open Scientific Meeting of the Hip Society CY MAR 22, 1998 CL NEW ORLEANS, LOUISIANA SP Hip Soc ID FEMORAL COMPONENTS; FOLLOW-UP; ARTHROPLASTIES; INTERFACE AB 0The question whether thin cement mantles around cemented femoral components led to an increased frequency of cracks in the cement was asked. Microscopically, multiple cross sections of eight femurs retrieved at autopsy from clinically successful total hip replacements after prolonged in vivo service containing well fixed Harris Design 2 cemented femoral components were studied. None of the components were loose by radiographic criteria, All were fixed solidly when loaded in vitro in simulated stair climbing and gait, as assessed by high resolution micromotion sensors, The specimens were sectioned transversely at 5-mm increments. The cross sections were examined under a dissecting microscope at x100. A thin mantle arbitrarily was defined as a mantle of less than 1 mm in thickness. The analysis of the contact radiographs showed that the routine anteroposterior and lateral radiographs underestimated the prevalence of thin cement mantles and mantle defects. Although overall on all the cross sections 9% of the aggregated cement mantles was classified as having thin cement, 92 of the 101 cement cracks occurred in areas of the mantles that were less than 1 mm thick. C1 Massachusetts Gen Hosp, Orthopaed Biomech Lab, Boston, MA 02114 USA. Nara Med Univ, Dept Orthopaed Surg, Nara, Japan. Washington Univ, Dept Orthopaed Surg, Sch Med, St Louis, MO USA. Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Hip & Implant Unit, Boston, MA 02114 USA. RP Harris, WH (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech Lab, 55 Fruit St, Boston, MA 02114 USA. NR 20 TC 52 Z9 52 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD OCT PY 1998 IS 355 BP 70 EP 76 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 141MX UT WOS:000077148700008 PM 9917592 ER PT J AU Dowd, JE Cha, CW Trakru, S Kim, SY Yang, CH Rubash, HE AF Dowd, JE Cha, CW Trakru, S Kim, SY Yang, CH Rubash, HE TI Failure of total hip arthroplasty with a precoated prosthesis - 4- to 11-year results SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT 26th Open Scientific Meeting of the Hip Society CY MAR 22, 1998 CL NEW ORLEANS, LOUISIANA SP Hip Soc ID 10-YEAR FOLLOW-UP; IMPROVED CEMENTING TECHNIQUES; FEMORAL COMPONENT; RADIOGRAPHIC ANALYSIS; REPLACEMENT; FIXATION; STRAIN AB A series of early femoral component failures prompted a detailed retrospective clinical and radiographic review of 176 hybrid cemented total hip arthroplasties using a polymethylmethacrylate coated femoral prosthesis. All surgeries were performed using third generation cement techniques. Average length of followup was 6.3 years (range, 3-12 years). Twenty-one patients died, and one underwent revision surgery because of sepsis. Of the remaining 154 total hip arthroplasties, 23 (15%) of the femoral components failed (21 revised, two definitely loose). The average time to revision was 3.9 years. None of the acetabular components failed. Comparison between the failure and nonfailure groups revealed that poor cement mantles (Grades C or D) with distal cement mantle deficiencies were statistically significant predictors of femoral failure. The mast common mechanism of failure was progressive, circumferential cement-bone interface osteolysis with relative preservation of the cement-metal interface. Debonding of the cement column from the prosthesis was a late finding and occurred in only 45% of failed cases. Incorporating the techniques of centralization and centrifugation significantly improved clinical results. Strengthening of the cement-prosthesis interface may magnify the deleterious effects of a poor cement mantle and predisposes the cement-bone interface to failure. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Univ Pittsburgh, Med Ctr, Dept Orthopaed Surg, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Div Adult Reconstruct Surg, Pittsburgh, PA USA. RP Rubash, HE (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, White Bldg,Room 601,55 Fruit St, Boston, MA 02114 USA. NR 64 TC 41 Z9 42 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD OCT PY 1998 IS 355 BP 123 EP 136 PG 14 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 141MX UT WOS:000077148700013 PM 9917597 ER PT J AU Harris, WH AF Harris, WH TI Long term results of cemented femoral stems with roughened precoated surfaces SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT 26th Open Scientific Meeting of the Hip Society CY MAR 22, 1998 CL NEW ORLEANS, LOUISIANA SP Hip Soc ID TOTAL HIP-REPLACEMENT; PROSTHESIS INTERFACE; FOLLOW-UP; ARTHROPLASTY; COMPONENT; STRENGTH; FATIGUE; IMPLANT AB Several recent articles have raised the question that rough surfaces with or without precoating may contribute to the loosening of cemented femoral stems. In this article the author collates selected reports of several different cemented femoral stem designs that have rough surfaces which have shown excellent long term results. Femoral stem loosening is generally multifactorial. It often is difficult to separate the effect of stem design or other changes from the effect of surface finish. Many rough surfaced cemented femoral stems have served well for decades. It is important to analyze all the pertinent factors in cases of early loosening. C1 Massachusetts Gen Hosp, Orthopaed Biomech Lab, Adult Reconstruct Serv, Boston, MA 02114 USA. Harvard Univ, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Harris, WH (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech Lab, Adult Reconstruct Serv, GRJ 1126,55 Fruit St, Boston, MA 02114 USA. NR 32 TC 23 Z9 23 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD OCT PY 1998 IS 355 BP 137 EP 143 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 141MX UT WOS:000077148700014 PM 9917598 ER PT J AU Glowacki, J AF Glowacki, J TI Angiogenesis in fracture repair SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Workshop on Fracture Healing Enhancement CY OCT, 1997 CL TAMPA, FLORIDA SP Assoc Bone & Joint Surgeons, Int Soc Fracture Repair ID FIBROBLAST GROWTH-FACTOR; ONLAY BONE-GRAFTS; RABBIT; NEOVASCULARIZATION; CHAMBER; MODEL; RAT; REVASCULARIZATION; VASCULARIZATION; PROLIFERATION AB Fracture of bone disrupts its circulation and leads to necrosis and hypoxia of adjacent bone. Under normal circumstances, fractured bone undergoes the orderly regeneration of its component tissues with complete restoration of mechanical properties. Reestablishment of the circulation is an early event in fracture healing. Several experimental models of protracted, impaired, or compromised healing have been developed to evaluate the effects of angiogenic factors in accelerating or enhancing repair. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg,Skeletal Biol Lab, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Skeletal Biol Res Ctr, Boston, MA 02115 USA. RP Glowacki, J (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Res, 75 Francis St, Boston, MA 02115 USA. NR 60 TC 132 Z9 135 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD OCT PY 1998 IS 355 SU S BP S82 EP S89 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 141YT UT WOS:000077173200011 ER PT J AU Trippel, SB AF Trippel, SB TI Potential role of insulinlike growth factors in fracture healing SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Workshop on Fracture Healing Enhancement CY OCT, 1997 CL TAMPA, FLORIDA SP Assoc Bone & Joint Surgeons, Int Soc Fracture Repair ID FACTOR BINDING-PROTEINS; IMMUNOREACTIVE SOMATOMEDIN-C; MESSENGER-RIBONUCLEIC-ACID; OSTEOBLAST-LIKE CELLS; FACTOR-I; FACTOR IGF; HYPOPHYSECTOMIZED RATS; BIOLOGICAL ACTIONS; RECEPTOR-BINDING; HYBRID RECEPTORS AB Several lines of evidence suggest that the insulinlike growth factors play a role in fracture healing, They promote cell proliferation and matrix synthesis by chondrocytes and osteoblasts, the two cell types largely responsible for the formation of fracture callus. Circulating levels of insulinlike growth factor I and bone mineral density decrease with increasing age, and administration of insulinlike growth factor I increases bone turnover in patients with low bone mineral density, Insulinlike growth factor I may accelerate the normal healing of intramembranous bone defects, inducing the healing of defects that otherwise would not heal, An important role of insulinlike growth factor I is to mediate many of the actions of growth hormone on the skeleton. Considerable effort has been devoted to testing the effect of growth hormone and, thereby, indirectly that of insulinlike growth factor I on fracture healing. These studies have yielded such disparate results that no general conclusions regarding the effect of growth hormone (or of growth hormone dependent insulinlike growth factor I) on fracture healing currently can be drawn. Additional studies are needed to clarify the role of the insulinlike growth factors in the fracture healing process and to determine how their anabolic actions can be enlisted in the clinical enhancement of fracture healing. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA USA. RP Trippel, SB (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St,Suite 607, Boston, MA 02114 USA. FU NIAMS NIH HHS [AR 31068] NR 88 TC 14 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD OCT PY 1998 IS 355 SU S BP S301 EP S313 PG 13 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 141YT UT WOS:000077173200032 PM 9917650 ER PT J AU Stilley, CS Miller, DJ Gayowski, T Marino, IR AF Stilley, CS Miller, DJ Gayowski, T Marino, IR TI Psychological characteristics of candidates for liver transplantation SO CLINICAL TRANSPLANTATION LA English DT Article DE coping; family environments; optimism; personality; psychological distress ID HEART-TRANSPLANTATION; PREDICTORS; OPTIMISM AB This study examined depression, anxiety, coping styles, optimism, selected personality characteristics, and perception of family environment among candidates for liver transplantation (OLTX); the goal was to measure and empirically describe psychosocial factors reported to impact on the experience and outcome of transplantation. Subjects were 73 US military veterans being considered for OLTX at the VAMC-Pittsburgh (UD) from 1994 to 1996. Psychological evaluation consisted of chart review, consultation with the transplant team, clinical interview and administration of published, standardized, and readily available psychological tests. Candidates displayed above normal levels of situational anxiety and depression, mainly adaptive coping styles, mild optimism, and positive family environments. Factor analysis of the data identified two dimensions of psychological distress, five coping styles, and three types of family environment. The composite MMPI-2 profile for the sample shows marked elevations of the neurotic triad and moderate elevations of psychasthenia and schizophrenia scales. Psychological distress, psychopathology, coping styles, optimism, and perceptions of family environment correlate with each other in the directions suggested by the literature. These findings support previous research with empirical data; results encourage the development of consistent psychological protocols and procedures to evaluate and treat organ transplant candidates. C1 Univ Pittsburgh, Sch Educ, Pittsburgh, PA 15260 USA. RP Miller, DJ (reprint author), VA Pittsburgh Healthcare Syst, 11B, Pittsburgh, PA 15240 USA. NR 26 TC 10 Z9 10 U1 2 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0063 J9 CLIN TRANSPLANT JI Clin. Transplant. PD OCT PY 1998 VL 12 IS 5 BP 416 EP 424 PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA 126RC UT WOS:000076306100010 PM 9787951 ER PT J AU Holz, GG Habener, JF AF Holz, GG Habener, JF TI Black widow spider alpha-latrotoxin: a presynaptic neurotoxin that shares structural homology with the glucagon-like peptide-1 family of insulin secretagogic hormones SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article DE presynaptic neurotoxin; peptide hormone; calcium; exocytosis; G protein-coupled receptor; stimulus-secretion coupling; pancreatic beta-cell; insulin secretion ID TERMINAL EXTRACELLULAR DOMAIN; LIGAND-RECEPTOR INTERACTION; PROTEIN-COUPLED RECEPTOR; PANCREATIC BETA-CELLS; GILA MONSTER VENOM; FUNCTIONAL EXPRESSION; PARATHYROID-HORMONE; GLP-1 RECEPTOR; EXENDIN-4; CLONING AB alpha-Latrotoxin is a presynaptic neurotoxin isolated from the venom of the black widow spider Latrodectus tredecimguttatus. It exerts toxic effects in the vertebrate central nervous system by depolarizing neurons, by increasing [Ca2+](i) and by stimulating uncontrolled exocytosis of neurotransmitters from nerve terminals. The actions of alpha-latrotoxin are mediated, in part, by a GTP-binding protein-coupled receptor referred to as GIRL or latrophilin. Exendin-4 is also a venom toxin, and it is derived from the salivary gland of the Gila monster Heloderma suspectum. It acts as an agonist at the receptor for glucagon-like peptide-1(7-36)-amide (GLP-1), thereby stimulating secretion of insulin from pancreatic beta-cells of the islets of Langerhans. Here is reported a surprising structural homology between alpha-latrotoxin and exendin-4 that is also apparent amongst all members of the GLP-l-like family of secretagogic hormones (GLP-1, glucagon, vasoactive intestinal polypeptide, secretin, pituitary adenylyl cyclase activating polypeptide). On the basis of this homology, we report the synthesis and initial characterization of a chimeric peptide (Black Widow GLP-1) that stimulates Ca2+ signaling and insulin secretion in human beta-cells and MIN6 insulinoma cells. It is also reported here that the GTP-binding protein-coupled receptors for alpha-latrotoxin and exendin-4 share highly significant structural similarity in their extracellularly-oriented amino-termini. We propose that molecular mimicry has generated conserved structural motifs in secretagogic toxins and their receptors, thereby explaining the evolution of defense or predatory strategies that are shared in common amongst distantly related species including spiders, lizards, and snakes. Evidently, the toxic effects of alpha-latrotoxin and exendin-4 are explained by their ability to interact with CTP-binding protein-coupled receptors that normally mediate the actions of endogenous hormones or neuropeptides. (C) 1998 Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Lab Mol Endocrinol, Boston, MA 02114 USA. RP Holz, GG (reprint author), NYU, Med Ctr, Dept Physiol & Neurosci, New York, NY 10016 USA. RI Holz, George/A-3386-2012 FU NIDDK NIH HHS [DK-45817, R01 DK045817, R01 DK045817-06A2, DK-30834, DK-52166, R01 DK030834] NR 40 TC 16 Z9 17 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0305-0491 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD OCT PY 1998 VL 121 IS 2 BP 177 EP 184 DI 10.1016/S0305-0491(98)10088-3 PG 8 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA 150WB UT WOS:000077687800008 PM 9972293 ER PT J AU Hemler, ME AF Hemler, ME TI Integrin associated proteins SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID PLASMINOGEN-ACTIVATOR RECEPTOR; FUNCTION-ASSOCIATED ANTIGEN-1; ALPHA(IIB)BETA(3) GPIIB-IIIA; CELL-CYCLE PROGRESSION; FOCAL ADHESION KINASE; CYTOPLASMIC DOMAIN; COMPLEMENT RECEPTOR-TYPE-3; MONOCLONAL-ANTIBODIES; ALPHA-ACTININ; HUMAN NEUTROPHILS AB Integrin cytoplasmic domains may interact directly with serveral different cytoskeletal proteins and intracellular signaling molecules. Also, integrins interact directly with other transmembrane structures, including transmembrane-4 superfamily (TM4SF) proteins. New evidence suggests that TM4SF proteins may act as linkers between extracellular integrin a chain domains and intracellular signaling molecules, such as phosphatidylinositol 4-kinase and protein kinase C. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, Rm D-1410,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA42368]; NIGMS NIH HHS [GM38903, GM46526] NR 86 TC 283 Z9 289 U1 1 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LE, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD OCT PY 1998 VL 10 IS 5 BP 578 EP 585 DI 10.1016/S0955-0674(98)80032-X PG 8 WC Cell Biology SC Cell Biology GA 128MB UT WOS:000076409600004 PM 9818167 ER PT J AU Auchincloss, H Wood, KJ AF Auchincloss, H Wood, KJ TI Transplantation - More questions than answers SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Surg Serv, Transplantat Unit, Boston, MA 02114 USA. Univ Oxford, John Radcliffe Hosp, Nuffield Dept Surg, Oxford OX3 9DU, England. RP Auchincloss, H (reprint author), Massachusetts Gen Hosp, Surg Serv, Transplantat Unit, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LE, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 1998 VL 10 IS 5 BP 505 EP 506 DI 10.1016/S0952-7915(98)80214-8 PG 2 WC Immunology SC Immunology GA 128MC UT WOS:000076409700003 ER PT J AU Manilay, JO Sykes, M AF Manilay, JO Sykes, M TI Natural killer cells and their role in graft rejection SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID CLASS-I MHC; DEFICIENT HEMATOPOIETIC-CELLS; PORCINE ENDOTHELIAL-CELLS; INHIBITORY RECEPTORS; NK CELLS; T-CELL; HLA-C; BONE-MARROW; SUPERFAMILY MEMBERS; ANTIGEN RECOGNITION AB Natural killer cells can weakly resist engraftment of allogeneic bone marrow transplants in mice. Functional studies suggest that natural killer cell tolerance can be induced by bone marrow transplantation. Human natural killer cell inhibitory receptor repertoires differ between individuals, depending on their MHC genotype. This supports the concept that the human natural killer cell repertoire, like that of mice, adapts to the MHC molecules presented in its environment. Natural killer cells play a greater role in rejecting xenogeneic than allogeneic bone marrow and have been implicated in the rejection of xenogeneic solid organ transplants. Natural killer cell inhibitory receptors may have a lower likelihood of cross-reacting with xenogeneic than with allogeneic MHC class I molecules; important glycosylation differences between species may affect the propensity of natural killer cells to kill xenogeneic targets. C1 Massachusetts Gen Hosp, Res Ctr, Transplant Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. RP Manilay, JO (reprint author), Massachusetts Gen Hosp, Res Ctr, Transplant Biol Res Ctr, Bone Marrow Transplantat Sect, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. EM sykes@helix.mgh.harvard.edu FU NHLBI NIH HHS [F31 HLO9733-02, R01 HL-49915] NR 77 TC 67 Z9 68 U1 1 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LE, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 1998 VL 10 IS 5 BP 532 EP 538 DI 10.1016/S0952-7915(98)80219-7 PG 7 WC Immunology SC Immunology GA 128MC UT WOS:000076409700008 PM 9794835 ER PT J AU Korsmeyer, SJ Greenberg, PD AF Korsmeyer, SJ Greenberg, PD TI Cancer - Tuning in on death programs SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material C1 Dana Farber Canc Inst, Dept Canc Immunol AIDS, Boston, MA 02115 USA. Univ Washington, Dept Immunol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. RP Korsmeyer, SJ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol AIDS, 1 Jimmy Fund Way,Room SM-758, Boston, MA 02115 USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LE, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 1998 VL 10 IS 5 BP 543 EP 544 DI 10.1016/S0952-7915(98)80221-5 PG 2 WC Immunology SC Immunology GA 128MC UT WOS:000076409700010 ER PT J AU Noramly, S Morgan, BA AF Noramly, S Morgan, BA TI BMPs mediate lateral inhibition at successive stages in feather tract development SO DEVELOPMENT LA English DT Article DE feather bud; lateral inhibition; bone morphogenetic protein; pattern formation ID SKIN APPENDAGE MORPHOGENESIS; SONIC-HEDGEHOG; MESENCHYMAL CONDENSATION; PATTERN-FORMATION; CHICK-EMBRYO; CELL-DEATH; LIMB; EXPRESSION; INDUCTION; GROWTH AB The spacing of feather buds in a tract is thought to arise from the interaction between an inducing signal from the dermis and an inhibitory signal generated in the nascent buds. Local BMP-2 expression in the ectoderm precedes the formation of the ectodermal placodes, which are the first morphological sign of bud differentiation. We have altered the activity of BMP-2 or BMP-4 in the ectoderm of the feather field by expressing them or their inhibitor noggin using retroviral vectors. These experiments demonstrate that BMP-2 is necessary and sufficient to mediate the lateral inhibition that positions buds in a tract. After buds are initiated, BMP-2 and BMP-4 continue to inhibit the adoption of bud fates and help to specify the size and shape of the bud. They may do so in part by their regulation of Fgf receptor expression in both the ectoderm and dermis, Additional insights into pattern formation in the feather bud can be inferred from the effects of altered BMP activity on bud morphogenesis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Cornell Univ, Grad Sch Med Sci, New York, NY 10021 USA. RP Morgan, BA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM bruce.morgan@cbrc2.mgh.harvard.edu NR 48 TC 142 Z9 148 U1 1 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD OCT PY 1998 VL 125 IS 19 BP 3775 EP 3787 PG 13 WC Developmental Biology SC Developmental Biology GA 132GE UT WOS:000076621300003 PM 9729486 ER PT J AU Napoli, R Gibson, L Hirshman, MF Boppart, MD Dufresne, SD Horton, ES Goodyear, LJ AF Napoli, R Gibson, L Hirshman, MF Boppart, MD Dufresne, SD Horton, ES Goodyear, LJ TI Epinephrine and insulin stimulate different mitogen-activated protein kinase signaling pathways in rat skeletal muscle SO DIABETES LA English DT Article ID MAP KINASE; GLYCOGEN-SYNTHASE; C-JUN; TRANSDUCTION PATHWAY; MOLECULAR MECHANISM; GENE-EXPRESSION; CELLS; STRESS; CAMP; INHIBITION AB Little is known about the regulation of the mitogen-activated protein (MAP) kinase signaling cascades by hormonal stimulation in vivo. The extracellular signal-regulated kinase (ERK) and the c-jun kinase (JNK) are two MAP kinase signaling pathways that could play a role in the cellular response to hormones such as insulin and epinephrine. me studied the effects of insulin (20 U/rat) and epinephrine (25 mu g/100 g body wt) injected in vivo on ERK and JNK signaling in skeletal muscle from Sprague-Dawley rats. Insulin significantly increased ERK phosphorylation and the activity of its downstream substrate, the p90 ribosomal S6 kinase 2 (RSK2), by 1.4-fold, but it had no effect on JNK activity. In contrast, epinephrine had no effect on ERK phosphorylation or RSK2 activity, but it increased JNK activity by twofold, an effect that was inhibited by the presence of combined a and beta blockade. Furthermore, the phosphorylation of both p46 and p55 isoforms of JNK, measured by phosphospecific antibody, was increased severalfold. The activity and phosphorylation of MAP kinase kinase (MKK)-4, an upstream regulator of JNK, was unchanged by epinephrine. Incubation of isolated soleus muscles in vitro with epinephrine (10(-5) mol/l) also increased JNK activity by twofold. These data are the first to demonstrate that epinephrine can increase JNK activity. Insulin and epinephrine have different effects on MAP kinase signaling pathways in skeletal muscle, which may be one of the underlying molecular mechanisms through which these hormones regulate opposing metabolic functions. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM goodyeal@joslab.harvard.edu OI NAPOLI, Raffaele/0000-0002-3366-2321 FU NIAMS NIH HHS [AR42238] NR 48 TC 24 Z9 24 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 1998 VL 47 IS 10 BP 1549 EP 1554 DI 10.2337/diabetes.47.10.1549 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 122FM UT WOS:000076061300003 PM 9753291 ER PT J AU Frykberg, RG Harvey, C Lavery, LA Harkless, L Pham, H Veves, A AF Frykberg, RG Harvey, C Lavery, LA Harkless, L Pham, H Veves, A TI Role of neuropathy and high foot pressures in diabetic foot ulceration SO DIABETES CARE LA English DT Article ID LIMITED JOINT MOBILITY; LOWER-EXTREMITY AMPUTATION; RISK; ULCERS; EPIDEMIOLOGY; PREVENTION; MELLITUS; FEET AB OBJECTIVE - High plantar foot pressures in association with peripheral neuropathy have been ascertained to be important risk factors for ulceration in the diabetic foot. Most studies investigating, these parameters have been limited by their size and the homogeneity of study subjects. The objective of this study was therefore to ascertain the risk of ulceration associated with high foot pressures and peripheral neuropathy in a large and diverse diabetic population. RESEARCH DESIGN AND METHODS - We studied a cross-sectional group of 251 diabetic patients of Caucasian (group C) (n = 121), black (group B) (n = 36), and Hispanic (group H) (n = 94) racial origins with an overall age of 58.5 +/- 12.5 years (range 20-83). There was an equal distribution of men and women across the entire study population. All patients underwent a complete medical history and lower extremity evaluation for neuropathy and foot pressures. Neuropathic parameters were dichotomized (0/1) into two high-risk variables: patients with a vibration perception threshold (VPT) greater than or equal to 25 V were categorized as HiVPT (n = 132) and those with Semmes-Weinstein monofilament tests greater than or equal to 5.07 were classified as HiSWF (n = 190). The mean dynamic foot pressures of three footsteps were measured using the F-scan mat system with patients walking without shoes. Maximum plantar pressures were dichotomized into a high-pressure variable (Pmax6) indicating those subjects with pressures greater than or equal to 6 kg/cm(2) (n = 96). A total of 99 patients had a current or prior history of ulceration at baseline. RESULTS - Joint mobility was significantly greater in the Hispanic cohort compared with the other groups at the first metatarsal-phalangeal joint (C 67 +/- 23 degrees, B 69 +/- 23 degrees, H 82 +/- 23 degrees, P = 0.000), while the subtalar joint mobility was reduced in the Caucasian group (C 21 +/- 8 degrees, B 26 +/- 7 degrees, H 27 +/- 11 degrees, P = 0.000). Maximum plantar fool pressures were significantly higher in the Caucasian group (C 6.7 +/- 2.9 kg/cm(2), B 5.7 +/- 2.8 kg/cm(2), H 4.4 +/- 1.9 kg/cm(2), P = 0.000). Univariate logistic regression for Pmax6 on the history of ulceration yielded an odds ratio (OR) of 3.9 (P = 0.000). For HiVPT, the OR was 11.7 (P = 0.000), and for HiSWF; the OR was 9.6 (P = 0.000). Controlling for age, diabetes duration. sex, and race (all P < 0.05), multivariate logistic regression yielded the following significant associations with ulceration: Pmax6 (OR = 2.1. P = 0.002), HiVPT (OR = 4.4, P = 0.000), and HiSWF (OR = 4.1, P = 0.000). CONCLUSIONS - We conclude that both high foot pressures (greater than or equal to 6 kg/cm(2)) and neuropathy are independently associated with ulceration in a diverse diabetic population, with the latter having the greater magnitude of effect. In black and Hispanic diabetic patients especially joint mobility and plantar pressures are less predictive of ulceration than in Caucasians. C1 Beth Israel Deaconess Med Ctr, Deaconess Joslin Foot Ctr, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Microcirculat Lab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Div Podiatry, Boston, MA USA. Univ Texas, Hlth Sci Ctr, Dept Orthoped, Div Podiatry, San Antonio, TX USA. Calif Coll Podiatr Med, San Francisco, CA USA. RP Frykberg, RG (reprint author), Beth Israel Deaconess Med Ctr, Deaconess Joslin Foot Ctr, 1 Deaconess Rd, Boston, MA 02215 USA. EM rgfdpm@aol.com OI Pham, Hau/0000-0003-4583-9873 NR 37 TC 176 Z9 188 U1 1 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 1998 VL 21 IS 10 BP 1714 EP 1719 DI 10.2337/diacare.21.10.1714 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 122FH UT WOS:000076060900023 PM 9773736 ER PT J AU Ferrigno, P Posas, F Koepp, D Saito, H Silver, PA AF Ferrigno, P Posas, F Koepp, D Saito, H Silver, PA TI Regulated nucleo/cytoplasmic exchange of HOG1 MAPK requires the importin beta homologs NMD5 and XPO1 SO EMBO JOURNAL LA English DT Article DE MAP kinase; nuclear transport; osmotic stress; protein phosphorylation ID PROTEIN-TYROSINE PHOSPHATASES; NUCLEAR IMPORT; KINASE CASCADE; SACCHAROMYCES-CEREVISIAE; PC12 CELLS; YEAST; RECEPTOR; TRANSPORT; BINDING; PATHWAY AB MAP kinase signaling modules serve to transduce extracellular signals to the nucleus of eukaryotic cells, but little is known about how signals cross the nuclear envelope, Exposure of yeast tells to increases in extracellular osmolarity activates the HOG1 MAP kinase cascade, which is composed of three tiers of protein kinases, namely the SSK2, SSK22 and STE11 MAP-KKKs, the PBS2 MAPKK, and the HOG1 MAPK, Using green fluorescent protein (GFP) fusions of these kinases, we found that HOG1, PBS2 and STE11 localize to the cytoplasm of unstressed cells, Following osmotic stress, HOG1, but neither PBS2 nor STE11, translocates into the nucleus. HOG1 translocation occurs very rapidly, is transient, and correlates with the phosphorylation and activation of the MAP kinase by its MAPKK, HOG1 phosphorylation is necessary and sufficient for nuclear translocation, because a catalytically inactive kinase when phosphorylated is translocated to the nucleus as efficiently as the wild-type. Nuclear import of the MAPK under stress conditions requires the activity of the small GTP binding protein Ran-GSP1, but not the NLS-binding importin alpha/beta heterodimer, Rather, HOG1 import requires the activity of a gene, NMD5, that encodes a novel importin beta homolog, Similarly, export of dephosphorylated HOG1 from the nucleus requires the activity of the NES receptor XPO1/CRM1, Our findings define the requirements For the regulated nuclear transport of a stress-activated MAP kinase. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM pamela_silver@dfci.harvard.edu RI Posas, Francesc/K-1364-2013 OI Posas, Francesc/0000-0002-4164-7076 FU NIGMS NIH HHS [GM50909, GM56699, R01 GM36373] NR 39 TC 288 Z9 292 U1 3 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD OCT 1 PY 1998 VL 17 IS 19 BP 5606 EP 5614 DI 10.1093/emboj/17.19.5606 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 129KW UT WOS:000076463200011 PM 9755161 ER PT J AU Seminara, SB Hayes, FJ Crowley, WF AF Seminara, SB Hayes, FJ Crowley, WF TI Gonadotropin-releasing hormone deficiency in the human (Idiopathic hypogonadotropic hypogonadism and Kallmann's syndrome: Pathophysiological and genetic considerations SO ENDOCRINE REVIEWS LA English DT Review ID ADRENAL HYPOPLASIA CONGENITA; FOLLICLE-STIMULATING-HORMONE; ORPHAN NUCLEAR RECEPTOR; STEROIDOGENIC FACTOR-I; FUNCTIONAL HYPOTHALAMIC AMENORRHEA; MULLERIAN-INHIBITING SUBSTANCE; SERUM LUTEINIZING-HORMONE; HALF-DISAPPEARANCE TIME; HUMAN MENSTRUAL-CYCLE; NEURAL CELL-ADHESION C1 Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. RP Seminara, SB (reprint author), Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, BHX-5,Fruit St, Boston, MA 02114 USA. FU NICHD NIH HHS [P30 HD028138, T32 HD007396, U54 HD028138, U54 HD029164, R01 HD015788] NR 215 TC 221 Z9 227 U1 0 U2 8 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 OCT PY 1998 VL 19 IS 5 BP 521 EP 539 DI 10.1210/er.19.5.521 PG 19 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 127UF UT WOS:000076368400001 PM 9793755 ER PT J AU Goalstone, ML Natarajan, R Standley, PR Walsh, MF Leitner, JW Carel, K Scott, S Nadler, J Sowers, JR Draznin, B AF Goalstone, ML Natarajan, R Standley, PR Walsh, MF Leitner, JW Carel, K Scott, S Nadler, J Sowers, JR Draznin, B TI Insulin potentiates platelet-derived growth factor action in vascular smooth muscle cells SO ENDOCRINOLOGY LA English DT Article ID CORONARY-HEART-DISEASE; INDEPENDENT RISK-FACTOR; PROTEIN-KINASE PATHWAY; PERMEABILITY FACTOR; COMPENSATORY HYPERINSULINEMIA; NONDIABETIC SUBJECTS; DIABETES-MELLITUS; ENDOTHELIAL-CELL; FASTING GLUCOSE; PLASMA-INSULIN AB Correlative studies have indicated that hyperinsulinemia is present in many individuals with atherosclerosis. Insulin resistance has also been linked to cardiovascular disease. It has proved to be difficult to decipher whether hyperinsulinemia or insulin resistance plays the most important role in the pathogenesis of atherosclerosis and coronary artery disease. In this study, we demonstrate that insulin increases the amount of farnesylated p21Ras in vascular smooth muscle cells (VSMC), thereby augmenting the pool of cellular Ras available for activation by platelet-derived growth factor (PDGF). In VSMC incubated with insulin for 24 h, PDGF's influence on GTP-loading of Ras was significantly increased. Furthermore, in cells preincubated with insulin, PDGF increased thymidine incorporation by 96% as compared with a 44% increase in control cells (a 2-fold increment). Similarly, preincubation of VSMC with insulin increased the ability of PDGF to stimulate gene expression of vascular endothelial growth factor 5- to 8-fold. The potentiating influence of insulin on PDGF action was abrogated in the presence of a farnesyltransferase inhibitor. Thus, the detrimental influence of hyperinsulinemia on the arterial wall may be related to the ability of insulin to augment farnesyltransferase activity and provide greater amounts of farnesylated p21Ras for stimulation by various growth promoting agents. C1 City Hope Natl Med Ctr, Dept Diabet Endocrinol & Metab, Duarte, CA 91010 USA. Wayne State Univ, Dept Med, Detroit, MI 48202 USA. Univ Colorado, Dept Med, Ctr Hlth Sci, Denver, CO 80220 USA. Univ Colorado, Denver VA Med Ctr, Ctr Hlth Sci, Denver, CO 80220 USA. RP Draznin, B (reprint author), VA Hosp, 151,1055 Clermont St, Denver, CO 80220 USA. EM bdramin@sembilan.ufhsc.edu NR 52 TC 52 Z9 52 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 OCT PY 1998 VL 139 IS 10 BP 4067 EP 4072 DI 10.1210/en.139.10.4067 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 121WE UT WOS:000076038100007 PM 9751484 ER PT J AU Takasu, H Bringhurst, FR AF Takasu, H Bringhurst, FR TI Type-1 parathyroid hormone (PTH) PTH-related peptide (PTHrP) receptors activate phospholipase C in response to carboxyl-truncated analogs of PTH(1-34) SO ENDOCRINOLOGY LA English DT Article ID ALKALINE-PHOSPHATASE ACTIVITY; RAT OSTEOSARCOMA CELLS; OSTEOBLAST-LIKE CELLS; KINASE-C; ADENYLYL-CYCLASE; TERMINAL REGION; OVARIECTOMIZED RATS; FRAGMENTS; BINDING; STIMULATION AB The carboxyl(C)-truncated human (h) PTH (hPTH) analog hPTH(1-31), which activates adenylyl cyclase (AC), but not protein kinase C, in rat osteosarcoma cells, exerts an anabolic effect on rat bone in vivo similar to that of hPTH(1-34). It has been proposed, therefore, that this action of PTH(1-34) is mediated exclusively by stimulation of AC via the rat type-1 PTH/PTH-related peptide (PTHrP) receptor (PTH1R). To determine whether this selective signaling pattern also might be a property of the hPTH1R, we studied signal transduction via heterologously expressed hPTH1Rs in response to activation by hPTH(1-34), hPTH(1-31), and a C-truncated analog that does not increase rat bone mass in vivo, hPTH(1-30). In porcine LLC-PK1 cells that stably expressed recombinant hPTH1Rs, these three peptides activated AC identically (EC50 = 1-2 nM). In cells with comparable expression of rat PTH1Rs, AC activation by hPTH(1-34) and hPTH(1-31) again was identical, whereas full activation by hPTH(1-30) required higher concentrations (EC50 = 10 nM vs. 1 nM). Surprisingly, hPTH(1-31) fully stimulated phospholipase C (PLC), via both species of PTH1Rs, with potency that was similar (hPTH1Rs) or slightly reduced (rat PTH1Rs), relative to that of hPTH(1-34). hPTH(1-30), however, was 5-fold less potent than hPTH(1-34) in activating PLC via hPTH1Rs and showed weak and only partial activity via the rat PTH1R. Comparable results were obtained when human and rat PTH1Rs were transiently expressed heterologously in COS-7 cells or homologously in HEK 293 and UMR 106-01 cells, respectively. Binding affinities of these C-truncated peptides to human and rat PTH1Rs were concordant with their relative potencies in activating PLC. We conclude that hPTH(1-31) and, to a lesser extent, hPTH(1-30) can activate PLC, as well as AC, via both rat and human PTH1Rs. Accordingly, a role for PLC activation in the anabolic action of PTH in vivo cannot be excluded. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. RP Bringhurst, FR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Wellman 5, Boston, MA 02114 USA. EM bringhurst.richard@mgh.harvard.edu NR 37 TC 26 Z9 26 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 OCT PY 1998 VL 139 IS 10 BP 4293 EP 4299 DI 10.1210/en.139.10.4293 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 121WE UT WOS:000076038100035 PM 9751512 ER PT J AU Li, YC Amling, M Pirro, AE Priemel, M Meuse, J Baron, R Delling, G Demay, MB AF Li, YC Amling, M Pirro, AE Priemel, M Meuse, J Baron, R Delling, G Demay, MB TI Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia in vitamin D receptor-ablated mice SO ENDOCRINOLOGY LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; BOVINE PARATHYROID CELLS; PRE-PROPARATHYROID HORMONE; D-DEFICIENT RATS; BONE HISTOMORPHOMETRY; GENE-EXPRESSION; D METABOLITES; CALCIUM; 1,25-DIHYDROXYVITAMIN-D3; PROLIFERATION AB 1,25-Dihydroxyvitamin D-3 plays a major role in intestinal calcium transport. To determine what phenotypic abnormalities observed in vitamin D receptor (VDR)-ablated mice are secondary to impaired intestinal calcium absorption rather than receptor deficiency, mineral ion levels were normalized by dietary means. VDR-ablated mice and control littermates were fed a diet that has been shown to prevent secondary hyperparathyroidism in vitamin D-deficient rats. This diet normalized growth and random serum ionized calcium levels in the VDR-ablated mice. The correction of ionized calcium levels prevented the development of parathyroid hyperplasia and the increases in PTH messenger RNA synthesis and in serum PTH levels. VDR-ablated animals fed this diet did not develop rickets or osteomalacia. However, alopecia was still observed in the VDR-ablated mice with normal mineral ions, suggesting that the VDR is required for normal hair growth. This study demonstrates that normalization of mineral ion homeostasis can prevent the development of hyperparathyroidism, osteomalacia, and rickets in the absence of the genomic actions of 1,25-dihydroxyvitamin D-3. C1 Harvard Univ, Endocrine Unit, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06510 USA. Univ Hamburg, Sch Med, Dept Bone Pathol, D-20246 Hamburg, Germany. RP Demay, MB (reprint author), Harvard Univ, Endocrine Unit, Massachusetts Gen Hosp, Sch Med, Wellman 501,32 Fruit St, Boston, MA 02114 USA. EM demay@helix.mgh.harvard.edu NR 42 TC 329 Z9 339 U1 2 U2 12 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 OCT PY 1998 VL 139 IS 10 BP 4391 EP 4396 DI 10.1210/en.139.10.4391 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 121WE UT WOS:000076038100046 PM 28200198 ER PT J AU Jensen, DM AF Jensen, DM TI Diagnosis and treatment of patients with severe hematochezia: A time for change SO ENDOSCOPY LA English DT Editorial Material ID URGENT COLONOSCOPY; HEMORRHAGE; PURGE C1 Univ Calif Los Angeles, CURE, W Los Angeles Vet Adm Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Ctr Hlth Sci, Los Angeles, CA 90073 USA. RP Jensen, DM (reprint author), Univ Calif Los Angeles, CURE, W Los Angeles Vet Adm Med Ctr, 11301 Wilshire Blvd,Bldg 115,Rm 318, Los Angeles, CA 90073 USA. NR 11 TC 5 Z9 5 U1 0 U2 0 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD OCT PY 1998 VL 30 IS 8 BP 724 EP 726 DI 10.1055/s-2007-1001397 PG 3 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 143TG UT WOS:000077272100012 PM 9865565 ER PT J AU Bozza, M Soares, MBP Bozza, PT Satoskar, AR Diacovo, TG Brombacher, F Titus, RG Shoemaker, CB David, JR AF Bozza, M Soares, MBP Bozza, PT Satoskar, AR Diacovo, TG Brombacher, F Titus, RG Shoemaker, CB David, JR TI The PACAP-type I receptor agonist maxadilan from sand fly saliva protects mice against lethal endotoxemia by a mechanism partially dependent on IL-10 SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE maxadilan; PACAP-type 1 receptor; LPS endotoxemia; cytokine; neuropeptide ID TUMOR-NECROSIS-FACTOR; CYCLASE-ACTIVATING POLYPEPTIDE; LUTZOMYIA-LONGIPALPIS; INTERLEUKIN-10 PRODUCTION; VASODILATOR PEPTIDE; POTENT VASODILATOR; VECTOR SALIVA; SEPTIC SHOCK; FACTOR-ALPHA; LIPOPOLYSACCHARIDE AB Sand fly saliva contains maxadilan, a peptide that causes vasodilation and modifies the secretion of pro-inflammatory cytokines by macrophages. We show that 1 to 10 mu g maxadilan protected BALB/c mice against a lethal dose of LPS. Maxadilan reduced serum levels of TNF-alpha by approximately tenfold, while it caused a threefold increase in IL-6 and IL-10. The protective effect of maxadilan is partially dependent on its ability to induce IL-10 production since maxadilan did not prevent death from endotoxic shock in IL-10(-/-) mice. Finally, maxadilan is a selective agonist of the pituitary adenylate cyclase-activating peptide (PACAP) type I receptor, and we found that the natural ligand of this receptor (PACAP 38) also protected mice against lethal endotoxemia. These results indicate that activation of the PACAP type I receptor may contribute to the control of systemic inflammation by a mechanism that is partially dependent on IL-10. C1 Fundao Oswaldo Cruz, Lab Appl Pharmacol, Dept Physiol & Pharmacodynam, BR-21045 Rio De Janeiro, Brazil. Harvard Univ, Sch Publ Hlth, Dept Trop Publ Hlth, Boston, MA USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Max Planck Inst Immunbiol, D-7800 Freiburg, Germany. Colorado State Univ, Coll Vet Med & Biomed Sci, Ft Collins, CO 80523 USA. RP Bozza, M (reprint author), Fundao Oswaldo Cruz, Lab Appl Pharmacol, Dept Physiol & Pharmacodynam, Av Brasil 4365, BR-21045 Rio De Janeiro, Brazil. OI Bozza, Patricia/0000-0001-8349-9529 FU NIAID NIH HHS [AI27511-09, AI22532-13] NR 44 TC 31 Z9 33 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 1998 VL 28 IS 10 BP 3120 EP 3127 DI 10.1002/(SICI)1521-4141(199810)28:10<3120::AID-IMMU3120>3.0.CO;2-3 PG 8 WC Immunology SC Immunology GA 131CY UT WOS:000076559200014 PM 9808180 ER PT J AU Begue-Kirn, C Krebsbach, PH Bartlett, JD Butler, WT AF Begue-Kirn, C Krebsbach, PH Bartlett, JD Butler, WT TI Dentin sialoprotein, dentin phosphoprotein, enamelysin and ameloblastin: tooth-specific molecules that are distinctively expressed during murine dental differentiation SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Article DE dentin sialoprotein; dentin phosphoprotein; enamelysin; ameloblastin; tooth mineralization ID SEQUENCE DETERMINATION; ODONTOBLAST DIFFERENTIATION; BONE SIALOPROTEIN; GENE-EXPRESSION; TGF-BETA; PROTEINS; LOCALIZATION; OSTEONECTIN; CLONING; GERMS AB Dentin sialophosphoprotein [designated DSPP and cleaved into dentin sialoprotein (DSP) and dentin phosphoprotein (DPP)I, enamelysin and ameloblastin are each expressed in unique fashions during tooth development. It is possible that these components participate in cell differentiation and the conversion of unmineralized matrix into mineralized structures. In order to delineate the timing and the positioning of these three molecules in a physiological context, we compared their expression profiles by performing in situ hybridization experiments on consecutive sections in developing mouse tissues. Hybridization signals were uniquely detected for DSPP mRNA in odontoblasts and preameloblasts, for enamelysin mRNA in odontoblasts and in the facing ameloblast layer, and for ameloblastin mRNA in preodontoblasts, polarizing odontoblasts and ameloblasts. Immunohistochemistry showed that DSP and ameloblastin transcripts were translated into proteins that were deposited at the apical pole of the differentiated cells (odontoblasts and ameloblasts, respectively). The interrelated expression profiles found for these tooth-specific molecules illustrate the importance of a specific molecular network to initiate highly regulated processes such as cytodifferentiation and the subsequent mineralization. C1 Univ Texas, Hlth Sci Ctr, Dent Branch, Dept Basic Sci, Houston, TX 77030 USA. Univ Michigan, Sch Dent, Dept Oral Med Pathol & Surg, Ann Arbor, MI 48109 USA. Forsyth Dent Ctr, Dept Biomineralizat, Boston, MA 02115 USA. RP Butler, WT (reprint author), Univ Texas, Hlth Sci Ctr, Dent Branch, Dept Basic Sci, Room 3-108C,6516 John Freeman Ave, Houston, TX 77030 USA. EM wbutler@mail.db.uth.tmc.edu FU NIDCR NIH HHS [R37 DE05092, R29 DE012098, DE12098] NR 50 TC 181 Z9 195 U1 2 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0909-8836 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD OCT PY 1998 VL 106 IS 5 BP 963 EP 970 DI 10.1046/j.0909-8836.1998.eos106510.x PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 127CQ UT WOS:000076333300010 PM 9786327 ER PT J AU Ahroni, JH Boyko, EJ Forsberg, R AF Ahroni, JH Boyko, EJ Forsberg, R TI Reliability of F-Scan in-shoe measurements of plantar pressure SO FOOT & ANKLE INTERNATIONAL LA English DT Article ID LIMB AB Research by our group and others indicates that many amputations of the lower limb occur after foot ulceration in patients with diabetes. It has been proposed that diabetic fool ulcers are mainly caused by repetitive trauma in areas of high plantar pressure during walking. Recent technology permits in-shoe measurement of plantar pressure. We assessed the reliability of the F-Scan in-shoe system for measurement of plantar pressure (Tekscan Inc., Boston, MA) in 51 subjects from a cohort of 977 diabetic veterans enrolled in a prospective study of risk factors for foot ulceration and amputation (the Seattle Diabetic Foot Study). Subjects were tested twice, wearing their own shoes. We used the coefficient of variation (CV) and the intraclass correlation coefficient (ICC) to estimate the reliability of F-Scan measurements of pressure. Peak pressure over the metatarsal heads proved to have the best indices of reliability, with CVs of 0.150 and 0.155, and ICCs of 0.755 and 0.751. Coefficients of variation for the heel, whole foot, and hallux ranged from 0.148 to 0.240, with ICCs ranging from 0.493 to 0.832. By published standards, peak pressures over the metatarsal heads and right hallux met the criteria for excellent reliability. Our ICCs for high pressures under the foot, heel, metatarsal heads, and hallux, and for peak pressures under the heel and left hallux represented fair-to-good reliability. No F-Scan plantar measurements could be judged by these criteria as having poor reliability. This clinical study found that for elderly patients with diabetes who were wearing their own shoes and were tested on two different days with different insoles, the F-Scan insole system was generally reliable for measurements of high pressure and peak pressure. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle Diabet Foot Study, Gen Internal Med Clin 111 M, Seattle, WA 98108 USA. Univ Washington, Sch Nursing, Dept Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA. RP Ahroni, JH (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Seattle Diabet Foot Study, Gen Internal Med Clin 111 M, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 16 TC 66 Z9 66 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1071-1007 J9 FOOT ANKLE INT JI Foot Ankle Int. PD OCT PY 1998 VL 19 IS 10 BP 668 EP 673 PG 6 WC Orthopedics SC Orthopedics GA 130ND UT WOS:000076525400004 PM 9801080 ER PT J AU Tucker, CA Ramirez, J Krebs, DE Riley, PO AF Tucker, CA Ramirez, J Krebs, DE Riley, PO TI Center of gravity dynamic stability in normal and vestibulopathic gait SO GAIT & POSTURE LA English DT Article DE human locomotion; gait control; biomechanics; vestibulopathy AB The purpose of this study was to examine the three-dimensional whole body center of gravity (CG) kinematics during free and paced gait in healthy subjects (n = 16) and individuals with vestibulopathy (n = 8). The cycle time, double and single stance phase durations, values and timing of CG forward velocity, and CG vertical displacement were recorded using an 11 segment, 66 degree of freedom whole body model. The free speed gait of the vestibulopathic individuals was remarkable for increased cycle time, increased percentage of time spent in the double stance phase. decreased forward velocity of the CG, and decreased vertical displacement of the CG. However, during paced gait, no statistically significant differences were found between the vestibulopathic and control groups in all measures. In all groups, CG horizontal velocity maxima and minima significantly lagged CG vertical minima and maxima respectively. We conclude that whole body CG control does not result purely from optimization of mechanical potential and kinetic energy exchanges: our temporal offsets in the maxima and minima of the CG horizontal velocity and vertical displacement make this mechanically impossible. Furthermore, individuals with vestibular impairment may self-select a slower walking speed to ease their biomechanic stability challenge despite being able to ambulate faster with 'normal' CG velocities and displacements. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Boston Univ, Sargent Coll Hlth & Rehabil Sci, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Orthopaed, Biomot Lab, Boston, MA 02114 USA. MGH Inst Hlth Profess, Dept Phys Therapy, Boston, MA 02114 USA. Spaulding Rehabil Hosp, Rehabil Engn Lab, Boston, MA 02114 USA. RP Tucker, CA (reprint author), Boston Univ, Dept Phys Therapy, 635 Common Wealth Ave, Boston, MA 02215 USA. RI Riley, Patrick/B-3053-2009 NR 21 TC 30 Z9 30 U1 0 U2 4 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 OCT PY 1998 VL 8 IS 2 BP 117 EP 123 DI 10.1016/S0966-6362(98)00030-7 PG 7 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA 135NA UT WOS:000076807400005 ER PT J AU McAlindon, ME Gray, T Galvin, A Sewell, HF Podolsky, DK Mahida, YR AF McAlindon, ME Gray, T Galvin, A Sewell, HF Podolsky, DK Mahida, YR TI Differential lamina propria cell migration via basement membrane pores of inflammatory bowel disease mucosa SO GASTROENTEROLOGY LA English DT Article ID INTESTINAL MONONUCLEAR-CELLS; INTRAEPITHELIAL LYMPHOCYTES; FUNCTIONAL-CHARACTERIZATION; ULCERATIVE-COLITIS; CROHNS-DISEASE; MACROPHAGES; DEGRADATION; PHAGOCYTES; EXPRESSION; ACTIVATION AB Background & Aims: In active inflammatory bowel disease (IBD), the intestinal mucosa is infiltrated by polymorphonuclear cells (PMNs), lymphocytes, and monocytes from the systemic circulation. Using an ex vivo model, we have investigated luminally directed migration of cells out of the lamina propria. Methods: Fresh untreated and deepithelialized mucosal samples were studied by electron microscopy. Cells migrating out of the lamina propria were investigated by immunohistochemistry and fluorescence-activated cell sorter analysis. Results: In intact IBD mucosal samples, tunnels containing cells were prominent in the lamina propria matrix, and PMNs, but not other cell types, were prominent in the epithelium. In deepithelialized mucosal samples, the basement membrane was either destroyed or contained numerous large pores. During culture of deepithelialized mucosal samples, many cells (3.3 [+/-0.8] x 10(5) . g tissue(-1) . h(-1)) migrated out of the lamina propria via basement membrane pores. PMNs and eosinophils were prominent during the first 3 hours of culture, but T cells predominated thereafter. Macrophages also migrated, but B cells were the minority population (< 2%) at all times. Conclusions: In active IBD mucosa with an intact epithelium, luminally directed migration of lamina propria cells is restricted mainly to PMNs. After loss of the epithelium, other cell types also migrate into the lumen via numerous, large, basement membrane pores. C1 Univ Nottingham Hosp, Queens Med Ctr, Div Gastroenterol, Nottingham NG7 2UH, England. Univ Nottingham Hosp, Div Pathol, Nottingham NG7 2UH, England. Univ Nottingham Hosp, Div Immunol, Nottingham NG7 2UH, England. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Mahida, YR (reprint author), Univ Nottingham Hosp, Queens Med Ctr, Div Gastroenterol, Nottingham NG7 2UH, England. FU Wellcome Trust NR 30 TC 26 Z9 26 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 OCT PY 1998 VL 115 IS 4 BP 841 EP 848 DI 10.1016/S0016-5085(98)70255-0 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 123QU UT WOS:000076136500010 PM 9753486 ER PT J AU Simpson, SJ De Jong, YP Shah, SA Comiskey, M Wang, B Spielman, JA Podack, ER Mizoguchi, E Bhan, AK Terhorst, C AF Simpson, SJ De Jong, YP Shah, SA Comiskey, M Wang, B Spielman, JA Podack, ER Mizoguchi, E Bhan, AK Terhorst, C TI Consequences of Fas-ligand and perforin expression by colon T cells in a mouse model of inflammatory bowel disease SO GASTROENTEROLOGY LA English DT Article ID VERSUS-HOST DISEASE; ULCERATIVE-COLITIS; CROHNS-DISEASE; SCID MICE; CD4(+); CYTOTOXICITY; LYMPHOCYTES; DEFICIENT; SELECTION; CYTOKINES AB Background & Aims: We describe a type of colitis that develops after transplantation of nonallogeneic wt bone marrow cells into T cell- and natural killer cell-deficient Tg epsilon 26 mice (BM-->Tg epsilon 26). In these animals, severe wasting and inflammation of the colon correlates with the expansion of mucosal T lymphocytes that displays cytotoxic activity, The aims of this study were to determine the relative contribution of perforin and Fas ligand (Fas-L) expression to the cytotoxic action of these T cells and to examine the influence of each pathway in this model of colitis. Methods: Colonic T cells were tested for their ability to mediate Fas- and perforin-dependent killing in redirected cytotoxicity assays. Bone marrow cells from donor mice lacking either Fas-L (gld mice) or perforin (PFPnull mice) or both molecules were used to reconstitute Tg epsilon 26 mice. Results: Colon cytotoxic T lymphocyte displayed both Fas- and perforin-dependent killing. Deficiency in perforin, but not Fas-L, resulted in reduced incidence of wasting and, to a lesser extent, severe colitis in BM-->Tg epsilon 26 animals. Conclusions: Colon T cells from BM-->Tg epsilon 26 mice express both perforin and Fas-L. Although neither pathway is critical in the development of colitis, perforin does have a measurable influence on disease in the BM-->Tg epsilon 26 colitis model. C1 Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Univ Miami, Sch Med, Dept Microbiol & Immunol, Miami, FL USA. RP Terhorst, C (reprint author), Beth Israel Deaconess Med Ctr, Div Immunol, 330 Brookline Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA59351]; NIDDK NIH HHS [P30DK433-51, DK47677-01] NR 36 TC 19 Z9 19 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 1998 VL 115 IS 4 BP 849 EP 855 DI 10.1016/S0016-5085(98)70256-2 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 123QU UT WOS:000076136500011 PM 9753487 ER PT J AU Kaplan, LM AF Kaplan, LM TI Leptin, obesity, and liver disease SO GASTROENTEROLOGY LA English DT Article ID INSULIN; MICE; RECEPTOR; CLONING C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Kaplan, LM (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ-802, Boston, MA 02114 USA. EM kaplan.lee@mgh.harvard.edu NR 34 TC 101 Z9 106 U1 0 U2 5 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 OCT PY 1998 VL 115 IS 4 BP 997 EP 1001 DI 10.1016/S0016-5085(98)70272-0 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 123QU UT WOS:000076136500027 PM 9753503 ER PT J AU Mycek, MA Schomacker, KT Nishioka, NS AF Mycek, MA Schomacker, KT Nishioka, NS TI Colonic polyp differentiation using time-resolved autofluorescence spectroscopy SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID LASER-INDUCED FLUORESCENCE; DIAGNOSIS; TISSUE; DYSPLASIA; MUCOSA AB Background: Steady-state autofluorescence spectroscopy has been examined previously as a technique for distinguishing polyp types during colonoscopy. Although time-resolved methods have shown promise for tissue diagnosis in vitro, they have never been applied endoscopically. The aim of this study was to examine the feasibility of performing time-resolved autofluorescence spectroscopy in vivo and to determine the diagnostic accuracy of the technique as applied to colonic dysplasia. Methods: A time-resolved spectrometer was used to measure the spectrally resolved transient decay of laser-induced autofluorescence emission from colonic tissue in vivo. Results: Seventeen patients with 24 polyps (13 adenomatous, 11 non-adenomatous) were studied. The autofluorescence decay from adenomas was faster than that from non-adenomas. The measured decay time provided a means of distinguishing adenomas from non-adenomas with a sensitivity of 85%, a specificity of 91%, a positive predictive value of 92%, and a negative predictive value of 83%. Conclusions: Time-resolved autofluorescence spectroscopy is a promising optical diagnostic technique for determining polyp types in vivo. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med Serv, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Nishioka, NS (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, Bartlett Hall 708,55 Fruit St, Boston, MA 02114 USA. NR 13 TC 114 Z9 115 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD OCT PY 1998 VL 48 IS 4 BP 390 EP 394 DI 10.1016/S0016-5107(98)70009-4 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 126RZ UT WOS:000076308600009 PM 9786112 ER PT J AU Sorensen, G Stoddard, A Macario, E AF Sorensen, G Stoddard, A Macario, E TI Social support and readiness to make dietary changes SO HEALTH EDUCATION & BEHAVIOR LA English DT Article ID SMOKING CESSATION; HEALTH PROMOTION; VEGETABLE INTAKE; ESTIMATE FRUIT; SELF-EFFICACY; UNITED-STATES; BASE-LINE; WORKSITE; BEHAVIOR; CANCER AB This article examines the relationship between reported social support and readiness to increase fruit and vegetable consumption, based on the Transtheoretical Stage of Change Model. Data were collected as part of the baseline assessments for a work site intervention study promoting increased consumption of fruits and vegetables. Among workers who did not live alone, household support was significantly higher for those of Hispanic and African American heritage than other groups, and was also higher among men, nonsmokers, and those living with adults compared to those living only with children. In multivariate analyses, coworker support was significantly associated with being in preparation compared to precontemplation/contemplation. Household support was not significantly related to readiness to change in multivariate analyses. The effectiveness of work site nutrition education interventions is likely to be enhanced by teaching participants to provide social support to coworkers and family members. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Univ Massachusetts, Amherst, MA 01003 USA. Porter Novelli Inc, Washington, DC USA. RP Sorensen, G (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [5 R01 CA59728] NR 60 TC 38 Z9 38 U1 3 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD OCT PY 1998 VL 25 IS 5 BP 586 EP 598 DI 10.1177/109019819802500506 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 119VK UT WOS:000075918700005 PM 9768379 ER PT J AU Biggs, PJ AF Biggs, PJ TI Determination of the shielding for an unoccupied roof of a radiation therapy facility to account for adjacent buildings - Modification of a computer program SO HEALTH PHYSICS LA English DT Article; Proceedings Paper CT 39th American-Association-of-Physicists-in-Medicine Annual Meeting CY JUL 27-31, 1997 CL MILWAUKEE, WI SP Amer Assoc Physicists Med DE radiation therapy; shielding; computers; exposure, occupational AB An addition has been made to an existing software program for calculating shielding thicknesses of barriers for megavoltage radiation therapy beams. This addition calculates the shielding thicknesses required for the roof of a single-story building when adjacent, multi-level buildings are occupied. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. NR 2 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD OCT PY 1998 VL 75 IS 4 BP 431 EP 435 DI 10.1097/00004032-199810000-00013 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 124VR UT WOS:000076203800015 PM 9753370 ER PT J AU Stankovic, KM Brown, D Alper, SL Adams, JC AF Stankovic, KM Brown, D Alper, SL Adams, JC TI Localization of pH regulating proteins H(+)ATPase and Cl-/HCO3- exchanger in the guinea pig inner ear (vol 114, pg 21, 1997) SO HEARING RESEARCH LA English DT Correction C1 Harvard Univ, Massachusetts Eye & Ear Infirm, MIT, Div Hlth Sci & Technol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Mol Med Unit, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Renal Unit, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02214 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02214 USA. RP Stankovic, KM (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, MIT, Div Hlth Sci & Technol, 243 Charles St, Boston, MA 02114 USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD OCT PY 1998 VL 124 IS 1-2 BP 191 EP 192 DI 10.1016/S0378-5955(98)00060-4 PG 2 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 132RU UT WOS:000076644200020 ER PT J AU Crawford, AR Bungard, D Bergman, CM Karpen, SJ Ruddle, NH Ferrara, JLM Crawford, JM AF Crawford, AR Bungard, D Bergman, CM Karpen, SJ Ruddle, NH Ferrara, JLM Crawford, JM TI Hepatic inflammation renders the murine liver more susceptible to endotoxin-induced cholestasis. SO HEPATOLOGY LA English DT Meeting Abstract C1 Yale Univ, Sch Med, Ctr Liver, New Haven, CT 06510 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 364 BP 253A EP 253A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100364 ER PT J AU Sturm, E Crawford, AR Zimmermann-Kraynak, TL Svetlov, SI Sundaram, P Bungard, D Ferrara, JLM Karpen, SJ Crawford, JM AF Sturm, E Crawford, AR Zimmermann-Kraynak, TL Svetlov, SI Sundaram, P Bungard, D Ferrara, JLM Karpen, SJ Crawford, JM TI Macrophages are capable of mediating the cholestatic effects of endotoxin on a hepatocyte line SO HEPATOLOGY LA English DT Meeting Abstract C1 Yale Univ, Sch Med, Ctr Liver, Program GI Pathol, New Haven, CT 06510 USA. Yale Univ, Sch Med, Ctr Liver, Sect Digest Dis, New Haven, CT 06510 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 363 BP 253A EP 253A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100362 ER PT J AU Wong, DKH Dohrenwend, PB Rosenberg, ES Chung, RT Robbins, GK Walker, BD AF Wong, DKH Dohrenwend, PB Rosenberg, ES Chung, RT Robbins, GK Walker, BD TI Vigorous and broadly-directed cellular immune response in acute HCV infection. SO HEPATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RI Robbins, Gregory/F-7988-2011 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 448 BP 274A EP 274A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100448 ER PT J AU Encke, HT Zu, J Wands, PJ AF Encke, HT Zu, J Wands, PJ TI Characterization of antisense oligodeoxynucleotides (ODN) and proteinase inhibitors that inhibit hepatitis C virus NS3 function. SO HEPATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Mol Hepatol Lab, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 494 BP 286A EP 286A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100495 ER PT J AU Heintges, T Putlitz, JZ Wands, JR AF Heintges, T Putlitz, JZ Wands, JR TI Cloning, bacterial expression and sequencing of human antibody fragments against hepatitis C virus NS3 by phage display of a combinatorial phagemid library. SO HEPATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Hepatol Lab, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 497 BP 287A EP 287A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100497 ER PT J AU Encke, J Wands, JR AF Encke, J Wands, JR TI Chronic ethanol consumption inhibits immune responses against hepatitis C virus nonstructural NS5 protein. SO HEPATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc,Mol Hepatol Lab, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 565 BP 304A EP 304A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100565 ER PT J AU Atkins, M Hunt, CM Brown, N Gray, F Sanathanan, L Woessner, M Lai, CL Dusheiko, G Dienstag, J Wright, T Barnard, J Bourne, E Condreay, L AF Atkins, M Hunt, CM Brown, N Gray, F Sanathanan, L Woessner, M Lai, CL Dusheiko, G Dienstag, J Wright, T Barnard, J Bourne, E Condreay, L TI Clinical significance of YMDD mutant hepatitis B virus (HBV) in a large cohort of lamivudine-treated hepatitis B patients. SO HEPATOLOGY LA English DT Meeting Abstract C1 Glaxo Wellcome, Greenford, Middx, England. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. Queen Mary Hosp, Hong Kong, Hong Kong. Royal Free Hosp, London NW3 2QG, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RI Lai, Ching Lung/C-4298-2009 NR 0 TC 30 Z9 37 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 625 BP 319A EP 319A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100625 ER PT J AU Liu, XL Takehara, T Takahashi, H AF Liu, XL Takehara, T Takahashi, H TI Elevated expression of Bcl-xL in human hepatocellular carcinomas. SO HEPATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Gastrointestinal Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 659 BP 327A EP 327A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100658 ER PT J AU Rosenberg, PM Toth, CM Pascual, M Dienstag, JL Cosimi, SB Chung, RT AF Rosenberg, PM Toth, CM Pascual, M Dienstag, JL Cosimi, SB Chung, RT TI HCV-associated fibrosing cholestatic hepatitis after renal transplantation: Response to interferon alfa therapy. SO HEPATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplant Surg Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 736 BP 346A EP 346A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100736 ER PT J AU Schiff, E Karavalcin, S Grimm, I Perrillo, R Dienstag, J Husa, P Schalm, S Crowther, L Sullivan, M Woessner, M McPhillips, P Brown, N AF Schiff, E Karavalcin, S Grimm, I Perrillo, R Dienstag, J Husa, P Schalm, S Crowther, L Sullivan, M Woessner, M McPhillips, P Brown, N CA Intl Lamivudine Investigator Grp TI A placebo-controlled study of lamivudine and interferon alpha-2b in patients with chronic hepatitis B who previously failed interferon therapy SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ Miami, Miami, FL 33152 USA. Ankara Univ, Sch Med, TR-06100 Ankara, Turkey. Univ N Carolina, Chapel Hill, NC 27515 USA. Alton Ochsner Med Fdn & Ochsner Clin, New Orleans, LA 70121 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Clin Infect Dis, Brno, Czech Republic. Acad Zienkenhuis Dijkzigt Rotterdam, Rotterdam, Netherlands. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. Glaxo Wellcome Inc, Greenford, Middx, England. NR 0 TC 52 Z9 56 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 901 BP 388A EP 388A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100900 ER PT J AU Ito, T Sasaki, Y Horimoto, M Wada, S Tanaka, Y Toyama, T Hayashi, N Hori, M Wands, JR AF Ito, T Sasaki, Y Horimoto, M Wada, S Tanaka, Y Toyama, T Hayashi, N Hori, M Wands, JR TI Promotion of hepatocarcinogenesis through utilization of Ras by insulin receptor substrate-1 (IRS-1) overexpression. SO HEPATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH Canc Ctr,Mol Hepatol Lab, Cambridge, MA 02138 USA. Osaka Univ, Sch Med, Dept Med 1, Osaka 553, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1013 BP 416A EP 416A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101012 ER PT J AU Encke, J Putlitz, JZ Geissler, M Wands, JR AF Encke, J Putlitz, JZ Geissler, M Wands, JR TI Genetic immunization against the nonstructural proteins NS3, NS4 and NS5 of hepatitis C virus generates broad based cellular and humoral immune responses and protection in a tumor model. SO HEPATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Hepatol Lab, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1210 BP 465A EP 465A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101210 ER PT J AU Encke, J Geissler, M de la Monte, S Schmidt, EV Wands, JR AF Encke, J Geissler, M de la Monte, S Schmidt, EV Wands, JR TI Genetic immunization breaks tolerance in hepatitis C virus (HCV) core transgenic mice. SO HEPATOLOGY LA English DT Meeting Abstract C1 Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Mol Hepatol Lab, Charlestown, MA USA. Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Tumor Biol Lab, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1214 BP 466A EP 466A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101214 ER PT J AU Encke, J Putlitz, JZ Wands, JR AF Encke, J Putlitz, JZ Wands, JR TI Immunostimulatory CpG motifs enhance antibody production but not cellular immune responses in vivo after genetic immunization. SO HEPATOLOGY LA English DT Meeting Abstract C1 Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Mol Hepatol Lab, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1215 BP 466A EP 466A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101213 ER PT J AU Eto, T Takahashi, H AF Eto, T Takahashi, H TI Inhibition of hepatitis B virus production by asialo-interferon. SO HEPATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1314 BP 491A EP 491A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101314 ER PT J AU Mohr, L Shankara, S Roberts, B Armentano, D Wands, JR AF Mohr, L Shankara, S Roberts, B Armentano, D Wands, JR TI Efficient tumor cell killing and pronounced bystander effect by adenovirus mediated transfer of the E-coli purine nucleoside phosphorylase gene to hepatocellular carcinoma cells. SO HEPATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Mol Hepatol Lab, MGH Canc Ctr, Charlestown, MA USA. Genzyme Corp, Framingham, MA 01701 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1367 BP 504A EP 504A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101365 ER PT J AU Putlitz, JZ Yu, Q Burke, JM Wands, JR AF Putlitz, JZ Yu, Q Burke, JM Wands, JR TI In vitro selected hairpin ribozymes inhibit hepatitis B virus replication in human hepatoma cells. SO HEPATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Hepatol Lab,Canc Ctr, Charlestown, MA USA. Univ Vermont, Dept Microbiol & Mol Genet, Burlington, VT 05405 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1420 BP 517A EP 517A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101419 ER PT J AU Yoon, SK Mohr, L O'Riordan, C Armentano, D Wands, JR AF Yoon, SK Mohr, L O'Riordan, C Armentano, D Wands, JR TI Targeting of recombinant adenovirus to hepatocellular carcinoma cells using a tumor specific bifunctional Fab complex SO HEPATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Mol Hepatol Lab, Charlestown, MA USA. Genzyme Corp, Framingham, MA 01701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1422 BP 518A EP 518A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101422 ER PT J AU Yoon, SK Mohr, L Armentano, D Wands, JR AF Yoon, SK Mohr, L Armentano, D Wands, JR TI Adenovirus-mediated gene transfer to hepatocellular carcinomas in nude mice. SO HEPATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Mol Hepatol Lab, Charlestown, MA USA. Genzyme Corp, Framingham, MA 01701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1423 BP 518A EP 518A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101421 ER PT J AU Yoon, SK de la Monte, S Armentano, D Wands, JR AF Yoon, SK de la Monte, S Armentano, D Wands, JR TI CD95(APO-1/Fas) and p53 mediated apoptosis associated with experimental adenoviral hepatitis. SO HEPATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Mol Hepatol Lab, MGH Canc Ctr, Charlestown, MA USA. Genzyme Corp, Framingham, MA 01701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1421 BP 518A EP 518A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101420 ER PT J AU Mohr, L Rainov, N Mohr, U Breakefield, XO Wands, JR AF Mohr, L Rainov, N Mohr, U Breakefield, XO Wands, JR TI The use of rabbit cytochrome P450 4B1 as new prodrug activator for gene therapy of hepatocellular carcinoma. SO HEPATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Mol Hepatol Lab, MGH Canc Ctr, Charlestown, MA USA. Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1425 BP 519A EP 519A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101424 ER PT J AU Putlitz, J Lanford, RE Carlson, RI Notvall, L de la Monte, SM Wands, JR AF Putlitz, J Lanford, RE Carlson, RI Notvall, L de la Monte, SM Wands, JR TI Properties of hepatitis B virus polymerase revealed by monoclonal antibodies SO HEPATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Ctr,Mol Hepatol Lab, Charlestown, MA USA. SW Fdn Biomed Res, Dept Virol & Immunol, San Antonio, TX 78227 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1672 BP 580A EP 580A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101671 ER PT J AU Putlitz, JZ Encke, J Wands, JR AF Putlitz, JZ Encke, J Wands, JR TI DNA-based immunization generates cellular immune responses against hepatitis B virus polymerase. SO HEPATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Ctr,Mol Hepatol Lab, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1676 BP 581A EP 581A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101675 ER PT J AU Leung, N Dienstag, J Schiff, E Sullivan, M Atkins, M Grice, R Woessner, M Brown, N Hunt, CM AF Leung, N Dienstag, J Schiff, E Sullivan, M Atkins, M Grice, R Woessner, M Brown, N Hunt, CM TI Clinical safety profile of lamivudine treatment in a large cohort of hepatitis B patients. SO HEPATOLOGY LA English DT Meeting Abstract C1 Prince Wales Hosp, Hong Kong, Hong Kong. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Miami, Miami, FL 33152 USA. Glaxo Wellcome Inc, Greenford, Middx, England. NR 0 TC 8 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1698 BP 587A EP 587A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101698 ER PT J AU Putlitz, JZ Skerra, A Wands, JR AF Putlitz, JZ Skerra, A Wands, JR TI An intracellular antibody fragment inhibits hepatitis B virus surface antigen secretion SO HEPATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hepatol Lab,Canc Ctr, Charlestown, MA USA. TH Darmstadt, Inst Biochem, Prot Chem Abt, D-64287 Darmstadt, Germany. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1711 BP 590A EP 590A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101709 ER PT J AU Encke, J zu Putlitz, J Carlson, R Wands, JR AF Encke, J zu Putlitz, J Carlson, R Wands, JR TI Development, characterization and mapping of monoclonal antibodies against hepatitis C virus nonstructural protein 3. SO HEPATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc,Mol Hepatol Lab, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 2074 BP 681A EP 681A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258102073 ER PT J AU Encke, J zu Putlitz, J Carlson, R Wands, JR AF Encke, J zu Putlitz, J Carlson, R Wands, JR TI Monoclonal antibodies generated against HCV nonstructural NS4 protein by a combination of protein and DNA-based immunization. SO HEPATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc,Mol Hepatol Lab, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 2073 BP 681A EP 681A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258102071 ER PT J AU Sorensen, AG Boland, G Zaheer, A AF Sorensen, AG Boland, G Zaheer, A TI X-ray computed tomographic (CT) analysis of tumor necrosis after tumoricidal therapy with intratumoral cisplatin/epinephrine injectable gel in patients with unresectable primary hepatocellular carcinoma and intrahepatic colorectal metastases. SO HEPATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 2373 BP 756A EP 756A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258102371 ER PT J AU Karlsson, JOM Yarmush, ML Toner, M AF Karlsson, JOM Yarmush, ML Toner, M TI Interaction between heat shock and interleukin 6 stimulation in the acute-phase response of human hepatoma (HepG2) cells SO HEPATOLOGY LA English DT Article ID GENE-EXPRESSION; ELEVATED-TEMPERATURE; MOLECULAR-BIOLOGY; CIRCULATORY SHOCK; HUMAN HEPATOCYTES; PLASMA-PROTEINS; FEVER; SERUM; HYPERTHERMIA; RAT AB Two characteristic elements of the acute-phase response are an altered pattern of circulating hepatic proteins and fever. Whereas a fever-induced heat shock response could affect expression of acute-phase proteins in the liver, the effects of a modest temperature increase on protein secretion in interleukin-6 (IL-6)-stimulated HepG2 cells were investigated. The response of HepG2 cells to IL-6 stimulation was significantly affected by heat treatment at 40 degrees C, Albumin secretion rates, which were reduced by a factor of 2 in response to either heat shock or IL-6 stimulation alone, were down-regulated by a factor of 4 when IL-6 was administered simultaneously with a continuous 40 degrees C heat shock. IL-6-induced fibrinogen up-regulation was significantly reduced by heat treatment (P < .01), and secretion rates were indistinguishable from control levels after 2 days (P > .10). Unexpectedly, heat shock at 40 degrees C induced a fivefold up-regulation of haptoglobin production in the absence of IL-6. Simultaneous heat shock and IL-6 stimulation caused a synergistic enhancement of haptoglobin expression, with secretion rates increasing up to 30-fold compared with unstimulated control cells. For all three proteins, the interaction between temperature and IL-6 concentration was statistically significant (P < .001). Heat treatment resulted in significant alterations of both the kinetics and sensitivity of IL-6-induced protein synthesis, suggesting a major modification of the mechanism of acute-phase protein regulation at 40 degrees C. In summary, the data show that heat shock can significantly modulate the pattern of acute-phase protein expression and that fever may be an important regulatory factor in the acute-phase response. C1 Univ Illinois, Dept Mech Engn, Chicago, IL 60680 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA USA. Shriners Burns Hosp, Boston, MA USA. RP Toner, M (reprint author), Shriners Res Ctr, 1 Kendall Sq,1400W, Cambridge, MA 02139 USA. NR 45 TC 5 Z9 5 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 BP 994 EP 1004 DI 10.1002/hep.510280414 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 124JW UT WOS:000076180000014 PM 9755236 ER PT J AU Gustafson, CE Levine, S Katsura, T McLaughlin, M Aleixo, MD Tamarappoo, BK Verkman, AS Brown, D AF Gustafson, CE Levine, S Katsura, T McLaughlin, M Aleixo, MD Tamarappoo, BK Verkman, AS Brown, D TI Vasopressin regulated trafficking of a green fluorescent protein-aquaporin 2 chimera in LLC-PK1 cells SO HISTOCHEMISTRY AND CELL BIOLOGY LA English DT Article ID TO-GOLGI TRANSPORT; WATER CHANNEL; COLLECTING DUCT; LIVING CELLS; RAT-KIDNEY; TRANSLOCATION; EXPRESSION; CLONING; CHIP28; LOCALIZATION AB Aquaporin 2 (AQP2) transfected into LLC-PK1 cells functions as a vasopressin-regulated water channel that recycles between intracellular vesicles and the plasma membrane upon vasopressin stimulation. The green fluorescent protein (GFP) of the jellyfish, Aequorea victoria, was used as an autofluorescent tag to monitor AQP2 trafficking in transfected LLC-PK1 cells. Two chimeras were constructed, one in which GFP was fused to the amino-terminus of AQP2 [GFP-AQP2(NT)] and the second in which it was fused to the carboxyl-terminus [AQP2-GFP(CT)]. The GFP-AQP2(NT) chimera trafficked in a regulated pathway from intracellular vesicles to the basolateral plasma membrane in response to vasopressin or forskolin stimulation of cells. In contrast, the AQP2-GFP(CT) chimera expressed in LLC-PK1 cells was localized constitutively on both apical and basolateral plasma membranes. The cellular location of this chimera was not modified by vasopressin or forskolin. Thus, while the GFP-AQP2(NT) chimera will be useful to study AQP(2) trafficking in vitro, the abnormal, constitutive membrane localization of the AQP2-GFP(CT) chimera suggests that one or more trafficking signals exist on the carboxyl-terminus of the AQP2 protein. C1 Massachusetts Gen Hosp E, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02129 USA. Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02129 USA. Univ Calif San Francisco, Cardiovasc Res Inst, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Cardiovasc Res Inst, Dept Physiol, San Francisco, CA 94143 USA. RP Brown, D (reprint author), Massachusetts Gen Hosp E, 149 13th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK 38452] NR 35 TC 34 Z9 36 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0301-5564 J9 HISTOCHEM CELL BIOL JI Histochem. Cell Biol. PD OCT PY 1998 VL 110 IS 4 BP 377 EP 386 DI 10.1007/s004180050298 PG 10 WC Cell Biology; Microscopy SC Cell Biology; Microscopy GA 123RF UT WOS:000076137600004 PM 9792416 ER PT J AU Raz, T Barrett, T Szargel, R Mandel, H Neufeld, EJ Nosaka, K Viana, MB Cohen, N AF Raz, T Barrett, T Szargel, R Mandel, H Neufeld, EJ Nosaka, K Viana, MB Cohen, N TI Refined mapping of the gene for thiamine-responsive megaloblastic anemia syndrome and evidence for genetic homogeneity SO HUMAN GENETICS LA English DT Article ID DIABETES-MELLITUS; SENSORINEURAL DEAFNESS; SACCHAROMYCES-CEREVISIAE; DIDMOAD SYNDROME; WOLFRAM-SYNDROME; LINKAGE; PYROPHOSPHOKINASE; TRANSPORT; MAP AB Thiamine-responsive megaloblastic anemia (TRMA, also known as Rogers syndrome, OMIM 249270) is a rare autosomal recessive disorder characterized by a triad of megaloblastic anemia, diabetes mellitus, and sensorineural deafness. Patients respond, to varying degrees, to treatment with megadoses of thiamine. We have recently shown genetic linkage of the TRMA gene to a 16-centimorgan (cM) region on 1q23.2-1q23.3 based on the analysis of four large, inbred families of Alaskan, Italian, and Israeli-Arab origin. Here we narrow the TRMA interval down to 4 cM based on genetic recombination, homozygosity mapping, and linkage disequilibrium (highest LOD score of 12.5 at D1S2799, at a recombination fraction of 0). We provide further evidence that the TRMA gene is located in this region and confirm the homogeneity of the disease. In this analysis, we genotyped seven additional families of diverse ethnic origin (Pakistani, Indian, Italian, Brazilian, and Japanese), and analyzed additional markers in two previously reported families showing evidence of linkage disequilibrium in a large area of their haplotypes. The multi-system manifestations of TRMA suggest that thiamine has a pivotal role in a multiplicity of physiological processes. Mapping the TRMA gene and understanding the molecular basis of the disease might, thus, shed light on the role of thiamine in common disorders such as deafness, anemia, and diabetes. C1 Technion Israel Inst Technol, Bruce Rappaport Fac Med, Dept Genet, Tamkin Human Mol Genet Res Facil, IL-31096 Haifa, Israel. Univ Birmingham, Dept Pediat & Child Hlth, Birmingham, W Midlands, England. Rambam Med Ctr, Dept Pediat, Haifa, Israel. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Dana Farber Canc Inst, Div Hematol, Boston, MA 02115 USA. Kyoto Prefectural Univ Med, Kyoto, Japan. Felichio Rocho Med Ctr, Dept Hematol, Belo Horizonte, MG, Brazil. RP Cohen, N (reprint author), Technion Israel Inst Technol, Bruce Rappaport Fac Med, Dept Genet, Tamkin Human Mol Genet Res Facil, POB 9649, IL-31096 Haifa, Israel. RI Neufeld, Ellis/F-9331-2011; OI Viana, Marcos/0000-0001-9665-2115 NR 34 TC 11 Z9 12 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD OCT PY 1998 VL 103 IS 4 BP 455 EP 461 DI 10.1007/s004390050850 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 144DA UT WOS:000077297400015 PM 9856490 ER PT J AU Eyaid, WM Clough, MV Root, H Scott, KM McCormick, MK Zhang, X Lisitsyn, NA Kearns, WG Francomano, CA Richards, JE McIntosh, I AF Eyaid, WM Clough, MV Root, H Scott, KM McCormick, MK Zhang, X Lisitsyn, NA Kearns, WG Francomano, CA Richards, JE McIntosh, I TI Physical mapping of the nail patella syndrome interval at 9q34: ordering of STSs and ESTs SO HUMAN GENETICS LA English DT Article ID YAC LIBRARY; CONSTRUCTION; GENOME; CLONES C1 Johns Hopkins Univ, Ctr Med Genet, Baltimore, MD 21287 USA. Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Ophthalmol, Ann Arbor, MI 48105 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. Eastern Virginia Med Sch, Dept Pediat, Norfolk, VA 23510 USA. Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48105 USA. RP McIntosh, I (reprint author), Johns Hopkins Univ, Ctr Med Genet, 600 N Wolfe St,Blalock 1012G, Baltimore, MD 21287 USA. FU NCI NIH HHS [CA64534]; NEI NIH HHS [EY09580]; NIAMS NIH HHS [AR44702] NR 9 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD OCT PY 1998 VL 103 IS 4 BP 525 EP 526 DI 10.1007/s004390050862 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 144DA UT WOS:000077297400027 PM 9856502 ER PT J AU Kern, PS Teng, MK Smolyar, A Liu, JH Liu, J Hussey, RE Spoerl, R Chang, HC Reinherz, EL Wang, JH AF Kern, PS Teng, MK Smolyar, A Liu, JH Liu, J Hussey, RE Spoerl, R Chang, HC Reinherz, EL Wang, JH TI Structural basis of CD8 coreceptor function revealed by crystallographic analysis of a murine CD8 alpha alpha ectodomain fragment in complex with H-2K SO IMMUNITY LA English DT Article ID T-CELL RECEPTOR; MHC CLASS-I; CYTOTOXIC LYMPHOCYTES-T; ALPHA-3 DOMAIN; BETA-CHAIN; CRYSTAL-STRUCTURE; VIRAL PEPTIDE; RECOGNITION; BINDING; MOLECULE AB The crystal structure of the two immunoglobulin variable-like domains of the murine CD8 alpha alpha homodimer complexed to the class I MHC H-2K(b) molecule at 2.8 A resolution shows that CD8 alpha alpha binds to the protruding MHC alpha 3 domain loop in an antibody-like manner. Comparison of mouse CD8 alpha alpha/H-2K(b) and human CD8 alpha alpha/HLA-A2 complexes reveals shared as well as species-specific recognition features. In both species, core-ceptor function apparently involves the participation of CD8 dimer in a bidentate attachment to an MHC class I molecule in conjunction with a T cell receptor without discernable conformational alteration of the peptide or MHC antigen-presenting platform. C1 Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Wang, JH (reprint author), Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. EM Ellis_Reinherz@dfci.harvard.edu; jwang@red.dfci.harvard.edu FU NIAID NIH HHS [AI39098, AI19807]; NIGMS NIH HHS [GM56008] NR 58 TC 145 Z9 149 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD OCT PY 1998 VL 9 IS 4 BP 519 EP 530 DI 10.1016/S1074-7613(00)80635-4 PG 12 WC Immunology SC Immunology GA 133HG UT WOS:000076680700010 PM 9806638 ER PT J AU Wang, JH Avitahl, N Cariappa, A Friedrich, C Ikeda, T Renold, A Andrikopoulos, K Liang, LB Pillai, S Morgan, BA Georgopoulos, K AF Wang, JH Avitahl, N Cariappa, A Friedrich, C Ikeda, T Renold, A Andrikopoulos, K Liang, LB Pillai, S Morgan, BA Georgopoulos, K TI Aiolos regulates B cell activation and maturation to effector state SO IMMUNITY LA English DT Article ID ANTIGEN RECEPTOR; IKAROS GENE; CD22-DEFICIENT MICE; DNA-REPLICATION; DEFICIENT MICE; BONE-MARROW; IG-BETA; IN-VIVO; IMMUNOGLOBULIN; FC-GAMMA-RIIB1 AB Aiolos encodes a zinc finger DNA-binding protein that is highly expressed in mature B cells and is homologous to Ikaros. In the periphery of mice homozygous for an Aiolos-null mutation, B cells exhibit an activated cell surface phenotype and undergo augmented antigen receptor (BCR)-mediated in vitro proliferative responses, even at limiting amounts of stimulant. In vivo, T cell-dependent B cell responses, including the formation of germinal centers and elevated serum IgG and IgE, are detected in Aiolos-deficient mice in the absence of immunization. Auto-antibodies and development of B cell lymphomas are frequently seen among aging Aiolos mutants. In sharp contrast to conventional B cells, B cells of the peritoneum, of the marginal zone, and the recirculating bone marrow population are greatly reduced. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Georgopoulos, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM Katia_Georgopoulos@CBRC.MGH.Harvar FU NIAID NIH HHS [R01 AI42254-01A1] NR 39 TC 192 Z9 200 U1 2 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD OCT PY 1998 VL 9 IS 4 BP 543 EP 553 DI 10.1016/S1074-7613(00)80637-8 PG 11 WC Immunology SC Immunology GA 133HG UT WOS:000076680700012 PM 9806640 ER PT J AU Shortman, K Vremec, D Corcoran, LM Georgopoulos, K Lucas, K Wu, L AF Shortman, K Vremec, D Corcoran, LM Georgopoulos, K Lucas, K Wu, L TI The linkage between T-cell and dendritic cell development in the mouse thymus SO IMMUNOLOGICAL REVIEWS LA English DT Review ID COLONY-STIMULATING FACTOR; PRECURSOR CELLS; NEGATIVE SELECTION; LINEAGE COMMITMENT; LYMPHOID ORGANS; SURFACE-MARKERS; NATURAL-KILLER; CD8 EXPRESSION; IKAROS GENE; STEM-CELLS AB Thymic dendritic cells (DC) mediate negative selection at a relatively late stage of the T-cell developmental pathway. We present evidence that the development of thymic DC and of T-lineage cells is linked via a common precursor at an early stage of thymocyte development. T-lineage precursor populations from the adult mouse thymus, prior to T-cell receptor gene rearrangement, display a capacity to produce DC as well as T cells in the thymus, and are very efficient precursors of DC in culture. These lymphoid/DC precursors have little capacity to form myeloid cells, indicating that thymic DC are a lymphoid-related rather than myeloid-related lineage. In contrast to myeloid-related DC, granulocyte-macrophage colony-stimulating factor is not required for the development of these lymphoid-related DC in vivo or in vitro. DC can develop in mutant mice lacking mature T cells, provided the common precursors are present. However, in mutant mice lacking functional Ikaros transcription factors, there are deficiencies in lymphoid precursor cells, in mature lymphoid cells and in DC. C1 Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA USA. RP Shortman, K (reprint author), Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia. RI Corcoran, Lynn/C-9316-2013 NR 42 TC 86 Z9 87 U1 1 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD OCT PY 1998 VL 165 BP 39 EP 46 DI 10.1111/j.1600-065X.1998.tb01228.x PG 8 WC Immunology SC Immunology GA 142FC UT WOS:000077188400004 PM 9850850 ER PT J AU Sleckman, BP Bassing, CH Bardon, CG Okada, A Khor, B Bories, JC Monroe, R Alt, FW AF Sleckman, BP Bassing, CH Bardon, CG Okada, A Khor, B Bories, JC Monroe, R Alt, FW TI Accessibility control of variable region gene assembly during T-cell development SO IMMUNOLOGICAL REVIEWS LA English DT Review ID RECEPTOR ALPHA/DELTA-LOCUS; CHAIN INTRON ENHANCER; EARLY-ALPHA TEA; TRANSCRIPTIONAL ENHANCER; V(D)J RECOMBINATION; TCR-ALPHA; TARGETED DELETION; GENOMIC ORGANIZATION; ALLELIC EXCLUSION; DELTA REGION AB T-cell development is a complex and ordered process that is regulated in part by the progressive assembly and expression of antigen receptor genes. T cells can be divided into two lineages based on expression of either an alpha beta or gamma delta T-cell antigen receptor (TCR). The genes that encode the TCR beta and gamma chains lie in distinct loci, whereas the genes that encode the TCR alpha and delta chains lie in a single locus (TCR alpha/delta locus). Assembly of TCR variable region genes is mediated by a site-specific recombination process that is common among all lymphocytes. Despite the common nature of this process, recombination of TCR genes is tightly regulated within the context of the developing T cell. TCR beta, gamma and delta variable region genes are assembled prior to TCR a variable region genes. Furthermore, assembly of TCR beta variable region genes is regulated within the context of allelic exclusion. The regulation of rearrangement and expression of genes within the TCR alpha/delta locus presents a complicated problem. TCR alpha and delta variable region genes are assembled at different stages of T-cell development, and fully assembled TCR alpha and delta variable region genes must be expressed in distinct Lineages of T cells, alpha beta and gamma delta, respectively We have developed several experimental approaches to assess the role of cis-acting elements in regulating recombination and expression of TCR genes. Here we describe these approaches and discuss our analyses of the regulation of accessibility of the TCR beta and TCR alpha/delta loci during T-cell development. C1 Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Ctr Blood Res, Boston, MA 02115 USA. RP Alt, FW (reprint author), Childrens Hosp, Howard Hughes Med Inst, Longwood Ave, Boston, MA 02115 USA. EM alt@rascal.med.harvard.edu FU NIAID NIH HHS [AI 20047, AI 01297-01] NR 59 TC 38 Z9 38 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD OCT PY 1998 VL 165 BP 121 EP 130 DI 10.1111/j.1600-065X.1998.tb01235.x PG 10 WC Immunology SC Immunology GA 142FC UT WOS:000077188400011 PM 9850857 ER PT J AU Ghia, P ten Boekel, E Rolink, AG Melchers, F AF Ghia, P ten Boekel, E Rolink, AG Melchers, F TI B-cell development: a comparison between mouse and man SO IMMUNOLOGY TODAY LA English DT Review ID SURROGATE LIGHT-CHAIN; LAMBDA-LIKE GENES; HUMAN-BONE-MARROW; PRE-B; IMMUNOGLOBULIN HEAVY; ESCAPE TOLERANCE; LINEAGE CELLS; SINGLE CELLS; H-CHAIN; EXPRESSION AB A common variable immunodeficiency (CVID) patient, who carries mutations on both alleles of the gene encoding the surrogate light chain component lambda 5/14.1, shows a similar phenotype of B-cell deficiency as thr lambda 5-deficient mutant mouse. As discussed here by Paolo Ghia and colleagues, this points to a remarkably similar developmental pathway of B cells in humans and mice. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Basel Inst Immunol, CH-4005 Basel, Switzerland. RP Ghia, P (reprint author), Inst Ric Cura Canc, Strada Prov 142,Km 3-95, I-10060 Turin, Italy. RI Ghia, Paolo/K-7138-2016 OI Ghia, Paolo/0000-0003-3750-7342 NR 55 TC 81 Z9 83 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD OCT PY 1998 VL 19 IS 10 BP 480 EP 485 DI 10.1016/S0167-5699(98)01330-9 PG 6 WC Immunology SC Immunology GA 126FK UT WOS:000076282200013 PM 9785673 ER PT J AU D'Amico, AV Cormack, R Tempany, CM Kumar, S Topulos, G Kooy, HM Coleman, CN AF D'Amico, AV Cormack, R Tempany, CM Kumar, S Topulos, G Kooy, HM Coleman, CN TI Real-time magnetic resonance image-guided interstitial brachytherapy in the treatment of select patients with clinically localized prostate cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate cancer; radiation therapy; magnetic resonance imaging; implant; dose-volume histogram ID PREDICT PATHOLOGICAL STAGE; RADICAL PROSTATECTOMY; RADIATION-THERAPY; ANTIGEN FAILURE; GLEASON SCORE; DOSIMETRY AB Purpose: This study was performed to establish the dose-localization capability and acute toxicity of a real-time intraoperative magnetic resonance (MR) image-guided approach to prostate brachytherapy in select patients with clinically localized prostate cancer. Methods and Materials: Nine patients with 1997 American Joint Commission on Cancer (AJCC) clinical stage T1cNxM0 prostate cancer, prostate-specific antigen (PSA) < 10 ng/ml, biopsy Gleason score not exceeding 3 + 4, and endorectal coil MR stage T2 disease were enrolled into this study. The prescribed minimum peripheral dose was 160 Gy to the clinical target volume (CTV), which was the MR-defined peripheral zone (PZ) of the prostate gland. Using a real-time 0.5 Tesla intraoperative MR imaging unit, 5-mm image planes were obtained throughout the prostate gland. The PZ of the prostate gland, anterior rectal wall, and prostatic urethra were identified on the T2 weighted axial images by an MR radiologist. An optimized treatment plan for catheter insertion was generated intraoperatively. Each catheter containing the (125)Iodine sources was placed under real-time MR guidance to ensure that its position in the coronal, sagittal, and axial planes was in agreement with the planned trajectory. Real-time dose- volume histogram analyses were used intraoperatively to optimize the dosimetry. Results: For the 9 study patients, 89-99% (median 94%) of the CTV received a minimum peripheral dose of 160 Gy and greater than or equal to 95% of the volume of the prostatic urethra and 42-89% (median 70%) of the volume of the anterior rectal wall received doses that were below the reported tolerance. All patients voided spontaneously within 3 h after discontinuation of the Foley catheter and no patient required more than a limited course (less than or equal to 3 weeks) of oral alpha-1 blockers for postimplant urethritis. Conclusions: Real-time MR-guided interstitial radiation therapy provided the ability to achieve the planned optimized dose-volume histogram profiles to the CTV and healthy juxtaposed structures intraoperatively, with minimal acute morbidity. (C) 1998 Elsevier Science Inc. C1 Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Anesthesiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP D'Amico, AV (reprint author), Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, 330 Brookline Ave,5th Floor, Boston, MA 02215 USA. OI Cormack, Robert/0000-0001-5553-9984 NR 18 TC 119 Z9 120 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 1998 VL 42 IS 3 BP 507 EP 515 DI 10.1016/S0360-3016(98)00271-5 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 133HL UT WOS:000076681100006 PM 9806508 ER PT J AU Mitsumori, M Shrieve, DC Alexander, E Kaiser, UB Richardson, GE Black, PM Loeffler, JS AF Mitsumori, M Shrieve, DC Alexander, E Kaiser, UB Richardson, GE Black, PM Loeffler, JS TI Initial clinical results of LINAC-based stereotactic radiosurgery and stereotactic radiotherapy for pituitary adenomas SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE pituitary adenoma; stereotactic radiosurgery; stereotactic radiotherapy; LINAC; clinical results ID TERM FOLLOW-UP; RADIATION-THERAPY; CHROMOPHOBE ADENOMAS; INTRACRANIAL LESIONS; CUSHINGS-DISEASE; TUMORS; IRRADIATION; SURGERY; GLAND AB Purpose: To retrospectively evaluate the initial clinical results of stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) for pituitary adenomas with regard to tumor and hormonal control and adverse effects of the treatment. Subjects and Methods: Forty-eight patients with pituitary adenoma who underwent SRS or SRT between September 1989 and September 1995 were analyzed. Of these, 18 received SRS and 30 received SRT, The median tumor volumes were 1.9 cm(3) for SRS and 5.7 cm(3) for SRT. Eleven of the SRS and 18 of the SRT patients were hormonally active at the time of the initial diagnosis. Four of the SRS and none of the SRT patients had a history of prior radiation therapy. Both SRS and SRT were performed using a dedicated stereotactic 6-MV linear accelerator (LINAC), The dose and normalization used for the SRS varied from 1000 cGy at 85% of the isodose line to 1500 cGy at 65% of the isodose line. For SRT patients, a total dose of 4500 cGy at 90% or 95% of the isodose line was delivered in 25 fractions of 180 cGy daily doses. Results: Disease control-The three year tumor control rate was 91.1% (100% for SRS and 85.3% for SRT), Normalization of the hormonal abnormality was achieved in 47% of the 48 patients (33% for SRS and 54% for SRT), The average time required for normalization was 8.5 months for SRS and 18 months for SRT, Adverse effects-The 3-year rate of freedom from central nervous system adverse effects was 89.7% (72.2% for SRS and 100% for SRT), Three patients who received SRS for a tumor in the cavernous sinus developed a ring enhancement in the temporal lobe as shown by follow-up magnetic resonance imaging. Two of these cases were irreversible and were considered to be radiation necrosis, None of the 48 patients developed new neurocognitive or visual disorders attributable to the irradiation. The incidence of endocrinological adverse effects were similar in the two groups, resulting in 3-year rates of freedom from newly initiated hormonal replacement of 78.4% (77.1% for SRS and 79.9% for SRT). Conclusion: Considering the relatively high incidence of morbidity observed in the SRS group, we recommend SRT as the primary method of radiation therapy for pituitary tumors. When treating a lesion in the cavernous sinus with SRS, special attention should be paid to dose distribution in the adjacent brain parenchyma, Longer follow-up is necessary before drawing any conclusions about the advantages of these techniques over conventional external beam radiation therapy. (C) 1998 Elsevier Science Inc. C1 Brigham & Womens Hosp, Childrens Hosp, Dana Faber Canc Inst, Joint Ctr Radiat Therapy,Brain Tumor Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg Neurosurg, Boston, MA USA. Harvard Univ, Sch Med, Dept Endocrinol, Boston, MA USA. RP Loeffler, JS (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 36 TC 123 Z9 124 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 1998 VL 42 IS 3 BP 573 EP 580 DI 10.1016/S0360-3016(98)00256-9 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 133HL UT WOS:000076681100015 PM 9806517 ER PT J AU Gerweck, LE Zaidi, ST Delaney, TF AF Gerweck, LE Zaidi, ST Delaney, TF TI Enhancement of fractionated-dose irradiation by retinoic acid plus interferon SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE retinoic acid; interferon; radiation; radiosensitization ID SQUAMOUS-CELL CARCINOMA; 13-CIS-RETINOIC ACID; IN-VITRO; RADIATION; THERAPY; RADIOSENSITIVITY; COMBINATION; DIFFERENTIATION; ALPHA-2A; PHASE AB Purpose: To evaluate the relative cytotoxicity of fractionated-dose radiation in the presence and absence of 13-cis-retinoic acid (RA) plus alpha-2a-interferon (IFN), as a function of overall treatment time. Methods and Materials: Studies were performed with the human squamous cell carcinoma line FaDu, in vitro. Attached exponential Phase cells were treated with RA + IFN for 8-10 h and then exposed to single graded doses of radiation, or 1 to 6 doses of radiation at 2 Gy per dose, or to 5 doses of radiation at 2 Gy/dose with a time interval of 4-24 h between treatments. Following irradiation, the cells were incubated with drugs present throughout colony formation, and the fraction of survivors in the presence and absence of the combined drugs was calculated. Results: For single graded-dose irradiation, the surviving fraction ratio at 2 Gy in the absence vs. presence of drugs was 1.27 +/- 0.19 in 3 repeat experiments. Following administration of 6 doses of radiation at 2 Gy/fraction with a 5-11 time interval between treatments and, after correcting for cell proliferation between treatments, the surviving fractions differed by a factor of 3,25, again indicating an average difference in survival of 1.26 after each of the 6 2-Gy/fractions, Treatment with 5 2-Gy doses of irradiation with 24 vs. 4 h elapsing between doses, resulted in a 3-fold greater decrease in survival in the presence of drugs vs. no drug, The relatively greater cell kill due to 24 vs. 4 h between treatments was due to drug inhibition of cell proliferation between the more prolonged treatments. Conclusions: The results of this study indicate that retinoic acid plus interferon both sensitizes and inhibits cell proliferation during treatment. These results suggest that this combination of radiation and drugs, when used concurrently, may be effective for inhibiting tumor cell proliferation or accelerated repopulation during clinical fractionated radiotherapy. (C) 1998 Elsevier Science Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Boston Univ, Med Ctr, Dept Radiat Oncol, Boston, MA 02118 USA. RP Gerweck, LE (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 302,100 Blossom St, Boston, MA 02114 USA. FU NCI NIH HHS [R03 CA 68106] NR 17 TC 6 Z9 6 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 1998 VL 42 IS 3 BP 611 EP 615 DI 10.1016/S0360-3016(98)00274-0 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 133HL UT WOS:000076681100020 PM 9806522 ER PT J AU Shankar, P Sprang, H Lieberman, J AF Shankar, P Sprang, H Lieberman, J TI Effective lysis of HIV-1-infected primary CD4(+) T cells by a cytotoxic T-lymphocyte clone directed against a novel A2-restricted reverse-transcriptase epitope SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE cytotoxic T lymphocyte; CD4 T-cell lysis; A2-restricted reverse-transcriptase epitope ID IMMUNODEFICIENCY-VIRUS TYPE-1; HIV TYPE-1; FINE SPECIFICITY; ANCHOR RESIDUES; INFECTION; MOLECULES; RECOGNIZE; PEPTIDES; PROTEIN; NEF AB Most HIV-specific cytotoxic T-lymphocyte (CTL) epitopes have been identified using peptide-pulsed and recombinant vaccinia virus-infected targets. These systems may not accurately reflect the ability of epitopes to be presented by HIV-infected T cells. Recent studies suggest, in fact, that some CTL epitopes are poorly presented on HIV-infected cells. In this study, we have identified a novel A2.1-restricted HIV reverse-transcriptase (RT) epitope and investigated the presentation of this epitope by HIV-infected primary CD4(+) T cells and T-cell lines. A CD8(+) CTL clone, isolated from a seropositive subject that recognized a novel A2-restricted epitope KYTAFTIPSI (aa 293-302) in RT, was used for these studies. Primary CD4(+) T cells and the CD4(+) T-cell line T1 were infected with virus from T1-nPLAP, a cell line stably transfected with HXB-nPLAP, a molecular construct of HIV linked to a placental alkaline phosphatase (PLAP) marker gene. A uniformly infected cell population, obtained by immunomagnetic selection for FLAP expression, was used as targets in CTL assays. HIV-infected T cells were lysed by CTL recognizing this RT epitope as effectively as peptide-pulsed targets. This suggests that some RT epitopes are good targets for CTL recognition. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. EM lieberman@cbr.med.harvard.edu RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [R29 AI38819] NR 29 TC 12 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1998 VL 19 IS 2 BP 111 EP 120 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 126EJ UT WOS:000076279700002 PM 9768618 ER PT J AU Schuster, MA Bell, RM Nakajima, GA Kanouse, DE AF Schuster, MA Bell, RM Nakajima, GA Kanouse, DE TI The sexual practices of Asian and Pacific Islander high school students SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE Asians; Pacific islanders; sexual practices; adolescents; acquired immunodeficiency syndrome prevention and control; contraception ID HIV-INFECTION; TRANSMITTED DISEASES; RISK BEHAVIORS; TEENAGE MEN; INNER-CITY; ADOLESCENTS; ETHNICITY; RACE; PREVENTION; KNOWLEDGE AB Purpose: To describe the sexual behaviors, beliefs, and attitudes of Asian and Pacific Islander California high school students and to compare them to other racial/ethnic groups. Methods: Data were collected from an anonymous self-administered survey of 2026 ninth to 12th graders in a Los Angeles County school district; 186 of the respondents described themselves as Asian and Pacific Islander. The survey was conducted in April 1992. Results: A higher percentage of Asian and Pacific Islander adolescents (73%) compared with African-American (28%, p<.001), Latino (43%, p<.001), white (50%, p <.001), and other (48%, p <.001) adolescents had never had vaginal intercourse. Asian and Pacific Islander adolescents were less likely than other adolescents to report having engaged in heterosexual genital sexual activities during the prior year, including masturbation of or by a partner, fellatio with ejaculation, cunnilingus, and anal intercourse. Few students in any group reported homosexual genital sexual activities. Asians and Pacific Islanders who had had vaginal intercourse were more likely than most other groups to have used a condom at first vaginal intercourse, but Asians and Pacific Islanders had not used condoms more consistently over the prior year. Asians and Pacific Islanders were more likely to expect parental disapproval if they had vaginal intercourse and less likely to think that their peers had had vaginal intercourse. Conclusions: Asian and Pacific Islander high school students in one California school district appear to be at lower sexual risk than other racial/ethnic groups. However, a large minority are engaging in activities that can transmit disease and lead to unwanted pregnancy. Therefore, current efforts to develop culturally sensitive clinical and community-based approaches to sexual risk prevention should include Asians and Pacific Islanders. (C) Society for Adolescent Medicine, 1998. C1 Rand Corp, Santa Monica, CA 90407 USA. Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. W Los Angeles Dept Vet Affairs Med Ctr, Dept Med, Los Angeles, CA USA. RP Schuster, MA (reprint author), Rand Corp, 1700 Main St,POB 2138, Santa Monica, CA 90407 USA. NR 45 TC 48 Z9 49 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD OCT PY 1998 VL 23 IS 4 BP 221 EP 231 DI 10.1016/S1054-139X(97)00210-3 PG 11 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 121MD UT WOS:000076016800006 PM 9763158 ER PT J AU Graybill, JR Bocanegra, R Najvar, LK Luther, MF Loebenberg, D AF Graybill, JR Bocanegra, R Najvar, LK Luther, MF Loebenberg, D TI SCH56592 treatment of murine invasive aspergillosis SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article ID AMPHOTERICIN-B; FUNGAL-INFECTIONS; ITRACONAZOLE; COMBINATION; MULTICENTER; FLUCONAZOLE; PREVENTION; THERAPY; MYCOSES; CANCER AB Mice were immunosuppressed using corticosteroids and infected with conidia of Aspergillus fumigatus. Beginning 1 day after infection, mice were treated orally either with Noble agar or with SCH56592 suspended in Noble agar, or intraperitoneally with amphotericin B. SCH56592 prolonged survival and reduced lung tissue counts of A. fumigatus, while amphotericin B had marginal benefit. SCH56592 merits further development for treatment of aspergillosis. C1 Audie L Murphy Mem Vet Hosp, Div Infect Dis 111F, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78284 USA. Schering Plough Corp, Res Inst, Kenilworth, NJ 07033 USA. RP Graybill, JR (reprint author), Audie L Murphy Mem Vet Hosp, Div Infect Dis 111F, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. EM Graybill@uthscsa.edu NR 25 TC 39 Z9 39 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD OCT PY 1998 VL 42 IS 4 BP 539 EP 542 DI 10.1093/jac/42.4.539 PG 4 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 132KR UT WOS:000076629400020 PM 9818757 ER PT J AU Rotenberg, SA Zhu, JW Hansen, H Li, XD Sun, XG Michels, CA Riedel, H AF Rotenberg, SA Zhu, JW Hansen, H Li, XD Sun, XG Michels, CA Riedel, H TI Deletion analysis of protein kinase C alpha reveals a novel regulatory segment SO JOURNAL OF BIOCHEMISTRY LA English DT Article DE cDNA expression; deletion mutagenesis; dequalinium; drug interaction; Saccharomyces cerevisiae ID PHORBOL ESTER BINDING; LIGAND REGULATION; IN-VIVO; YEAST; EXPRESSION; ACTIVATION; DOMAIN; REGION; TRANSLOCATION; GALACTOSE AB Using a combined pharmacological and genetic approach, we have identified aa 260-280 in the C2 region as a critical factor in the catalytic function of protein kinase C alpha (PKC alpha). Progressive truncations from the N-terminus as well as selected internal deletion mutants were expressed in Saccharomyces cerevisiae and tested for altered sensitivity to dequalinium, a PKC inhibitor whose target site was previously mapped to the catalytic domain. PKC mutants representing truncations of up to 158 amino acid residues (aa) from the N-terminus (ND84 and ND158) displayed 60-63% inhibition of kinase activity by 50 mu M dequalinium, somewhat more sensitive than the wild-type PKC alpha enzyme (45% inhibition). Mutant ND262, lacking N-terminal aa 1-262, was inhibited by almost 72% with 50 mu M dequalinium, but mutant ND278, which lacked an additional 16 as, was inhibited by only 9% of total activity. This result suggests that a C-terminal segment of the C2 region (aa 263-278) influences inhibition by dequalinium at low micromolar concentrations. An internal deletion mutant (D260-280) which retains the entire primary structure of PKC alpha except for aa 260-280, was similarly inhibited by only 4% with 50 mu M dequalinium. In the absence of dequalinium and despite the presence of a nearly complete regulatory domain, this mutant exhibited constitutive activity (both in vitro and in a phenotypic assay with S. cerervisiae) that could not be further stimulated even by the potent activator TPA, Taken together, our findings suggest that, in the native structure of PKC alpha, the segment described by as 260-280 regulates PKC alpha activity and influences the sensitivity of PKC alpha to dequalinium. C1 CUNY Queens Coll, Dept Chem & Biochem, Flushing, NY 11367 USA. CUNY Queens Coll, Dept Biol, Flushing, NY 11367 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Mol Biol Sect, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. RP Rotenberg, SA (reprint author), CUNY Queens Coll, Dept Chem & Biochem, Flushing, NY 11367 USA. FU NCI NIH HHS [CA60618] NR 34 TC 10 Z9 10 U1 0 U2 2 PU JAPANESE BIOCHEMICAL SOC PI TOKYO PA ISHIKAWA BLDG-3F, 25-16 HONGO-5-CHOME, BUNKYO-KU, TOKYO, 113, JAPAN SN 0021-924X J9 J BIOCHEM-TOKYO JI J. Biochem. (Tokyo) PD OCT PY 1998 VL 124 IS 4 BP 756 EP 763 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 129ED UT WOS:000076449600011 PM 9756620 ER PT J AU Busch, NA Reiken, SR Toner, M Yarmush, ML AF Busch, NA Reiken, SR Toner, M Yarmush, ML TI Intracellular calcium dynamics during photolysis SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article ID CYTOPLASMIC FREE CALCIUM; RAT PANCREATIC ACINI; ALUMINUM PHTHALOCYANINE SALPC; ANTIBODY-TARGETED PHOTOLYSIS; DIVALENT-CATION ENTRY; PHOTODYNAMIC-ACTION; SINGLET OXYGEN; ERYTHROCYTE-MEMBRANES; ENDOTHELIAL-CELLS; BLADDER-CANCER AB The objective of this investigation was to gain a deeper understanding of the intracellular events that precede photolysis of cells. A model system, consisting of malignant melanoma cells pretreated,vith the calcium sensitive fluorescent dye, Fluo-3, was used to examine the intracellular calcium dynamics in single-cell photolysis experiments. Exposure of the cells to 632 nm laser light in the presence of photosensitizer, tin chlorin e6, resulted in a rise in intracellular calcium. The increase in intracellular calcium,was blocked using a variety of calcium channel blocking agents, including verapamil, nifedipine, and nickel. Treatment with the channel blockers was also effective in either decreasing or eliminating cell death despite the presence of lethal doses of photosensitizer and irradiation. These results show that intracellular calcium rises prior to plasma membrane lysis, and that this early rise in intracellular calcium is necessary for membrane rupture. C1 Massachusetts Gen Hosp, Ctr Engn Med, Lab Surg Sci & Engn, Boston, MA 02114 USA. Shriners Burns Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Massachusetts Gen Hosp, Ctr Engn Med, Lab Surg Sci & Engn, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM-07035] NR 57 TC 3 Z9 3 U1 0 U2 1 PU ASME PI NEW YORK PA TWO PARK AVE, NEW YORK, NY 10016-5990 USA SN 0148-0731 EI 1528-8951 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD OCT PY 1998 VL 120 IS 5 BP 570 EP 578 DI 10.1115/1.2834746 PG 9 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 127YF UT WOS:000076377600003 PM 10412433 ER PT J AU Chan, EK Brown, DT Kovach, IS Welch, AJ AF Chan, Eric K. Brown, Dennis T. Kovach, Ian S. Welch, Ashley J. TI LASER ASSISTED SOLDERING: EFFECTS OF HYDRATION ON SOLDER-TISSUE ADHESION SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE tissue welding; albumin-based solder; tissue fusion; photocoagulation; wound repair AB Wound stabilization is critical in early wound healing. Other than superficial skin wounds, most tissue repair is exposed to a hydrated environment postoperatively. To simulate the stability of laser-soldered tissue in a wet environment, we studied the effects of hydration on laser soldered rat dermis and baboon articular cartilage. In this in vitro study, we used a solder composed of human serum albumin, sodium hyaluronate, and Indocyanine Green. A 2 mu L solder droplet was deposited on each tissue specimen and then the solder was irradiated with a scanning laser beam (808 nm and 27 W/cm(2)). After photocoagulation, each tissue specimen was cut into two halves dividing the solder. One half was reserved as control while the other half was soaked in saline for a designated period before fixation (1 h, 1, 2, and 7 days). All tissue specimens were prepared for scanning electron microscopy (SEM). SEM examinations revealed nonuniform coagulation across the solder thickness for most of the specimens, likely a result of the temperature gradient generated by laser heating. Closer to the laser beam, the uppermost region of the solder formed a dense coagulum. The solder aggregated into small globules in the region anterior to the solder-tissue interface. All cartilage specimens soaked in saline suffered coagulum detachment from tissue surface. We noted a high concentration of the protein globules in the detached coagulum. These globules were likely responsible for solder detachment from the cartilage surface. Solder adhered better to the dermis than to cartilage. The dermal layer of the skin, composed of collagen matrix, provided a better entrapment of the solder than the smooth surface of articular cartilage. Insufficient laser heating of solder formed protein globules. Unstable solder-tissue fusion was likely a result of these globules being detached from tissue substrate when the specimen was submerged in a hydrated environment. The solder-tissue bonding was compromised as a result of this phenomenon. (C) 1998 Society of Photo-Optical Instrumentation Engineers. C1 [Chan, Eric K.; Welch, Ashley J.] Univ Texas Austin, Biomed Engn Laser Lab, Austin, TX 78712 USA. [Brown, Dennis T.] N Carolina State Univ, Dept Biochem, Raleigh, NC 27695 USA. [Kovach, Ian S.] Massachusetts Gen Hosp, Dept Orthoped, Boston, MA 02114 USA. RP Chan, EK (reprint author), Indigo Med Inc, 10123 Alliance Rd, Cincinnati, OH 45242 USA. EM echan@eesus.jnj.com FU Office of Naval Research Free Electron Laser Biomedical Science Program [N00014-91-J-1564] FX The authors thank Dr. Pascal Valax for his suggestions and ideas; Drs. Lawrence Bass, Dieter Pohl, and Dragon Dimitrov for the lessons on laser soldering; and Mr. John Mendenhall for his assistance on SEM analysis. This study was supported in part by grants from the Office of Naval Research Free Electron Laser Biomedical Science Program (N00014-91-J-1564), and the Albert W. and Clemmie A. Caster Foundation. A. J. Welch is the Marion E. Forsman Centennial Professor of Electrical and Computer Engineering and Biomedical Engineering. NR 29 TC 9 Z9 9 U1 1 U2 1 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD OCT PY 1998 VL 3 IS 4 BP 456 EP 461 DI 10.1117/1.429895 PG 6 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA V32RN UT WOS:000208968400011 PM 23015146 ER PT J AU Gebhardt, MC AF Gebhardt, MC TI Orthopaedic workforce issues from the perspective of the Residency Review Committee and the American Board of Orthopaedic Surgery, Incorporated SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article; Proceedings Paper CT Symposium on the Orthopaedic Workforce in the Next Millennium at the Annual Meeting of the American-Orthopaedic-Association CY JUL 05, 1998 CL ASHEVILLE, NORTH CAROLINA SP Amer Orthopaed Assoc, Amer Acad Orthopaed Surgeons C1 Massachusetts Gen Hosp, Orthopaed Oncol Serv, Boston, MA 02114 USA. RP Gebhardt, MC (reprint author), Massachusetts Gen Hosp, Orthopaed Oncol Serv, Gray Bldg 606,55 Fruit St, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD OCT PY 1998 VL 80A IS 10 BP 1539 EP 1541 PG 3 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 133AP UT WOS:000076664500019 ER PT J AU Crommie, D Hemler, ME AF Crommie, D Hemler, ME TI beta 1 integrin cytoplasmic domain regulates the constitutive conformation detected by MAb 15/7, but not the ligand-induced conformation SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE integrin; activation epitopes; ligand binding; focal adhesions; cytoplasmic domains ID ACTIVATION-DEPENDENT EPITOPE; BETA(1) INTEGRIN; CELL-ADHESION; ALPHA(4)BETA(1) INTEGRIN; MONOCLONAL-ANTIBODIES; FIBRONECTIN RECEPTOR; SIGNAL-TRANSDUCTION; EXPRESSION; BINDING; AGGREGATION AB The anti-integrin beta 1 MAb 15/7 sometimes may be a reporter of integrin activation or ligand occupancy. However, certain beta 1 tail deletions eliminate ligand binding despite inducing maximal constitutive 15/7 expression [Puzon-Mclaughlin el al. (1996): J Biol Chem 271 : 16580-16585]. Here we describe beta 1 tail mutations (e.g., double point mutations [D759L/F763L, F766L/E769L], or replacement of the beta 1 tail by the beta 5 tail) that prevent rather than induce constitutive appearance of the 15/7 epitope. Despite variable losses of constitutive 15/7 epitope, these mutants ail retained a similar inducible 15/7 epitope component as seen upon incubation with GRCDSP peptide ligand. In addition, constitutive 15/7 expression did not correlate with integrin localization into focal adhesions. In conclusion, we show for the first time for a fully functional integrin that specific mutations with in the beta 1 tail can down-regulate the constitutive appearance of an extracellular conformation defined by MAb 15/7. Because this regulation occurs away from the ligand binding site and does not correlate with responsiveness to integrin ligand, cell adhesion, or localization into focal adhesions, a novel type of conformational regulation is suggested. (C) 1998 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Rm M413,44 Binney St, Boston, MA 02115 USA. EM martin.hemler@dfci.harvard.edu FU NCI NIH HHS [CA42368] NR 50 TC 7 Z9 7 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD OCT 1 PY 1998 VL 71 IS 1 BP 63 EP 73 DI 10.1002/(SICI)1097-4644(19981001)71:1<63::AID-JCB7>3.0.CO;2-# PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 114RD UT WOS:000075621900007 PM 9736455 ER PT J AU Li, N Oberley, TD AF Li, N Oberley, TD TI Modulation of antioxidant enzymes, reactive oxygen species, and glutathione levels in manganese superoxide dismutase-overexpressing NIH/3T3 fibroblasts during the cell cycle SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID KIDNEY TUBULAR CELLS; SIGNAL-TRANSDUCTION; HYDROGEN-PEROXIDE; PROTEIN-KINASE; HAMSTER-KIDNEY; FREE-RADICALS; RAT-LIVER; TUMOR; EXPRESSION; PROLIFERATION AB NIH/3T3 mouse embryo fibroblasts were transfected with the cDNA for manganese superoxide dismutase (MnSOD). Previous studies showed characteristic unique AE profiles in nonsynchronous populations of parental, control plasmid-transfected, and MnSOD-overexpressing NIH/3T3 cell lines. However, the present study showed that during S and M phases of the cell cycle, antioxidant enzyme (AE) levels were altered in MnSOD-overexpressing cell lines towards levels in S and M phases of parental and control plasmid-transfected cells. Because of the demonstration that MnSOD overexpression inhibits cell growth in both nonmalignant and malignant cells, the present study was designed to measure AEs, reactive oxygen species (ROS), and glutathione levels in various phases of the cell cycle in both parental NIH/3T3 cells and NIH/3T3 cells overexpressing MnSOD, to try to determine whether AEs, ROS, and glutathione levels could have a possible regulatory role in cell cycle progression. In all cell lines studied, ROS levels were lower in M than S phase of the cell cycle. Total glutathione and glutathione disulfide levels were greatly increased during the M phase of the cell cycle compared with quiescence and S phase in all cell lines studied. This suggests that oxidative stress exists in M phase of the cell cycle with total glutathione levels increased to decrease oxidative stress. Analysis of MnSOD-overexpressing cell clones showed a correlation of decreased cell growth with an increase in ROS in S phase of the cell cycle and a decrease in glutathione in mitosis. The data strongly suggest that specific levels of cell redox state are necessary for cells to successfully progress through the various phases of the cell cycle. Cell. Physiol. 177:148-160, 1998. (C) 1998 Wiley-Liss, Inc. C1 William S Middleton Mem Vet Hosp, Pathol & Lab Med Serv, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Madison, WI USA. RP Oberley, TD (reprint author), William S Middleton Mem Vet Hosp, Pathol & Lab Med Serv, Room A35,2500 Overlook Terrace, Madison, WI 53705 USA. NR 52 TC 50 Z9 52 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 OCT PY 1998 VL 177 IS 1 BP 148 EP 160 DI 10.1002/(SICI)1097-4652(199810)177:1<148::AID-JCP16>3.0.CO;2-9 PG 13 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 114RB UT WOS:000075621700016 PM 9731755 ER PT J AU Fink, K Zhu, JM Namura, S Shimizu-Sasamata, M Endres, M Ma, JY Dalkara, T Yuan, JY Moskowitz, MA AF Fink, K Zhu, JM Namura, S Shimizu-Sasamata, M Endres, M Ma, JY Dalkara, T Yuan, JY Moskowitz, MA TI Prolonged therapeutic window for ischemic brain damage caused by delayed caspase activation SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE transient focal cerebral ischemia; mild ischemia; CPP32; caspase inhibitor; neuroprotection ID INTERLEUKIN-1-BETA CONVERTING-ENZYME; CYSTEINE PROTEASE; CELL-DEATH; ICE/CED-3 PROTEASE; ICE-LIKE; APOPTOSIS; CED-3; INHIBITION; IDENTIFICATION; CPP32 AB Apoptotic cell death is prominent in neurodegenerative disorders, such as Alzheimer's disease and Huntington's disease? and is found in cerebral ischemia. Using a murine model of delayed cell death, we determined that cleavage of zDEVD-amino-4-trifluoromethyl coumarin (zDEVD-afc) in brain homogenate, a measure of caspase activation, increased initially 9 hours after brief (30 minutes) middle cerebral artery occlusion along with caspase-3p20 immunoreactive cleavage product as determined by immunoblotting. zDEVD-afc cleavage activity was blocked by pretreatment or posttreatment with the caspase-inhibitor N-benzyloxycarbonyl-Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-fluoromethyl-ketone (zDEVD-fmk), and ischemic damage was reduced when the drug was injected up to 9 hours after reperfusion. The protection was long lasting (21 days). Hence, the period before caspase activation defined the therapeutic opportunity for this neuroprotective agent after mild ischemic brain injury. Prolonged protection after caspase inhibition plus the extended treatment window may be especially relevant to the treatment of neurodegenerative disorders. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Charlestown, MA 02129 USA. Hacettepe Univ Hosp, Dept Neurol, TR-06100 Ankara, Turkey. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. RP Moskowitz, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 149 13th St,Room 6403, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS10828] NR 31 TC 167 Z9 172 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 1998 VL 18 IS 10 BP 1071 EP 1076 DI 10.1097/00004647-199810000-00003 PG 6 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 126WD UT WOS:000076316900004 PM 9778183 ER PT J AU Spencer, T Biederman, J Harding, M O'Donnell, D Wilens, T Faraone, S Coffey, B Geller, D AF Spencer, T Biederman, J Harding, M O'Donnell, D Wilens, T Faraone, S Coffey, B Geller, D TI Disentangling the overlap between Tourette's disorder and ADHD SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES LA English DT Article DE Tourette's syndrome; attention deficit disorder; adolescence; school children; comorbidity ID ATTENTION-DEFICIT HYPERACTIVITY; OBSESSIVE-COMPULSIVE DISORDER; NERVOUS-SYSTEM STIMULANTS; GENETIC-RELATIONSHIP; LEARNING-DISORDERS; FAMILY HISTORY; CHILDREN; METHYLPHENIDATE; COMORBIDITY; DEPRESSION AB Objective: To identify similarities and differences in neuropsychiatric correlates in children with Tourette's syndrome (TS) and those with ADHD. Method: The sample consisted of children with Tourette's syndrome with ADHD (N = 79), children with Tourette's syndrome without ADHD (N = 18), children with ADHD (N = 563), psychiatrically referred children (N = 212), and healthy controls (N = 140). Results: Disorders specifically associated with Tourette's syndrome were obsessive compulsive disorder (OCD) and simple phobias. Rates of other disorders, including other disruptive behavioral, mood, and anxiety disorders, neuropsychologic correlates, and social and school functioning were indistinguishable in children with Tourette's and ADHD. However, children with Tourette's syndrome plus ADHD had more additional comorbid disorders overall and lower psychosocial function than children with ADHD. Conclusions: These findings confirm previously noted associations between Tourette's syndrome and OCD but suggest that disruptive behavioral, mood, and anxiety disorders as well as cognitive dysfunctions may be accounted for by comorbidity with ADHD. However, Tourette's syndrome plus ADHD appears to be a more severe condition than ADHD alone. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Inst Psychiat Epidemiol & Genet, Brockton W Roxbury Vet Affairs Med Ctr, Brockton, MA USA. McLean Hosp, Belmont, MA 02178 USA. RP Spencer, T (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, ACC-725,Fruit St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [K20 MH01169-01] NR 70 TC 110 Z9 115 U1 3 U2 8 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry Allied Discip. PD OCT PY 1998 VL 39 IS 7 BP 1037 EP 1044 DI 10.1017/S0021963098002984 PG 8 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 132BG UT WOS:000076609500011 PM 9804036 ER PT J AU Faraone, SV Biederman, J Mennin, D Russell, R Tsuang, MT AF Faraone, SV Biederman, J Mennin, D Russell, R Tsuang, MT TI Familial subtypes of attention deficit hyperactivity disorder: A 4-year follow-up study of children from antisocial-ADHD families SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES LA English DT Article DE hyperactivity; conduct disorder; attention deficit disorder; genetics; outcome ID CONDUCT DISORDER; LEARNING-DISABILITIES; COMORBIDITY; ADOLESCENTS; DIAGNOSIS; TAXONOMY; GENDER; ISSUES; MANIA; RISK AB ADHD is a familial disorder with high rates of comorbidity with conduct disorder in childhood and antisocial personality and substance use disorders in adulthood. A growing literature suggests that ADHD with antisocial comorbidity may be nosologically distinct from other forms of ADHD. Previously, we proposed a family-based stratification that defined Antisocial families as those with either conduct disorder or antisocial personality disorder in the probands or relatives. To provide predictive validity for that stratification, we assessed psychopathology in these families 4 years after their initial assessment. Results show that the probands and siblings from Antisocial families had higher rates of psychopathology during the 4-year follow-up period compared with siblings from Non-antisocial and control families. They also had more deviant ratings on the Child Behavior Checklist (especially for anxious/depressed, delinquent, and aggressive behavior). We found fewer group differences in the academic, psychosocial, and intellectual correlates of ADHD. These results confirm and extend previous work indicating that Antisocial ADHD may be a nosologically and clinically meaningful subform of ADHD. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brockton W Roxbury Vet Affairs Med Ctr, Brockton, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, ACC 725,Fruit St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 NR 40 TC 52 Z9 56 U1 2 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry Allied Discip. PD OCT PY 1998 VL 39 IS 7 BP 1045 EP 1053 DI 10.1017/S0021963098002996 PG 9 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 132BG UT WOS:000076609500012 PM 9804037 ER PT J AU Oliver, LC AF Oliver, LC TI Asbestos in building: Management and related health effects SO JOURNAL OF CLEAN TECHNOLOGY ENVIRONMENTAL TOXICOLOGY AND OCCUPATIONAL MEDICINE LA English DT Article DE building; custodian; friable; malignant mesothelioma; pleural plaque ID PLEURAL MESOTHELIOMA; CHRYSOTILE ASBESTOS; EXPOSURE; DISEASE; WORKERS; MORTALITY; CONSTRUCTION; ABNORMALITIES; CUSTODIANS; EMPLOYEES C1 Harvard Univ, Sch Med, Boston, MA USA. RP Oliver, LC (reprint author), Massachusetts Gen Hosp, Pulm Crit Care Unit, Bulfinch 1, Boston, MA 02114 USA. NR 40 TC 0 Z9 0 U1 1 U2 1 PU PRINCETON SCIENTIFIC PUBL INC PI PRINCETON PA PO BOX 2155, PRINCETON, NJ 08543 USA SN 1052-1062 J9 J CLEAN TECHNOL E T JI J. Clean Technol. Environ. Toxicol. Occup. Med. PD OCT-DEC PY 1998 VL 7 IS 4 BP 433 EP 443 PG 11 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA ZX732 UT WOS:000074549100006 ER PT J AU Milberger, S Biederman, J Faraone, SV Jones, J AF Milberger, S Biederman, J Faraone, SV Jones, J TI Further evidence of an association between maternal smoking during pregnancy and attention deficit hyperactivity disorder: Findings from a high-risk sample of siblings SO JOURNAL OF CLINICAL CHILD PSYCHOLOGY LA English DT Article ID CHILDREN; NICOTINE; EXPOSURE; FAMILY; BRAIN; AGE; SCHIZOPHRENIA; PERFORMANCE; INTERVIEW; DYSLEXIA AB Investigated the role of maternal smoking during pregnancy in the etiology of attention deficit hyperactivity disorder (ADHD). Siblings of ADHD (N = 174) and non-ADHD (N = 129) probands were studied. Information on maternal smoking was obtained from mothers in a standardized manner blind to the sibling's ADHD and high-risk status (i.e., whether a sibling of an ADHD or non-ADHD proband). Fifteen (47%) of the high-risk siblings with ADHD has a history of maternal smoking during pregnancy compared with 33 (24%) of the siblings without ADHD (p = 0.009). This positive association remained significant after adjusting for socioeconomic status, parental IQ, and parental ADHD status. Lower IQ scores were found among those high-risk siblings whose mothers smoked during pregnancy compared with those whose mothers did not smoke. These findings extend our previous findings of an association between maternal smoking during pregnancy and ADHD. Moreover, they highlight the importance of programs aimed at smoking prevention in nonsmoking women and smoking cessation in smoking women of child-bearing age. C1 Massachusetts Gen Hosp, Pediat Pharmacol Unit, Boston, MA 02114 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Pharmacol Unit, ACC 725,15 Parkman St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIDA NIH HHS [1 K01 DA00294]; NIMH NIH HHS [R01 MH-41314-01A2] NR 48 TC 121 Z9 122 U1 4 U2 7 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0047-228X J9 J CLIN CHILD PSYCHOL JI J. Clin. Child Psychol. PD OCT PY 1998 VL 27 IS 3 BP 352 EP 358 DI 10.1207/s15374424jccp2703_11 PG 7 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 123FM UT WOS:000076115200011 PM 9789194 ER PT J AU Swearingen, B Barker, FG Katznelson, L Biller, BMK Grinspoon, S Klibanski, A Moayeri, N Black, PMCL Zervas, NT AF Swearingen, B Barker, FG Katznelson, L Biller, BMK Grinspoon, S Klibanski, A Moayeri, N Black, PMCL Zervas, NT TI Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT Annual Meeting of the Congress-of-Neurological-Surgeons CY SEP 27-OCT 02, 1997 CL NEW ORLEANS, LA SP Congress Neurol Surgeons ID SECRETING PITUITARY-ADENOMAS; FOLLOW-UP; SURVIVAL; ADENOMECTOMY; DIAGNOSIS; MICROSURGERY; EPIDEMIOLOGY; DETERMINANTS; MANAGEMENT AB To analyze the long term outcome after multimodality therapy for acromegaly, a retrospective review was performed on 162 patients who underwent transsphenoidal surgery at Massachusetts General Hospital between 1978 and 1996. The surgical cure rate for microadenomas was 91%, that for macroadenomas was 48%, and it was 57% overall. The surgical cure rate was significantly dependent on tumor size, but was not dependent on age or sex. An improvement in the surgical cure rate was noted over the course of the review, from 45% before 1987 to 73% since 1991. Long term follow-up was obtained in 99% of U.S, residents (149 of 151), with a mean follow-up period of 7.8 yr. Adjuvant radiation and/or pharmacological therapy was given to 61 patients. Of the entire group, 83% (124 of 149) were in biochemical remission as determined by normalization of serum insulin-like growth factor I levels or by GH suppression after oral glucose tolerance testing at last contact or at death. The recurrence rate was 6% at 10 yr and 10% at 15 yr after surgery in those patients who initially met the criteria for surgical cure. The 10-yr survival rate was 88%, and there were 12 deaths at postoperative intervals of 2-12 yr, with the most common cause of death being cardiovascular disease. A Cox proportional hazards model showed that patient-years with persistent disease carried a 3.5-fold [95% confidence interval(CI), 1.0-12; P = 0.02] relative mortality risk compared to those patient-years in remission. A Poisson person-years regression analysis showed no significant difference in survival between those 86 patients cured at operation and an age- and sex-matched sample from the U.S. population [standardized mortality ratio (SMR), 0.84; 95% CI, 0.3-2.2; P = 0.35]. A similar analysis on the entire group of 149 patients showed no significant difference in survival from that in a control sample (SMR, 1.16; 95% CI, 0.66-2.0; P = 0.3). Mortality risk for patient-years with persistent active disease after unsuccessful treatment us. that in the U.S. population sample remained increased (SMR, 1.8; 95% CI, 0.9-3.6; P = .05). This analysis suggests that the decreased survival previously reported to be associated with acromegaly can be normalized by successful surgical and adjunctive therapy. C1 Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Swearingen, B (reprint author), Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, ACC 331,Fruit St, Boston, MA 02114 USA. NR 34 TC 434 Z9 451 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 OCT PY 1998 VL 83 IS 10 BP 3419 EP 3426 DI 10.1210/jc.83.10.3419 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 126CN UT WOS:000076275500007 PM 9768641 ER PT J AU Choukroun, G Hajjar, R Kyriakis, JM Bonventre, JV Rosenzweig, A Force, T AF Choukroun, G Hajjar, R Kyriakis, JM Bonventre, JV Rosenzweig, A Force, T TI Role of the stress-activated protein kinases in endothelin-induced cardiomyocyte hypertrophy SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE hypertrophy; endothelin; stress-activated protein kinase; c-Jun NH2-terminal kinase; cardiomyocyte ID SIGNAL-REGULATED KINASE; CARDIAC GENE-EXPRESSION; MUSCLE CELL HYPERTROPHY; C-JUN; VENTRICULAR MYOCYTES; PARACRINE MECHANISM; TERMINAL KINASES; MAMMALIAN-CELLS; GROWTH-FACTORS; SAP KINASES AB The signal transduction pathways governing the hypertrophic response of cardiomyocytes are not well defined. Constitutive activation of the stress-activated protein kinase (SAPK) family of mitogen-activated protein (MAP) kinases or another stress-response MAP kinase, p38, by overexpression of activated mutants of various components of the pathways is sufficient to induce a hypertrophic response in cardiomyocytes, but it is not clear what role these pathways play in the response to physiologically relevant hypertrophic stimuli. To determine the role of the SAPKs in the hypertrophic response, we used adenovirus-mediated gene transfer of SAPK/ERK kinase-1 (KR) [SEK-1(KR)], a dominant inhibitory mutant of SEK-1, the immediate upstream activator of the SAPKs, to block signal transmission down the SAPK pathway in response to the potent hypertrophic agent, endothelin-1 (ET-1). SEK-1(KR) completely inhibited ET-1-induced SAPK activation without affecting activation of the other MAP kinases implicated in the hypertrophic response, p38 and extracellular signal-regulated protein kinases (ERK)-1/ERK-2, Expression of SEK-1(KR) markedly inhibited the ET-1-induced increase in protein synthesis. In contrast, the MAPK/ERK kinase inhibitor, PD98059, which blocks ERK activation, and the p38 inhibitor, SB203580, had no effect on ET-1-induced protein synthesis. ET-1 also induced a significant increase in atrial natriuretic factor mRNA expression as well as in the percentage of cells with highly organized sarcomeres, responses which were also blocked by expression of SEK-1(KR), In summary, inhibiting activation of the SAPK pathway abrogated the hypertrophic response to ET-1, These data are the first demonstration that the SAPKs are necessary for the development of agonist-induced cardiomyocyte hypertrophy, and suggest that in response to ET-1, they transduce critical signals governing the hypertrophic response. C1 Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Force, T (reprint author), Massachusetts Gen Hosp E, 149-4002 13th St, Charlestown, MA 02129 USA. EM force@helix.mgh.harvard.edu OI Force, Thomas/0000-0002-0450-8659 FU NHLBI NIH HHS [HL50361, HL57623]; NIGMS NIH HHS [GM46577] NR 63 TC 157 Z9 161 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT 1 PY 1998 VL 102 IS 7 BP 1311 EP 1320 DI 10.1172/JCI3512 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 127ZE UT WOS:000076380100005 PM 9769323 ER PT J AU Koziel, H Eichbaum, Q Kruskal, BA Pinkston, P Rogers, RA Armstrong, WYK Richards, FF Rose, RM Ezekowitz, RAB AF Koziel, H Eichbaum, Q Kruskal, BA Pinkston, P Rogers, RA Armstrong, WYK Richards, FF Rose, RM Ezekowitz, RAB TI Reduced binding and phagocytosis of Pneumocystis carinii by alveolar macrophages from persons infected with HIV-1 correlates with mannose receptor downregulation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE alveolar macrophages; mannose receptor; innate immunity; P-carinii; HIV-1 ID ACQUIRED IMMUNODEFICIENCY SYNDROME; TERM CELL-CULTURE; DOWN-REGULATION; MYCOBACTERIUM-TUBERCULOSIS; BRONCHOALVEOLAR LAVAGE; INTERFERON-GAMMA; FC-RECEPTORS; VIRUS TYPE-1; PNEUMONIA; EXPRESSION AB The macrophage mannose receptor, a pattern recognition molecule and component of innate immunity, mediates binding and phagocytosis of Pneumocystis carinii and likely represents an important clearance mechanism in the lungs of immunocompetent hosts. The purpose of this study was to examine the ability of alveolar macrophages from HIV-infected individuals to bind and phagocytose P. carinii, and to investigate the role of the macrophage mannose receptor in mediating this interaction. Compared with healthy individuals, alveolar macrophage phagocytosis of P. carinii from HIV+ persons was reduced up to 74% (P = 0.02), primarily reflecting a reduction in the number of organisms associated with each macrophage (P = 0.019). Furthermore, macrophages from HIV+ individuals demonstrated up to an 80% (P < 0.05) reduction in mannose receptor surface expression and endocytosis. Mannose receptor affinity was unaltered, and mRNA levels were modestly reduced (P < 0.05). Cells from HIV+ individuals with CD4(+) counts < 200 cells/mm(3) (representing individuals at high clinical risk for P. carinii pneumonia) demonstrated the lowest levels of P. carinii phagocytosis and mannose receptor endocytosis. In vitro HIV infection of alveolar macrophages from healthy individuals reduced mannose receptor endocytosis to 53.2% (P < 0.05) and P. carinii binding and phagocytosis to 67.4% (P < 0.05) of control. Our studies suggest that HIV infection may alter innate immunity in the lungs, and that impaired alveolar macrophage mannose receptor-mediated binding and phagocytosis of P. carinii may contribute to the susceptibility of HIV-infected individuals to this opportunistic pulmonary pathogen. C1 Beth Israel Deaconess Med Ctr, Div Pulm & Crit Care Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Pediat, Lab Dev Immunol, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Resp Biol Program, Boston, MA 02115 USA. Yale Univ, Sch Med, MacArthur Ctr Mol Parasitol, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Internal Med, Pulm Crit Care Sect, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Stem Cells Inc, La Jolla, CA 92067 USA. RP Koziel, H (reprint author), Beth Israel Deaconess Med Ctr, Div Pulm & Crit Care Med, Dept Med, Palmer Bldg,Room 108,W Campus,1 Deaconess Rd, Boston, MA 02215 USA. EM hkoziel@bidmc.harvard.edu FU NHLBI NIH HHS [HL-43510] NR 68 TC 109 Z9 110 U1 1 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT 1 PY 1998 VL 102 IS 7 BP 1332 EP 1344 DI 10.1172/JCI560 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 127ZE UT WOS:000076380100007 PM 9769325 ER PT J AU Argyropoulos, G Brown, AM Willi, SM Zhu, JG He, YF Reitman, M Gevao, SM Spruill, I Garvey, WT AF Argyropoulos, G Brown, AM Willi, SM Zhu, JG He, YF Reitman, M Gevao, SM Spruill, I Garvey, WT TI Effects of mutations in the human uncoupling protein 3 gene on the respiratory quotient and fat oxidation in severe obesity and type 2 diabetes SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE UCP3; mutation; obesity; fat oxidation; respiratory quotient; African American ID BROWN ADIPOSE-TISSUE; GLYCOSYLATED HEMOGLOBIN; NUCLEOTIDE-BINDING; THYROID-HORMONE; EXPRESSION; LEPTIN; IDENTIFICATION; SENSITIVITY; TRANSPORT; CLONING AB Human uncoupling protein 3 (UCP3) is a mitochondrial transmembrane carrier that uncouples oxidative ATP phosphorylation. With the capacity to participate in thermogenesis and energy balance, UCP3 is an important obesity candidate gene. A missense polymorphism in exon 3 (V102I) was identified in an obese and diabetic proband. A mutation introducing a stop codon in exon 4 (R143X) and a terminal polymorphism in the splice donor junction of exon 6 were also identified in a compound heterozygote that was morbidly obese and diabetic. Allele frequencies of the exon 3 and exon 6 splice junction polymorphisms were determined and found to be similar in Gullah-speaking African Americans and the Mende tribe of Sierra Leone, but absent in Caucasians. Moreover, in exon 6-splice donor heterozygotes, basal fat oxidation rates were reduced by 50%, and the respiratory quotient was markedly increased compared with wild-type individuals, implicating a role for UCP3 in metabolic fuel partitioning. C1 Med Univ S Carolina, Dept Med, Div Endocrinol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. Univ Sierra Leone, Coll Med & Allied Hlth Sci, Freetown, Sierra Leone. RP Argyropoulos, G (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol, 171 Ashley Ave, Charleston, SC 29425 USA. EM argyrog@musc.edu RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 FU NCRR NIH HHS [3MO1RR01070-20S2]; NIDDK NIH HHS [DK-38765, DK-47461] NR 35 TC 163 Z9 172 U1 2 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT 1 PY 1998 VL 102 IS 7 BP 1345 EP 1351 DI 10.1172/JCI4115 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 127ZE UT WOS:000076380100008 PM 9769326 ER PT J AU Choi, SJ Devlin, RD Menaa, C Chung, H Roodman, GD Reddy, SV AF Choi, SJ Devlin, RD Menaa, C Chung, H Roodman, GD Reddy, SV TI Cloning and identification of human sea as a novel inhibitor of osteoclast formation and bone resorption SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE osteoclast bone marrow cultures; hSca; expression cloning; inhibitors ID GROWTH-FACTOR-BETA; LY-6 FAMILY; OSTEOTROPIC HORMONES; ANCHORED PROTEINS; MARROW CULTURES; CELLS; DIFFERENTIATION; MEMBER AB Increased osteoclast activity is responsible for the enhanced bone destruction in postmenopausal osteoporosis, Paget's disease, bone metastasis, and hypercalcemia of malignancy. However, the number of known inhibitory factors that block osteoclast formation and bone resorption are limited. Therefore, we used an expression-cloning approach to identify novel factors produced by osteoclasts that inhibit osteoclast activity. A candidate clone was identified and isolated from a human osteoclast-like multinucleated cell (MNC) cDNA library, named osteoclast inhibitory peptide-1 (OIP-1), and the cDNA sequence was determined. This sequence matched that of the recently identified human stem cell antigen, was structurally similar to the mouse Ly-6 gene family, and the sequence predicted it was a glycosyl phosphatidyl inositol (GPI)-anchored protein that had a cleavable COOH-terminal peptide. Western blot analysis of conditioned media from 293 cells transfected with the OIP-1 cDNA clone confirmed that OIP-1 was released into the media as a membrane-bound GPI-linked protein. Interestingly, both recombinant OIP-1 expressed in Escherichia coli (which does not have GPI linker) and OIP-1 expressed by mammalian cells significantly reduced osteoclast-like MNC formation induced by 1,25-dihydroxyvitamin D-3 or PTH-related protein in mouse and human bone marrow cultures, and inhibited Ca-45 release from prelabeled bone in fetal rat organ cultures. In contrast, recombinant OIP-1 did not inhibit the growth of a variety of other cell types. These data indicate that OIP-1 is a novel, specific inhibitor of osteoclast formation and bone resorption. C1 Univ Texas, Hlth Sci Ctr, Dept Med Hematol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Reddy, SV (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med Hematol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIA NIH HHS [AG13625]; NIADDK NIH HHS [AM35188]; NIAMS NIH HHS [AR41336] NR 28 TC 23 Z9 23 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT 1 PY 1998 VL 102 IS 7 BP 1360 EP 1368 DI 10.1172/JCI2667 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 127ZE UT WOS:000076380100010 PM 9769328 ER PT J AU Kirkpatrick, WR Revankar, SG McAtee, RK Lopez-Ribot, JL Fothergill, AW McCarthy, DI Sanche, SE Cantu, RA Rinaldi, MG Patterson, TF AF Kirkpatrick, WR Revankar, SG McAtee, RK Lopez-Ribot, JL Fothergill, AW McCarthy, DI Sanche, SE Cantu, RA Rinaldi, MG Patterson, TF TI Detection of Candida dubliniensis in oropharyngeal samples from human immunodeficiency virus-infected patients in North America by primary CHROMagar Candida screening and susceptibility testing of isolates SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID IN-VITRO; FLUCONAZOLE; IDENTIFICATION; RESISTANCE; ALBICANS; YEASTS AB Candida dubliniensis has been associated with oropharyngeal candidiasis in patients infected with human immunodeficiency virus (HIV), C, dubliniensis isolates may have: been improperly characterized as atypical Candida albicans due to the phenotypic similarity between the two species. Prospective screening of oral rinses from 63 HIV-infected patients detected atypical dark green isolates on CHROMagar Candida compared to typical C, albicans isolates, which are light green, Forty-eight atypical isolates and three control strains were characterized by germ tube formation, differential growth at 37, 42, and 45 degrees C, identification by API 20C, fluorescence, chlamydoconidium production, and fingerprinting by Ca3 probe DNA hybridization patterns. All isolates were germ tube positive, Very poor or no growth occurred at 42 degrees C with 22 of 51 isolates. All 22 poorly growing isolates at 42 degrees C and one isolate with growth at 42 degrees C showed weak hybridization of the Ca3 probe with genomic DNA, consistent with C. dubliniensis identification. No C. dubliniensis isolate but only 18 of 28C, albicans isolates grew at 45 degrees C, Other phenotypic or morphologic tests were less reliable in differentiating C, dubliniensis from C, albicans, Antifungal susceptibility testing showed fluconazole MICs ranging from less than or equal to 0.125 to 64 mu g/ml. Two isolates were resistant to fluconazale (MIC, 64 mu g/ml) and one strain was dose dependent susceptible (MIC, 16 mu g/ml). MICs of other azoles, including voriconazole, itraconazole, and SCH 56592, for these isolates were lower. C, dubliniensis was identified in 11 of 63 (17%) serially evaluated patients, Variability in phenotypic characteristics dictates the use of molecular and biochemical techniques to identify C, dubliniensis, This study identifies C, dubliniensis in HIV-infected patients from San Antonio, Tex,, and shows that C, dubliniensis is frequently detected in those patients by using a primary CHROMagar screen. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Audie L Murphy Div, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. RP Patterson, TF (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM patterson@uthscsa.edu RI Lopez-Ribot, Jose/D-2048-2010 FU NCRR NIH HHS [M01-RR-01346, M01 RR001346]; NIAID NIH HHS [1 R29 AI42401]; NIDCR NIH HHS [1 RO1 DE11381, R01 DE011381] NR 19 TC 139 Z9 147 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 OCT PY 1998 VL 36 IS 10 BP 3007 EP 3012 PG 6 WC Microbiology SC Microbiology GA 119LD UT WOS:000075896800035 PM 9738058 ER PT J AU Tulpule, A Yung, RC Wernz, J Espina, BM Myers, A Scadden, DT Cabriales, S Ilaw, M Boswell, W Gill, PS AF Tulpule, A Yung, RC Wernz, J Espina, BM Myers, A Scadden, DT Cabriales, S Ilaw, M Boswell, W Gill, PS TI Phase II trial of liposomal daunorubicin in the treatment of AIDS-related pulmonary Kaposi's sarcoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; IMMUNE-DEFICIENCY SYNDROME; DOXORUBICIN; MANIFESTATIONS; BLEOMYCIN; CRITERIA AB Purpose: Kaposi's sarcoma (KS) is the most common tumor in patients with AIDS and can be fatal in patients with lung involvement. Systemic chemotherapy is the most effective treatment for pulmonary KS. We thus conducted this study to determine the efficacy of liposomal daunorubicin in the treatment of patients with pulmonary KS. Methods: Patients with biopsy-proven, symptomatic pulmonary KS were accrued. Liposomal daunorubicin was given at a dose of 60 mg/m(2) intravenously every 2 weeks. Response wets monitored by chest radiographs, pulmonary function tests, arterial blood gases, and grading of pulmonary symptoms. Results: Fifty-three male patients were accrued. The median CD4(+) lymphocyte count was 13/mu L (range, 0 to 200); 70% reported a prior AIDS-defining opportunistic infection. All patients were symptomatic, with cough reported in all patients, shortness of breath in 94%, and hemoptysis in 55%. The mean study entry diffusing capacity of carbon monoxide (DLCO) was 58.5% (percent of predicted). The median dose of liposomal daunorubicin delivered was 360 mg/m(2) (range, 60 to 1,380). More than 75% of patients had complete or partial resolution of baseline pulmonary symptoms. Complete or partial improvement in DLCO was observed in 22%; complete or partial resolution of radiographic abnormalities was reported in 32%. The most common treatment-related toxicity was neutropenia, which occurred in 85%. There were no instances of cardiac toxicity observed, even at high cumulative doses. Conclusion: Liposomal daunorubicin at 60 mg/m(2) is safe and active in patients with pulmonary KS. Trials combining liposomal daunorubicin with other active agents in KS should be considered. (C) 1998 by American Society of Clinical Oncology. C1 Norris Canc Hosp & Res Inst, Dept Med, Div Hematol Oncol & Pulmonol, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Res Inst, Los Angeles, CA 90089 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NYU, Med Ctr, New York, NY 10016 USA. Denver Gen Hosp, Denver, CO USA. RP Gill, PS (reprint author), Norris Canc Hosp & Res Inst, Dept Med, Div Hematol Oncol & Pulmonol, 1441 Eastlake Ave,MS-34, Los Angeles, CA 90033 USA. NR 25 TC 29 Z9 30 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 OCT PY 1998 VL 16 IS 10 BP 3369 EP 3374 PG 6 WC Oncology SC Oncology GA 127JJ UT WOS:000076347100022 PM 9779714 ER PT J AU Demetri, GD Kris, M Wade, J Degos, L Cella, D AF Demetri, GD Kris, M Wade, J Degos, L Cella, D CA Procrit Study Grp TI Quality-of-life benefit in chemotherapy patients treated with epoetin alfa is independent of disease response or tumor type: Results from a prospective community oncology study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Hematology CY DEC 05-09, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; FUNCTIONAL ASSESSMENT; CANCER-THERAPY; CHRONIC ANEMIA; BREAST-CANCER; RELIABILITY; INSTRUMENT; PREDICTION; VALIDITY; OUTCOMES AB Purpose: To evaluate prospectively the effectiveness of epoetin alfa as an adjunct to chemotherapy in patients with cancer based on changes in quality-of-life parameters and hemoglobin levels, and to correlate these changes with antitumor response. Patients and Methods: Two thousand three hundred seventy patients with nonmyeloid malignancies who received chemotherapy were enrolled onto this study from 621 US community-based practices. Patients received epoetin alfa 10,000 U three times weekly, which could be increased to 20,000 U three times weekly depending on the hemoglobin response at 4 weeks, Treatment continued for a maximum of 16 weeks in patients who showed evidence of hematologic response. Results: Two thousand two hundred eighty-nine patients (97%) were eligible for efficacy analyses. Epoetin alfa therapy was associated with improved quality of life parameters; these improvements correlated significantly with hemoglobin levels and were independent of tumor response, Provider reported Karnofsky performance scores did not correlate with the improved quality-of-life changes. Epoetin alfa therapy was also associated with a significant increase in hemoglobin levels and decrease in transfusion use, Tumor type, chemotherapy agent/regimen, prior chemotherapy, baseline hemoglobin level, and baseline erythropoietin level were not predictive of a positive response to treatment. Epoetin alfa was well tolerated. Conclusion: Epoetin alfa appears to have a beneficial impact on patient reported functional capacity and quality of life in patients with cancer who received chemotherapy independent of tumor response, Concordantly, epoetin alfa appeared to increase hemoglobin levels and decrease transfusion use. patients responded across all tumor types, The results suggest that epoetin alfa effectively improves functional outcomes in patients with cancer who receive chemotherapy. (C) 1998 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Canc Care Specialists Cent Florida, Decatur, IL USA. Univ Paris, Hop St Louis, F-75252 Paris, France. Northwestern Univ, Evanston Northwestern Healthcare, Evanston, IL USA. RP Demetri, GD (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 25 TC 560 Z9 571 U1 0 U2 5 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 OCT PY 1998 VL 16 IS 10 BP 3412 EP 3425 PG 14 WC Oncology SC Oncology GA 127JJ UT WOS:000076347100029 PM 9779721 ER PT J AU Emanuel, EJ Patterson, WB Rennie, D AF Emanuel, EJ Patterson, WB Rennie, D TI Scientific misconduct in cancer clinical trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Emanuel, EJ (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT PY 1998 VL 16 IS 10 BP 3433 EP 3438 PG 6 WC Oncology SC Oncology GA 127JJ UT WOS:000076347100031 PM 9779723 ER PT J AU Maiden, MFJ Tanner, ACR Macuch, PJ Murray, L Kent, RL AF Maiden, MFJ Tanner, ACR Macuch, PJ Murray, L Kent, RL TI Subgingival temperature and microbiota in initial periodontitis SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE subgingival temperature; subgingival microbiota; health; gingivitis; initial periodontitis ID SUPRAGINGIVAL PLAQUE CONTROL; ATTACHMENT LOSS; POCKETS; PATHOGENS; COUNTS; FLORA AB The association between subgingival temperature, other clinical characteristics! and the subgingival microbiota was examined in adult subjects with initial periodontitis and differing levels of gingival inflammation. 43 subjects were measured at 6 sites per tooth for pocket depth, attachment level, presence of plaque, gingival redness, bleeding on probing and subgingival temperature at 3-month intervals for 1 year. Subgingival plaque was sampled from 15 initial active periodontitis sites (10 subjects), 121 gingivitis, sites (20 subjects) and 202 healthy sites (13 subjects), and included the 5 hottest and 5 coldest sites in each subject. Plaque samples were analyzed for 13 subgingival species using whole-genomic DNA probes. The major influences on the subgingival microbiota were the clinical status of sites, pocket depth, and the presence of supragingival plaque. No significant association between species and site temperature was observed. Initial active sites were associated with Bacteroides forsythus and Campylobacter rectus, and had a higher mean subgingival temperature and deeper mean pocket depth than inactive sites. A weak association between pocket depth and site temperature was noted. The major influence on subgingival temperature of sites was the anterior to posterior anatomical temperature gradient in the mandible and maxilla. C1 Forsyth Dent Ctr, Boston, MA 02115 USA. RP Tanner, ACR (reprint author), Forsyth Dent Ctr, 140 Fenway, Boston, MA 02115 USA. EM atanner@forsyth.org FU NIDCR NIH HHS [DE 09513] NR 22 TC 4 Z9 5 U1 0 U2 0 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 OCT PY 1998 VL 25 IS 10 BP 786 EP 793 DI 10.1111/j.1600-051X.1998.tb02371.x PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 122RB UT WOS:000076084300004 PM 9797050 ER PT J AU Blais, MA Benedict, KB Norman, DK AF Blais, MA Benedict, KB Norman, DK TI Establishing the psychometric properties of the DSM-III-R personality disorders: Implications for DSM-V SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article ID PSYCHIATRIC CLASSIFICATION; IV; CRITERIA; ISSUES AB In this study, symptom (item) level data were used to perform a psychometric analysis of the DSM-III-R personality disorders (PDs). Determined for each PD criteria set were convergent validity, discriminant validity, and internal consistency. The results indicated that the majority of the PD criteria sets (6 of the 11) possessed adequate convergent validity, although discriminant validity was problematic for most of these disorders. Internal consistency was also weak for the PD criteria sets, with only 3 of the 11 exceeding a minimum cutoff score of .70. The present study employed a methodology modeled after the one reported by Morey (1988a), and the results of the two studies were highly similar. Consistent findings across the two data sets can be taken to reflect the actual psychometric properties of the DSM-III-R PDs. The success of our replication demonstrates the potential that large-scale psychometric investigations hold for aiding the development and refinement of the DSM PDs. (C) 1998 John Wiley & Sons, Inc. C1 Massachusetts Gen Hosp, Inpatient Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Blais, MA (reprint author), Massachusetts Gen Hosp, Inpatient Psychiat Serv, Blake 2,55 Fruit St, Boston, MA 02114 USA. NR 29 TC 5 Z9 5 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD OCT PY 1998 VL 54 IS 6 BP 795 EP 802 DI 10.1002/(SICI)1097-4679(199810)54:6<795::AID-JCLP6>3.0.CO;2-G PG 8 WC Psychology, Clinical SC Psychology GA 120KM UT WOS:000075955600006 PM 9783659 ER PT J AU Meadows, KN Hajjar, RJ Gwathmey, JK AF Meadows, KN Hajjar, RJ Gwathmey, JK TI Effects of pH and temperature on myocardial calcium-activation in Pterygoplichthys (catfish) SO JOURNAL OF COMPARATIVE PHYSIOLOGY B-BIOCHEMICAL SYSTEMIC AND ENVIRONMENTAL PHYSIOLOGY LA English DT Article DE myofilaments; skinned muscle; catfish; pH; temperature ID SKINNED MUSCLE-FIBERS; SARCOPLASMIC-RETICULUM; VENTRICULAR MUSCLE; CARDIAC MYOFIBRILS; INDUCED RELEASE; RAINBOW-TROUT; RAT; SENSITIVITY; TENSION; FORCE AB Fish are chronically exposed to a wide range of temperatures and acidic environments. Fish hearts have to therefore adapt to these changes in order to maintain contractility. Myofibrillar responsiveness to Ca2+ is exquisitely sensitive to both temperature and pH in mammalian myocardium. To evaluate myofilament calcium-activation, we chemically skinned ventricular myocardium from catfish (Pterygoplichthys). A decrease in pH from 7.5 to 6.8, irrespective of temperature change, shifted the calcium-force curve towards higher calcium concentrations without affecting maximal Ca2+-activated force. The contractile elements are therefore sensitive to changes in pH. In intact muscle preparations the active twitch force was decreased with increasing temperature (10-22 degrees C). However, the sensitivity of the myofilaments to Ca2+ was independent of temperature. These data suggest a possible role of the sarcoplasmic reticulum (SR) in mediating the effects of temperature. The response of intact muscle preparations to changes in temperature is therefore not likely due to temperature-dependent changes in myofilament calcium responsiveness. C1 Inst Cardiovasc Dis & Muscle Res Inc, Cambridge, MA 02138 USA. Boston Univ, Sch Med, Integrated Physiol Res Labs, Boston, MA 02118 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Inst Cardiovasc Dis & Muscle Res Inc, 763 Bldg E,Concord Ave, Cambridge, MA 02138 USA. EM gwathmey@tiac.net FU NHLBI NIH HHS [R44 HL52249, KO8-HL03561, R01 HL-49574] NR 34 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0174-1578 EI 1432-136X J9 J COMP PHYSIOL B JI J. Comp. Physiol. B-Biochem. Syst. Environ. Physiol. PD OCT PY 1998 VL 168 IS 7 BP 526 EP 532 DI 10.1007/s003600050173 PG 7 WC Physiology; Zoology SC Physiology; Zoology GA 132EV UT WOS:000076618100007 PM 9810717 ER PT J AU Margolis, HC AF Margolis, HC TI Edgard C. Moreno, PhD: A tribute to his major contributions to oral biology research SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE adsorption; amelogenesis; biomineralization; dental calculus; caries mechanisms; fluoride ID HUMAN SALIVARY PROTEINS; DEMINERALIZATION IN-VITRO; CRYSTAL-GROWTH; CALCIUM APATITES; STREPTOCOCCUS-SANGUIS; INHIBITORY ACTIVITY; CARIES FORMATION; DILUTE-SOLUTIONS; HYDROXYAPATITE; FLUORIDE AB The seminal contributions of Dr. Edgard C. Moreno to physical chemical aspects of oral biology research are reviewed, with personal insights provided by the author. Dr. Moreno has made major contributions to our understanding of fundamental processes which occur within the oral cavity and which control the formation of mineralized tissues. These contributions include extensive research in the areas of: the chemistry of synthetic calcium phosphates and biominerals, the interaction of salivary proteins and other molecules of biological interest with calcium phosphate surfaces, the mechanism of dental caries formation and the effects of fluoride on this process, the mechanism of dental calculus formation and prevention, and the mechanism of dental enamel formation. C1 Forsyth Dent Ctr, Dept Biomineralizat, Boston, MA 02115 USA. RP Margolis, HC (reprint author), Forsyth Dent Ctr, Dept Biomineralizat, 140 Fenway, Boston, MA 02115 USA. NR 42 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD OCT PY 1998 VL 77 IS 10 BP 1767 EP 1771 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 130FG UT WOS:000076508800003 PM 9786632 ER PT J AU Jellinek, M AF Jellinek, M TI Pediatric psychosocial screening: Of sufficient benefit to encourage SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jellinek, M (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD OCT PY 1998 VL 19 IS 5 BP 353 EP 354 PG 2 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 128NT UT WOS:000076413400007 PM 9809267 ER PT J AU Hall, JE Taylor, AE Hayes, FJ Crowley, WF AF Hall, JE Taylor, AE Hayes, FJ Crowley, WF TI Insights into hypothalamic-pituitary dysfunction in polycystic ovary syndrome SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Article DE luteinizing hormone; follicle stimulating hormone; gonadotropin-releasing hormone; androgens; reproduction ID GONADOTROPIN-RELEASING-HORMONE; FOLLICLE-STIMULATING-HORMONE; MESSENGER RIBONUCLEIC-ACIDS; LUTEINIZING-HORMONE; DEFICIENT MEN; NORMAL WOMEN; GENE-EXPRESSION; MENSTRUAL-CYCLE; INHIBIN LEVELS; SECRETION AB Polycystic ovary syndrome (PCOS) is characterized by menstrual dysfunction and hyperandrogenism in the absence of other known causes. While the pathogenesis of PCOS remains elusive and is likely to involve abnormalities in several systems, there has long been an association of abnormal gonadotropin secretion with this disorder. In recent studies we have determined that 94% of women meeting the broad criteria for PCOS have an increased LH/FSH ratio. Several lines of evidence suggest that the mechanisms underlying the increased LH/FSH ratio in PCOS include an increased frequency of GnRH secretion. Decreased sensitivity to progesterone negative feedback on the GnRH pulse generator may play a role in this neuroendocrine defect. Additional factors which may contribute to the low to normal FSH levels in the face of increased LH include chronic mild estrogen increases and possibly inhibin. In addition to these effects on the differential control of FSH, there is increased pituitary sensitivity of LH secretion to GnRH. Both estrogen and androgens have been proposed as candidates mediating these effects. Superimposed on these underlying abnormalities in gonadotropin secretion is a marked inhibitory effect of obesity on LH secretion which may be mediated at either a pituitary or hypothalamic level. (J. Endocrinol. Invest. 21: 602-611, 1998) (C) 1998, Editrice Kurtis. C1 Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Hall, JE (reprint author), Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR01066]; NICHD NIH HHS [P30-HD-28138, U54-HD-29164] NR 66 TC 31 Z9 32 U1 0 U2 2 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD OCT PY 1998 VL 21 IS 9 BP 602 EP 611 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 141ZG UT WOS:000077174500009 PM 9856414 ER PT J AU Yap-Veloso, MIR Simmons, RB Echelman, DA Gonzales, TK Veira, WJX Simmons, RJ AF Yap-Veloso, MIR Simmons, RB Echelman, DA Gonzales, TK Veira, WJX Simmons, RJ TI Intraocular pressure control after contact transscleral diode cyclophotocoagulation in eyes with intractable glaucoma SO JOURNAL OF GLAUCOMA LA English DT Article DE transscleral diode cyclophotocoagulation; intraocular pressure control; intractable glaucoma ID ND-YAG CYCLOPHOTOCOAGULATION; LASER CYCLOPHOTOCOAGULATION; UNCONTROLLED GLAUCOMA; NEODYMIUM; CYCLOCRYOTHERAPY; CYCLOCOAGULATION AB Purpose: The effect of contact transscleral diode cyclophotocoagulation (TDC) on intraocular pressure (IOP) and its safety was determined in eyes with intractable glaucoma. Methods: The charts of 41 consecutive patients (43 eyes) who underwent the laser procedure were reviewed. After surgery, data were collected from chart entries at 1 hour, 1 day, 4 to 6 weeks, 4 to 6 months, and at the final visit (6-24 months). Mean differences in IOP before and after treatment were compared using the paired Student t test. Associated complications also were assessed. Results: The mean +/- standard deviation follow-up period was 11.9 +/- 5.3 months (range, 6-24 months). One patient who died after 1 month of follow-up and another patient with neovascular glaucoma who underwent an anterior chamber washout 1 week after laser to treat an uncontrolled IOP spike were excluded from the study. Repeat treatment was done in 12 (28%) eyes. At each follow-up visit postoperatively, a significant reduction from preoperative IOP was obtained (mean reduction of 50% at the final visit). At the final visit, 64% of patients achieved an IOP of <22 mmHg and a reduction of greater than or equal to 20%. An IOP spike occurred in three (7%) eyes. Long-term complications included loss of vision (greater than or equal to 2 lines) in eight (22%) patients, corneal decompensation in one (2%), phthisis bulbi in one (2%), and corneal graft rejection in one (2%). Conclusion: Although effective IOP reduction was demonstrated in eyes with intractable glaucoma after TDC, a significant proportion (26%) of eyes had severe long-term complications. C1 Ophthalm Consultants Boston, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA USA. New England Glaucoma Res Fdn Inc, Boston, MA USA. Fallon Clin, Worcester, MA USA. RP Simmons, RB (reprint author), Ophthalm Consultants Boston, 50 Staniford St, Boston, MA 02114 USA. NR 28 TC 39 Z9 42 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1057-0829 J9 J GLAUCOMA JI J. Glaucoma PD OCT PY 1998 VL 7 IS 5 BP 319 EP 328 PG 10 WC Ophthalmology SC Ophthalmology GA 125QV UT WOS:000076249300006 PM 9786561 ER PT J AU O'Donnell, CJ Kannel, WB AF O'Donnell, CJ Kannel, WB TI Cardiovascular risks of hypertension: lessons from observational studies SO JOURNAL OF HYPERTENSION LA English DT Article; Proceedings Paper CT 8th European Meeting on Hypertension CY JUN 13-16, 1997 CL MILAN, ITALY DE cardiovascular risk; diastolic blood pressure; hypertension; risk factor; systolic blood pressure ID ISOLATED SYSTOLIC HYPERTENSION; CORONARY HEART-DISEASE; BLOOD-PRESSURE; FRAMINGHAM; MORTALITY; STROKE AB Hypertension is an acknowledged major risk factor for cardiovascular disease and death in both men and women. Despite a historical focus by clinicians on the importance of diastolic blood pressure (DBP) risks, epidemiologic data from numerous large-scale studies have clearly demonstrated that both systolic blood pressure (SBP) and DBP are important determinants of cardiovascular risk. Recent analyses have described notable risks associated with isolated and borderline elevations of SEP, which predominate in the elderly, emphasizing the independent contribution of elevated SEP in determining overall risk. Overviews of large-scale treatment trials show that antihypertensive drug treatment confers a favorable net clinical benefit in patients with diastolic and isolated systolic hypertension, and the magnitude of risk reduction is comparable to that expected from the observational data. However, at any level of SEP or DBP, the absolute magnitude of risk varies widely depending on the burden of coexisting risk factors present. Therefore, it is essential that decisions regarding the urgency, risks and benefits of antihypertensive drug treatments be informed by accurate determinations of overall cardiovascular risk (C) 1998 Lippincott Williams & Wilkins. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiac Unit, Cambridge, MA 02138 USA. Boston Univ, Sch Med, Med Ctr, Dept Med, Boston, MA 02118 USA. RP O'Donnell, CJ (reprint author), Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. NR 21 TC 18 Z9 18 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD OCT PY 1998 VL 16 SU 6 BP S3 EP S7 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 145WH UT WOS:000077394400002 PM 9856377 ER PT J AU Carrizosa, AM Nicholson, LB Farzan, M Southwood, S Sette, A Sobel, RA Kuchroo, VK AF Carrizosa, AM Nicholson, LB Farzan, M Southwood, S Sette, A Sobel, RA Kuchroo, VK TI Expansion by self antigen is necessary for the induction of experimental autoimmune encephalomyelitis by T cells primed with a cross-reactive environmental antigen SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; RELAPSING PARALYSIS; PROTEOLIPID PROTEIN; MULTIPLE-SCLEROSIS; SUPERANTIGEN; HOMOLOGY; PEPTIDES; VIRUS AB Cross-reactivity with environmental antigens has been postulated as a mechanism responsible for the induction of autoimmune disease, Experimental autoimmune encephalomyelitis is a T cell-mediated autoimmune disease model inducible in susceptible strains of laboratory animals by immunization with protein constituents of myelin. We used myelin proteolipid protein (PLP) peptide 139-151 and its analogues to define motifs to search a protein database for structural homologues of PLP139-151 and identified five peptides derived from microbial Ags that elicit immune responses that cross-react with this self peptide. Exposure of naive SJL mice to the cross-reactive environmental peptides alone was insufficient to induce autoimmune disease even when animals were treated with Ag-nonspecific stimuli (superantigen or LPS). However, immunization of SJL mice with suboptimal doses of PLP139-151 after priming with cross-reactive environmental peptides consistently induced experimental autoimmune encephalomyelitis. Furthermore, T cell lines from mice immunized with cross-reactive environmental peptides and restimulated in vitro with PLP139-151 could induce disease upon transfer into naive recipients. These data suggest that expansion by self Ag is required to break the threshold to autoimmune disease in animals primed with cross-reactive peptides. C1 Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Div Human Retrovirol, Boston, MA 02115 USA. Epimmune, San Diego, CA 92121 USA. Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. Vet Adm Med Ctr, Palo Alto, CA 94304 USA. RP Kuchroo, VK (reprint author), Brigham & Womens Hosp, Ctr Neurol Dis, 77 Louis Pasteur Ave, Boston, MA 02115 USA. EM kuchroo@cnd.bwh.harvard.edu FU NINDS NIH HHS [R01NS35685, NS26773, R01NS30843] NR 24 TC 43 Z9 44 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 OCT 1 PY 1998 VL 161 IS 7 BP 3307 EP 3314 PG 8 WC Immunology SC Immunology GA 122GY UT WOS:000076064700014 PM 9759846 ER PT J AU Dutt, P Wang, JF Groopman, JE AF Dutt, P Wang, JF Groopman, JE TI Stromal cell-derived factor-1 alpha and stem cell factor kit ligand share signaling pathways in hemopoietic progenitors: A potential mechanism for cooperative induction of chemotaxis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HEMATOPOIETIC GROWTH-FACTORS; PROTEIN-KINASE ACTIVATION; FOCAL TYROSINE KINASE; MAP KINASE; C-KIT; LYMPHOCYTE CHEMOATTRACTANT; PERIPHERAL-BLOOD; MAMMALIAN-CELLS; HIV-1 ENTRY; IN-VITRO AB Stromal cell-derived factor (SDF-1 alpha), the ligand for CXCR4, is a chemokine that acts as a potent chemoattractant for hemopoietic progenitor cells. Stem cell factor/kit ligand (SCF/KL), an early acting cytokine, has recently been reported to enhance the chemotaxis induced by SDF-1 alpha. However, very little is known about downstream signaling events following these receptor-ligand interactions. To investigate these events, we utilized a model progenitor cell line, CTS, which expresses both the CXCR4 and c-kit receptors. We observed strong Ca2+ mobilization and enhancement of chemotaxis following treatment with SDF-1 alpha or SCF/KL. A combination of these factors enhanced this chemotaxis in CTS cells as well as in CD34(+) bone marrow cells, Prior treatment of CTS cells with pertussis toxin inhibited the SDF-1 alpha-induced chemotaxis, suggesting that SDF-1 alpha signaling involves a pertussis-sensitive G(1)-coupled protein, SDF-1 alpha treatment resulted in a rapid phosphorylation of the focal adhesion molecules RAFTK (related adhesion focal tyrosine kinase), paxillin, and p130(cas), which then declined within minutes. SCF/KL alone or in combination with SDF-1 alpha induced a rapid and sustained effect on phosphorylation of these substrates. SDF-1 alpha treatment resulted in a rapid and robust activation of p44/42 mitogen-activated protein kinase compared with the relatively weak and delayed effect of SCF/KL treatment. Interestingly, a delayed but sustained activation of mitogen-activated protein kinase activation was observed when the factors were used in combination. Such cooperativity in downstream signaling pathways may explain the enhanced chemotaxis of progenitors observed with SDF-1 alpha in combination with SCF/KL. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. Harvard Univ, Inst Med, BIDMC, Div Expt Med,Sch Med, Boston, MA 02115 USA. RP Groopman, JE (reprint author), Harvard Univ, Inst Med, BIDMC, Div Expt Med,Sch Med, 4 Blackfan Circle, Boston, MA 02115 USA. EM jgroopma@west.bidmc.harvard.edu FU NHLBI NIH HHS [HL43510, HL55187, HL53745] NR 48 TC 133 Z9 135 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 OCT 1 PY 1998 VL 161 IS 7 BP 3652 EP 3658 PG 7 WC Immunology SC Immunology GA 122GY UT WOS:000076064700057 PM 9759889 ER PT J AU Oesterle, S Nguyen, T Allen, K AF Oesterle, S Nguyen, T Allen, K TI Percutaneous myocardial laser revascularization SO JOURNAL OF INTERVENTIONAL CARDIOLOGY LA English DT Article ID LONG-TERM; PRESSURE AB Transmyocardial laser revascularization (TMR) is an experimental procedure for intractable angina that has demonstrated clinical benefit. The majority of patients who had TMR have significant reduction of angina. TMR has been performed exclusively by thoracic and cardiac surgeons using a handhold CO2 laser device. The development of a prototype percutaneous device that delivers mid-infrared laser energy (Ho:YAG) through a 9Fr coaxial catheter system recently has been reported. The long-term benefits of this percutaneous approach is being defined in the context of the randomized PACIFIC Trial. The initial follow-up suggested significant relief of angina in the majority of treated patients, and the results are likely to be equal or similar to those of surgical TMR. The safety data of percutaneous myocardial revascularization (PMR) with the CardioGenesis system showed exceedingly low morbidity and mortality. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiol Sect, Boston, MA 02114 USA. RP Oesterle, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiol Sect, 32 Fruit St, Boston, MA 02114 USA. NR 24 TC 0 Z9 0 U1 0 U2 1 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 0896-4327 J9 J INTERV CARDIOL JI J. Interv. Cardiol. PD OCT PY 1998 VL 11 IS 5 SU S BP S134 EP S136 DI 10.1111/j.1540-8183.1998.tb00204.x PN 2 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 137JU UT WOS:000076912300023 ER PT J AU Shubrooks, SJ AF Shubrooks, SJ TI Update on interventions in saphenous vein grafts SO JOURNAL OF INTERVENTIONAL CARDIOLOGY LA English DT Article ID TRANSLUMINAL EXTRACTION CATHETER; TRANS-LUMINAL ANGIOPLASTY; CORONARY-BYPASS SURGERY; TERM FOLLOW-UP; BALLOON ANGIOPLASTY; DIRECTIONAL ATHERECTOMY; PERCUTANEOUS REVASCULARIZATION; DISTAL EMBOLIZATION; STENT IMPLANTATION; VENOUS GRAFTS AB Interventions in saphenous vein grafts present some of the most challenging problems in preventing acute complications and limiting restenosis. Available options include repeat bypass surgery, balloon angioplasty, directional atherectomy, transluminal extraction atherectomy, rotational atherectomy, laser angioplasty, and stenting. Stenting appears to provide the best acute and long-term results. Debulking with directional atherectomy prior to stenting may be helpful but its role is unproven. With any device, it is essential to attain the lowest possible residual stenosis with the least amount of manipulation. Complications with vein graft interventions are most commonly related to distal embolization, which occurs most frequently in older vein grafts with diffuse disease, large plaque volume or thrombus, or those with total occlusion. Use of thrombolytics, glycoprotein IIb/IIIa receptor inhibitors, and thrombectomy devices may be helpful when thrombus is present. Calcium channel blockers may be beneficial when embolization of plaque debris results in slow flow or no-flow during interventions. C1 Beth Israel Deaconnes Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. RP Shubrooks, SJ (reprint author), Beth Israel Deaconnes Med Ctr, Div Cardiovasc, 110 Francis St, Boston, MA 02215 USA. NR 40 TC 0 Z9 0 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 0896-4327 J9 J INTERV CARDIOL JI J. Interv. Cardiol. PD OCT PY 1998 VL 11 IS 5 SU S BP S36 EP S41 DI 10.1111/j.1540-8183.1998.tb00186.x PN 2 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 137JU UT WOS:000076912300005 ER PT J AU Beissert, S Hosoi, J Stratigos, A Brissette, J Grabbe, S Schwarz, T Granstein, RD AF Beissert, S Hosoi, J Stratigos, A Brissette, J Grabbe, S Schwarz, T Granstein, RD TI Differential regulation of epidermal cell tumor-antigen presentation by IL-1 alpha and IL-1 beta SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE Langerhans cells; TNF alpha; tumor immunology ID ULTRAVIOLET-RADIATION; LANGERHANS CELLS; HISTOCOMPATIBILITY ANTIGENS; INTERLEUKIN-1 RECEPTOR; IMMUNE-RESPONSE; SUPPRESSION; HYPERSENSITIVITY; STIMULATION; MECHANISMS; MODULATION AB IL-1 exists in two forms, termed IL-1 alpha and IL-1 beta, which exert similar effects in a number of biologic models, Recently, there have been reports of some differences in the activities of these two species in some systems. To address this issue with. regard to Langerhans cells, Langerhans cell-enriched preparations of epidermal cells were treated with either IL-1 alpha or IL-1 beta before pulsing with S1509a tumor-associated antigens and subsequent use for immunization of naive mice to S1509a. While epidermal cells treated with 100 U IL-1 beta per ml were able to induce protective tumor immunity (as indicated by the rejection of a subsequent tumor challenge with viable S1509a tumor cells), epidermal cells treated with 100 U IL-1 alpha per ml failed to confer protective immunity. At 1000 U per ml, IL-1 beta also inhibited the ability of epidermal cells to induce tumor immunity. To investigate the effects of the two IL-1 forms on elicitation of tumor immunity, naive mice were immunized against the S1509a tumor by s.c. injection of dead S1509a cells, Epidermal cells enriched for Langerhans cells were treated with either 100 U IL-1 alpha or IL-1 beta per ml before tumor-associated antigens-pulsing. Epidermal cells were then washed and injected into a hind footpad of tumor immune mice and 24 h footpad swelling was assessed as a measure of delayed-type hypersensitivity. Exposure to IL-1 alpha led to suppressed elicitation of delayed-type hypersensitivity, whereas IL-1 beta treated epidermal cells elicited a normal (100 U per ml) or enhanced (1000 U per ml) level of delayed-type hypersensitivity. Previous experiments indicated that the suppressive effects of IL-1 alpha on induction of immunity may be mediated by TNF alpha, Therefore, the ability of IL-1 alpha or IL-1 beta to induce epidermal cell production of TNF alpha was assessed. IL-1 alpha induced epidermal cells to secrete significantly higher amounts of TNF alpha protein compared with stimulation with IL-1 beta, IL-1 alpha and IL-1 beta appear to differentially regulate epidermal cell antigen presenting capability. C1 Univ Munster, Dept Dermatol, D-48149 Munster, Germany. Massachusetts Gen Hosp E, Dept Dermatol, Massachusetts Gen Hosp, Harvard Cutaneous Biol Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Cornell Univ, Coll Med, Dept Dermatol, New York, NY USA. RP Beissert, S (reprint author), Univ Munster, Dept Dermatol, von Esmarch Str 56, D-48149 Munster, Germany. RI Schwarz, Thomas/A-9148-2010 FU NIAMS NIH HHS [AR 40667, AR 44240] NR 25 TC 13 Z9 13 U1 0 U2 0 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 OCT PY 1998 VL 111 IS 4 BP 609 EP 615 DI 10.1046/j.1523-1747.1998.00291.x PG 7 WC Dermatology SC Dermatology GA 123XE UT WOS:000076150300011 PM 9764841 ER PT J AU van Hoek, AN Yang, B Kirmiz, S Brown, D AF van Hoek, AN Yang, B Kirmiz, S Brown, D TI Freeze-fracture analysis of plasma membranes of CHO cells stably expressing aquaporins 1-5 SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE freeze fracture; orthogonal, square array; intramembrane particle; aquaporin; Chinese Hamster ovary cell; transfection ID CHIP28 WATER CHANNELS; COLLECTING DUCT; VASOPRESSIN; ORGANIZATION; PERMEABILITY; LOCALIZATION; EPITHELIUM; PARTICLES; TRANSPORT; LIPOSOMES AB Several studies suggest that aquaporin water channels can be identified in membranes by freeze-fracture electron microscopy. For this report, Chinese Hamster ovary cells were stably transfected with cDNAs encoding aquaporins 1-5. Measurement of the osmotic water permeability of the cells confirmed that functional protein was expressed and delivered to the plasma membrane.. By freeze-fracture electron microscopy, a 20% increase in intramembrane particle (IMP) density was found in plasma membranes of cells expressing AQP2, 3 and 5, and a 100% increase was measured in AQP1-expressing cells, when compared to mock-transfected cells. On membranes of cells expressing AQP4, large aggregates of IMPs were organized into orthogonal arrays, which occupied 10-20% of the membrane surface. IMP aggregates were never seen in AQP2-transfected cells. Hexagonally packed IMP clusters were detected in similar to 5% of the membranes from AQP3-expressing cells. Particle size-distribution analysis of rotary shadowed IMPs showed a significant shift from 13.5 (control cells) to 8.5 nm or less in AQP-expressing cells; size distribution analysis of unidirectionally shadowed IMPs also showed a significant change when compared to control. Some IMPs in AQP expressing cells had features consistent with the idea that aquaporins are assembled as tetramers. The results demonstrate that in transfected CHO cells, AQP transfection modifies the general appearance and number of IMPs on the plasma membrane, and show that only AQP4 assembles into well-defined IMP arrays. C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Calif San Francisco, Cardiovasc Res Inst, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Cardiovasc Res Inst, Dept Physiol, San Francisco, CA 94143 USA. RP van Hoek, AN (reprint author), Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-35124, R01 DK 55864, DK38452] NR 36 TC 23 Z9 23 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD OCT 1 PY 1998 VL 165 IS 3 BP 243 EP 254 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 124NK UT WOS:000076188500006 PM 9767678 ER PT J AU Schmidt, U Hajjar, RJ Helm, PA Kim, CS Doye, AA Gwathmey, JK AF Schmidt, U Hajjar, RJ Helm, PA Kim, CS Doye, AA Gwathmey, JK TI Contribution of abnormal sarcoplasmic reticulum ATPase activity to systolic and diastolic dysfunction in human heart failure SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE systolic calcium; diastolic calcium; SR Ca2+ ATPase activity; muscle force ID HUMAN MYOCARDIUM; DILATED CARDIOMYOPATHY; VENTRICULAR MYOCYTES; PHOSPHOLAMBAN; CA2+-ATPASE; EXPRESSION; RESPONSIVENESS; FORCE; CA-2+; GENE AB Two of the most significant characteristics of failing human myocardium are an increased diastolic [Ca2+](i) and a prolonged diastolic relaxation. These abnormalities are more pronounced at higher frequencies of stimulation and may be caused by an altered Ca2+ resequestration into the sarcoplasmic reticulum (SR). The force-frequency relationship was determined in multicellular preparations obtained from non-failing (n = 6) and failing human myocardium (n = 11). The active force in non-failing tissue increased as a function of the frequency of stimulation. In failing myocardium, an increase in frequency of stimulation (>1 Hz) was accompanied by a decrease in active force. Changes in the frequency of stimulation and active force were also associated with changes in intracellular calcium concentrations. The diastolic force in failing myocardium was augmented following an increase in frequency of stimulation, whereas in non-failing tissue, no increase in diastolic force was observed. Associated with the increase in diastolic force was an increase in intracellular diastolic calcium concentrations. The SR Ca2+ ATPase activity was reduced in failing compared to non-failing myocardium. SR Ca2+ ATPase was positively correlated with diastolic force in non-failing myocardium. The relationship between Ca2+ ATPase activity at 1 mu mol/l [Ca2+] and active force between 0.5 and 2.0 Hz was different between failing and non-failing myocardium. The diastolic force demonstratd an inverse relationship with the SR Ca2+ ATPase activity in failing myocardium. These data suggest that a reduction in SR Ca2+ ATPase activity contributes to the impairment in both systolic and diastolic function of failing human hearts. (C) 1998 Academic Press. C1 Boston Univ, Sch Med,Integrated Physiol Res Labs, Dept Cardiovasc Med,Cardiovasc Div, Evans Dept Med,Whitaker Cardiovasc Inst, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. GwI, Cambridge, MA USA. RP Boston Univ, Sch Med, Integrated Physiol Labs, 763 Bldg E Concord Ave, Cambridge, MA 02138 USA. FU NHLBI NIH HHS [R01 HL49574] NR 27 TC 124 Z9 129 U1 0 U2 4 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 OCT PY 1998 VL 30 IS 10 BP 1929 EP 1937 DI 10.1006/jmcc.1998.0748 PG 9 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 134CQ UT WOS:000076725600003 PM 9799647 ER PT J AU Hajjar, RJ Muller, FU Schmitz, W Schnabel, P Bohm, M AF Hajjar, RJ Muller, FU Schmitz, W Schnabel, P Bohm, M TI Molecular aspects of adrenergic signal transduction in cardiac failure SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE heart failure; signal transduction; G proteins; SERCA; adrenergic system ID ELEMENT-BINDING PROTEIN; FAILING HUMAN-HEART; SARCOPLASMIC-RETICULUM CA2+-ATPASE; HUMAN VENTRICULAR MYOCARDIUM; ADENOVIRAL GENE-TRANSFER; DILATED CARDIOMYOPATHY; MESSENGER-RNA; RAT-HEART; ALPHA-ADRENOCEPTORS; BETA-ADRENOCEPTORS AB Abnormal beta-adrenergic signal transduction and intracellular Ca2+ handling appear to be a major cause of systolic and diastolic dysfunction in humans with heart failure. The precise mechanisms which cause an alteration in Ca2+ handling have been a subject of investigation in recent years. Several lines of evidence suggest that activation of neurohormonal systems plays a central role. Altered Ca2+-handling (increased diastolic concentrations, reduced systolic Ca2+ release) have a strong impact on diastolic and systolic performance of failing hearts. Sarcoplasmic reticulum Ca2+ ATPase is reduced in activity and in steady-state mRNA concentration. The Na+-Ca2+ exchanger is upregulated at the mRNA and protein levels. Phospholamban depends strongly on cAMP-dependent phosphorylation. A strong sympathetic activation has been shown to desensitize the cAMP system. At the receptor level, there is downregulation of beta(1)-adrenergic receptors. An uncoupling of beta(2)-adrenoceptors has been attributed to an increased activity and gene expression of beta-adrenergic receptor kinase in failing myocardium, leading to phosphorylation and uncoupling of receptors. Finally, recent evidence suggests that cAMP-dependent transcription mechanisms may play a role during beta-adrenergic stimulation and cardiomyopathy with heart failure - by means of altered actions of cAMP response element binding protein, the cAMP response element modulator, or the activating transcription factor 1. The exact characterization of signal transduction defects could offer novel approaches to the pharmacological treatment of heart failure. C1 Univ Cologne, Innere Med Klin 3, D-50924 Cologne, Germany. Univ Munster, Inst Pharmakol & Toxikol, D-48149 Munster, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Cardiovasc, Charlestown, MA 02129 USA. RP Bohm, M (reprint author), Univ Cologne, Innere Med Klin 3, Joseph Stelzmann Str 9, D-50924 Cologne, Germany. NR 65 TC 38 Z9 41 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD OCT PY 1998 VL 76 IS 11 BP 747 EP 755 DI 10.1007/s001090050276 PG 9 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 127XJ UT WOS:000076375600004 PM 9826119 ER PT J AU Nikolakopoulos, J Zachariah, C de Freitas, DM Stubbs, EB Ramasamy, R Castro, GMCA Geraldes, CFGC AF Nikolakopoulos, J Zachariah, C de Freitas, DM Stubbs, EB Ramasamy, R Castro, GMCA Geraldes, CFGC TI Li-7 nuclear magnetic resonance study for the determination of Li+ properties in neuroblastoma SH-SY5Y cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE perfusion; agarose gel threads; shift reagents; veratridine; Na+ channels ID RED-BLOOD-CELLS; HUMAN-ERYTHROCYTES; NMR-SPECTROSCOPY; SHIFT-REAGENT; GEL THREADS; TRANSPORT; BINDING; EXPRESSION; MEMBRANE; AGONISTS AB Lithium has been used clinically in the treatment of manic depression, However, its pharmacologic mode of action remains unclear, Characteristics of Li+ interactions in red blood cells (RBCs) have been identified. We investigated Li+ interactions on human neuroblastoma SH-SY5Y cells by developing a novel Li-7 NMR method that provided a clear estimation of the intra- and extracellular amounts of Li+ in the presence of the shift reagent thulium-1,4,7,10-tetrazacyclododecane-N, N',N ", N'''-tetramethylene phosphonate (HTmDOTP4-). The first-order rate constants of Li+ influx and efflux for perfused, agarose-embedded SH-SY5Y cells in the presence of 3 mM HTmDOTP4- were 0.055 +/- 0.006 (n = 4) and -0.025 +/- 0.006 min(-1) (n = 3), respectively, Significant increases in the rate constants of Li+ influx and efflux in the presence of 0.05 mM veratridine indicated the presence of Nai channel-mediated Li+ transport in SH-SY5Y cells. Li-7 NMR relaxation measurements showed that Li+ is immobilized more in human neuroblastoma SH-SY5Y cells than in human RBCs. C1 Loyola Univ, Dept Chem, Chicago, IL 60626 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Serv Neurol, Hines, IL 60141 USA. Loyola Univ, Med Ctr, Dept Neurol, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Mol & Cellular Biochem, Maywood, IL 60153 USA. Columbia Univ Coll Phys & Surg, Div Cardiol, New York, NY USA. Univ Coimbra, Dept Biochem, Coimbra, Portugal. Univ Coimbra, Ctr Neurosci, Coimbra, Portugal. RP de Freitas, DM (reprint author), Loyola Univ, Dept Chem, 6525 N Sheridan Rd, Chicago, IL 60626 USA. OI Castro, Maria Margarida/0000-0001-6811-3878; Geraldes, Carlos/0000-0002-0837-8329 FU NIMH NIH HHS [MH45926] NR 33 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 1998 VL 71 IS 4 BP 1676 EP 1684 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 120MJ UT WOS:000075959900039 PM 9751202 ER PT J AU Enochs, WS Ackerman, RH Kaufman, JA Candia, M AF Enochs, WS Ackerman, RH Kaufman, JA Candia, M TI Gadolinium-enhanced MR angiography of the carotid arteries SO JOURNAL OF NEUROIMAGING LA English DT Article DE arteries; carotid; arteries; MR; gadolinium; magnetic resonance; contrast enhancement; magnetic resonance; vascular studies ID MAGNETIC-RESONANCE ANGIOGRAPHY; CONVENTIONAL ANGIOGRAPHY; CT ANGIOGRAPHY; STENOSIS; ARTERIOGRAPHY AB To assess the efficacy of gadolinium (Gd)-enhanced magnetic resonance angiography (gdMRA) in overcoming signal dropout artifacts on conventional MRA (cMRA), the authors examined 13 patients with suspected neurovascular stenotic/occlusive lesions on MRA pre- and post-gadolinium enhancement. The sample consisted of 18 internal carotid artery (ICA) lesions (16 extracranial, 2 cranial). In 13 of 16 stenotic vessels, gdMRA better characterized the pathoanatomy of moderate to severe stenotic lesions, changing MRA diagnosis in 3 patients. In zero of three vessels with no flow enhancement by cMRA, the lumen remained nonvisualized on gdMRA. For an ICA lesion at the skull base, enhancement of surrounding normal structures limited the usefulness of the technique. The authors conclude that Gd MRA is a fast, accurate, and convenient noninvasive technique for documenting the morphology and severity of carotid stenotic disease, especially extracranially. C1 Massachusetts Gen Hosp, Neurovasc Lab, Dept Radiol, Boston, MA 02114 USA. Thomas Jefferson Univ Hosp, Dept Radiol, Philadelphia, PA 19107 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Ackerman, RH (reprint author), Massachusetts Gen Hosp, Neurovasc Lab, Dept Radiol, GRB 254,Fruit St, Boston, MA 02114 USA. NR 18 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1051-2284 J9 J NEUROIMAGING JI J. Neuroimaging PD OCT PY 1998 VL 8 IS 4 BP 185 EP 190 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 126MT UT WOS:000076297900001 PM 9780848 ER PT J AU Eskandar, EN Cosgrove, GR Shinobu, LA Penney, JB AF Eskandar, EN Cosgrove, GR Shinobu, LA Penney, JB TI The importance of accurate lesion placement in posteroventral pallidotomy - Report of two cases SO JOURNAL OF NEUROSURGERY LA English DT Article DE pallidotomy; Parkinson's disease; basal ganglion; stereotaxis ID ADVANCED PARKINSONS-DISEASE; MEDIAL PALLIDOTOMY; GPI PALLIDOTOMY; NEURONS AB Pallidotomy has become a widely used treatment for medically refractory Parkinson's disease. However, the optimal lesion size and location within the pallidum have not yet been determined, and the role of repeated pallidotomy remains undefined. The authors present two patients who had unsatisfactory results after their first unilateral pallidotomy but attained dramatic and long-lasting improvement with repeated surgery. The results obtained in these cases indicate that patients who have a good clinical outcome initially but relapse rapidly after surgery should be considered for repeated pal lidotomy if the initial lesion was not placed in the optimal location. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Movement Disorders Ctr, Boston, MA 02114 USA. RP Cosgrove, GR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. NR 23 TC 17 Z9 17 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD OCT PY 1998 VL 89 IS 4 BP 630 EP 634 DI 10.3171/jns.1998.89.4.0630 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 122LL UT WOS:000076073000017 PM 9761058 ER PT J AU Kales, SN Aldrich, JM Polyhronopoulos, GN Artzerounian, D Gassert, T Hu, H Kelsey, K Sweet, C Christiani, DC AF Kales, SN Aldrich, JM Polyhronopoulos, GN Artzerounian, D Gassert, T Hu, H Kelsey, K Sweet, C Christiani, DC TI Fitness for duty evaluations in hazardous materials firefighters SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID MEDICAL SURVEILLANCE; WASTE WORKERS; EXPOSURE AB We analyzed results from the medical examinations of 340 hazardous materials firefighters and applied various objective standards in simulated fitness for duty determinations. Ten percent had elevated blood pressures, 13% had far visual acuity worse than 20/30 in one or both eyes, and 38% had abnormal audiometry. The strictest standards for resting blood pressure and corrected visual acuity would have failed 2% and 1% of the cohort, respectively. For audiometry, 0%-5% of the cohort would have failed, depending on the hearing requirements set. The strictest hearing standard did not allow for corrective devices so that few failures would be reversible. Visual and audiometric testing and measurement of resting blood pressure all have significant clinical yields. Studies of simulated firefighting are needed to establish minimum hearing requirements and determine whether corrective devices can be worn safely during duty. C1 Cambridge Hosp, Dept Med, Cambridge, MA 02139 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Holyoke Hosp, Work Connect, Holyoke, MA USA. UMASS, Med Ctr, Dept Community & Family Med, Worcester, MA USA. Massachusetts Resp Hosp, Ctr Occupat & Environm Hlth, Braintree, MA 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. FU NIEHS NIH HHS [1K07ES00266, ES00002]; NIOSH CDC HHS [1 K01 OH00156] NR 13 TC 12 Z9 12 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD OCT PY 1998 VL 40 IS 10 BP 925 EP 931 DI 10.1097/00043764-199810000-00014 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 129EE UT WOS:000076449700014 PM 9800179 ER PT J AU Biederman, J Mick, E Faraone, SV AF Biederman, J Mick, E Faraone, SV TI Normalized functioning in youths with persistent attention-deficit/hyperactivity disorder SO JOURNAL OF PEDIATRICS LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; FOLLOW-UP; PSYCHIATRIC STATUS; RISK-FACTORS; CHILDREN; BOYS; ADOLESCENCE AB Objective: The goal of this study was to examine normalization of functioning among youths with persistent attention-deficit hyperactivity/disorder (ADHD) symptoms. Research design: Subjects were 85 referred boys with persistent ADHD as defined by the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) who were followed up prospectively into mid adolescence and 68 boys without ADHD. These subjects were assessed at baseline and follow-up visits by using measures from 3 domains of functioning: school, social, and emotional. For each of these domains, we defined boys with ADHD as having normalized Functioning if they attained scores above the 5th percentile of scores in the non-ADHD group. Results: Twenty percent of boys with ADHD were functioning poorly in all 3 domains, 20% were functioning well in all 3 domains, and 60% had intermediate outcomes. Increased exposure to maternal psychopathology, larger family size, DSM-III-R psychiatric comorbidity, and symptoms of impulsivity were negatively associated with normalization of functioning among children with persistent ADHD. Conclusion: Our results show that children with ADHD have a variable emotional, educational, and social adjustment despite syndromatic persistence. This suggests that normalization of functioning and syndromatic persistence of ADHD may be partially independent. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Psychiat Serv, ACC 725,15 Parkman St, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH41314-08] NR 29 TC 32 Z9 34 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD OCT PY 1998 VL 133 IS 4 BP 544 EP 551 DI 10.1016/S0022-3476(98)70065-4 PG 8 WC Pediatrics SC Pediatrics GA 127XL UT WOS:000076375800017 PM 9787695 ER PT J AU Dibart, S Chapple, ILC Skobe, Z Shusterman, S Nedleman, HL AF Dibart, S Chapple, ILC Skobe, Z Shusterman, S Nedleman, HL TI Microbiological findings in prepubertal periodontitis. A case report SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE periodontitis, early-onset microbiology; periodontitis, juvenile microbiology; tooth loss pathogenesis; dental plaque microbiology; dentition mixed ID PREVOTELLA-INTERMEDIA; DISEASE AB GENERALIZED PRE-PUBERTAL PERIODONTITIS (GPP) is a rare entity that usually affects children with severe systemic diseases. We report the case of a 7-year-old male patient diagnosed with GPP, with no apparent systemic condition, who lost all his primary teeth to periodontal disease. Before extractions, while he was still in mixed dentition the subgingival plaque was collected and analyzed using DNA probes to 40 different microorganisms. Putative periodontopathogens such as Prevotella intermedia, Selenomonas noxia, Fusobacterium nucleatum, and Actinobacillus actinomycetemcomitans could be identified throughout the mouth. More intriguing was the colonization of the sulcus of some secondary teeth by potentially harmful microorganisms found in pockets of diseased adjacent primary teeth. C1 Boston Univ, Goldman Sch Dent Med, Dept Periodontol & Oral Biol, Boston, MA 02118 USA. Childrens Hosp, Dept Dent, Boston, MA 02115 USA. Birmingham Sch Dent, Dept Periodontol, Birmingham, W Midlands, England. Forsyth Dent Ctr, Dept Electron Microscopy, Boston, MA 02115 USA. RP Dibart, S (reprint author), Boston Univ, Goldman Sch Dent Med, Dept Periodontol & Oral Biol, 100 E Newton St, Boston, MA 02118 USA. NR 20 TC 9 Z9 9 U1 0 U2 0 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD OCT PY 1998 VL 69 IS 10 BP 1172 EP 1175 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 130JY UT WOS:000076518000015 PM 9802719 ER PT J AU Rodgers, MM Bar-Or, O Childress, DS Zajac, F Langbein, WE van der Woude, LHV Sowell, TT Cooper, RA AF Rodgers, MM Bar-Or, O Childress, DS Zajac, F Langbein, WE van der Woude, LHV Sowell, TT Cooper, RA TI A memorial tribute to Roger M. Glaser, PhD SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Biographical-Item C1 Maryland VA Healthcare Syst, Rehabil R&D Ctr Excellence, Baltimore, MD USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Vrije Univ Amsterdam, Inst Fundamental & Clin Movement Sci, Amsterdam, Netherlands. Univ Pittsburgh, Sch Hlth & Rehabil Sci, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Wingate Inst Phys Educ & Sports, Netanya, Israel. Northwestern Univ, Rehabil Engn Program, Chicago, IL 60611 USA. Prosthet Res Lab, Chicago, IL USA. VA Palo Alto Hlth Care Syst, Rehabil R&D Ctr Excellence, Palo Alto, CA USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. RP Maryland VA Healthcare Syst, Rehabil R&D Ctr Excellence, Baltimore, MD USA. RI Childress, Dudley/B-6967-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 EI 1938-1352 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD OCT PY 1998 VL 35 IS 4 BP VII EP IX PG 3 WC Rehabilitation SC Rehabilitation GA 183RA UT WOS:000079566200001 ER PT J AU Allen, DN Goldstein, G Heyman, RA Rondinelli, T AF Allen, DN Goldstein, G Heyman, RA Rondinelli, T TI Teaching memory strategies to persons with multiple sclerosis SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE cognitive rehabilitation; memory; multiple sclerosis AB A memory-training program previously used effectively upon persons with head-injury (HI) was conducted upon eight subjects with multiple sclerosis (MS). The program involved computer-assisted teaching of imagery-based mnemonic strategies for recall of lengthy lists of words, and for associating names with faces. Results were similar to those found in individuals with HI, but the MS subjects learned the strategies quickly, and did not appear to require the lengthy training needed by persons with HI. It was concluded that memory training of those with MS may sometimes only require teaching of mnemonic strategies without extensive practice. C1 VA Pittsburgh Healthcare Syst, Highland Dr Div 151R, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15261 USA. RP Goldstein, G (reprint author), VA Pittsburgh Healthcare Syst, Highland Dr Div 151R, 7180 Highland Dr, Pittsburgh, PA 15206 USA. NR 15 TC 30 Z9 31 U1 3 U2 5 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD OCT PY 1998 VL 35 IS 4 BP 405 EP 410 PG 6 WC Rehabilitation SC Rehabilitation GA 183RA UT WOS:000079566200006 PM 10220218 ER PT J AU Teri, L McCurry, SM Buchner, DM Logsdon, RG LaCroix, AZ Kukull, WA Barlow, WE Larson, EB AF Teri, L McCurry, SM Buchner, DM Logsdon, RG LaCroix, AZ Kukull, WA Barlow, WE Larson, EB TI Exercise and activity level in Alzheimer's disease: A potential treatment focus SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE Alzheimer's disease; caregivers; exercise; physical function ID FUNCTIONAL REACH; PUBLIC-HEALTH; RISK-FACTORS; DEMENTIA; FALLS AB This article provides information on the baseline health and physical function of 30 individuals with Alzheimer's disease (AD); describes a community-based program designed to increase balance, flexibility, strength, and endurance in these persons by the training of caregivers to facilitate and supervise exercise activity; and documents the adherence of these subjects and their caregivers to this intervention. Subjects were recruited from an ongoing, community-based Alzheimer's Disease Patient Registry, and met NINCDS-ADRDA criteria for probable or possible AD. Caregivers were family members living with the demented individuals in the community. Physical performance was measured using walking speed, functional reach, and standing balance. Health status was measured with the Medical Outcomes Study Short Form, the Sickness Impact Profile, and caregiver reports of subject's restricted activity days, bed disability days, falls, and exercise participation. Baseline data indicated that persons with AD were impaired on measures of physical performance and function, compared to published data on nondemented older adults. During a 12-wk treatment period, caregivers were taught to guide their demented charges in an individualized program of endurance activities (primarily walking), strength training, and balance and flexibility exercises. Adherence data indicated that 100% of the subjects were compliant with some exercise recommendations, and one-third completed all assigned exercises during the training period. Caregivers were able to learn and direct subjects during scheduled exercise activities. These findings indicate that the integration of exercise training into the care of persons with AD is both needed and feasible. Further research is currently underway to determine the efficacy of this approach for reducing additional physical disability in these individuals. C1 Univ Washington, Sch Nursing, Dept Psychosocial & Community Hlth, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, NW Ctr Outcomes Res & Older Adults, Seattle, WA 98108 USA. Grp Hlth Cooperat Puget Sound, Dept Prevent & Community Serv, Seattle, WA 98101 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Teri, L (reprint author), Univ Washington, Sch Nursing, Dept Psychosocial & Community Hlth, Box 357263, Seattle, WA 98195 USA. OI Kukull, Walter/0000-0001-8761-9014 NR 28 TC 41 Z9 44 U1 2 U2 13 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD OCT PY 1998 VL 35 IS 4 BP 411 EP 419 PG 9 WC Rehabilitation SC Rehabilitation GA 183RA UT WOS:000079566200007 PM 10220219 ER PT J AU Biederman, J AF Biederman, J TI Resolved: Mania is mistaken for ADHD in prepubertal children - Affirmative SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material ID DEFICIT HYPERACTIVITY DISORDER; BIPOLAR DISORDER; ONSET MANIA; CHILDHOOD; ADOLESCENCE; FAMILY C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Joint Clin Res Program, Boston, MA 02114 USA. McLean Hosp, Boston, MA USA. Columbia Univ, Dept Psychiat, New York, NY USA. RP Biederman, J (reprint author), New York State Psychiat Inst, Dept Clin Psychol, 722 W 168th St,Unit 80, New York, NY 10032 USA. FU NIMH NIH HHS [MHCRC 43878, MHCRC 30906] NR 15 TC 166 Z9 170 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD OCT PY 1998 VL 37 IS 10 BP 1091 EP 1093 DI 10.1097/00004583-199810000-00020 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 125EC UT WOS:000076223600020 PM 9785721 ER PT J AU Landefeld, CS Chren, MM AF Landefeld, CS Chren, MM TI Preventing disability in older people with chronic disease: What is a doctor to do? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material ID COMPREHENSIVE GERIATRIC ASSESSMENT; RANDOMIZED TRIAL; HEART-FAILURE; ELDERLY PATIENTS; CARE; EXERCISE; ADULTS; INTERVENTION; METAANALYSIS; OUTCOMES C1 Univ Calif San Francisco, Mt Zion Ctr Aging, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, Natl Qual Scholars Program, San Francisco, CA USA. RP Landefeld, CS (reprint author), Univ Calif San Francisco, Mt Zion Ctr Aging, San Francisco, CA 94143 USA. NR 26 TC 2 Z9 2 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 1998 VL 46 IS 10 BP 1314 EP 1316 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 127HT UT WOS:000076345400021 PM 9777919 ER PT J AU Hamilton, JD Workman, RH AF Hamilton, JD Workman, RH TI Persistence of combat-related posttraumatic stress symptoms for 75 years SO JOURNAL OF TRAUMATIC STRESS LA English DT Article DE posttraumatic stress disorder-course; dementia; aged; dreams ID VETERANS; DISORDER; ILLNESS AB Investigations of the duration of combat-related posttraumatic stress symptoms have focused mainly on survivors of World War II and the Vietnam War with little attention to surviving veterans of World War I. The authors describe a case in which posttraumatic stress symptoms persisted for 75 years in a World War I combat veteran and increased in frequency toward the end of his life accompanied by advancing dementia and hospitalization. The case illustrates that posttraumatic stress symptoms may be lifelong and exacerbated by various consequences of aging, even if they are not disabling. C1 Houston VA Med Ctr, Psychiat Serv 116A, Houston, TX 77030 USA. RP Hamilton, JD (reprint author), Houston VA Med Ctr, Psychiat Serv 116A, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 15 TC 11 Z9 11 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 1998 VL 11 IS 4 BP 763 EP 768 DI 10.1023/A:1024449517730 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 148TE UT WOS:000077548000011 PM 9870226 ER PT J AU Oh, WK Kantoff, PW AF Oh, WK Kantoff, PW TI Management of hormone refractory prostate cancer: Current standards and future prospects SO JOURNAL OF UROLOGY LA English DT Review DE prostatic neoplasms; hormones; drug therapy; chemotherapy, adjuvant ID ANTIANDROGEN WITHDRAWAL SYNDROME; ANDROGEN-RECEPTOR GENE; FLUTAMIDE WITHDRAWAL; PHASE-II; MEGESTROL-ACETATE; ORAL CYCLOPHOSPHAMIDE; ESTROGEN THERAPY; RANDOMIZED TRIAL; ANTIGEN DECLINE; CLINICAL-TRIALS AB Purpose: Recent advances in the biology and treatment of hormone refractory prostate cancer are reviewed. Materials and Methods: A MEDLINE literature search of secondary hormonal therapy and chemotherapy for hormone refractory prostate cancer was performed. Recent advances in the biology of hormone refractory prostate cancer, changes in the measurement of response to therapy, and testing of new drugs and combinations of drugs were reviewed. Results: Historically the treatment of hormone refractory prostate cancer has been disappointing. Useful parameters to monitor clinical response have been lacking but perhaps more importantly a scarcity of apparently active drugs has contributed to these results. Recently several developments have improved the outlook for treatment of hormone refractory prostate cancer. Recognition of antiandrogen withdrawal responses has had important ramifications for clinical trial interpretation and patient care. Secondary hormonal therapies, such as alternative antiandrogens and anti-adrenal agents, are well tolerated and can provide significant clinical benefits. Combining prostate specific antigen values with quality of life and measurable disease responses has made clinical trial end points more objective and more clinically relevant for the patient. Furthermore, a better understanding of the biology of hormone refractory prostate cancer, refinements in measuring response to treatment and availability of agents with proved palliative capabilities and/or generating greater than 50% response have all lead to improvements in treatment management. In 2 randomized studies mitoxantrone in combination with steroids has demonstrated significant palliative benefit compared with steroids alone. In phase II studies more than half of patients respond to estramustine combinations with vinblastine, etoposide or paclitaxel. Other novel combinations and new drugs currently are being tested. Conclusions: Recent advances suggest that available therapies for hormone refractory prostate cancer can have a meaningful impact on the disease. Improving treatment of hormone refractory prostate cancer remains an area of active investigation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Oh, WK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 106 TC 205 Z9 225 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD OCT PY 1998 VL 160 IS 4 BP 1220 EP 1229 DI 10.1016/S0022-5347(01)62501-1 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 120YZ UT WOS:000075986600002 PM 9751323 ER PT J AU Teichman, JMH Harris, JM Currie, DM Barber, DB AF Teichman, JMH Harris, JM Currie, DM Barber, DB TI Malone antegrade continence enema for adults with neurogenic bowel disease SO JOURNAL OF UROLOGY LA English DT Article DE bladder, neurogenic; fecal incontinence; enema; urinary incontinence ID SPINAL-CORD INJURY; FECAL INCONTINENCE; COLONIC ENEMA; CHILDREN; MANAGEMENT; URINARY; CONSTIPATION; DYSFUNCTION AB Purpose: We describe the outcomes of adults with neurogenic bowel disease who underwent a Malone antegrade continence enema procedure with or without concomitant urinary diversion. Materials and Methods: Consecutive adult patients with neurogenic bowel disease who underwent an antegrade continence enema procedure (continent catheterizable appendicocecostomy for fecal impaction) were retrospectively reviewed. Results: Of the 7 patients who underwent an antegrade continence enema synchronous urinary procedure (ileal conduit, augmentation ileocystoplasty with continent catheterizable abdominal stoma or augmentation ileocystoplasty) was also performed in 6. Mean patient age was 32 years and mean followup was 11 months. Of the 7 patients 6 who self-administered antegrade continence enemas regularly were continent of stool per rectum and appendicocecostomy, using the appendicocecostomy as the portal for antegrade enemas. All 6 compliant patients reported decreased toileting time and improved quality of life. Preoperative autonomic dysreflexia resolved postoperatively in 3 patients. All urinary tracts were stable. In 4 patients 5 complications occurred, including antegrade continence enema stomal stenosis requiring appendicocutaneous revision (1), antegrade continence enema stomal stenosis requiring dilation (1), superficial wound infection (1), small bowel obstruction requiring lysis of adhesions (1) and urinary incontinence (1 who underwent continent urinary diversion). Conclusions: Patients with neurogenic bladder and bowel disease may benefit from antegrade continence enema performed synchronously with a urinary procedure. Antegrade continence enema may be indicated alone for neurogenic bowel. Patient selection is important. C1 Univ Texas, Hlth Sci Ctr, Div Urol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Rehabil Med, San Antonio, TX USA. Audie L Murphy Vet Affairs Med Ctr, Spinal Cord Injury Unit, San Antonio, TX USA. RP Teichman, JMH (reprint author), Univ Texas, Hlth Sci Ctr, Div Urol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 20 TC 27 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD OCT PY 1998 VL 160 IS 4 BP 1278 EP 1281 DI 10.1016/S0022-5347(01)62515-1 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 120YZ UT WOS:000075986600016 PM 9751335 ER PT J AU Lepor, H Williford, WO Barry, MJ Haakenson, C Jones, K AF Lepor, H Williford, WO Barry, MJ Haakenson, C Jones, K CA Veterans Affairs Cooperative Studies Benign Pro TI The impact of medical therapy on bother due to symptoms, quality of life and global outcome, and factors predicting response SO JOURNAL OF UROLOGY LA English DT Article DE placebos; finasteride; drug therapy; prostatic hypertrophy ID BENIGN PROSTATIC HYPERPLASIA; TRANSITION ZONE; HEALTH-STATUS; DOUBLE-BLIND; MEN; FINASTERIDE; MULTICENTER; DOXAZOSIN; TERAZOSIN; INDEX AB Purpose: We determine the effect of placebo, finasteride, terazosin and a combination of drugs on bother due to symptoms, quality of life and patient perception of improvement, and identify baseline clinical factors that predict clinical response to medical therapy. Materials and Methods: A total of 1,229 subjects with clinical benign prostatic hyperplasia (BPH) were randomized to 1 year of placebo, finasteride, terazosin or drug combination. The primary outcome measures were American Urological Association (AUA) symptom score and peak flow rate. Relevant secondary outcome measures were symptom problem score, BPH impact score and global rating of improvement. Results: Group mean differences in symptom problem and BPH impact scores between the finasteride versus placebo, and terazosin versus combination groups were not statistically or clinically significant. Group mean differences in all outcome measures were highly statistically significant between the terazosin and finasteride, and combination and finasteride groups. The percentage of subjects who rated improvement as marked or moderate with placebo, finasteride, terazosin and combination was 39, 44, 61 and 65%, respectively. In the subsets of men in the placebo, finasteride, terazosin and combination groups with prostates greater than 50 cm.(3) group mean decrease from baseline in AUA symptom score was -2.5, -3.6, -6 and -7, group mean increase in peak flow rate was 0.6, 2.7, 3.6 and 3.7 mi. per second, group mean decrease in symptom problem score was -2.2, -1.9, -3.1 and -4.5, and group mean decrease in BPH impact score was -0.6, -0.3, -1.1 and -1.5, respectively. A correlational analysis failed to show a significant relationship between baseline prostate volume and treatment response to finasteride. There was a significant but weak relationship between change in AUA symptom score and peak flow rate in the finasteride and combination groups. The symptom responses with terazosin were independent of baseline peak flow rate. Conclusions: In men with clinical BPH finasteride and placebo are equally effective, while terazosin and combination are significantly more effective. In men with clinical BPH and large prostates the advantage of finasteride over placebo in terms of symptom reduction, impact on bother due to symptoms and quality of life is small at best, while the advantage of terazosin and combination over finasteride and placebo is highly significant. Baseline prostate volume was not a predictor of response to finasteride in the overall study population. On the basis of our results oil blockers, such as terazosin, should be first line medical treatment for BPH. C1 Vet Affairs Med Ctr, New York, NY 10010 USA. NYU, Med Ctr, New York, NY 10016 USA. Vet Affairs Med Ctr, Cooperat Studies Program, Coordinating Ctr, Perry Point, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Med Practices Evaluat Ctr, Boston, MA USA. Vet Affairs Med Ctr, Cooperat Studies Program, Clin Res Pharm Coordinating Ctr, Albuquerque, NM USA. Vet Affairs Med Ctr, Milwaukee, WI USA. RP Lepor, H (reprint author), Vet Affairs Med Ctr, New York, NY 10010 USA. NR 36 TC 102 Z9 106 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD OCT PY 1998 VL 160 IS 4 BP 1358 EP 1367 DI 10.1016/S0022-5347(01)62536-9 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 120YZ UT WOS:000075986600037 PM 9751354 ER PT J AU Roelvink, PW Lizonova, A Lee, JGM Li, Y Bergelson, JM Finberg, RW Brough, DE Kovesdi, I Wickham, TJ AF Roelvink, PW Lizonova, A Lee, JGM Li, Y Bergelson, JM Finberg, RW Brough, DE Kovesdi, I Wickham, TJ TI The coxsackievirus-adenovirus receptor protein can function as a cellular attachment protein for adenovirus serotypes from subgroups A, C, D, E, and F SO JOURNAL OF VIROLOGY LA English DT Article ID TYPE-5 FIBER PROTEIN; BINDING DOMAIN; SEQUENCE CHARACTERIZATION; NUCLEOTIDE-SEQUENCE; GENE; CELLS; TROPISM; HEMAGGLUTINATION; REPLACEMENT; RESOLUTION AB Attachment of an adenovirus (Ad) to a cell is mediated by the capsid fiber protein. To date, only the cellular fiber receptor for subgroup C serotypes 2 and 5, the so-called coxsackievirus-adenovirus receptor (CAR) protein, has been identified and cloned. Previous data suggested that the fiber of the subgroup D serotype Ad9 also recognizes CAR, since Ad9 and Ad2 fiber knobs cross-blocked each other's cellular binding. Recombinant fiber knobs and H-3-labeled Ad virions from serotypes representing all six subgroups (A to F) were used to determine whether the knobs cross-blocked the binding of virions from different subgroups. With the exception of subgroup B, all subgroup representatives cross-competed, suggesting that they use CAR as a cellular fiber receptor as well. This result was confirmed by shelving that CAR, produced in a soluble recombinant form (sCAR), bound to nitrocellulose-immobilized virions from the different subgroups except subgroup B. Similar results were found for blotted fiber knob proteins. The subgroup F virus Ad41 has both short and long fibers, but only the long fiber bound sCAR. The sCAR protein blocked the attachment of all virus serotypes that bound CAR. Moreover, CHO cells expressing human CAR, in contrast to untransformed CHO cells, all specifically bound the sCAR-binding serotypes. We conclude therefore that Ad serotypes from subgroups A, C, D, E, and F all use CAR as a cellular fiber receptor. C1 GenVec Inc, Rockville, MD 20852 USA. Childrens Hosp Philadelphia, Div Immunol & Infect Dis, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Infect Dis, Boston, MA 02115 USA. RP Roelvink, PW (reprint author), GenVec Inc, 12111 Parklawn Dr, Rockville, MD 20852 USA. RI Finberg, Robert/E-3323-2010 NR 59 TC 426 Z9 439 U1 1 U2 14 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 OCT PY 1998 VL 72 IS 10 BP 7909 EP 7915 PG 7 WC Virology SC Virology GA 118WN UT WOS:000075864100023 PM 9733828 ER PT J AU Etemad-Moghadam, B Karlsson, GB Halloran, M Sun, Y Schenten, D Fernandes, M Letvin, NL Sodroski, J AF Etemad-Moghadam, B Karlsson, GB Halloran, M Sun, Y Schenten, D Fernandes, M Letvin, NL Sodroski, J TI Characterization of simian-human immunodeficiency virus envelope glycoprotein epitopes recognized by neutralizing antibodies from infected monkeys SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; AMINO-ACID-SEQUENCE; AIDS-LIKE DISEASE; TYPE-1 GP120; RHESUS-MONKEYS; NUCLEOTIDE-SEQUENCE; HIV-1 ENTRY; V3 DOMAIN; CHIMPANZEES; RECEPTOR AB We characterized human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein epitopes recognized by neutralizing antibodies from monkeys recently infected by molecularly cloned simian-human immunodeficiency virus (SHIV) variants. The early neutralizing antibody response in each infected animal was directed mainly against a single epitope. This primary neutralizing epitope, however, differed among individual monkeys infected by identical viruses. Two such neutralization epitopes were determined by sequences in the V2 and V3 loops of the gp120 envelope glycoprotein, while a third neutralization epitope, apparently discontinuous, was determined by both V2 and V3 sequences. These results indicate that the early neutralizing antibody response in SHIV-infected monkeys is monospecific and directed against epitopes composed of the gp120 V2 and V3 variable loops. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, JFB 824,44 Binney St, Boston, MA 02115 USA. NR 72 TC 39 Z9 40 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 OCT PY 1998 VL 72 IS 10 BP 8437 EP 8445 PG 9 WC Virology SC Virology GA 118WN UT WOS:000075864100094 PM 9733899 ER PT J AU Simon, M Cleary, TG Hernandez, JD Abboud, HE AF Simon, M Cleary, TG Hernandez, JD Abboud, HE TI Shiga toxin 1 elicits diverse biologic responses in mesangial cells SO KIDNEY INTERNATIONAL LA English DT Article DE monocyte chemotactic protein-1; protein synthesis inhibition; hemolytic uremic syndrome; glycosphingolipid globotriaosylceramide; cell injury; edema; glomerulosclerosis ID HEMOLYTIC-UREMIC SYNDROME; TUMOR-NECROSIS-FACTOR; MONOCYTE CHEMOATTRACTANT PROTEIN-1; VASCULAR ENDOTHELIAL-CELLS; ESCHERICHIA-COLI; GLYCOLIPID-BINDING; BUTYRIC-ACID; FACTOR-ALPHA; CYTO-TOXIN; VEROCYTOTOXIN AB Background. Shiga toxin 1 (Stx1) is a causative agent in hemolytic uremic syndrome (HUS). Its receptor, the glycosphingolipid elobotriaosylceramide (Gb(3)), is expressed on cultured human endothelial and mesangial cells. Mesangial cell injury in HUS ranges from mild cellular edema to severe mesangiolysis and eventual glomerulosclerosis. We hypothesized that, in addition to endothelial cells, mesangial cells are targets of Stx1. Methods. Human mesangial cells were exposed to Stx1. Protein synthesis was measured using [S-35]-methionine/cysteine. Cell viability was measured as the lysosomal uptake of Neutral Red. Monocyte chemotactic peptide (MCP-1) mRNA and protein were analyzed by Northern blotting and ELISA. Results. Stx1 (0.25 to 2500 ng/ml) resulted in a dose-dependent inhibition of protein synthesis. This effect of Stx1 was potentiated by preincubation of the cells with interleukin-1 alpha (IL-1 alpha; 2 ng/ml) or tumor necrosis-alpha (TNF-alpha; 500 U/ml). Stx1 had little effect on mesangial cell viability during the first 24 hours of exposure to Stx1. However, prolonged incubation with Stx1 for 48 and 72 hours resulted in a 68% and 80% decrease in cell-viability, respectively. Stx1 elicited a dose and time dependent increase in the levels of MCP-I mRNA, an effect that was potentiated by preincubation with IL-1 alpha. Conclusion. These data indicate that mesangial cells are susceptible to the effects of Stx1 in vitro. Stx1 exerts a spectrum of biologic effects on mesangial cells ranging from activation of chemokine genes to a lethal toxic injury. Immunoinflammatory cytokines potentiate the effects of Stx1. Thus, glomerular pathology in HUS may also result from a direct effect of Stx1 on mesangial cells. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Affairs Hosp, San Antonio, TX USA. Univ Texas, Sch Med, Dept Pediat, Div Infect Dis, Houston, TX USA. RP Abboud, HE (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIDDK NIH HHS [DK 43988, DK 33665] NR 50 TC 35 Z9 35 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 OCT PY 1998 VL 54 IS 4 BP 1117 EP 1127 DI 10.1046/j.1523-1755.1998.00085.x PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 122XN UT WOS:000076096900009 PM 9767527 ER PT J AU Laposata, M MacMillan, DH Vasek, J AF Laposata, M MacMillan, DH Vasek, J TI Reflex testing; Glucose tolerance testing SO LABORATORY MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Clin Labs, Boston, MA 02114 USA. SUNY Stony Brook Hosp, Chem Lab, Stony Brook, NY USA. SUNY Stony Brook, Med Ctr, Chem Lab, Stony Brook, NY 11794 USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Clin Labs, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0007-5027 J9 LAB MED JI Lab. Med. PD OCT PY 1998 VL 29 IS 10 BP 595 EP 597 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 124PC UT WOS:000076190000011 ER PT J AU Lown, B Bukachi, F Xavier, R AF Lown, B Bukachi, F Xavier, R TI Health information in the developing world SO LANCET LA English DT Article ID AFRICA C1 Lown Cardiovasc Ctr, Brookline, MA 02146 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. SatelLife HealthNet Kenya, Nairobi, Kenya. RP Lown, B (reprint author), Lown Cardiovasc Ctr, 21 Longwood Ave, Brookline, MA 02146 USA. NR 30 TC 14 Z9 14 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD OCT PY 1998 VL 352 SU 2 BP 34 EP 38 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 125PR UT WOS:000076246600011 ER PT J AU Machens, HG Morgan, JR Berthiaume, F Stefanovich, P Reimer, R Berger, AC AF Machens, HG Morgan, JR Berthiaume, F Stefanovich, P Reimer, R Berger, AC TI Genetically modified fibroblasts induce angiogenesis in the rat epigastric island flap SO LANGENBECKS ARCHIVES OF SURGERY LA English DT Article DE angiogenesis; flaps; gene transfer ID ENDOTHELIAL GROWTH-FACTOR; ARTERIAL GENE-TRANSFER; THERAPEUTIC ANGIOGENESIS; IN-VIVO; MICE; NEOVASCULARIZATION; EXPRESSION; ISCHEMIA; TISSUE AB Methods: Gene therapy was tested for inducing functional angiogenesis in the superficial rat epigastric island flap to allow earlier pedicle division. Autologous rat fibroblasts were grown, harvested, cultured and retrovirally transfected to produce platelet-derived growth factor AA (PDGF-AA), an angiogenetically active protein. Stable gene expression was monitored by PDGF-AA enzyme-linked immunosorbent assay (ELISA). One hundred and eighty animals were divided into three groups (I-III) and a bilateral flap created in each animal. In all experiments, the right-sided flap was subjected to experimental treatment and the left-sided flap served as control (1 ml saline 0.9%). During flap elevation, group I received 5 x 10(6) GMFB (genetically modified fibroblasts) plus 1 ml Dulbecco's modified Eagle's medium. Group TT was treated with 5 x 10(6) NMFB (non-modified fibroblasts) plus 1 ml medium and group III received 1 ml medium only. The flaps were sutured back and the vascular pedicle was bilaterally ligated and divided in each of ten animals during the following 6 days. After 7 days, the flaps were harvested, the amount of necrosis measured and histologically examined. Results: The GMFB produced up to 560 times more PDGF-AA than the NMFB, measured by ELISA. The GMFB-treated flaps tolerated surgical division of the vascular pedicle significantly earlier than groups II and III. Histologically, fibroblasts persisted in all flaps of groups I and II, without major inflammatory reaction. In all GMFB-treated naps, massive angiogenesis could be demonstrated. Conclusion: By means of retroviral gene transfer, autologous rat fibroblasts can be genetically modified for stable expression of the PDGF-A gene to produce high amounts of PDGF-AA, which is angiogenetically active. After injection into the panniculus carnosus, these cells induce functional angiogenesis to permit earlier division of the vascular pedicle in this flap model. C1 Hannover Med Sch, Clin Plast Hand & Reconstruct Surg, D-30659 Hannover, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Shriners Burns Inst, Boston, MA 02114 USA. RP Machens, HG (reprint author), Hannover Med Sch, Clin Plast Hand & Reconstruct Surg, Podbielskistr 380, D-30659 Hannover, Germany. OI Morgan, Jeffrey/0000-0002-7546-3443 NR 34 TC 15 Z9 16 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1435-2443 J9 LANGENBECK ARCH SURG JI Langenbecks Arch. Surg. PD OCT PY 1998 VL 383 IS 5 BP 345 EP 350 DI 10.1007/s004230050146 PG 6 WC Surgery SC Surgery GA 141RU UT WOS:000077157900011 PM 9860229 ER PT J AU Davidov, O Zelen, M AF Davidov, O Zelen, M TI Um sampling and the proportional hazard model SO LIFETIME DATA ANALYSIS LA English DT Article DE censoring; permutation distribution; proportional hazards; urn sampling ID CENSORED-DATA; RANK-TESTS AB This paper investigates the urn sampling analogue for the score statistic relating survival to covariates assuming a proportional hazard model. The exact permutation distribution can be calculated as well as the exact low order moments for arbitrary censoring patterns. The asymptotic distribution of the score statistic is an easy consequence. The method is naturally extended to deal with the multivariate case, time varying covariates and interval censoring. Finally the relationship between the censoring process, the survival times and covariates are studied considering different reference sets for the distribution of the score statistic. Some assumptions about the censoring process are investigated and as a consequence the effect of censoring is clarified. C1 Fred Hutchinson Canc Res Ctr, Biostat Program, Seattle, WA 98109 USA. Harvard Univ, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Davidov, O (reprint author), Fred Hutchinson Canc Res Ctr, Biostat Program, 1100 Fairview Ave N,MPE-665, Seattle, WA 98109 USA. NR 17 TC 5 Z9 5 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD OCT PY 1998 VL 4 IS 4 BP 309 EP 327 DI 10.1023/A:1009626002246 PG 19 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 151UK UT WOS:000077738900001 PM 9880993 ER PT J AU Polanczyk, CA Rohde, LEP Philbin, EA Di Salvo, TG AF Polanczyk, CA Rohde, LEP Philbin, EA Di Salvo, TG TI A new casemix adjustment index for hospital mortality among patients with congestive heart failure SO MEDICAL CARE LA English DT Article DE congestive heart failure; comorbidities; casemix adjustment; mortality; outcome prediction ID CLINICAL COMORBIDITY INDEX; ICD-9-CM ADMINISTRATIVE DATA; RISK ADJUSTMENT; ADMISSION SEVERITY; POOR-QUALITY; DATA-BASES; RATES; CARE; SURVIVAL; SURGERY AB OBJECTIVES. Comparative analysis of hospital outcomes requires reliable adjustment for casemix. Although congestive heart failure is one of the most common indications for hospitalization, congestive heart failure casemix adjustment has not been widely studied. The purposes of this study were (1) to describe and validate a new congestive heart failure-specific casemix adjustment index to predict in-hospital mortality and (2) to compare its performance to the Charlson comorbidity index. METHODS. Data from all 4,608 admissions to the Massachusetts General Hospital from January 1990 to July 1996 with a principal ICD-9-CM discharge diagnosis of congestive heart failure were evaluated. Massachusetts General Hospital patients were randomly divided in a derivation and a validation set. By logistic regression, odds ratios for in-hospital death were computed and weights were assigned to construct a new predictive index in the derivation set. The performance of the index was tested in an internal Massachusetts General Hospital validation set and in a non-Massachusetts General Hospital external validation set incorporating data from all 1995 New York state hospital discharges with a primary discharge diagnosis of congestive heart failure. RESULTS. Overall in-hospital mortality was 6.4%.. Based on the new index, patients were assigned to six categories with incrementally increasing hospital mortality rates ranging from 0.5% to 31%. By logistic regression, "c" statistics of the congestive heart failure-specific index (0.83 and 0.78, derivation and validation set) were significantly superior to the Charlson index (0.66). Similar incrementally increasing hospital mortality rates were observed in the New York database with the congestive heart failure-specific index ("c" statistics 0.75). CONCLUSION. In an administrative database, this congestive heart failure-specific index may be a more adequate casemix adjustment tool to predict hospital mortality in patients hospitalized for congestive heart failure. C1 Massachusetts Gen Hosp, MGH Heart Failure Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Polanczyk, CA (reprint author), Massachusetts Gen Hosp, MGH Heart Failure Ctr, Bigelow 628,55 Fruit St, Boston, MA 02114 USA. EM polanczyk.carisi@mgh.harvard.edu RI Polanczyk, Carisi/D-6208-2013; Rohde, Luis Eduardo/I-4216-2013 NR 51 TC 55 Z9 57 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0025-7079 J9 MED CARE JI Med. Care PD OCT PY 1998 VL 36 IS 10 BP 1489 EP 1499 DI 10.1097/00005650-199810000-00007 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 131AR UT WOS:000076554000007 PM 9794342 ER PT J AU Schrag, D Kuntz, KM Garber, JE Weeks, JC AF Schrag, D Kuntz, KM Garber, JE Weeks, JC TI Impact of prophylactic surgery on life expectancy for women with breast cancer and BRCA1/2 mutations SO MEDICAL DECISION MAKING LA English DT Meeting Abstract C1 Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD OCT-DEC PY 1998 VL 18 IS 4 BP 465 EP 465 PG 1 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 128TM UT WOS:000076422700073 ER PT J AU Venditti, LN Lee, SJ Venditti, CP Peters, C AF Venditti, LN Lee, SJ Venditti, CP Peters, C TI A decison-analytic model to assess the effectiveness of bone marrow transplantation for children with Hurler syndrome SO MEDICAL DECISION MAKING LA English DT Meeting Abstract C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD OCT-DEC PY 1998 VL 18 IS 4 BP 471 EP 471 PG 1 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 128TM UT WOS:000076422700113 ER PT J AU D'Amato, RM D'Aquila, RA Wein, LM AF D'Amato, RM D'Aquila, RA Wein, LM TI Management of antiretroviral therapy for HIV infection: Modeling when to change therapy SO MEDICAL DECISION MAKING LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD OCT-DEC PY 1998 VL 18 IS 4 BP 477 EP 477 PG 1 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 128TM UT WOS:000076422700145 ER PT J AU Gerard, HC Kohler, L Branigan, PJ Zeidler, H Schumacher, HR Hudson, AP AF Gerard, HC Kohler, L Branigan, PJ Zeidler, H Schumacher, HR Hudson, AP TI Viability and gene expression in Chlamydia trachomatis during persistent infection of cultured human monocytes SO MEDICAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE Chlamydia; persistent infection; monocytes; transcription ID REACTIVE ARTHRITIS; REITERS-SYNDROME; SYNOVIAL TISSUE; SEQUENCE-ANALYSIS; PROTEIN GENE; ANTIGEN; IDENTIFICATION; HYBRIDIZATION; PATHOGENESIS; NUCLEOTIDE AB The principal host cell for persistently infecting synovial Chlamydia trachomatis is the macrophage. During infection of human monocytes/macrophages in culture this bacterium displays aberrant morphology and produces no new elementary bodies, reflecting the situation in synovium. Here we investigate the metabolic status of C. trachomatis (serovar K) during an extended infection of human peripheral monocytes in vitro. Using reverse transcription-polymerase chain reaction assays, we have shown that primary transcripts from the chlamydial rRNA operons are present throughout a 10-day course of infection. Other assays targeting mRNAs from chlamydial genes encoding r-proteins S5 and L5, the glycyl-tRNA synthetase, the 60-kDa cysteine-rich outer membrane protein, and the KDO transferase indicate that these messengers are also present throughout the entire 10-day period. The gene encoding the 57-kDa heat-shock protein (hsp60) is expressed by the bacterium throughout the 10-day infection of cultured monocytes, but transcript levels from the gene encoding the major outer membrane protein (omp1) appear to be attenuated. Western analyses targeting these latter proteins confirm the presence of the hsp60 gene product, and the virtual absence of major outer membrane protein, in chlamydia-infected cultured human monocytes. Thus, during extended infection of human monocytes in vitro, chlamydia are non-productive but transcriptionally active; the pattern of transcriptional activity reflects that known for persistent C. trachomatis infection in vivo in synovial tissue. C1 Med Hsch Hannover, Abt Rheumatol, D-30625 Hannover, Germany. Wayne State Univ, Sch Med, Dept Immunol & Microbiol, Detroit, MI 48201 USA. Dept Vet Affairs Med Ctr, Med Res, Philadelphia, PA 19104 USA. RP Kohler, L (reprint author), Med Hsch Hannover, Abt Rheumatol, Carl Neuberg Str 1, D-30625 Hannover, Germany. FU NIAMS NIH HHS [AR-42541] NR 29 TC 49 Z9 49 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0300-8584 J9 MED MICROBIOL IMMUN JI Med. Microbiol. Immunol. PD OCT PY 1998 VL 187 IS 2 BP 115 EP 120 DI 10.1007/s004300050082 PG 6 WC Immunology; Microbiology SC Immunology; Microbiology GA 134LQ UT WOS:000076744900008 PM 9832326 ER PT J AU Fraass, B Doppke, K Hunt, M Kutcher, G Starkschall, G Stern, R Van Dyke, J AF Fraass, B Doppke, K Hunt, M Kutcher, G Starkschall, G Stern, R Van Dyke, J TI American Association of Physicists in Medicine radiation therapy committee task group 53: Quality assurance for clinical radiotherapy treatment planning SO MEDICAL PHYSICS LA English DT Article DE treatment planning; quality assurance; 3D treatment planning ID DOSE CALCULATION; BRAIN-TUMORS; INTEGRATION; ACCURACY; SYSTEMS; BEAMS; BRACHYTHERAPY; GENERATION; VERIFICATION; CONVOLUTION AB In recent years, the sophistication and complexity of clinical treatment planning and treatment planning systems has increased significantly, particularly including three-dimensional (3D) treatment planning systems, and the use of conformal treatment planning and delivery techniques. This has led to the need for a comprehensive set of quality assurance (QA) guidelines that can be applied to clinical treatment planning. This document is the report of Task Group 53 of the Radiation Therapy Committee of the American Association of Physicists in Medicine. The purpose of this report is to guide and assist the clinical medical physicist in developing and implementing a comprehensive but viable program of quality assurance for modern radiotherapy treatment planning. The scope of the QA needs for treatment planning is quite broad, encompassing image-based definition of patient anatomy, 3D beam descriptions for complex beams including multileaf collimator apertures, 3D dose calculation algorithms, and complex plan evaluation tools including dose volume histograms. The Task Group recommends an organizational framework for the task of creating a QA program which is individualized to the needs of each institution and addresses the issues of acceptance testing, commissioning the planning system and planning process, routine quality assurance, and ongoing QA of the planning process. This report, while not prescribing specific QA tests, provides the framework and guidance to allow radiation oncology physicists to design comprehensive and practical treatment planning QA programs for their clinics. (C) 1998 American Association of Physicists in Medicine. [S0094-2405(98)03410-5]. C1 Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. MD Anderson Canc Ctr, Houston, TX USA. Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. London Reg Canc Ctr, London, ON N6A 4L6, Canada. RP Fraass, B (reprint author), Univ Michigan, Med Ctr, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. RI Grams, Michael/G-5197-2011 NR 80 TC 381 Z9 411 U1 1 U2 18 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 OCT PY 1998 VL 25 IS 10 BP 1773 EP 1829 DI 10.1118/1.598373 PG 57 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 129FE UT WOS:000076452500001 PM 9800687 ER PT J AU Welt, CK Kinsley, BT Simonson, DC AF Welt, CK Kinsley, BT Simonson, DC TI Recurrent hypoglycemia does not impair the cortisol response to adrenocorticotropin infusion in healthy humans SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article; Proceedings Paper CT 77th Annual Meeting of the Endocrine-Society CY JUN 12-17, 1995 CL WASHINGTON, D.C. SP Endocrine Soc, Minist Educ, Sci & Culture Japan, Dtsch ForschGemeinsch ID DEPENDENT DIABETES-MELLITUS; COUNTERREGULATORY HORMONE RESPONSES; INSULIN-INDUCED HYPOGLYCEMIA; GLUCOSE COUNTERREGULATION; GLYCEMIC CONTROL; GROWTH-HORMONE; MODERATE HYPOGLYCEMIA; BRAIN; GLUCAGON; STIMULUS AB Previous studies have shown that hypoglycemia may reduce counterregulatory responses to subsequent hypoglycemia in healthy subjects and in patients with diabetes. The effect of hypoglycemia on the hormonal response to a nonhypoglycemic stimulus is uncertain. To test the hypothesis that the cortisol response to corticotropin (ACTH) infusion is independent of antecedent hypoglycemia, 10 healthy subjects received a standard ACTH infusion (0.25 mg Cosyntropin [Organon, West Orange, NJ] intravenously over 240 minutes) at 8:00 AM on day 1 and day 3 and a hypoglycemic insulin clamp study (1 mU/kg/min) at 8:00 AM on day 2. During the hypoglycemic clamp, plasma glucose decreased from 5.0 mmol/L to 2.8 mmol/L for two periods of 120 minutes (mean glucose, 2.9 +/- 0.03 and 2.8 +/- 0.02 mmol/L, respectively) separated by a 60-minute interval of euglycemia (mean glucose, 4.7 +/- 0.01 mmol/L). Seven subjects also had paired control studies in random order during which a 330-minute euglycemic clamp (mean glucose, 5.0 +/- 0.11 mmol/L) instead of a hypoglycemic clamp was performed on day 2. Basal ACTH (4.6 +/- 0.7 v 2.6 +/- 0.4 pmol/L, P < .02) and basal cortisol (435 +/- 46 v 317 +/- 40 nmol/L, P < .02) both decreased from day 1 to day 3 following intervening hypoglycemia. In contrast, with intervening euglycemia, neither basal ACTH (5.9 +/- 1.5 v 4.5 +/- 1.0 pmol/L) nor basal cortisol (340 +/- 38 v 318 +/- 60 nmol/L) were reduced significantly on day 3 compared with day 1. Following interval hypoglycemia, the area under the curve (AUC) for the cortisol response to successive ACTH infusions was increased (4,734 +/- 428 nmol/L over 240 minutes [day 3] v 3,526 +/- 434 nmol/L over 240 minutes [day 1], P < .01). The maximum incremental cortisol response was also significantly increased (805 +/- 63 nmol/L (day 3) v 583 +/- 58 nmol/L (day 1), P < .05). In contrast, the AUC for the cortisol response to successive ACTH infusions with interval euglycemia (3,402 +/- 345 nmol/L over 240 minutes [day 3] v 3.709 +/- 391 nmol/L over 240 minutes [day 1] and the incremental cortisol response (702 +/- 62 nmol/L [day 3] v 592 +/- 85 nmol/L [day 1] were unchanged. Following exposure to intermittent hypoglycemia in healthy humans, fasting morning ACTH and cortisol levels are reduced and the incremental cortisol response to an infusion of ACTH is enhanced. The enhanced cortisol response to exogenous ACTH infusion after intervening hypoglycemia (but not intervening euglycemia) may reflect priming of the adrenal gland by endogenous ACTH produced during the hypoglycemia. These data suggest that adrenal function testing by exogenous ACTH administration is not impaired by prior exposure to hypoglycemia. Moreover, the reduced cortisol response to recurrent hypoglycemia in patients with well-controlled diabetes is not likely the result of impaired adrenal responsiveness. Copyright (C) 1998 by W.B. Saunders Company. C1 Joslin Diabet Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Welt, CK (reprint author), Massachusetts Gen Hosp, Bartlett Hall Extens,511 Fruit St, Boston, MA 02114 USA. OI Welt, Corrine/0000-0002-8219-5504 FU NCRR NIH HHS [RR-02635]; NIDDK NIH HHS [DK-36836] NR 47 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD OCT PY 1998 VL 47 IS 10 BP 1252 EP 1257 DI 10.1016/S0026-0495(98)90332-8 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 128FP UT WOS:000076395300015 PM 9781630 ER PT J AU Johnston, KA Polymenis, M Wang, S Branda, J Schmidt, EV AF Johnston, KA Polymenis, M Wang, S Branda, J Schmidt, EV TI Novel regulatory factors interacting with the promoter of the gene encoding the mRNA cap binding protein (eIF4E) and their function in growth regulation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INITIATION-FACTOR 4E; RNA-POLYMERASE-II; C-MYC; MESSENGER-RNA; TRANSLATION INITIATION; TRANSCRIPTION INITIATION; CELL-GROWTH; RETINOBLASTOMA PROTEIN; INCREASED EXPRESSION; CHAIN-REACTION AB Regulation of the mRNA cap binding protein (eIF4E) is critical to the control of cellular proliferation since this protein is the rate-limiting factor in translation initiation and transforms fibroblasts and since eIF4E mutants arrest budding yeast in the G(1) phase of the cell cycle (cdc33). We previously demonstrated regulation of eIF4E by altered transcription of its mRNA in serum-stimulated fibroblasts and in response to c-myc. To identify additional factors regulating eIF4E transcription, we used linker-scanning constructs to characterize sites in the promoter of the eIF4E gene required for its expression. Promoter activity was dependent on sites at -5, -25, -45, and -75; the site at -75 included a previously described myc box. Electrophoretic mobility shift assays identified DNA-protein interactions at -25 and revealed a binding site (TTACCCCCCCTT) that is unique to the eIF4E promoter. Proteins of 68 and 97 kDa bound this site in UV cross-linking and Southwestern experiments. Levels of 4E regulatory factor activities correlated with c-Myc levels, eIF4E expression levels, and protein synthesis in differentiating U937 and HL60 cells, suggesting that these activities may function to regulate protein synthesis rates during differentiation. Since the eIF4E promoter lacked typical TATA and initiator elements, further studies of this novel initiator-homologous element should provide insights into mechanisms of transcription initiation and growth regulation. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Childrens Serv, Boston, MA 02114 USA. RP Schmidt, EV (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. FU NCI NIH HHS [R01-CA63117, R01 CA063117] NR 75 TC 20 Z9 20 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1998 VL 18 IS 10 BP 5621 EP 5633 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 120WT UT WOS:000075980900001 PM 9742079 ER PT J AU Posas, F Witten, EA Saito, H AF Posas, F Witten, EA Saito, H TI Requirement of STE50 for osmostress-induced activation of the STE11 mitogen-activated protein kinase kinase kinase in the high-osmolarity glycerol response pathway SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; SIGNAL-TRANSDUCTION; YEAST; CASCADE; STRESS; GENE; OSMOSENSOR; INTERACTS; MECHANISM; MAPKK AB Exposure of yeast cells to increases in extracellular osmolarity activates the HOG1 mitogen-activated protein (MAP) kinase cascade, which is composed of three tiers of protein kinases: (i) the SSK2, SSK22, and STE11 MAB kinase kinase kinases (MAPKKKs), (ii) the PBS2 MAPKK, and (iii) the HOG1 MAP kinase. Activation of the MAP kinase cascade is mediated by two upstream mechanisms. The SLN1-YPD1-SSK1 two-component osmosensor activates the SSK2 and SSK22 MAPKKKs by direct interaction of the SSK1 response regulator with these MAPKKKs. The second mechanism of HOG1 MAP kinase activation is independent of the two-component osmosensor and involves the SHO1 transmembrane protein and the STE11 MAPKKK. Only PBS2 and HOG1 are common to the two mechanisms. We conducted an exhaustive mutant screening to identify additional elements required for activation of STE11 by osmotic stress. We found that strains with mutations in the STE50 gene, in combination with ssk2 Delta ssk22 Delta mutations, were unable to induce HOG1 phosphorylation after osmotic stress. Both two-hybrid analyses and coprecipitation assays demonstrated that the N-terminal domain of STE50 binds strongly to the N-terminal domain of STE11. The binding of STE50 to STE11 is constitutive and is mot affected by osmotic stress. Furthermore, the two proteins relocalize similarly after osmotic shock. It was concluded that STE50 fulfills an essential role in the activation of the high-osmolarity glycerol response pathway by acting as an integral subunit of the STE11 MAPKKK. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM haruo_saito@dfci.harvard.edu RI Posas, Francesc/K-1364-2013 OI Posas, Francesc/0000-0002-4164-7076 FU NIGMS NIH HHS [GM50909, GM56699] NR 28 TC 113 Z9 117 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1998 VL 18 IS 10 BP 5788 EP 5796 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 120WT UT WOS:000075980900018 PM 9742096 ER PT J AU Naf, D Kupfer, GM Suliman, A Lambert, K D'Andrea, AD AF Naf, D Kupfer, GM Suliman, A Lambert, K D'Andrea, AD TI Functional activity of the Fanconi anemia protein FAA requires FAC binding and nuclear localization SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID C-PROTEIN; CELLS; GENE; COMPLEMENTATION; APOPTOSIS; BRCA1; PHOSPHORYLATION; INACTIVATION; POLYPEPTIDE; INTERFERON AB Fanconi anemia (FA) is an autosomal recessive disease characterized by genomic instability, cancer susceptibility, and cellular hypersensitivity to DNA-cross-linking agents, Eight complementation groups of FA (FA-A through FA-H) have been identified. Two FA genes, corresponding to complementation groups FA-A and FA-C, have been cloned, but the functions of the encoded FAA and FAC proteins remain unknown. We have recently demonstrated that FAA and FAC interact to form a nuclear complex, In this study, we have analyzed a series of mutant forms of the FAA protein with respect to functional activity, FAC binding, and nuclear localization. Mutation or deletion of the amino-terminal nuclear localization signal (NLS) of FAA results in loss of functional activity, loss of FAC binding, and cytoplasmic retention of FAA, Replacement of the NLS sequence with a heterologous NLS sequence, derived from the simian virus 40 T antigen, results in nuclear localization but does not rescue functional activity or FAC binding. Nuclear localization of the FAA protein is therefore necessary but not sufficient for FAA function, Mutant forms of FAA which fail to bind to FAC also fail to promote the nuclear accumulation of FAC, In addition, wild-type FAC promotes the accumulation of wild-type FAA in the nucleus. Our results suggest that FAA and FAC perform a concerted function in the cell nucleus, required for the maintenance of chromosomal stability. C1 Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat, Boston, MA USA. RP D'Andrea, AD (reprint author), Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. EM a_dandrea@farber.harvard.edu FU NCI NIH HHS [P01 CA039542, P0CA39542]; PHS HHS [R01-H15725, K08-H10340] NR 41 TC 96 Z9 96 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1998 VL 18 IS 10 BP 5952 EP 5960 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 120WT UT WOS:000075980900034 PM 9742112 ER PT J AU Wang, K Gross, A Waksman, G Korsmeyer, SJ AF Wang, K Gross, A Waksman, G Korsmeyer, SJ TI Mutagenesis of the BH3 domain of BAX identifies residues critical for dimerization and killing SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INDUCED CELL-DEATH; BCL-2 FAMILY; APOPTOSIS; PROTEIN; HETERODIMERIZATION; INHIBITION; BCL-X(L); MEMBERS; HOMODIMERIZATION; DISTINCT AB The BCL-2 family of proteins is comprised of proapoptotic as well as antiapoptotic members (S. N. Farrow and R. Brown, Curr. Opin. Genet. Dev. 6:45-49, 1996), A prominent death agonist, BAX, forms homodimers and heterodimerizes with multiple antiapoptotic members, Death agonists have an amphipathic or helix, called BH3; however, the initial assessment of BH3 in BAX has yielded conflicting results. Our BAX deletion constructs and minimal domain constructs indicated that the BH3 domain was required for BAX homodimerization and heterodimerization with BCL-2, BCL-X-L, and MCL-1. An extensive site-directed mutagenesis of BH3 revealed that substitutions along the hydrophobic face of BH3, especially charged substitutions, had the greatest affects on dimerization patterns and death agonist activity. Particularly instructive was the BAX mutant mIII-1 (L63A, G67A, L70A, and M74A), which replaced the hydrophobic face of BH3 with alanines, preserving its amphipathic nature. BAXmIII-1 failed to form heterodimers or homodimers by yeast two-hybrid or immunoprecipitation analysis yet retained proapoptotic activity. This suggests that BAX's killing function reflects mechanisms beyond its binding to BCL-2 or BCL-X-L to inhibit them or simply displace other protein partners. Notably, BAXmIII-1 was found predominantly in mitochondrial membranes, where it was homodimerized as assessed by homobifunctional cross-linkers. This characteristic of BAXmIII-1 correlates with its capacity to induce mitochondrial dysfunction, caspase activation, and apoptosis, These data are consistent with a model in which BAX death agonist activity may require an intramembranous conformation of this molecule that is not assessed accurately by classic binding assays. C1 Washington Univ, Sch Med, Dept Med, Div Mol Oncol,Howard Hughes Med Inst, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pathol, Div Mol Oncol,Howard Hughes Med Inst, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. RP Korsmeyer, SJ (reprint author), Dana Farber Canc Inst, Dept Immunol & AIDS, Smith Bldg,Rm 758,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 49712] NR 29 TC 169 Z9 171 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 OCT PY 1998 VL 18 IS 10 BP 6083 EP 6089 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 120WT UT WOS:000075980900047 PM 9742125 ER PT J AU Zhang, R Averboukh, L Zhu, WM Zhang, H Jo, H Dempsey, PJ Coffey, RJ Pardee, AB Liang, P AF Zhang, R Averboukh, L Zhu, WM Zhang, H Jo, H Dempsey, PJ Coffey, RJ Pardee, AB Liang, P TI Identification of rCop-1, a new member of the CCN protein family, as a negative regulator for cell transformation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TISSUE GROWTH-FACTOR; IMMEDIATE-EARLY GENE; DIFFERENTIAL DISPLAY; INDUCIBLE GENE; EXPRESSION; P53; RAS; CYR61; OVEREXPRESSION; COOPERATION AB By using a model system for cell transformation mediated by the cooperation of the activated H-ras oncogene and the inactivated p53 tumor suppressor gene, rCop-1 was identified by mRNA differential display as a gene whose expression became lost after cell transformation. Homology analysis indicates that rCop-1 belongs to an emerging cysteine-rich growth regulator family called CCN, which includes connective-tissue growth factor, CYR61, CEF10 (v-src inducible), and the product of the nov proto-oncogene. Unlike the other members of the CCN gene family, rCop-1 is not an immediate-early gene, it lacks the conserved C-terminal domain which was shown to confer both growth stimulating and heparin-binding activities, and its expression is lost in cells transformed by a variety of mechanisms, Ectopic expression of rCop-1 by retroviral gene transfers led to cell death in a transformation-specific manner. These results suggest that rCop-1 represents a new class of CCN family proteins that have functions opposing those of the previously identified members. C1 Vanderbilt Univ, Dept Cell Biol, Vanderbilt Canc Ctr, Nashville, TN 37232 USA. Dana Farber Canc Inst, Div Cell Growth & Regulat, Boston, MA 02115 USA. RP Liang, P (reprint author), Vanderbilt Univ, Dept Cell Biol, Vanderbilt Canc Ctr, 658 Med Res Bldg 2, Nashville, TN 37232 USA. FU NCI NIH HHS [CA74067, P30 CA068485, CA68485] NR 38 TC 116 Z9 123 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 OCT PY 1998 VL 18 IS 10 BP 6131 EP 6141 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 120WT UT WOS:000075980900052 PM 9742130 ER PT J AU Yauch, RL Berditchevski, F Harler, MB Reichner, J Hemler, ME AF Yauch, RL Berditchevski, F Harler, MB Reichner, J Hemler, ME TI Highly stoichiometric, stable, and specific association of integrin alpha 3 beta 1 with CD151 provides a major link to phosphatidylinositol 4 kinase, and may regulate cell migration SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID LEUKEMIA-VIRUS TYPE-1; TRANSMEMBRANE-4 SUPERFAMILY; MONOCLONAL-ANTIBODIES; EXTRACELLULAR-MATRIX; SIGNAL-TRANSDUCTION; CYCLE PROGRESSION; BASEMENT-MEMBRANE; TM4SF PROTEINS; LIGAND-BINDING; T-CELLS AB Here we describe an association between alpha 3 beta 1 integrin and transmembrane-4 superfamily (TM4SF) protein CD151. This association is maintained in relatively stringent detergents and thus is remarkably stable in comparison with previously reported integrin-TM4SF protein associations. Also, the association is highly specific (i.e., observed in vitro in absence of any other cell surface proteins), and highly stoichiometric (nearly 90% of alpha 3 beta 1 associated with CD151). In addition, alpha 3 beta 1 and CD151 appeared in parallel on many cell lines and showed nearly identical skin staining patterns. Compared with other integrins, alpha 3 beta 1 exhibited a considerably higher level of associated phosphatidylinositol-4-kinase (PtdIns 4-kinase) activity, most of which was removed upon immunodepletion of CD151. Specificity for CD151 and PtdIns 4-kinase association resided in the extracellular domain of alpha 3 beta 1, thus establishing a novel paradigm for the specific recruitment of an intracellular signaling molecule. Finally, antibodies to either CD151 or alpha 3 beta 1 caused a similar to 88-92% reduction in neutrophil motility in response to f-Met-Leu-Phe on fibronectin, suggesting an functionally important role of these complexes in cell migration. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Birmingham, CRC, Inst Canc Studies, Birmingham B15 2TA, W Midlands, England. Rhode Isl Hosp, Dept Surg Res, Providence, RI 02903 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. OI Reichner, Jonathan/0000-0002-7349-6321 FU NIAID NIH HHS [F32 AI009490]; NIGMS NIH HHS [GM-38903, GM-51493, GM-46526, R01 GM038903] NR 64 TC 232 Z9 242 U1 1 U2 8 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD OCT PY 1998 VL 9 IS 10 BP 2751 EP 2765 PG 15 WC Cell Biology SC Cell Biology GA 128DC UT WOS:000076389100005 PM 9763442 ER PT J AU Grossman, SR Perez, M Kung, AL Joseph, M Mansur, C Xiao, ZX Kumar, S Howley, PM Livingston, DM AF Grossman, SR Perez, M Kung, AL Joseph, M Mansur, C Xiao, ZX Kumar, S Howley, PM Livingston, DM TI p300/MDM2 complexes participate in MDM2-mediated p53 degradation SO MOLECULAR CELL LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; DNA-DAMAGING AGENTS; LARGE T-ANTIGEN; P53-MEDIATED TRANSACTIVATION; TRANSCRIPTIONAL COACTIVATORS; P300/CBP-ASSOCIATED FACTOR; TRANSFORMED-CELLS; TERMINAL DOMAIN; MDM-2 ONCOGENE; E6 ONCOPROTEIN AB Control of p53 turnover is critical to p53 function. E1A binding to p300/CBP translates into enhanced p53 stability, implying that these coactivator proteins normally operate in p53 turnover control. In this regard, the p300 C/H1 region serves as a specific in vivo binding site for both p53 and MDM2, a naturally occurring p53 destabilizer. Moreover, most of the endogenous MDM2 is bound to p300, and genetic analysis implies that specific interactions of p53 and MDM2 with p300 C/H1 are important steps in the MDM2-directed turnover of p53. A specific role for p300 in endogenous p53 degradation is underscored by the p53-stabilizing effect of overproducing the p300 C/H1 domain. Taken together, the data indicate that specific interactions between p300/CBP C/H1, p53, and MDM2 are intimately involved in the MDM2-mediated control of p53 abundance. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. New England Med Ctr, Dept Dermatol, Boston, MA 02111 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. RP Livingston, DM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. OI Kung, Andrew/0000-0002-9091-488X NR 56 TC 327 Z9 336 U1 0 U2 6 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 OCT PY 1998 VL 2 IS 4 BP 405 EP 415 DI 10.1016/S1097-2765(00)80140-9 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 133GN UT WOS:000076678900001 PM 9809062 ER PT J AU Seel, WG Hanstein, B Brown, M Moore, DD AF Seel, WG Hanstein, B Brown, M Moore, DD TI Inhibition of estrogen receptor action by the orphan receptor SHP (Short heterodimer partner) SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID NUCLEAR HORMONE-RECEPTOR; ADRENAL HYPOPLASIA CONGENITA; DNA-BINDING DOMAIN; GROWTH-HORMONE; CYCLIN D1; SUPERFAMILY; TRANSACTIVATION; ACTIVATION; CLONING; MEMBER AB SHP (short heterodimer partner) is an unusual orphan receptor that lacks a conventional DNA-binding domain. Previous results have shown that it interacts with several other nuclear hormone receptors, including the retinoid and thyroid hormone receptors, and inhibits their ligand-dependent transcriptional activation. Here we show that SHP also interacts with estrogen receptors and inhibits their function, In mammalian and yeast two-hybrid systems as well as glutathione-S-transferase pull-down assays, SHP interacts specifically with estrogen receptor-alpha (ER alpha) in an agonist-dependent manner, The same assay systems using various deletion mutants of SHP map the interaction domain with ER alpha to the same SHP sequences required for interaction with the nonsteroid hormone receptors such as retinoid X receptor and thyroid hormone receptor. In transient cotransfection assays, SHP inhibits estradiol -dependent activation by ER alpha by about 5-fold. In contrast, SHP interacts with ER beta independent of ligand and reduces its ability to activate transcription by only 50%. These data suggest that SHP functions to regulate estrogen signaling through a direct interaction with ER alpha. C1 Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Moore, DD (reprint author), Baylor Coll Med, Dept Cell Biol, 1 Baylor Plaza, Houston, TX 77030 USA. EM moore@bcm.tmc.edu OI Brown, Myles/0000-0002-8213-1658 NR 30 TC 18 Z9 18 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD OCT PY 1998 VL 12 IS 10 BP 1551 EP 1557 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 123WR UT WOS:000076149000007 ER PT J AU Arbiser, JL Kraeft, SK van Leeuwen, R Hurwitz, SJ Selig, M Dickersin, GR Flint, A Byers, HR Chen, LB AF Arbiser, JL Kraeft, SK van Leeuwen, R Hurwitz, SJ Selig, M Dickersin, GR Flint, A Byers, HR Chen, LB TI Clioquinol-zinc chelate: A candidate causative agent of subacute myelo-optic neuropathy SO MOLECULAR MEDICINE LA English DT Article AB Background: 5-chloro-7-iodo-8-hydroxyquinoline (clioquinol) was used clinically three decades ago as an oral antiparasitic agent and to increase intestinal absorption of zinc in patients with acrodermatitis enteropathica, a genetic disorder of zinc absorption. Use of clioquinol was epidemiologically linked to subacute myelo-optic neuropathy (SMON), characterized by peripheral neuropathy and blindness, which affected 10,000 patients in Japan. Discontinuation of oral clioquinol use led to elimination of SMON, however, the mechanism of how clioquinol induces neurotoxicity is unclear. Materials and Methods: We tested the effect of clioquinol-metal chelates on neural crest-derived melanoma cells. The effect of clioquinol chelates on cells was further studied by electron microscopy and by a mitochondrial potential-sensitive fluorescent dye. Results: Of the ions tested, only clioquinol-zinc chelate demonstrated cytotoxicity. The cytotoxicity of clioquinol-zinc chelate was extremely rapid, suggesting that its primary effect was on the mitochondria. Electron microscopic analysis demonstrated that clioquinol-zinc chelate caused mitochondrial damage. This finding was further confirmed by the observation that clioquinol-zinc chelate caused a decrease in mitochondrial membrane potential. Conclusions: We demonstrate that clioquinol, in the presence of zinc, is converted to a potent mitochondrial toxin. The phenomenon of clioquinol mediated toxicity appears to be specific to zinc and is not seen with other metals tested. Since clioquinol has been shown to cause increased systemic absorption of zinc in humans, it is likely that clioquinol-zinc chelate was present in appreciable levels in patients with SMON and may be the ultimate causative toxin of SMON. C1 Emory Univ, Sch Med, Dept Dermatol, Atlanta, GA 30322 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Leiden Univ, Dept Dermatol, Leiden, Netherlands. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Dept Genet, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. RP Arbiser, JL (reprint author), Emory Univ, Sch Med, Dept Dermatol, Woodruff Mem Bldg,Rm 5309, Atlanta, GA 30322 USA. FU NIAMS NIH HHS [R03AR44947] NR 16 TC 46 Z9 48 U1 1 U2 4 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 OCT PY 1998 VL 4 IS 10 BP 665 EP 670 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 135YF UT WOS:000076829900004 PM 9848083 ER PT J AU Minassian, BA Lee, JR Herbrick, JA Huizenga, J Soder, S Mungall, AJ Dunham, I Gardner, R Fong, CG Carpenter, S Jardim, L Satishchandra, P Andermann, E Snead, OC Lopes-Cendes, I Tsui, LC Delgado-Escueta, AV Rouleau, GA Scherer, SW AF Minassian, BA Lee, JR Herbrick, JA Huizenga, J Soder, S Mungall, AJ Dunham, I Gardner, R Fong, CG Carpenter, S Jardim, L Satishchandra, P Andermann, E Snead, OC Lopes-Cendes, I Tsui, LC Delgado-Escueta, AV Rouleau, GA Scherer, SW TI Mutations in a gene encoding a novel protein tyrosine phosphatase cause progressive myoclonus epilepsy SO NATURE GENETICS LA English DT Article ID LAFORAS-DISEASE; FORM; DIAGNOSIS AB Lafora's disease (LD; OMIM 254780) is an autosomal recessive form of progressive myoclonus epilepsy characterized by seizures and cumulative neurological deterioration. Onset occurs during late childhood and usually results in death within ten years of the first symptoms(1,2). With few exceptions, patients follow a homogeneous clinical course despite the existence of genetic heterogeneity(3). Biopsy of various tissues, including brain, revealed characteristic polyglucosan inclusions called Lafora bodies(4-8), which suggested LD might be a generalized storage disease(6,9). Using a positional cloning approach, we have identified at chromosome 6q24 a novel gene, EPM2A. that encodes a protein with consensus amino acid sequence indicative of a protein tyrosine phosphatase (PTP). mRNA transcripts representing alternatively spliced forms of EPM2A were found in every tissue examined, including brain. Six distinct DNA sequence variations in EPM2A in nine families, and one homozygous microdeletion in another family have been found to cosegregate with LD. These mutations are predicted to cause deleterious effects in the putative protein product, named laforin, resulting in LD. C1 Univ Toronto, Hosp Sick Children, Dept Genet, Toronto, ON M5G 1X8, Canada. Univ Toronto, Hosp Sick Children, Dept Paediat, Div Neurol, Toronto, ON M5G 1X8, Canada. Sanger Ctr, Hinxton CB10 1SA, Cambs, England. Salisbury Dist Hosp, Salisbury Hlth Care NHS Trust, Wessex Reg Genet Lab, Salisbury SP2 8BJ, Wilts, England. Univ Calif Los Angeles, Sch Med, Calif Comprehens Epilepsy Program, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Toronto, Toronto Hosp, Dept Pathol, Toronto, ON M5T 2S8, Canada. Hosp Clin Porto Alegre, Med Genet Serv, BR-90035003 Porto Alegre, RS, Brazil. Deemed Univ, Natl Inst Mental Hlth & Neurosci, Bangalore 560029, Karnataka, India. McGill Univ, Dept Human Genet, Montreal, PQ, Canada. Montreal Gen Hosp, Res Inst, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada. Univ Toronto, Dept Mol & Med Genet, Toronto, ON M5S 1A8, Canada. RP Scherer, SW (reprint author), Univ Toronto, Hosp Sick Children, Dept Genet, Toronto, ON M5G 1X8, Canada. RI Tsui, Lap-chee/A-1081-2010; Howe, Jennifer/I-9013-2012; Jardim, Laura/B-6149-2013; Lopes-Cendes, Iscia/B-9416-2013; Scherer, Stephen /B-3785-2013 OI Lopes-Cendes, Iscia/0000-0002-6221-6822; Scherer, Stephen /0000-0002-8326-1999 FU NINDS NIH HHS [5P01-NS21908]; Wellcome Trust NR 24 TC 272 Z9 281 U1 0 U2 13 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 1998 VL 20 IS 2 BP 171 EP 174 DI 10.1038/2470 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 125HL UT WOS:000076231300019 PM 9771710 ER PT J AU Tanzi, RE AF Tanzi, RE TI Of calcium, caspases, and cognitive decline SO NATURE MEDICINE LA English DT Editorial Material ID ALZHEIMERS-DISEASE; APOPTOSIS C1 Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Unit, Charlestown, MA 02129 USA. RP Tanzi, RE (reprint author), Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Unit, Charlestown, MA 02129 USA. NR 13 TC 4 Z9 5 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 1998 VL 4 IS 10 BP 1127 EP 1128 DI 10.1038/2622 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 125GY UT WOS:000076230100029 PM 9771743 ER PT J AU Elmquist, JK Maratos-Flier, E Saper, CB Flier, JS AF Elmquist, JK Maratos-Flier, E Saper, CB Flier, JS TI Unraveling the central nervous system pathways underlying responses to leptin SO NATURE NEUROSCIENCE LA English DT Review ID OBESE GENE-PRODUCT; RECEPTOR MESSENGER-RNA; FORM SPLICE VARIANT; NORMAL FEMALE MICE; NEUROPEPTIDE-Y; OB/OB MICE; ARCUATE NUCLEUS; OB-R; VENTROMEDIAL HYPOTHALAMUS; DORSOMEDIAL HYPOTHALAMUS AB Here we summarize recent progress in the biology of leptin, concentrating on its central nervous system (CNS) actions. The product of the ob gene, leptin is a circulating hormone produced by white adipose tissue that has potent effects on feeding behavior, thermogenesis and neuroendocrine responses. Leptin regulates energy homeostasis, as its absence in rodents and humans causes severe obesity. We consider the physiological mechanisms underlying leptin action, along with several novel hypothalamic neuropeptides that affect food intake and body weight. The molecular causes of several other obesity syndromes are discussed to illuminate how the CNS regulates body weight. We describe neural circuits that are downstream of leptin receptors and propose a model linking populations of leptin-responsive neurons with effector neurons underlying leptin's endocrine, autonomic and behavioral effects. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Endocrinol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Elmquist, JK (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Endocrinol, 325 Res N,99 Brookline Ave, Boston, MA 02215 USA. NR 107 TC 362 Z9 370 U1 1 U2 12 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 OCT PY 1998 VL 1 IS 6 BP 445 EP 450 DI 10.1038/2164 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 128LE UT WOS:000076406900008 PM 10196541 ER PT J AU Freire, MBS van Dijk, DJ Erman, A Boner, G Warram, JH Krolewski, AS AF Freire, MBS van Dijk, DJ Erman, A Boner, G Warram, JH Krolewski, AS TI DNA polymorphisms in the ACE gene, serum ACE activity and the risk of nephropathy in insulin-dependent diabetes mellitus SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article ID CONVERTING-ENZYME GENE; INSERTION DELETION POLYMORPHISM; RENIN-ANGIOTENSIN SYSTEM; MYOCARDIAL-INFARCTION; RENAL COMPLICATIONS; IGA NEPHROPATHY; HEART-DISEASE; IDDM PATIENTS; PROGRESSION; MICROALBUMINURIA AB Background. To determine the relationship between DNA polymorphisms in the angiotensin I converting enzyme (ACE) gene, serum ACE activity and the risk of diabetic nephropathy. Methods. A case-control study was carried out in a population of Jewish insulin-dependent diabetes mellitus (IDDM) patients. Cases (77 IDDM patients with diabetic nephropathy) and controls (89 IDDM patients with normoalbuminuria) were genotyped with PCR protocols for detecting two DNA polymorphisms in the ACE gene: one in intron 7 detected with the restriction enzyme PstI and the other in intron 16 identified as an insertion/deletion (I/D). Results. The risk of nephropathy was increased only in patients homozygous for the allele with the PstI site. These homozygotes had a nephropathy risk that was 2.3 times (95% C.I.: 1.2-4.5) that of the other genotypes. Furthermore, these individuals did not have elevated serum ACE activity. Conclusions. The results of this study are evidence that the risk of diabetic nephropathy in IDDM is influenced by genetic variability at the ACE locus, but the responsible Variant is not the I/D polymorphism in intron 16. Our findings require further studies in other populations. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Beilinson Med Ctr, Rabin Med Ctr, Inst Hypertens & Kidney Dis, Petah Tiqwa, Israel. Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. RP Krolewski, AS (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK4156] NR 35 TC 18 Z9 20 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD OCT PY 1998 VL 13 IS 10 BP 2553 EP 2558 DI 10.1093/ndt/13.10.2553 PG 6 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 128HD UT WOS:000076399200027 PM 9794558 ER PT J AU Klivenyi, P St Clair, D Wermer, M Yen, HC Oberley, T Yang, LC Beal, MF AF Klivenyi, P St Clair, D Wermer, M Yen, HC Oberley, T Yang, LC Beal, MF TI Manganese superoxide dismutase overexpression attenuates MPTP toxicity SO NEUROBIOLOGY OF DISEASE LA English DT Article DE MPTP; Parkinson's disease; free radicals; oxidative damage; superoxide dismutase ID NEURONAL NITRIC-OXIDE; NEURODEGENERATIVE DISEASES; TRANSGENIC MICE; IN-VIVO; NEUROTOXICITY; GENERATION; INHIBITION; SYNTHASE; BRAIN AB There is substantial evidence implicating mitochondrial dysfunction and free radical generation in the neurotoxicity of MPTP. Manganese superoxide dismutase (MnSOD) is the primary antioxidant enzyme protecting against superoxide radicals produced within mitochondria. Overexpression of human MnSOD in transgenic mice resulted in increased MnSOD localized to mitochondria in neurons and a 50% increase in total MnSOD activity in brain homogenates. We found that MPTP toxicity was significantly attenuated in the MnSOD transgenic mice which overexpress the human manganese superoxide dismutase gene, with these mice showing threefold greater dopamine levels than controls following MPTP. There were no alterations in MPP+ levels, suggesting that the effects were not due to altered metabolism of MPTP. A significant increase in 3-nitrotyrosine levels was seen in littermate controls but not in transgenic mice overexpressing human MnSOD. These results provide further evidence implicating mitochondrial dysfunction and oxidative damage in the pathogenesis of MPTP neurotoxicity. (C) 1998 Academic Press. C1 Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Kentucky, Grad Ctr Toxicol, Lexington, KY 40506 USA. Univ Wisconsin, Vet Adm Hosp, Dept Pathol & Lab Med, Madison, WI 53706 USA. RP Klivenyi, P (reprint author), Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. FU NCI NIH HHS [CA49797]; NINDS NIH HHS [NS31579, NS32365] NR 24 TC 109 Z9 111 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD OCT PY 1998 VL 5 IS 4 BP 253 EP 258 DI 10.1006/nbdi.1998.0191 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 137QH UT WOS:000076926500005 PM 9848095 ER PT J AU Casey, BJ Cohen, JD O'Craven, K Davidson, RJ Irwin, W Nelson, CA Noll, DC Hu, XP Lowe, MJ Rosen, BR Truwitt, CL Turski, P AF Casey, BJ Cohen, JD O'Craven, K Davidson, RJ Irwin, W Nelson, CA Noll, DC Hu, XP Lowe, MJ Rosen, BR Truwitt, CL Turski, P TI Reproducibility of fMRI results across four institutions using a spatial working memory task SO NEUROIMAGE LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; PREFRONTAL CORTEX; ACTIVATION; PET; HUMANS; BRAIN AB Four U.S. sites formed a consortium to conduct a multisite study of fMRI methods. The primary purpose of this consortium was to examine the reliability and reproducibility of fMRI results. FMRI data were collected on healthy adults during performance of a spatial working memory task at four different institutions. Two sets of data from each institution were made available. First, data from two subjects were made available from each site and were processed and analyzed as a pooled data set. Second, statistical maps from five to eight subjects per site were made available. These images were aligned in stereotactic space and common regions of activation were examined to address the reproducibility of fMRI results when both image acquisition and analysis vary as a function of site. Our grouped and individual data analyses showed reliable patterns of activation in dorsolateral prefrontal cortex and posterior parietal cortex during performance of the working memory task across all four sites. This multisite study, the first of its kind using fMRI data, demonstrates highly consistent findings across sites. (C) 1998 Academic Press. C1 Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Rowland Inst Sci Inc, Charlestown, MA 02129 USA. Univ Wisconsin, Madison, WI 53706 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Indiana Univ, Indianapolis, IN 46202 USA. RP Casey, BJ (reprint author), Univ Pittsburgh, Med Ctr, 3811 OHara St, Pittsburgh, PA 15213 USA. EM bjcasey@pitt.edu RI Noll, Douglas/D-8124-2014 OI Noll, Douglas/0000-0002-0983-3805 NR 28 TC 155 Z9 157 U1 1 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT PY 1998 VL 8 IS 3 BP 249 EP 261 DI 10.1006/nimg.1998.0360 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 130NN UT WOS:000076526300003 PM 9758739 ER PT J AU Kim, TW Tanzi, RE AF Kim, TW Tanzi, RE TI Neuronal intranuclear inclusions in polyglutamine diseases: Nuclear weapons or nuclear fallout? SO NEURON LA English DT Review ID GLUTAMINE REPEATS; HUNTINGTIN; PROTEIN; TRACT C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Unit, Charlestown, MA 02129 USA. RP Tanzi, RE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Unit, Charlestown, MA 02129 USA. NR 20 TC 45 Z9 46 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD OCT PY 1998 VL 21 IS 4 BP 657 EP 659 DI 10.1016/S0896-6273(00)80581-4 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 133QM UT WOS:000076697300008 PM 9808451 ER PT J AU Tong, F Nakayama, K Vaughan, JT Kanwisher, N AF Tong, F Nakayama, K Vaughan, JT Kanwisher, N TI Binocular rivalry and visual awareness in human extrastriate cortex SO NEURON LA English DT Article ID PERCEPTION AB We used functional magnetic resonance imaging (fMRI) to monitor stimulus-selective responses of the human fusiform face area (FFA) and parahippocampal place area (PPA) during binocular rivalry in which, a face and a house stimulus were presented to different eyes. Though retinal stimulation remained constant, subjects perceived changes from house to face that were accompanied by increasing FFA and decreasing PPA activity; perceived changes from face to house led to the opposite pattern of responses. These responses during rivalry were equal in magnitude to those evoked by nonrivalrous stimulus alternation, suggesting that activity in the FFA and PPA reflects the perceived rather than the retinal stimulus, and that neural competition during binocular rivalry has been resolved by these stages of visual processing. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Tong, F (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. NR 16 TC 455 Z9 464 U1 5 U2 48 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD OCT PY 1998 VL 21 IS 4 BP 753 EP 759 DI 10.1016/S0896-6273(00)80592-9 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 133QM UT WOS:000076697300019 PM 9808462 ER PT J AU Maxwell, M Galanopoulos, T Neville-Golden, J Hedley-Whyte, ET Antoniades, HN AF Maxwell, M Galanopoulos, T Neville-Golden, J Hedley-Whyte, ET Antoniades, HN TI Cellular localization of PDGF mRNAs in developing human forebrain SO NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY LA English DT Article DE PDGF; growth factor; protooncogene; glia; neurons; gliogenesis ID CENTRAL-NERVOUS-SYSTEM; GROWTH-FACTOR PDGF; LATERAL GENICULATE-NUCLEUS; FACTOR B-CHAIN; SPINAL-CORD; GLIAL-CELLS; NEURONAL CELLS; RECEPTOR GENES; A-CHAIN; EXPRESSION AB Platelet-derived growth factor (PDGF) has been implicated in the processes regulating gliogenesis in the CNS. Conflicting in vivo data in rodents have variously implicated either glia or neurons as being the primary source of PDGF. We have used in situ hybridization and immunocytochemical analysis to study the in vivo expression and cellular localization of PDGF-A, sis/PDGF-B, together with the two PDGF receptors alpha and beta, in developing human forebrain, In this study we demonstrate the strong expression of mRNA and protein of both EDGE chains, A and B, and their receptors, alpha and beta, in human embryonic glial cells. The neurons, in contrast to glial cells, expressed lower levels of PDGF and PDGF-receptor mRNAs and protein. Identification of the cell types expressing the PDGF and PDGF-receptor mRNAs was achieved by counterstaining with antibodies specific for glial cells (GFAP) and neurons (NF). The predominant glial-specific expression of both PDGF-A and PDGF-B, together with the coexpression of their receptors alpha and beta, suggests an important role for the PDGF isoforms in the development of human embryonic glial cells and neurons in vivo. C1 Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neuropathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Canc Biol, Boston, MA 02115 USA. Univ Oxford, Radcliffe Infirm, Dept Neuropathol, Oxford OX2 6HE, England. RP Maxwell, M (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, House Mail, Boston, MA 02114 USA. NR 31 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0305-1846 J9 NEUROPATH APPL NEURO JI Neuropathol. Appl. Neurobiol. PD OCT PY 1998 VL 24 IS 5 BP 337 EP 345 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 137YF UT WOS:000076944100001 PM 9821163 ER PT J AU Wyszynski, M Kim, E Yang, FC Sheng, M AF Wyszynski, M Kim, E Yang, FC Sheng, M TI Biochemical and immunocytochemical characterization of GRIP, a putative AMPA receptor anchoring protein, in rat brain SO NEUROPHARMACOLOGY LA English DT Article; Proceedings Paper CT 7th Neuropharmacology Conference CY NOV 05-07, 1998 CL LOS ANGELES, CALIFORNIA DE excitatory synapses; PSD-95; glutamate receptors; PDZ domain; cytoskeleton; postsynaptic density ID SELECTIVE GLUTAMATE RECEPTORS; TUMOR-SUPPRESSOR PROTEIN; POSTSYNAPTIC DENSITY; GUANYLATE KINASES; SUBUNIT COMPOSITION; CLUSTERING ACTIVITY; CA2+ PERMEABILITY; PSD-95 FAMILY; FASCICLIN-II; K+ CHANNELS AB The mechanisms by which glutamate receptors are concentrated in brain excitatory synapses are believed to involve interactions between receptor subunits and postsynaptic anchoring or scaffolding proteins. Recently GRIP, a protein containing seven PDZ domains, was identified as an AMPA receptor binding protein and implicated in the synaptic targeting of AMPA receptors. Here we show that GRIP mRNA is also expressed in some tissues outside of the brain, including testis and kidney. Specific antibodies were raised to study GRIP protein. On Western blots, GRIP protein appears as a heterogeneous band(similar to 130 kilodaltons) which is expressed in widespread brain regions and throughout postnatal development. Biochemical studies reveal that GRIP is largely membrane associated and enriched in the postsynaptic density (PSD), though not as highly concentrated in the PSD as is PSD-95. By immunohistochemistry, GRIP is distributed in a somatodendritic pattern in neurons of adult rat brain, with especially prominent expression in a subset of interneurons. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Neurobiol, Boston, MA 02114 USA. Pusan Natl Univ, Dept Pharmacol, Pusan 609735, South Korea. RP Sheng, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Neurobiol, 50 Blossom St, Boston, MA 02114 USA. RI Kim, Eunjoon/C-1566-2011 FU NCI NIH HHS [CA66268-02]; NINDS NIH HHS [NS35050] NR 42 TC 60 Z9 61 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD OCT-NOV PY 1998 VL 37 IS 10-11 BP 1335 EP 1344 DI 10.1016/S0028-3908(98)00120-8 PG 10 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 142UU UT WOS:000077219400014 PM 9849669 ER PT J AU Seidman, LJ Breiter, HC Goodman, JM Goldstein, JM Woodruff, PWR Rosen, BR AF Seidman, LJ Breiter, HC Goodman, JM Goldstein, JM Woodruff, PWR Rosen, BR TI A functional magnetic resonance imaging study of auditory vigilance with low and high information processing demands SO NEUROPSYCHOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 01-05, 1996 CL NEW YORK, NY SP Soc Biol Psychiat ID POSITRON EMISSION TOMOGRAPHY; SPATIAL WORKING-MEMORY; CONTINUOUS PERFORMANCE-TEST; ANTERIOR CINGULATE CORTEX; HUMAN PREFRONTAL CORTEX; GLUCOSE METABOLIC-RATE; SUSTAINED ATTENTION; HUMAN-BRAIN; FRONTAL-CORTEX; ACTIVATION AB This study identified the brain activations associated with auditory vigilance tasks, using functional magnetic resonance imaging. We created auditory continuous performance tests (CPTs) in which a demanding task (working memory task) was made more difficult than a simple vigilance task by increasing working memory and interference filtering demands. Two cohorts of normal male controls performed significantly worse on the working memory CPT than on the vigilance task. Compared to the Vigilance task, performance of the working memory task produced significant signal change in lateral and medial prefrontal cortex, precentral cortex, temporal lobe, including insula and hippocampus, parietal-occipital cortex, cingulate, thalamus, and superior colliculus. Performance and degree of activation was associated with an estimate of IQ. Further research should clarify the contributions of working memory and interference filtering to the activated network. C1 Massachusetts Mental Hlth Ctr, Neuropsychol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA USA. Harvard Univ, Sch Med, Dept Neurol & Radiol Serv, Boston, MA USA. Rowland Inst Sci Inc, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Ctr Funct Brain Mapping, Boston, MA 02114 USA. Univ Manchester, Sch Psychiat & Behav Sci, Manchester M13 9PL, Lancs, England. RP Seidman, LJ (reprint author), Massachusetts Mental Hlth Ctr, Neuropsychol Lab, 74 Fenwood Rd, Boston, MA 02115 USA. EM larrys@warren.med.harvard.edu RI Woodruff, Peter/B-5998-2009 FU NIDA NIH HHS [DA 00265]; NIMH NIH HHS [MH 00976 SDA, MH 43518] NR 77 TC 82 Z9 82 U1 0 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD OCT PY 1998 VL 12 IS 4 BP 505 EP 518 DI 10.1037/0894-4105.12.4.505 PG 14 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 131YD UT WOS:000076602100002 PM 9805320 ER PT J AU Daws, LC Lopez, R Frazer, A AF Daws, LC Lopez, R Frazer, A TI Effects of antidepressant treatment on inhibitory avoidance behavior and amygdaloid beta-adrenoceptors in rats SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE inhibitory avoidance; desipramine; phenelzine; fluoxetine; beta(1)-adrenoceptors; amygdala ID POST-TRAINING EPINEPHRINE; ANTI-DEPRESSANT DRUGS; PASSIVE-AVOIDANCE; MEMORY STORAGE; QUANTITATIVE AUTORADIOGRAPHY; TRICYCLIC ANTIDEPRESSANTS; NEUROMODULATORY SYSTEMS; NORADRENERGIC SYSTEM; POTENTIATED STARTLE; INVOLVEMENT AB Chronic treatment of mts with a variety of antidepressants results in the down-regulation of beta(1)-adrenoceptors ill the amygdaloid nuclei. The present study sought to determine if this specific neurochemical effect caused air alteration in inhibitory az,avoidance conditioning, a behavior considered to be mediated by beta-adrenoceptors in the amygdala. Rats treated chronically with either desipramine (DMI) or phenelzine (PHEN), which down-regulate beta(1)-adrenoceptors in the amygdala, or fluoxetine (FLUOX), which does not no this, did not exhibit a deficit in the retention of the inhibitory avoidance task. However, when scopolamine was given prior to acquisition of the task in a nose that, by itself, did not affect retention, DMI- and PHEN-treated rats showed a marked deficit in retention. This effect was also observed after acute administration of these drugs, although they did not down-regulate amygdaloid beta(1)-adrenoceptors at this time. It seems that the ability of these antidepressants to potentiate the amnesic effect of scopolamine is unrelated to their effect on beta(1)-adrenoceptor number in the amygdala and that the extent of antidepressant-induced amygdaloid beta(1)-adrenoceptor down-regulation is not sufficient, by itself, to cause a deficit in an inhibitory avoidance task. (C) 1998 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Mem Vet Hosp, San Antonio, TX USA. RP Daws, LC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIMH NIH HHS [MH29094] NR 60 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 OCT PY 1998 VL 19 IS 4 BP 300 EP 313 DI 10.1038/sj.npp.1395200 PG 14 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 109RN UT WOS:000075337100006 PM 9718593 ER PT J AU Kano, T Shimizu-Sasamata, M Huang, PL Moskowitz, MA Lo, EH AF Kano, T Shimizu-Sasamata, M Huang, PL Moskowitz, MA Lo, EH TI Effects of nitric oxide synthase gene knockout on neurotransmitter release in vivo SO NEUROSCIENCE LA English DT Article DE nitric oxide; glutamate; GABA; NMDA; microdialysis ID LONG-TERM POTENTIATION; IN-VIVO; MICE LACKING; HIPPOCAMPUS; INHIBITION; ACID; NORADRENALINE; ENHANCEMENT; DEFICIENT; MESSENGER AB Nitric oxide serves as a diffusible messenger within the neuronal networks of the brain, Recent studies have suggested that nitric oxide may amplify neurotransmitter release via its ability to diffuse in a retrograde manner from postsynaptic to presynaptic neurons, Two isoforms of nitric oxide synthase may be present in neurons: Type I nitric oxide synthase (neuronal isoform) and Type III nitric oxide synthase (endothelial isoform). In this study, we examined the role of nitric oxide as an amplifier of neurotransmitter release by using K+ and N-methyl-D-aspartate stimulations via microdialysis probes located in cortex, striatum, and hippocampus, We compared responses obtained in wild-type mice versus knockout mice deficient in either neuronal isoform of nitric oxide synthase or endothelial isoform of nitric oxide synthase gene expression. No significant differences in glutamate and GABA release were observed between knockout mice and wild-type mice after K+ stimulations. In contrast, N-methyl-D-aspartate-stimulated glutamate release in cortex was significantly reduced in the neuronal NOS knockout mice, and N-methyl-D-aspartate-stimulated GABA release was significantly reduced in all brain regions of endothelial NOS knockout mice. These data suggest that the two nitric oxide synthase isoforms, most likely due to their specific neuronal localizations, may serve different roles in the modulation of excitatory versus inhibitory neurotransmission in mammalian brain, (C) 1998 IBRO, Published by Elsevier Science Ltd. C1 Harvard Univ, Dept Neurol, Neuroprotect Res Lab, Massachusetts Gen Hosp,Sch Med, Charlestown, MA 02129 USA. Harvard Univ, Dept Radiol, Neuroprotect Res Lab, Massachusetts Gen Hosp,Sch Med, Charlestown, MA 02129 USA. Harvard Univ, Dept Neurol, Stroke & Neurovasc Regulat Lab, Massachusetts Gen Hosp,Sch Med, Charlestown, MA 02129 USA. Harvard Univ, Dept Neurosurg, Stroke & Neurovasc Regulat Lab, Massachusetts Gen Hosp,Sch Med, Charlestown, MA 02129 USA. Harvard Univ, Cardiovasc Res Ctr, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Lo, EH (reprint author), Harvard Univ, Dept Neurol, Neuroprotect Res Lab, Massachusetts Gen Hosp,Sch Med, E Bldg 149,Room 2322, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS32806, NS10828, NS37074] NR 36 TC 81 Z9 86 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD OCT PY 1998 VL 86 IS 3 BP 695 EP 699 DI 10.1016/S0306-4522(98)00179-1 PG 5 WC Neurosciences SC Neurosciences & Neurology GA ZX492 UT WOS:000074521600001 PM 9692709 ER PT J AU Kosinski, CM Standaert, DG Testa, CM Penney, JB Young, AB AF Kosinski, CM Standaert, DG Testa, CM Penney, JB Young, AB TI Expression of metabotropic glutamate receptor 1 isoforms in the substantia nigra pars compacta of the rat SO NEUROSCIENCE LA English DT Article DE basal ganglia; substantia nigra; excitotoxicity; Parkinson's disease; metabotropic glutamate receptors; rat ID ALTERNATIVELY SPLICED FORMS; MESSENGER-RNA EXPRESSION; CENTRAL-NERVOUS-SYSTEM; MESENCEPHALIC NEURONS; CELLULAR-LOCALIZATION; BRAIN-FUNCTION; IN-VITRO; MGLUR1; AGONIST; ACTIVATION AB Metabotropic glutamate receptors, which are linked via G-proteins to second messenger systems, have been implicated in the physiological regulation of dopaminergic neurons of the substantia nigra pars compacta as well as in neurodegeneration. Of the eight known metabotropic glutamate receptors, metabotropic glutamate receptor 1 is the most abundant subtype in the substantia nigra pars compacta. Metabotropic glutamate receptor 1 is alternatively spliced at the carboxy terminal region to yield five variants: 1a, 1b, 1c, 1d and a form recently identified in human brain, 1g. We used an antibody recognizing metabotropic glutamate receptor 1, and another recognizing the splice form 1a only, to study the localization of these receptors in dopaminergic neurons identified by the presence of tyrosine hydroxylase. Metabotropic glutamate receptor immunoreactivity was present within the somata, axons, and dendrites of substantia nigra pars compacta neurons. The 1a splice form specific antibody, however, did not label these cells, suggesting that they express a metabotropic glutamate receptor 1 splice form different from 1a. In situ hybridization with splice form-specific oligonucleotide probes was used to determine which of the other known metabotropic glutamate receptor 1 splice forms might be present in the substantia nigra pars compacta. Each probe produced a very distinct labelling pattern in the rat brain with the exception of the 1g specific probe which produced only background signal. Substantia nigra pars compacta neurons were most intensely labelled by the metabotropic glutamate receptor 1d splice form specific probe. Metabotropic glutamate receptor 1a was expressed weakly whereas there was no detectable 1b, c, or g signal in the substantia nigra pars compacta. These data demonstrate thar metabotropic glutamate receptor 1 protein is present within the perikarya and processes of dopaminergic neurons in the substantia nigra pars compacta. The majority of this protein is not the la splice form. which is abundant in other brain regions, and may be the 1d isoform. Since splicing alters the carboxy terminus of the receptor, it is likely to affect the interaction of the receptor with intracellular signalling systems. (C) 1998 IBRO. Published by Elsevier Science Ltd. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Young, AB (reprint author), Massachusetts Gen Hosp, Dept Neurol, Fruit St, Boston, MA 02114 USA. OI Standaert, David/0000-0003-2921-8348 FU NIA NIH HHS [AG13671]; NINDS NIH HHS [NS31579] NR 47 TC 46 Z9 46 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD OCT PY 1998 VL 86 IS 3 BP 783 EP 798 DI 10.1016/S0306-4522(97)00654-4 PG 16 WC Neurosciences SC Neurosciences & Neurology GA ZX492 UT WOS:000074521600009 PM 9692717 ER PT J AU Boppart, SA Brezinski, ME Pitris, C Fujimoto, JG AF Boppart, SA Brezinski, ME Pitris, C Fujimoto, JG TI Optical coherence tomography for neurosurgical imaging of human intracortical melanoma SO NEUROSURGERY LA English DT Article DE imaging; infrared; margins; microscopy; optical; stereotactic; tumor ID TUMOR MARGINS; BIOPSY; CT AB OBJECTIVE: Intraoperative identification of brain tumors and tumor margins has been limited by either the resolution of the in vivo imaging technique or the time required to obtain histological specimens. Our objective was to evaluate the feasibility of using optical coherence tomography (OCT) as a high-resolution, real-time intraoperative imaging technique to identify an intracortical melanoma. INSTRUMENTATION: OCT is a new, noncontact, high-speed imaging technology capable of resolutions on the micrometer scale. OCT is analogous to ultrasound B-mode imaging, except that reflections of infrared light, rather than sound, are detected. OCT uses inherent tissue contrast, rather than enhancement with dyes, to differentiate tissue types. The compact, fiberoptic-based design is readily integrated with surgical instruments. METHODS: A portable handheld OCT surgical imaging probe has been constructed for imaging within the surgical field. Cadaveric human cortex with metastatic melanoma was harvested and imaged in two and three dimensions. Changes in optical backscatter intensity were used to identify regions of tumor and to locate tumor margins. Structures within the optical coherence tomographic images were compared with the histological slides. RESULTS: Two-dimensional images showed increased optical backscatter from regions of tumor, which was quantitatively used to determine the tumor margin. The images correlated well with the histological findings. Three-dimensional reconstructions revealed regions of tumor penetrating normal cortex and could be resectioned at arbitrary planes. Subsurface cerebral vascular structures could be identified and were therefore avoided. CONCLUSION: OCT can effectively differentiate normal cortex from intracortical melanoma based on variations in optical backscatter. The high-resolution, high-speed imaging capabilities of OCT may permit the intraoperative identification of tumor and the more precise localization of tumor margins. C1 MIT, Dept Elect Engn & Comp Sci, Elect Res Lab, Cambridge, MA 02139 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. RP Boppart, SA (reprint author), MIT, Dept Elect Engn & Comp Sci, Elect Res Lab, 77 Massachusetts Ave,Room 36-345, Cambridge, MA 02139 USA. RI Boppart, Stephen/C-7338-2009; OI Pitris, Costas/0000-0002-5559-1050 FU NCI NIH HHS [9-RO1-CA75289-01]; NEI NIH HHS [9-RO1-EY11289-12]; NHLBI NIH HHS [1-R29-HL55686-01A1] NR 29 TC 67 Z9 68 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD OCT PY 1998 VL 43 IS 4 BP 834 EP 841 DI 10.1097/00006123-199810000-00068 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 121MT UT WOS:000076018200062 PM 9766311 ER PT J AU Ogilvy, CS Quinones-Hinojosa, A AF Ogilvy, CS Quinones-Hinojosa, A TI Surgical treatment of vertebral and posterior inferior cerebellar artery aneurysms SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article ID INTRACRANIAL DISSECTING ANEURYSM; SUBARACHNOID HEMORRHAGE; MR-ANGIOGRAPHY; ENDOVASCULAR TREATMENT; CIRCULATION ANEURYSMS AB Aneurysms of the vertebral and posterior inferior cerebellar artery (PICA) are uncommon. Surgical approaches to vertebral artery and PICA aneurysms and patient outcome using surgical or endovascular techniques are discussed in this article. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. RP Ogilvy, CS (reprint author), Massachusetts Gen Hosp, Fruit St,Vincent Burnham 710, Boston, MA 02114 USA. NR 51 TC 12 Z9 12 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD OCT PY 1998 VL 9 IS 4 BP 851 EP + PG 11 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 133QL UT WOS:000076697200016 PM 9738111 ER PT J AU Krag, D Weaver, D Ashikaga, T Moffat, F Klimberg, VS Shriver, C Feldman, S Kusminsky, R Gadd, M Kuhn, J Harlow, S Beitsch, P AF Krag, D Weaver, D Ashikaga, T Moffat, F Klimberg, VS Shriver, C Feldman, S Kusminsky, R Gadd, M Kuhn, J Harlow, S Beitsch, P TI The sentinel node in breast cancer - A multicenter validation study SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GAMMA-PROBE; LYMPH-NODE; AXILLARY DISSECTION; MALIGNANT-MELANOMA; SURGERY; ARM; LYMPHADENECTOMY; LOCALIZATION; CARCINOMA; BIOPSY AB Background Pilot studies indicate that probe-guided resection of radioactive sentinel nodes (the first nodes that receive drainage from tumors) can identify regional metastases in patients with breast cancer. To confirm this finding, we conducted a multicenter study of the method as used by 11 surgeons in a variety of practice settings. Methods We enrolled 443 patients with breast cancer. The technique involved the injection of 4 mi of technetium-99m sulfur colloid (1 mCi [37 MBq]) into the breast around the tumor or biopsy cavity. "Hot spots" representing underlying sentinel nodes were identified with a gamma probe. Sentinel nodes subjacent to hot spots were removed. All patients underwent a complete axillary lymphadenectomy. Results The overall rate of identification of hot spots was 93 percent (in 413 of 443 patients). The pathological status of the sentinel nodes was compared with that of the remaining axillary nodes. The accuracy of the sentinel nodes with respect to the positive or negative status of the axillary nodes was 97 percent (392 of 405); the specificity of the method was 100 percent, the positive predictive value was 100 percent, the negative predictive value was 96 percent (291 of 304), and the sensitivity was 89 percent (101 of 114). The sentinel nodes were outside the axilla in 8 percent of cases and outside of level 1 nodes in 11 percent of cases. Three percent of positive sentinel nodes were in nonaxillary locations. Conclusions Biopsy of sentinel nodes can predict the presence or absence of axillary-node metastases in patients with breast cancer. However, the procedure can be technically challenging, and the success rate varies according to the surgeon and the characteristics of the patient. (N Engl J Med 1998; 339:941-6.) (C)1998, Massachusetts Medical Society. C1 Univ Vermont, Ctr Canc, Burlington, VT 05405 USA. Univ Vermont, Dept Surg, Burlington, VT 05405 USA. Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. Univ Vermont, Dept Biometry, Burlington, VT 05405 USA. Sylvester Canc Ctr, Miami, FL USA. Arkansas Canc Res Ctr, Little Rock, AR USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. Benedictine Hosp, Kingston, NY USA. Charleston Area Med Ctr, Charleston, WV USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Baylor Univ, Med Ctr, Dallas, TX USA. St Paul Hosp, Dallas, TX USA. RP Krag, D (reprint author), Univ Vermont, Ctr Canc, Given Bldg E309, Burlington, VT 05405 USA. FU NCI NIH HHS [U01 CA65121-02, P30CA22435] NR 34 TC 1357 Z9 1413 U1 5 U2 26 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 1 PY 1998 VL 339 IS 14 BP 941 EP 946 DI 10.1056/NEJM199810013391401 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 124MW UT WOS:000076186900001 PM 9753708 ER PT J AU Ristow, M Muller-Wieland, D Pfeiffer, A Krone, W Kahn, CR AF Ristow, M Muller-Wieland, D Pfeiffer, A Krone, W Kahn, CR TI Obesity associated with a mutation in a genetic regulator of adipocyte differentiation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID INSULIN-RESISTANCE; RECEPTOR; ADIPOGENESIS; PHOSPHORYLATION; CLONING; GAMMA AB Background There is increasing evidence of genetic factors leading to obesity, but the exact genes involved have not been defined. Peroxisome-proliferator-activated receptor gamma 2 (PPAR gamma 2) is a transcription factor that has a key role in adipocyte differentiation, and therefore mutations of the gene for this factor might predispose people to obesity. Methods We studied 358 unrelated German subjects, including 121 obese subjects (defined as those with a body-mass index [the weight in kilograms divided by the square of the height in meters] of more than 29). We evaluated these subjects for mutations in the gene for PPAR gamma 2 at or near a site of serine phosphorylation at position 114 that negatively regulates the transcriptional activity of the protein, using a polymerase-chain-reaction-based assay coupled with specific endonuclease digestion. The activity of the mutation identified was analyzed by retroviral transfection and overexpression in murine fibroblasts. Results Four of the 121 obese subjects had a missense mutation in the gene for PPAR gamma 2 that resulted in the conversion of proline to glutamine at position 115, as compared with none of the 237 subjects of normal weight (P=0.01). All the subjects with the mutant allele were markedly obese, with body-mass-index values ranging from 37.9 to 47.3, as compared with a mean of 33.6 in the other obese subjects. Overexpression of the mutant gene in murine fibroblasts led to the production of a protein in which the phosphorylation of serine at position 114 was defective, as well as to accelerated differentiation of the cells into adipocytes and greater cellular accumulation of triglyceride than with the wild-type PPAR gamma 2. These effects were similar to those of an in vitro mutation created directly at the Ser114 phosphorylation site. Conclusions A Pro115Gln mutation in PPAR gamma 2 accelerates the differentiation of adipocytes and may cause obesity. (N Engl J Med 1998;339:953-9.) (C)1998, Massachusetts Medical Society. C1 Joslin Diabet Ctr, Div Res, Sect Cellular & Mol Physiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Univ Cologne, Klin & Poliklin Innere Med 2, Cologne, Germany. Ruhr Univ Bochum, Bergmannsheil, Med Klin & Poliklin, D-4630 Bochum, Germany. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Div Res, Sect Cellular & Mol Physiol, 1 Joslin Pl, Boston, MA 02215 USA. RI Ristow, Michael/O-9858-2014 OI Ristow, Michael/0000-0003-2109-2453 FU NIDDK NIH HHS [2 P30 DK 36836, DK 45935] NR 31 TC 387 Z9 408 U1 1 U2 5 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 1 PY 1998 VL 339 IS 14 BP 953 EP 959 DI 10.1056/NEJM199810013391403 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 124MW UT WOS:000076186900003 PM 9753710 ER PT J AU Duska, LR Toth, TL Goodman, A AF Duska, LR Toth, TL Goodman, A TI Fertility options for patients with stages IA2 and IB cervical cancer: Presentation of two cases and discussion of technical and ethical issues SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID CARCINOMA; PREGNANCY; THERAPY AB Background: Ten percent to 15% of women diagnosed with cervical cancer are in their childbearing years. Traditional therapy for stage IA2 and IB lesions, radical hysterectomy, negates future fertility potential. Assisted reproductive technology might offer these women fertility options. Cases: Two cases of young nulliparous women with stage IA2 cervical cancer, who underwent ovarian stimulation and oocyte retrieval followed by radical hysterectomy, were presented to illustrate the technical difficulties of oocyte stimulation and retrieval in the setting of cervical carcinoma. Conclusion: Many issues should be considered when counseling a woman with early-stage cervical cancer about future fertility. These include ethical issues of embryo freezing and gestational surrogacy and practical issues of ovarian preservation and transposition. No current guidelines exist to identify appropriate candidates for assisted reproductive technology in this setting. (Obstet Gynecol 1998;92:656-8. (C) 1998 by The American College of Obstetricians and Gynecologists.) C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol & Reprod Endocrinol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Vincent Obstet & Gynecol, Boston, MA 02114 USA. RP Duska, LR (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol & Reprod Endocrinol, Vincent 1, Boston, MA 02114 USA. EM duska.linda@mgh.harvard.edu NR 7 TC 6 Z9 7 U1 0 U2 1 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 OCT PY 1998 VL 92 IS 4 SU S BP 656 EP 658 DI 10.1016/S0029-7844(98)00290-7 PN 2 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 124BF UT WOS:000076159900008 PM 9764652 ER PT J AU Somerville, RPT Shoshan, Y Eng, C Barnett, G Miller, D Cowell, JK AF Somerville, RPT Shoshan, Y Eng, C Barnett, G Miller, D Cowell, JK TI Molecular analysis of two putative tumour suppressor genes, PTEN and DMBT, which have been implicated in glioblastoma multiforme disease progression SO ONCOGENE LA English DT Article DE glioma; PTEN; DMBT; mutation; tumour suppressor; 10q24-26 ID GERMLINE MUTATIONS; HUMAN GLIOMAS; HEREDITARY RETINOBLASTOMA; BRAIN-TUMORS; CHROMOSOME-10; HETEROZYGOSITY; PHOSPHATASE; REGIONS; LOCI AB The transition from low grade astrocytoma to glioblastoma multiforme is almost always accompanied by the loss of genetic markers from chromosome 10. Recently two genes, PTEN/MMAC1/TEP1 and DMBT, have been isolated from chromosome 10q. We have analysed these two genes for mutations in 21 primary glioblastomas, An exon by exon screen of the PTEN gene using SSCP failed to identify any mutations in this tumour series, In contrast, 38% of tumours showed intragenic homozygous deletions in the DMBT gene, The fact that the majority of gliomas do not carry mutations in either of these genes suggests that there may still be other genes on chromosome 10 which are important in the development of glioblastoma multiforme. C1 Cleveland Clin Fdn, Lerner Res Inst, Dept Neurosci, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Neurosurg, Cleveland, OH 44195 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Somerville, RPT (reprint author), Cleveland Clin Fdn, Lerner Res Inst, Dept Neurosci, 9500 Euclid Ave,NC30, Cleveland, OH 44195 USA. OI Cowell, John/0000-0002-2079-5950; Eng, Charis/0000-0002-3693-5145 NR 28 TC 60 Z9 60 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 1 PY 1998 VL 17 IS 13 BP 1755 EP 1757 DI 10.1038/sj.onc.1202066 PG 3 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 124UH UT WOS:000076200100015 PM 9796706 ER PT J AU Bunnell, CA Winer, EP AF Bunnell, CA Winer, EP TI Oral 5-FU analogues in the treatment of breast cancer SO ONCOLOGY-NEW YORK LA English DT Article ID CONTINUOUS 5-FLUOROURACIL; INFUSION; LEUCOVORIN; CARCINOMA; CYCLOPHOSPHAMIDE; FLUOROURACIL; COMBINATION; THERAPY; CALCIUM; TRIAL AB Three oral 5-fluorouracil (5-FU) therapies have been approved by the US Food and DI ng Administration or are in development for the treatment of patients with breast cancer: capecitabine, UFT, and 5-FU/eniluracil. Capecitabine has been approved for breast cancer patients whose disease is paclitaxel-resistant, and either anthracycline-resistant or for whom further anthracycline use in not indicated A response rate of 20% was observed in an open-label phase II trial of capecitabine in heavily pretreated patients with metastatic breast cancer Diarrhea and hand-foot syndrome were the most frequently reported toxicities. In a randomized phase II study of capecitabine vs paclitaxel in breast cancer patients who had failed anthracyclines, response rates were 36% for capecitabine vs 21% for paclitaxel, Several phase II trials of 5-FU/eniluracil in breast cancer are ongoing, Preliminary response data from one of these trials on 31 patients with anthracycline- and taxane-resistant advanced breast cancer showed a 16% partial response rate, Grade 3-4 treatment-related toxicities included diarrhea (8%), nausea (3%), and granulocytopenia (3%). In Japan, UFT is widely used for the treatment of breast cancer in both the adjuvant and metastatic settings, through studies in the United Stares are just getting under way, A phase II trial conducted in Madrid, Spain evaluated the combination of UFT, methotrexate, and leucovorin as salvage therapy for breast cancer patients. The overall response rate was 38% among 21 patients, and diarrhea was the most common toxicity, Many questions remain unanswered about the optimal use of oral 5-FU agents in breast cancer. There seems little question that these agents have substantial activity and will find a glace in the therapeutic armamentarium. C1 Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA. RP Winer, EP (reprint author), Dana Farber Canc Inst, Breast Oncol Ctr, 44 Binney St, Boston, MA 02115 USA. NR 33 TC 19 Z9 19 U1 0 U2 1 PU P R R INC PI HUNTINGTON PA 17 PROSPECT ST, HUNTINGTON, NY 11743 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD OCT PY 1998 VL 12 IS 10 SU 7 BP 39 EP 43 PG 5 WC Oncology SC Oncology GA 140BU UT WOS:000077067500007 PM 9830624 ER PT J AU Wallner, KE AF Wallner, KE TI The Stock/Ferrari/Stone article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID PROSTATE-CANCER; RADIATION C1 VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Seattle, WA USA. RP Wallner, KE (reprint author), VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Seattle, WA USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI HUNTINGTON PA 17 PROSPECT ST, HUNTINGTON, NY 11743 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD OCT PY 1998 VL 12 IS 10 BP 1475 EP 1476 PG 2 WC Oncology SC Oncology GA 139QC UT WOS:000077039500012 ER PT J AU Ayyala, RS Zurakowski, D Smith, JA Monshizadeh, R Netland, PA Richards, DW Layden, WE AF Ayyala, RS Zurakowski, D Smith, JA Monshizadeh, R Netland, PA Richards, DW Layden, WE TI A clinical study of the Ahmed glaucoma valve implant in advanced glaucoma SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Ophthalmology CY OCT 29, 1997 CL SAN FRANCISCO, CALIFORNIA SP Amer Acad Ophthalmol ID PLATE MOLTENO IMPLANT; CHAMBER TUBE SHUNT; COMPLICATED GLAUCOMAS; SINGLE-PLATE; NEOVASCULAR GLAUCOMA; ENCIRCLING BAND; EXPERIENCE; TRIAL AB Objective: To assess clinical outcomes and establish the incidence and management of a hypertensive phase (HP) (defined as intraocular pressure [IOP] > 21 mmHg in the first 6 postoperative months) in patients with Ahmed glaucoma valve implant. Design: Retrospective noncomparative case series. Participants A total of 85 patients were included in the current study, including consecutive patients who had intractable glaucoma and underwent Ahmed valve implant insertion at the University Glaucoma Center, Tampa, Florida (DWR and WEL) and the Massachusetts Eye and Ear Infirmary (PAN) between January 1993 and June 1997, Only patients with a minimum of 6 months' follow-up were included. Intervention: Ahmed glaucoma-valve implant insertion to control intractable glaucoma was performed. Main Outcome Measures: Success was defined as IOP less than 22 mmHg and greater than 4 mmHg on the last two visits, a decrease of no more than two lines in the visual acuity and no additional surgical interventions to control IOP. Results: The cumulative probability of success at 12 months was 77%, A total of 26 patients (30.6%) failed during the study period, and 70 patients (82%) exhibited HP. Hypertensive phase peaked at 1 month after the operation and stabilized at 6 months. There were 34 patients (48%) with HP who were controlled with additional medications: 14 (20%) with needling and 5-fluorouracil injections and 20 (28%) who needed secondary surgical intervention, There were 8 patients (9.4%) who exhibited hypotony (<5 mmHg) on postoperative day 1 and 3 (3.5%) at 3 months. Visual acuity returned to baseline between 3 and 6 months after the operation. The major complications associated with the valve were hyphema in 14 cases (16.5%), suprachoroidal hemorrhage in 4 cases (4.7%), end-plate exposure in 10 cases (11.7%), tube exposure in 6 cases (7%), tube block in 4 cases (4.7%), loss of vision in 5 cases (5.8%), and corneal graft failure in 4 (30%) of 13 cases with clear grafts. Conclusions: The overall success rate is comparable to that of prior studies using different implants. The majority of the patients exhibit an HP that peaks at 1 month, with gradual stabilization over 6 months. One third of the patients needed secondary surgical intervention to control the HP. The incidence of postoperative hypotony and flat or shallow anterior chambers is very low after Ahmed glaucoma valve insertion. C1 Univ S Florida, Inst Eye, Dept Ophthalmol, Tampa, FL 33612 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Radiol Res Comp & Biostat, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Boston Univ, Med Ctr Hosp, Univ Eye Associates Inc, Boston, MA 02215 USA. Univ Tennessee, Dept Ophthalmol, Memphis, TN 38163 USA. Univ Tampa, Glaucoma Ctr, Tampa, FL 33606 USA. RP Ayyala, RS (reprint author), Univ S Florida, Inst Eye, Dept Ophthalmol, 12901 Bruce B Downs Blvd,MDC 21, Tampa, FL 33612 USA. NR 17 TC 149 Z9 157 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD OCT PY 1998 VL 105 IS 10 BP 1968 EP 1976 DI 10.1016/S0161-6420(98)91049-1 PG 9 WC Ophthalmology SC Ophthalmology GA 127JW UT WOS:000076348300049 PM 9787371 ER PT J AU Smith, DJ King, WF Akita, H Taubman, MA AF Smith, DJ King, WF Akita, H Taubman, MA TI Association of salivary immunoglobulin A antibody and initial mutans streptococcal infection SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE Streptococcus mutans; salivary; IgA antibody; colonization ID IGA ANTIBODY; VIRIDANS STREPTOCOCCI; INFANTS; COLONIZATION; ACQUISITION; PREDENTATE; CHILDREN; ANTIGENS; MOTHERS; HUMANS AB We explored the relationship between mutans streptococcal infection and the development of salivary IgA antibody during initial colonization. Repetitive swabbing (n=292) of the teeth of 33 children revealed that 45% became infected with mutans streptococci between 13 and 36 months of age. In contrast, mutans streptococci could not be detected in 18 children whose last sample was taken at 39-81 months of age (median age=62 months). During the period of mutans streptococcal infectivity, immunoglobulin A (IgA) antibody to several mutans streptococcal antigens appeared in most children, whether or not infection had been demonstrated. Robust responses to mutans streptococcal components occurred during or shortly after, but not before the period of mutans streptococcal infectivity. No consistent differences were observed among the summarized patterns of response of infected and uninfected groups of children, although the IgA Western blot patterns of individual subjects were often quite distinct. For example, sets of siblings, who would be presumed to be challenged with similar maternal mutans streptococcal clonotypes, were shown to develop qualitatively different salivary IgA responses to mutans streptococcal components. These results support a discrete period for mutans streptococcal infection and may suggest that the level of maternal infection is a factor in the success of infection of the child during this period. The data also suggest that exposure to mutans streptococci is a sufficient condition for robust mucosal IgA responses to mutans streptococcal antigens during the period of infectivity and that these responses may be different, even among siblings. C1 Forsyth Dent Ctr, Dept Immunol, Boston, MA 02115 USA. Tohoku Univ, Sch Dent, Oral Anat Dept 2, Sendai, Miyagi, Japan. RP Smith, DJ (reprint author), Forsyth Dent Ctr, Dept Immunol, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-06153] NR 32 TC 29 Z9 31 U1 0 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD OCT PY 1998 VL 13 IS 5 BP 278 EP 285 DI 10.1111/j.1399-302X.1998.tb00708.x PG 8 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA 123HG UT WOS:000076119300003 PM 9807119 ER PT J AU Miller, EJ Dodson, TB AF Miller, EJ Dodson, TB TI The risk of serious odontogenic infections in HIV-positive patients - A pilot study SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-C; PROGRESSION; AIDS AB Objective. The purpose of this study was to perform a preliminary test of the hypothesis that patients infected with the human immunodeficiency virus (HIV) have an increased risk for serious odontogenic infections in comparison with HIV-negative patients. Study design. To address the research purpose, we used a case-control study design. A case was a serious odontogenic infection requiring inpatient management. A central was a nonserious odontogenic infection that could be managed on an outpatient basis. The ratio of controls to cases was 2:1. HIV status was determined by record review. Results. The sample was composed of 300 patients. Sixteen patients (5%) were HIV-positive. Overall, 37.5% of the HIV-positive patients had serious infections; this compared with 33% of the HIV-negative patients (odds ratio = 1.21; 95% confidence interval = 0.43-3.44; P = .79). Conclusions, The results of this pilot study suggest that HIV-positive patients do not have an increased risk for developing serious odontogenic infections. C1 Emory Univ, Sch Med, Dept Surg, Div Oral Maxillofacial Surg, Atlanta, GA 30322 USA. RP Dodson, TB (reprint author), Massachusetts Gen Hosp, Dept Oral Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. NR 19 TC 12 Z9 12 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD OCT PY 1998 VL 86 IS 4 BP 406 EP 409 DI 10.1016/S1079-2104(98)90364-X PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 129RN UT WOS:000076476900007 PM 9798222 ER PT J AU Harthorne, JW AF Harthorne, JW TI Theft deterrent systems: A threat for medical device recipients or an industry cat fight? SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Editorial Material ID INTERFERENCE; PACEMAKERS C1 Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. RP Harthorne, JW (reprint author), Massachusetts Gen Hosp, Cardiac Unit, CC 478,55 Fruit St, Boston, MA 02114 USA. NR 7 TC 9 Z9 10 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD OCT PY 1998 VL 21 IS 10 BP 1845 EP 1846 DI 10.1111/j.1540-8159.1998.tb00001.x PG 2 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 126WZ UT WOS:000076318800001 PM 9793078 ER PT J AU Cassidy, LJ Jellinek, MS AF Cassidy, LJ Jellinek, MS TI Approaches to recognition and management of childhood psychiatric disorders in pediatric primary care SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID CHILDRENS DEPRESSION INVENTORY; MANIFEST ANXIETY SCALE; MENTAL-HEALTH; SYMPTOM CHECKLIST; RATING-SCALES; COMORBIDITY; SAMPLE; PSYCHOPATHOLOGY; MORBIDITY; SERVICES AB Psychosocial dysfunction in children, first recognized more than 20 years ago as the "new morbidity" in pediatric practice, is now the leading cause of disability in childhood and adolescence.(15-17, 30) Epidemiologic research indicates that 14% to 20% of American children have one or more psychiatric disorders in the moderate to severe range,(10) and the overall prevalence is rising.(1) As many as half of all pediatric office visits reflect behavioral, psychosocial, and educational concerns, and most children in the United States with a psychiatric disorder receive care only from their pediatricians, making primary care clinics the "de facto mental health service" for most children in need of such care.(14) In addition, with the advent of managed care, pediatricians are increasingly becoming "gatekeepers" who identify and refer children with mental health problems. Despite the growing prevalence of psychiatric illness in children, four out of five children with diagnosable behavioral and emotional problems are not identified by their pediatricians, and even fewer receive mental health services.(14) Furthermore, children are more likely to be recognized and treated if their behavior upsets or annoys adults than if their psychiatric symptoms lead to school failure and poor functioning at home. Poor children are among the least likely to receive adequate mental health attention.(44) Numerous studies have shown that untreated mental health problems result in high rates of medical services(29) and place children at high risk for chronic psychosocial morbidity, including antisocial and self-injurious behavior.(31, 33, 40) Some obstacles to recognition by pediatricians are long-standing. Parents may be reluctant to raise psychosocial concerns, pediatricians map wish to avoid stigmatizing labels, pediatric training underemphasizes mental health and behavioral problems, and reimbursement for psychosocial services is low or unavailable for pediatricians. New hurdles have emerged as efforts to contain medical costs, such as managed care systems and capitation, have led to shortened office visits, larger panel sizes, constraints on referrals, and even disincentives to recognize children in need.(23) This introduction describes the most common psychiatric conditions presenting to pediatric clinics and discusses approaches to identification, assessment of severity, and treatment planning. Within treatment planning are highlighted guidelines for consulting a pediatric psychopharmacologist because medication is often an important feature of a comprehensive treatment plan. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Child Psychiat Serv, Boston, MA 02114 USA. McLean Hosp, Child Psychiat Serv, Boston, MA USA. RP Cassidy, LJ (reprint author), Charlestown Hlth Care Ctr, 73 High St, Charlestown, MA 02129 USA. NR 45 TC 57 Z9 57 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD OCT PY 1998 VL 45 IS 5 BP 1037 EP + DI 10.1016/S0031-3955(05)70061-4 PG 17 WC Pediatrics SC Pediatrics GA 125UX UT WOS:000076256400003 PM 9884674 ER PT J AU Daly, JM Wilens, T AF Daly, JM Wilens, T TI The use of tricyclic antidepressants in children and adolescents SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; OBSESSIVE-COMPULSIVE DISORDER; MAJOR DEPRESSIVE DISORDER; SUDDEN-DEATH; PHARMACOKINETIC PARAMETERS; CLOMIPRAMINE TREATMENT; DESIPRAMINE TREATMENT; IMIPRAMINE TREATMENT; TOURETTES-SYNDROME; ANXIETY DISORDERS AB Tricyclic antidepressants (TCAs) have had a substantial role in the pharmacotherapy of children and adolescents over the past three decades. Recent concern about the TCA-associated adverse cardiovascular effects in the pediatric population has resulted in decreased use of these medications based on a limited amount of data. This article reviews the current literature regarding the clinical indications, pharmacology, and adverse effects of TCAs. Also, suggested practice guidelines based on research data and the authors' clinical experience are provided. C1 Four Winds Hosp, Dept Pediat, Div Child & Adolescent Psychiat, Saratoga Springs, NY 12866 USA. Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. RP Daly, JM (reprint author), Four Winds Hosp, Dept Pediat, Div Child & Adolescent Psychiat, 30 Crescent Ave, Saratoga Springs, NY 12866 USA. NR 92 TC 31 Z9 34 U1 3 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD OCT PY 1998 VL 45 IS 5 BP 1123 EP + DI 10.1016/S0031-3955(05)70065-1 PG 14 WC Pediatrics SC Pediatrics GA 125UX UT WOS:000076256400007 PM 9884678 ER PT J AU Devellis, P Thomas, SH Wedel, SK Stein, JP Vinci, RJ AF Devellis, P Thomas, SH Wedel, SK Stein, JP Vinci, RJ TI Prehospital fentanyl analgesia in air-transported pediatric trauma patients SO PEDIATRIC EMERGENCY CARE LA English DT Article DE pediatric analgesia; trauma; fentanyl; prehospital; aeromedical transport ID CONSCIOUS SEDATION; EMERGENCY; CHILDREN AB Objective: To review the 5.5-year safety record of a protocol guiding fentanyl administration to pediatric trauma patients undergoing aeromedical transport. Methods: Retrospective review of an urban aeromedical program's trauma scene responses from October 1991 to March 1997 identified the study population as all pediatric patients (age <15 years) receiving fentanyl for analgesia during air transport. Patients receiving fentanyl concurrently with other agents, eg, paralytics, were not studied. The air transport team consisted of a flight nurse and flight paramedic who provided protocol-driven patient care with off-line medical control. Study patients' flight records were reviewed to determine vital signs (systolic blood pressure [SBP], heart rate [HR], and oxygen saturation [SAT]) before and after fentanyl administration. Postfentanyl vital signs were reviewed for evidence of hemodynamic or ventilatory compromise, Pre- and postfentanyl vital signs were compared with the paired t test (P < 0.05). Flight records mere also analyzed for narrative information, eg, naloxone administration and assisted ventilation, indicative of fentanyl side effects. Results: Fentanyl (0.33-5.0 mu g/kg) was administered 211 times to 131 patients who had a median age of 6.2 years (0.1-14 years), median Glasgow coma score (GCS) of 9 (3-15), and a mean pediatric trauma score of 8.3 +/- 2.4. Seventy-nine (60.3%) patients were intubated; these patients received 139 (65.9%) of the 211 total fentanyl doses. No adverse effects from fentanyl were noted in flight record narratives. The median interval between fentanyl administration and postfentanyl vital sign assessment was 9.5 minutes (1-35 minutes). Median postfentanyl changes in SEP and HR were -4.7 and -2.9%, respectively, No patient became hypotensive after fentanyl administration. In nonintubated patients, mean postfentanyl SAT (99.2 +/- 1.3%) was not significantly different (P = 0.70) from prefentanyl SAT (99.1 +/- 1.3%), and no patient was noted to have clinically significant SAT decrement after fentanyl. Conclusion: Retrospective review of more than five years of prehospital fentanyl administration revealed no untoward events. Although prospective definitive demonstration of fentanyl's field use is pending, it is reasonable to continue discretionary fentanyl administration to injured pediatric children in pain. C1 Harvard Univ, Dept Emergency Med, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Thomas, SH (reprint author), Harvard Univ, Dept Emergency Med, Massachusetts Gen Hosp, Sch Med, 32 Fruit St,Clin 116, Boston, MA 02114 USA. NR 12 TC 20 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0749-5161 J9 PEDIATR EMERG CARE JI Pediatr. Emerg. Care PD OCT PY 1998 VL 14 IS 5 BP 321 EP 323 PG 3 WC Emergency Medicine; Pediatrics SC Emergency Medicine; Pediatrics GA 133CD UT WOS:000076668100001 PM 9814395 ER PT J AU Karron, RA Ambrosino, DM AF Karron, RA Ambrosino, DM TI Respiratory syncytial virus vaccines SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article ID MESSENGER-RNA; IMMUNOGENICITY; EXPRESSION; CHILDREN; SAFETY C1 Johns Hopkins Univ, Baltimore, MD 21218 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Karron, RA (reprint author), Johns Hopkins Univ, Baltimore, MD 21218 USA. NR 10 TC 10 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD OCT PY 1998 VL 17 IS 10 BP 919 EP 920 DI 10.1097/00006454-199810000-00014 PG 2 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 131CE UT WOS:000076557500013 PM 9802636 ER PT J AU Amin-Hanjani, S Robertson, R Arginteanu, MS Scott, RM AF Amin-Hanjani, S Robertson, R Arginteanu, MS Scott, RM TI Familial intracranial arteriovenous malformations - Case report and review of the literature SO PEDIATRIC NEUROSURGERY LA English DT Article DE arteriovenous malformation, familial; heredity; magnetic resonance imaging ID HEREDITARY HEMORRHAGIC TELANGIECTASIA; BRAIN AB Familial intracranial arteriovenous malformations (AVMs) are rare, We describe a father and son both presenting in childhood with cerebral AVMs, Both patients underwent successful surgical extirpation of the AVM, Familial AVMs present at a young age and tend to be multiple, as was the case in one of our patients. Imaging of asymptomatic family members may detect previously undiagnosed AVMs, and we recommend screening of the relatives of patients with a strong family history of such lesions. C1 Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Mt Sinai Hosp, Dept Neurosurg, New York, NY 10029 USA. RP Scott, RM (reprint author), Childrens Hosp, Dept Neurosurg, 300 Longwood Ave, Boston, MA 02115 USA. OI Robertson, Richard/0000-0001-8811-4405 NR 27 TC 13 Z9 13 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1016-2291 J9 PEDIATR NEUROSURG JI Pediatr. Neurosurg. PD OCT PY 1998 VL 29 IS 4 BP 208 EP 213 DI 10.1159/000028723 PG 6 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 159JD UT WOS:000078168100007 PM 9876251 ER PT J AU Weissig, V Whiteman, KR Torchilin, VP AF Weissig, V Whiteman, KR Torchilin, VP TI Accumulation of protein-loaded long-circulating micelles and liposomes in subcutaneous Lewis lung carcinoma in mice SO PHARMACEUTICAL RESEARCH LA English DT Article DE tumor targeting; protein delivery; drug carriers; micelles; long-circulating liposomes; Lewis lung carcinoma; tumor targeting ID HUMAN TUMOR XENOGRAFT; CANCER-CHEMOTHERAPY; PERMEABILITY; DELIVERY; AGENTS AB Purpose. The purpose of our work was to compare the biodistribution and tumor accumulation of a liposome- or micelle-incorporated protein in mice bearing subcutaneously-established Lewis lung carcinoma. Methods. A model protein, soybean trypsin inhibitor (STI) was modified with a hydrophobic residue of N-glutaryl-phosphatidyl-ethanolamine (NGPE) and incorporated into both polyethyleneglycol (MW 5000)-distearoyl phosphatidyl ethanolamine (PEG-DSPE) micelles (< 20 nm) and PEG-DSPE-modified long-circulating liposomes (ca. 100 nm). The protein was labeled with In-111 via protein-attached diethylene triamine pentaacetic acid (DTPA), and samples of STI-containing liposomes or micelles were injected via the tail vein into mice bearing subcutaneously-established Lewis lung carcinoma. At appropriate time points, mice were sacrified and the radioactivity accumulated in the tumor and main organs was determined. Results. STI incorporated into PEG-lipid micelles accumulates in subcutaneously established Lewis lung carcinoma in mice better than the same protein anchored in long-circulating PEG-liposomes. Conclusions. Small-sized long-circulating delivery systems, such as PEG-lipid micelles, are more efficient in the delivery of protein to Lewis lune carcinoma than larger long-circulating liposomes. C1 Massachusetts Gen Hosp, Dept Radiol, Ctr Imaging & Pharmaceut Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Torchilin, VP (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Imaging & Pharmaceut Res, 149 13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [1 R01 HL55519-01A2] NR 17 TC 121 Z9 127 U1 2 U2 10 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD OCT PY 1998 VL 15 IS 10 BP 1552 EP 1556 DI 10.1023/A:1011951016118 PG 5 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 128JL UT WOS:000076402600008 PM 9794497 ER PT J AU Lin, GC Tsoukas, ML Lee, MS Gonzalez, S Vibhagool, C Anderson, RR Kollias, N AF Lin, GC Tsoukas, ML Lee, MS Gonzalez, S Vibhagool, C Anderson, RR Kollias, N TI Skin necrosis due to photodynamic action of benzoporphyrin depends on circulating rather than tissue drug levels: Implications for control of photodynamic therapy SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID MOUSE-TUMOR MODEL; LIGHT DOSE DEPENDENCE; L-ASPARTYL CHLORIN-E6; RING-A BPD; PHOTOSENSITIZING PROPERTIES; MURINE TUMOR; HEMATOPORPHYRIN; INVIVO; INVITRO; PHOTOIMMUNOTHERAPY AB In an ideal world, photodynamic therapy (PDT) of abnormal tissue would reliably spare the surrounding normal tissue. Normal tissue responses set the limits for light and drug dosimetry. The threshold fluence for necrosis (TFN) was measured in normal skin following intravenous infusion with a photosensitizer, benzoporphyrin derivative monoacid ring A (BPD-MA) Verteporfin(R) as a function of drug dose (0.25-2.0 mg/kg), wavelength of irradiation (458 and 690 mm) and time interval (0-5 h) between drug administration and irradiation. The BPDMA levels were measured in plasma and skin tissue to elucidate the relationship between TFN, drug kinetics and biodistribution. The PDT response of normal skin was highly reproducible. The TFN for 458 and 690 mn wavelengths was nearly identical and the estimated quantum efficiency for skin response was equal at these two wavelengths. Skin phototoxicity, quantified in terms of 1/TFN, closely correlated with the plasma pharmacokinetics rather than the tissue pharmacokinetics and was quadratically dependent on the plasma drug concentration regardless of the administered drug dose or time interval between drug and light exposure. This study strongly suggests that noninvasive measurements of the circulating drug level at the time of light treatment will be important for setting optimal light dosimetry for PDT with liposomal BPD-MA, a vascular photosensitizer. C1 Harvard Univ, Sch Med, Wellman Labs Photomed, Dept Dermatol,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kollias, N (reprint author), Harvard Univ, Sch Med, Wellman Labs Photomed, Dept Dermatol,Massachusetts Gen Hosp, BHX 630, Boston, MA 02114 USA. EM kollias@helix.mgh.harvard.edu FU NIAMS NIH HHS [2-T32-AR07098-21, 2-T32-AR07098-20] NR 52 TC 21 Z9 21 U1 1 U2 4 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD OCT PY 1998 VL 68 IS 4 BP 575 EP 583 DI 10.1111/j.1751-1097.1998.tb02516.x PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 130VB UT WOS:000076540100022 PM 9796441 ER PT J AU Biggs, PJ AF Biggs, PJ TI Evidence for a significant timer error on a linear accelerator: consequences for a special therapy application SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 39th American-Association-of-Physicists-in-Medicine Annual Meeting CY JUL 27-31, 1997 CL MILWAUKEE, WISCONSIN SP Amer Assoc Physicists Med AB A significant timer error has been found on a linear accelerator used for intraoperative radiation therapy. Since typical treatment doses range up to 20 Gy, calibrations that do not account for this effect can incur a large dosimetry error. The effect is dose rate dependent, but energy independent. For a dose rate of 900 cGy min(-1), the error in dose calibration varies between 2 and 3% for an average of 2.5%. At dose rates of 600 and 300 cGy min(-1), the error was 1.7% and 0.8% respectively. The average timer error at 900 cGy min(-1) was found to be 1.2 +/- 0.1 monitor units. It is argued that even a small timer error has serious dosimetry consequences for the implementation of intensity modulated radiation therapy. C1 Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiat Oncol, Div Radiat Biophys, Boston, MA 02114 USA. RP Biggs, PJ (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiat Oncol, Div Radiat Biophys, Boston, MA 02114 USA. NR 2 TC 10 Z9 10 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD OCT PY 1998 VL 43 IS 10 BP 3139 EP 3143 DI 10.1088/0031-9155/43/10/031 PG 5 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 130PR UT WOS:000076529300031 PM 9814540 ER PT J AU Miller, TA Wyatt, LE Rudkin, GH AF Miller, TA Wyatt, LE Rudkin, GH TI Staged skin and subcutaneous excision for lymphedema: A favorable report of long-term results SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT 76th Annual Meeting of the American-Association-of-Plastic-Surgeons CY MAY 18-21, 1997 CL PORTLAND, OREGON SP Amer Assoc Plast Surgeons ID VENOUS ANASTOMOSES; LYMPHOEDEMA; EXTREMITIES; OPERATION AB Numerous surgical procedures have been proposed for the management of lymphedema. The postoperative results vary, and unfortunately none of the procedures are curative. As a result, some degree of recurrence of leg edema is seen in all patients postoperatively. Reported here is a long-term follow-up of patients with lower extremity lymphedema managed by skin and subcutaneous tissue excision. Thirty-eight patients (6 male; 32 female) with with lower extremity lymphedema have been followed up for an average of 14 (3 to 27) years after staged subcutaneous excisions performed beneath skin flaps. Seven patients had been treated previously by other procedures. Of the 38 lymphedema patients, 10 patients developed edema after pelvic or grain ablative surgery, radiation therapy, or both. Results were documented by various methods: physical examination, circumferential measurements, volume displacement, serial photography, lymphoscintigraphy, and patient survey. Of these, it is believed that photographs are the easiest and as representative as any other method, all of which have seat variability. Of the 35 patients, 30 patients had significant and long-lasting reduction in extremity size associated with improved function and extremity contour. Episodes of recurrent cellulitis were reduced or completely eliminated. No differences in the long-term results were seen in patients with acquired as opposed to congenital lymphedema. Men did not have as much improvement as women. Two patients had no change in leg swelling, and six patients (three men) had progressive swelling after surgery. Partial wound separation occurred immediately postoperatively in one patient, and three patients had loss (less than 2 cm) of the skin flap, all in the ankle region. None of these instances required further surgery, and no other significant complications were encountered. Staged skin and subcutaneous excision beneath skin flaps appears to provide long-lasting improvement for lower extremity lymphedema, regardless of cause, in the majority of patients treated. C1 Univ Calif Los Angeles, Ctr Med, Div Plast & Reconstruct Surg, Sch Med, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Plast Surg Sect, Los Angeles, CA 90073 USA. RP Miller, TA (reprint author), Univ Calif Los Angeles, Ctr Med, Div Plast & Reconstruct Surg, Sch Med, 200 Med Plaza,Suite 669, Los Angeles, CA 90095 USA. NR 40 TC 39 Z9 43 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD OCT PY 1998 VL 102 IS 5 BP 1486 EP 1498 DI 10.1097/00006534-199810000-00022 PG 13 WC Surgery SC Surgery GA 126PL UT WOS:000076285500022 PM 9774002 ER PT J AU Heffel, DF Miller, TA AF Heffel, DF Miller, TA TI Treatment of photodamaged skin with topical tretinoin: An update - Discussion SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Editorial Material ID RECEPTORS C1 Univ Calif Los Angeles, Hlth Sci Ctr, Dept Surg, Div Plast & Reconstruct Surg,Res & Surg Serv, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Plast Surg Sect, Res & Surg Serv, Los Angeles, CA USA. RP Miller, TA (reprint author), 200 UCLA Med Plaza,Suite 465, Los Angeles, CA 90095 USA. NR 10 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD OCT PY 1998 VL 102 IS 5 BP 1672 EP 1675 DI 10.1097/00006534-199810000-00054 PG 4 WC Surgery SC Surgery GA 126PL UT WOS:000076285500054 ER PT J AU Yaremchuk, MJ Israeli, D AF Yaremchuk, MJ Israeli, D TI Paranasal implants for correction of midface concavity SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID RECONSTRUCTION AB Central midface concavity was corrected with the placement of porous polyethylene implants in the paranasal area. This simulated the effect of skeletal osteotomies and advancement without altering dental occlusion. Implants were placed to correct congenital, posttraumatic, and cleft-related skeletal midface retrusion in nine patients. In seven of the patients, paranasal augmentation was performed in conjunction with rhinoplasty. There have been no implant-related complications during a mean 33-month follow-up (range 5 to 83 months). Screw fixation of these implants ensures stable positioning and allows precise final contouring during surgery. C1 Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Yaremchuk, MJ (reprint author), Massachusetts Gen Hosp, Div Plast Surg, WACC-453, Boston, MA 02114 USA. NR 18 TC 25 Z9 25 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD OCT PY 1998 VL 102 IS 5 BP 1676 EP 1684 DI 10.1097/00006534-199810000-00055 PG 9 WC Surgery SC Surgery GA 126PL UT WOS:000076285500055 PM 9774030 ER PT J AU Cooley, J Mathieu, B Remold-O'Donnell, E Mandle, RJ AF Cooley, J Mathieu, B Remold-O'Donnell, E Mandle, RJ TI Production of recombinant human monocyte neutrophil elastase inhibitor (rM/NEI) SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID CYSTIC-FIBROSIS; CATHEPSIN-G; POLYMORPHONUCLEAR LEUKOCYTE; PROTEASE; CELLS; EMPHYSEMA; PROTEINASE-3; INFLAMMATION; EXPRESSION; SPUTUM AB Recombinant human monocyte/neutrophil elastase inhibitor (rM/NEI) was expressed with a baculovirus expression system. The purified recombinant protein was shown to inhibit human neutrophil elastase by the formation of a stable equimolar complex, as had been shown for M/NEI isolated from monocyte-derived cell lines. rM/NEI was remarkably stable in aqueous buffers from pH 6 to pH 8, but not in buffers below pH 6. rM/NEI activity was stable when subjected to freeze-thaw cycles and low temperature storage in Tris or phosphate buffers, rM/NEI could also be lyophilized without significant loss of activity. A 1.6-g batch of greater than 95% purity in rM/NEI was obtained by anion exchange and size exclusion chromatography with yields of 7 to 8 mg per liter of cultured insect cells. Methods and protocols were chosen for compatibility with large-scale cGMP production and were suitable for biochemical characterization and preclinical evaluation of rM/NEI as a therapeutic agent for cystic fibrosis. The availability of large amounts of purified rM/NEI will facilitate clinical evaluation of rM/NEI for prevention of the elastase-mediated destruction of lung tissue associated with the morbidity and mortality of cystic fibrosis. (C) 1998 Academic Press. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. CBR Labs Inc, Boston, MA 02115 USA. RP Cooley, J (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL52290] NR 29 TC 12 Z9 12 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD OCT PY 1998 VL 14 IS 1 BP 38 EP 44 DI 10.1006/prep.1998.0951 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 127GB UT WOS:000076341500006 PM 9758749 ER PT J AU Hartman, N Caskey, NH Olmstead, RE Jarvik, ME AF Hartman, N Caskey, NH Olmstead, RE Jarvik, ME TI Nicotine craving and psychiatric diagnosis: Past, present, and future SO PSYCHIATRIC ANNALS LA English DT Article ID SMOKING WITHDRAWAL SYMPTOMS; TRANSDERMAL NICOTINE; TOBACCO WITHDRAWAL; CESSATION; DEPENDENCE; RELAPSE; QUESTIONNAIRE; PREDICTORS; ABSTINENCE; CIGARETTES AB This article provides a brief history of smoking behavior and its transition from accepted norm to medically treatable syndrome. The common methods used to assess craving are described, and the role of the concept of craving within the substance abuse field and its use in diagnosis is characterized. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. RP Olmstead, RE (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,691-B151D T-350, Los Angeles, CA 90073 USA. NR 47 TC 3 Z9 3 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD OCT PY 1998 VL 28 IS 10 BP 547 EP + PG 6 WC Psychiatry SC Psychiatry GA 132TQ UT WOS:000076646500003 ER PT J AU Aravagiri, M Yuwiler, A Marder, SR AF Aravagiri, M Yuwiler, A Marder, SR TI Distribution after repeated oral administration of different dose levels of risperidone and 9-hydroxy risperidone in the brain and other tissues of rat SO PSYCHOPHARMACOLOGY LA English DT Article DE risperidone; 9-hydroxy-risperidone; antipsychotics; tissue distribution; regional brain distribution; brain to plasma level ratio; dose-tissue level relationship; rat ID SCHIZOPHRENIC-PATIENTS; 5-HT2; D-2; METABOLITES; EXCRETION; EFFICACY AB Rats were treated with daily oral doses of 1, 4, and 6 mg/kg risperidone (RSP) and its metabolite, 9-hydroxy-risperidone (9-OH-RSP), for 15 consecutive days. Concentrations of RSP and 9-OH-RSP were measured in plasma, brain, liver, kidney, lungs and fat tissue by high-performance liquid chromatography with electrochemical detection. Non-specific distribution of RSP and 9-OH-RSP in various brain regions was also studied after administration of 6 mg/kg per day oral dose for 15 days. After RSP treatment, concentrations of 9-OH-RSP were higher than those of RSP in plasma and tissues except in brain, where both compounds were present in nearly equal concentrations. Similarly, after 9-OH-RSP treatment, levels of 9-OH-RSP were higher than levels of either RSP or 9-OH-RSP or the sum of RSP and 9-OH-RSP levels measured after treatment with RSP. There was a moderate relationship between RSP dose and tissue levels of RSP and 9-OH-RSP (all r(s) greater than or equal to 0.62, P < 0.01), except in fat. There was also a strong relationship between the dose and tissue levels of 9-OH-RSP (all r(s) 2 0.68, P < 0.005). A significant relationship was found between plasma levels of RSP and brain levels of RSP and 9-OH-RSP (all r(s) greater than or equal to 0.571 P < 0.03) after treatment with RSP. After 9-OH-RSP treatment, a much stronger relationship was observed between plasma and brain 9-OH-RSP levels (r(s) greater than or equal to 0.90, P < 0.005). The plasma concentrations of RSP and 9-OH-RSP appear to reflect their concentrations in brain. The tissue-to-plasma ratios of RSP and 9-OH-RSP were relatively low compared to other antipsychotics. In liver, kidney and lung the tissue to plasma ratio for RSP and 9-OH-RSP after treating with RSP ranged from 0.85 to 3.4. The brain to plasma ratio for RSP and 9-OH-RSP was several-fold lower than that in peripheral tissues. After RSP administration, the mean brain to plasma level ratio for RSP was 0.22, and for 9-OH-RSP to it was 0.04. The brain to plasma ratio of 9-OH-RSP after giving 9-OH-RSP was similarly low (0.04). The low brain/plasma ratio of high potency RSP and 9-OH-RSP may in parr be due to their low lipophilicity, log P = 3.04 and 2.32, respectively, resulting in limited non-specific accumulation in brain tissue. C1 Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Psychopharmacol Unit, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Neurobiochem Lab, Los Angeles, CA 90073 USA. RP Aravagiri, M (reprint author), Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Psychopharmacol Unit, Bldg 210 4,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM kannan@ucla.edu FU NIMH NIH HHS [MH41573] NR 24 TC 51 Z9 55 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD OCT PY 1998 VL 139 IS 4 BP 356 EP 363 DI 10.1007/s002130050726 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 125VN UT WOS:000076257900007 PM 9809856 ER PT J AU Drucker, EA Rivitz, SM Shepard, JAO Boiselle, PM Trotman-Dickenson, B Welch, TJ Maus, TP Miller, SW Kaufman, JA Waltman, AC McLoud, TC Athanasoulis, CA AF Drucker, EA Rivitz, SM Shepard, JAO Boiselle, PM Trotman-Dickenson, B Welch, TJ Maus, TP Miller, SW Kaufman, JA Waltman, AC McLoud, TC Athanasoulis, CA TI Acute pulmonary embolism: Assessment of helical CT for diagnosis SO RADIOLOGY LA English DT Article DE computed tomography (CT), comparative studies; embolism, pulmonary; pulmonary angiography; pulmonary arteries, CT ID VENTILATION-PERFUSION SCINTIGRAPHY; SPIRAL CT; ANGIOGRAPHY; THROMBOEMBOLISM AB PURPOSE: To determine the sensitivity and specificity of helical computed tomography (CT) for the diagnosis of acute pulmonary embolism. MATERIALS AND METHODS: This prospective study included 47 patients who underwent pulmonary arteriography for evaluation for possible acute pulmonary embolism. Tailored helical CT and pulmonary arteriography were performed within 24 hours of each other. Each CT scan was interpreted by two chest radiologists, blinded to arteriographic results, at two institutions. CT scan interpretations were com pared with findings on bilateral selective pulmonary arteriograms interpreted by two vascular radiologists at one institution. RESULTS: Fifteen (32%) of 47 patients had angiographically proved pulmonary embolism. For the readers at the first institution, helical CT had 60% sensitivity, 81% specificity, 60% positive predictive value, 81% negative predictive value, and 75% overall accuracy. For the readers at the second institution, helical CT had 53% sensitivity, 97% specificity, 89% positive predictive value, 82% negative predictive value, and 83% accuracy. CONCLUSION: Detection of pulmonary embolism with helical CT may be less,accurate than previously reported. Given its high specificity but relatively low sensitivity, helical CT may not have the ideal attributes of a first-line imaging study for the diagnosis of pulmonary embolism. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Mayo Clin, Rochester, MN USA. RP Drucker, EA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Founders House,202 Fruit St, Boston, MA 02114 USA. NR 27 TC 155 Z9 167 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 1998 VL 209 IS 1 BP 235 EP 241 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 121QK UT WOS:000076024700038 PM 9769837 ER PT J AU Gaylor, D Ryan, L Krewski, D Zhu, YL AF Gaylor, D Ryan, L Krewski, D Zhu, YL TI Procedures for calculating benchmark doses for health risk assessment SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE benchmark dose; risk assessment; quantal data; clustered data; continuous data ID DEVELOPMENTAL TOXICITY EXPERIMENTS; LONGITUDINAL DATA-ANALYSIS; RESPONSE MODELS; TOXICOLOGICAL EXPERIMENTS; FETAL WEIGHT; TERATOLOGICAL EXPERIMENTS; TRINOMIAL RESPONSES; CONTINUOUS OUTCOMES; BINARY DATA; MALFORMATION AB Safety assessment for noncancer health effects generally has been based upon dividing a no observed adverse effect (NOAEL) by uncertainty (safety) factors to provide an acceptable daily intake (ADI) or reference dose (RfD). Since the NOAEL does not utilize all of the available dose-response data, allows higher ADI from poorer experiments, and may have an unknown, unacceptable level of risk, the benchmark dose (BD) with a specified, controlled low level of risk has become popular as an adjunct to the NOAEL or the low observed adverse effect level (LOAEL) in the safety assessment process. The purpose of this paper is to summarize statistical procedures available for calculating BDs and their confidence limits for noncancer endpoints. Procedures are presented and illustrated for quantal (binary), quasicontinuous (proportion), and continuous data. Quasicontinuous data arise in developmental studies where the measure of an effect for a fetus is quantal (normal or abnormal) but the experimental unit is the mother (litter) so that results can be expressed as the proportion of abnormal fetuses per litter. However, the correlation of effects among fetuses within a litter poses some additional statistical problems. Also, developmental studies usually include some continuous measures, such as fetal body weight or length. With continuous data there generally is not a clear demarcation between normal and adverse measurements. In such cases, extremely high and/or low measurements at some designated percentile(s) can be considered abnormal. Then the probability (risk) of abnormal individuals can be estimated as a function of dose. The procedure for estimating a ED with continuous data is illustrated using neurotoxicity data. When multiple measures of adverse effects are available, a BD can be estimated based on a selected endpoint or the appearance of any combination of endpoints. Multivariate procedures are illustrated using developmental and reproductive toxicity data. (C) 1998 Academic Press. C1 Univ S Florida, Dept Epidemiol & Biostat, Tampa, FL 33612 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Hlth Canada, Hlth Protect Branch, Ottawa, ON K1A 0L2, Canada. Carleton Univ, Dept Math & Stat, Ottawa, ON K1A 0L2, Canada. RP Zhu, YL (reprint author), Univ S Florida, Dept Epidemiol & Biostat, 13201 Bruce B Downs Blvd, Tampa, FL 33612 USA. EM yzhu@com1.med.usf.edu RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 62 TC 72 Z9 77 U1 0 U2 8 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD OCT PY 1998 VL 28 IS 2 BP 150 EP 164 DI 10.1006/rtph.1998.1247 PG 15 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 167EV UT WOS:000078620300010 PM 9927564 ER PT J AU Spengler, CM Banzett, RB Systrom, DM Shannon, DC Shea, SA AF Spengler, CM Banzett, RB Systrom, DM Shannon, DC Shea, SA TI Respiratory sensations during heavy exercise in subjects without respiratory chemosensitivity SO RESPIRATION PHYSIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Brain and Breathing - From Cellular Mechanisms to Clinical Implications CY SEP, 1997 CL BOCHUM, GERMANY DE chemosensitivity, hypercapnic response; control of breathing, breathlessness; disease, congenital central hypoventilation syndrome; hypercapnia, breathlessness; mammals, humans, infants; sensation, breathlessness ID CENTRAL HYPOVENTILATION SYNDROME; VENTILATORY RESPONSES; LIMITING FACTOR; BREATHLESSNESS; CHILDREN; HUMANS; HYPERCAPNIA; SYSTEM AB Breathlessness arises from increased medullary respiratory center activity projecting to the forebrain (respiratory corollary discharge hypothesis). Subjects with congenital central hypoventilation syndrome (CCHS) lack the normal hyperpnea and breathlessness during hypercapnia. The corollary discharge hypothesis predicts that if CCHS subjects have normal hyperpnea during exercise, they will experience normal breathlessness during exercise. To test this, we studied four CCHS subjects and six matched controls during an exhausting constant-load cycling test requiring substantial anaerobiosis. CCHS subjects rated significantly less breathlessness at the end of the test than controls, but ventilation (index of respiratory corollary discharge) was also somewhat lower in CCHS (not significant). In both groups, breathlessness increased disproportionately more than ventilation towards the end of exercise. These data failed to disprove the corollary discharge hypothesis of breathlessness, but do suggest that the relationship between ventilation and breathlessness is non-linear and/or that projections of chemoreceptor afferents to the forebrain (presumed lacking in CCHS) is one source of breathlessness in normals. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Publ Hlth, Physiol Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Pulm Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Spengler, CM (reprint author), Swiss Fed Inst Technol, Winterthurerstr 190, CH-8057 Zurich, Switzerland. RI Spengler, Christina M./E-9776-2012 OI Spengler, Christina M./0000-0002-4598-3595 FU PHS HHS [NIH 46690] NR 22 TC 23 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0034-5687 J9 RESP PHYSIOL JI Respir. Physiol. PD OCT PY 1998 VL 114 IS 1 BP 65 EP 74 DI 10.1016/S0034-5687(98)00073-5 PG 10 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 146CV UT WOS:000077411200008 PM 9858052 ER PT J AU Mavroidis, C Flanz, J Dubowsky, S Drouet, P Goitein, M AF Mavroidis, C Flanz, J Dubowsky, S Drouet, P Goitein, M TI High performance medical robot requirements and accuracy analysis SO ROBOTICS AND COMPUTER-INTEGRATED MANUFACTURING LA English DT Article DE medical robot; patient positioning; positioning accuracy; repeatability ID MULTIAXIS MACHINES; ERRORS; SENSITIVITY; MECHANISMS; TOOL AB The treatment of disease using particle beams requires highly accurate patient positioning. Patients must be well immobilized and precisely aligned with the treatment beam to take full advantage of the dose localization potential. Robots can be used as high accuracy patient positioning systems. In this paper, the first such implementation using robotics techniques for patient positioning will be discussed. This robot is being developed for the Northeast Proton Therapy Center at the Massachusetts General Hospital. The unique requirements and design characteristics of the patient positioning system are presented. Of special interest is the system's patient positioning accuracy. A systematic methodology to perform the error analysis of serial link manipulators and its application to the PPS is described. Experimental measurements that verified the validity of the method are shown. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Rutgers State Univ, Dept Aerosp & Mech Engn, Piscataway, NJ 08854 USA. Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. Univ Poitiers, Mecan Solides Lab, F-86960 Futuroscope, France. RP Mavroidis, C (reprint author), Rutgers State Univ, Dept Aerosp & Mech Engn, 98 Brett Rd,Room B-217, Piscataway, NJ 08854 USA. EM mavro@jove.rutgers.edu NR 35 TC 13 Z9 14 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5845 J9 ROBOT CIM-INT MANUF JI Robot. Comput.-Integr. Manuf. PD OCT-DEC PY 1998 VL 14 IS 5-6 BP 329 EP 338 DI 10.1016/S0736-5845(98)00022-2 PG 10 WC Computer Science, Interdisciplinary Applications; Engineering, Manufacturing; Robotics SC Computer Science; Engineering; Robotics GA 157DX UT WOS:000078045800001 ER PT J AU Fraser, IP Koziel, H Ezekowitz, RAB AF Fraser, IP Koziel, H Ezekowitz, RAB TI The serum mannose-binding protein and the macrophage mannose receptor are pattern recognition molecules that link innate and adaptive immunity SO SEMINARS IN IMMUNOLOGY LA English DT Review DE macrophage; mannose binding protein; mannose receptor; pattern recognition ID PNEUMOCYSTIS-CARINII PNEUMONIA; MONOCYTE-DERIVED MACROPHAGES; MOUSE PERITONEAL-MACROPHAGES; ALVEOLAR MACROPHAGES; INTERFERON-GAMMA; DOWN-REGULATION; MEDIATED PHAGOCYTOSIS; CANDIDA-ALBICANS; DENDRITIC CELLS; MYCOBACTERIUM-TUBERCULOSIS AB The innate immune system evolved to protect the host in the early phases of an infectious challenge. The soluble mannose binding protein, and the cell surface mannose receptor are two key pattern recognition molecules of innate immunity. The ligand binding specificity of these molecules enables them to differentiate 'self from 'non-self. These pattern recognition capabilities are coupled to effector functions, which enable them to interact with other molecules of the immune system. In this way, these pattern recognition molecules are able to serve as a link between the innate and adaptive immune systems. C1 Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Div Pulm & Crit Care Med, Dept Med, Boston, MA USA. RP Fraser, IP (reprint author), Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. NR 94 TC 147 Z9 158 U1 3 U2 17 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD OCT PY 1998 VL 10 IS 5 BP 363 EP 372 DI 10.1006/smim.1998.0141 PG 10 WC Immunology SC Immunology GA 133VG UT WOS:000076706800004 PM 9799711 ER PT J AU Berg, D AF Berg, D TI Managing the side effects of chemotherapy for colorectal cancer SO SEMINARS IN ONCOLOGY LA English DT Article; Proceedings Paper CT Symposium on Colorectal Cancer - Therapeutic Update CY DEC 10, 1997 CL SAN ANTONIO, TEXAS ID PHASE-II; FLUOROURACIL; IRINOTECAN; MODULATION C1 Dana Farber Canc Inst, Gastrointestinal Canc Ctr, Boston, MA 02115 USA. RP Berg, D (reprint author), Dana Farber Canc Inst, Gastrointestinal Canc Ctr, 44 Binney St, Boston, MA 02115 USA. NR 17 TC 11 Z9 11 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 1998 VL 25 IS 5 SU 11 BP 53 EP 59 PG 7 WC Oncology SC Oncology GA 128VP UT WOS:000076429300008 PM 9786317 ER PT J AU Lee, SGP Jupiter, JB AF Lee, SGP Jupiter, JB TI Differentiating serious and nonserious fractures of the distal radius in athletes SO SPORTS MEDICINE AND ARTHROSCOPY REVIEW LA English DT Article DE fracture; distal radius ID COLLES FRACTURES; EXTERNAL FIXATION; INJURIES; WRIST AB Fractures of the distal radius are common and account for approximately 75% of all fractures of the forearm. Young athletes involved in high-velocity injuries to the wrist often sustain comminuted intra-articular distal radius fractures, which can produce great challenges to the physicians treating them. The comminution of the cortex and distal fragment frequently involve the distal radioulnar joint and radiocarpal joint, and inadequate treatment may result in functional limitation and chronic pain. The authors describe a systematic approach to evaluation and treatment of distal radius fractures, the indications and techniques for various types of surgery, and potential complications. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand Surg Serv, Boston, MA 02114 USA. RP Lee, SGP (reprint author), WACC 527,15 Parkman St, Boston, MA 02114 USA. NR 63 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-8592 J9 SPORTS MED ARTHROSC JI Sports Med. Arthrosc. Rev. PD OCT-DEC PY 1998 VL 6 IS 4 BP 287 EP 298 PG 12 WC Sport Sciences SC Sport Sciences GA 259MX UT WOS:000083898600008 ER PT J AU Shimizu-Sasamata, M Kano, T Rogowska, J Wolf, GL Moskowitz, MA Lo, EH AF Shimizu-Sasamata, M Kano, T Rogowska, J Wolf, GL Moskowitz, MA Lo, EH TI YM872, a highly water-soluble AMPA receptor antagonist, preserves the hemodynamic penumbra and reduces brain injury after permanent focal ischemia in rats SO STROKE LA English DT Article DE cerebral ischemia, focal; neuroprotection; penumbra; receptor antagonist, AMPA; tomography, emission computed; rats ID MIDDLE CEREBRAL-ARTERY; TEMPORAL CORRELATION-ANALYSIS; HIGH-RESOLUTION MEASUREMENT; TRACER BOLUS PASSAGES; BLOOD-FLOW; BARRIER PERMEABILITY; NITRIC-OXIDE; OCCLUSION; MODEL; TIME AB Background and Purpose-We recently described an image analysis technique based on the temporal correlation mapping (TCM) of injected contrast agents that can be used to distinguish the hemodynamic core and hemodynamic penumbra after focal ischemia. In this study we used this technique for the first time to investigate the effects of the water-soluble AMPA receptor antagonist YM872 in permanent focal ischemia, Methods-Fischer 344 rats were subjected to permanent occlusion of the middle cerebral artery. Approximately 30 minutes after ischemia, functional CT images were collected with the use of a dynamic scanning protocol with bolus injections of nonionic contrast agent iohexol (1 mL/kg). TCM analysis defined the distributions of hemodynamic core and hemodynamic penumbra, Cerebral perfusion indices were calculated on the basis of the area under the first-pass transit curves. One hour after ischemia, animals were randomly treated with YM872 (n=8, 20 mg/kg per hour over 4 hours) or normal saline (n=10). Twenty-four hours later, neurological deficits were evaluated, and conventional CT and triphenyltetrazolium chloride staining were used to define volumes of ischemic damage. Results-At 24 hours after ischemia, hypodense lesions were visible on conventional CT scans that were highly correlated with triphenyltetrazolium chloride lesion volumes. YM872 improved neurological deficits and reduced volumes of ischemic damage in cortex (90+/-14 versus 170+/-16 mm(3) in controls) but not striatum (57+/-14 versus 79+/-6 mm3 in controls). Comparison of early TCM images with conventional CT scans of ischemic injury showed that the hemodynamic core was always damaged in all rats. In controls, 54% of the tissue within the hemodynamic penumbra evolved into ischemic damage compared with 24% in YM872-treated rats. Furthermore, the perfusion index corresponding to the ischemic damage threshold was significantly reduced by YM872 (28+/-2% versus 37+/-2% in controls). Conclusions-These results indicate that YM872 is a neuroprotective compound that ameliorates the deterioration of the hemodynamic penumbra after focal ischemia. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Neurol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Radiot, Neuroprotect Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Neurol, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Neurosurg, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Radiol, Ctr Imaging & Pharmaceut Res, Charlestown, MA 02129 USA. RP Lo, EH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Neurol, Neuroprotect Res Lab, 149 13th St,Room 2322, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS10828, NS32806] NR 43 TC 37 Z9 38 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 1998 VL 29 IS 10 BP 2141 EP 2147 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 124TR UT WOS:000076198600025 PM 9756596 ER PT J AU Schwesinger, WH Page, CP Strodel, WE Ghiatis, AA Chopra, S Gross, GWW Sirinek, KR AF Schwesinger, WH Page, CP Strodel, WE Ghiatis, AA Chopra, S Gross, GWW Sirinek, KR TI Biliary sludge formation during enteral nutrition: Prevalence and natural history SO SURGERY LA English DT Article; Proceedings Paper CT 55th Annual Meeting of the Central-Surgical-Association CY MAR 05-07, 1998 CL ANN ARBOR, MICHIGAN SP Cent Surg Assoc ID TOTAL PARENTERAL-NUTRITION; NEEDLE-CATHETER JEJUNOSTOMY; GALLBLADDER SLUDGE; COMPLICATIONS; BILIRUBIN; CALCIUM; DISEASE; BILE AB Background. Total parenteral nutrition is an etiologic factor in the formation of biliary sludge. We stud led whether enteral nutrition is also a risk factor for sludge. Methods. Fifty patients with a needle catheter jejunostomy (NCJ) placed during a major abdominal operation underwent preoperative and weekly postoperative ultrasonography until NCJ feedings were discontinued (1 to 6 weeks). Results. All patients were men. The mean age was 63.2 +/- 1.6 years. Fourteen asymptomatic patients (28.0%) had biliary sludge within 2 weeks of beg-inning enteral feedings through a NCJ. Complete ultrasonographic resolution of sludge was observed in 13 of the 14 positive patients within 1 to 2 weeks of resuming an oral diet. One patient was lost to follow-up after 14 week; a positive sonogram had persisted but the patient remained asymptomatic. During the period of observation, no other patient had signs of biliary tract disease. Conclusions. (1) Biliary sludge may form in some patients during enteral feeding with NCJ. (2) Sludge is cleared by the gallbladder once nit oral diet is resumed. (3) There appears to be little risk of complications during postoperative enteral feeding. C1 Univ Texas, Hlth Sci Ctr, Dept Surg, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Schwesinger, WH (reprint author), Univ Texas, Hlth Sci Ctr, Dept Surg, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 20 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD OCT PY 1998 VL 124 IS 4 BP 768 EP 772 DI 10.1067/msy.1998.92011 PG 5 WC Surgery SC Surgery GA 126XN UT WOS:000076320400024 PM 9781000 ER PT J AU Tarazi, FI Campbell, A Yeghiayan, SK Baldessarini, RJ AF Tarazi, FI Campbell, A Yeghiayan, SK Baldessarini, RJ TI Localization of ionotropic glutamate receptors in caudate-putamen and nucleus accumbens septi of rat brain: Comparison of NMDA, AMPA, and kainate receptors SO SYNAPSE LA English DT Article DE AMPA; autoradiography; cerebral cortex; glutamate; kainate; lesioning; NMDA; receptors ID D-ASPARTATE RECEPTORS; AMINO-ACID RECEPTORS; MEDIAL FOREBRAIN-BUNDLE; STRIATAL C-FOS; KAINIC ACID; DOPAMINE RELEASE; BINDING-SITES; AUTORADIOGRAPHIC CHARACTERIZATION; INDUCED EXPRESSION; NERVOUS-SYSTEM AB Changes in binding of selective radioligands at NMDA ([H-3]MK-801), AMPA ([H-3]CNQX), and kainate ([H-3]kainic acid) glutamate (GLU) ionotropic receptors in rat caudate-putamen (CPu) and nucleus accumbens (NAc) were examined by quantitative autoradiography following: 1) unilateral surgical ablation of frontal cerebral cortex to remove descending corticostriatal GLU projections, 2) unilateral injection of kainic acid (KA) into CPu or NAc to degenerate local intrinsic neurons, or 3) unilateral injections of 6-hydroxydopamine (6-OH-DA) into substantia nigra to degenerate ascending nigrostriatal dopamine (DA) projections. Cortical ablation significantly decreased NMDA receptor binding in ipsilateral medial CPu (20%), and NAc (16%), similar to previously reported losses of DA D-4 receptors. KA lesions produced large losses of NMDA receptor labeling in CPu and NAc (both by 52%), AMPA (41% and 45%, respectively), and kainate receptors (40% and 45%, respectively) that were similar to the loss of D-2 receptors in CPu and NAc after KA injections. Nigral 6-OH-DA lesions yielded smaller but significant losses in NMDA (17%), AMPA (12%), and kainate (11%) receptor binding in CPu. The results indicate that most NMDA, AMPA, and kainate receptors in rat CPu and NAc occur on intrinsic postsynaptic neurons. Also, some NMDA, but not AMPA or kainate, receptors are also found on corticostriatal projections in association with Dg receptors; these may, respectively, represent excitatory presynaptic NMDA autoreceptors and inhibitory D-4 heteroceptors that regulate GLU release from corticostriatal axons in medial CPu and NAc. Conversely, the loss of all three GLU receptor subtypes after lesioning DA neurons supports their role as excitatory heteroceptors promoting DA release from nigrostriatal neurons. Synapse 30:227-235, 1998, (C) 1998 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Tarazi, FI (reprint author), McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02178 USA. FU NIMH NIH HHS [MH-47370, MH-19905, MH-39006] NR 65 TC 72 Z9 73 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 0887-4476 J9 SYNAPSE JI Synapse PD OCT PY 1998 VL 30 IS 2 BP 227 EP 235 DI 10.1002/(SICI)1098-2396(199810)30:2<227::AID-SYN13>3.0.CO;2-Z PG 9 WC Neurosciences SC Neurosciences & Neurology GA 110HN UT WOS:000075375500013 PM 9723793 ER PT J AU Duntas, LH Pekary, E AF Duntas, LH Pekary, E TI A portrait of thyrotropin-releasing hormone: From New Orleans to Kos: On the occasion of the International TRH Meeting in Kos, Greece SO THYROID LA English DT Editorial Material C1 Univ Athens, Sch Med, Evgenid Hosp, Endocrine Unit, Athens 11528, Greece. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Duntas, LH (reprint author), Univ Athens, Sch Med, Evgenid Hosp, Endocrine Unit, 20 Papadiamantopoulou St, Athens 11528, Greece. NR 8 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD OCT PY 1998 VL 8 IS 10 BP 869 EP 870 DI 10.1089/thy.1998.8.869 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 135NM UT WOS:000076808900001 PM 9827652 ER PT J AU Sattin, A AF Sattin, A TI A heuristic model of mental depression derived from basic and applied research on thyrotropin-releasing hormone SO THYROID LA English DT Article; Proceedings Paper CT Thyrotropin-Releasing Hormone and Related Peptides on the Dawning of a New Millennium Symposium CY JUN 05-07, 1998 CL KOS, GREECE ID TEMPORAL-LOBE EPILEPSY; RAT LIMBIC FOREBRAIN; CEREBRAL BLOOD-FLOW; EYE-MOVEMENT SLEEP; MAJOR DEPRESSION; CEREBROSPINAL-FLUID; MOOD DISORDERS; ELECTROCONVULSIVE SEIZURES; ANXIETY DISORDERS; CLINICAL-RESPONSE AB Recent clinical reports have shown that intrathecal administration of thyrotropin-releasing hormone (TRH) can induce 2 to 3 day remissions of major depression more reliably than i.v. administration. Although clinically impractical, these remissions are rapid, occur within hours, and they survive at least one night's sleep. TRH and related peptides have regulatory effects in the limbic forebrain. Electroconvulsive shock (ECS) in rats induces synthesis of TRH in multiple subcortical limbic and frontal cortical regions, which are known in humans to be involved in both depression and in sleep. The increases in TRH and related peptides are regionally specific. The quantitative TRH increases in individual limbic regions have been correlated with the amount of forced-swimming done by the individual animal after ECS. Intraperitoneal TRH also gives a positive response in this test, as do all effective antidepressants. This article provides a heuristic framework for interdisciplinary neuroscientific study of the interrelated fields of depression and sleep, with a focus on TRH. preclinical data suggest that glutamatergic, subcortical limbic circuits contain TRH and related peptides as inhibitory cotransmitters that may normally restrain glutamatergic hyperactivity. It is suggested that, in depression, pathologically overdriven glutamatergic circuits escape inhibitory regulation by TRH. This escape is especially pronounced during rapid eye movement (REM) sleep, and these phenomena may explain the prolonged latency of antidepressant treatment. C1 W Los Angeles Vet Affairs Med Ctr, ECT Serv, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. Sepulveda VA Med Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. RP Sattin, A (reprint author), W Los Angeles Vet Affairs Med Ctr, ECT Serv, POB 84122, Los Angeles, CA 90073 USA. NR 67 TC 11 Z9 12 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD OCT PY 1998 VL 8 IS 10 BP 957 EP 962 DI 10.1089/thy.1998.8.957 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 135NM UT WOS:000076808900015 PM 9827666 ER PT J AU Pekary, AE AF Pekary, AE TI Is Ps4 (prepro-TRH [160-169]) more than an enhancer for thyrotropin-releasing hormone? SO THYROID LA English DT Article; Proceedings Paper CT Thyrotropin-Releasing Hormone and Related Peptides on the Dawning of a New Millennium Symposium CY JUN 05-07, 1998 CL KOS, GREECE ID CYCLASE ACTIVATING POLYPEPTIDE; FOLLICULO-STELLATE CELLS; RAT REPRODUCTIVE-SYSTEM; POTENTIATING PEPTIDE; HOMOLOGOUS PEPTIDE; HUMAN-SEMEN; CONNECTING PEPTIDES; INVITRO PRODUCTION; NEWBORN RATS; PITUITARY AB Ps4 (thyrotropin-releasing hormone [TRH]-enhancing peptide), one of the cryptic peptides resulting from the proteolytic processing of prepro-TRH to produce TRH, has a growing list of functions in addition to its well-established ability to enhance the TRH-induced release of thyrotropin (TSH) and prolactin from the pituitary. Intramedullary coadministration of Ps4 and TRH increased gastric acid secretion above the level produced by TRH alone and intracisternal infusion of Ps4 resulted in a substantial reduction in the levels of prepro-TRH-derived peptide levels in the rat pituitary, including Ps4. High-affinity receptors for Ps4 are widely distributed. In addition to the very high Ps4 binding capacity of the folliculo-stellate cells of the anterior pituitary, abundant Ps4 receptors are found in the urinary bladder, vas deferens, central nervous system, reproductive tissues, and pancreas. Targeted prepro-TRH gene disruption results in hyperglycemia as well as the expected hypothyroidism. The observed disregulation of thyroid and glucose homeostasis in the TRH "knockout" mouse clearly demonstrates that prepro-TRH-derived peptides and their cognate receptors within the pituitary, pancreas, and other neural and endocrine systems are of fundamental importance to a variety of physiological systems and merit structural and functional characterization. C1 W Los Angeles Vet Affairs Med Ctr, Endocrinol Res Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. RP Pekary, AE (reprint author), W Los Angeles Vet Affairs Med Ctr, Endocrinol Res Lab, Bldg 114,Rm 200,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 41 TC 11 Z9 11 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD OCT PY 1998 VL 8 IS 10 BP 963 EP 968 DI 10.1089/thy.1998.8.963 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 135NM UT WOS:000076808900016 PM 9827667 ER PT J AU Uglialoro, AM Turbay, D Pesavento, PA Delgado, JC McKenzie, FE Gribben, JG Hartl, D Yunis, EJ Goldfeld, AE AF Uglialoro, AM Turbay, D Pesavento, PA Delgado, JC McKenzie, FE Gribben, JG Hartl, D Yunis, EJ Goldfeld, AE TI Identification of three new single nucleotide polymorphisms in the human tumor necrosis factor-alpha gene promoter SO TISSUE ANTIGENS LA English DT Article DE Cambodians; Caucasians; disease susceptibility; evolution; HLA; MHC; TNF-alpha gene regulation; TNF-alpha promoter polymorphisms ID MAJOR HISTOCOMPATIBILITY COMPLEX; EXTENDED HAPLOTYPES; T-CELLS; PCR; LIPOPOLYSACCHARIDE; INDUCIBILITY; RELEVANCE; ATF-2/JUN; ALLELES; REGION AB We have identified three new human tumor necrosis factor-or (TNF-alpha promoter polymorphisms with single nucleotide (nt) substitutions at -862, -856, and -574 nt relative to the TNF-alpha transcription start site. The -862 and -856 nt TNF-alpha promoter polymorphisms occur with. high frequency in Caucasian and Cambodian individuals and are each non-randomly associated with three extended HLA haplotypes. This study, in which 61 independent TNF-alpha promoters were analyzed spanning from -977 to +93 nt relative to the TNF-alpha mRNA cap site, establishes a new canonical TNF-alpha promoter sequence. Furthermore, we show that none of the three navel polymorphisms at -862, -856 and -574 nt or polymorphisms previously described at positions -238, -308 and +70 have an effect upon TNF-alpha gene expression in activated lymphocytes. Thus, these TNF-alpha promoter polymorphisms likely serve as markers for neighboring genes encoding HLA or other undefined molecules in the MHC that may influence disease susceptibility. C1 Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Dept Organism & Evolut Biol, Cambridge, MA 02138 USA. RP Goldfeld, AE (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU Intramural NIH HHS [Z99 TW999999]; NCI NIH HHS [CA58735]; NHLBI NIH HHS [R01 HL059838, HL59838, HL29583, P01 HL029583] NR 38 TC 201 Z9 207 U1 2 U2 5 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD OCT PY 1998 VL 52 IS 4 BP 359 EP 367 DI 10.1111/j.1399-0039.1998.tb03056.x PG 9 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 131GD UT WOS:000076567100006 PM 9820599 ER PT J AU Webb, IJ Jiroutek, M Cohen, CA Schott, DM Doss, D Freeman, A Ritz, J Schlossman, RL Anderson, KC AF Webb, IJ Jiroutek, M Cohen, CA Schott, DM Doss, D Freeman, A Ritz, J Schlossman, RL Anderson, KC TI High leukapheresis component Cd34+ cell purity improves CD34+ cell purity following CD34+ cell selection. SO TRANSFUSION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1998 VL 38 IS 10 SU S MA S164 BP 46S EP 46S PG 1 WC Hematology SC Hematology GA 124FM UT WOS:000076171800184 ER PT J AU Vamvakas, EC Carven, JH AF Vamvakas, EC Carven, JH TI Transfusion and postoperative pneumonia in coronary artery bypass graft surgery: Effect of the length of storage of transfused red cells. SO TRANSFUSION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 OCT PY 1998 VL 38 IS 10 SU S MA S283 BP 76S EP 76S PG 1 WC Hematology SC Hematology GA 124FM UT WOS:000076171800303 ER PT J AU Kruskall, MS AuBuchon, JP Anthony, KY Herschel, L Pickard, C Biehl, R Horowitz, M Popovsky, MA Clibourn, D AF Kruskall, MS AuBuchon, JP Anthony, KY Herschel, L Pickard, C Biehl, R Horowitz, M Popovsky, MA Clibourn, D TI Transfusion of enzymatically converted (group B to group O) red cells to patients: A phase II trial. SO TRANSFUSION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Deaconess Med Ctr, Boston, MA 02115 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Amer Red Cross, Dedham, MA USA. ZymeQuest Inc, N Andover, MA USA. NR 0 TC 0 Z9 0 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 OCT PY 1998 VL 38 IS 10 SU S MA S324 BP 86S EP 86S PG 1 WC Hematology SC Hematology GA 124FM UT WOS:000076171800344 ER PT J AU Kaelin, WG Maher, ER AF Kaelin, WG Maher, ER TI The VHL tumour-suppressor gene paradigm SO TRENDS IN GENETICS LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; VONHIPPEL-LINDAU DISEASE; RENAL-CARCINOMA CELLS; GERMLINE MUTATIONS; PRODUCT; PROTEIN; EXPRESSION; CANCER; IDENTIFICATION; PHENOTYPE AB The VHL, tumour-suppressor gene (TSG) has a critical 'gatekeeper' role in regulating growth and differentiation of human kidney cells, and inactivation of the VHL gene is the most frequent genetic event in human kidney cancer. There are many similarities between tbe genetics of the VHL asd retinoblastoma TSGs, but the VHL tumourigenesis model is more complex, Here, we examine tbe current knowledge of the genetics and functional aspects of tbe VHL TSG, and emphasize How the VHL gene provides a paradigm that Illustrates many aspects of TSG biology. C1 Dana Farber Canc Hosp, Div Adult Oncol, Boston, MA 02116 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02116 USA. Univ Birmingham, Dept Paediat & Child Hlth, Div Med & Mol Genet, Birmingham B15 2TT, W Midlands, England. RP Kaelin, WG (reprint author), Dana Farber Canc Hosp, Div Adult Oncol, Boston, MA 02116 USA. RI MAHER, EAMONN/A-9507-2008 OI MAHER, EAMONN/0000-0002-6226-6918 NR 46 TC 177 Z9 179 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD OCT PY 1998 VL 14 IS 10 BP 423 EP 426 DI 10.1016/S0168-9525(98)01558-3 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 134NK UT WOS:000076749300011 PM 9820032 ER PT J AU Ebb, D Tang, DC Drew, L Chin, K Berg, PE Rodgers, GP AF Ebb, D Tang, DC Drew, L Chin, K Berg, PE Rodgers, GP TI Identification of upstream regulatory elements that repress expression of adult beta-like globin genes in a primitive erythroid environment SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE globin gene; transcription; silencer; mutagenesis; human erythroleukemia cells ID HUMAN GAMMA-GLOBIN; KRUPPEL-LIKE FACTOR; TRANSGENIC MICE; DEVELOPMENTAL REGULATION; DNA INTERACTIONS; TRANSCRIPTION; ACTIVATION; CHROMATIN; SEQUENCE; PROTEIN AB Our investigations have focused on localizing cis-elements responsible for the down regulation of the adult beta-like globin genes (delta and beta) in immature, or primitive erythroid tissues. We studied their activity after transfection into K562 cells, an erythroleukemia cell line with an embryonic-fetal phenotype. Analyzed DNA sequences included delta and beta 5' flanking regions extending from approximately -500 to +50bp (promoter regions), truncated delta and beta 5' flanking regions extending from approximately -250 to +50 bp, and chimeric promoter constructions, which consisted of a distal delta or beta fragment fused to a proximal beta or delta sequence, In CAT reporter constructions no appreciable level of CAT activity was supported by the beta globin promoter, and only low level activity by the delta promoter. Truncation of the beta globin promoter led to a 2-3 fold increase in promoter activity. In contrast, deletion of the upstream portion of the delta promoter led to a 10 fold decrease in expression. Coupling of the upstream beta globin sequence from approximately -500 to -250 bp to the truncated delta promoter fragment led to complete extinction of transcriptional activity, consistent with a negative regulatory effect of the beta globin gene upstream element(s), Fusion of the upstream portion of the delta promoter to the truncated beta globin promoter yielded a modest increase in promoter strength relative to the truncated beta gene promoter, indicating the presence of a positive transcriptional element(s) in the upstream delta globin regulatory region. Site-directed mutagenesis of binding sites for the repressor proteins BP1 and BP2 in the upstream portion of the beta globin gene flanking region led to a 4-6 fold increase in promoter activity, DNase I footprinting of the upstream delta-globin region revealed protected sequences corresponding to consensus binding sites for GATA-1 and BP2. These results confirm that sequences in the upstream promoter region of the adult beta globin gene contribute to its factor-mediated suppression early in development and then may modulate its expression at a later stage. (C) 1998 Academic Press. C1 NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Pediat Hematol Oncol, Boston, MA 02114 USA. Univ Maryland, Sch Med, Dept Pediat Hematol Oncol, Baltimore, MD 21201 USA. RP Rodgers, GP (reprint author), NIDDK, Mol & Clin Hematol Branch, NIH, Bldg 10,Room 9N318,10 Ctr Dr, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [R01 DK53533] NR 36 TC 11 Z9 11 U1 0 U2 0 PU BLOOD CELLS FOUNDATION PI LA JOLLA PA C/O ERNEST BEUTLER SCRIPPS RES INST, DEPT MOLECULAR EXP MEDICINE, LA JOLLA, CA 92037 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD SEP 30 PY 1998 VL 24 IS 18 BP 356 EP 369 DI 10.1006/bcmd.1998.0202 PG 14 WC Hematology SC Hematology GA 124YM UT WOS:000076210400001 PM 10087993 ER PT J AU Finkelstein, JS Klibanski, A Arnold, AL Toth, TL Hornstein, MD Neer, RM AF Finkelstein, JS Klibanski, A Arnold, AL Toth, TL Hornstein, MD Neer, RM TI Prevention of estrogen deficiency-related bone loss with human parathyroid hormone-(1-34) - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID X-RAY ABSORPTIOMETRY; GROWTH FACTOR-I; POSTMENOPAUSAL WOMEN; OVARIECTOMIZED RATS; MINERAL DENSITY; CORTICAL BONE; UNITED-STATES; OSTEOPOROSIS; THERAPY; MASS AB Context.-Short-term intermittent administration of parathyroid hormone (PTH) prevents bone loss from the spine in women treated with a gonadotropin-releasing hormone (GnRH) analog. However, the effects of a longer period of PTH administration on bone mass in estrogen-deficient women, particularly on the hip and on cortical bone of the total body, are unknown. Objective.-To determine whether more prolonged PTH administration can prevent estrogen deficiency bone loss from the hip, spine, and total body in young women with endometriosis receiving GnRH analog (nafarelin acetate) therapy. Design.-Randomized controlled trial. Setting.-General Clinical Research Center of a tertiary care, university-affiliated hospital. Patients.-Forty-three women between the ages of 21 and 45 years with symptomatic endometriosis. Intervention.-Nafarelin alone (200 mu g intranasally twice daily) or nafarelin plus human parathyroid hormone-(1-34) (hPTH-[1-34]) (40 mu g subcutaneously daily). Main Outcome Measures.-The primary end points were bone mineral density (BMD) of the anterior-posterior and lateral spine, femoral neck, trochanter, radial shaft, and total body at 12 months of treatment. Results.-In the women who received nafarelin alone, the mean (SEM) BMDs of the anterior-posterior spine, lateral spine, femoral neck, trochanter, and total body were 4.9% (0.6%) (P<.001), 4.9% (0.8%) (P<.001), 4.7% (1.1%) (P<.001), 4.3% (0.9%) (P<.001), and 2.0% (0.6%) (P=.003) lower than at baseline after 12 months of therapy. In contrast, coadministration of hPTH-(1-34) increased BMD of the anterior-posterior spine by 2.1% (1.1%) (P=.09) and lateral spine by 7.5% (1.9%) (P=.002) and prevented bone loss from the femoral neck, trochanter, and total body, despite severe estrogen deficiency. Radial shaft BMD did not change significantly in either group. Serum bone-specific alkaline phosphatase and osteocalcin concentrations and urinary excretion of hydroxyproline and deoxypyridinoline increased 2-fold to 3-fold during the first 6 to 9 months of therapy in the women who received nafarelin plus hPTH-(1-34) and then declined. Changes in urinary deoxypyridinolone excretion were strongly predictive (r=0.85) of changes in spinal BMD in the women who received nafarelin plus hPTH-(1-34). Conclusions.-Parathyroid hormone prevents bone loss from the proximal femur and total body and increases lumbar spinal BMD in young women with GnRH analog-induced estrogen deficiency. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. RP Finkelstein, JS (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Bulfinch 327,55 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [RR-1066]; NIDDK NIH HHS [R29 DK43341] NR 50 TC 116 Z9 119 U1 1 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 SEP 30 PY 1998 VL 280 IS 12 BP 1067 EP 1073 DI 10.1001/jama.280.12.1067 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 121FJ UT WOS:000076002400035 PM 9757854 ER PT J AU Biederman, J AF Biederman, J TI A 55-year-old man with attention-deficit/hyperactivity disorder SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID DEFICIT-HYPERACTIVITY DISORDER; PSYCHIATRIC STATUS; CHILDHOOD-ONSET; RISK-FACTORS; QUANTITATIVE MORPHOLOGY; CAUDATE-NUCLEUS; CORPUS-CALLOSUM; DOUBLE-BLIND; CHILDREN; ADULTS C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Biederman, J (reprint author), Care of Hartman EE, Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, 330 Brookline Ave,LY318, Boston, MA 02215 USA. NR 52 TC 10 Z9 10 U1 7 U2 8 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 SEP 30 PY 1998 VL 280 IS 12 BP 1086 EP 1092 DI 10.1001/jama.280.12.1086 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 121FJ UT WOS:000076002400038 PM 9757857 ER PT J AU Huggins, GS Pasternak, RC Alpert, NM Fischman, AJ Gewirtz, H AF Huggins, GS Pasternak, RC Alpert, NM Fischman, AJ Gewirtz, H TI Effects of short-term treatment of hyperlipidemia on coronary vasodilator function and myocardial perfusion in regions having substantial impairment of baseline dilator reverse SO CIRCULATION LA English DT Article DE blood flow; ischemia; heart diseases; simvastatin ID POSITRON EMISSION TOMOGRAPHY; ISCHEMIC-HEART-DISEASE; LOW-FAT DIET; ARTERY DISEASE; FLOW RESERVE; BLOOD-FLOW; NITRIC-OXIDE; QUANTITATIVE ARTERIOGRAPHY; RELAXING FACTOR; ENDOTHELIUM AB Background-We tested the hypothesis that correction of hyperlipidemia improves coronary vasodilator response and maximal perfusion in myocardial regions having substantial impairment of pretreatment vasodilator capacity. Methods and Results-Measurements of myocardial blood flow were made with PET [N-13]ammonia in 12 patients with ischemic heart disease (11 men; age, 65+/-8 years [mean+/-SD]) at rest and during adenosine at 70 and then 140 mu g.kg(-1).min(-1) for 5 minutes each before and approximate to 4 months after simvastatin treatment (40 mg daily). Simvastatin reduced LDL (171+/-13 before versus 99+/-18 mg/dL after simvastatin, P<0.001) and increased HDL (39+/-8 versus 45+/-9 mg/dL, P<0.05). Myocardial segments were classified on the basis of pretreatment blood flow response to 140 mu g.kg(-1).min(-1) adenosine as normal (flow greater than or equal to 2 mL.min(-1).g(-1)) or abnormal (flow <2 mL.min(-1).g(-1)). In normal segments, baseline myocardial blood flow (0.95+/-0.32) increased (P<0.001) at both low- (1.62+/-0.81) and high- (2.63+/-0.41) dose adenosine and was unchanged both at rest and with adenosine after simvastatin. In abnormal segments, myocardial blood flow at rest (0.73+/-0.19) increased at low- (1.06+/-0.59, P<0.02) and high- (1.29+/-0.33, P<0.01) dose adenosine. After simvastatin, myocardial blood flow increased more compared with pretreatment at both low- (1.37+/-0.66, P<0.05 versus pretreatment) and high- (1.89+/-0.79, P<0.01 versus pretreatment) dose adenosine. Conclusions-Short-term lipid-lowering therapy increases stenotic segment maximal myocardial blood flow by approximate to 45%. The mechanism involves enhanced, flow-mediated dilation of stenotic epicardial conduit vessels and may account at least in part for the efficacy of lipid lowering in secondary prevention trials and in reducing ischemic episodes in ambulatory patients. C1 Harvard Univ, Cardiac Unit, Massachusetts Gen Hosp, Med Sch,Dept Med, Boston, MA 02114 USA. Harvard Univ, Cardiac Unit, Massachusetts Gen Hosp, Med Sch,Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Cardiac Unit, Massachusetts Gen Hosp, Med Sch,Dept Nucl Med, Boston, MA 02114 USA. RP Harvard Univ, Cardiac Unit, Massachusetts Gen Hosp, Med Sch,Dept Med, Vincent Burnham 3, Boston, MA 02114 USA. EM gewirtz.henry@mgh.harvard.edu NR 35 TC 97 Z9 104 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD SEP 29 PY 1998 VL 98 IS 13 BP 1291 EP 1296 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 123AC UT WOS:000076102800009 PM 9751677 ER PT J AU Alon, R Chen, SQ Fuhlbrigge, R Puri, KD Springer, TA AF Alon, R Chen, SQ Fuhlbrigge, R Puri, KD Springer, TA TI The kinetics and shear threshold of transient and rolling interactions of L-selectin with its ligand on leukocytes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HIGH ENDOTHELIAL VENULES; P-SELECTIN; HYDRODYNAMIC SHEAR; ADHESION MOLECULE; HUMAN NEUTROPHILS; IN-VITRO; FLOW; LYMPHOCYTE; IDENTIFICATION; RECEPTOR AB The kinetics of rolling and transient adhesions through selectins may depend on the kinetics and mechanical properties of the selectin:ligand bond, as well as on cellular properties including receptor-anchoring to the cell membrane and cytoskeleton. Kinetics are known to depend on the selectin and may also be ligand dependent. Here, we study the kinetics of transient and rolling interactions of leukocytes with L-selectin immobilized on a substrate. Remarkably, ail properties examined are similar to those seen when the sidedness is opposite, i.e., when the L-selectin ligand is on the substrate and when the ligand is isolated from HEV rather than present on leukocytes. The similar properties include rolling velocity, a threshold shear stress above 0.4 dyn/cm(2) required to support rolling, a k(off)degrees of 7.0 to 6.8 s(-1) for the L-selectin tether bond, and a mechanical bond length of 0.24 to 0.20 Angstrom. Our results argue against a model in which L-selectin shedding mediates rolling. Furthermore, the fast and force-resistant kinetic properties suggest that L-selectin is specialized dynamically for tethering leukocytes to vessel walls and adherent leukocytes. C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL48675, P01 HL048675] NR 37 TC 86 Z9 87 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 SEP 29 PY 1998 VL 95 IS 20 BP 11631 EP 11636 DI 10.1073/pnas.95.20.11631 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 125DM UT WOS:000076222200026 PM 9751717 ER PT J AU Iliopoulos, O Ohh, M Kaelin, WG AF Iliopoulos, O Ohh, M Kaelin, WG TI pVHL(19) is a biologically active product of the von Hippel-Lindau gene arising from internal translation initiation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TUMOR-SUPPRESSOR GENE; ENDOTHELIAL GROWTH-FACTOR; MESSENGER-RNA; RENAL-CARCINOMA; SOMATIC MUTATIONS; HUMAN TISSUES; PROTEIN; DISEASE; BINDING; FAMILY AB The von Hippel-Lindau (VHL) gene encodes a protein consisting of 213 amino acid residues with an apparent molecular mass of 30 kDa (pVHL(30)). Here we show that cells also produce a VHL protein (pVHL(19)) that appears to arise as a result of internal translation from the second methionine within the VHL ORF, pVHL(30) resides primarily in the cytosol, with less amounts found in the nucleus or associated with cell membranes. In contrast pVHL(19), in biochemical fractionation experiments, is equally distributed between the nucleus and cytosol and is not found in association with membranes. pVHL(19), like pVHL(30), can bind to elongin B, elongin C, and Hs-Cul2 in coimmunoprecipitation assays and can inhibit the production of hypoxia-inducible proteins such as vascular endothelial growth factor (VEGF) and GLUT1 when reintroduced into renal carcinoma cells that lack a wild-type VHL allele, Thus, cells contain two biologically active VHL gene products. C1 Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02116 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02116 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Iliopoulos, O (reprint author), Dana Farber Canc Inst, Howard Hughes Med Inst, 44 Binney St, Boston, MA 02116 USA. EM william_kaelin@dfci.harvard.edu NR 46 TC 152 Z9 156 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 SEP 29 PY 1998 VL 95 IS 20 BP 11661 EP 11666 DI 10.1073/pnas.95.20.11661 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 125DM UT WOS:000076222200031 PM 9751722 ER PT J AU Juppner, H Schipani, E Bastepe, M Cole, DEC Lawson, ML Mannstadt, M Hendy, GN Plotkin, H Koshiyama, H Koh, T Crawford, JD Olsen, BR Vikkula, M AF Juppner, H Schipani, E Bastepe, M Cole, DEC Lawson, ML Mannstadt, M Hendy, GN Plotkin, H Koshiyama, H Koh, T Crawford, JD Olsen, BR Vikkula, M TI The gene responsible for pseudohypoparathyroidism type Ib is paternally imprinted and maps in four unrelated kindreds to chromosome 20q13.3 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ALBRIGHT HEREDITARY OSTEODYSTROPHY; HORMONE-RELATED PEPTIDE; GRADIENT GEL-ELECTROPHORESIS; ALPHA-SUBUNIT GENE; PARATHYROID-HORMONE; RECEPTOR GENE; G-PROTEIN; DEOXYRIBONUCLEIC-ACID; SKIN FIBROBLASTS; DNA METHYLATION AB Hypocalcemia and hyperphosphatemia caused by parathyroid hormone (PTH)-resistance are the only discernible abnormalities in pseudohypoparathyroidism type nb (PHP-Ib). Because mutations in the PTH/PTH-related peptide receptor, a plausible candidate gene, had been excluded previously, we conducted a genome-wide search with four PHP-Ib, kindreds and established linkage to a small telomeric region on chromosome 20q, which contains the stimulatory G protein gene. We, furthermore, showed that the genetic defect is imprinted paternally and thus is inherited in the same mode as the PTH-resistant hypocalcemia in kindreds with PHP-Ia and/or pseudo-pseudohypoparathyroidism, two related disorders caused by different stimulatory G protein mutations. C1 Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Endocrine Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Endocrine Unit, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Endocrine Unit, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Toronto, Lab Med & Pathobiol, Toronto, ON M5B 1L5, Canada. Childrens Hosp Eastern Ontario, Ottawa, ON K1H 8L1, Canada. McGill Univ, Royal Victoria Hosp, Dept Med, Calcium Res Lab, Montreal, PQ H3A 1A1, Canada. McGill Univ, Royal Victoria Hosp, Dept Physiol, Calcium Res Lab, Montreal, PQ H3A 1A1, Canada. McGill Univ, Royal Victoria Hosp, Dept Human Genet, Calcium Res Lab, Montreal, PQ H3A 1A1, Canada. Hyogo Prefectural Amagasaki Hosp, Div Endocrinol & Metab, Dept Internal Med, Amagasaki, Hyogo 6600828, Japan. Kyoto City Hosp, Dept Internal Med, Div Endocrinol, Kyoto 604, Japan. W Haven Vet Affairs Med Ctr, Div Endocrinol & Metab, W Haven, CT 06516 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Wellman 5, Boston, MA 02114 USA. EM jueppner@helix.mgh.harvard.edu RI Koshiyama, Hiroyuki/H-3877-2011; OI Vikkula, Miikka/0000-0002-6236-338X; Lawson, Margaret/0000-0002-2370-9552 FU PHS HHS [R01 36819, R01 46718-06] NR 46 TC 117 Z9 119 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 SEP 29 PY 1998 VL 95 IS 20 BP 11798 EP 11803 DI 10.1073/pnas.95.20.11798 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 125DM UT WOS:000076222200054 PM 9751745 ER PT J AU Marti, F Xu, CW Selvakumar, A Brent, R Dupont, B King, PD AF Marti, F Xu, CW Selvakumar, A Brent, R Dupont, B King, PD TI LCK-phosphorylated human killer cell-inhibitory receptors recruit and activate phosphatidylinositol 3-kinase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CLASS-I MOLECULES; TYROSINE KINASES; SIGNAL-TRANSDUCTION; CD28; ASSOCIATION; EXPRESSION; SYSTEM; IDENTIFICATION; PHOSPHATASES; INVOLVEMENT AB HLA-specific killer cell inhibitory receptors (KIR) are thought to impede natural killer (NK) and T cell activation programs through recruitment of the SH2 domain-containing tyrosine phosphatases, SHP-1 and SHP-2, to their cytoplasmic tails (CYT). To identify other SH2 domain-containing proteins that bind KIR CYT, we used the recently described yeast two-bait interaction trap and a modified version of this system, both of which permit tyrosine phosphorylation of bait proteins, Using these systems, we show that KIR CYT, once phosphorylated by the src-family tyrosine kinase LCK, additionally bind the p85 alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase. Furthermore, we show that in an NK cell line, NK3.3, cross-linking of KIR results in recruitment of p85 alpha to KIR and activation of PI 3-kinase lipid kinase activity. One consequence of KIR coupling to PI 3-kinase is downstream activation of the antiapoptotic protein kinase AKT. Therefore, in addition to providing negative signals, KIR may also contribute positive signals for NK and T cell growth and/or survival. C1 Cornell Univ, Hosp Special Surg, Med Ctr, Div Rheumatol,Res Lab 317, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10021 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP King, PD (reprint author), Cornell Univ, Hosp Special Surg, Med Ctr, Div Rheumatol,Res Lab 317, 535 E 70th St, New York, NY 10021 USA. RI King, Phil/C-7104-2013 FU NCI NIH HHS [P30 CA008748, CA08748]; NIAID NIH HHS [AI37294] NR 41 TC 50 Z9 51 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 SEP 29 PY 1998 VL 95 IS 20 BP 11810 EP 11815 DI 10.1073/pnas.95.20.11810 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 125DM UT WOS:000076222200056 PM 9751747 ER PT J AU Gauthier, L Smith, KJ Pyrdol, J Kalandadze, A Strominger, JL Wiley, DC Wucherpfennig, KW AF Gauthier, L Smith, KJ Pyrdol, J Kalandadze, A Strominger, JL Wiley, DC Wucherpfennig, KW TI Expression and crystallization of the complex of HLA-DR2 (DRA, DRB1*1501) and an immunodominant peptide of human myelin basic protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CLASS-II MOLECULES; ALPHA-BETA-HETERODIMERS; T-CELL CLONES; MULTIPLE-SCLEROSIS; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; IDENTIFICATION; SUSCEPTIBILITY; RECOGNITION; COLLAGEN AB HLA-DR2 is associated with susceptibility to multiple sclerosis (MS), A peptide from human myelin basic protein (MBP, residues 85-99) was previously found to bind to purified HLA-DR2 (DRA, DRB1*1501) and to be recognized by human MBP-specific T cell clones, Soluble HLA-DR2 was expressed in the baculovirus system by replacing the hydrophobic transmembrane regions and cytoplasmic segments of DR alpha and DR beta with leucine zipper dimerization domains from the transcription factors Fos and Jun. In the expression construct, the MBP(85-99) sequence was covalently linked to the N terminus of the mature DR beta chain, The recombinant protein was secreted by Sf9 cells infected with the recombinant baculovirus and purified by affinity chromatography. The leucine zipper dimerization domains were then cleaved from the assembled HLA-DR2/MBP peptide complex with V8 protease, and the protein was further purified by anion-exchange HPLC, Analysis by HPLC gel filtration indicated that the HLA-DR2/MBP peptide complex did not have a tendency to aggregate, The purified HLA-DR2/MBP peptide complex readily crystallized by the hanging drop method in 15-18% polyethylene glycol 6000/100 mM glycine, pH 3.5. At a synchrotron radiation source, a crystal with a tetragonal space group diffracted to a resolution of 2.6 Angstrom. The expression of such homogenous HLA-DR/peptide complexes may facilitate cocrystallization with T cell receptors as well as other molecules involved in T cell receptor recognition and signaling. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Childrens Hosp, Dept Mol Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Dept Cellular & Mol Biol, Cambridge, MA 02139 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM wucherpf@mbcrr.harvard.edu FU NIAID NIH HHS [AI 42316]; NICHD NIH HHS [HD-17461] NR 28 TC 30 Z9 31 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 29 PY 1998 VL 95 IS 20 BP 11828 EP 11833 DI 10.1073/pnas.95.20.11828 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 125DM UT WOS:000076222200059 PM 9751750 ER PT J AU Li, TS Sandberg, MA Pawlyk, BS Rosner, B Hayes, KC Dryja, TP Berson, EL AF Li, TS Sandberg, MA Pawlyk, BS Rosner, B Hayes, KC Dryja, TP Berson, EL TI Effect of vitamin A supplementation on rhodopsin mutants threonine-17 -> methionine and proline-347 -> serine in transgenic mice and in cell cultures SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DOMINANT RETINITIS-PIGMENTOSA; RETINOIC ACID; LIQUID-CHROMATOGRAPHY; PHOTORECEPTORS; DETERMINANTS; SEGMENTS; LIGHT AB A therapeutic effect of vitamin A supplementation on the course of photoreceptor degeneration, previously reported for patients with retinitis pigmentosa, was tested in two transgenic mouse models of this disease, each carrying a dominant rhodopsin mutation. The threonine-17 --> methionine (T17M) mutation is a class II rhodopsin mutation, characterized by a thermal instability/folding defect and minimal regeneration with the chromophore. The proline-347 --> serine (P347S) mutation belongs to class I, comprised of a smaller number of mutations that exhibit no recognized biochemical abnormality in vitro. In the present study, each of the two mouse models was fed a diet containing 2.5 mg of vitamin A palmitate (control) or 102.5 mg of vitamin A palmitate (high vitamin A) per kilogram of diet. Dark-adapted, full-field electroretinograms showed that the high vitamin A diet significantly reduced the rate of decline of a-wave acid b-wave amplitudes in the T17M mice but had no significant effect on the decline of electroretinogram amplitude in the P347S mice. Correspondingly, histologic evaluation revealed that the treatment was associated with significantly longer photoreceptor inner and outer segments and a thicker outer nuclear layer in the T17M mice but had no effect on photoreceptor morphology in the P347S mice. In a separate series of experiments, the instability defect of the T17M mutant opsin expressed in vitro was partially alleviated by inclusion of 11-cis-retinal in the culture media, These results show that vitamin A supplementation slows the rate of photoreceptor degeneration caused by a class II rhodopsin mutation. Vitamin A supplementation may confer therapeutic benefit by stabilizing mutant opsins through increased availability of the chromophore. C1 Harvard Univ, Berman Gund Lab, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. Brandeis Univ, Foster Biomed Res Lab, Waltham, MA 02453 USA. Massachusetts Eye & Ear Infirm, Ocular Mol Genet Inst, Boston, MA 02114 USA. RP Li, TS (reprint author), Harvard Univ, Berman Gund Lab, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02115 USA. FU NEI NIH HHS [R37 EY000169, EY00169, R01 EY000169, R01 EY010309, EY10309] NR 21 TC 115 Z9 117 U1 1 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 SEP 29 PY 1998 VL 95 IS 20 BP 11933 EP 11938 DI 10.1073/pnas.95.20.11933 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 125DM UT WOS:000076222200077 PM 9751768 ER PT J AU Harrington, EA Bruce, JL Harlow, E Dyson, N AF Harrington, EA Bruce, JL Harlow, E Dyson, N TI pRB plays an essential role in cell cycle arrest induced by DNA damage SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RETINOBLASTOMA-PROTEIN; GROWTH SUPPRESSION; TUMOR-SUPPRESSOR; ANTICANCER AGENTS; G1 ARREST; S-PHASE; P53; INHIBITION; FIBROBLASTS; KINASES AB To maintain genome stability, cells with damaged DNA must arrest to allow repair of mutations before replication, Although several key components required to elicit this arrest have been discovered, much of the pathway remains elusive, Here we report that PRE acts as a central mediator of the proliferative block induced by a diverse range of DNA damaging stimuli. Rb-/- mouse embryo fibroblasts are defective in arrest after gamma-irradiation, UV irradiation, and treatment with a variety of chemotherapeutic drugs, In contrast, the pRB related proteins p107 and p130 do not play an essential part in the DNA damage response. pRB is required specifically for the G(1)/S phase checkpoint induced by gamma-irradiation, Despite a defect in G(1)/S phase arrest, levels of p53 and p21 are increased normally in Rb-/- cells in response to gamma-irradiation, These results lead us to propose a model in which pRB acts as an essential downstream target of the DNA damage-induced arrest pathway. The ability of pRB to prevent replication of damaged DNA is likely to inhibit the propagation of carcinogenic mutations and may therefore contribute to its role as a tumor suppressor. Furthermore, because many cancer therapies act by damaging DNA, these findings also have implications for the treatment of tumors in which pRB is inactivated. C1 Massachusetts Gen Hosp, Ctr Canc, Oncol Mol Lab, Boston, MA 02129 USA. RP Harrington, EA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Oncol Mol Lab, Bldg 149,13th St, Boston, MA 02129 USA. NR 50 TC 182 Z9 183 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 SEP 29 PY 1998 VL 95 IS 20 BP 11945 EP 11950 DI 10.1073/pnas.95.20.11945 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 125DM UT WOS:000076222200079 PM 9751770 ER PT J AU Murray, B Alessandrini, A Cole, AJ Yee, AG Furshpan, EJ AF Murray, B Alessandrini, A Cole, AJ Yee, AG Furshpan, EJ TI Inhibition of the p44/42 MAP kinase pathway protects hippocampal neurons in a cell-culture model of seizure activity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NERVE GROWTH-FACTOR; TYROSINE PHOSPHORYLATION; SYNAPSIN-I; CEREBRAL-ISCHEMIA; INDUCED APOPTOSIS; CORTICAL-NEURONS; RAT HIPPOCAMPUS; CALCIUM INFLUX; ACTIVATION; BRAIN AB Excessive release of glutamate and the subsequent influx of calcium are associated with a number of neurological insults that result in neuronal death. The calcium-activated intracellular signaling pathways responsible for this excitotoxic injury are largely unknown. Here, we report that PD098059, a selective inhibitor of the calcium-activated p44/42 mitogen-activated protein kinase (MAP kinase) pathway, reduces neuronal death in a cell-culture model of seizure activity. Dissociated hippocampal neurons grown chronically in the presence of kynurenate, a broad spectrum glutamate-receptor antagonist, and elevated amounts of magnesium exhibit intense seizure-like activity after the removal of these blockers of excitatory synaptic transmission. A 30-min removal of the blockers produced extensive neuronal death within 24 h as assayed by the uptake of trypan blue and the release of lactate dehydrogenase. Phospho-p44/42 MAP kinase immunoreactivity after 30 min of seizure-like activity was present in many neuronal somata and dendrites as well as some synaptic terminals, consistent with both the presynaptic and postsynaptic effects of this pathway. The addition of PD098059 (40 mu M; EC50 = 10 mu M) during a 30-min washout of synaptic blockers inhibited the phosphorylation of p44/42 MAP kinase and reduced both the trypan-blue staining (n = 13) and the release of lactate dehydrogenase (n = 16) by 73% +/- 18% and 75% +/- 19% (mean +/- SD), respectively. The observed neuroprotection could be caused by an effect of PD098059 on seizure-like events or on downstream signaling pathways activated by the seizure-like events. Either possibility suggests a heretofore unknown function for the p44/42 MAP kinase pathway in neurons. C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Renal Unit, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Epilepsy Res Lab, Boston, MA 02114 USA. RP Furshpan, EJ (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, 220 Longwood Ave, Boston, MA 02115 USA. NR 55 TC 189 Z9 198 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 29 PY 1998 VL 95 IS 20 BP 11975 EP 11980 DI 10.1073/pnas.95.20.11975 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 125DM UT WOS:000076222200084 PM 9751775 ER PT J AU Wang, TJ Stafford, RS AF Wang, TJ Stafford, RS TI National patterns and predictors of beta-blocker use in patients with coronary artery disease SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; INVASIVE CARDIAC PROCEDURES; OF-VETERANS-AFFAIRS; HEART-DISEASE; PRIMARY PREVENTION; UNSTABLE ANGINA; DRUG THERAPIES; TRIALS; FAILURE; RISK AB Background: Prior studies suggest underuse of beta-blockers in patients with coronary artery disease, but these studies have been based on selected populations of recently hospitalized patients. Objective: To describe national patterns and determinants of beta-blocker use in the ambulatory setting. Methods: We analyzed 11745 visits by patients with coronary artery disease to randomly selected, office-based physicians in the National Ambulatory Medical Care Surveys for 1980, 1981, 1985, and 1989 through 1996. We used multiple logistic regression to determine the independent effect of sociodemographic and clinical factors on beta-blocker use. Outcome Measure: beta-Blocker use at patient visits. Results: beta-Blocker use was reported in only 20.9% of office visits by patients with coronary artery disease and no strong contraindications between 1993 and 1996. In multivariate analyses, age younger than 75 years, residence in the Northeast, and visits to cardiologists and internists compared with family and general practitioners predicted greater use of beta-blocker therapy. White race and private insurance also were significant predictors of beta-blocker use between 1980 and 1996. Longitudinal analyses revealed a significant decline in beta-blocker use from 1980 to 1990, followed by a gradual increase in recent years. Conclusions: beta-Blockers appear to be underused in ambulatory patients with coronary artery disease. Our data suggest that nonclinical factors may influence rates of use, indicating the need for closer scrutiny of variations in physician prescribing practices. C1 Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Stafford, RS (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. NR 52 TC 51 Z9 52 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 SEP 28 PY 1998 VL 158 IS 17 BP 1901 EP 1906 DI 10.1001/archinte.158.17.1901 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 124DV UT WOS:000076166800006 PM 9759686 ER PT J AU Delfs, JM Zhu, Y Druhan, JP Aston-Jones, GS AF Delfs, JM Zhu, Y Druhan, JP Aston-Jones, GS TI Origin of noradrenergic afferents to the shell subregion of the nucleus accumbens: Anterograde and retrograde tract-tracing studies in the rat SO BRAIN RESEARCH LA English DT Article DE nucleus tractus solitarius; medulla; noradrenergic; ventral striatum ID DOPAMINE-BETA-HYDROXYLASE; GAMMA-AMINOBUTYRIC-ACID; VENTRAL TEGMENTAL AREA; FREELY MOVING RATS; B SUBUNIT CTB; OPIATE WITHDRAWAL; LOCUS COERULEUS; CATECHOLAMINERGIC NEURONS; IONTOPHORETIC APPLICATION; HORSERADISH-PEROXIDASE AB The nucleus accumbens (NAcc) can be subdivided into 'core' and 'shell' based on anatomical connections and histochemical markers. Previous studies have demonstrated dopamine-beta-hydroxylase immunoreactive (DBH-ir) fibers in the NAcc shell, but the source of these noradrenergic (NE) afferents has not been determined. Therefore, we have investigated in detail the anatomy of NE afferents to this subregion. Dual immunohistochemistry for DBH and substance P demonstrated numerous DBH-ir fibers in the caudal NAcc shell. Neurons projecting to the NAcc were identified with Fluoro-Gold (FG) or cholera toxin B (CTb) retrograde tracing and tyrosine hydroxylase (TH) immunohistochemistry. Single- and double-labeled neurons were observed in the A2 and Al NE cell groups following FG injections into the caudal NAcc shell. Numerous FG and CTb single-labeled neurons were found in the rostral locus coeruleus (LC), subcoeruleus and pericoerulear dendritic region, with an occasional double-labeled neuron in the LC. Few labeled neurons were seen in the brainstem after FG injections into the NAcc core, consistent with the lack of DBH-ir in this subterritory. To confirm these results, injections of Phaseolus vulgaris leucoagglutinin or biotinylated dextran amine were made into the LC or nucleus tractus solitarius (NTS). Virtually no labeled fibers were observed in the NAcc following injections into central LC. However, fibers were observed in the NAcc shell after injections in the NTS, These results indicate that the primary source(s) of NE afferents to the NAcc shell is the A2 region of the NTS, with lesser contributions from Al and LC. (C) 1998 Published by Elsevier Science B.V. All rights reserved. C1 Univ Penn, Lab Neuromodulat & Behav, Dept Psychiat, Sch Med,Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Aston-Jones, GS (reprint author), Univ Penn, Lab Neuromodulat & Behav, Dept Psychiat, Sch Med,Vet Affairs Med Ctr, Univ & Woodland Ave, Philadelphia, PA 19104 USA. FU NIDA NIH HHS [DA06214, DA05810, DA10088] NR 86 TC 156 Z9 157 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 SEP 28 PY 1998 VL 806 IS 2 BP 127 EP 140 DI 10.1016/S0006-8993(98)00672-6 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 125ML UT WOS:000076241300001 PM 9739125 ER PT J AU Lambrigts, D Menard, MT Alexandre, GPJ Franssen, C Meurisse, M Van Calster, P Coignoul, F Mawulawde, K Choo, JK Yamada, K Erhorn, AE Slisz, JK Chiotellis, P Aretz, HT Sachs, DH Madsen, JC AF Lambrigts, D Menard, MT Alexandre, GPJ Franssen, C Meurisse, M Van Calster, P Coignoul, F Mawulawde, K Choo, JK Yamada, K Erhorn, AE Slisz, JK Chiotellis, P Aretz, HT Sachs, DH Madsen, JC TI Creation of the "thymoheart" allograft - Implantation of autologous thymus into the heart prior to procurement SO TRANSPLANTATION LA English DT Article ID TRANSPLANTATION TOLERANCE; MINIATURE SWINE; EPITHELIUM; INDUCTION; BARRIER; GRAFTS; CELLS; MICE; PIG AB Background. A state of tolerance may be more easily achieved if fully vascularized and functional donor thymus is transferred to the recipient at the time of whole organ transplantation. Methods. A composite "thymoheart" allograft was created by implanting autologous thymus into a donor heart 60-90 days before organ procurement. Successful intracardiac engraftment of autologous thymus was documented by histology and by flow cytometric analysis. Results. Histology of the thymic autografts at explantation revealed viable thymus with preservation of normal thymic architecture. Cells retrieved from thymic autografts 60 days after implantation exhibited the same MHC class I and class II staining profiles by flow cytometry as cells taken from the residual native thymus. Conclusion. We have created a novel composite organ that confers vascularized and functional donor thymus to heart allograft recipients at the time of transplantation without affecting cardiac function. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Sch Med,Div Cardiac Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Sch Med,Transplantat Biol Res Ctr, Boston, MA 02114 USA. Univ Liege, Ctr Interdisciplinaire Rech Xenotransplantat, Liege, Belgium. RP Madsen, JC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Sch Med,Div Cardiac Surg, 55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [R01-HL54211] NR 16 TC 18 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD SEP 27 PY 1998 VL 66 IS 6 BP 810 EP 814 DI 10.1097/00007890-199809270-00019 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 125RA UT WOS:000076249800019 PM 9771848 ER PT J AU Woods, SC Figlewicz, DP Madden, L Porte, D Sipols, AJ Seeley, RJ AF Woods, SC Figlewicz, DP Madden, L Porte, D Sipols, AJ Seeley, RJ TI NPY and food intake: Discrepancies in the model SO REGULATORY PEPTIDES LA English DT Article DE neuropeptide Y; conditioned taste aversion; pica; geophagia; appetitive behavior; consummatory behavior; salt appetite ID NEUROPEPTIDE-Y DISTRIBUTION; RAT-BRAIN; INTRACEREBROVENTRICULAR INJECTION; ENERGY-METABOLISM; FEEDING-BEHAVIOR; GENE-EXPRESSION; PEPTIDE-YY; HYPOTHALAMUS; INHIBITION; INSULIN AB The evidence that NPY is an endogenous neurotransmitter that modulates both sides of the energy equation is clear and compelling. While agreeing with this land indeed contributing to the growing literature supporting the concept), we have found that the interpretation of the increased food intake stimulated by intraventricular (ivt) NPY is more complex than first appears. We discuss evidence suggesting that NPY additionally land presumably at other receptor populations in the brain) causes sensations that produce aversion or illness. Specifically, the ivt administration of NPY at doses that stimulate eating also cause the formation of a conditioned taste aversion and the animal engages in a form of pica behavior (kaolin consumption). It also suppresses an otherwise robust increase of sodium consumption. We discuss evidence suggesting that whereas NPY activates feeding behavior by stimulating the complex sequence of behaviors beginning with the seeking and finding of food and ending with food ingestion, NPY does not stimulate increased eating in the absence of the anticipatory preliminary behaviors. Finally, we briefly review evidence suggesting that whatever sensation is aroused by ivt NPY, it is not necessarily the same sensation that is aroused when animals are food-deprived. Hence, one must be cautious in interpreting NPY as solely an orexigen. (C) 1998 Published by Elsevier Science B.V. All rights reserved. C1 Univ Washington, Dept Psychol, Seattle, WA 98195 USA. Univ Washington, Dept Neurobiol & Behav, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Cincinnati, Dept Psychiat, Milwaukee, OH USA. VA Puget Sound Hlth Care Syst, Seattle Div, Washington, DC USA. Latvian Acad Med, Riga, Latvia. RP Woods, SC (reprint author), Univ Washington, Dept Psychol, Seattle, WA 98195 USA. FU NIDDK NIH HHS [DK 17844, DK 40943, DK 12829] NR 38 TC 62 Z9 62 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD SEP 25 PY 1998 VL 75-6 BP 403 EP 408 DI 10.1016/S0167-0115(98)00095-0 PG 6 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 130DC UT WOS:000076503300050 PM 9802436 ER PT J AU Raines, DE Krishnan, NS AF Raines, DE Krishnan, NS TI Agonist binding and affinity state transitions in reconstituted nicotinic acetylcholine receptors revealed by single and sequential mixing stopped-flow fluorescence spectroscopies SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE acetylcholine receptor; cholesterol; lipid-protein interaction; reconstitution ID TORPEDO POSTSYNAPTIC MEMBRANES; GATED ION CHANNELS; NONCOMPETITIVE ANTAGONIST; FUNCTIONAL ARCHITECTURE; LIPID MODULATION; CHOLESTEROL; DESENSITIZATION; MARMORATA; KINETICS; VESICLES AB The affinity state of nicotinic acetylcholine receptors (nAcChoRs) reconstituted into either dioleoylphosphatidylcholine (DOPC) or a mixture of dioleoylphosphatidylcholine, dioleoylphosphatidic acid, and cholesterol (DOPC/DOPA/cholesterol) has been determined using single and sequential mixing stopped-flow fluorescence spectroscopies. These techniques have millisecond temporal resolution, permitting low- and high-affinity conformational states of the nAcChoR to be resolved following mixing with the fluorescent partial agonist Dns-C-6-Cho from their characteristic Dns-C-6-Cho dissociation rates. Our studies reveal that prior to agonist-induced affinity state conversion, nAcChoRs reconstituted into either DOPC or DOPC/DOPA/cholesterol are predominantly in a conformational state that has a low affinity for agonist. Prolonged exposure to Dns-C-6-Cho converts nearly all DOPC/DOPA/cholesterol-reconstituted nAcChoRs to the high-affinity state. In contrast, Dns-C-6-Cho converts only half of all DOPC-reconstituted nAcChoRs to the high-affinity state. The other half persists in a low-affinity state characterized by a K-d for Dns-C-6-Cho of 0.61 +/- 0.07 mu M. This K-d is Similar to that previously reported for Dns-C-6-Cho binding to low-affinity, resting-state nAcChoRs in native membranes. However, affinity state conversion of DOPC-reconstituted nAcChoRs may be facilitated by re-reconstituting them into bilayers composed of DOPC/DOPA/cholesterol. These results indicate that the lipid bilayer composition modulates nAcChoR agonist-induced affinity state transitions. 0005-2736/98/$ - see front matter (C) 1998 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Raines, DE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 32 Fruit St, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM53481] NR 36 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD SEP 23 PY 1998 VL 1374 IS 1-2 BP 83 EP 93 DI 10.1016/S0005-2736(98)00133-3 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 124NG UT WOS:000076188200009 PM 9814855 ER PT J AU Huang, WW Garcia-Zepeda, EA Sauty, A Oettgen, HC Rothenberg, ME Luster, AD AF Huang, WW Garcia-Zepeda, EA Sauty, A Oettgen, HC Rothenberg, ME Luster, AD TI Molecular and biological characterization of the murine leukotriene B-4 receptor expressed on eosinophils SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE chemotactic factor; eosinophil; leukotriene B-4; asthma; G protein-coupled receptor ID BRONCHOALVEOLAR LAVAGE FLUID; PLATELET-ACTIVATING-FACTOR; GUINEA-PIG LUNG; POLYMORPHONUCLEAR LEUKOCYTES; 5-LIPOXYGENASE INHIBITOR; CHEMOATTRACTANT RECEPTOR; ALLERGIC INFLAMMATION; CHEMOKINE RECEPTORS; AIRWAY INFLAMMATION; TRANSGENIC MICE AB The movement of leukocytes into tissues is regulated by the local production of chemical mediators collectively referred to as chemoattractants. Although chemoattractants constitute a diverse array of molecules, including proteins, peptides, and lipids, they all appear to signal leukocytes through a related family of seven transmembrane-spanning G protein-coupled receptors. The eosinophil is a potent proinflammatory cell that is attracted into tissues during allergic inflammation, parasitic infection, and certain malignancies. Since the molecular mechanisms controlling eosinophil recruitment are incompletely understood, we performed a degenerate polymerase chain reaction on cDNA isolated from murine eosinophils to identify novel chemoattractant receptors. We report the isolation of a cDNA that encodes a 351-amino acid glycoprotein that is 78% identical to a human gene that has been reported to be a purinoceptor (P2Y(7)) and a leukotriene B-4 (LTB4) receptor (BLTR). Chinese hamster ovary (CHO) cells transfected with this cDNA specifically bound [H-3]LTB4 with a dissociation constant of 0.6 +/- 0.1 nM. Furthermore, LTB4 induced a dose-dependent intracellular calcium nux in transfected CHO cells. In contrast, [S-35]dATP did not specifically bind to these transfectants. This mRNA was expressed at high levels in interleukin 5-exposed eosinophils, elicited peritoneal macrophages and neutrophils, and to a lesser extent interferon gamma stimulated macrophages. Low levels of expression were detected in the lung, lymph node, and spleen of unchallenged mice. Western blot analysis detected the mBLTR protein in murine eosinophils and alveolar macrophages as well as human eosinophils. In addition, elevated levels of mBLTR mRNA were found in the lungs of mice in a murine model of allergic pulmonary inflammation in a time course consistent with the influx of eosinophils. Our findings indicate that this murine receptor is an LTB4 receptor that is highly expressed on activated leukocytes, including eosinophils, and may play an important role in mediating eosinophil recruitment into inflammatory foci. C1 Massachusetts Gen Hosp, Dept Med, Ctr AIDS Res, Infect Dis Unit, Charlestown, MA 02129 USA. Harvard Med Sch, Charlestown, MA 02129 USA. Childrens Hosp, Div Immunol, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA 02115 USA. Childrens Hosp, Med Ctr, Div Pulm Med Allergy & Clin Immunol, Dept Pediat, Cincinnati, OH 45229 USA. RP Luster, AD (reprint author), Massachusetts Gen Hosp East, 149 13th St, Charlestown, MA 02129 USA. EM luster@helix.mgh.harvard.edu NR 70 TC 113 Z9 115 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 21 PY 1998 VL 188 IS 6 BP 1063 EP 1074 DI 10.1084/jem.188.6.1063 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 123EK UT WOS:000076112700007 PM 9743525 ER PT J AU Boesiger, J Tsai, M Maurer, M Yamaguchi, M Brown, LF Claffey, KP Dvorak, HF Galli, SJ AF Boesiger, J Tsai, M Maurer, M Yamaguchi, M Brown, LF Claffey, KP Dvorak, HF Galli, SJ TI Mast cells can secrete vascular permeability factor vascular endothelial cell growth factor and exhibit enhanced release after immunoglobulin E-dependent upregulation of Fc epsilon receptor I expression SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE allergy; angiogenesis; c-kit; stem cell factor; vascular permeability ID NECROSIS-FACTOR-ALPHA; ASCITES-FLUID; TUMOR-GROWTH; FACTOR-BETA; KIT-LIGAND; RAT; ANGIOGENESIS; HEPARIN; VITRO; VIVO AB Vascular permeability factor/vascular endothelial cell growth factor (VPF/VEGF) can both potently enhance vascular permeability and induce proliferation of vascular endothelial cells. We report here that mouse or human mast cells can produce and secrete VPF/VEGF. Mouse mast cells release VPF/VEGF upon stimulation through Fc epsilon receptor I (Fc epsilon RI) or c-kit, or after challenge with the protein kinase C activator, phorbol myristate acetate, or the calcium ionophore, A23187; such mast cells can rapidly release VPF/VEGF, apparently from a preformed pool, and can then sustain release by secreting newly synthesized protein. Notably, the Fc epsilon RI-dependent secretion of VPF/VEGF by either mouse or human mast cells can be significantly increased in cells which have undergone upregulation of Fc epsilon RI surface expression by a 4-d preincubation with immunoglobulin E. These finding; establish that at least one cell type, the mast cell, can be stimulated to secrete VPF/VEGF upon immunologically specific activation via a member of the multichain immune recognition receptor family. Our observations also identify a new mechanism by which mast cells can contribute to enhanced vascular permeability and/or angiogenesis, in both allergic diseases and other settings. C1 Beth Israel Deaconess Med Ctr E, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Galli, SJ (reprint author), Beth Israel Deaconess Med Ctr E, Dept Pathol, POB 15707, Boston, MA 02215 USA. EM sgalli@bidmc.harvard.edu FU NCI NIH HHS [CA/AI-72074, R01 CA050453, R01 CA064436, R01 CA072074, R29 CA064436]; NIAID NIH HHS [AI-41955, AI/GM-23990, R01 AI023990, R37 AI023990] NR 43 TC 219 Z9 222 U1 0 U2 7 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 SEP 21 PY 1998 VL 188 IS 6 BP 1135 EP 1145 DI 10.1084/jem.188.6.1135 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 123EK UT WOS:000076112700014 PM 9743532 ER PT J AU Karlsson, GB Halloran, M Schenten, D Lee, J Racz, P Tenner-Racz, K Manola, J Gelman, R Etemad-Moghadam, B Desjardins, E Wyatt, R Gerard, NP Marcon, L Margolin, D Fanton, J Axthelm, MK Letvin, NL Sodroski, J AF Karlsson, GB Halloran, M Schenten, D Lee, J Racz, P Tenner-Racz, K Manola, J Gelman, R Etemad-Moghadam, B Desjardins, E Wyatt, R Gerard, NP Marcon, L Margolin, D Fanton, J Axthelm, MK Letvin, NL Sodroski, J TI The envelope glycoprotein ectodomains determine the efficiency of CD4(+) T lymphocyte depletion in simian-human immunodeficiency virus-infected macaques SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HTLV-III/LAV ENVELOPE; RHESUS-MONKEYS; HIV-1 INFECTION; PERSISTENT INFECTION; TYPE-1; RECEPTOR; AIDS; PLASMA; RETROVIRUS; ISOLATE AB CD4(+) T lymphocyte depletion in human immunodeficiency virus type 1 (HIV-1)-infected humans underlies the development of acquired immune deficiency syndrome. Using a model in which rhesus macaques were infected with chimeric simian-human immunodeficiency viruses (SHIVs), we show that both the level of viremia and the structure of the HIV-1 envelope glycoprotein ectodomains individually contributed to the efficiency with which CD4(+) T lymphocytes were depleted. The envelope glycoproteins of recombinant SHIVs that efficiently caused loss of CD4(+) T lymphocytes exhibited increased chemokine receptor binding and membrane-fusing capacity compared with those of less pathogenic viruses. These studies identify the HIV-1 envelope glycoprotein ectodomains as determinants of CD4(+) T lymphocyte loss in vivo and provide a foundation for studying pathogenic mechanisms. 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 Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Isreal Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02115 USA. Bernhard Nocht Inst Trop Med, Dept Pathol, D-20359 Hamburg, Germany. Bernhard Nocht Inst Trop Med, Korber Lab, D-20359 Hamburg, Germany. Harvard Univ, Sch Med, Beth Istrael Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Istrael Deaconess Med Ctr, Dept Pediat, Boston, MA 02115 USA. Univ Padua, Sch Med, Inst Microbiol, I-35121 Padua, Italy. Oregon Reg Primate Res Ctr, Beaverton, OR 97006 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. EM Joseph_Sodroski@dfci.harvard.edu FU NCI NIH HHS [CA-06516, CA-50139, P30 CA006516, R01 CA050139]; NCRR NIH HHS [K01 RR000163, K26 RR000168, P51 RR000163, T32 RR007000, P51 RR000168]; NIAID NIH HHS [AI-20729, P30 AI028691, R01 AI020729, R01 AI033832, R37 AI020729] NR 48 TC 94 Z9 95 U1 1 U2 3 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 SEP 21 PY 1998 VL 188 IS 6 BP 1159 EP 1171 DI 10.1084/jem.188.6.1159 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 123EK UT WOS:000076112700016 PM 9743534 ER PT J AU Petersen, LA AF Petersen, LA TI Recent advances - General medicine SO BRITISH MEDICAL JOURNAL LA English DT Review ID CORONARY HEART-DISEASE; MYOCARDIAL-INFARCTION; RANDOMIZED TRIAL; HIV-1 RNA; CARDIOVASCULAR-DISEASE; POSTMENOPAUSAL WOMEN; ALCOHOL-CONSUMPTION; FOLLOW-UP; RISK; MORTALITY C1 Dept Vet Affairs Med Ctr, Hlth Serv Res & Dev, Houston, TX 77030 USA. RP Petersen, LA (reprint author), Dept Vet Affairs Med Ctr, Hlth Serv Res & Dev, Houston, TX 77030 USA. NR 29 TC 0 Z9 0 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD SEP 19 PY 1998 VL 317 IS 7161 BP 792 EP 795 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 122RA UT WOS:000076084200034 PM 9740570 ER PT J AU Fukumura, D Xavier, R Sugiura, T Chen, Y Park, EC Lu, NF Selig, M Nielsen, G Taksir, T Jain, RK Seed, B AF Fukumura, D Xavier, R Sugiura, T Chen, Y Park, EC Lu, NF Selig, M Nielsen, G Taksir, T Jain, RK Seed, B TI Tumor induction of VEGF promoter activity in stromal cells SO CELL LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY; ANTIANGIOGENIC THERAPY; FACTOR EXPRESSION; TRANSGENIC MICE; MESSENGER-RNA; UP-REGULATION; ANGIOGENESIS; HYPOXIA; MECHANISMS AB We have established a line of transgenic mice expressing the A. victoria green fluorescent protein (GFP) under the control of the promoter for vascular endothelial growth factor (VEGF). Mice bearing the transgene show green cellular fluorescence around the healing margins and throughout the granulation tissue of superficial ulcerative wounds. Implantation of solid tumors in the transgenic mice leads to an accumulation of green fluorescence resulting from tumor induction of host VEGF promoter activity. With time, the fluorescent cells invade the tumor and can be seen throughout the tumor mass. Spontaneous mammary tumors induced by oncogene expression in the VEGF-GFP mouse show strong stromal, but not tumor, expression of GFP. In both wound and tumor models the predominant GFP-positive cells are fibroblasts. The finding that the VEGF promoter of nontransformed cells is strongly activated by the tumor microenvironment points to a need to analyze and understand stromal cell collaboration in tumor angiogenesis. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Melvin B & Barbara K Nessel Gene Therapy Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. FU NCI NIH HHS [R35-CA-56591]; NIAID NIH HHS [AI27849]; NIDDK NIH HHS [DK43031] NR 38 TC 644 Z9 670 U1 0 U2 27 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD SEP 18 PY 1998 VL 94 IS 6 BP 715 EP 725 DI 10.1016/S0092-8674(00)81731-6 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 121NX UT WOS:000076021200005 PM 9753319 ER PT J AU Vadlamudi, RK Shin, J AF Vadlamudi, RK Shin, J TI Genomic structure and promoter analysis of the p62 gene encoding a non-proteasomal multiubiquitin chain binding protein SO FEBS LETTERS LA English DT Article DE p62; ubiquitin chain; TATA-less; CpG island ID PHOSPHOTYROSINE-INDEPENDENT LIGAND; DNA METHYLATION; SH2 DOMAIN; SEQUENCE; TRANSCRIPTION; P56(LCK) AB p62 is a novel immediate early response gene encoding a ubiquitin chain binding protein. To investigate the mechanism of p62 gene expression, we isolated and characterized the 20 kb long human p62 gene. The p62 gene contains seven introns and eight exons, The splice sites conformed to the GT/AG rule, except introns 6 and 7 which used the unusual GC dinucleotides, The p62 promoter is TATA-less, and 357 nucleotides of the 5'-flanking region contain basic machineries for transcription. A reporter gene linked to 1800 nucleotides of the 5'-flanking region was rapidly activated by various extracellular signals. The presence of a CpG island as well as multiple binding sites for SP-1, AP-1, NF-kappa B, and Ets-1 family in the promoter region supports the regulated activation of the p62 gene. (C) 1998 Federation of European Biochemical Societies. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Tumor Virol, Boston, MA 02115 USA. RP Shin, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Tumor Virol, 44 Binney St, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM48961] NR 21 TC 34 Z9 35 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD SEP 18 PY 1998 VL 435 IS 2-3 BP 138 EP 142 DI 10.1016/S0014-5793(98)01021-7 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 123RL UT WOS:000076138100002 PM 9762895 ER PT J AU Allen, M Chu, S Brill, S Stotler, C Buckler, A AF Allen, M Chu, S Brill, S Stotler, C Buckler, A TI Restricted tissue expression pattern of a novel human rasGAP-related gene and its murine ortholog SO GENE LA English DT Article ID GTPASE-ACTIVATING-PROTEIN; PHOSPHOLIPID-BINDING; EXON AMPLIFICATION; DOMAIN; IDENTIFICATION; MUTANTS; FAMILY; CALMODULIN; MECHANISM; COMPLEX AB The mammalian rasGAPs constitute a group of widely expressed proteins involved in the negative regulation of ras-mediated signaling. In this study we have isolated a novel human gene, RASAL (Ras GTPase-activating-like) and its murine ortholog, MRASAL which are most similar to the GAP1 family of rasGAP proteins, based upon the presence and organization of specific conserved domains. Full-length human and murine mRNA sequences are predicted to encode 804 and 799 amino acid polypeptides, respectively. Sequence analysis of these two proteins revealed the presence of two N-terminal calcium-dependent phospholipid binding C2 domains, a conserved GAP related domain (GRD) and a C-terminal pleckstrin homology (PH) domain. Northern blot and mRNA in situ hybridization analyses indicate that RASAL, in contrast to other mammalian rasGAP proteins, has a limited expression pattern; RASAL is highly expressed :in the follicular cells of the thyroid and the adrenal medulla and expressed at lower levels in brain, spinal cord and trachea. Human RASAL has been localized by radiation hybrid mapping to chromosome 12q23-24. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Axys Pharmaceut, La Jolla, CA 92037 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Allen, M (reprint author), Axys Pharmaceut, Suite 160,11099 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM maxine_allen@sequana.com FU NHGRI NIH HHS [HG 00672-06] NR 40 TC 26 Z9 30 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD SEP 18 PY 1998 VL 218 IS 1-2 BP 17 EP 25 DI 10.1016/S0378-1119(98)00394-1 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 124VW UT WOS:000076204300003 PM 9751798 ER PT J AU Laser, M Kasi, VS Hamawaki, M Cooper, G Kerr, CM Kuppuswamy, D AF Laser, M Kasi, VS Hamawaki, M Cooper, G Kerr, CM Kuppuswamy, D TI Differential activation of p70 and p85 S6 kinase isoforms during cardiac hypertrophy in the adult mammal SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE; SIGNAL-TRANSDUCTION; IN-VITRO; PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE PHOSPHORYLATION; DEPENDENT ACTIVATION; GENE-EXPRESSION; CYCLIC-AMP; PHAS-I; RAPAMYCIN AB An adult feline right ventricular pressure overload (RVPO) model was used to examine the two S6 kinase (S6K) isoforms, p70(S6K) and p85(S6K), that are involved in translational and transcriptional activation. Biochemical and confocal microscopy analyses at the level of the cardiocyte revealed that p70(S6K) is present predominantly in the cytosol, substantially activated in 1-h RVPO (>12 fold), and phosphorylated in the pseudosubstrate domain at the Ser-411, Thr-421, and Ser-424 sites. p85(S6K), which was localized exclusively in the nucleus, showed activation subsequent to p70(S6K). With a sustained increase in phosphorylation for up to 48 h of RVPO at equivalent sites of p70(S6K), Thr-421 and Ser-424, but not at Ser-411. Neither isoform translocated between the cytosol and the nucleus. Further studies to determine potential upstream elements of S6K activation revealed: (i) similar time course of activation for protein kinase C isoforms (alpha, gamma, and epsilon) and c-Raf, (ii) absence of accompanying phosphatidylinositol S-kinase activation, (iii) activation of c-Src subsequent to p70(S6K), and (iv) similar changes in adult cardiocytes after treatment with 12-O-tetradecanoylphorbol-13-acetate. Thus, these studies suggest that a protein kinase C-mediated pathway couples pressure overload to growth induction via differential activation of S6K isoforms in cardiac hypertrophy. C1 Med Univ S Carolina, Dept Med, Div Cardiol, Charleston, SC 29425 USA. Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Physiol, Charleston, SC 29425 USA. Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Cell Biol, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Kuppuswamy, D (reprint author), Med Univ S Carolina, Dept Med, Div Cardiol, 171 Ashley Ave, Charleston, SC 29425 USA. FU NHLBI NIH HHS [HL-487788] NR 57 TC 55 Z9 57 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 SEP 18 PY 1998 VL 273 IS 38 BP 24610 EP 24619 DI 10.1074/jbc.273.38.24610 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 121HL UT WOS:000076007300048 PM 9733756 ER PT J AU Tsukaguchi, H Shayakul, C Berger, UV Mackenzie, B Devidas, S Guggino, WB van Hoek, AN Hediger, MA AF Tsukaguchi, H Shayakul, C Berger, UV Mackenzie, B Devidas, S Guggino, WB van Hoek, AN Hediger, MA TI Molecular characterization of a broad selectivity neutral solute channel SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID KIDNEY COLLECTING DUCT; WATER CHANNELS; UREA TRANSPORTER; XENOPUS-OOCYTES; RAT-KIDNEY; FUNCTIONAL EXPRESSION; CLONING; MEMBRANE; GLYCEROL; CELLS AB In all living cells, coordination of solute and water movement across cell membranes is of critical importance for osmotic balance. The current concept is that these processes are of distinct biophysical nature. Here we report the expression cloning of a Liver cDNA encoding a unique promiscuous solute channel (AQP9) that confers high permeability for both solutes and water. AQP9 mediates passage of a wide variety of non-charged solutes including carbamides, polyols, purines, and pyrimidines in a phloretin- and mercury-sensitive manner, whereas amino acids, cyclic sugars, Na+, K+, Cl-, and deprotonated monocarboxylates are excluded. The properties of AQP9 define a new evolutionary branch of the major intrinsic protein family of aquaporin proteins and describe a previously unknown mechanism by which a large variety of solutes and water can pass through a single pore, enabling rapid cellular uptake or exit of metabolites with minimal osmotic perturbation. C1 Brigham & Womens Hosp, Div Renal, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02129 USA. RP Hediger, MA (reprint author), Brigham & Womens Hosp, Div Renal, Dept Med, 77 Ave Louis Pasteur, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK32753, DK38452, DK46289] NR 30 TC 303 Z9 311 U1 1 U2 9 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 SEP 18 PY 1998 VL 273 IS 38 BP 24737 EP 24743 DI 10.1074/jbc.273.38.24737 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 121HL UT WOS:000076007300066 PM 9733774 ER PT J AU Counter, SA Buchanan, LH Rosas, HD Ortega, F AF Counter, SA Buchanan, LH Rosas, HD Ortega, F TI Neurocognitive effects of chronic lead intoxication in Andean children SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE lead; neurotoxicity; motor; neurocognitive ID COGNITIVE-DEVELOPMENT; EXPOSURE; DENTIN AB Lead (Pb) intoxication in children has been associated with neurodevelopmental disabilities which may result in motor and cognitive impairment. We conducted blood lead (PbB) measurements, neurological examinations and cognitive tests on children living in Ecuadorian villages where Pb is used extensively in the glazing of ceramics. Group I consisted of 55 children with a mean PbB level of 48.0 mu g/dl (SD: 26.4, range: 9.2-119.1 mu g/dl) who received PbB tests and complete neurological examinations. An appreciable number of the children with elevated PbB levels were normal on specific components of the neurological examination. Among the children who showed neurological deficits, higher PbB levels were associated with abnormal tendon reflexes, finger tapping, visual pursuit, size discrimination, draw-a-person, and math calculation skills. Group II consisted of 41 children with a mean PbB level of 47.4 mu g/dl (SD: 22.0, range: 6.6-84.7 mu g/dl) who were administered Raven's Coloured Progressive Matrices (RCPM) non-verbal reasoning test. Performance on RCPM was abnormal in 22 (53.7%) of 41 children. Children with abnormal RCPM scores had higher PbB levels (t-test: P=0.030). There was a significant inverse correlation between RCPM scores and PbB levels for children ages 9 years and older (r=-0.618, P=0.011). Males had higher mean PbB levels as a function of age than females (t-test: P=0.037), and more males showed neurocognitive deficits. The results demonstrate a range of neurological responses in children with chronically elevated PbB levels from apparent exceptional neuro-physiological tolerance of PbB intoxication, to some fine motor and cognitive deficits. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Dept Neurol, Biol Labs, Cambridge, MA 02138 USA. Karolinska Inst, Dept Physiol & Pharmacol, S-17176 Stockholm, Sweden. Harvard Univ, Shriver Ctr, Dept Audiol, Waltham, MA 02154 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ San Francisco, Dept Med, Quito, Ecuador. RP Counter, SA (reprint author), Harvard Univ, Dept Neurol, Biol Labs, Cambridge, MA 02138 USA. EM allen_Counter@harvard.edu NR 23 TC 27 Z9 28 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 SEP 18 PY 1998 VL 160 IS 1 BP 47 EP 53 DI 10.1016/S0022-510X(98)00180-4 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 129XU UT WOS:000076490000007 PM 9804116 ER PT J AU Tarazi, FI Tomasini, EC Baldessarini, RJ AF Tarazi, FI Tomasini, EC Baldessarini, RJ TI Postnatal development of dopamine and serotonin transporters in rat caudate-putamen and nucleus accumbens septi SO NEUROSCIENCE LETTERS LA English DT Article DE autoradiography; caudate-putamen; dopamine transporter; nucleus accumbens; postnatal development; serotonin transporter ID UPTAKE SITES; BRAIN; BINDING; RECEPTORS; DISORDER; STRIATUM; DRUGS AB Density of dopamine transporter (DA(T)) and serotonin transporter (5-HTT) membrane proteins in the caudate-putamen (CPu) and nucleus accumbens (NAc) of rat brain was assessed at seven ages at: postnatal days (PD) 7-60, by in vitro quantitative autoradiography. Binding of [H-3]GBR-12935 (to DA(T)) and [H-3]paroxetine (to 5-HTT) increased steadily and very similarly, from low levels at PD-7 to maximal levels, to 6-7-fold higher density at PD-60 in both regions. These findings indicate that DA(T) and 5-HTT follow a synchronized course of development in rat CPu and NAc. In contrast to reported elimination of excessive receptors in CPu and NAc during maturation, there was no evidence of pruning of DA(T) or 5-HTT in these regions of rat forebrain. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mailman Res Ctr,McLean Div, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Tarazi, FI (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mailman Res Ctr,McLean Div, 115 Mill St, Belmont, MA 02178 USA. FU NIMH NIH HHS [MH-19905, MH-34006, MH-47370] NR 20 TC 105 Z9 105 U1 1 U2 2 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 SEP 18 PY 1998 VL 254 IS 1 BP 21 EP 24 DI 10.1016/S0304-3940(98)00644-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 122VC UT WOS:000076091300006 PM 9780082 ER PT J AU Bracy, JL Sachs, DH Iacomini, J AF Bracy, JL Sachs, DH Iacomini, J TI Inhibition of xenoreactive natural antibody production by retroviral gene therapy SO SCIENCE LA English DT Article ID XENOTRANSPLANTATION; PIG; REJECTION; BARRIERS; SAFE; LINE AB The major barrier to transplantation across discordant species, such as from pig to human, is rejection mediated by xenoreactive natural antibodies (XNA) that bind the carbohydrate epitope Gal alpha 1-3Gal beta 1-4GlcNAc-R (alpha Gal) on donor tissues. This epitope is synthesized by the enzyme glucosyltransferase uridine 5'-diphosphate galactose:beta-D-galactosyl-1.4-N-acetyl-D-glucosaminide alpha(1-3)galactosyltransferase (E.C. 2.4.1.151), pr simply alpha GT. When a functional alpha GT gene was introduced by retroviral gene transfer into bone marrow cells, alpha GaL XNA production in a murine model ceased. Thus, genetic engineering of bone marrow may overcome humoral rejection of discordant xenografts and may be useful for inducing B cell tolerance. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Allegheny Univ Hlth Sci, Mol & Cellular Biol Program, Philadelphia, PA 19129 USA. RP Iacomini, J (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bldg 149-5210,13th St, Boston, MA 02129 USA. NR 25 TC 98 Z9 103 U1 0 U2 1 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 SEP 18 PY 1998 VL 281 IS 5384 BP 1845 EP 1847 DI 10.1126/science.281.5384.1845 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 121HK UT WOS:000076007100051 PM 9743496 ER PT J AU Albertsen, PC Hanley, JA Gleason, DF Barry, MJ AF Albertsen, PC Hanley, JA Gleason, DF Barry, MJ TI Competing risk analysis of men aged 55 to 74 years at diagnosis managed conservatively for clinically localized prostate cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID LONG-TERM SURVIVAL; RADICAL PROSTATECTOMY; MORTALITY; ANTIGEN AB Context.-The appropriate therapy for men with localized prostate cancer is uncertain. Until results of clinical trials are available, men and their physicians need guidance. Objective.-To estimate survival based on a competing risk analysis stratified by age at diagnosis and histologic findings for men diagnosed as having clinically localized prostate cancer and who were managed conservatively. Design.-Retrospective cohort study, Setting.-Connecticut Tumor Registry. Patients.-A total of 767 men with localized prostate cancer diagnosed between 1971 and 1984, aged 55 to 74 years at diagnosis, either not treated or treated with immediate pr delayed hormonal therapy, and followed up for 10 to 20 years after diagnosis. Main Outcome Measures.-Estimates of the probability of dying from prostate cancer or other competing hazards, Results.-Men with tumors that have Gleason scores of 2 to 4, 5, 6, 7, and 8 to 10 face a 4% to 7%, 6% to 11%, 18% to 30%, 42% to 70%, and 60% to 87% chance, respectively, of dying from prostate cancer within 15 years of diagnosis depending on their age at diagnosis, Conclusions.-Men whose prostate biopsy specimens show Gleason score 2 to 4 disease face a minimal risk of death from prostate cancer within 15 years of diagnosis, Conversely, men whose biopsy specimens show Gleason score 7 to 10 disease face a high risk of death from prostate cancer when treated conservatively, even when cancer is diagnosed as late as age 74 years, Men with Gleason score 5 or 6 tumors face a modest risk of death from prostate cancer that increases slowly over at least 15 years of follow-up. C1 Univ Connecticut, Ctr Hlth, Div Urol, Farmington, CT 06030 USA. McGill Univ, Dept Epidemiol & Biostat, Montreal, PQ, Canada. Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. RP Albertsen, PC (reprint author), Univ Connecticut, Ctr Hlth, Div Urol, 263 Farmington Ave, Farmington, CT 06030 USA. FU AHRQ HHS [HS 08397]; NCRR NIH HHS [M01 RR06192] NR 22 TC 458 Z9 473 U1 2 U2 7 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 SEP 16 PY 1998 VL 280 IS 11 BP 975 EP 980 DI 10.1001/jama.280.11.975 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 119JC UT WOS:000075891400030 PM 9749479 ER PT J AU Smith-Bindman, R Kerlikowske, K AF Smith-Bindman, R Kerlikowske, K TI Is there a downside to elderly women undergoing screening mammography? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID BREAST-CANCER; AGE C1 San Francisco Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Kerlikowske, K (reprint author), San Francisco Vet Affairs Med Ctr, Gen Internal Med Sect, Sect 111A1,4150 Clement St, San Francisco, CA 94121 USA. FU NCI NIH HHS [P50CA58207, 1U01CA63740] NR 15 TC 13 Z9 13 U1 0 U2 0 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 SEP 16 PY 1998 VL 90 IS 18 BP 1322 EP 1323 DI 10.1093/jnci/90.18.1322 PG 2 WC Oncology SC Oncology GA 120NT UT WOS:000075963000002 PM 9747859 ER PT J AU Weissman, NJ Sheris, SJ Picard, MH Bach, DS Sklar, J Cohen, JL AF Weissman, NJ Sheris, SJ Picard, MH Bach, DS Sklar, J Cohen, JL TI Effect of atenolol or metoprolol on arbutamine stress echocardiography in patients suspected of waving coronary artery disease SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MYOCARDIAL-ISCHEMIA; DOBUTAMINE; EXERCISE; ATROPINE; ACCURACY; AGENT AB Arbutamine stress echocardiography was performed in 81 patients with suspected coronary artery disease. Arbutamine infusion, using a dedicated closed-loop delivery device, provided comparable myocardial stress in patients receiving p-l blockers versus those who were not. C1 Georgetown Univ, Med Ctr, Div Cardiol, Washington, DC 20007 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Marin Heart Inst, Larkspur, CA USA. Vet Adm Med Ctr, E Orange, NJ 07019 USA. RP Weissman, NJ (reprint author), Georgetown Univ, Med Ctr, Div Cardiol, 3800 Reservoir Rd NW, Washington, DC 20007 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 15 PY 1998 VL 82 IS 6 BP 830 EP + DI 10.1016/S0002-9149(98)00479-2 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 122CK UT WOS:000076053100028 PM 9761104 ER PT J AU Caroff, SN Mann, SC Keck, PE AF Caroff, SN Mann, SC Keck, PE TI Specific treatment of the neuroleptic malignant syndrome SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID LETHAL CATATONIA; ELECTROCONVULSIVE-THERAPY; ANIMAL-MODEL; ONE ENTITY; DANTROLENE C1 Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Cincinnati, Coll Med, Dept Psychiat, Biol Psychiat Program, Cincinnati, OH 45267 USA. RP Caroff, SN (reprint author), Univ Penn, Sch Med, Dept Psychiat, Univ Ave, Philadelphia, PA 19104 USA. NR 43 TC 22 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 15 PY 1998 VL 44 IS 6 BP 378 EP 381 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 121LM UT WOS:000076015300002 PM 9777166 ER PT J AU Maher, BA Manschreck, TC Yurgelun-Todd, DA Tsuang, MT AF Maher, BA Manschreck, TC Yurgelun-Todd, DA Tsuang, MT TI Hemispheric asymmetry of frontal and temporal gray matter and age of onset in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE hemispheric asymmetry; schizophrenia; age of onset ID LATERALITY AB Background: Investigators have reported lack of normal asymmetry of lateralization in some schizophrenic patients, as measured postmortem and by preference and/or performance. It has been suggested that this lack of asymmetry is related to early onset of schizophrenia. The present study extends the inquiry by magnetic resonance imaging (MRI) measurement of volumetric asymmetry. Methods: Hemispheric asymmetry of volume in regional gray matter was examined in 16 schizophrenic patients who had undergone MRI of brain volume. Results: Low levels of hemispheric asymmetry in the frontal and temporal areas were strongly associated with early onset of schizophrenia, the association with frontal volume being more marked than with temporal volume. No relationship was found in the other brain areas that were scanned The findings were not artifacts of chronological age, nor of extreme scores in a small sample. Conclusions: These findings are consistent with the hypothesis that failure to develop asymmetry is an important component of the pathology underlying some forms of schizophrenia. (C) 1998 Society of Biological Psychiatry. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Vet Adm Hosp, Brockton, MA 02401 USA. Corrigan Mental Hlth Ctr, Fall River, MA USA. Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. Harvard Univ, Sch Publ Hlth, Dept Psychol, Cambridge, MA 02138 USA. RP Maher, BA (reprint author), Harvard Univ, Dept Psychol, 1120 William James Hall, Cambridge, MA 02138 USA. NR 19 TC 30 Z9 30 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 15 PY 1998 VL 44 IS 6 BP 413 EP 417 DI 10.1016/S0006-3223(98)00076-6 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 121LM UT WOS:000076015300006 PM 9777170 ER PT J AU Wirshing, DA Bartzokis, G Pierre, JM Wirshing, WC Sun, A Tishler, TA Marder, SR AF Wirshing, DA Bartzokis, G Pierre, JM Wirshing, WC Sun, A Tishler, TA Marder, SR TI Tardive dyskinesia and serum iron indices SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; neuroleptics; tardive dyskinesia; serum ferritin; akathisia; iron ID INDUCED MOVEMENT-DISORDERS; VITAMIN-E TREATMENT; BRAIN IRON; MYOCARDIAL-INFARCTION; MR EVALUATION; RAT-BRAIN; SCHIZOPHRENIA; MEN; CHLORPROMAZINE; DEFICIENCY AB Background: This study was undertaken to evaluate whether peripheral (serum) markers of iron status are associated with severity of the choreoathetoid movements seen in tardive dyskinesia (TD). Methods: Serum iron indices (ferritin, iron, and total iron binding capacity) and fluphenazine levels were measured in a group of 30 male DSM-III diagnosed schizophrenic patients chronically treated with fluphenazine decanoate. The severity of choreoathetoid movements was assessed with the Abnormal Involuntary Movement Scale (AIMS), and akathisia was assessed with the Barnes scale. Results: A significant positive correlation was observed between AIMS scores and serum ferritin. This relationship remained significant after controlling for age and plasma fluphenazine levels. No significant correlations were observed between serum iron or total iron binding capacity and choreoathetoid movement ratings. There were no significant associations between serum iron indices and akathisia ratings. Conclusions: The data suggest that choreoathetoid movements are associated with serum ferritin levels in chronically medicated male schizophrenic patients. This relationship does not seem to be caused by an association of these variable with age or plasma fluphenazine levels, in addition, the relationship seems to be specific, since other iron indices and another extrapyramidal side effect (akathisia) do not demonstrate a similar relationship. In view of reports that antipsychotic medications change normal iron metabolism and increase iron uptake into the brain, the current results could be interpreted to suggest that serum ferritin levels may be a risk factor for TD in patients treated with "classic" antipsychotic medications. Published 1998 Society of Biological Psychiatry. C1 W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. RP W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, 11301 Wilshire Blvd,Mail Code B-151H, Los Angeles, CA 90073 USA. RI Bartzokis, George/K-2409-2013 NR 48 TC 6 Z9 6 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 15 PY 1998 VL 44 IS 6 BP 493 EP 498 DI 10.1016/S0006-3223(97)00453-8 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 121LM UT WOS:000076015300018 PM 9777182 ER PT J AU Quackenbush, EJ Wershil, BK Aguirre, V Gutierrez-Ramos, JC AF Quackenbush, EJ Wershil, BK Aguirre, V Gutierrez-Ramos, JC TI Eotaxin modulates myelopoiesis and mast cell development from embryonic hematopoietic progenitors SO BLOOD LA English DT Article ID MOUSE BONE-MARROW; MURINE YOLK-SAC; STEM-CELLS; KIT-LIGAND; C-KIT; EXPRESSION; DIFFERENTIATION; ANTIGEN; IDENTIFICATION; MIGRATION AB Eotaxin is a potent chemoattractant for eosinophils during inflammation and allergic reactions in the adult, but its role in the embryonic development of the hematopoietic system has not been examined. We report here that eotaxin and its receptor, CCR-3, are expressed by embryonic tissues responsible for blood development, such as fetal liver (FL), yolk sac (YS), and peripheral blood. We found that eotaxin acts synergistically with stem cell factor to accelerate the differentiation of embryonic mast cell progenitors, and this response can he suppressed by pertussis toxin, an inhibitor of chemokine-induced signaling through Gi, protein and chemotaxis. Eotaxin promotes the differentiation of fetal mast cell progenitors into differentiated mast cells as defined by the expression of mast cell specific proteases. Furthermore, in combination with stem cell factor (SCF), it promotes the growth of Mac-1(+) myeloid cells from Embryonic progenitors. These studies suggest that eotaxin may be involved in the growth of granulocytic progenitors and the differentiation and/or function of mast cells during embryogenesis and/or pathological conditions that induce high levels of eotaxin, such as allergic responses. (C) 1998 by The American Society of Hematology. C1 Millennium Pharmaceuts Inc, Cambridge, MA 02139 USA. Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Childrens Hosp, Div Clin Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA USA. Beth Israel Deaconess Hosp, Div Expt Pathol, Boston, MA USA. RP Gutierrez-Ramos, JC (reprint author), Millennium Pharmaceuts Inc, 640 Mem Dr, Cambridge, MA 02139 USA. FU NIDDK NIH HHS [DK40561, DK33506, DK46819] NR 52 TC 40 Z9 42 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 1998 VL 92 IS 6 BP 1887 EP 1897 PG 11 WC Hematology SC Hematology GA 118HJ UT WOS:000075832200006 PM 9731045 ER PT J AU Kalemkerian, GP Jiroutek, M Ettinger, DS Dorighi, JA Johnson, DH Mabry, M AF Kalemkerian, GP Jiroutek, M Ettinger, DS Dorighi, JA Johnson, DH Mabry, M TI A phase II study of all-trans-retinoic acid plus cisplatin and etoposide in patients with extensive stage small cell lung carcinoma - An Eastern Cooperative Oncology Group Study SO CANCER LA English DT Article DE lung carcinoma; all-trans-retinoic acid; combination chemotherapy; cisplatin; etoposide; experimental therapeutics ID ACUTE PROMYELOCYTIC LEUKEMIA; GROWTH-INHIBITION; TUMOR PROGRESSION; SOLID TUMORS; CANCER; LINES; EXPRESSION; DIFFERENTIATION; CHEMOTHERAPY; THERAPY AB BACKGROUND. The dysregulation of both myc gene expression and retinoid signaling pathways commonly occurs in small cell lung carcinoma (SCLC). Because preclinical data showed that all-trans-retinoic acid (RA) inhibited SCLC growth, altered myc expression, and blocked transition to a treatment-resistant phenotype, a Phase II trial was designed to determine the effects of the combination of RA, cisplatin, and etoposide in patients with SCLC. METHODS. Patients with untreated, extensive stage SCLC were treated with up to 8 cycles of cisplatin, 60 mg/m(2), intravenously (i.v.) on Day 1 and etoposide, 120 mg/m(2), i.v. on Days 1-3 in addition to up to 1 year of oral RA, 150 mg/m(2)/day. RESULTS. Of 22 assessable patients 1 had a complete response and 9 had a partial response, for an overall. response rate of 45% (95% confidence interval, 24-68%). The median survival was 10.9 months and the 1-year survival was 41%, The median duration of chemotherapy was 6 cycles and the median duration of RA treatment was 2.8 months. Thirteen patients discontinued RA prematurely due to toxicity and only 4 responders were receiving RA at the time of recurrence, Toxicity-limiting RA treatment mainly was comprised of mucocutaneous changes and headaches. CONCLUSIONS. RA at a dose of 150 mg/m2/day was tolerated poorly in combination with cisplatin plus etoposide, leading to early discontinuation of RA in the majority of patients. The hematologic toxicity, response rate, and survival were similar to those associated with cisplatin and etoposide in prior trials. Further studies with more active and less toxic agents will be required to determine the role of retinoids in the treatment of SCLC. (C) 1998 American Cancer Society. C1 Johns Hopkins Oncol Ctr, Dept Med Oncol, Baltimore, MD USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. Swedish Amer Hosp, Dept Oncol, Rockford, IL USA. Vanderbilt Univ, Sch Med, Div Med Oncol, Nashville, TN 37212 USA. RP Kalemkerian, GP (reprint author), Harper Grace Hosp, Hudson Bldg,Room 515,3990 John R, Detroit, MI 48201 USA. RI Johnson, David/A-7437-2009 FU NCI NIH HHS [CA16116, CA23318, CA49957] NR 38 TC 22 Z9 24 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD SEP 15 PY 1998 VL 83 IS 6 BP 1102 EP 1108 DI 10.1002/(SICI)1097-0142(19980915)83:6<1102::AID-CNCR8>3.0.CO;2-9 PG 7 WC Oncology SC Oncology GA 118GM UT WOS:000075830100008 PM 9740074 ER PT J AU Bloomfield, CD Lawrence, D Byrd, JC Carroll, A Pettenati, MJ Tantravahi, R Patil, SR Davey, FR Berg, DT Schiffer, CA Arthur, DC Mayer, RJ AF Bloomfield, CD Lawrence, D Byrd, JC Carroll, A Pettenati, MJ Tantravahi, R Patil, SR Davey, FR Berg, DT Schiffer, CA Arthur, DC Mayer, RJ TI Frequency of prolonged remission duration after high-dose cytarabine intensification in acute myeloid leukemia varies by cytogenetic subtype SO CANCER RESEARCH LA English DT Article ID ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; INTENSIVE POSTREMISSION CHEMOTHERAPY; CLINICAL-SIGNIFICANCE; CYTOSINE-ARABINOSIDE; CURE RATE; KARYOTYPE; TRANSLOCATION; ABNORMALITIES; DAUNORUBICIN AB Advances in the treatment of acute myeloid leukemia (AML) have occurred with the introduction of new therapies including high-dose cytarabine and the identification of powerful prognostic factors such as cytogenetics that predict for long-term outcome. To date, the prognostic impact of cytarabine dose escalation within various cytogenetic groups of AML has not been assessed. We describe 285 newly diagnosed patients with primary AML who had adequate karyotypes and were enrolled on a prospective Cancer and Leukemia Group B cytogenetic study. All patients were randomly assigned to postremission treatment with standard-, intermediate-, or high-dose cytarabine intensification. Patients were categorized to one of three cytogenetic groups: (a) core binding factor type [(CBF); ie., t(8;21) inv(16), t(16;16), and del(16)]; (b) normal; and (c) other abnormality karyotype, An evaluation of these patients after a median follow-up time of over 7 years was performed to determine the relationship of intensification to outcome by cytogenetic group. Patients included 57 patients with CBF AML, 140 patients with normal karyotype AML, and 88 patients with other cytogenetic abnormalities. The treatment outcome of CBF AML patients was superior, with an estimated 50% still in complete remission (CR) after 5 years as compared with 32 and 15% for patients with normal karyotype AML and other abnormality AML, respectively (P < 0.001). Univariate analysis showed the following nonkaryotype factors to predict a prolonged CR duration: (a) younger age (P < 0.008); (b) lower leukocyte count (P = 0.01); (c) the presence of Auer rods (P = 0.004); (d) a lower percentage of bone marrow blasts (P = 0.001) at the time of diagnosis, (e) and a higher postremission cytarabine dose (P < 0.001). The impact of cytarabine dose an long-term remission was most marked (P < 0.001) in the CBF AML group (after 5 years, 78% of those with a dose of 3 g/m(2) were still in CR, 57% of those with a dose of 400 mg/m(2) were still in CR, and 16% of those with a dose of 100 mg/m(2) were still in CR) followed by normal karyotype AML (P = 0.01; after 5 years, 40% of those with a dose of 3 g/m2 were still in CR, 37% of those with a dose of 400 mg/m(2) were still in CR, and 20% of those with a dose of 100 mg/m2 were still in CR), In contrast, cytarabine at all doses produced only a 21% or less chance of long-term continuous CR for patients with other cytogenetic abnormalities. A multivariate analysis of CR duration assessed the independent impact of each of these variables on cure, Significant factors entering this model in descending order of importance were cytogenetic group (CBF > normal > other abnormality; P = 0.00001), cytarabine dose (3 g/m2 > 400 mg/m2 > 100 mg/m2; P = 0.00001),logarithm of leukocyte count at the time of diagnosis (P = 0.0005), and histological subtype of AML (P = 0.005). This study demonstrates that the curative impact of cytarabine intensification varies significantly among cytogenetic groups and results in a substantial prolongation of CR among patients with CBF and normal karyotypes, but not in those with other karyotypic abnormalities. These findings support the use of pretreatment cytogenetics in risk stratification of postremission AML therapy. C1 Walter Reed Army Med Ctr, Hematol Oncol Serv, Washington, DC 20307 USA. Ohio State Univ, Columbus, OH 43210 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Univ Alabama, Birmingham, AL 35229 USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC 27157 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Iowa, Iowa City, IA 52242 USA. SUNY Hlth Sci Ctr, Syracuse, NY 13210 USA. Univ Maryland, Ctr Canc, Baltimore, MD 21201 USA. Univ Minnesota, Minneapolis, MN 55455 USA. RP Byrd, JC (reprint author), Walter Reed Army Med Ctr, Hematol Oncol Serv, Ward 78, Washington, DC 20307 USA. FU PHS HHS [26806, 16058, 31946] NR 39 TC 490 Z9 498 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1998 VL 58 IS 18 BP 4173 EP 4179 PG 7 WC Oncology SC Oncology GA 120ZM UT WOS:000075987800030 PM 9751631 ER PT J AU Schwaller, J Frantsve, J Aster, J Williams, IR Tomasson, MH Ross, TS Peeters, P Van Rompaey, L Van Etten, RA Ilaria, R Marynen, P Gilliland, DG AF Schwaller, J Frantsve, J Aster, J Williams, IR Tomasson, MH Ross, TS Peeters, P Van Rompaey, L Van Etten, RA Ilaria, R Marynen, P Gilliland, DG TI Transformation of hematopoietic cell lines to growth-factor independence and induction of a fatal myelo- and lymphoproliferative disease in mice by retrovirally transduced TEL/JAK2 fusion genes SO EMBO JOURNAL LA English DT Article DE animal model; leukemogenesis; Stat 5; TEL-JAK2 fusion gene; transformation ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOMONOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; COLONY-STIMULATING FACTOR; DNA-BINDING ACTIVITY; BCR-ABL ONCOGENE; TYROSINE KINASE; CONSTITUTIVE ACTIVATION; SIGNAL-TRANSDUCTION; T-LYMPHOCYTES AB Recent reports have demonstrated fusion of the TEL gene on 12p13 to the JAK2 gene on 9p24 in human leukemias. Three variants have been identified that fuse the TEL pointed (PNT) domain to (i) the JAK2 JH1-kinase domain, (ii) part of and (iii) all of the JH2 pseudokinase domain. We report that all of the human TEL/JAK2 variants, and a human/mouse chimeric hTEL/mJAK2(JH1) fusion gene, transform the interleukin-3 (IL-3)-dependent murine hematopoietic cell line Ba/F3 to IL-3-independent growth. Transformation requires both the TEL PNT domain and JAK2 kinase activity. Furthermore, all TEL/JAK2 variants strongly activated STAT 5 by phosphotyrosine Western blots and by electrophoretic mobility shift assays (EMSA). Mice (n = 40) transplanted with bone marrow infected with the MSCV retrovirus containing either the hTEL/mJAK2(JH2) fusion or its human counterpart developed a fatal mixed myeloproliferative and T-cell lymphoproliferative disorder,vith a latency of 2-10 weeks. In contrast, mice transplanted with a TEL/JAK2 mutant lacking the TEL PNT domain (n = 10) or a kinase-inactive TEL/JAK2(JH1) mutant (n = 10) did not develop the disease. We conclude that all human TEL/JAK2 fusion variants are oncoproteins in vitro that strongly activate STAT 5, and cause lethal myelo- and lymphoproliferative syndromes in murine bone marrow transplant models of leukemia. C1 Brigham & Womens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Emory Univ, Dept Pathol, Atlanta, GA USA. Katholieke Univ Leuven, Ctr Human Genet, Louvain, Belgium. RP Gilliland, DG (reprint author), Brigham & Womens Hosp, Div Hematol & Oncol, 75 Francis St, Boston, MA 02115 USA. EM gilliland@calvin.bwh.harvard.edu RI Williams, Ifor/D-3648-2011; schwaller, juerg/A-3044-2016 OI Williams, Ifor/0000-0002-8810-2911; FU NCI NIH HHS [P0I CA 66996, P01 CA066996]; NIDDK NIH HHS [P01 DK050654, P0I DK 50654] NR 74 TC 210 Z9 216 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD SEP 15 PY 1998 VL 17 IS 18 BP 5321 EP 5333 DI 10.1093/emboj/17.18.5321 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 123LC UT WOS:000076125800007 PM 9736611 ER PT J AU Sif, S Stukenberg, PT Kirschner, MW Kingston, RE AF Sif, S Stukenberg, PT Kirschner, MW Kingston, RE TI Mitotic inactivation of a human SWI/SNF chromatin remodeling complex SO GENES & DEVELOPMENT LA English DT Article DE SWI/SNF complex; nucleosomes; phosphorylation; mitosis; chromatin ID TATA-BINDING-PROTEIN; CELL-CYCLE; TRANSCRIPTIONAL ACTIVATORS; MULTISUBUNIT COMPLEX; NUCLEOSOMAL DNA; GENE-PRODUCTS; HUMAN HOMOLOG; YEAST; COMPONENTS; STIMULATION AB During mitosis, chromatin is condensed into mitotic chromosomes and transcription is inhibited, processes that might be opposed by the chromatin remodeling activity of the SWI/SNF complexes. Brg1 and hBrm, which are components of human SWI/SNF (hSWIISNF) complexes, were recently shown to be phosphorylated during mitosis. This suggested that phosphorylation might be used as a switch to modulate SWI/SNF activity. Using an epitope-tag strategy, we have purified hSWI/SNF complexes at different stages of the cell cycle, and found that hSWI/SNF was inactive in cells blocked in G(2)-M. Mitotic hSWI/SNF contained Brg1 but trot hBrm, and was phosphorylated on at least two subunits, hSWI3 and Brg1. In vitro, active hSWI/SNF from asynchronous cells can be phosphorylated and inactivated by ERK1, and reactivated by dephosphorylation. hSWI/SNF isolated as cells traversed mitosis regained activity when its subunits were dephosphorylated either in vitro or in vivo. We propose that this transitional inactivation and reactivation of hSWI/SNF is required for formation of a repressed chromatin structure during mitosis and reformation of an active chromatin structure as cells leave mitosis. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM kingston@frodo.mgh.harvard.edu FU NIGMS NIH HHS [R01 GM048405, GM48405, R37 GM048405] NR 48 TC 199 Z9 200 U1 0 U2 0 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 SEP 15 PY 1998 VL 12 IS 18 BP 2842 EP 2851 DI 10.1101/gad.12.18.2842 PG 10 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 123ZB UT WOS:000076154600004 PM 9744861 ER PT J AU Glass, DJ AF Glass, DJ TI Phytoremediation applications - An emerging market for the introduction of specialty crops and transgenic plants SO GENETIC ENGINEERING NEWS LA English DT Article C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0270-6377 J9 GENET ENG NEWS JI Genet. Eng. News PD SEP 15 PY 1998 VL 18 IS 16 BP 17 EP + PG 0 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V2648 UT WOS:000165537000011 ER PT J AU Freeman, GJ Cardoso, AA Boussiotis, VA Anumanthan, A Groves, RW Kupper, TS Clark, EA Madler, LM AF Freeman, GJ Cardoso, AA Boussiotis, VA Anumanthan, A Groves, RW Kupper, TS Clark, EA Madler, LM TI The BB1 monoclonal antibody recognizes both cell surface CD74 (MHC class II associated invariant chain) as well as B7-1 (CD80), resolving the question regarding a third CD28/CTLA-4 counterreceptor SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTIGEN-PRESENTING CELLS; ACTIVATED B-CELLS; HELPER T-CELLS; COSTIMULATORY MOLECULE; SIGNAL TRANSDUCTION; HUMAN KERATINOCYTES; MESSENGER-RNA; EXPRESSION; CD28; CTLA-4 AB The identification of all CD28/CTLA-4 counterreceptors is critical to our understanding of this pivotal pathway of T cell activation. Clouding our understanding has been the reported discrepancies in expression and function of the B7-1 (CD80) molecule based upon the use of the BB1 vs other anti-B7-l mAbs, To resolve this issue, we have cloned a BB1-binding molecule from the BB1(+)B7-1(-) NALM-6 pre-B cell line, Here, we demonstrate that this BB1-binding molecule is identical to the cell surface form of CD74 (MHC class II-associated invariant chain). CD74-transfected cells bound the BB1 mAb but not other anti-CD80 mabs, CD28-Ig, or CTLA4Ig, absorption and blocking experiments confirmed the reactivity of BB1 mAb with CD74, A region of weak homology was identified between CD74 and the region of B7-1 encoding the BB1 epitope, Therefore, the BB1 mAb binds to a protein distinct from B7-1, and this epitope is also present on the B7-1 protein. Many of the puzzling observations in the literature concerning the expression of human B7-1 are resolved by an understanding that BB1 staining is the summation of CD74 plus B7-1 expression. This observation requires the field to reconsider studies using BB1 mAb in the analysis of CD80 expression and function. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Dermatol, Boston, MA USA. Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. RP Freeman, GJ (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. EM freeman@macmailgw.dfci.harvard.edu FU NCI NIH HHS [CA 40216]; NIAID NIH HHS [AI 39671, AI 25082] NR 58 TC 34 Z9 34 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 SEP 15 PY 1998 VL 161 IS 6 BP 2708 EP 2715 PG 8 WC Immunology SC Immunology GA 118WU UT WOS:000075864600007 PM 9743327 ER PT J AU Anumanthan, A Bensussan, A Boumsell, L Christ, AD Blumberg, RS Voss, SD Patel, AT Robertson, MJ Nadler, LM Freeman, GJ AF Anumanthan, A Bensussan, A Boumsell, L Christ, AD Blumberg, RS Voss, SD Patel, AT Robertson, MJ Nadler, LM Freeman, GJ TI Cloning of BY55, a novel Ig superfamily member expressed on NK cells, CTL, and intestinal intraepithelial lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; HUMAN GUT EPITHELIUM; COMPLEX CLASS-I; CD8(+) T-CELLS; INHIBITORY RECEPTORS; MEDIATED CYTOTOXICITY; PERIPHERAL-BLOOD; PROLIFERATIVE RESPONSES; MONOCLONAL-ANTIBODY; ANCHORED PROTEINS AB Expression of the BY55 protein has been shown to be tightly associated with NK and CD8(+) T lymphocytes with cytolytic effector activity. To determine the function of this protein, we molecularly cloned BY55 cDNA. The cDNA sequence predicts a cysteine-rich, glycosylphosphatidylinositol-anchored protein of 181 amino acids with a single Ig-like domain weakly homologous to killer inhibitory receptors, Reduction and carboxyamidomethylation of immunoprecipitated BY55 gave a band of 27 kDa, whereas reduction alone led to an 80-kDa species, suggesting that BY55 is a tightly disulfide-linked multimer, RNA blot analysis revealed BY55 mRNAs of 1.5 and 1.6 kb whose expression was highly restricted to NK and T cells. BY55 was expressed on the CD56(dim), CD16(+) subset of NK cells, which have high cytolytic activity, but was not expressed and was not induced on the CD56(bright), CD16(-) subset of NK cells, a subset with high proliferative, but low cytolytic, capacity, In human tissues, BY55 mRNA was expressed only in spleen, PBL, and small intestine tin gut lymphocytes), BY55 was expressed on all intestinal Intraepithelial lymphocytes, which were predominantly CD3(+)TCR alpha/beta(+)CD4(-)CD8(+)CD11b(+)CD28(-)CD45RO(+)CD56(-)CD101(+)CD103(+) (alpha(E)beta(7) integrin). In addition, BY55 was expressed on most CD8(+)CD28(-) peripheral blood T cells. These phenotypic relationships suggest that CD8(+)CD28(+) precursor CTL may terminally differentiate into CD8(+)CD28(-)BY55(+) effector CTL and that some of the peripheral blood CD8(+)CD28(-) subset may represent recirculation from mucosal epithelial immune sites. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Fac Med Creteil, INSERM, U448, Paris, France. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Gastroenterol, Boston, MA USA. RP Freeman, GJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. EM gordon_freeman@macmailgw.dfci.harvard.edu RI Bensussan, Armand/E-5434-2017 FU NCI NIH HHS [CA40216]; NIAID NIH HHS [AI25082, AI39671] NR 78 TC 84 Z9 91 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 SEP 15 PY 1998 VL 161 IS 6 BP 2780 EP 2790 PG 11 WC Immunology SC Immunology GA 118WU UT WOS:000075864600016 PM 9743336 ER PT J AU Brown, EN Frank, LM Tang, DD Quirk, MC Wilson, MA AF Brown, EN Frank, LM Tang, DD Quirk, MC Wilson, MA TI A statistical paradigm for neural spike train decoding applied to position prediction from ensemble firing patterns of rat hippocampal place cells SO JOURNAL OF NEUROSCIENCE LA English DT Article DE hippocampal place cells; Bayesian statistics; information encoding; decoding algorithm; nonlinear recursive; filter; random walk; inhomogeneous Poisson process; point process ID POPULATION CODES; UNIT-ACTIVITY; DIRECTION; SEQUENCES; SLEEP AB The problem of predicting the position of a freely foraging rat based on the ensemble firing patterns of place cells recorded from the CA1 region of its hippocampus is used to develop a two-stage statistical paradigm for neural spike train decoding. In the first, or encoding stage, place cell spiking activity is modeled as an inhomogeneous Poisson process whose instantaneous rate is a function of the animal's position in space and phase of its theta rhythm. The animal's path is modeled as a Gaussian random walk. In the second, or decoding stage, a Bayesian statistical paradigm is used to derive a nonlinear recursive causal filter algorithm for predicting the position of the animal from the place cell ensemble firing patterns. The algebra of the decoding algorithm defines an explicit map of the discrete spike trains into the position prediction. The confidence regions for the position predictions quantify spike train information in terms of the most probable locations of the animal given the ensemble firing pattern. Under our inhomogeneous Poisson model position was a three to five times stronger modulator of the place cell spiking activity than theta phase in an open circular environment. For animal 1 (2) the median decoding error based on 34 (33) place cells recorded during 10 min of foraging was 8.0 (7.7) cm. Our statistical paradigm provides a reliable approach for quantifying the spatial information in the ensemble place cell firing patterns and defines a generally applicable framework for studying information encoding in neural systems. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,Stat Res Lab, Boston, MA 02114 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Brown, EN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,Stat Res Lab, 32 Fruit St,Clin 3, Boston, MA 02114 USA. OI Frank, Loren/0000-0002-1752-5677 NR 35 TC 257 Z9 257 U1 1 U2 11 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 SEP 15 PY 1998 VL 18 IS 18 BP 7411 EP 7425 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 119JR UT WOS:000075893000034 PM 9736661 ER PT J AU Guarente, L Ruvkun, G Amasino, R AF Guarente, L Ruvkun, G Amasino, R TI Aging, life span, and senescence SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT 9th Annual Frontiers of Science Symposium CY NOV 07-09, 1997 CL IRVINE, CALIFORNIA SP Natl Acad Sci (NAS) ID CAENORHABDITIS-ELEGANS; LEAF SENESCENCE; SACCHAROMYCES-CEREVISIAE; FAMILY MEMBER; LONGEVITY; GENE; CYTOKININ; DAF-16; ARABIDOPSIS; DIAPAUSE C1 MIT, Dept Biol, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA. RP Guarente, L (reprint author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. NR 20 TC 32 Z9 34 U1 2 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 SEP 15 PY 1998 VL 95 IS 19 BP 11034 EP 11036 DI 10.1073/pnas.95.19.11034 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 120LD UT WOS:000075957100005 PM 9736682 ER PT J AU Duke-Cohan, JS Gu, JJ McLaughlin, DF Xu, YH Freeman, GJ Schlossman, SF AF Duke-Cohan, JS Gu, JJ McLaughlin, DF Xu, YH Freeman, GJ Schlossman, SF TI Attractin (DPPT-L), a member of the CUB family of cell adhesion and guidance proteins, is secreted by activated human T lymphocytes and modulates immune cell interactions SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FIBROBLAST GROWTH-FACTOR; DIPEPTIDYL PEPTIDASE-IV; INTEGRAL MEMBRANE PROTEASE; MOLECULAR-CLONING; EXTRACELLULAR-MATRIX; SIGNAL SEQUENCE; ANTIGEN; CD26; EXPRESSION; CYTOKINES AB Attractin is a normal human serum glycoprotein of 175 kDa that is rapidly expressed on activated T cells and released extracellularly after 45-72 hr, We have cloned attractin and find that, as in its natural serum form, it mediates the spreading of monocytes that become the focus for the clustering of nonproliferating T lymphocytes, There are two mRNA species with hematopoietic tissue-specific expression that code for a 134-kDa protein with a putative serine protease catalytic serine, four EGF-Iilie motifs, a CUB domain, a C type lectin domain, and a domain homologous with the ligand-binding region of the common gamma cytokine chain. Except for the latter two domains, the overall structure shares high homology with the Caenorhabditis elegans F33C8.1 protein, suggesting that attractin has evolved new domains and functions in parallel with the development of cell-mediated immunity. C1 Harvard Univ, Sch Med, Div Tumor Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Mol & Struct, 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. RP Duke-Cohan, JS (reprint author), Harvard Univ, Sch Med, Div Tumor Immunol, 44 Binney St, Boston, MA 02115 USA. RI Duke-Cohan, Jonathan/A-5812-2010 OI Duke-Cohan, Jonathan/0000-0002-9478-9609 FU NIAID NIH HHS [AI 12069-24] NR 34 TC 103 Z9 105 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 15 PY 1998 VL 95 IS 19 BP 11336 EP 11341 DI 10.1073/pnas.95.19.11336 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 120LD UT WOS:000075957100060 PM 9736737 ER PT J AU David, D Bani, L Moreau, JL Treilhou, MP Nakarai, T Joussemet, M Ritz, J Dupont, B Pialoux, G Theze, J AF David, D Bani, L Moreau, JL Treilhou, MP Nakarai, T Joussemet, M Ritz, J Dupont, B Pialoux, G Theze, J TI Regulatory dysfunction of the interleukin-2 receptor during HIV infection and the impact of triple combination therapy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; GAMMA-CHAIN; T-CELLS; EXPRESSION; LYMPHOCYTES; ACTIVATION; CYTOKINE; IL-2; SUBUNIT AB The interleukin-2 (IL-2)/IL-2 receptor (IL-2R) system is the main regulatory determinant of T cell reactivity. Although it is well known that IL-2 secretion is impaired during HN infection, up to now IL-2R expression has not been extensively studied in HIV-infected patients despite the use of IL-2 in clinical therapy trials. We show here that IL-2R expression in HIV patients with high viral load (group 1 in the study) is greatly enhanced on B lymphocytes, CD8 T lymphocytes, and monocytes, but not on CD4 T lymphocytes, compared with noninfected individuals. Paradoxically, this modified IL-2R expression does not lead to increased IL-2 responsiveness, except for B lymphocytes. In patients receiving triple combination therapy (TCT, two reverse transcriptase inhibitors and one protease inhibitor) that has triggered a drastic reduction in plasma viral load and an increase in CD4 counts (group 2 patients), IL-2R expression is significantly lower than in group 1 patients. Moreover, cells involved in cellular immunity and CD4 T lymphocytes have the capacity to respond to IL-2 after TCT. These results allow us to anticipate a beneficial role of IL-2 immunotherapy in combination with TCT. C1 Inst Pasteur, Dept Immunol, Unite Immunogenet Cellulaire, F-75724 Paris, France. Hop Inst Pasteur, Paris, France. Dana Farber Canc Inst, Div hematol Malignancies, Boston, MA 02115 USA. Ctr Transfus Sanguine Jean Julliard, Clamart, France. RP Theze, J (reprint author), Inst Pasteur, Dept Immunol, Unite Immunogenet Cellulaire, F-75724 Paris, France. EM jtheze@pasteur.fr RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA41619] NR 36 TC 42 Z9 42 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 SEP 15 PY 1998 VL 95 IS 19 BP 11348 EP 11353 DI 10.1073/pnas.95.19.11348 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 120LD UT WOS:000075957100062 PM 9736739 ER PT J AU Bush, K Kivlahan, DR McDonell, MB Fihn, SD Bradley, KA AF Bush, K Kivlahan, DR McDonell, MB Fihn, SD Bradley, KA CA Ambulatory Care Quality Improvement Project TI The AUDIT alcohol consumption questions (AUDIT-C) - An effective brief screening test for problem drinking SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PRIMARY-CARE PATIENTS; RANDOMIZED CONTROLLED TRIAL; IDENTIFICATION TEST AUDIT; GENERAL-PRACTICE PATIENTS; MENTAL-DISORDERS; PROBLEM DRINKERS; CAGE QUESTIONNAIRE; LIKELIHOOD RATIOS; ELDERLY VETERANS; SELF-REPORT AB Objective: To evaluate the 3 alcohol consumption questions from the Alcohol Use Disorders Identification Test (AUDIT-C) as a brief screening test for heavy drinking and/or active alcohol abuse or dependence. Methods: Patients from 3 Veterans Affairs general medical clinics were mailed questionnaires. A random, weighted sample of Health History Questionnaire respondents, who had 5 or more drinks over the past year, were eligible for telephone interviews (N = 447). Heavy drinkers were oversampled 2:1; Patients were excluded if they could not be contacted by telephone, were too ill for interviews, or were female (n = 54). Areas under receiver operating characteristic curves (AUROCs) were used to compare mailed alcohol screening questionnaires (AUDIT-C and full AUDIT) with 3 comparison standards based on telephone interviews: (1) past year heavy drinking (>14 drinks/week or greater than or equal to 5 drinks/occasion); (2) active alcohol abuse or dependence according to the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, criteria; and (3) either. Results: Of 393 eligible patients, 243 (62%) completed AUDIT-C and interviews. For detecting heavy drinking, AUDIT-C had a higher AUROC than the full AUDIT (0.891 vs 0.881; P = .03). Although the full AUDIT performed better than AUDIT-C for detecting active alcohol abuse or dependence (0.811 vs 0.786; P < .001), the 2 questionnaires performed similarly for detecting heavy drinking and/or active abuse or dependence (0.880 vs 0.881). Conclusions: Three questions about alcohol consumption (AUDIT-C) appear to be a practical, valid primary care screening test for heavy drinking and/or active alcohol abuse or dependence. C1 VA Puget Sound Hlth Care Syst, Seattle Div, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Seattle Div, Med Serv, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Serv, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Bush, K (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div, Ctr Excellence Subst Abuse Treatment & Educ, Mailstop 152,1660 S Columbian Way, Seattle, WA 98108 USA. NR 57 TC 1385 Z9 1388 U1 14 U2 70 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 SEP 14 PY 1998 VL 158 IS 16 BP 1789 EP 1795 DI 10.1001/archinte.158.16.1789 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 118GC UT WOS:000075829200007 PM 9738608 ER PT J AU Metlay, JP Stafford, RS Singer, DE AF Metlay, JP Stafford, RS Singer, DE TI National trends in the use of antibiotics by primary care physicians for adult patients with cough SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 01-03, 1997 CL WASHINGTON, D.C. SP Soc Gen Internal Med ID RESISTANT STREPTOCOCCUS-PNEUMONIAE; ACUTE BRONCHITIS; UNITED-STATES; ANTIMICROBIAL RESISTANCE; AMBULATORY CARE; INFECTIONS; PREVALENCE; EMERGENCE; CHILDREN; BACTERIA AB Background: Increased antibiotic use for outpatient illnesses has been identified as an important determinant of the recent rise in antibiotic resistance among common respiratory pathogens. Efforts to reduce the inappropriate use will need to be evaluated against current trends in the outpatient use of antibiotics. Objectives: To examine national trends in the use of antibiotics by primary care physicians in the care of adult patients with cough and identify patient factors that may influence antibiotic use for these patients. Methods: This study was based on a serial analysis of results from all National Ambulatory Medical Care Surveys beginning in 1980 (when therapeutic drug use was first recorded) to 1994 (the most recent survey year available). These surveys are a random sampling of visits to US office-based physicians in 1980, 1981, 1985, and annually from 1989-1994. Eligible visits included those by adults presenting to general internists, family practitioners, or general practitioners with a chief complaint of cough. A total of 3416 visits for cough were identified over the survey years. Survey results were extrapolated, based on sampling weights in each year, to project national rates of antibiotic use for patients with cough. Additional analyses examined the rates of antibiotic use stratified by patient age, race, and clinical diagnosis. Results: Overall, an antibiotic was prescribed 66% of the time during office visits for patients with cough: 59% of patient visits in 1980 rising to 70% of visits in 1994 (P = .002 for trend). In every study year, white, non-Hispanic patients and patients younger than 65 years were more likely to receive antibiotics compared with nonwhite patients and patients 65 years or older, respectively. Conclusions: The rate of antibiotic use by primary care physicians for patients with cough remained high from 1980 to 1994, and was influenced by nonclinical characteristics of patients. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Metlay, JP (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Room 712 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. FU BHP HRSA HHS [5T32PE11001-08] NR 27 TC 50 Z9 53 U1 0 U2 5 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 SEP 14 PY 1998 VL 158 IS 16 BP 1813 EP 1818 DI 10.1001/archinte.158.16.1813 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 118GC UT WOS:000075829200011 PM 9738612 ER PT J AU Bouma, BE AF Bouma, BE TI Focus issue: Optical coherence tomography - Introduction SO OPTICS EXPRESS LA English DT Editorial Material C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Bouma, BE (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD SEP 14 PY 1998 VL 3 IS 6 BP 198 EP 198 PG 1 WC Optics SC Optics GA 123LU UT WOS:000076127300001 PM 19384361 ER PT J AU Nathan, DM AF Nathan, DM TI Some answers, more controversy, from UKPDS SO LANCET LA English DT Editorial Material ID DEPENDENT DIABETES-MELLITUS; COMPLICATIONS C1 Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. RP Nathan, DM (reprint author), Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. NR 10 TC 115 Z9 122 U1 0 U2 4 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD SEP 12 PY 1998 VL 352 IS 9131 BP 832 EP 833 DI 10.1016/S0140-6736(98)22937-0 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 118UA UT WOS:000075857300002 PM 9742972 ER PT J AU Garcia-Cozar, FJ Okamura, H Aramburu, JF Shaw, KTY Pelletier, L Showalter, R Villafranca, E Rao, A AF Garcia-Cozar, FJ Okamura, H Aramburu, JF Shaw, KTY Pelletier, L Showalter, R Villafranca, E Rao, A TI Two-site interaction of nuclear factor of activated T cells with activated calcineurin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR NFAT1; CYCLOSPORINE-A; NF-AT; LIMITED PROTEOLYSIS; FAMILY; DOMAIN; EXPRESSION; BINDING; COMPLEX; FK506 AB Transcription factors belonging to the nuclear factor of activated T cells (NFAT) family regulate the expression of cytokine genes and other inducible genes during the immune response. The functions of NFAT proteins are directly controlled by the calcium- and calmodulin-dependent phosphatase calcineurin, Here we show that the binding of calcineurin to NFAT is substantially increased when calcineurin is activated with calmodulin and calcium. FK506-FKBP12 drug-immunophilin complexes inhibited the interaction of NFAT with activated calcineurin much more effectively than they inhibited the interaction with inactive calcineurin, suggesting that part of the interaction with activated calcineurin involved the enzyme active site. We have previously shown that NFAT is targeted to inactive calcineurin at a region distinct from the calcineurin active site (Aramburu, J,, Garcia-Cozar, F, J,, Raghavan, A, Okamura, H,, Rao, A., and Hogan, P, G, (1998) Mel. Cell 1, 627-637); this region is also involved in NFAT binding to activated calcineurin, since binding is inhibited by an NFAT peptide spanning the calcineurin docking site on NFAT, The interacting surfaces are located on the catalytic domain of the calcineurin A chain and on an 86-amino acid fragment of the NFAT regulatory domain. NFAT binding to the calcineurin catalytic domain was inhibited by the calcineurin autoinhibitory domain and the RII substrate peptide, which bind in the calcineurin active site, as well as by the NFAT docking site peptide, which binds to a region of calcineurin distinct from the active site.; We propose that, in resting cells, NFAT is targeted to a region of the calcineurin catalytic domain that does not overlap the calcineurin active site, Upon cell activation, displacement of the autoinhibitory domain by calmodulin binding allows NFAT to bind additionally to the calcineurin active site, thus positioning NFAT for immediate dephosphorylation at functional phosphoserine residues. C1 Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, Boston, MA 02115 USA. Agouron Pharmaceut Inc, San Diego, CA 92121 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. RI Garcia-Cozar, Francisco/A-6212-2013; Aramburu, J/G-8991-2014 OI Garcia-Cozar, Francisco/0000-0003-3720-259X; Aramburu, J/0000-0001-9279-9523 FU NIAID NIH HHS [AI 40127] NR 40 TC 71 Z9 73 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 SEP 11 PY 1998 VL 273 IS 37 BP 23877 EP 23883 DI 10.1074/jbc.273.37.23877 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 119JT UT WOS:000075893100041 PM 9727000 ER PT J AU Goalstone, ML Leitner, JW Wall, K Dolgonos, L Rother, KI Accili, D Draznin, B AF Goalstone, ML Leitner, JW Wall, K Dolgonos, L Rother, KI Accili, D Draznin, B TI Effect of insulin on farnesyltransferase - Specificity of insulin action and potentiation of nuclear effects of insulin-like growth factor-1, epidermal growth factor, and platelet-derived growth factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; 3T3-L1 ADIPOCYTES; RAS; RECEPTOR; MEMBRANE AB We have previously demonstrated that insulin activates, farnesyltransferase (FTase) and augments the amounts of farnesylated p21(ras) (Goalstone, NI, L., and Draznin, B. (1996) J. Biol, Chem. 271, 27585-27589). We postulated that this aspect of insulin action might explain the "priming effect" of insulin on the cellular response to other growth factors. In the present study, we show the specificity of the effect of insulin on FTase. Insulin, but not insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), or platelet-derived growth factor (PDGF), stimulated the phosphorylation of the alpha-subunit of FTase and the amounts of farnesylated p21(ras). Even though all four growth factors utilized the Ras pathway to stimulate DNA synthesis, only insulin used this pathway to influence FTase, Insulin failed to stimulate FTase in cells expressing the chimeric insulin/ IGF-I receptor and in cells derived from the insulin receptor knock-out animals. Insulin potentiated the effects of IGF-1, EGF, and PDGF on DNA synthesis in cells expressing the wild type insulin receptor, but this potentiation was inhibited in the presence of the FTase inhibitor, alpha-hydroxyfarnesylphosphonic acid. We conclude that the effect of insulin on FTase is specific, requires the presence of an intact insulin receptor and selves as a conduit for the "priming" influence of insulin on the nuclear effects of other growth factors. C1 Denver Vet Affairs Med Ctr, Res Serv, Denver, CO 80220 USA. Denver Vet Affairs Med Ctr, Dept Med, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80220 USA. NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Draznin, B (reprint author), VA Hosp 151, 1055 Clermont St, Denver, CO 80220 USA. NR 19 TC 50 Z9 50 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 SEP 11 PY 1998 VL 273 IS 37 BP 23892 EP 23896 DI 10.1074/jbc.273.37.23892 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 119JT UT WOS:000075893100043 PM 9727002 ER PT J AU Ness, SL Edelmann, W Jenkins, TD Liedtke, W Rustgi, AK Kucherlapati, R AF Ness, SL Edelmann, W Jenkins, TD Liedtke, W Rustgi, AK Kucherlapati, R TI Mouse keratin 4 is necessary for internal epithelial integrity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID WHITE SPONGE NEVUS; EPIDERMOLYSIS-BULLOSA SIMPLEX; INTERMEDIATE FILAMENTS; MESSENGER-RNAS; CELL TYPE; EXPRESSION; MUTATION; DIFFERENTIATION; HYPERKERATOSIS; GENES AB Keratins are intermediate filaments ts of epithelial cells. Mutations in keratin genes expressed in skis lead to human disorders, including epidermolysis bullosa simplex and epidermolytic hyperkeratosis. We examined the role of keratin 4 (K4) in maintaining the integrity of internal epithelial linings by using gene targeting to generate mice containing a null mutation in the epithelial K4 gene. Homozygous mice that do not express K4 develop a spectrum of phenotypes that affect several organs which express K4 including the esophagus, tongue, and cornea. The cellular phenotypes include basal hyperplasia, Hack of maturation, hyperkeratosis, atypical nuclei, perinuclear clearing, and cell degeneration. These results are consistent with the notion that K4 is required for internal epithelial cell integrity. As mutations in K4 in humans lead to a disorder called white sponge nevus, the K4-deficient mice may serve as models Tor white sponge nevus and for understanding the role of K4 in cellular proliferation and differentiation. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hematol Oncol Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Pathol, Div Neuropathol, Bronx, NY 10461 USA. Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10023 USA. RP Kucherlapati, R (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Mol Genet, 1300 Morris Pk Ave, Bronx, NY 10461 USA. RI Liedtke, Wolfgang/G-4633-2011 FU NCI NIH HHS [CA 13330]; NIDDK NIH HHS [DK40561]; NIGMS NIH HHS [T32GM07288] NR 37 TC 49 Z9 49 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 SEP 11 PY 1998 VL 273 IS 37 BP 23904 EP 23911 DI 10.1074/jbc.273.37.23904 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 119JT UT WOS:000075893100045 PM 9727004 ER PT J AU Opitz, OG Jenkins, TD Rustgi, AK AF Opitz, OG Jenkins, TD Rustgi, AK TI Transcriptional regulation of the differentiation-linked human K4 promoter is dependent upon esophageal-specific nuclear factors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID K3 KERATIN GENE; TRANSGENIC MICE; EPIDERMOLYTIC HYPERKERATOSIS; INTERMEDIATE FILAMENTS; EPITHELIAL-CELLS; EXPRESSION; ELEMENT; PROTEIN; AP-1; MUTAGENESIS AB The stratified squamous epithelium comprises actively proliferating basal cells that undergo a program of differentiation accompanied by morphological, biochemical, and genetic changes. The transcriptional regulatory signals and the genes that orchestrate this snitch from proliferation to differentiation can he studied through the keratin gene family. Givers the localization of keratin 4 (K4) to the early differentiated suprabasal compartment sand leaving previously demonstrated that targeted disruption of this gene in murine embryonic stem cells results in impairment of the normal differentiation program in esophageal and corneal epithelial cells, we studied the transcriptional regulation of the human K4 promoter. A panel of K4 promoter deletions were found in transient transfection assays to be predominantly active in esophageal and corneal cell lines. A critical cis-regulatory element resides between -163 and -140 bp and contains an inverted CACACCT motif. A site-directed mutated version of this motif within the K4 promoter renders it inactive, whereas the wild-type version is active in a heterologous promoter system. It specifically binds esophageal-specific zinc-dependent transcriptional factors. Our studies demonstrate that regulation of the human K4 promoter is in part mediated through tissue-specific transcriptional factors. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hematol Oncol Unit, Boston, MA 02114 USA. RP Rustgi, AK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Jackson 904,50 Blossom St, Boston, MA 02114 USA. EM rustgi@helix.mgh.harvard.edu FU NIDCR NIH HHS [1P01 DE12467-01A1]; NIDDK NIH HHS [R01-DK53377, 5P30DK43357-08] NR 47 TC 13 Z9 13 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 SEP 11 PY 1998 VL 273 IS 37 BP 23912 EP 23921 DI 10.1074/jbc.273.37.23912 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 119JT UT WOS:000075893100046 PM 9727005 ER PT J AU Sunder-Plassmann, R Reinherz, EL AF Sunder-Plassmann, R Reinherz, EL TI A p56(lck)-independent pathway of CD2 signaling involves Jun kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID T-CELL ACTIVATION; PROTEIN-TYROSINE KINASES; NATURAL-KILLER-CELLS; LYMPHOCYTE-T; ANTIGEN RECEPTOR; CYTOPLASMIC DOMAIN; INTERLEUKIN-2 GENE; C-JUN; TRANSCRIPTION FACTORS; INOSITOL PHOSPHATES AB The p56(lck) Src family non-receptor tyrosine kinase has been shown to be critical for T lymphocyte differentiation and activation. Hence in the absence of p56(lck), T cell receptor triggered activation does not occur. We now provide evidence for a CD2-based signaling pathway which, in contrast to that of the T cell receptor, is independent of p56(lck). CD2-mediated interleukin-a production occurs via activation of Jun kinase in cell lines lacking p56(lck). Jun kinase then facilitates the binding of c-Jun/c-Fos heterodimers to the AP-1 consensus site and the subsequent transcriptional activity of the interleukin-a promoter. These data elucidate differences between TCR and CD2 signaling pathways in the same T cells. C1 Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Reinherz, EL (reprint author), Dana Farber Canc Inst, Immunobiol Lab, 44 Binney St, Boston, MA 02115 USA. EM ellis_reinherz@dfci.harvard.edu FU NIAID NIH HHS [AI21226, AI19807] NR 91 TC 21 Z9 22 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 SEP 11 PY 1998 VL 273 IS 37 BP 24249 EP 24257 DI 10.1074/jbc.273.37.24249 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 119JT UT WOS:000075893100090 PM 9727049 ER PT J AU Juo, P Kuo, CJ Yuan, JY Blenis, J AF Juo, P Kuo, CJ Yuan, JY Blenis, J TI Essential requirement for caspase-8/FLICE in the initiation of the Fas-induced apoptotic cascade SO CURRENT BIOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; DRUG-INDUCED APOPTOSIS; PROTEIN-TYROSINE-PHOSPHATASE; ICE/CED-3 FAMILY PROTEASES; MEDIATED CELL-DEATH; NF-KAPPA-B; SIGNALING COMPLEX; MONOCLONAL-ANTIBODY; ADAPTER MOLECULE; LEUKEMIA-CELLS AB Background: Fas (APO-1/CD95) is a member of the tumor necrosis factor receptor (TNF-R) family and induces apoptosis when crosslinked with either Fas ligand or agonistic antibody (Fas antibody), The Fas-Fas ligand system has an important role in the immune system where it is involved in the downregulation of immune responses and the deletion of peripheral autoreactive T lymphocytes. The intracellular domain of Fas interacts with several proteins including FADD (MORT-I), DAXX, RIP, FAF-1, FAP-I and Sentrin, The adaptor protein FADD can, in turn, interact with the cysteine protease caspase-8 (FLICE/MACH/Mch5). Results: In a genetic screen for essential components of the Fas-mediated apoptotic cascade, we isolated a Jurkat T lymphocyte cell line deficient in caspase-8 that was completely resistant to Fas-induced apoptosis. Complementation of this cell line with wild-type caspase-8 restored Fas-mediated apoptosis, Fas activation of multiple caspases and of the stress kinases p38 and c-Jun NH2-terminal kinase (JNK) was completely blocked in the caspase-8-deficient cell line. Furthermore, the cell line was severely deficient in cell death induced by TNF-alpha and was partially deficient in cell death induced by ultraviolet irradiation, adriamycin and etoposide. Conclusions: This study provides the first genetic evidence that caspase-8 occupies an essential and apical position in the Fas signaling pathway and suggests that caspase-8 may participate broadly in multiple apoptotic pathways. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Blenis, J (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. NR 57 TC 424 Z9 433 U1 1 U2 7 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD SEP 10 PY 1998 VL 8 IS 18 BP 1001 EP 1008 DI 10.1016/S0960-9822(07)00420-4 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 118VU UT WOS:000075862000016 PM 9740801 ER PT J AU Bodennec, J Zwingelstein, G Koul, O Brichon, G Portoukalian, J AF Bodennec, J Zwingelstein, G Koul, O Brichon, G Portoukalian, J TI Phytosphingosine biosynthesis differs from sphingosine in fish leukocytes and involves a transfer of methyl groups from [H-3-methyl] methionine precursor SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE phytosphingosine; sphingosine; ceramides; serine; methionine; leukocytes ID BICINCHONINIC ACID; DIACYLGLYCEROL; SEPARATION; LIPIDS AB We have studied the incorporation of radioactivity from either [3-H-3]serine as the direct or [H-3-methyl]methionine as the indirect precursor into sphingoid bases of free ceramides in lymphocytes from fish. Radioactivity from serine was incorporated mostly in the sphingosine moiety of ceramides, In contrast, the radioactivity from methionine was exclusively incorporated into phytosphingosine base (i.e., 4-hydroxy-sphinganine) and the incorporation increased by about twofold in the presence of folic acid or niacinamide, Identity of the long-chain bases, phytosphingosine and sphingosine, was established chemically by thin-layer chromatography, chemical degradation, and gas-liquid chromatography. (C) 1998 Academic Press. C1 Univ Lyon 1, Fac Med Lyon Sud, Lab Tumor Glycobiol, F-69921 Oullins, France. Univ Lyon 1, Inst Michel Pacha, F-83500 La Seyne Sur Mer, France. Eunice Kennedy Shriver Ctr Mental Retardat Inc, Waltham, MA 02452 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Portoukalian, J (reprint author), Univ Lyon 1, Fac Med Lyon Sud, Lab Tumor Glycobiol, BP 12, F-69921 Oullins, France. EM portouk@Lsgrisn1.univ-lyon1.fr FU NICHD NIH HHS [HD05515]; NIDDK NIH HHS [DK52122] NR 21 TC 5 Z9 5 U1 0 U2 1 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 SEP 8 PY 1998 VL 250 IS 1 BP 88 EP 93 DI 10.1006/bbrc.1998.9273 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 119RY UT WOS:000075912000018 PM 9735337 ER PT J AU Scherrer-Crosbie, M Steudel, W Hunziker, PR Foster, GP Garrido, L Liel-Cohen, N Zapol, WM Picard, MH AF Scherrer-Crosbie, M Steudel, W Hunziker, PR Foster, GP Garrido, L Liel-Cohen, N Zapol, WM Picard, MH TI Determination of right ventricular structure and function in normoxic and hypoxic mice - A transesophageal echocardiographic study SO CIRCULATION LA English DT Article DE echocardiography; ventricles; hypoxia ID ANGIOTENSIN-CONVERTING ENZYME; NITRIC-OXIDE SYNTHASE; IN-VIVO VALIDATION; PULMONARY-HYPERTENSION; 3-DIMENSIONAL ECHOCARDIOGRAPHY; GENE; PERFORMANCE; HYPERTROPHY; VOLUME; MASS AB Background-Noninvasive cardiac evaluation is of great importance in transgenic mice. Transthoracic echocardiography can visualize the left ventricle well but has not been as successful for the right ventricle (RV). We developed a method of transesophageal echocardiography (TEE) to evaluate murine RV size and function. Methods and Results-Normoxic and chronically hypoxic mice (FIO2=0.11, 3 weeks) and agarose RV casts were scanned with a rotating 3.5F/30-MHz intravascular ultrasound probe. In vivo, the probe was inserted in the mouse esophagus and withdrawn to obtain contiguous horizontal planes at 1-mm intervals. In vitro, the probe was withdrawn along the left ventricular posterior wall of excised hearts. The borders of the RV were traced on each plane, allowing calculation of diastolic and systolic volumes, RV mass, RV ejection fraction, stroke volume, and cardiac output. RV wall thickness was measured, Echo volumes obtained in vitro were compared with cast volumes. Echo-derived cardiac output was compared with measurements of an ascending aortic Doppler flow probe. Echo-derived RV free wall mass was compared with true RV free wall weight. There was excellent agreement between cast and TEE volumes (y=0.82x+6.03, r=0.88, P<0.01) and flow-probe and echo cardiac output (y=1.00x+0.45, r=0.99, P<0.0001), Although echo-derived RV mass and wall thickness were well correlated with true RV weight, echo-derived RV mass underestimated true weight (y=0.53x+2.29, r=0.81, P<0.0001). RV mass and wall thickness were greater in hypoxic mice than in normoxic mice (0.78+/-0.19 versus 0.51+/-0.14 mg/g, P<0.03, 0.50+/-0.03 versus 0.38+/-0.03 mm, P<0.04). Conclusions-TEE with an intravascular ultrasound catheter is a simple, accurate, and reproducible method to study RV size and function in mice, C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiac Unit,Cardiac Ultrasound Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Scherrer-Crosbie, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiac Unit,Cardiac Ultrasound Lab, VBK 508,55 Fruit St, Boston, MA 02114 USA. RI Garrido, Leoncio/K-3092-2014 OI Garrido, Leoncio/0000-0002-7587-1260 FU NHLBI NIH HHS [HL-42397] NR 22 TC 53 Z9 56 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 8 PY 1998 VL 98 IS 10 BP 1015 EP 1021 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 116HC UT WOS:000075717600012 PM 9737522 ER PT J AU Adebanjo, OA Moonga, BS Yamate, T Sun, L Minkin, C Abe, E Zaidi, M AF Adebanjo, OA Moonga, BS Yamate, T Sun, L Minkin, C Abe, E Zaidi, M TI Mode of action of interleukin-6 on mature osteoclasts. Novel interactions with extracellular Ca2+ sensing in the regulation of osteoclastic bone resorption SO JOURNAL OF CELL BIOLOGY LA English DT Article DE IL-6; Ca2+ sensing; Ca2+ receptor; osteoporosis; ryanodine receptor ID LEUKEMIA INHIBITORY FACTOR; CYTOSOLIC FREE CALCIUM; SIGNAL-TRANSDUCTION; INTRACELLULAR CALCIUM; OSTEOBLASTIC CELLS; RAT OSTEOCLASTS; IL-6 RECEPTOR; MECHANISMS; MARROW; GP130 AB We describe a physiologically significant mechanism through which interleukin-6 (IL-6) and a rising ambient Ca2+ interact to regulate osteoclastic bone resorption. VOXEL-based confocal microscopy of nonpermeabilized osteoclasts incubated with anti-IL-6 receptor antibodies revealed intense, strictly peripheral plasma membrane fluorescence. IL-6 receptor expression in single osteoclasts was confirmed by in situ reverse transcriptase PCR histochemistry. IL-6 (5 ng/l to 10 mu g/l), but not IL-11 (10 and 100 mu g/l), reversed the inhibition of osteoclastic bone resorption induced by high extracellular Ca2+ (15 mM). The IL-6 effect was abrogated by excess soluble IL-6 receptor (500 mu g/l). Additionally, IL-6 (5 pg/l to 10 mu g/l) inhibited cytosolic Ca2+ signals triggered by high Ca2+ or Ni2+. In separate experiments, osteoclasts incubated in 10 mM Ca2+ or on bone released more IL-6 than those in 1.25 mM Ca2+. Furthermore, IL-6 mRNA histostaining was more intense in osteoclasts in 10 or 20 mM Ca2+ than cells in 1.25 mM Ca2+. Similarly, IL-6 receptor mRNA histostaining was increased in osteoclasts incubated in 5 or 10 mM Ca2+. Thus, while high Ca2+ enhances IL-6 secretion, the released IL-6 attenuates Ca2+ sensing and reverses inhibition of resorption by Ca2+. Such an autocrine-paracrine loop may sustain osteoclastic activity in the face of an inhibitory Ca2+ level generated locally during resorption. C1 Vet Affairs Med Ctr, Ctr Osteoporosis & Skeletal Aging, Philadelphia, PA 19104 USA. Med Coll Penn & Hahnemann Univ, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Arkansas Med Sci, Div Endocrinol, Little Rock, AR 72205 USA. Univ So Calif, Sch Dent, Los Angeles, CA 90089 USA. RP Zaidi, M (reprint author), Vet Affairs Med Ctr, Ctr Osteoporosis & Skeletal Aging, Woodlands & Univ Ave, Philadelphia, PA 19104 USA. EM zaidim@auhs.edu FU NIA NIH HHS [R01 AG14917-02] NR 43 TC 56 Z9 60 U1 1 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD SEP 7 PY 1998 VL 142 IS 5 BP 1347 EP 1356 DI 10.1083/jcb.142.5.1347 PG 10 WC Cell Biology SC Cell Biology GA 119ZP UT WOS:000075929400017 PM 9732294 ER PT J AU Hocker, M Rosenberg, I Xavier, R Henihan, RJ Wiedenmann, B Rosewicz, S Podolsky, DK Wang, TC AF Hocker, M Rosenberg, I Xavier, R Henihan, RJ Wiedenmann, B Rosewicz, S Podolsky, DK Wang, TC TI Oxidative stress activates the human histidine decarboxylase promoter in AGS gastric cancer cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHORBOL 12-MYRISTATE 13-ACETATE; OXYGEN METABOLITE PRODUCTION; ISCHEMIA-REPERFUSION; LIPID-PEROXIDATION; HYDROGEN-PEROXIDE; ORNITHINE DECARBOXYLASE; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; PROTEIN-KINASE; OXIDANT STRESS AB Oxidant stress is thought to play a role in the pathogenesis of many gastric disorders. We have recently reported that histidine decarboxylase (HDC) promoter activity is stimulated by gastrin through a protein kinase C- and extracellular signal-regulating kinase (ERK)-dependent pathway in gastric cancer (AGS-B) cells, and this transcriptional response is mediated by a downstream cis-acting element, the gastrin response element (GAS-RE). To study the mechanism through which oxidant stress affects gastric cells, we examined the effects of hydrogen peroxide (H2O2) on HDC promoter activity and intracellular signaling in AGS-B cells. H2O2 (10 mM) specifically activated the HDC promoter 10-12-fold, and this activation was blocked by both mannitol and N-acetylcysteine. Hydrogen peroxide treatment of AGS-B cells increased the phosphorylation and kinase activity of ERK-1 and ERK-2, but did not affect Jun kinase tyrosine phosphorylation or kinase activity. In addition, treatment of AGS-B cells with H2O2 resulted in increased c-fos/c-jun mRNA expression and AP-1 activity, and also led to increased phosphorylation of epidermal growth factor receptor (EGFR) and Shc. H2O2-dependent stimulation of HDC promoter activity was completely inhibited by kinase-deficient ERKs, dominant-negative (N17 and N15) Ras, and dominant-negative Raf, and partially blocked by a dominant-negative EGFR mutant. In contrast, protein kinase C blockade did not inhibit H2O2-dependent induction of the HDC promoter. Finally, deletion analysis demonstrated that the H2O2 response element could be mapped to the GAS-RE (nucleotides 2 to 24) of the basal HDC promoter. Overall, these studies suggest that oxidant stress activates the HDC promoter through the GAS-RE, and through an Ras-, Raf-, and ERK-dependent pathway at least partially involving the EGFR. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Free Univ Berlin, Klinikum Benjamin Franklin, Berlin, Germany. Humboldt Univ, Klinikum Charite, Med Klin, Schwerpunkt Hepatol & Gastroenterol, Berlin, Germany. RP Wang, TC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 724,32 Fruit St, Boston, MA 02114 USA. EM Wang@Helix.MGH.Harvard.Edu FU NIDDK NIH HHS [DK41557, DK48077] NR 46 TC 49 Z9 49 U1 1 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 SEP 4 PY 1998 VL 273 IS 36 BP 23046 EP 23054 DI 10.1074/jbc.273.36.23046 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 117JL UT WOS:000075778100030 PM 9722530 ER PT J AU Ganju, RK Brubaker, SA Meyer, J Dutt, P Yang, YM Qin, SX Newman, W Groopman, JE AF Ganju, RK Brubaker, SA Meyer, J Dutt, P Yang, YM Qin, SX Newman, W Groopman, JE TI The alpha-chemokine, stromal cell-derived factor-1 alpha, binds to the transmembrane G-protein-coupled CXCR-4 receptor and activates multiple signal transduction pathways SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FOCAL ADHESION KINASE; NF-KAPPA-B; TYROSINE KINASE; HIV-1 ENTRY; PHOSPHATIDYLINOSITOL 3-KINASE; LYMPHOCYTE CHEMOATTRACTANT; HUMAN NEUTROPHILS; T-LYMPHOCYTES; CLONING; PHOSPHORYLATION AB The alpha-chemokine stromal cell-derived factor (SDF)-1 alpha binds to the seven transmembrane G-protein-coupled CXCR-4 receptor and acts to modulate cell migration and proliferation. The signaling pathways that mediate the effects of SDF-1 alpha are not well. characterized. We studied events following SDF-1 alpha binding to CXCR-4 in a model murine pre-B cell line transfected with human CXCR-4. There was enhanced tyrosine phosphorylation and association of components of focal adhesion complexes such as the related adhesion focal tyrosine kinase, paxillin, and Crk. We also observed activation of phosphatidylinositol 3-kinase. Wortmannin, a selective inhibitor of phosphatidylinositol 3-kinase, partially in hibited the SDF-1 alpha-induced migration and tyrosine phosphorylation of paxillin. SDF-1 alpha treatment selectively activated p44/42 mitogen-activated protein kinase (Erk 1 and Erk 2) and its upstream kinase mitogen-activated protein kinase kinase but not p38 mitogen-activated protein kinase, c-Jun amino-terminal kinase or mitogen activated protein kinase kinase. We also observed that SDF-1 alpha treatment increased NF-kappa B activity in nuclear extracts from the CXCR-4 transfectants. Taken together, these studies revealed that SDF-1 alpha activates distinct signaling pathways that may mediate cell growth, migration, and transcriptional activation. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Expt Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. LeukoSite Inc, Cambridge, MA 02142 USA. RP Groopman, JE (reprint author), Harvard Univ, Inst Med, BIDMC, Div Expt Med, 4 Blackfan Circle, Boston, MA 02115 USA. EM jgroopma@west.bidmc.harvard.edu FU NHLBI NIH HHS [HL 53745, HL 43510, HL 55187] NR 61 TC 469 Z9 483 U1 0 U2 11 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 SEP 4 PY 1998 VL 273 IS 36 BP 23169 EP 23175 DI 10.1074/jbc.273.36.23169 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 117JL UT WOS:000075778100046 PM 9722546 ER PT J AU Supko, JG Soglia, JR Nair, RV AF Supko, JG Soglia, JR Nair, RV TI Assay for the quinocarmycin analog DX-52-1 in human plasma using high-performance liquid chromatography with automated column switching and low wavelength ultraviolet detection SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE quinocarmycin; DX-52-1 ID KW2152; MICE AB The hydrocyanated derivative of the antitumor antibiotic quinocarmycin, DX-52-1 (I), exhibits impressive activity against human melanoma xenograft models in vivo. Phase I clinical trials to evaluate this compound as an antineoplastic agent have been initiated by the US National Cancer Institute. We have developed an HPLC assay for the determination of I in human plasma involving automated column switching and UV detection at 210 nm. The preparation of samples for chromatographic analysis entails the preliminary removal of plasma proteins by precipitation with acetonitrile, acidifying the clear supernatant to pH 4.5, then extracting twice with tert.-butyl methyl ether to recover the drug. A heart-cutting procedure employing two HPLC columns with contrasting retention characteristics under isocratic reversed-phase conditions was used to achieve the selectivity required for low wavelength UV detection of the analyte. The sample extract was initially loaded onto a column packed with a cyanopropyl stationary phase. During the predetermined time interval that I eluted from this column, a fully automated six-position switching valve was used to direct the effluent onto an octadecylsilane analytical column. The assay has been thoroughly validated with regard to linearity, inter- and intra-day accuracy and precision, recovery, selectivity and specificity. Using a sample volume of 1.0 mi, the lowest concentration of I quantified with acceptable day-to-day reproducibility was found to be 2.56 ng/ml (R.S.D. 18.9%, n = 21, 4 months). This proved to be sufficiently sensitive for pharmacokinetic drug level monitoring in cancer patients treated with a 6-h continuous intravenous infusion of I, even at the starting dose of 3 mg/m(2). The successful performance and reliability of the assay has been demonstrated through extensive application to the routine analysis of plasma specimens acquired during a phase I clinical trial of the drug. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Clin Pharmacol Lab, Div Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Supko, JG (reprint author), Massachusetts Gen Hosp, Clin Pharmacol Lab, Div Hematol Oncol, 55 Fruit St,GRJ1025, Boston, MA 02114 USA. NR 10 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B PD SEP 4 PY 1998 VL 714 IS 2 BP 341 EP 353 DI 10.1016/S0378-4347(98)00214-X PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 119BC UT WOS:000075874600025 PM 9766875 ER PT J AU Mody, FV Singh, BN Mohiuddin, IH Coyle, KB Buxton, DB Hansen, HW Sumida, R Schelbert, HR AF Mody, FV Singh, BN Mohiuddin, IH Coyle, KB Buxton, DB Hansen, HW Sumida, R Schelbert, HR TI Trimetazidine-induced enhancement of myocardial glucose utilization in normal and ischemic myocardial tissue: An evaluation by positron emission tomography SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LUMPED CONSTANT; METABOLIC-RATE; EFFORT ANGINA; FLUORODEOXYGLUCOSE; HEARTS; DEOXYGLUCOSE; PROPRANOLOL; NIFEDIPINE; RABBITS; INSULIN AB Trimetazidine has an anti-ischemic effect in angina pectoris. This agent has no hemodynamic effects, and its benefit is presumed to be based on a metabolic mechanism of action. A group of 33 dogs undergoing open-chest left anterior descending coronary artery (LAD) ligation causing prolonged ischemia were imaged with quantitative positron emission tomography (PET) using 2-[F-18]fluoro-2-deoxy-D-glucose ((18)FDG) to measure regional glucose metabolic utilization (rGMU) and [C-11]acetate to measure regional monoexponential washout rate constant (K-mono) for oxidative metabolism in nonrisk and ischemic-risk myocardium. A fetal of 20 dogs were pretreated with trimetazidine at low dose (n = 10, 1 mg/kg) and high dose (n = 10, 5 mg/kg) and compared with 13 control dogs. Microsphere-measured myocardial blood flow (mL/min/g) was measured preocclusion and repeated hourly after occlusion and expressed as a ratio of preocclusion myocardial blood flow to verify a stable level of ischemia during PET. No differences were seen in postocclusion ischemic risk/nonrisk myocardial blood flow between treatment groups (p = not significant [NS]). Preocclusion and hourly measurements of heart rate and blood pressure corrected for baseline revealed no difference in control dogs versus trimetazidine (low-dose and high-dose) groups (p = NS) (18)FDG-derived rGMU (mu mol/min/g) was increased in high-dose trimetazidine versus control dogs in nonrisk and ischemic risk groups, respectively (1.16 +/- 0.57 vs 0.51 +/- 0.38 and 0.43 +/- 0.29 vs 0.20 +/- 0.14; p <0.05). rGMU was increased proportionately in nonrisk and ischemic risk in all groups without significant differences when corrected for nonrisk rGMU (ischemic risk/nonrisk was 0.92 +/- 1.3 vs 0.64 +/- 0.66 vs 0.40 +/- 0.22 for control dogs, all trimetazidine and high-dose trimetazidine groups). K-mono (min(-1)) was not altered in any group (nonrisk = 0.13 +/- 0.03 vs 0.13 +/- 0.03 vs 0.14 +/- 0.02 and ischemic risk = 0.18 +/- 0.05 vs 0.17 +/- 0.06 vs 0.16 +/- 0.06 for control dogs, all trimetazidine and high-dose trimetazidine groups, respectively; p NS for nonrisk vs ischemic risk, between and within groups). Our data verify that trimetazidine does not alter hemodynamic parameters. It increases total glucose utilization (oxidative and glycolytic) in myocardium without preferential increase in ischemic tissue. Absence of change in total oxidative metabolism suggests increased glucose metabolism is predominantly glycolysis or an increase in glucose oxidation with similar decrease in fatty acid oxidation. (C) 1998 by Excerpta Medica, Inc. C1 Univ Calif Los Angeles, Sch Med, Div Cardiol W111E, W Los Angeles Vet Adm Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Div Nucl Med & Biophys, Los Angeles, CA USA. Univ Calif Los Angeles, Div Nucl Med, Lab Struct Biol & Mol Med, Los Angeles, CA USA. RP Mody, FV (reprint author), Univ Calif Los Angeles, Sch Med, Div Cardiol W111E, W Los Angeles Vet Adm Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NHLBI NIH HHS [HL27845]; PHS HHS [331770] NR 35 TC 22 Z9 26 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 3 PY 1998 VL 82 IS 5A SI SI BP 42K EP 49K DI 10.1016/S0002-9149(98)00536-0 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 118BN UT WOS:000075818000007 PM 9737485 ER PT J AU Palepu, A Carr, PL Friedman, RH Amos, H Ash, AS Moskowitz, MA AF Palepu, A Carr, PL Friedman, RH Amos, H Ash, AS Moskowitz, MA TI Minority faculty and academic rank in medicine SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PROMOTION; WOMEN; SCHOOLS; MEN AB Context.-Previous studies have found that fewer minority medical school faculty hold senior professorial ranks than do majority faculty and may not be promoted as rapidly. Objective.-To determine whether minority faculty were as likely as majority faculty to have attained senior rank (associate professor or full professor) after adjusting for other factors that typically influence promotion. Design.-A self-administered mailed survey of US medical school faculty using the Association of American Medical Colleges database. The sample was stratified by department, graduation cohort, and sex. Participants.-A stratified random sample of 3013 full-time faculty at 24 representative US medical schools. All underrepresented minority faculty at these schools were sampled. Main Outcome Measure.-Attainment of senior academic rank (associate professor or full professor). Results.-Of 3013 faculty surveyed, 1807 (60.0%) responded, including 1463 white (81.0%), 154 black (8.5%), 136 Asian (7.5%), and 54 Hispanic (3.0%), Overall, 980 faculty (54%) had attained senior academic rank, including 47 (30.5%) of 154 black faculty; 59 (43.4%) of 136 Asian faculty, 22 (40.8%) of 54 Hispanic faculty, and 852 (58.3%) of 1463 white faculty. White faculty had significantly more first-authored and total peer-reviewed publications than the other groups. After adjusting for the medical school, department, years as medical school faculty, number of peer-reviewed publications, receipt of research grant funding, proportion of time in clinical activities, sex, and tenure status, we found that the odds ratios of holding senior rank relative to white faculty were 0.33 (95% confidence interval [CI], 0.17-0.63) for black faculty, 0.36 (95% CI, 0.12-1.08) for Hispanic faculty, and 0.58 (95% CI, 0.30-1.12) for Asian faculty. Conclusions.-Minority faculty were less likely than white faculty to hold senior academic rank. This finding was not explained by potential confounders such as years as a faculty member or measures of academic productivity. C1 Boston Univ, Boston Med Ctr, Dept Med, Gen Internal Med Sect,MISU, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02114 USA. Harvard Univ, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Palepu, A (reprint author), Boston Univ, Boston Med Ctr, Dept Med, Gen Internal Med Sect,MISU, DOB 1102,720 Harrison Ave, Boston, MA 02118 USA. EM anita@hivnet.ubc.ca OI Palepu, Anita/0000-0002-7881-4800 NR 23 TC 74 Z9 74 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 SEP 2 PY 1998 VL 280 IS 9 BP 767 EP 771 DI 10.1001/jama.280.9.767 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 114LA UT WOS:000075609900003 PM 9729986 ER PT J AU Parsons, GN Kinsman, SB Ubel, PA AF Parsons, GN Kinsman, SB Ubel, PA TI Encourage qualitative research to improve students' clinical skills! SO ACADEMIC MEDICINE LA English DT Editorial Material C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Parsons, GN (reprint author), Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD SEP PY 1998 VL 73 IS 9 BP 933 EP 934 DI 10.1097/00001888-199809000-00009 PG 2 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 119VM UT WOS:000075918900010 PM 9759093 ER PT J AU Aronen, HJ Niemi, P Kwong, KK Pardo, FS Davis, RL AF Aronen, HJ Niemi, P Kwong, KK Pardo, FS Davis, RL TI The effect of paramagnetic contrast media on T1 relaxation times in brain tumors SO ACTA RADIOLOGICA LA English DT Article DE brain neoplasms, contrast media; MR imaging ID MR; DTPA; GADOTERIDOL; EXPERIENCE AB Purpose: To study T1 relaxation times in brain tumors before and after paramagnetic contrast medium injection. Material and Methods: Seventeen patients with a known or suspected brain tumor were studied with an echo planar inversion recovery imaging sequence using 10 different inversion times. Double injections of Gd chelate (0.1 mmol/ kg + 0.2 mmol/kg were administered in 5 patients, and a single 0.2-mmol/kg dose in 12 patients. Results. After the 0.2-mmol/kg dose, T1 decreased from 1121 +/- 130 ms to 987 +/- 103 ms in gray matter (p < 0.001), and from 666 +/- 29 ms to 646 +/- 27 ms in white matter p < 0.001). Tumor T1 shortened from 1515 +/- 319 ms to 717 +/- 383 ms. After the 0.1-mmol/kg;g dose (n = 5), tumor TI decreased from 1116 +/- 261 ms to 793 +/- 202 ms and after the additional 0.2-mmol/kg dose it, decreased further to 526 +/- 141 ms. Conclusion: Postcontrast T1 relaxation times in tumors showed considerable variation and remained, on average, relatively long compared to white matter. This should be taken into account when deciding which pulse sequences, imaging parameters, and contrast agent doses are optimal for brain tumor imaging. C1 Univ Helsinki, Cent Hosp, Dept Radiol, FIN-00290 Helsinki, Finland. Massachusetts Gen Hosp, Dept Radiol, NMR Ctr, Charlestown, MA USA. Turku Univ Hosp, Dept Radiol, FIN-20520 Turku, Finland. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Aronen, HJ (reprint author), Univ Helsinki, Cent Hosp, Dept Radiol, Haartmaninkatu 4, FIN-00290 Helsinki, Finland. FU FIC NIH HHS [1 F05 TW04520]; NCI NIH HHS [R01-CA40303]; NHLBI NIH HHS [R01-HL39810] NR 16 TC 3 Z9 5 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0284-1851 J9 ACTA RADIOL JI Acta Radiol. PD SEP PY 1998 VL 39 IS 5 BP 474 EP 481 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 119ZW UT WOS:000075930000003 PM 9755693 ER PT J AU Allen, J Anton, RF Babor, TF Carbonari, J Carroll, KM Connors, GJ Cooney, NL Del Boca, FK Di-Clemente, CC Donovan, D Kadden, RM Litt, M Longabaugh, R Mattson, M Miller, WR Randall, CL Rounsaville, BJ Rychtarik, RG Stout, RL Tonigan, JS Wirtz, PW Zweben, A AF Allen, J Anton, RF Babor, TF Carbonari, J Carroll, KM Connors, GJ Cooney, NL Del Boca, FK Di-Clemente, CC Donovan, D Kadden, RM Litt, M Longabaugh, R Mattson, M Miller, WR Randall, CL Rounsaville, BJ Rychtarik, RG Stout, RL Tonigan, JS Wirtz, PW Zweben, A CA Project MATCH Res Grp TI Matching alcoholism treatments to client heterogeneity: Project MATCH three-year drinking outcomes SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE long-term outcome; matching; alcoholism treatment; client attributes; Project MATCH ID SCALE; RELIABILITY; PREDICTORS; INSTRUMENT; DRINKERS; PATTERNS AB This study reports 3-year outcomes for clients who had been treated in the five outpatient sites of Project MATCH, a multisite clinical trial designed to test a priori client treatment matching hypotheses. The main purpose of this study was to characterize the status of the matching hypotheses at the 3-year follow-up. This entailed investigating which matching findings were sustained or even strengthened across the 3-year study period, and whether any hypotheses that were not supported earlier eventually emerged at 3 years, or conversely, whether matching findings discerned earlier dissipated at this later time. This research also examines the prognostic effects of the client matching attributes, characterizes the overall outcomes at 37 to 39 months, and explores differential effects of the three treatments at extended follow-up. With regard to the matching effects, client anger demonstrated the most consistent interaction in the trial, with significant matching effects evident at both the 1-year and 3-year follow-ups. As predicted, clients high in anger fared better in Motivational Enhancement Therapy (MET) than in the other two MATCH treatments: Cognitive-Behavioral Therapy (CBT) and Twelve-Step Facilitation (TSF). Among subjects in the highest third of the anger variable, clients treated in MET had on average 76.4% abstinent days, whereas their counterparts in the other two treatments (CBT and TSF) had on average 66% abstinent days. Conversely, clients low in anger performed better after treatment in CBT and TSF than in MET. Significant matching effects for the support for drinking variable emerged in the 3-year outcome analysis, such that clients whose social networks were more supportive of drinking derived greater benefit from TSF treatment than from MET. Among subjects in the highest third of the support for drinking variable, TSF participants were abstinent 16.1% more days than MET participants. At the lower end of this variable, difference in percent days abstinent between MET and TSF was 3%, with MET clients having more abstinent days. A significant matching effect for psychiatric severity that appeared in the first year posttreatment was not observed after 3 years. Of the 21 client attributes used in testing the matching hypotheses, 11 had prognostic value at 3 years. Among these, readiness-to-change and self-efficacy emerged as the strongest predictors of long-term drinking outcome. With regard to the overall outcomes, the reductions in drinking that were observed in the first year after treatment were sustained over the 3-year follow-up period: almost 30% of the subjects were totally abstinent in months 37 to 39, whereas those who did report drinking nevertheless remained abstinent an average of two-thirds of the time. As in the 1-year follow-up, there were few differences among the three treatments, although TSF continued to show a possible slight advantage. C1 Med Univ S Carolina, Charleston, SC 29425 USA. Univ Houston, Houston, TX 77004 USA. Yale Univ, Sch Med, Vet Affairs Connecticut Healthcare Syst, Res Inst Addict, New Haven, CT 06520 USA. Univ S Florida, Tampa, FL 33620 USA. Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. Univ Washington, Seattle, WA 98195 USA. Univ Connecticut, Sch Med & Dent, Vet Affairs Puget Sound Hlth Care Syst, Storrs, CT 06269 USA. Brown Univ, Providence, RI 02912 USA. Univ New Mexico, Albuquerque, NM 87131 USA. George Washington Univ, Washington, DC 20052 USA. Univ Wisconsin, Madison, WI 53706 USA. Univ Connecticut, Sch Med, Farmington, CT USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Vet Affairs Med Ctr, Charleston, SC 29403 USA. Res Inst Addict, Buffalo, NY 14203 USA. Univ Wisconsin, Milwaukee, WI 53201 USA. RP Allen, J (reprint author), NIAAA, Willco Bldg,Suite 409,6000 Execut Blvd, Bethesda, MD 20892 USA. RI Carroll, Kathleen/A-7526-2009; Cooney, Ned/C-5176-2014; OI Cooney, Ned/0000-0001-6698-8312; Carroll, Kathleen/0000-0003-3263-3374; Litt, Mark/0000-0002-8319-6090 NR 48 TC 141 Z9 146 U1 6 U2 25 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 1998 VL 22 IS 6 BP 1300 EP 1311 PG 12 WC Substance Abuse SC Substance Abuse GA 120KV UT WOS:000075956300016 ER PT J AU Philbin, EF DiSalvo, TG AF Philbin, EF DiSalvo, TG TI Managed care for congestive heart failure: Influence of payer status on process of care, resource utilization, and short-term outcomes SO AMERICAN HEART JOURNAL LA English DT Article ID HEALTH SYSTEM REFORM; FEE-FOR-SERVICE; MEDICAL OUTCOMES; ELDERLY PATIENTS; HOSPITAL LENGTH; QUALITY; PREPAID; PLANS; SPECIALTIES; PERFORMANCE AB Background Although health maintenance organizations (HMO) are insuring an increasing number of Americans, there are concerns that cost-reduction strategies may limit access to medical care or jeopardize its quality. This study was conducted to examine the influence of insurance payer status on the process of care and resource utilization among patients hospitalized for congestive heart failure (CHF). Methods and Results Administrative information on all 1995 New York State hospital discharges assigned ICD-9-CM codes indicative of CHF in the principal diagnosis position were obtained from the Statewide Planning and Research Cooperative System database. The following were compared among patients with HMO, indemnity, Medicaid fee-for-service, and Medicare fee-for-service insurance coverage: demographics, comorbid illness, process of care, length of stay, hospital charges, mortality rate, and CHF readmission rate. A total of 43,157 patients were identified (HMO, 1322; indemnity, 4350; Medicaid, 3878; Medicare, 33 607). Noninvasive procedures were used with similar frequency, whereas greater use of invasive techniques was observed among HMO and indemnity patients. After adjustment for patient characteristics and hospital type and location, HMO care was associated with shorter length of stay and lower hospital charges, the tatter partially explained by fewer hospital days. Medicaid patients had the longest length of stay, greatest hospital charges, and highest CHF readmission rate. The adjusted risk of death during the index hospitalization did not vary among insurance groups. Conclusions Though insuring only a small proportion of New Yorkers hospitalized for CHF, managed care plans provide similar access to clinical services while generating fewer charges. Whether these observed differences in short-term outcomes derive from patient mix or quality of care is uncertain and deserves wider prospective study. C1 Massachusetts Gen Hosp, Cardiac Unit, Heart Failure & Transplantat Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Philbin, EF (reprint author), Henry Ford Hosp, Div Cardiovasc Med, Heart Failure & Heart Transplantat Program, 2799 W Grand Blvd, Detroit, MI 48202 USA. NR 34 TC 30 Z9 30 U1 1 U2 2 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 SEP PY 1998 VL 136 IS 3 BP 553 EP 561 DI 10.1016/S0002-8703(98)70234-0 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 116LT UT WOS:000075713500029 PM 9736151 ER PT J AU Grinspoon, S Corcoran, C Miller, K Wang, E Hubbard, J Schoenfeld, D Anderson, E Basgoz, N Klibanski, A AF Grinspoon, S Corcoran, C Miller, K Wang, E Hubbard, J Schoenfeld, D Anderson, E Basgoz, N Klibanski, A TI Determinants of increased energy expenditure in HIV-infected women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE energy expenditure; HIV; human immunodeficiency virus; women; leptin; weight; fat-free mass; resting energy expenditure ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; BODY-COMPOSITION; VIRUS INFECTION; LEPTIN CONCENTRATIONS; NORMAL-WEIGHT; OBESE GENE; HUMANS; MEN AB Background: Little is known about sex-specific effects of HIV infection on energy expenditure. Objective: We investigated the determinants of energy expenditure in HIV-infected women. Design: Resting energy expenditure (REE), body composition, and hormonal and nutritional indexes were compared in 33 ambulatory, premenopausal HIV-infected women and 26 weight-matched, healthy premenopausal control subjects. REE was determined by indirect calorimetry and body composition by dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis, and skinfold-thickness analysis. Hormonal indexes included leptin, testosterone, estradiol, and insulin-like growth factor I. Results: HIV-infected subjects had a higher REE than control subjects [6794 +/- 1374 compared with 6011 +/- 607 kJ/d (1624 +/- 329 compared with 1437 +/- 145 kcal/d), P = 0.0096]. On average, REE was 119 +/- 23% of Harris-Benedict predictions in HIV-infected subjects compared with 102 +/- 9% for control subjects (P = 0.0007). In HIV-infected subjects, REE was highly correlated with fat-free mass (FFM) by DXA (R = 0.641, P < 0.001), but not with weight or disease status. The slope of the regression equation for REE and FFM was significantly greater (P = 0.027, analysis of covariance) for HIV-infected subjects [REE (kJ/d) = 203.5 (kg FFM) - 1237] than for control subjects [REE (kJ/d) = 77.4 (kg FFM) + 2923]. In a stepwise regression analysis, FFM was the most significant variable (P = 0.005), followed by free testosterone (P = 0.029), which together explained 4946 of the variation in REE. The final equation was REE (kJ/d)= 230.8 (kg FFM) + 395.9 (free testosterone, pmol/L) - 3304. Conclusions: Energy expenditure was higher in HIV-infected women than in control women. FFM is the primary determinant of REE in HIV-infected women, but energy expenditure is greater per kg FFM in HIV-infected subjects than in control subjects, which may contribute to the wasting syndrome. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR01066]; NIDDK NIH HHS [P32-DK07028, R01-DK49302] NR 24 TC 44 Z9 44 U1 1 U2 1 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD SEP PY 1998 VL 68 IS 3 BP 720 EP 725 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 115CN UT WOS:000075646100032 PM 9734753 ER PT J AU Nellissery, MJ Padalecki, SS Brkanac, Z Singer, FR Roodman, GD Unni, KK Leach, RJ Hansen, MF AF Nellissery, MJ Padalecki, SS Brkanac, Z Singer, FR Roodman, GD Unni, KK Leach, RJ Hansen, MF TI Evidence for a novel osteosarcoma tumor-suppressor gene in the chromosome 18 region genetically linked with Paget disease of bone SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID FAMILIAL EXPANSILE OSTEOLYSIS; BECKWITH-WIEDEMANN-SYNDROME; OSTEOGENIC-SARCOMA; P53 GENE; RETINOBLASTOMA; IDENTIFICATION; LINKAGE; DNA; NEUROFIBROMATOSIS; LOCALIZATION AB Paget disease of bone, or "osteitis deformans," is a bone disorder characterized by rapid bone remodeling resulting in abnormal bone formation. It is the second most common metabolic bone disease after osteoporosis, affecting 3%-5% of subjects aged >40 years. Recent evidence suggests that predisposition to Paget disease may have a genetic component. Genetic linkage analysis of families with multigenerational Paget disease shows linkage to a region of chromosome 18q near the polymorphic locus D18S42. Approximately 1% of Paget patients develop osteosarcoma, which represents an increase in risk that is several thousandfold over that of the general population. Osteosarcoma in Paget patients is the underlying basis for a significant fraction of osteosarcomas occurring after age 60 years. Our analysis of tumor-specific loss of constitutional heterozygosity (LOH) in 96 sporadic osteosarcomas has identified a putative tumor-suppressor locus that maps to chromosome 18q. We have localized this tumor-suppressor locus between D18S60 and D18S42, a region tightly linked to familial Paget disease. Analysis of osteosarcomas from patients with Paget disease revealed that these tumors also undergo LOH in this region. These findings suggest that the association between Paget disease and osteosarcoma is the result of a single gene or two tightly linked genes on chromosome 18. C1 Temple Univ, Sch Med, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19140 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, Dept Med, San Antonio, TX 78284 USA. St Johns Hosp & Hlth Ctr, John Wayne Canc Inst, Santa Monica, CA USA. Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. RP Hansen, MF (reprint author), Temple Univ, Sch Med, Fels Inst Canc Res & Mol Biol, 3307 N Broad St, Philadelphia, PA 19140 USA. EM mfh@sgi1.fels.temple.edu FU NCI NIH HHS [CA 53318]; NIAMS NIH HHS [AR 44904, AR44919] NR 52 TC 67 Z9 71 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 1998 VL 63 IS 3 BP 817 EP 824 DI 10.1086/302019 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 119VN UT WOS:000075919000020 PM 9718349 ER PT J AU Parker, RA Himmelfarb, J Tolkoff-Rubin, N Chandran, P Wingard, RL Hakim, RM AF Parker, RA Himmelfarb, J Tolkoff-Rubin, N Chandran, P Wingard, RL Hakim, RM TI Prognosis of patients with acute renal failure requiring dialysis: Results of a multicenter study SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article ID CRITICALLY-ILL PATIENTS; INTENSIVE-CARE UNIT; ACUTE TUBULAR-NECROSIS; CONTINUOUS VENOVENOUS HEMODIAFILTRATION; APACHE-II; HOSPITALIZED ADULTS; RISK-FACTORS; MORTALITY; PREDICTION; HEMODIALYSIS AB Despite several decades of clinical experience, the mortality rate for patients with acute renal failure (ARF) requiring dialysis remains high, and the evaluation of the patients prognosis has been difficult. To date, the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring system has been used more frequently for prediction in studies of ARF than any other scoring system, but has not been prospectively validated in controlled multicenter studies of this entity. In a multicenter, prospective, controlled trial evaluating the use of biocompatible hemodialysis membranes (BCMs) in patients with ARF, we evaluated the extent to which the APACHE II scoring system, based on the physiological variables in the 24 hours before the onset of dialysis and the presence or absence of oliguria, is predictive of outcome. Analysis of survival and recovery of renal function for the 153 patients treated in this study show that APACHE II scores are predictive both of survival and recovery of renal function, whether analyzed separately by type of dialysis membrane used (BCM or bioincompatible [BICM]) or for both groups combined (all P < 0.01). There was no evidence of a significant center effect or interaction of APACHE II score with dialysis membrane in our study. After adjusting for the APACHE II score, there was a positive effect of the BCM on both probability of survival (P < 0.05) and recovery of renal function (P < 0.01). In patients dialyzed with BCMs, oliguria at onset of dialysis had an adverse effect on both survival and recovery of renal function (both P < 0.01). Receiver operator curves (ROCs) using APACHE II score and the use of BCMs in nonoliguric patients yielded a statistically significant improvement versus the use of APACHE II score alone in the area under the curve (AUC) for survival (0.747 to 0.801; P < 0.05) and recovery of renal function (0.712 to 0.775; P < 0.05). We conclude that the use of the APACHE II score determined at the time of initiation of dialysis for patients with ARF is a statistically significant predictor of patient survival and recovery of renal function. The use of the APACHE II score measured at the time of dialysis initiation, especially when modified by the presence or absence of oliguria, should help in predicting outcome when evaluating interventions for patients with ARF. (C) 1998 by the National Kidney Foundation, Inc. C1 Beth Israel Deaconess Med Ctr, Biometr Ctr GZ 800, Boston, MA 02215 USA. Maine Med Ctr, Portland, ME 04102 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Iowa Methodist Med Ctr, Des Moines, IA USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. RP Parker, RA (reprint author), Beth Israel Deaconess Med Ctr, Biometr Ctr GZ 800, E Campus,330 Brookline Ave, Boston, MA 02215 USA. NR 56 TC 54 Z9 55 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 1998 VL 32 IS 3 BP 432 EP 443 DI 10.1053/ajkd.1998.v32.pm9740160 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 116RA UT WOS:000075737300013 PM 9740160 ER PT J AU Poses, RM Berlin, JA Noveck, H Lawrence, VA Huber, EC O'Hara, DA Spence, RK Duff, A Strom, BL Carson, JL AF Poses, RM Berlin, JA Noveck, H Lawrence, VA Huber, EC O'Hara, DA Spence, RK Duff, A Strom, BL Carson, JL TI How you look determines what you find: Severity of illness and variation in blood transfusion for hip fracture SO AMERICAN JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the Society-for-Medical-Decision-Making CY OCT 13-16, 1996 CL TORONTO, CANADA SP Soc Med Decis Making ID ACADEMIC MEDICAL-CENTERS; SMALL AREA ANALYSIS; MANAGED-CARE; CELL TRANSFUSIONS; DISEASE; PHYSICIANS; SURGERY; POPULATION; MORTALITY; MORBIDITY AB PURPOSE: Utilization report cards are commonly used to assess hospitals. However, in practice, they rarely account for differences in patient populations among hospitals. Our study questions were: (1) How does transfusion utilization for hip fracture patients vary among hospitals! (2) What patient characteristics are associated with transfusion and how do those characteristics vary among hospitals? (3) Is the apparent pattern of variation of utilization among hospitals altered by controlling for these patient characteristics! SUBJECTS AND METHODS: We included consecutive hip fracture patients aged 60 years or older who underwent surgical repair between 1982 and 1993 in 19 hospitals from four states, excluding those who refused blood transfusion, had multiple trauma, metastatic cancer, multiple myeloma, an above the knee amputation, or were paraplegic or quadriplegic. The outcome of interest was postoperative blood transfusion. "Trigger hemoglobin" was the lowest hemoglobin recorded before transfusion or recorded at any time during the week before or after surgery for patients who were not transfused. RESULTS: There was considerable variation in transfusion among hospitals postoperatively (range 31.2% to 54.0%, P = 0.001). Trigger hemoglobin also varied considerably among hospitals. In unadjusted analyses, four of nine teaching and two of nine nonteaching hospitals had postoperative transfusion rates significantly higher than the reference (teaching) hospital, while one nonteaching hospital had a lower rate. In an analysis controlling for trigger hemoglobin and multiple clinical variables, one of nine teaching and four of nine nonteaching hospitals had rates higher than the reference hospital, while four teaching hospitals and one nonteaching hospital had lower rates. CONCLUSIONS: The apparent pattern of variation of transfusion among hospitals varies according to how one adjusts for relevant patient characteristics. Utilization report cards that fail to adjust for these characteristics may be misleading. (C) 1998 by Excerpta Medica, Inc. C1 Mem Hosp, Div Gen Internal Med, Pawtucket, RI 02860 USA. Brown Univ, Sch Med, Div Gen Internal Med, Providence, RI 02912 USA. Brown Univ, Sch Med, Dept Med, Providence, RI 02912 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Div Gen Internal Med, New Brunswick, NJ USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med, New Brunswick, NJ USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, Div Gen Internal Med, San Antonio, TX USA. Virginia Commonwealth Univ, Med Coll Virginia, Div Gen Internal Med, Richmond, VA 23298 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Anesthesia, New Brunswick, NJ USA. Staten Isl Univ Hosp, Staten Isl, NY USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Poses, RM (reprint author), Mem Hosp, Div Gen Internal Med, 111 Brewster St, Pawtucket, RI 02860 USA. FU AHRQ HHS [HS07322] NR 52 TC 22 Z9 21 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP PY 1998 VL 105 IS 3 BP 198 EP 206 DI 10.1016/S0002-9343(98)00236-8 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 120XF UT WOS:000075982200005 PM 9753022 ER PT J AU Haidet, P Hamel, MB Davis, RB Wenger, N Reding, D Kussin, PS Connors, AF Lynn, J Weeks, JC Phillips, RS AF Haidet, P Hamel, MB Davis, RB Wenger, N Reding, D Kussin, PS Connors, AF Lynn, J Weeks, JC Phillips, RS CA SUPPORT Investigators TI Outcomes, preferences for resuscitation, and physician-patient communication among patients with metastatic colorectal cancer SO AMERICAN JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 19th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 02-04, 1996 CL WASHINGTON, D.C. SP Soc Gen Internal Med ID QUALITY-OF-LIFE; SERIOUSLY ILL PATIENTS; CARDIOPULMONARY-RESUSCITATION; BIOCHEMICAL MODULATION; ADVANCE DIRECTIVES; SURVIVAL; CARCINOMA; CHEMOTHERAPY; EXPERIENCE; PROGNOSIS AB PURPOSE: To describe characteristics, outcomes, and decision making in patients with colorectal cancer metastatic to the liver, and to examine the relationship of doctor-patient communication with patient understanding of prognosis and physician understanding of patients' treatment preferences. PATIENTS AND METHODS: The Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) was a prospective cohort study conducted at five teaching hospitals in the United States between 1989 and 1994. Participants in this study were hospitalized patients 18 years of age or older with known liver metastases who had been diagnosed with colorectal cancer at least 1 month earlier. Data were collected by patient interview and chart review at study entry; patients were inteviewed again at 2 and 6 months. Data collected by physician interview included estimates of survival and impressions of patients' preferences for cardiopulmonary resuscitation (CPR). Patients and physicians were also asked about discussions about prognosis and resuscitation preferences. RESULTS: We studied 520 patients with metastatic colorectal cancer (median age 64, 56% male, 80% white, 2-month survival 78%, 6-month survival 56%). Quality of life (62% "good" to "excellent") and functional status (median number of disabilities = 0) were high at study entry and remained so among interviewed survivors at 2 and 6 months. Of 339 patients with available information, 212 (63%) of 339 wanted CPR in the event of a cardiopulmonary arrest. Factors independently associated with preference for resuscitation included younger age, better quality of life, absence of lung metastases, and greater patient estimate of 2-month prognosis. Of the patients who preferred not to receive CPR, less than half had a do-not-resuscitate note or order written. Patients' self-assessed prognoses were less accurate than those of their physicians. Physicians incorrectly identified patient CPR preferences in 30% of cases. Neither patient prognostication nor physician understanding of preferences were significantly better when discussions were reported between doctors and patients. CONCLUSIONS: A majority of patients with colorectal cancer have preferences regarding end of life care. The substantial misunderstanding between patients and their physicians about prognosis and treatment preferences appears not to be improved by direct communication. Future research focused on enhancing the effectiveness of communication between patients and physicians about end of life issues is needed. (C) 1998 by Excerpta Medica, Inc. C1 Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA USA. George Washington Univ, Med Ctr, Washington, DC USA. Univ Virginia, Sch Med, Charlottesville, VA USA. Marshfield Clin, Marshfield, WI USA. Duke Univ, Med Ctr, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Phillips, RS (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, 330 Brookline Ave, Boston, MA 02215 USA. FU BHP HRSA HHS [PE11001-09] NR 54 TC 81 Z9 81 U1 5 U2 10 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP PY 1998 VL 105 IS 3 BP 222 EP 229 DI 10.1016/S0002-9343(98)00242-3 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 120XF UT WOS:000075982200008 PM 9753025 ER PT J AU Curtin, HD AF Curtin, HD TI Detection of perineural spread: Fat is a friend SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Editorial Material C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Curtin, HD (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD SEP PY 1998 VL 19 IS 8 BP 1385 EP 1386 PG 2 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 121WW UT WOS:000076039600003 PM 9763363 ER PT J AU McKenna, MJ Kristiansen, AG Bartley, ML Rogus, JJ Haines, JL AF McKenna, MJ Kristiansen, AG Bartley, ML Rogus, JJ Haines, JL TI Association of COL1A1 and otosclerosis - Evidence for a shared genetic etiology with mild osteogenesis imperfecta SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article; Proceedings Paper CT 113th Annual Meeting of the American-Otological-Society CY MAY 10-11, 1997 CL SCOTTSDALE, ARIZONA SP Amer Otol Soc DE otosclerosis; osteogenesis imperfecta; collagen; gene; association ID HUMAN GLIAL-CELLS; MEASLES-VIRUS; I COLLAGEN; NULL ALLELES; EXTRACELLULAR-MATRIX; ACTIVE OTOSCLEROSIS; TEMPORAL BONE; LINKAGE; HETEROGENEITY; EXPRESSION AB Hypothesis: Otosclerosis is related to mild osteogenesis imperfecta with genetic defects in type I collagen. Background: Otosclerosis is a common bone disease of the human otic capsule that has an underlying hereditary predisposition. The histopathology and clinical manifestations are strikingly similar to the milder forms of osteogenesis imperfecta in which mutations of type I collagen genes have been established as the underlying cause. Methods: The authors investigated the genetic basis of otosclerosis by conducting an association study using polymorphic DNA markers from patients with clinical otosclerosis and random control subjects. Results: This study showed a significant association between clinical otosclerosis and the type I collagen COL1Al gene using three different polymorphic markers within the gene. Conclusions: Some cases of clinical otosclerosis may be related to mutations within the COL1Al gene that are similar to those found in mild forms of osteogenesis imperfecta and result in null expression of the mutant allele. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Program Populat Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. RP McKenna, MJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. RI Haines, Jonathan/C-3374-2012 FU NIDCD NIH HHS [KO8 DC00065] NR 53 TC 60 Z9 60 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD SEP PY 1998 VL 19 IS 5 BP 604 EP 610 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 188RV UT WOS:000079863000014 PM 9752968 ER PT J AU Thomas, GV Szigeti, K Murphy, M Draetta, G Pagano, M Loda, M AF Thomas, GV Szigeti, K Murphy, M Draetta, G Pagano, M Loda, M TI Down-regulation of p27 is associated with development of colorectal adenocarcinoma metastases SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID DEPENDENT KINASE INHIBITOR; GROWTH-FACTOR-BETA; CELL-CYCLE; BREAST-CANCER; MICE LACKING; P27(KIP1); PROTEIN; GENE; EXPRESSION; D1 AB The cyclin-dependent kinase inhibitor p27 is a negative regulator of the cell cycle and a potential tumor suppressor gene. Because we had previously demonstrated that loss of p27 protein is associated with aggressive behavior in colorectal adenocarcinomas, we used immunohistochemistry and in situ hybridization to evaluate the potential role of alterations in p27 expression in primary and metastatic colorectal adenocarcinomas. Parallel immunostaining was performed for Ki-67 and p53. We evaluated 13 cases of metachronous and 25 cases of synchronous primary and metastatic colorectal tumor pairs. In the synchronous subgroup (Stage IV tumors), 57% of the primary tumor and metastases pairs did not express p27 protein and the remainder were low expressors. In the metachronous subgroup, 54% of the primary tumors were low expressors and the remainder high expressors of p27 protein. There was a significant reduction in the expression of p27 in the metachronous metastases (mean positive cells: 14.5%) when compared to the corresponding primary tumors (mean positive cells: 41.8%), P = 0.0023. All the primary and metastatic tumors in the metachronous subgroup showed high levels of p27 mRNA expression. There was no association between loss of p27 and either Ki-67 count or p53 expression. Because p27 is known to be up-regulated when epithelial cells are grown ia suspension, the down-regulation of p27 in circulating tumor cells may confer the ability to grow in an environment of altered extracellular matrix or intercellular adhesion properties, two situations which may facilitate metastases. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Adult Oncol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. European Inst Oncol, Milan, Italy. NYU, Med Ctr, Kaplan Comprehens Canc Ctr, Dept Pathol, New York, NY 10016 USA. RP Loda, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Adult Oncol, 44 Binney St, Boston, MA 02215 USA. FU NCI NIH HHS [CA 76584-01A1, R37 CA076584, CA44704-09, R01 CA076584]; NIGMS NIH HHS [R01 GM057587, GM/CA 57587-01] NR 45 TC 132 Z9 142 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 1998 VL 153 IS 3 BP 681 EP 687 DI 10.1016/S0002-9440(10)65610-6 PG 7 WC Pathology SC Pathology GA 116VJ UT WOS:000075745500004 PM 9736017 ER PT J AU Zuk, A Bonventre, JV Brown, D Matlin, KS AF Zuk, A Bonventre, JV Brown, D Matlin, KS TI Polarity, integrin, and extracellular matrix dynamics in the postischemic rat kidney SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE beta(1)-integrin; epithelial polarity; fibronectin; acute renal failure ID ACUTE-RENAL-FAILURE; ISCHEMIA-INDUCED LOSS; PROXIMAL TUBULE; CELL-CELL; MONOCLONAL-ANTIBODIES; EPITHELIAL POLARITY; CYTOPLASMIC DOMAIN; BETA-1 INTEGRIN; POTENTIAL ROLE; RGD PEPTIDES AB Acute renal failure (ARF) as a consequence of ischemic injury is a common disease affecting 5% of the hospitalized population. Despite the fact that mortality from ARF is high, there has been Little improvement in survival rates over the last 40 years. The pathogenesis of ARF may be related to substantial changes in cell-cell and cell-extracellular matrix interactions mediated by beta(1)-integrins. On the basis of in vitro and in vivo studies, reorganization of beta(1)-integrins from basal to apical surfaces of injured tubular epithelia has been suggested to facilitate epithelial detachment, contributing to tubular obstruction and backleak of glomerular filtrate. In this study, we examine integrin and extracellular matrix dynamics during epithelial injury and repair using an in vivo rat model of unilateral ischemia. We find that, soon after reperfusion, beta(1)-integrins newly appear on lateral borders in epithelial cells of the S3 segment but are not on the apical surface. At later times, as further injury and regeneration coordinately occur, epithelia adherent to the basement membrane localize beta(1) predominantly to basal surfaces even while the polarity of other marker proteins is lost. At the same time, amorphous material consisting of depolarized exfoliated cells fills the luminal space. Notably, beta(1)-integrins are not detected on exfoliated cells. A novel finding is the presence of fibronectin, a glycoprotein of plasma and the renal interstitium, in tubular spaces of the distal nephron and to a lesser extent S3 segments. These results indicate that beta(1)-integrins dramatically change their distribution during ischemic injury and epithelial repair, possibly contributing to cell exfoliation initially and to epithelial regeneration at later stages. Together with the appearance of large amounts of fibronectin in tubular lumens, these alterations may play a significant role in the pathophysiology of ARF. C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Institute Technology, Sch Med, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Zuk, A (reprint author), Beth Israel Deaconess Med Ctr, Dept Surg, E Campus,330 Brookline Ave,RW 873, Boston, MA 02215 USA. FU NIDDK NIH HHS [R01-DK-42956, P01-DK-38452, R01-DK-46768] NR 83 TC 101 Z9 108 U1 1 U2 1 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 SEP PY 1998 VL 275 IS 3 BP C711 EP C731 PG 21 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 114QP UT WOS:000075620600013 PM 9730955 ER PT J AU Cutaia, MV Parks, N Centracchio, J Rounds, S Yip, KP Sun, AM AF Cutaia, MV Parks, N Centracchio, J Rounds, S Yip, KP Sun, AM TI Effect of hypoxic exposure on Na+/H+ antiport activity, isoform expression, and localization in endothelial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE chronic hypoxia; pulmonary arterial endothelial cells; intracellular pH; membrane ion transport ID INTRACELLULAR PH; PULMONARY-HYPERTENSION; ACTIN CYTOSKELETON; RAT; EXCHANGE; CHANNEL; PHOSPHORYLATION; NA+,K+-ATPASE; REOXYGENATION; MECHANISMS AB Little is known about the effects of prolonged hypoxic exposure on membrane ion transport activity. The Na+/H+ antiport is an ion transport site that regulates intracellular pH in mammalian cells. We determined the effect of prolonged hypoxic exposure on human pulmonary arterial endothelial cell antiport activity, gene expression, and localization. Monolayers were incubated under hypoxic or normoxic conditions for 72 h. Antiport activity was determined as the rate of recovery from intracellular acidosis. Antiport isoform identification and gene expression were determined with RT-PCR and Northern and Western blots. Antiport localization and F-actin cytoskeleton organization were defined with immunofluorescent staining. Prolonged hypoxic exposure decreased antiport activity, with no change in cell viability compared with normoxic control cells. One antiport isoform [Na+/H+ exchanger isoform (NHE) 1] that was localized to the basolateral cell surface was present in human pulmonary arterial endothelial cells. Hypoxic exposure had no effect on NHE1 mRNA transcript expression, but NHE1 protein expression was upregulated. Immunofluorescent staining demonstrated a significant alteration of the F-actin cytoskeleton after hypoxic exposure but no change in NHE1 localization. These results demonstrate that the decrease in NHE1 activity after prolonged hypoxic exposure is not related to altered gene expression. The change in NHE1 activity may have important consequences for vascular function. C1 Univ Penn, Sch Med, Vet Affairs Med Ctr, Dept Med,Pulm Dis Div, Philadelphia, PA USA. Vet Affairs Med Ctr, Dept Med, Pulm & Crit Care Sect, Providence, RI 02908 USA. Brown Univ, Sch Med, Providence, RI 02908 USA. Rhode Isl Hosp, Dept Med, Div Renal, Providence, RI 02903 USA. Brown Univ, Dept Physiol, Div Biol & Med, Providence, RI 02906 USA. RP Cutaia, MV (reprint author), Vet Adm Med Ctr, Res Serv, 3900 Univ & Woodland Ave, Philadelphia, PA 19104 USA. RI Yip, Kay-Pong/H-4639-2012 OI Yip, Kay-Pong/0000-0003-4364-6701 FU NIDDK NIH HHS [R29-DK-47403] NR 47 TC 25 Z9 25 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD SEP PY 1998 VL 275 IS 3 BP L442 EP L451 PG 10 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 116VF UT WOS:000075745200003 PM 9728038 ER PT J AU Nakamura, H Haley, KJ Nakamura, T Luster, AD Lilly, CM AF Nakamura, H Haley, KJ Nakamura, T Luster, AD Lilly, CM TI Differential regulation of eotaxin expression by TNF-alpha and PMA in human monocytic U-937 cells SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE dexamethasone; protein kinase C; nuclear factor-kappa B; cycloheximide ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; TRANSCRIPTION FACTOR; CC-CHEMOKINE; ALVEOLAR MACROPHAGES; EPITHELIAL-CELLS; GENE-EXPRESSION; CHEMOATTRACTANT; EOSINOPHILS; ACTIVATION AB Regulation of eotaxin expression was investigated in U-937 cells, a human monocytelike cell line. Eotaxin mRNA was induced by tumor necrosis factor-alpha (TNF-alpha; 0.1-100 ng/ml) and phorbol 12-myristate 13-acetate (PMA; 0.01-1 mu M). PMA-induced eotaxin mRNA expression was of greater magnitude and was maximal at a later time point than TNF-alpha-induced expression (16 h vs. 2 h after stimulation), which was consistent with eotaxin protein expression detected by immunocytochemistry. Dexamethasone (0.01-10 mu M) decreased eotaxin mRNA expression in both TNF-alpha- and PMA-stimulated U-937 cells. PMA-induced eotaxin mRNA expression was inhibited by cycloheximide (10 mu g/ml), whereas TNF-alpha-induced expression was not. The protein kinase C (PKC) inhibitor staurosporine (10-50 nM) inhibited PMA-induced eotaxin mRNA expression, whereas TNF-alpha-induced expression was enhanced by this reagent. These results suggest that eotaxin expression can be induced by more than one mechanism: the PMA-triggered pathway is mediated by PKC activation and requires new protein synthesis, whereas the TNF-alpha-triggered pathway is independent of PKC and protein synthesis. TNF-alpha- and PMA-induced pathways are both associated with nuclear factor-kappa B, because its binding activity was enhanced in the presence of these stimuli, and both pathways were limited by its inhibitor, diethyldithiocarbamate. C1 Brigham & Womens Hosp, Div Resp, Dept Med, Combined Program Pulm & Crit Care Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 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. FU NHLBI NIH HHS [HL-03283]; NIAID NIH HHS [AI-40618] NR 33 TC 16 Z9 16 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD SEP PY 1998 VL 275 IS 3 BP L601 EP L610 PG 10 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 116VF UT WOS:000075745200021 PM 9728056 ER PT J AU Brown, D Katsura, T Gustafson, CE AF Brown, D Katsura, T Gustafson, CE TI Cellular mechanisms of aquaporin trafficking SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article; Proceedings Paper CT Experimental Biology 97 Conference CY APR 06-10, 1997 CL NEW ORLEANS, LA DE vasopressin; phosphorylation ID NEPHROGENIC DIABETES-INSIPIDUS; COLLECTING DUCT CELLS; WATER CHANNEL; EPITHELIAL-CELLS; RAT-KIDNEY; F-ACTIN; VASOPRESSIN; EXPRESSION; PROTEIN; PHOSPHORYLATION AB Aquaporins (AQPs) are a family of functionally important water channel proteins that are of special cell biological interest because of their diverse intracellular targeting and trafficking properties. AQPs have been found in many different cells and tissues. This short review summarizes recent work that addresses the regulation of AQP2 trafficking in response to vasopressin. C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Brown, D (reprint author), Massachusetts Gen Hosp East, Renal Unit, Boston, MA 02129 USA. FU NIDDK NIH HHS [DK-38452] NR 39 TC 70 Z9 72 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD SEP PY 1998 VL 275 IS 3 BP F328 EP F331 PG 4 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 117VE UT WOS:000075802700004 PM 9729503 ER PT J AU Smoller, JW Tsuang, MT AF Smoller, JW Tsuang, MT TI Panic and phobic anxiety: Defining phenotypes for genetic studies SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Review ID POPULATION-BASED TWIN; QUANTITATIVE TRAIT LOCI; MAJOR DEPRESSION; SOCIAL PHOBIA; PSYCHIATRIC-DISORDERS; BEHAVIORAL-INHIBITION; FAMILIAL TRANSMISSION; SEPARATION ANXIETY; CARBON-DIOXIDE; COMPLEX TRAITS AB Objective: With recent advances in molecular genetics, the rate-limiting step in identifying susceptibility genes for psychiatric disorders has become phenotype definition. The success of psychiatric genetics may require the development of a "genetic nosology" that can classify individuals in terms of the heritable aspects of psychopathology. The authors' aim is to begin to apply this analysis to the anxiety disorders, focusing on panic and phobic disorders. Method: Two parallel traditions of defining anxiety phenotypes are reviewed: the first, more closely identified with clinical psychiatry has identified categorical diagnoses (e.g., panic disorder and social phobia). The other, more closely identified with psychological studies of personality development, has examined dimensional traits (e.g., neuroticism) and anxious temperament (e.g., behavioral inhibition). Results: The authors suggest that a genetic nosology of panic and phobic disorders may incorporate features of both traditions and discuss strategies for optimizing genetic approaches to anxiety including I) studying phenotypic extremes, 2) identifying biological trait markers, and 3) using animal models to identify candidate loci. Conclusions: An important dividend from the effort to define the boundaries of heritable phenotypes for genetic studies of anxiety may be a refinement of the nosology of anxiety disorders. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Smoller, JW (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WACC-815, Boston, MA 02114 USA. EM smoller@warren.med.harvard.edu FU NIMH NIH HHS [MH-17119] NR 105 TC 105 Z9 105 U1 8 U2 12 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 1998 VL 155 IS 9 BP 1152 EP 1162 PG 11 WC Psychiatry SC Psychiatry GA 116KF UT WOS:000075723000003 PM 9734536 ER PT J AU Tsai, GC Goff, DC Chang, RW Flood, J Baer, L Coyle, JT AF Tsai, GC Goff, DC Chang, RW Flood, J Baer, L Coyle, JT TI Markers of glutamatergic neurotransmission and oxidative stress associated with tardive dyskinesia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ELECTRON-TRANSPORT CHAIN; VITAMIN-E TREATMENT; INHIBIT COMPLEX-I; AMINO-ACIDS; RAT-BRAIN; NEUROLEPTIC MEDICATIONS; NEUROPSYCHIATRIC DISORDERS; CEREBROSPINAL-FLUID; LIPID-PEROXIDATION; FREE-RADICALS AB Objective: Tardive dyskinesia is a movement disorder affecting 20%-40% of patients treated chronically with neuroleptic drugs. The dopamine supersensitivity hypothesis cannot account for the time course of tardive dyskinesia or for the persistence of tardive dyskinesia and the associated structural changes after neuroleptics are discontinued. The authors hypothesized that neuroleptics enhance striatal glutamatergic neurotransmission by blocking presynaptic dopamine receptors, which causes neuronal damage as a consequence of oxidative stress. Method: CSF was obtained from 20 patients with schizophrenia, 11 of whom had tardive dyskinesia. Markers for oxidative stress, including superoxide dismutase, lipid hydroperoxide, and protein carbonyl groups, and markers for excitatory neurotransmission, including N-acetylaspartate, N-acetylaspartylglutamate, aspartate, and glutamate, were measured in the CSF specimens. Patients were also rated for tardive dyskinesia symptoms with the Abnormal Involuntary Movement Scale. Results: Tardive dyskinesia patients had significantly higher concentrations of N-acetylaspartate, N-acetylaspartylglutamate, and aspartate in their CSF than patients without tardive dyskinesia when age and neuroleptic dose were controlled for. The significance of the higher levels of protein-oxidized products associated with tardive dyskinesia did not pass Bonferroni correction, however. Tardive dyskinesia symptoms correlated positively with markers of excitatory neurotransmission and protein carbonyl group and negatively with CSF superoxide dismutase activity. Conclusions: These findings suggest that there are elevated levels of oxidative stress and glutamatergic neurotransmission in tardive dyskinesia, both of which may be relevant to the pathophysiology of tardive dyskinesia. C1 Harvard Univ, Sch Med, Dept Psychiat, Lab Mol & Dev Neurosci, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Harvard Univ, Sch Med, Dept Psychiat, Lab Mol & Dev Neurosci, 115 Mill St, Belmont, MA 02178 USA. FU NIMH NIH HHS [MH-51290]; NINDS NIH HHS [NS-13584, NS-13584-17] NR 46 TC 157 Z9 162 U1 1 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 1998 VL 155 IS 9 BP 1207 EP 1213 PG 7 WC Psychiatry SC Psychiatry GA 116KF UT WOS:000075723000011 PM 9734544 ER PT J AU Reimherr, FW Amsterdam, JD Quitkin, FM Rosenbaum, JF Fava, M Zajecka, J Beasley, CM Michelson, D Roback, P Sundell, K AF Reimherr, FW Amsterdam, JD Quitkin, FM Rosenbaum, JF Fava, M Zajecka, J Beasley, CM Michelson, D Roback, P Sundell, K TI Optimal length of continuation therapy in depression: A prospective assessment during long-term fluoxetine treatment SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 150th Annual Meeting of the American-Psychiatric-Association CY MAY 17-23, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Psychiat Assoc ID RECURRENT DEPRESSION; MAINTENANCE THERAPIES; MAJOR DEPRESSION; CONTROLLED TRIAL; EPISODES; AMITRIPTYLINE; IMIPRAMINE; LITHIUM; ILLNESS AB Objective: The purpose of this study was to determine prospectively the optimal length of therapy in a long-term, placebo-controlled continuation study of patients who responded to acute fluoxetine treatment for major depression (defined by DSM-III-R). Method: The study was conducted at five outpatient psychiatric clinics in the United States. Patients who met criteria for remission after 12 or 14 weeks of open-label acute fluoxetine therapy, 20 mg/day (N=395 of 839 patients), were randomly assigned to one of four arms of a double-blind treatment study (50 weeks of placebo, 14 weeks of fluoxetine and then 36 weeks of placebo, 38 weeks of fluoxetine and then 12 weeks of placebo, or 50 weeks of fluoxetine). Relapse rate was the primary outcome measure, Both Kaplan-Meier estimates and observed relapse rates were assessed in three fixed 12-week intervals after double-blind transfers from fluoxetine to placebo at the start of the double-blind period and after 14 and 38 weeks of continued fluoxetine treatment. Results: Relapse rates (Kaplan-Meier estimates) were lower among the patients who continued to take fluoxetine compared with those transferred to placebo in both the first interval, after 24 total weeks of treatment (fluoxetine, 26.4%; placebo, 48.6%), and the second interval, after 38 total weeks of treatment (fluoxetine, 9.0%; placebo, 23.2%). In the third interval, after 62 total weeks of treatment, rates were not significantly different between the groups (fluoxetine, 10.7%; placebo, 16.2%). Conclusions: Patients treated with fluoxetine for 12 weeks whose depressive symptoms remit should continue treatment with fluoxetine for at least an additional 26 weeks to minimize the risk of relapse. C1 Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. Univ Utah, Dept Psychiat, Salt Lake City, UT USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Columbia Univ, Dept Psychiat, New York, NY USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Rush Med Ctr, Dept Psychiat, Chicago, IL USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. RP Michelson, D (reprint author), Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. OI Beasley, Charles/0000-0001-8743-7691 NR 25 TC 143 Z9 144 U1 1 U2 3 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 1998 VL 155 IS 9 BP 1247 EP 1253 PG 7 WC Psychiatry SC Psychiatry GA 116KF UT WOS:000075723000017 PM 9734550 ER PT J AU Lee, SI Chew, FS AF Lee, SI Chew, FS TI Radiology in the emergency department: Technique for quantitative description of use and results SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Roentgen-Ray-Society 98th CY APR 26-MAY 01, 1998 CL SAN FRANCISCO, CALIFORNIA SP Amer Roentgen Ray Soc ID CERVICAL-SPINE; RADIOGRAPHY; GUIDELINES AB OBJECTIVE. We sought to develop quantitative methods to describe the use and results of imaging studies in emergency department patients. MATERIALS AND METHODS. A computerized nonrelational database containing records of 3.5 million diagnostic reports generated by our radiology department from 1988 to 1997 was queried using Boolean and natural language search tools, Each record contained data fields for patient demographics, examination description and billing code, names of interpreting radiologists and referring physicians, patient history, report body, and report impression. RESULTS, Emergency department admissions and imaging studies were stable from 1991 to 1997, averaging 60,000 and 52,000 per year, respectively. Bone radiographs comprised 45.1% of examinations; chest radiographs, 44.6%; and abdominal radiographs, 10.4%, The percentages of radiographs interpreted as normal were 75.9% in 1992 and 75.3% in 1996, with cervical spine (88.7%), thoracic spine (86.3%), and knee (86.3%) yielding the highest proportion of studies with normal findings. The number of CT studies of the body increased from 1840 in 1993 to 3101 in 1997. Studies of the abdomen accounted for most of this increase (52.3% in 1993 to 66.0% in 1997), During evaluations for cervical spine injury, a mean of 6.5% of radiographic studies were followed by CT studies, and the findings of 89.0% of those CT studies were interpreted as normal. CONCLUSION. Radiology report databases represent a resource from which broad descriptions of the use and results of imaging studies can be obtained. Such descriptions may be useful in departmental and hospital administration, technology assessment, cost-effectiveness studies, and health policy formulation. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Chew, FS (reprint author), Wake Forest Univ, Sch Med, Dept Radiol, Med Ctr Blvd, Winston Salem, NC 27157 USA. OI Chew, Felix/0000-0003-2711-2013 NR 21 TC 5 Z9 6 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 SEP PY 1998 VL 171 IS 3 BP 559 EP 564 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 112LT UT WOS:000075496700005 PM 9725273 ER PT J AU Bernstein, SM Russ, PD AF Bernstein, SM Russ, PD TI Midgut volvulus: A rare cause of acute abdomen in an adult patient SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID INTESTINAL MALROTATION; COMPLICATION; DIAGNOSIS C1 Univ Colorado, Hlth Sci Ctr, Dept Radiol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Imaging Serv, Denver, CO 80220 USA. RP Russ, PD (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Radiol, Box C277,4200 E 9th Ave, Denver, CO 80262 USA. NR 10 TC 27 Z9 28 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 SEP PY 1998 VL 171 IS 3 BP 639 EP 641 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 112LT UT WOS:000075496700023 PM 9725289 ER PT J AU Dupuy, DE Rosenberg, AE Punyaratabandhu, T Tan, MH Mankin, HJ AF Dupuy, DE Rosenberg, AE Punyaratabandhu, T Tan, MH Mankin, HJ TI Accuracy of CT-guided needle biopsy of musculoskeletal neoplasms SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID SOFT-TISSUE TUMORS; PRIMARY BONE-TUMORS; TRU-CUT BIOPSY; ASPIRATION CYTOLOGY; CLOSED BIOPSY; LESIONS; DIAGNOSIS; SPINE AB OBJECTIVE. The purpose of our study was to assess the accuracy of CT-guided biopsy of musculoskeletal neoplasms with respect to technique, anatomic site, and histology. MATERIALS AND METHODS. During a 3-year period (January 1992 to December 1994), 176 core needle biopsies and 45 fine-needle aspirations were performed under CT guidance on patients with musculoskeletal neoplasms. To assess the accuracy of these procedures, compared the diagnosis at biopsy with the final diagnosis as determined at the time of definitive treatment of the lesion. All biopsy findings were categorized as a primary malignancy (excluding round cell lesions), round cell lesion, local recurrence, or metastatic carcinoma. In addition. each lesion was analyzed according to which biopsy technique was used, whether frozen tissue section or rapid cytologic evaluation was used, and at which anatomic site the mass was found. RESULTS. The accuracy for needle biopsy was 93% and that for fine-needle aspiration was 80%, The complication rate for both techniques was less than 1%. Accuracy rates for the four categories of primary malignancy, round cell lesion, local recurrence, and metastatic carcinoma were 87%, 75%, 94%, and 100%, respectively. The mismatch rates were similar in soft-tissue lesions (5/52) and bone lesions (16/169). Diminished accuracy was associated with round cell lesions (20%) and lesions located in the spine or the perivertebral region (20%). Nondiagnostic and insufficient specimens were found in 18 (8%) of the 221 patients. CONCLUSION. CT-guided biopsy of musculoskeletal malignancies is a safe and effective procedure if performed by a team of clinicians, pathologists, and radiologists who pos sess subspecialty expertise. C1 Massachusetts Gen Hosp, Dept Radiol, Connect Tissue Oncol Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Orthopaed Serv, Connect Tissue Oncol Ctr, Boston, MA 02114 USA. RP Dupuy, DE (reprint author), Rhode Isl Hosp, 593 Eddy St, Providence, RI 02903 USA. OI Dupuy, Damian/0000-0003-0524-5982 NR 34 TC 107 Z9 117 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 1998 VL 171 IS 3 BP 759 EP 762 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 112LT UT WOS:000075496700046 PM 9725312 ER PT J AU Jones, AR Pichot, JT AF Jones, AR Pichot, JT TI Stimulant use in sports SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID PERFORMANCE; DRUGS; COCAINE AB The authors provide an overview of the topic of stimulant use in psychiatric sports medicine. They address the following areas: I) the history of stimulant use in sports; 2) recent events related to the use of stimulants in sports, including a new stimulant used at the 1996 Olympic competition in Atlanta, GA; 3) ergogenic or ergolytic (i.e., performance-impairing) potential of several major categories of stimulants, including amphetamines, beta, agonists, caffeine, and cocaine; 4) review of how the brain reward circuit is affected by stimulants; 5) individual factors that induce athletes to utilize stimulants; and 6) sports organizational factors that induce athletes to use stimulants. C1 Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. RP Pichot, JT (reprint author), Audie L Murphy Mem Vet Hosp, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. EM pichot@connecti.com NR 44 TC 8 Z9 8 U1 0 U2 6 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD FAL PY 1998 VL 7 IS 4 BP 243 EP 255 PG 13 WC Substance Abuse SC Substance Abuse GA 136YJ UT WOS:000076886400001 PM 9809128 ER PT J AU Gariti, PW Alterman, AI Ehrman, RN Pettinati, HM AF Gariti, PW Alterman, AI Ehrman, RN Pettinati, HM TI Reliability and validity of the aggregate method of determining number of cigarettes smoked per day SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article AB The authors evaluated the reliability of two pretreatment assessments (screening and intake) of cigarettes smoked per day (CPD) by the commonly used aggregate method The validity of the aggregate method was also determined by comparison with results of the timeline followback? (TLFB) method for the identical periods. The study participants were 49 outpatients undergoing nicotine patch treatment. The reliability of the two aggregate method evaluations of CPD was quite high by Pearson product-moment correlation (r) and good when based on the intraclass correlation. Correspondence between the CPD assessments based on the aggregate and TI;FB methods for the two time-points ranged from fair (screening) to good (intake). Overall, the study findings indicate that the aggregate method provides reasonably consistent data. C1 Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Gariti, PW (reprint author), Treatment Res Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. FU NIDA NIH HHS [DA 10070] NR 7 TC 18 Z9 18 U1 1 U2 4 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD FAL PY 1998 VL 7 IS 4 BP 283 EP 287 PG 5 WC Substance Abuse SC Substance Abuse GA 136YJ UT WOS:000076886400005 PM 9809132 ER PT J AU Viguera, A Welch, C Bigatello, L Drop, LJ AF Viguera, A Welch, C Bigatello, L Drop, LJ TI Hemodynamic responses to electroconvulsive therapy in a hypertensive patient with end-stage pulmonary fibrosis SO ANESTHESIA AND ANALGESIA LA English DT Article ID NITRIC-OXIDE C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Drop, LJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NR 17 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD SEP PY 1998 VL 87 IS 3 BP 737 EP 741 DI 10.1097/00000539-199809000-00050 PG 5 WC Anesthesiology SC Anesthesiology GA 114QW UT WOS:000075621200050 PM 9728867 ER PT J AU Bishop, MJ Kim, ES AF Bishop, MJ Kim, ES TI Endotracheal intubation, but not laryngeal mask airway insertion, produces reversible bronchoconstriction SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98108 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1998 VL 89 IS 3A SU S MA A1238 BP U976 EP U976 PG 1 WC Anesthesiology SC Anesthesiology GA 117YR UT WOS:000075810901232 ER PT J AU Christopherson, R Murphy, JA Marshall, P Ostrowski, KJ Chien, GL DAvis, RF AF Christopherson, R Murphy, JA Marshall, P Ostrowski, KJ Chien, GL DAvis, RF TI Unplanned admission of ambulatory surgery patients is associated with spinal anesthesia, time of day, length of case, and neurological disease SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Dept Anesthesiol, Portland, OR 97201 USA. Portland VA Med Ctr, Anesthesiol Serv, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1998 VL 89 IS 3A SU S MA A6 BP U115 EP U115 PG 1 WC Anesthesiology SC Anesthesiology GA 117YR UT WOS:000075810900007 ER PT J AU Fahmy, NR AF Fahmy, NR TI Does anesthesia influence the outcome of femoral neck fractures in the elderly? SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Critical Care, Boston, MA 02114 USA. NR 2 TC 0 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1998 VL 89 IS 3A SU S MA A819 BP U382 EP U382 DI 10.1097/00000542-199809140-00002 PG 1 WC Anesthesiology SC Anesthesiology GA 117YR UT WOS:000075810901426 ER PT J AU Fahmy, NR Carr, DB AF Fahmy, NR Carr, DB TI Changes in plasma beta endorphin, catecholamines, and renin activity. Their correlation to tourniquet-induced hypertension in man. SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Crit Care, Boston, MA 02114 USA. Tufts Univ, New England Med Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1998 VL 89 IS 3A SU S MA A588 BP U432 EP U432 PG 1 WC Anesthesiology SC Anesthesiology GA 117YR UT WOS:000075810900586 ER PT J AU Fahmy, NR AF Fahmy, NR TI The rate of reduction of arterial blood pressure modifies the hemodynamic response to nitroprusside. SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1998 VL 89 IS 3A SU S MA A1194 BP U954 EP U954 PG 1 WC Anesthesiology SC Anesthesiology GA 117YR UT WOS:000075810901188 ER PT J AU Fahmy, NR AF Fahmy, NR TI Mode of administration of bupivacaine for spinal anesthesia modifies the circulatory and anesthetic effects in humans. SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1998 VL 89 IS 3A SU S MA A856 BP U782 EP U782 PG 1 WC Anesthesiology SC Anesthesiology GA 117YR UT WOS:000075810900850 ER PT J AU Fulling, PD Peterfreund, RA AF Fulling, PD Peterfreund, RA TI Alkalinization of ropivacaine with sodium bicarbonate: pH adjustment and precipitation characteristics SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia, Sch Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Crit Care, Sch Med, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1998 VL 89 IS 3A SU S MA A844 BP U776 EP U776 PG 1 WC Anesthesiology SC Anesthesiology GA 117YR UT WOS:000075810900838 ER PT J AU Greenwald, SD Glass, PS Payne, FB Rosow, CE Sebel, PS Devlin, PH AF Greenwald, SD Glass, PS Payne, FB Rosow, CE Sebel, PS Devlin, PH TI Changes in heart rate variability predict responses during anesthesia SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Duke Univ, Dept Anesthesiol, Durham, NC USA. Fayetteville Ambulatory Surg Ctr, Dept Anesthesiol, Fayetteville, AR USA. Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anesthesiol, Boston, MA USA. Emory Univ, Dept Anesthesiol, Atlanta, GA 30322 USA. Aspect Med Syst, Dept Anesthesiol, Natick, MA USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1998 VL 89 IS 3A SU S MA A898 BP U803 EP U803 PG 1 WC Anesthesiology SC Anesthesiology GA 117YR UT WOS:000075810900892 ER PT J AU Ibebunjo, C Martyn, J AF Ibebunjo, C Martyn, J TI Hypersensitivity to succinylcholine after immobilization is short-lived in the rat SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia, Boston, MA 02114 USA. Shriners Burns Hosp, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1998 VL 89 IS 3A SU S MA A985 BP U847 EP U847 PG 1 WC Anesthesiology SC Anesthesiology GA 117YR UT WOS:000075810900979 ER PT J AU Martinez-Ruiz, R Hromi, J Montero-Huerta, P Zapol, WM Head, A AF Martinez-Ruiz, R Hromi, J Montero-Huerta, P Zapol, WM Head, A TI Inhaled nitric oxide prolongs survival in transgenic sickle cell (SAD) mice model during acute hypoxia SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1998 VL 89 IS 3A SU S MA A1385 BP U1051 EP U1051 PG 1 WC Anesthesiology SC Anesthesiology GA 117YR UT WOS:000075810901377 ER PT J AU Michalowski, P Dershwitz, M Rosow, CE Conlay, LA Chang, YC AF Michalowski, P Dershwitz, M Rosow, CE Conlay, LA Chang, YC TI Total intravenous anesthesia with remifentanil or alfentanil in ambulatory orthopedic surgery carries minimal risk of postoperative nausea and vomiting SO ANESTHESIOLOGY LA English DT Meeting Abstract ID OUTPATIENT C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1998 VL 89 IS 3A SU S MA A34 BP U129 EP U129 DI 10.1097/00000542-199809010-00034 PG 1 WC Anesthesiology SC Anesthesiology GA 117YR UT WOS:000075810900035 ER PT J AU Miller, KW Addona, GH Cohen, JB Forman, SA Husain, SS Kloczewiak, MA Olsen, RW AF Miller, KW Addona, GH Cohen, JB Forman, SA Husain, SS Kloczewiak, MA Olsen, RW TI Probing anesthetic sites of action with a novel general anesthetic; 3,3-Azi-octan-1-ol. SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Univ Calif Los Angeles, Sch Med, Dept Pharmacol, Los Angeles, CA 90095 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1998 VL 89 IS 3A SU S MA A732 BP U721 EP U721 PG 1 WC Anesthesiology SC Anesthesiology GA 117YR UT WOS:000075810900730 ER PT J AU Raines, DE Zachariah, VT AF Raines, DE Zachariah, VT TI Isoflurane increases the apparent affinity of acetylcholine for the nicotinic acetylcholine receptor resting state SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1998 VL 89 IS 3A SU S MA A720 BP U715 EP U715 PG 1 WC Anesthesiology SC Anesthesiology GA 117YR UT WOS:000075810900718 ER PT J AU Small, SD AF Small, SD TI What participants learn from anesthesia crisis resource management training SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NR 4 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1998 VL 89 IS 3A SU S MA A71 BP U153 EP U153 PG 1 WC Anesthesiology SC Anesthesiology GA 117YR UT WOS:000075810900072 ER PT J AU Wallington, CL Peters, DM Gelb, C Peterfreund, RA AF Wallington, CL Peters, DM Gelb, C Peterfreund, RA TI Differential regulation of Orphanin and Mu opioid receptor mRNA levels in human SH-SY5Y neuroblastoma cells SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1998 VL 89 IS 3A SU S MA A737 BP U724 EP U724 PG 1 WC Anesthesiology SC Anesthesiology GA 117YR UT WOS:000075810900735 ER PT J AU Walsh, J Dershwitz, M Rosow, C Connors, P Morishige, R Rubsamen, R AF Walsh, J Dershwitz, M Rosow, C Connors, P Morishige, R Rubsamen, R TI Intravenous and inhaled morphine pharmacokinetics and pharmacodynamics as measured by pupillometry SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Aradigm Corp, Hayward, CA 94545 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1998 VL 89 IS 3A SU S MA A521 BP U398 EP U398 PG 1 WC Anesthesiology SC Anesthesiology GA 117YR UT WOS:000075810900520 ER PT J AU Zhou, Q Forman, SA AF Zhou, Q Forman, SA TI Hydrophobic scanning mutagenesis maps the hexanol site in the nicotinic receptor pore SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1998 VL 89 IS 3A SU S MA A702 BP U706 EP U706 PG 1 WC Anesthesiology SC Anesthesiology GA 117YR UT WOS:000075810900700 ER PT J AU Klein, C Pramstaller, PP Castellan, CC Breakefield, XO Kramer, PL Ozelius, LJ AF Klein, C Pramstaller, PP Castellan, CC Breakefield, XO Kramer, PL Ozelius, LJ TI Clinical and genetic evaluation of a family with a mixed dystonia phenotype from South Tyrol SO ANNALS OF NEUROLOGY LA English DT Article ID IDIOPATHIC TORSION DYSTONIA; NON-JEWISH FAMILY; CHROMOSOME 9Q34; ASHKENAZI JEWS; DYT1 LOCUS; EXCLUSION AB The gene causing early-onset torsion dystonia (DYT1) has recently been identified, and two new dystonia genes, one for adult-onset focal dystonia (DYT7) and one for a mixed dystonia phenotype (DYT6), have been mapped. We evaluated clinically a family from South Tyrol (Northern Italy) with 6 definitely affected individuals who display an unusually large phenotypic range of dystonic symptoms. We excluded the GAG deletion in the DYT1 gene and linkage to any of the above-mentioned dystonia loci, thus suggesting an as yet undefined dystonia gene in our family. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Reg Gen Hosp, Dept Neurol, Bolzano Bozen, Italy. Reg Gen Hosp, Dept Genet, Bolzano Bozen, Italy. Oregon Hlth Sci Univ, Dept Neurogenet, Portland, OR 97201 USA. RP Ozelius, LJ (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, CNY 149,Room 6221,13th St, Charlestown, MA 02129 USA. RI Pramstaller, Peter/C-2357-2008 FU NINDS NIH HHS [NS28384] NR 14 TC 16 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 1998 VL 44 IS 3 BP 394 EP 398 DI 10.1002/ana.410440318 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 116VB UT WOS:000075744700017 PM 9749609 ER PT J AU Beal, MF AF Beal, MF TI Excitotoxicity and nitric oxide in Parkinson's disease pathogenesis SO ANNALS OF NEUROLOGY LA English DT Article; Proceedings Paper CT Symposium on Neuroprotection in Parkinsons Disease CY OCT 31-NOV 02, 1997 CL CANNES, FRANCE ID METHYL-D-ASPARTATE; 1-METHYL-4-PHENYLPYRIDINIUM ION MPP+; MPTP-INDUCED NEUROTOXICITY; SUBSTANTIA-NIGRA; GLUTAMATE NEUROTOXICITY; DOPAMINE DEPLETION; KNOCKOUT MICE; MK-801 FAILS; CELL-DEATH; BLACK MICE AB A potential role for excitotoxic processes in Parkinson's disease (PD) has been strengthened by the recent observations that there appears to be a mitochondrially encoded defect in complex I activity of the electron transport chain. An impairment of oxidative phosphorylation will enhance vulnerability to excitotoxicity. Substantia nigra neurons possess N-methyl-D-aspartate receptors and there are glutamatergic inputs into the substantia nigra from both the cerebral cortex and the subthalamic nucleus. After activation of excitatory amino acid receptors, there is an influx of calcium followed by activation of neuronal nitric oxide (NO) synthase, which can then lead to the generation of peroxynitrite. Consistent with such a mechanism, studies of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity in both mice and primates have shown that inhibition of neuronal NO synthase exerts neuroprotective effects. Studies utilizing excitatory amino acid receptor antagonists have been inconsistent in mice but show significant neuroprotective effects in primates. These results raise the prospect that excitatory amino acid antagonists for neuronal NO synthase inhibitors might be useful in the treatment of PD. C1 Massachusetts Gen Hosp, Neurol Serv Warren 408, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Beal, MF (reprint author), Massachusetts Gen Hosp, Neurol Serv Warren 408, Neurochem Lab, 32 Fruit St, Boston, MA 02114 USA. FU NINDS NIH HHS [NS10828, NS31579] NR 46 TC 169 Z9 173 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 1998 VL 44 IS 3 SU 1 BP S110 EP S114 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 118BX UT WOS:000075818800015 PM 9749581 ER PT J AU Goldhirsch, A Coates, AS Castiglione-Gertsch, M Gelber, RD AF Goldhirsch, A Coates, AS Castiglione-Gertsch, M Gelber, RD TI New treatments for breast cancer: Breakthroughs for patient care or just steps in the right direction? SO ANNALS OF ONCOLOGY LA English DT Editorial Material DE adjuvant paclitaxel; breast cancer; Herceptin (TM); prevention; Raloxifene; Tamoxifen ID WOMEN AB Three areas of clinical research in breast cancer treatment led to news breaking presentations at the American Society of Clinical Oncology (ASCO) meeting, 1998. in Los Angeles. All three subjects represent important advances in cancer medicine. Prevention: Two related drugs, tamoxifen and raloxifene, were found in placebo controlled trials to significantly reduce the incidence of breast cancer for women at increased risk of developing the disease. Patterns of relapse showed that the reduced rate of breast cancer was exclusively observed for tumors expressing estrogen receptors, while the rate of tumors classified as estrogen-receptor negative was similar for the treatment and the control groups. This may indicate that the observed reduction in breast cancer incidence is due to a treatment effect on occult disease rather than its prevention. We certainly have no adequate information on mortality prevention. Adjuvant therapies: Taxol given every three weeks for four courses following an adjuvant treatment with four courses of doxorubicin and cyclophosphamide (AC) combination was found to be superior to not adding treatment after the four courses of AC in a trial involving 3170 patients. At 22 months of median follow-up, the quoted P-values were P = 0.0077 for disease-free survival and P = 0.039 for overall survival, but these did not cross the prospectively defined interim analysis boundaries for statistical significance at the 0.05 level. The difference was observed early during follow-up, and was exclusively seen in the 40% of patients who had ER-negative primaries and, therefore, did not receive tamoxifen following chemotherapy. One may thus argue that the early difference observed was primarily due to differences in the duration of the treatment regimens in the two groups and the early entry into the trial of patients with particularly aggressive neoplasia (e.g., ER-negative primaries) who would have benefited from a longer duration treatment. Treatment of advanced disease: The use of monoclonal anti bodies to c-erb-B2 was found to induce responses in metastatic breast cancer. Patients with tumors expressing c-erb-B2 responded to weekly infusions of this biological agent. It was particularly impressive that the response rate for patients receiving infusion of the monoclonal antibodies together with the cytotoxics was superior to that with chemotherapy alone in a randomized trial. It is important to note that only patients with tumors overexpressing c-erbB-2 (the overall incidence is about 20%) were tested. It must still be demonstrated that the effect of these monoclonal antibodies is indeed confined to cells overexpressing c-erbB-2. Treatment related cardiac toxicity remains a problem, and the effects of treatment in various subsets of patients need to be defined before starting investigations in the adjuvant setting, which is a clear further objective of this specific research. The significant findings from clinical research opened several new questions, which must be answered before allowing them to be employed in routine patient care. C1 European Inst Oncol, Int Breast Canc Study Grp, Dept Med Oncol, I-20141 Milan, Italy. Royal Prince Alfred Hosp, Dept Clin Oncol, Special Unit E9, Camperdown, NSW 2050, Australia. Univ Bern, Dept Med Oncol, Bern, Switzerland. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Goldhirsch, A (reprint author), European Inst Oncol, Int Breast Canc Study Grp, Dept Med Oncol, Via Ripamonti 435, I-20141 Milan, Italy. EM agoldhirsch@sakk.ch FU NCI NIH HHS [CA-75362] NR 13 TC 4 Z9 4 U1 0 U2 1 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 SEP PY 1998 VL 9 IS 9 BP 973 EP 976 DI 10.1023/A:1008436810268 PG 4 WC Oncology SC Oncology GA 136BP UT WOS:000076838200014 PM 9818070 ER PT J AU Zeitels, SM Hochman, L Hillman, RE AF Zeitels, SM Hochman, L Hillman, RE TI Adduction arytenopexy: A new procedure for paralytic dysphonia with implications for implant medialization SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Laryngological-Association CY MAY 09-10, 1998 CL PALM BEACH, FLORIDA SP Amer Laryngol Assoc DE arytenoid; dysphonia; hoarseness; laryngoplasty; thyroplasty; vocal cord paralysis; vocal fold paralysis ID THYROPLASTY TYPE-I; VOCAL FOLD PARALYSIS; LARYNGEAL NERVE PARALYSIS; CADAVER LARYNGES; CORD PARALYSIS; VOICE; CONFIGURATION; EXPERIENCE; REINNERVATION; PHONOSURGERY AB Arytenoid adduction was designed to enhance posterior glottal closure in patients with paralytic dysphonia by reproducing lateral cricoarytenoid muscle function. However, this procedure can exaggerate normal medial rotation of the vocal process, because the agonist-antagonist function of the interarytenoid, lateral thyroarytenoid, and posterior criconrgtenoid muscles is not simulated. Therefore, a new adduction procedure (adduction arytenopexy) was devised to affix the arytenoid on the cricoid facet in a more optimal position for glottal sound production. The adduction arytenopexy procedure was designed on fresh cadavers. In this technique, the lateral aspect of the cricoarytenoid joint is opened widely and the body of the arytenoid is manually medialized along the cricoid facet. A specially designed single suture is then placed through the posterior cricoid and the body or the muscular process of the arytenoid to achieve 2-point fixation. This draws the arytenoid posteriorly, superiorly, and medially for precise positioning. The arytenoid is rocked internally on the cricoid facet, and suture tension is adjusted appropriately to simulate normal cricoarytenoid adduction. In the first study, the adduction arytenopexy was compared with the classic arytenoid adduction in 10 fresh cadaver larynges. The new arytenopexy procedure resulted in an average increase of 2.1 mm (p < .01) in the length of the musculomembranous vocal fold, whereas the classic arytenoid adduction did not reveal a significant change in length. Additionally, the adduction arytenopexy resulted in a consistently higher vocal fold and a more normally contoured arytenoid than the classic adduction procedure. The second study consisted of a clinical trial in which 12 patients, who presented with a widely patent posterior glottis, underwent adduction arytenopexy in conjunction with implant medialization. The procedure was successful in all patients, and there were minimal complications. In the third study, preoperative and postoperative vocal assessment measures (stroboscopic, aerodynamic, acoustic, and perceptual) were analyzed in 9 of the 12 patients. The most striking preoperative stroboscopic observation was that 8 of the 9 patients presented with an aperiodic vibrational flutter during phonation due to severe valvular incompetence. Postoperatively, all patients developed complete closure of the glottal chink and effective entrained oscillation of the vocal folds. This visual improvement in function was commensurate with comparable changes in most of the other objective and subjective measures of vocal function. The new adduction arytenopexy procedure closely simulates the biomechanics underlying normal glottal closure and cricoarytenoid adduction. In turn, complex implant design shapes are not necessary to achieve proper alignment of the arytenoid and the vocal fold. Because the arytenoid is properly positioned prior to the medialization, implants can be sized more precisely and are unencumbered by an anterior thyroid lamina suture. These procedural innovations resulted in enhanced entrained oscillation of the glottal valve and, in turn, improved laryngeal sound production. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Zeitels, SM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 110 TC 18 Z9 18 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD SEP PY 1998 VL 107 IS 9 SU 173 BP 2 EP 24 PN 2 PG 23 WC Otorhinolaryngology SC Otorhinolaryngology GA 120FL UT WOS:000075944500001 ER PT J AU Mankarious, LA Smith, RJH AF Mankarious, LA Smith, RJH TI External rhinoplasty approach for extirpation and immediate reconstruction of congenital midline nasal dermoids SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE external rhinoplasty; nasal dermoid; surgical approach ID SINUS AB Surgical extirpation is the treatment of choice for nasal dermoids in the pediatric population. Approaches include vertical-dorsal rhinotomy, lateral rhinotomy, transverse rhinotomy, and external rhinoplasty. While short-term results suggest that the last approach is cosmetically most acceptable, the required wide undermining of the nasal tip and dorsum may affect subsequent nasal growth. To assess long-term results, we reviewed our experience with 8 cases encountered over the past 10 years. Modifications of the technique to minimize midline dorsal depression are described. C1 Univ Iowa Hosp & Clin, Dept Otolaryngol Head & Neck Surg, Iowa City, IA 52242 USA. RP Mankarious, LA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 6 TC 12 Z9 12 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD SEP PY 1998 VL 107 IS 9 BP 786 EP 789 PN 1 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 119WA UT WOS:000075920100009 PM 9749549 ER PT J AU Yoon, SS Carroll, NM Chiocca, EA Tanabe, KK AF Yoon, SS Carroll, NM Chiocca, EA Tanabe, KK TI Cancer gene therapy using a replication-competent herpes simplex virus type 1 vector SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 118th Annual Scientific Session of the American-Surgical-Association CY APR, 1998 CL PALM BEACH, FLORIDA SP Amer Surg Assoc ID COLON-CARCINOMA; IN-VIVO; LIVER; METASTASES; EFFICIENCY AB Objective The authors investigate the efficacy of hrR3, a viral vector derived from herpes simplex virus type 1 (HSV 1), in destroying colon carcinoma cells in vitro and in vivo. The effect of adding the prodrug ganciclovir in combination with hrR3 infection also is assessed. Summary Background Data Most cancer gene therapy strategies use viral vectors that are incapable of replication. The HSV I vector hrR3 is capable of replication, and its replication is cytotoxic to cells. hrR3 also possesses the HSV-thymidine kinase gene, which converts ganciclovir into a toxic metabolite. Thus, the addition of ganciclovir to hrR3-infected cells may enhance the ability of hrR3 to destroy tumor cells. To increase specificity for tumor cells, hrRS has a mutated ribonucleotide reductase gene and replicates selectively in cells with high levels of endogenous ribonucleotide reductase. Actively dividing cells such as tumor cells have high levels of endogenous ribonucleotide reductase for synthesis of DNA precursors. The authors are interested in the use of HSV 1 vectors to treat liver metastases from colorectal cancer. Methods Ribonucleotide reductase expression in several colon carcinoma cell lines and in primary cultures of human hepatocytes was determined by Western blot analysis. hrR3-mediated cytotoxicity in the colon carcinoma cell lines was determined using an in vitro assay. The human colon carcinoma cell line HT29 was injected into the flanks of nude mice followed by intratumoral injection of hrR3. Tumor growth rate was assessed with and without the addition of intraperitoneal ganciclovir. Results Ribonucleotide reductase levels in colon carcinoma cell lines are much higher than in primary cultures of human hepatocytes, hrR3 efficiently destroys colon carcinoma cell lines in vitro. A single intratumoral injection of hrR3 into HT29 flank tumors significantly reduces tumor growth rate, and the administration of ganciclovir has no additive effect. Conclusions The inherent cytotoxicity of hrR3 replication effectively destroys colon carcinoma cells in vitro and in viva. This cytotoxicity is not enhanced in vivo by the addition of ganciclovir. in the future, more efficacious and selective HSV 1 vectors may be useful in the treatment of cancer. C1 Massachusetts Gen Hosp, Div Surg Oncol, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Dept Surg, Cox 626,100 Blossom St, Boston, MA 02114 USA. FU NCI NIH HHS [CA64454]; NIDDK NIH HHS [DK43351]; NINDS NIH HHS [NS242279] NR 22 TC 66 Z9 67 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD SEP PY 1998 VL 228 IS 3 BP 366 EP 372 DI 10.1097/00000658-199809000-00009 PG 7 WC Surgery SC Surgery GA 119VJ UT WOS:000075918600016 PM 9742919 ER PT J AU Dobrin, PB Mrkvicka, R AF Dobrin, PB Mrkvicka, R TI Chronic loading and extension increases the acute breaking strength of polypropylene sutures SO ANNALS OF VASCULAR SURGERY LA English DT Article ID ANASTOMOTIC FALSE ANEURYSMS; CAROTID ENDARTERECTOMY; ELECTRON-MICROSCOPY; TENSILE-STRENGTH; FRACTURE AB Polypropylene sutures provide satisfactory strength for construction of vascular anastomoses, but occasionally they break. Experimental studies show that they break at reduced forces when they are subjected to chronic loads. Moreover, in patients, sutures are subject to acute loads superimposed on chronic loads. For example, an episode of hypertension applies acute load that is added to the baseline chronic load in a suture that has been used to close an arteriotomy. The purpose of the present study was to examine the breaking force of 6-0 polypropylene sutures subjected to acute loads after they had been loaded with chronic loads. One hundred sixty-five 6-0 polypropylene sutures were subjected to 50-175 g chronic loads in vitro. After 38 days they were subjected to additional increasing acute loads until they broke. Five hundred ninety other sutures were subjected to "injuries" of manipulation before chronic loading. A stray knot was simulated by placing a knot in the center of 90 sutures. Nurse's tugs used to straighten folded sutures in the operating room were simulated by applying brief loads of 75-275 g to 452 other sutures. Intraoperative injuries were simulated in 48 other sutures by pinching them with DeBakey forceps. Surprisingly, chronic loading of polypropylene sutures increased their acute breaking force. it is suggested that this may have resulted from increased orientation of crystals in the core of the filaments. By contrast, disturbing the outer surface of the filament by placing a stray knot, or pinching with forceps decreased acute breaking strength. These data suggest that if polypropylene sutures do not break soon after they have been placed in a patient, they may gain strength over time. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Loyola Univ, Med Ctr, Dept Surg, Maywood, IL 60153 USA. RP VA Med Ctr, 500 Foothill Dr, Salt Lake City, UT 84148 USA. NR 39 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0890-5096 EI 1615-5947 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD SEP PY 1998 VL 12 IS 5 BP 424 EP 429 DI 10.1007/s100169900179 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 115CY UT WOS:000075647000004 PM 9732419 ER PT J AU Slominski, A Paus, R Mihm, MC AF Slominski, A Paus, R Mihm, MC TI Inhibition of melanogenesis as an adjuvant strategy in the treatment of melanotic melanomas: Selective review and hypothesis SO ANTICANCER RESEARCH LA English DT Article DE melanogenesis; immunosuppression; progression; therapy ID L-DOPA; L-TYROSINE; MALIGNANT-MELANOMA; HAMSTER MELANOMA; HUMAN-LYMPHOCYTES; CELLS; THERAPY; DNA; PIGMENTATION; RESTRICTION AB Melanogenesis generates immunosuppressive and mutagenic environment and alters cellular metabolism. Melanin can protect malignant melanocytes against chemo-, radio-, and photodynamic therapy. Therefore, we propose to inhibit melanogenesis as an adjuvant treatment modality during immuno-, radio-, chemo- and photodynamic therapy, and as a measure of reducing the probability of melanoma progression. C1 Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. Humboldt Univ, Charite Hosp, Dept Dermatol, Berlin, Germany. Massachusetts Gen Hosp, Dept Dermatopathol, Boston, MA 02114 USA. RP Slominski, A (reprint author), Loyola Univ, Med Ctr, Dept Pathol, 2160 S 1st Ave, Maywood, IL 60153 USA. EM aslomin@wpo.it.luc.edu NR 84 TC 58 Z9 58 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP-OCT PY 1998 VL 18 IS 5B BP 3709 EP 3715 PG 7 WC Oncology SC Oncology GA 148KN UT WOS:000077504500014 PM 9854482 ER PT J AU Graybill, JR Najvar, LK Bocanegra, R Hector, RF Luther, MF AF Graybill, JR Najvar, LK Bocanegra, R Hector, RF Luther, MF TI Efficacy of nikkomycin Z in the treatment of murine histoplasmosis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CANDIDA-ALBICANS; HOST DEFENSE; CAPSULATUM; FUNGI AB Immune-competent ICR and BALB/c athymic (nude) mice were infected intravenously with Histoplasma capsulatum and treated with either fluconazole or nikkomycin Z or 5% dextrose (controls). In immune-competent ICR mice, fIuconazole and nikkomycin Z both prolonged survival when given at 5 mg/kg of body weight twice daily. When administered in doses as low as 2.5 mg/kg twice daily, nikkomycin Z reduced fungal counts in both the spleen and liver. When both drugs were combined, there was no antagonism, and in combined therapy spleen and liver counts were reduced more than for either drug alone. However, nikkomycin Z had no effect on brain fungal burden, In nude mice fluconazole and nikkomycin Z had an additive effect in prolongation of survival and reduction of liver and spleen burden. Nikkomycin Z is well tolerated, is at least as effective as fluconazole, and may interact beneficially,vith fluconazole for treatment of murine histoplasmosis. C1 Audie L Murphy Mem Vet Hosp, Div Infect Dis 111F, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78284 USA. Shaman Pharmaceut, S San Francisco, CA 94080 USA. RP Graybill, JR (reprint author), Audie L Murphy Mem Vet Hosp, Div Infect Dis 111F, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. NR 15 TC 24 Z9 25 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 SEP PY 1998 VL 42 IS 9 BP 2371 EP 2374 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 116RB UT WOS:000075737400039 PM 9736565 ER PT J AU Hyman, BT AF Hyman, BT TI New neuropathological criteria for Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Editorial Material ID NEUROFIBRILLARY TANGLES; PLAQUES C1 Massachusetts Gen Hosp, Alzheimer Res Unit, Charlestown, MA 02129 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Alzheimer Res Unit, 149 13th St,Room 6405, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG08487, AG05134] NR 17 TC 66 Z9 67 U1 0 U2 3 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 SEP PY 1998 VL 55 IS 9 BP 1174 EP 1176 DI 10.1001/archneur.55.9.1174 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 117HD UT WOS:000075775100001 PM 9740109 ER PT J AU Haroutunian, V Perl, DP Purohit, DP Marin, D Khan, K Lantz, M Davis, KL Mohs, RC AF Haroutunian, V Perl, DP Purohit, DP Marin, D Khan, K Lantz, M Davis, KL Mohs, RC TI Regional distribution of neuritic plaques in the nondemented elderly and subjects with very mild Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID MINI-MENTAL-STATE; SENILE PLAQUES; DEMENTIA; TANGLES; SEVERITY; SCALE AB Background: Identification of the neuropathological lesions that are most closely associated with the earliest symptoms of Alzheimer disease (AD) is crucial to the understanding of the disease process and the development of treatment strategies to affect its progress. Do the classical neuropathological lesions of AD precede, follow, or occur in synchrony with the earliest signs of cognitive deterioration? Design and Outcome Measures: We examined the extent of neuritic plaque (NP) formation in 5 neocortical regions and the hippocampus, entorhinal cortex, and amygdala in 66 elderly subjects with no dementia, questionable dementia, or mild dementia as assessed using the Clinical Dementia Rating Scale (CDR). Setting and Patients: Postmortem study of nursing home residents. Results: Even questionable dementia (CDR, 0.5) was associated with a significant (P = .04) increase in neocortical NP density. The density of NPs increased further with increasing dementia severity in all brain regions examined. However, subjects with questionable dementia or definite but mild dementia did not differ significantly from each other. Density of NPs was nearly maximal in subjects with moderate dementia (CDR = 2.0), suggesting that other neuropathological changes may be responsible for cognitive deficits beyond this level. Dementia severity correlated significantly with the density of NPs in all brain regions examined (r range, 0.47-0.56; P<.001), even when subjects with a CDR of 0 were excluded. Conclusions: These findings are consistent with the hypothesis that NPs are among the earliest neuropathological lesions in AD. Even very mild or questionable dementia is associated with increased density of neocortical NPs that do not distinguish between clinically questionable vs definite dementia. C1 Bronx Vet Affairs Med Ctr, Psychiat Serv, Bronx, NY 10468 USA. CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Pathol, New York, NY 10029 USA. Jewish Home & Hosp Aged, Manhattan, NY USA. RP Haroutunian, V (reprint author), Bronx Vet Affairs Med Ctr, Psychiat Serv, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. FU NIA NIH HHS [P01-AG02219] NR 24 TC 200 Z9 202 U1 1 U2 2 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 SEP PY 1998 VL 55 IS 9 BP 1185 EP 1191 DI 10.1001/archneur.55.9.1185 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 117HD UT WOS:000075775100004 PM 9740112 ER PT J AU Azar, DT Pluznik, D Jain, S Khoury, JM AF Azar, DT Pluznik, D Jain, S Khoury, JM TI Gelatinase B and A expression after laser in situ keratomileusis and photorefractive keratectomy SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID CORNEAL LIGHT-SCATTERING; METALLOPROTEINASES; ANGIOSTATIN AB Objective: To compare the expression of gelatinases in the corneal epithelium and stroma after laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK). Methods: Rabbit eyes were treated with LASIK( (n=11), PRK (n=12), or corneal flap construction (n=12);4 eyes served as unwounded controls. Zymography was per formed on the central epithelium and the stroma 1, 3, and 7 days after surgery to determine the expression of gelatinases. Results: Epithelial expression of gelatinase B in the LASIK group (0%-25%) was lower than that in the PRK group at all time points (50%-100%) and was identical to the corneal flap group. Stromal expression of gelatinases A and B was similar after LASIK and PRK, but was minimal after corneal flap construction at all time points. Epithelial expression of gelatinase A was similar for the first 3 days after LASIK and PRK but not thereafter. Conclusions: Gelatinase B epithelial expression was upregulated after PRK but not after LASIK. Gelatinase B stromal expression was up-regulated after both procedures. Clinical Relevance: Differences in wound healing and subepithelial scarring after these 2 procedures may be related to gelatinase B. C1 Harvard Univ, Corneal & Refract Surg Serv, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Schepens Eye Res Inst, Boston, MA USA. Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD USA. RP Azar, DT (reprint author), Harvard Univ, Corneal & Refract Surg Serv, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY10101] NR 18 TC 38 Z9 42 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD SEP PY 1998 VL 116 IS 9 BP 1206 EP 1208 PG 3 WC Ophthalmology SC Ophthalmology GA 119TG UT WOS:000075912800009 PM 9747680 ER PT J AU Laposata, M Green, D Van Cott, EM Barrowcliffe, TW Goodnight, SH Sosolik, RC AF Laposata, M Green, D Van Cott, EM Barrowcliffe, TW Goodnight, SH Sosolik, RC TI College of American Pathologists Conference XXXI on Laboratory Monitoring of Anticoagulant Therapy - The clinical use and laboratory monitoring of low-molecular-weight heparin, danaparoid, hirudin and related compounds, and argatroban SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID DEEP-VEIN THROMBOSIS; INTRAVENOUS UNFRACTIONATED HEPARIN; TOTAL HIP-REPLACEMENT; ACUTE VENOUS THROMBOEMBOLISM; ACUTE MYOCARDIAL-INFARCTION; ACUTE ISCHEMIC STROKE; INDUCED THROMBOCYTOPENIA; RECOMBINANT HIRUDIN; CORONARY ANGIOPLASTY; ORGARAN ORG-10172 AB Objective.-To review the role of the laboratory in monitoring therapy with low-molecular-weight heparin, danaparoid, hirudin, and argatroban, as reflected in the medical literature and the consensus opinion of recognized experts in the field. Data Sources.-Review of the medical literature and current clinical practice by a panel of 6 international experts in the field of anticoagulant therapy. Data Extraction and Synthesis.-The experts made an extensive review of the published literature and prepared a draft manuscript, which included preliminary recommendations. The draft manuscript was circulated to participants in the College of American Pathologists Conference XXXI on Laboratory Monitoring of Anticoagulant Therapy prior to the conference. The manuscript and recommendations were then presented at the Conference for discussion. Recommendations were accepted if a consensus of the 26 experts attending the Conference was reached. The results of the discussion were used to revise the manuscript into its final form. Conclusions.-This report reviews the mechanism of action and potential uses of these newer anticoagulant agents. General guidelines for monitoring these agents and 9 specific recommendations for laboratory monitoring of low-molecular-weight heparin and danaparoid are provided, along with citation of the appropriate supporting literature. Issues for which a consensus was not reached at the Conference are also discussed. C1 Massachusetts Gen Hosp, Div Lab Med, Boston, MA 02114 USA. Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. Natl Inst Biol Stand & Control, S Mimms, Herts, England. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. So Ohio Med Ctr, Dept Pathol, Portsmouth, OH USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Div Lab Med, Gray Bldg,Room 235,32 Fruit St, Boston, MA 02114 USA. NR 117 TC 154 Z9 160 U1 1 U2 5 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 SEP PY 1998 VL 122 IS 9 BP 799 EP 807 PG 9 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 116RM UT WOS:000075738400004 PM 9740137 ER PT J AU Murphy, JM Pagano, ME Nachmani, J Sperling, P Kane, S Kleinman, RE AF Murphy, JM Pagano, ME Nachmani, J Sperling, P Kane, S Kleinman, RE TI The relationship of school breakfast to psychosocial and academic functioning - Cross-sectional and longitudinal observations in an inner-city school sample SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID CHILDRENS DEPRESSION; MALNUTRITION; PERFORMANCE; SUPPLEMENTATION; DISORDERS; CHILDHOOD; INVENTORY; AGE AB Objective: To determine if a relationship exists between participation in a school breakfast program and measures of psychosocial and academic functioning in school-aged children. Methods: Information on participation in a school breakfast program, school record data, and in-depth interviews with parents and children were collected in 1 public school in Philadelphia, Pa, and 2 public schools in Baltimore, Md, prior to the implementation of a universally free (UF) breakfast program and again after the program had been in place for 4 months. One hundred thirty-three low-income students had complete data before and after the UF breakfast program on school breakfast participation and school-recorded measures, and 85 of these students had complete psychosocial interview data before and after the UF breakfast program. Teacher ratings of behavior-before and after the UF breakfast program were available for 76 of these students. Results: Schoolwide data showed that prior to the UF breakfast program, 240 (15%) of the 1627 students in the 3 schools were eating a school-supplied breakfast each day. Of the 133 students in the interview sample, 24 (18%) of the students ate a school-supplied breakfast often, 26 (20%) ate a school-supplied breakfast sometimes, and 83 (62%) ate a school-supplied breakfast rarely or never. Prior to the UF breakfast program, students who ate a school-supplied breakfast often or sometimes had significantly higher math scores and significantly lower scores on child-, parent-, and teacher-reported symptom questionnaires than children who ate a school-supplied breakfast rarely or never. At the end of the school term 4 months after the implementation of the UF breakfast program, school-supplied breakfast participation had nearly doubled and 429 (27%) of the 1612 children in the 3 schools were participating in the school breakfast program each day. In the interview sample, almost half of the children had increased their participation. Students who increased their participation in the school breakfast program had significantly greater increases in their math grades and significantly greater decreases in the rates of school absence and tardiness than children whose participation remained the same or decreased. Child and teacher ratings of psychosocial problems also decreased to a significantly greater degree for children with increased participation in the school breakfast program. Conclusion: Both cross-sectional and longitudinal data from this study provide strong evidence that higher rates of participation in school breakfast programs are associated in the short-term with improved student functioning on a broad range of psychosocial and academic measures. C1 Massachusetts Gen Hosp, Child Psychiat Serv, Wang Ambulatory Care Ctr 725, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Gastroenterol & Nutr Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Northwestern Univ, Dept Human Dev, Chicago, IL 60611 USA. Sch Dist Philadelphia, Philadelphia, PA USA. Baltimore Publ Sch, Baltimore, MD USA. RP Murphy, JM (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, Wang Ambulatory Care Ctr 725, Boston, MA 02114 USA. NR 40 TC 110 Z9 112 U1 1 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD SEP PY 1998 VL 152 IS 9 BP 899 EP 907 PG 9 WC Pediatrics SC Pediatrics GA 117UZ UT WOS:000075802100012 PM 9743037 ER PT J AU Ruan, CM Escobedo, E Harrison, S Goldstein, B AF Ruan, CM Escobedo, E Harrison, S Goldstein, B TI Magnetic resonance imaging of nonhealing pressure ulcers and myocutaneous flaps SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article ID BONE-SCINTIGRAPHY; OSTEOMYELITIS; SORES; INFECTION; DIAGNOSIS; FOOT AB Objective: To evaluate the use of magnetic resonance imaging (MRI) in making clinical decisions when assessing nonhealing pressure ulcers and nonhealing myocutaneous flaps for the presence of an abscess, osteomyelitis, sinus tracts, and fluid collections. Design: Retrospective review of patient charts and radiographic studies. Setting: Regional spinal cord injury center. Subjects: Twelve patients who had MRI as part of their evaluation for a nonhealing pressure ulcer or myocutaneous flap. Results: Seven patients had MRI for preoperative evaluation, four with a previous flap that had recurrent breakdown and three with a new grade III or IV ulcer. Five patients had MRI for postoperative evaluation of myocutaneous flaps with delayed healing. MRI was useful in identifying osteomyelitis in three patients and sinus tracts that required surgical revision in six patients. MRI was also used in two patients to assess the size of fluid collections postoperatively in determining whether the patients should be mobilized after surgery. These chronic nonhealing wounds resulted in multiple admissions and lengthy hospital stays and required multiple surgical revisions. Patients who did poorly with healing or had repeated breakdown tended to have concurrent issues such as poor self care, increased age, increased time of spinal cord injury, poor nutrition, or other medical problems. Conclusion: Chronic nonhealing pressure ulcers and myocutaneous flaps can be difficult to treat and evaluate with conventional methods. There are multiple reasons for failure to heal. MRI can be a useful tool for identifying some of these factors including osteomyelitis, fluid collections, abcesses, and sinus tracts in the perioperative period. Identifying the appropriate patient populations and clinical indications for the optimal use of MRI should be subject of further study. (C) 1998 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Dept Radiol, Seattle, WA USA. Univ Washington, Med Ctr, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Washington, Med Ctr, Dept Radiol, Seattle, WA 98195 USA. RP Ruan, CM (reprint author), VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv, Seattle, WA USA. NR 28 TC 18 Z9 18 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD SEP PY 1998 VL 79 IS 9 BP 1080 EP 1088 DI 10.1016/S0003-9993(98)90175-7 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 118FX UT WOS:000075828700011 PM 9749688 ER PT J AU Appel, H Gauthier, L Wucherpfennig, K AF Appel, H Gauthier, L Wucherpfennig, K TI Multivalent HLA-DR/peptide complexes for detection of antigen-specific human T cells SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 297 BP S82 EP S82 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215600298 ER PT J AU Brower, D Bhimji, S Schumacher, HR Hillstrom, H AF Brower, D Bhimji, S Schumacher, HR Hillstrom, H TI A pilot study of the immediate effects of conservative realignment therapies of varus knee osteoarthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Drexel Univ, Philadelphia, PA 19104 USA. Penn Coll Podiat Med, Philadelphia, PA 19107 USA. Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 1556 BP S292 EP S292 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215601556 ER PT J AU Choi, HK Merkel, PA Niles, JL AF Choi, HK Merkel, PA Niles, JL TI High prevalence of drug-associated vasculitis in patients with high titers of anti-myeloperoxidase ANCA. SO ARTHRITIS AND RHEUMATISM 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 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 541 BP S123 EP S123 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215600542 ER PT J AU Chopra, A Lavin, P Chitre, D Patwardhan, B Polisson, R AF Chopra, A Lavin, P Chitre, D Patwardhan, B Polisson, R TI A clinical study of an Ayurvedic (Asian Indian) medicine in OA knees. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Ctr Rheumat Dis, Poona 411001, Maharashtra, India. Boston Biostat USA, Boston, MA USA. Ayurcore Inc USA, Boston, MA USA. Pune Univ, Pune, Maharashtra, India. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Patwardhan, Bhushan/F-1583-2011 OI Patwardhan, Bhushan/0000-0003-3918-2609 NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 992 BP S198 EP S198 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215600993 ER PT J AU Gehsler, T Utz, P Hottelet, M Zhang, CH Schlossman, S Anderson, P AF Gehsler, T Utz, P Hottelet, M Zhang, CH Schlossman, S Anderson, P TI Immunization of mice with apoptotic cells leads to the development of autoantibodies. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 1319 BP S252 EP S252 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215601320 ER PT J AU Gikeson, GS Garrnier, G Circolo, A Wetsel, R Holers, VM Feagin, A Colten, HR AF Gikeson, GS Garrnier, G Circolo, A Wetsel, R Holers, VM Feagin, A Colten, HR TI Modulation of renal disease in lupus mice deficient in complement component C3. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC USA. Ralph H Johnson VAMC, Charleston, SC USA. Washington Univ, Sch Med, St Louis, MO 63110 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. Northwestern Univ, Sch Med, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 859 BP S176 EP S176 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215600860 ER PT J AU Hahre, W Matthews, C Schumacher, HR AF Hahre, W Matthews, C Schumacher, HR TI Presenting clinical syndromes in an early arthritis clinic are strong predictors of long term outcome. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 1422 BP S269 EP S269 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215601423 ER PT J AU James, JA Kendall, JS Davis, AL Harley, JB AF James, JA Kendall, JS Davis, AL Harley, JB TI Anti-Sm responses in pediatric systemic lupus erythematosus vary from those in adult patients. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 73104 USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK 73104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 1865 BP S343 EP S343 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215601864 ER PT J AU MacLean, CH Leake, B Paulus, HE Brook, RH Shekelle, PG AF MacLean, CH Leake, B Paulus, HE Brook, RH Shekelle, PG TI Quality of care for comorbid disease and health care maintenance in rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 1296 BP S248 EP S248 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215601297 ER PT J AU MaClean, CH Leake, B Paulus, HE Brook, RH Shekelle, PG AF MaClean, CH Leake, B Paulus, HE Brook, RH Shekelle, PG TI Patterns of drug use in rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 266 BP S77 EP S77 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215600267 ER PT J AU McClain, M Kaufman, KM Harley, JB James, JA AF McClain, M Kaufman, KM Harley, JB James, JA TI Fine specificity mapping of the anti-Sm D3 autoimmune response in systemic lupus erythematosus. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 US Dept Vet Affairs, Med Ctr, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 1325 BP S253 EP S253 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215601326 ER PT J AU Oates, JC Reilly, CM Christensen, EF Gilkeson, GS AF Oates, JC Reilly, CM Christensen, EF Gilkeson, GS TI Nitric oxide is increased during lupus disease activity. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC USA. Med Univ S Carolina, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 229 BP S71 EP S71 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215600230 ER PT J AU Paul, CB Brower, D Lankinski, RE Keenan, G Wheril, S Schumacher, HR AF Paul, CB Brower, D Lankinski, RE Keenan, G Wheril, S Schumacher, HR TI Proton NMR spectroscopy studies of osteoarthritic (OA) synovial fluids (SF) show changes after intra articular hyaluronic acid (HA) therapy. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. CHOP, Philadelphia, PA USA. Vet Affairs Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 682 BP S146 EP S146 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215600683 ER PT J AU Perell, K Guerrero, E Fang, M Bragas, M Miyamoto, E Peralta, M AF Perell, K Guerrero, E Fang, M Bragas, M Miyamoto, E Peralta, M TI Comparison of gait kinetics across disease severity in knee osteoarthritis subjects. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 322 BP S86 EP S86 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215600323 ER PT J AU Peters, JH Carsons, S Kalunian, K Ko, FC McDougall, S Hahn, TJ AF Peters, JH Carsons, S Kalunian, K Ko, FC McDougall, S Hahn, TJ TI Differential expression of the alternatively spliced EIIIA segment of fibronectin in synovial fluid in osteoarthritis and rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Winthrop Univ Hosp, Mineola, NY 11501 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 340 BP S89 EP S89 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215600341 ER PT J AU Robinson, CP Brayer, J Yamachika, S Esch, TR Peck, AB Stewart, CA Peen, E Jonsson, R Humphreys-Beher, M AF Robinson, CP Brayer, J Yamachika, S Esch, TR Peck, AB Stewart, CA Peen, E Jonsson, R Humphreys-Beher, M TI Transfer of human serum IgG to nonobese diabetic Ig mu(null) mice reveals a role for autoantibodies in the loss of secretory function of exocrine tissues in Sjogren's syndrome. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Univ Florida, Gainesville, FL 32611 USA. Forsyth Dent Ctr, Boston, MA 02115 USA. Univ Bergen, N-5021 Bergen, Norway. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 1931 BP S354 EP S354 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215601930 ER PT J AU Zhang, HD Gao, GN Williams, WV Wang, GF Wilson, JM Schumacher, HR AF Zhang, HD Gao, GN Williams, WV Wang, GF Wilson, JM Schumacher, HR TI Effects of Fas ligand (FasL) gene transfer on the apoptosis of synovial fibroblasts from rheumatoid arthritis patients in vitro. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Philadelphia, PA 19104 USA. SmithKline Beecham, Philadelphia, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 660 BP S142 EP S142 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215600661 ER PT J AU Levin, NW Yang, PM Hatch, DA Dubrow, AJ Caraiani, NS Ing, TS Gandhi, VC Alto, A Davila, SM Prosl, FR Polaschegg, HD Megerman, J AF Levin, NW Yang, PM Hatch, DA Dubrow, AJ Caraiani, NS Ing, TS Gandhi, VC Alto, A Davila, SM Prosl, FR Polaschegg, HD Megerman, J TI New access device for hemodialysis SO ASAIO JOURNAL LA English DT Article; Proceedings Paper CT 44th Annual Conference of the American-Society-for-Artificial-Internal-Organs CY APR 23-25, 1998 CL NEW YORK, NEW YORK SP Amer Soc Artificial Internal Organs ID INTERNAL JUGULAR-VEIN; VASCULAR ACCESS; EXPERIENCE; CATHETERS AB A new subcutaneous device (Dialock(TM); Biolink Corp., Middleboro, MA) provides vascular access to patients who currently require hemodialysis (HD). The device consists of a port-like valve, implanted subcutaneously below the clavicle, which provides a linear flow passage to two catheters placed in the right atrium via the jugular vein. The valve is accessed percutaneously with needle-cannulas that functionally convert the device to twin catheters for connecting the patient to the HD lines. Interdialytic patency is maintained using a standard heparin lock. The device has been implanted in 10 outpatients under local anesthesia, with almost immediate use for HD (median, 3 days) and has functioned successfully for more than 6 months (mean +/- SD, 4.0 +/- 1.7; > 400 dialysis sessions). Blood flows over 300 ml/min were consistently achieved (average, 320 +/- 50) with venous and arterial pressures of 197 +/- 42 mmHg and -241 +/- 31 mmHg, respectively. After 40 patient-months, condition of the needle puncture sites remains satisfactory. Four systemic infections have occurred in three patients; all have resolved without the need for device removal. There have been no infections at the puncture sites. One patient whose heparin lock was not changed for 23 days (for reasons unrelated to the device) required fibrin sheath stripping of his catheters. Patient and nurse acceptance has been excellent. The device may offer substantial improvement over conventional devices for HD access. C1 Biolink Corp, Clin Affairs, Middleboro, MA 02346 USA. Renal Res Inst, New York, NY USA. Beth Israel Med Ctr, New York, NY 10003 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. RP Megerman, J (reprint author), Biolink Corp, Clin Affairs, 47 E Grove St, Middleboro, MA 02346 USA. NR 11 TC 13 Z9 13 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1058-2916 J9 ASAIO J JI Asaio J. PD SEP-OCT PY 1998 VL 44 IS 5 BP M529 EP M531 DI 10.1097/00002480-199809000-00042 PG 3 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 128NJ UT WOS:000076412600042 PM 9804487 ER PT J AU Solomon, KR Mallory, MA Finberg, RW AF Solomon, KR Mallory, MA Finberg, RW TI Determination of the non-ionic detergent insolubility and phosphoprotein associations of glycosylphosphatidylinositol-anchored proteins expressed on T cells SO BIOCHEMICAL JOURNAL LA English DT Article ID SIGNAL-TRANSDUCING MOLECULE; KIDNEY MICROVILLAR MEMBRANE; TYROSINE KINASES P56(LCK); DECAY-ACCELERATING FACTOR; ALKALINE-PHOSPHATASE; HUMAN MONOCYTES; ECTO-ENZYMES; ACTIVATION; MICRODOMAINS; TRANSPORT AB Glycosylphosphatidylinositol (GPI)-anchored proteins are poorly solublized in non-ionic detergents such as Triton X-100 and Nonidet P40, but are easily solublized by detergents with high critical micelle concentrations such as octylglucoside. This solubility profile has been suggested to be due to the localization of GPI-anchored proteins to lipid microdomains rich in cholesterol and sphingolipids. Additionally, GPI-anchored proteins expressed on haemopoietic cells have been shown to associate with src-family tyrosine kinases and heterotrimeric G proteins. Despite these observations, the non-ionic detergent insolubility of GPI-anchored proteins on haemopoietic cells has not been quantified nor has a relationship between the non-ionic detergent insolubility of these proteins and their association with signal transduction molecules been identified. Here we show that GPI-anchored proteins found on T-cell tumours and activated T cells, although significantly more insoluble then transmembrane proteins, are not uniform in their detergent insolubility. Whereas CD59 was between 4%, and 13% soluble, CD48 was between 13% and 25% soluble, CD55 was between 20% and 30% soluble, and CD109 was between 34% and 75% soluble. The ability of these GPI-anchored proteins to associate with phosphoproteins was correlated with their detergent insolubility: the more detergent-insoluble that a GPI-anchored protein was, the greater the level of phosphoprotein associations. These experiments reveal a relationship between non-ionic detergent insolubility and association with signal-transduction molecules and suggest a cause-and-effect relationship between these two properties. In total, these experiments support the hypothesis that the association of GPI-anchored proteins with signalling molecules is due to their sorting to lipid microdomains. C1 Dana Farber Canc Inst, Infect Dis Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Solomon, KR (reprint author), Dana Farber Canc Inst, Infect Dis Unit, 44 Binney St, Boston, MA 02115 USA. RI Finberg, Robert/E-3323-2010 FU NIAID NIH HHS [T32 AI 07061-19] NR 49 TC 62 Z9 64 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD SEP 1 PY 1998 VL 334 BP 325 EP 333 PN 2 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 123EG UT WOS:000076112400004 PM 9716490 ER PT J AU Lipsitz, SR Ibrahim, JG AF Lipsitz, SR Ibrahim, JG TI Estimating equations with Incomplete categorical covariates in the Cox model SO BIOMETRICS LA English DT Article DE ignorable missing data; missing at random; Monte Carlo methods; noninformative censoring ID CENSORED SURVIVAL-DATA; REGRESSION-MODELS; EM ALGORITHM AB Incomplete covariate data is a common occurrence in many studies in which the outcome is survival time. When a full likelihood is specified, a useful technique for obtaining parameter estimates is the EM algorithm. We propose a set of estimating equations to estimate the parameters of Cox's proportional hazards model when some covariate values are missing. These estimating equations can be solved by an algorithm similar to the EM algorithm. Because of the computational burden of finding a solution to these estimating equations, we propose obtaining parameter estimates via Monte Carlo methods. Asymptotic variances of the parameter estimates are also derived. We present a clinical trials example with three covariates, two of which have some missing values. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. RP Lipsitz, SR (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 55576, CA 57253, CA 70101] NR 17 TC 44 Z9 44 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 SEP PY 1998 VL 54 IS 3 BP 1002 EP 1013 DI 10.2307/2533852 PG 12 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 192TY UT WOS:000080096700018 PM 9750248 ER PT J AU Sundaram, S Roth, CM Yarmush, ML AF Sundaram, S Roth, CM Yarmush, ML TI Pressure-induced dissociation of antigen-antibody complexes SO BIOTECHNOLOGY PROGRESS LA English DT Article ID HIGH HYDROSTATIC-PRESSURE; FLUORESCENCE POLARIZATION; MONOCLONAL-ANTIBODIES; LYSOZYME; PROTEINS; IMMUNOADSORPTION; ELUTION; BINDING; ALBUMIN; DIMER AB Pressures on the order of 1000-4000 bar have been reported to reversibly dissociate a number of oligomeric protein complexes without gross changes in protein structure. Here, we report that hydrostatic pressure can also dissociate some antigen-antibody complexes in solution. The association of fluorescent-labeled antigens with monoclonal antibodies was monitored via increases in the fluorescence anisotropy upon binding. Previously, we had found that pressures of 2000 atm were able to dissociate bovine serum albumin (BSA) from immunoadsorbents formed from certain antibodies but not others. In this study, we have found that the sensitivity to pressure in solution is present for the interaction of BSA with MAb 9.1 and absent for the interaction of BSA with MAb 6.1; this behavior is consistent with the immunoadsorbent study. The interaction of hen egg white lysozyme with two monoclonal antibodies was also measured. Interestingly, the complex with the greater electrostatic character (HyHEL-5) did not exhibit pressure sensitivity, as would be expected due to electrostriction effects, whereas the more hydrophobic complex (HyHEL-10) exhibited a strong pressure sensitivity. In each of the systems displaying pressure sensitivity, the free energy of association was found to increase linearly with pressure, indicating a constant change in volume between the free and bound states. Overall, these results indicate that some antigen-antibody complexes exhibit significant sensitivity to pressure, whereas others do not; the mechanisms that discriminate between these cases remain unresolved. Understanding and manipulation of this phenomenon may prove useful in a variety of processes involving the recovery from antigens of antibodies. C1 Rutgers State Univ, Dept Chem & Biochem Engn, Piscataway, NJ 08854 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med Surg Serv, Boston, MA 02114 USA. Shriners Burns Hosp, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Massachusetts Gen Hosp, Ctr Engn Med, Bigelow 1401, Boston, MA 02114 USA. OI Roth, Charles/0000-0002-4924-0721 NR 52 TC 16 Z9 16 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD SEP-OCT PY 1998 VL 14 IS 5 BP 773 EP 781 DI 10.1021/bp980066m PG 9 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 156VG UT WOS:000078022300015 PM 9758668 ER PT J AU Larson, RA Dodge, RK Linker, CA Stone, RM Powell, BL Lee, EJ Schulman, P Davey, FR Frankel, SR Bloomfield, CD George, SL Schiffer, CA AF Larson, RA Dodge, RK Linker, CA Stone, RM Powell, BL Lee, EJ Schulman, P Davey, FR Frankel, SR Bloomfield, CD George, SL Schiffer, CA TI A randomized controlled trial of filgrastim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic leukemia: CALGB study 9111 SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; CLASSIFICATION; CSF AB Recombinant human granulocyte colony-stimulating factor (G-CSF; filgrastim) shortens the time to neutrophil recovery after intensive chemotherapy, but its role in the treatment of adults with acute lymphoblastic leukemia (ALL) is uncertain. We randomly assigned 198 adults with untreated ALL (median age, 35 years; range, 16 to 83) to receive either placebo or G-CSF (5 mu g/kg/d) subcutaneously, beginning 4 days after starting intensive remission induction chemotherapy and continuing until the neutrophil count was greater than or equal to 1,000/mu L for 2 days. The study assignment was unblinded as individual patients achieved a complete remission (CR). Patients initially assigned to G-CSF then continued to receive G-CSF through 2 monthly courses of consolidation therapy. Patients assigned to placebo received no further study drug. The median time to recover neutrophils greater than or equal to 1,000/mu L during the remission induction course was 16 days (interquartile range [IQR], 15 to 18 days) for the patients assigned to receive G-CSF and 22 days (IQR, 19 to 29 days) for the patients assigned to placebo (P < .001). Patients in the G-CSF group had significantly shorter durations of neutropenia (< 1,000/mu L) and thrombocytopenia (< 50,000/mu L) and fewer days in the hospital (median, 22 days v 28 days; P = .02) compared with patients receiving placebo. The patients assigned to receive G-CSF had a higher CR rate and fewer deaths during remission induction than did those receiving placebo (P = .04 by the chi-square test for trend). During Courses IIA and IIB of consolidation treatment, patients in the G-CSF group had significantly more rapid recovery of neutrophils greater than or equal to 1,000/mu L than did the control group by approximately 6 to 9 days. However, the patients in the G-CSF group did not complete the planned first 3 months of chemotherapy any more rapidly than did the patients in the placebo group. Overall toxicity was not lessened by the use of G-CSF. After a median follow-up of 4.7 years, there were no significant differences in either the disease-free survival (P = .53) or the overall survival (P = .25) for the patients assigned to G-CSF (medians, 2.3 years and 2.4 years, respectively) compared with those assigned to placebo (medians, 1.7 and 1.8 years, respectively). Adults who received intensive chemotherapy for ALL benefited from G-CSF treatment, but its use did not markedly affect the ultimate outcome. (C) 1998 by The American Society of Hematology. C1 Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Ctr Stat, Canc & Leukemia Grp B, Durham, NC USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Univ Maryland, Baltimore, MD 21201 USA. N Shore Univ Hosp, Manhasset, NY USA. SUNY Hlth Sci Ctr, Syracuse, NY 13210 USA. Roswell Pk Canc Inst, Buffalo, NY USA. Ohio State Univ, Columbus, OH 43210 USA. Canc & Leukemia Grp B, Chicago, IL USA. RP Larson, RA (reprint author), Univ Chicago, Med Ctr, 5841 S Maryland Ave,MC2115, Chicago, IL 60637 USA. OI Larson, Richard/0000-0001-9168-3203 FU NCI NIH HHS [CA33601, CA31946, CA37027] NR 17 TC 155 Z9 157 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 1998 VL 92 IS 5 BP 1556 EP 1564 PG 9 WC Hematology SC Hematology GA 113NP UT WOS:000075558400011 PM 9716583 ER PT J AU Lecine, P Villeval, JL Vyas, P Swencki, B Xu, YH Shivdasani, RA AF Lecine, P Villeval, JL Vyas, P Swencki, B Xu, YH Shivdasani, RA TI Mice lacking transcription factor NF-E2 provide in vivo validation of the proplatelet model of thrombocytopoiesis and show a platelet production defect that is intrinsic to megakaryocytes SO BLOOD LA English DT Article ID ENDOTHELIAL-CELLS; MPL LIGAND; RELEASE; THROMBOPOIETIN; MARROW; FRAGMENTATION; CIRCULATION; STIMULATION; CLONING; INVITRO AB Mechanisms of platelet production and release by mammalian megakaryocytes are poorly understood. We used thrombocytopenic knockout mice to better understand these processes. Proplatelets are filamentous extensions of terminally differentiated megakaryocytes that are thought to represent one mechanism of platelet release; however, these structures have largely been recognized in cultured cells and there has been no correlation between thrombocytopoiesis in vivo and proplatelet formation. Mice lacking transcription factor NF-E2 have a late arrest in megakaryocyte maturation, resulting in profound thrombocytopenia. In contrast to normal megakaryocytes, which generate abundant proplatelets, cells from these mice never produce proplatelets, even after prolonged stimulation with c-MpI ligand. Similarly, megakaryocytes from thrombocytopenic mice with lineage-selective loss of transcription factor GATA-1 produce proplatelets very rarely. These findings establish a significant correlation between thrombocytopoiesis and proplatelet formation and suggest that the latter represents a physiologic mechanism of platelet release. We further show that proplatelet formation by normal megakaryocytes and its absence in cells lacking NF-EP are independent of interactions with adherent (stromal) cells. Similarly, thrombocytopenia in NF-E2(-/-) mice reflects intrinsic defects in the megakaryocyte lineage. These observations improve our understanding of platelet production and validate the study of proplatelets in probing the underlying mechanisms. (C) 1998 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Childrens Hosp, Med Ctr, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Lecine, Patrick/H-9338-2016 NR 32 TC 111 Z9 113 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 1998 VL 92 IS 5 BP 1608 EP 1616 PG 9 WC Hematology SC Hematology GA 113NP UT WOS:000075558400016 PM 9716588 ER PT J AU Reiter, A Sohal, J Kulkarni, S Chase, A Macdonald, DHC Aguiar, RCT Goncalves, C Hernandez, JM Jennings, BA Goldman, JM Cross, NCP AF Reiter, A Sohal, J Kulkarni, S Chase, A Macdonald, DHC Aguiar, RCT Goncalves, C Hernandez, JM Jennings, BA Goldman, JM Cross, NCP TI Consistent fusion of ZNF198 to the fibroblast growth factor receptor-1 in the t(8;13)(p11;q12) myeloproliferative syndrome SO BLOOD LA English DT Article ID CHRONIC MYELOMONOCYTIC LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; GENE; TRANSLOCATION; ABL; TEL; BCR; ACTIVATION; DISORDERS; PROTEIN AB The 8p11 myeloproliferative syndrome is a rare, aggressive condition associated with reciprocal translocations of chromosome band 8p11, most commonly the t(8;13)(p11;q12). To identify the genes involved in this translocation, we used fluorescence in situ hybridization (FISH) analysis to show that the chromosome 8 breakpoints fel within YAC 899e2 and that the chromosome 13 breakpoints are clustered in a region flanked by YACs 929f11 and 911h8. FISH using chromosome 13 PAC clones indicated that the t(8;13) is not simply a reciprocal translocation but also involves an inversion of 13q11-12. Exon trapping of a PAC that spanned the chromosome 13 translocation breakpoints led to the identification of a gene, ZNF198, that detected rearranged bands when used as a probe against Southern blots of patient DNA. Conceptual translation of the full-length ZNF198 cDNA sequence predicts a protein of 1377 amino acids that shows significant homology to the DXS6673E/KIAA0385 and KIAA0425 proteins. Alignment of these three proteins revealed a novel, conserved Zn-finger-related motif (MYM domain) of the general form CX2C19-22CX3CX13-19CX2CX19-25FCX3CX3F/Y that is repeated five times in each protein. To identify the translocation partner gene on chromosome 8, 5' and 3' RACE polymerase chain reactions (PCRs) were performed on patient RNA with several combinations of ZNF198 primers. Clones were identified in which the ZNF198 was fused to exon 9 of the fibroblast growth factor receptor-1 (FGFR1), a gene known to map to 8p11. An identical ZNF198-FGFR1 fusion was detected in the three patients with a t(8;13) for whom RNA was available; reciprocal FGFR1-ZNF198 transcripts were not detected. Rearrangements of both ZNF198 and FGFR1 were found in two further patients by Southern blotting. ZNF198-FGFR1 includes the five MYM domains of ZNF198 and the intracellular tyrosine kinase domain of FGFR1. We hypothesize that this fusion leads to constitutive activation of the FGFR1 tyrosine kinase in a manner analogous to the activation of ABL by BCR in chronic myeloid leukemia. (C) 1998 by The American Society of Hematology. C1 Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Sch Med, Dept Haematol, London W12 0NN, England. Dana Farber Canc Inst, Boston, MA 02115 USA. Hosp Geral de Santo Antonio, Oporto, Portugal. Hosp Univ Salamanca, Salamanca, Spain. Norfolk & Norwich Hosp, Norwich NR1 3SR, Norfolk, England. RP Cross, NCP (reprint author), Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Sch Med, Dept Haematol, Du Cane Rd, London W12 0NN, England. RI Cross, Nicholas/B-4817-2009; Hernandez-Rivas, Jesus Maria/B-5459-2017 OI Cross, Nicholas/0000-0001-5481-2555; Hernandez-Rivas, Jesus Maria/0000-0002-9661-9371 NR 39 TC 132 Z9 138 U1 2 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 1998 VL 92 IS 5 BP 1735 EP 1742 PG 8 WC Hematology SC Hematology GA 113NP UT WOS:000075558400031 PM 9716603 ER PT J AU Treon, SP Teoh, G Urashima, M Ogata, A Chauhan, D Webb, IJ Anderson, KC AF Treon, SP Teoh, G Urashima, M Ogata, A Chauhan, D Webb, IJ Anderson, KC TI Anti-estrogens induce apoptosis of multiple myeloma cells SO BLOOD LA English DT Article ID BREAST-CANCER CELLS; HIGH-DOSE TAMOXIFEN; PHASE-I TRIAL; PURE ANTIESTROGEN; PERIPHERAL-BLOOD; GROWTH-FACTOR; INTERLEUKIN-6; EXPRESSION; RECEPTOR; LINES AB Previous studies have suggested that multiple myeloma (MM) cells express estrogen receptors (ER). In the present study, we characterized the effects of estrogen agonists and antagonists (anti-estrogens [AE]) on growth of MM cell lines and MM patient cells. In addition to antagonizing estrogen binding to ER, AE can trigger apoptosis. Hence, we also determined whether estrogens or AE altered MM cell survival. Immunoblotting showed that ER-a is expressed in 4 of 5 MM cell lines (ARH-77, RPMI 8226, S6B45, and U266, but not OCl-My-5 cells), as well as in freshly isolated MM cells from 3 of 3 patients. 17 beta-estradiol (E2) did not significantly alter proliferation of MM cell lines or MM patient cells. In contrast, two structurally distinct AE, tamoxifen (TAM) and ICI 182,780 (ICI), significantly inhibited the proliferation of all 5 MM cell lines and MM cells from 2 of 2 patients (IC50, 2 to 4 mu mol/L). Proliferation of these cell lines was also inhibited by the hydroxylated TAM derivative, 4-hydroxytamoxifen (4HTAM), although this derivative was less potent than TAM (IC50, 3 to 25 mu mol/L). In contrast, the dehalogenated TAM derivative toremifene (TOR) did not inhibit MM cell proliferation. We next examined the effects of these agents on MM cell survival. TAM, ICI, and, to a lesser extent; 4HTAM and TOR triggered apoptosis in both ER-alpha-positive as well as ER-alpha-negative MM cell lines and patient MM cells, evidenced both by fluorescence-activated cell sorting (FACS) analysis using propidium iodide staining and the TUNEL assay. TAM-induced growth inhibition and apoptosis of ER-alpha-positive S6B45 NIM cells was not blocked by coculture with excess E2. TAM-induced apoptosis of S6B45 MM cells was also unaffected by addition of exogenous interleukin-6. Importantly, both the inhibition of MM cell proliferation and the induction of MM cell apoptosis were achieved at concentrations of TAM (0.5 and 5.0 mu mol/L) that did not significantly alter in vitro growth of normal hematopoietic progenitor cells. Similar plasma levels of TAM have been achieved using high-dose oral TAM therapy, with an acceptable toxicity profile. These studies therefore provide the rationale for trials to define the utility of AE therapy in MM. (C) 1998 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Singapore Gen Hosp, Dept Haematol, Singapore 0316, Singapore. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02215 USA. EM Kenneth-Anderson@dfci.harvard.edu FU NCI NIH HHS [CA50947] NR 50 TC 43 Z9 44 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 1998 VL 92 IS 5 BP 1749 EP 1757 PG 9 WC Hematology SC Hematology GA 113NP UT WOS:000075558400033 PM 9716605 ER PT J AU Adcock, D Kressin, D Marlar, RA AF Adcock, D Kressin, D Marlar, RA TI The effect of time and temperature variables on routine coagulation tests SO BLOOD COAGULATION & FIBRINOLYSIS LA English DT Article DE coagulation testing; prothrombin time; activated partial thromboplastin time; stability; temperature; storage variables; NCCLS; ECAT; heparin ID MONITORING HEPARIN-THERAPY; PLASMA AB This study evaluates the effects of time and temperature variables on routine coagulation assays [Prothrombin Time test and Activated Partial Thromboplastin Time (APTT) test]. Four different groups were studied: healthy volunteers, hospitalized patients not receiving anticoagulants, patients receiving oral anticoagulant therapy and patients receiving unfractionated heparin therapy. Samples were subjected to one of four conditions: (1) centrifuged immediately and stored at room temperature (20-22 degrees C); (2) centrifuged immediately and stored on ice (4 degrees C); (3) stored as whole blood without centrifugation, at room temperature and (4) stored without centrifugation, on ice. Coagulation tests were performed as soon as possible after phlebotomy and at specified times up to 24 h. Our data demonstrate that prothrombin time results are stable for up to 24 h, remaining constant regardless of storage conditions. APTT assays are stable for up to 8 h, except for patients receiving unfractionated heparin therapy. Heparinized samples, when stored uncentrifuged at room temperature, demonstrate a clinically significant shortening of the APTT and individual samples demonstrate a greater than 50% decrease in ex-vivo heparin levels at 4 h. Blood Coag Fibrinol 9:463-470 (C) 1998 Lippincott Williams & Wilkins. C1 Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. Denver VA Med Ctr, Lab Serv 113, Denver, CO 80220 USA. Colorado Kaiser Permanente Med Grp, Dept Pathol, Denver, CO USA. RP Marlar, RA (reprint author), Denver VA Med Ctr, Lab Serv 113, 1055 Clermont St, Denver, CO 80220 USA. EM rmarlar@calvin.uchsc.edu NR 19 TC 52 Z9 54 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0957-5235 J9 BLOOD COAGUL FIBRIN JI Blood Coagul. Fibrinolysis PD SEP PY 1998 VL 9 IS 6 BP 463 EP 470 DI 10.1097/00001721-199809000-00002 PG 8 WC Hematology SC Hematology GA 133FN UT WOS:000076676300002 PM 9818995 ER PT J AU Kerner, JA Standaert, DG Penney, JB Young, AB Landwehrmeyer, GB AF Kerner, JA Standaert, DG Penney, JB Young, AB Landwehrmeyer, GB TI Simultaneous isotopic and nonisotopic in situ hybridization histochemistry with cRNA probes SO BRAIN RESEARCH PROTOCOLS LA English DT Article DE in situ hybridization; histochemistry; gene expression; mRNA; PCR; cRNA; digoxigenin; radioactive ID RADIOLABELED OLIGODEOXYRIBONUCLEOTIDE PROBES; SUBUNIT MESSENGER-RNA; RAT NEOSTRIATUM; EXPRESSION; NEURONS; INTERNEURONS; HIPPOCAMPUS; NEOCORTEX AB In situ hybridization histochemistry is widely used to study gene expression at the mRNA level in tissues and cells. Double label in situ hybridization allows for coexpression studies. We describe a protocol for the simultaneous hybridization of two cRNA probes tagged with S-CTP and digoxigenin-UTP, respectively, to frozen brain tissue sections. Hybridization signals of digoxigenin-tagged probes appear as purple cytoplasmic staining following detection of digoxigenin residues by an alkaline-phosphatase-(AP)-linked antibody. Signals resulting from hybridization of radiolabeled probes are detected as silver grains overlying cellular profiles in sections coated with autoradiographic emulsion. Grain counting allows for semiquantitatively estimates of the cellular expression levels of transcripts. Suitable cRNA-probes can be derived from linear templates generated by polymerase chain reaction (PCR) using nested primers which contain RNA-polymerase promotor sites. The cRNA-probes are sensitive and allow an application of this protocol to the detection of a wide range of mRNAs of medium or low abundance. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Freiburg, Dept Neurol, D-7800 Freiburg, Germany. RP Young, AB (reprint author), Massachusetts Gen Hosp, Dept Neurol, Fruit St, Boston, MA 02114 USA. OI Standaert, David/0000-0003-2921-8348 FU NIA NIH HHS [AG11337]; NINDS NIH HHS [NS34361, NS31579] NR 15 TC 27 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1385-299X J9 BRAIN RES PROTOC JI Brain Res. Protoc. PD SEP PY 1998 VL 3 IS 1 BP 22 EP 32 DI 10.1016/S1385-299X(98)00017-8 PG 11 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 134TU UT WOS:000076760200004 PM 9767088 ER PT J AU Lu, C Stomper, PC Drislane, FW Wen, PY Block, CC Humphrey, CC Collins, CA Jolesz, F Talcott, JA AF Lu, C Stomper, PC Drislane, FW Wen, PY Block, CC Humphrey, CC Collins, CA Jolesz, F Talcott, JA TI Suspected spinal cord compression in breast cancer patients: A multidisciplinary risk assessment SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer; metastases; models; retrospective studies; risk; spinal cord compression ID EPIDURAL METASTASES; RADIATION-THERAPY; BACK PAIN; EARLY DIAGNOSIS; MYELOGRAPHY; MANAGEMENT; PROGNOSIS; DISEASE; TUMOR AB Breast cancer is the most common cause of metastatic epidural spinal cord compression (SCC) in women, and this condition results in significant neurologic dysfunction and morbidity. Prior studies of patients with suspected SCC did not employ multivariate analysis techniques, often included persons with a wide variety of malignancies, and generally focused on identifying associated neurologic and radiologic features. We therefore conducted a study examining a more comprehensive set of potential clinical risk factors in breast cancer patients with suspected SCC. We retrospectively analysed 123 episodes of suspected SCC among 93 breast cancer patients evaluated by spine computed tomography (CT) scanning. Multiple logistic regression analysis was employed to identify independent predictors of SCC. Clinically significant metastatic epidural cancer was defined as thecal sac compression (TSC), which occurred in 33 episodes (27%). Four independent predictors of TSC were identified and included oncologic features (known bone metastases greater than or equal to 2 years, metastatic disease at initial diagnosis) in addition to neurologic and radiologic features (objective weakness, vertebral compression fracture on spine radiograph). These four predictors stratified episodes into subgroups with widely varying risks of TSC, ranging from 12% (0 risk factors) to 85% (greater than or equal to 3 risk factors). These results suggest that the evaluation of breast cancer patients with suspected SCC should include clinical information about their disease course in addition to neurologic examination and prior imaging studies. If confirmed, these predictors may help clinicians assess risk in this patient population. C1 Brigham & Womens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Roswell Pk Canc Inst, Dept Diagnost Radiol, Buffalo, NY 14205 USA. Beth Israel Hosp, Dept Neurol, Boston, MA 02215 USA. Dana Farber Canc Inst, Div Clin Epidemiol, Boston, MA 02115 USA. RP Talcott, JA (reprint author), Ctr Outcomes Res, MGH-B75 230,55 Fruit St, Boston, MA 02114 USA. FU PHS HHS [2T3209172-22] NR 34 TC 19 Z9 20 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD SEP PY 1998 VL 51 IS 2 BP 121 EP 131 DI 10.1023/A:1006002823626 PG 11 WC Oncology SC Oncology GA 155BH UT WOS:000077925700003 PM 9879774 ER PT J AU Carapeti, M Aguiar, RCT Sill, H Goldman, JM Cross, NCP AF Carapeti, M Aguiar, RCT Sill, H Goldman, JM Cross, NCP TI Aberrant transcripts of the FHIT gene are expressed in normal and leukaemic haemopoietic cells SO BRITISH JOURNAL OF CANCER LA English DT Article DE FHIT; FRA3B; loss of heterozygosity; leukaemia; tumour-suppressor gene; 3p14.2 ID CHRONIC MYELOID-LEUKEMIA; TUMOR-SUPPRESSOR GENE; 3P14.2 FRAGILE SITE; SHORT ARM; LUNG-CANCER; HOMOZYGOUS DELETIONS; MOLECULAR ANALYSIS; BREAST CARCINOMAS; FRA3B REGION; SOLID TUMORS AB Deletions and apparent transcriptional abnormalities of the FHIT gene at 3p14.2 have recently been reported in a wide variety of solid tumours. To determine whether lesions of this gene also occur in leukaemia, we have analysed a total of 97 patients (chronic myeloid leukaemia, CML, in chronic phase or blast crisis, n = 71, de novo acute leukaemia, n = 26) and 16 normal individuals, intact FHIT transcripts from all cases were amplified using RT-PCR. In addition, smaller size bands that were less intense than the full-length products were amplified from several samples from patients with leukaemia and also from normal leucocytes. Sequencing of the small products revealed that they were derived from FHIT transcripts lacking whole exons. Using single-strand conformation polymorphism analysis, no mutations in the coding sequence were detected in any patient, Furthermore, loss of heterozygosity was not seen in any of 36 informative patients at D3S1300 or D3S1481, markers located within the FHIT locus. We conclude that the FHIT gene and other uncharacterized tumour-suppressor genes at 3p14.2 are unlikely to be involved in the pathogenesis of acute leukaemia or progression of CML from chronic phase to blast crisis. Moreover, low-abundance FHIT transcripts that lack whole exons are not specific to malignant cells and should not be taken as evidence of an abnormality in the absence of demonstrable genomic DNA lesions. C1 Hammersmith Hosp, Imperial Coll Sch Med, Dept Haematol, London W12 0NN, England. Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. Karl Franzens Univ Graz, Dept Internal Med, A-8036 Graz, Austria. RP Cross, NCP (reprint author), Hammersmith Hosp, Imperial Coll Sch Med, Dept Haematol, Du Cane Rd, London W12 0NN, England. RI Cross, Nicholas/B-4817-2009 OI Cross, Nicholas/0000-0001-5481-2555 NR 39 TC 13 Z9 14 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD SEP PY 1998 VL 78 IS 5 BP 601 EP 605 DI 10.1038/bjc.1998.547 PG 5 WC Oncology SC Oncology GA 112MK UT WOS:000075498200008 PM 9744498 ER PT J AU Sherman, SI Brierley, JD Sperling, M Ain, KB Bigos, ST Cooper, DS Haugen, BR Ho, MN Klein, I Ladenson, PW Robbins, J Ross, DS Specker, B Taylor, T Maxon, HR AF Sherman, SI Brierley, JD Sperling, M Ain, KB Bigos, ST Cooper, DS Haugen, BR Ho, MN Klein, I Ladenson, PW Robbins, J Ross, DS Specker, B Taylor, T Maxon, HR CA Natl Thyr Canc Treatm Coop Stud Reg Grp TI Prospective multicenter study of thyroid carcinoma treatment - Initial analysis of staging and outcome SO CANCER LA English DT Article; Proceedings Paper CT 69th Annual Meeting of the American-Thyroid-Association CY NOV 13-17, 1996 CL SAN DIEGO, CALIFORNIA SP Amer Thyroid Assoc DE thyroid neoplasms; neoplasm staging; prognosis; comparative study; prospective studies; papillary carcinoma; follicular carcinoma; medullary carcinoma; anaplastic carcinoma ID PROGNOSTIC SCORING SYSTEM; PAPILLARY; CANCER; SURVIVAL AB BACKGROUND. A novel prognostic staging classification encompassing all forms of thyroid carcinoma was created for the National Thyroid Cancer Treatment Cooperative Study (NTCTCS) Registry, with the goal of prospective validation and comparison with Other available staging classifications. METHODS. Patient information was recorded prospectively from 14 institutions. Clinicopathologic staging was based on patient age at diagnosis, tumor histology, tumor size, intrathyroidal multifocality, extraglandular invasion, metastases, and tumor differentiation. RESULTS. Between 1987 and 1995, 1607 patients were! registered. Approximately 43% of patients were classified as NTCTCS Stage I, 24% Stage II, 24% Stage III, and 9% Stage IV. Patients with follicular carcinoma were mc,re likely to have "high risk" Stage III or IV disease than those with papillary carcinoma. Of 1562 patients for whom censored follow-up was available (median follow-up, 40 months), 78 died of thyroid carcinoma or complications of its treatment. I:ive-year product-limit patient disease specific survival was 99.8% for Stage I, 100% for Stage II, 91.9% for Stage III, and 48.9% for Stage TV (P < 0.0001). The frequency of remaining disease free also declined significantly with increasing stage (94.3% for Stage I, 93.1% for Stage II, 77.8% for Stage III, and 24.6% for Stage nr). The same patients also were staged applying six previously published classifications as appropriate for their tumor type. The predictive value of the NTCTCS Registry staging classification consistently was among the highest for disease specific mortality and for remaining disease free, regardless of the tumor type. CONCLUSIONS. The NTCTCS Registry staging classification provides a prospectively validated scheme for predicting short term prognosis for patients with thyroid carcinoma. [See editorial counterpoint on pages 844-7 and reply to counterpoint on pages 848-50, this issue.] (C) 1998 American Cancer Society. C1 Univ Texas, MD Anderson Cancer Ctr, Sect Endocrine Neoplasia & Hormonal Disorders, Houston, TX 77030 USA. Princess Margaret Hosp, Dept Radiat Oncol, Toronto, ON M4X 1K9, Canada. Univ Cincinnati, Med Ctr, Dept Nucl Med, Cincinnati, OH 45267 USA. Univ Kentucky, Med Ctr, Dept Med, Lexington, KY 40536 USA. Maine Med Ctr, Dept Med, Portland, ME 04102 USA. Sinai Hosp, Dept Med, Baltimore, MD 21215 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. N Shore Univ Hosp, Dept Med, Manhasset, NY 11030 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Thyroid Unit, Boston, MA 02114 USA. S Dakota State Univ, Martin Program Human Nutr, Brookings, SD 57007 USA. Bayer Pharmaceut, New Haven, CT 06511 USA. RP Sherman, SI (reprint author), Univ Texas, MD Anderson Cancer Ctr, Sect Endocrine Neoplasia & Hormonal Disorders, 1515 Holcombe Blvd,Box 15, Houston, TX 77030 USA. RI Ain, Kenneth/A-5179-2012; OI Ain, Kenneth/0000-0002-2668-934X; Sherman, Steven/0000-0002-3079-5153 NR 31 TC 258 Z9 262 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 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 1998 VL 83 IS 5 BP 1012 EP 1021 PG 10 WC Oncology SC Oncology GA 115FQ UT WOS:000075653200028 PM 9731906 ER PT J AU Wright, JE Pardo, M Tretyakov, A Alperin, WL Trites, D Rosowsky, A AF Wright, JE Pardo, M Tretyakov, A Alperin, WL Trites, D Rosowsky, A TI Pharmacokinetics, antifolate activity and tissue distribution of PT523 in SCC VII tumor-bearing mice SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE pharmacokinetics; tissue distribution; nonpolyglutamatable antifolate; murine tumor model ID HUMAN DIHYDROFOLATE-REDUCTASE; FOLYLPOLYGLUTAMATE SYNTHETASE-ACTIVITY; CELL LUNG-CANCER; METHOTREXATE POLYGLUTAMATES; THYMIDYLATE SYNTHASE; TERNARY COMPLEXES; SIDE-CHAIN; INHIBITION; TRANSPORT; INVITRO AB Purpose: To monitor the pharmacokinetics of PT523 and methotrexate in C3H mice with transplanted SCC VII tumors; to compare the impact of PT523 and methotrexate on tumor and normal host 5,10-methylenetetrahydrofolate levels; and to synthesize [(14)C]PT523 and determine its time-dependent tissue distribution in tumor and host tissues. Methods: C3H mice bearing SCC VII tumors were given i.p. PT523 or methotrexate. Plasma drug levels and tumor,,out and marrow 5,10-methylenetetrahydrofolate were assayed. [(14)C]PT523 was synthesized and administered i.v. to tumor-bearing mice for tissue distribution analysis. Results: Areas under the curve, mean residence times, whole body clearances, apparent distribution volumes, and plasma protein binding of PT523 vs methotrexate were, respectively, 4311 vs 6472 mu M.min(-1): 20 vs 16 min; 0.56 vs 0.36 ml.min(-1) 532 vs 325 ml.kg(-1); and 70% vs 30%. Both PT523 and methotrexate caused time-dependent declines in 5,10-methylenetetrahydrofolate in tumor and gut mucosa, but not in marrow. Gut levels began to recover within 4 h in the PT523-treated group only. [(14)C]PT523 distributed mainly into the liver, duodenum, kidneys, lungs, tumor, pancreas and muscle; less into the spleen, blood cells, heart, brain and testicles; and very little into bone marrow. Only 35% of the dose was excreted, and 2.9-fold more in feces than urine. Conclusions: Despite its more rapid clearance, accumulation of PT523 in extravascular tissues was greater than that of methotrexate. Consequently, less PT523 was recovered in feces and urine and its apparent volume of distribution was greater. PT523 selectively depleted 5,10-methylenetetrahydrofolate pools in tumor and, less persistently, in gut mucosa, but spared the marrow. [(14)C]PT523 tissue distribution correlated with organ mass and blood supply. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Wright, JE (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA25394, R01-CA19589] NR 46 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD SEP PY 1998 VL 42 IS 4 BP 300 EP 306 DI 10.1007/s002800050821 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 118FG UT WOS:000075827300007 PM 9744775 ER PT J AU Eder, JP Chan, V Wong, J Wong, YW Ara, G Northey, D Rizvi, N Teicher, BA AF Eder, JP Chan, V Wong, J Wong, YW Ara, G Northey, D Rizvi, N Teicher, BA TI Sequence effect of irinotecan (CPT-11) and topoisomerase II inhibitors in vivo SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE irinotecan; CPT-11; topoisomerase I; topoisomerase II; treatment sequence effects ID ANTITUMOR-ACTIVITY; CAMPTOTHECIN ANALOG; EXPRESSION; INVITRO; CYCLOOXYGENASE; RESISTANCE; TIME; MICE AB The DNA topoisomerases I and II are the target of several clinically important antineoplastic agents which produce DNA cleavage by stabilization of the covalent DNA-protein bond with resultant cell death after DNA synthesis is attempted. Depletion of the target topoisomerase and reciprocal changes in the other occur with drug treatment. Purpose and Methods: To develop empiric treatment regimens of combinations and sequences of agents directed against topoisomerase I (irinotecan/CPT-11) and II (etoposide and doxorubicin), in vivo studies were performed in mice bearing the EMT-6 mammary tumor to assess efficacy, host tolerance and the resultant biochemical changes in topoisomerase mRNA and protein. Results: At 24 h after therapy, depletion of the target topoisomerase mRNA and protein with reciprocal increases in the alternate topoisomerase mRNA and, to a lesser extent, protein were noted. No therapeutic antagonism was found with any combination or sequence of agents, and therapeutic antagonism was noted with concurrent irinotecan/etoposide and sequential doxorubicin/irinotecan. Depletion of target topoisomerases by combined therapy beyond a threshold necessary for therapeutic efficacy produced no additional benefit. Conclusions: Antineoplastic therapy with combinations of topoisomerase I and II agents is feasible and may produce therapeutic synergy. The appropriate sequence may depend on the particular agents used. The rationale for such therapy, that topoisomerases I and II may have reciprocal and compensatory interactions, is supported by the biochemical data. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Ohio State Univ, Dept Obstet & Gynecol, Div Gynecol Oncol, Columbus, OH 43210 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. RP Teicher, BA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 35 TC 43 Z9 43 U1 2 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD SEP PY 1998 VL 42 IS 4 BP 327 EP 335 DI 10.1007/s002800050825 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 118FG UT WOS:000075827300011 PM 9744779 ER PT J AU Do, T Parker, RG Do, C Tran, L Do, L Dolkar, D AF Do, T Parker, RG Do, C Tran, L Do, L Dolkar, D TI Salvage radiotherapy for biochemical and clinical failures following radical prostatectomy SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Article DE radiation; prostate; prostatectomy; recurrence ID ADJUVANT RADIATION-THERAPY; LOCAL RECURRENCE; ANTIGEN LEVELS; CANCER; ADENOCARCINOMA; CARCINOMA; IRRADIATION; MARKER AB PURPOSE The proportion of prostate cancer patients undergoing radical prostatectomy has increased over the past 10 to 15 years. It is conceivable that a corresponding increase in local tumor recurrences after prostateaomies will be observed. The role of salvage radiotherapy is presently unclear. In this study, the results of salvage radiotherapy for patients with biochemical evidence of local recurrence, as evidenced from rising prostate-specific antigen (PSA) levels, after radical prostatectomy at UCLA Medical Center and the West Los Angeles Veterans Administration Medical Center are described. PATIENTS AND METHODS Between 1990 and 1997, 69 patients were diagnosed with presumed local tumor recurrence after radical prostatectomy. Of these patients, 60 patients were referred to radiotherapy for salvage treatments. Tumor recurrence was detected biochemically, with or without a palpable nodule on digital rectal examination, and a metastatic workup revealing no evidence of extrapelvic disease. Biochemical failure after salvage radiotherapy was defined as two consecutive rises in serum PSA lad after a PSA nadir or an absence of a PSA nadir after radiation treatments, as nas earlier defined at the ASTRO Consensus Panel on PSA Guidelines. Patients referred for adjuvant postoperative radiation treatment and patients with metastatic disease at presentation were excluded from the study. Patients were treated with a four-field approach (anteroposterior/posteroanterior and opposing laterals) to a median dose of 64.8 Gy in 1.8-Gy fractions. Follow-up evaluations included serum PSA level and digital rectal examination every 3 to 6 months. RESULTS At last follow-up (mean follow-up, 36 months after salvage radiotherapy), 40 of 60 patients (67%) were biochemically free of disease. Thirty of 60 patients (50%) had undetectable PSA levels, and 55 of 60 (92%) had achieved some initial decrease after salvage radiation treatments. Three-year and 5-year actuarial biochemical disease-free survival was 63% and 55%, respectively of the 20 patients with biochemical failure after salvage radiation therapy, 10 patients (50%) developed distant metastases, and two (10%) patients were found to have persistent local disease. The mean time to biochemical relapse after salvage radiotherapy was 10 months, and the mean time to distant metastasis after salvage radiotherapy was 20 months. Evaluation of the remaining eight biochemical failures (43%) revealed no evidence of local disease progression or distant metastasis to date. Univariate and multivariate analyses revealed that both PSA > 1.0 ng/ml, at the time of salvage radiotherapy and perineural invasion significant prognosticators for biochemical relapse after salvage radiotherapy. Likewise, both univariate and multivariate analyses revealed that prognosticators for distant metastasis included seminal vesicle invasion and perineural invasion. DISCUSSION Salvage radiation therapy is a viable option for post prostatectomy local tumor recurrences. Of the patients who fail biochemically after salvage radiotherapy, 50% were eventually found to have distant metastases. In addition, biopsy-proven local recurrence after prostatectomy nas found not to confer an adverse outcome after salvage radiotherapy. C1 Univ Calif Los Angeles, Med Ctr, Dept Radiat Therapy, Los Angeles, CA 90095 USA. W Los Angeles Vet Adm Med Ctr, Dept Radiat Therapy, Los Angeles, CA USA. Univ Calif Santa Cruz, Sch Biol Sci, Santa Cruz, CA 95064 USA. RP Do, L (reprint author), Univ Calif Los Angeles, Med Ctr, Dept Radiat Therapy, 200 Med Plaza,Suite B 265, Los Angeles, CA 90095 USA. NR 24 TC 56 Z9 56 U1 0 U2 1 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 USA SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD SEP-OCT PY 1998 VL 4 IS 5 BP 324 EP 330 PG 7 WC Oncology SC Oncology GA 124RG UT WOS:000076195200009 PM 9815297 ER PT J AU Kovacs, DM Tanzi, RE AF Kovacs, DM Tanzi, RE TI Monogenic determinants of familial Alzheimer's disease: Presenilin-1 mutations SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE PS1; presenilin-1; Alzheimer's disease; FAD; neurodegeneration; beta-amyloid; mutations ID AMYLOID-BETA-PROTEIN; PRECURSOR PROTEIN; IN-VIVO; NEURONAL DIFFERENTIATION; DEVELOPMENTAL REGULATION; CAENORHABDITIS-ELEGANS; MISSENSE MUTATIONS; MAMMALIAN-CELLS; SENILE PLAQUES; MESSENGER-RNA AB Presenilin-1 (PSI) mutations account for the greatest portion of early onset familial Alzheimer's disease (FAD) cases. The exact cellular function of PSI is not known. To date, PSI mutations have been shown to alter two potential biological roles of the protein, either of which could make neurons more susceptible to neurodegeneration. First, PSI mutations result in elevated A beta 42/A beta 40 ratios in plasma of FAD patients, in transgenic mice and in transfected cell lines. A beta 42 is the more hydrophobic and most neurotoxic form of the peptide. A common molecular event that has been associated with all of the known early onset FAD genes is the excessive production or accumulation of the A beta peptide in the brain. PSI mutations have also been found to alter the Notch signalling pathway, but the mechanism by which this may affect neurodegeneration remains to be determined. Future studies will be needed to elucidate whether PSI mutations lead directly to neuronal dysfunction and degeneration or cause cell death by increasing A beta 42 generation and deposition. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Genet & Aging Unit, Charlestown, MA 02129 USA. RP Tanzi, RE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Genet & Aging Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu NR 86 TC 23 Z9 23 U1 1 U2 5 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD SEP PY 1998 VL 54 IS 9 BP 902 EP 909 DI 10.1007/s000180050219 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 127EA UT WOS:000076336600003 PM 9791532 ER PT J AU Schwammenthal, E Nakatani, S He, SQ Hopmeyer, J Sagie, A Weyman, AE Lever, HM Yoganathan, AP Thomas, JD Levine, RA AF Schwammenthal, E Nakatani, S He, SQ Hopmeyer, J Sagie, A Weyman, AE Lever, HM Yoganathan, AP Thomas, JD Levine, RA TI Mechanism of mitral regurgitation in hypertrophic cardiomyopathy - Mismatch of posterior to anterior leaflet length and mobility SO CIRCULATION LA English DT Article DE mitral valve; echocardiography; regurgitation; cardiomyopathy ID DYNAMIC SUBAORTIC OBSTRUCTION; DOPPLER ECHOCARDIOGRAPHY; VENA CONTRACTA; VALVE PROLAPSE; MOTION; FLOW; VALIDATION; MYECTOMY; JETS; SIZE AB Background-In hypertrophic cardiomyopathy: a spectrum of mitral leaflet abnormalities has been related to the mechanism of mitral systolic anterior motion (SAM), which causes both subaortic obstruction and mitral regurgitation. In the individual patient, SAM and regurgitation vary in parallel; clinically, however, great interindividual differences in mitral regurgitation can occur fur comparable degrees of SAM. We hypothesized that these differences relate to variations in posterior leaflet length and mobility, restricting its ability to follow the anterior leaflet (participate in SAM) and coapt effectively. Methods and Results-Different mitral geometries produced surgically in porcine valves were studied in vitro. Comparable degrees of SAM resulted in more severe mitral regurgitation for geometries characterized by limited posterior leaflet excursion. Mitral geometry was also analyzed in 23 patients with hypertrophic cardiomyopathy by intraoperative transesophageal echocardiography. All had typical anterior leaflet SAM with significant outflow tract gradients but considerably more variable mitral regurgitation; therefore, regurgitation did not correlate with obstruction, Ln contrast, mitral regurgitation correlated inversely with the length over which the leaflets coapted (r= -0.89), the most severe regurgitation occurring with a visible gap. Regurgitation increased with increasing mismatch of anterior to posterior leaflet length (r=0.77) and decreasing posterior leaflet mobility (r= -0.79). Conclusions-SAM produces greater mitral regurgitation if the posterior leaflet is limited in its ability to move anteriorly, participate in SAM, and coapt effectively. This can explain interindividual differences in regurgitation for comparable degrees of SAM. Thus, the spectrum of leaflet length and mobility that affects subaortic obstruction also influences mitral regurgitation in patients with SAM. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Noninvas Cardiac Lab, Boston, MA USA. Cleveland Clin Fdn, Cardiovasc Imaging Ctr, Dept Cardiol, Cleveland, OH 44195 USA. Georgia Inst Technol, Sch Chem Engn, Cardiovasc Fluid Mech Lab, Atlanta, GA 30332 USA. RP Schwammenthal, E (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Vincent Burnham 5 VBK 523, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-38176]; PHS HHS [53702] NR 36 TC 45 Z9 46 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 1 PY 1998 VL 98 IS 9 BP 856 EP 865 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 114VH UT WOS:000075629500008 PM 9738640 ER PT J AU Frei, E Elias, A Wheeler, C Richardson, P Hryniuk, W AF Frei, E Elias, A Wheeler, C Richardson, P Hryniuk, W TI The relationship between high-dose treatment and combination chemotherapy: The concept of summation dose intensity SO CLINICAL CANCER RESEARCH LA English DT Article ID METASTATIC BREAST-CANCER; ADVANCED HODGKINS-DISEASE; ADJUVANT CHEMOTHERAPY; MARROW TRANSPLANTATION; OSTEOGENIC-SARCOMA; ALKYLATING-AGENTS; RANDOMIZED TRIAL; CLINICAL-TRIAL; THERAPY; RESISTANCE AB The most important variables for the clinical use of antitumor agents (AAs) are dose and combination chemotherapy. The objectives of this study were to analyze the relationship between these two variables and to propose a unified conceptual framework for the construct and interpretation of clinical trials. Definitions and variables with respect to dose include potency, therapeutic index, standard dose, efficacy, relative efficacy, dose-limiting toxicity (DLT), dose rate, dose density, dose intensity, and fractional dose intensity. Our overarching concept, that is, summation dose intensity (SDI), was calculated in several ways, depending upon the nature of the data, and included the relative efficacy method, the unit regimen method, and the high dose method. The SDI concept was then applied to disease categories and strategies to determine its usefulness and effectiveness in integrating dose and combinations. The tumors and settings were: mustargen-vincristine-procarbazine-prednisone in Hodgkin's disease, combination chemotherapy for acute lymphocytic leukemia in children, metastatic breast cancer including dose and combinations, selected other solid tumors, alternating chemotherapy, and high dose studies in the leukemias and lymphomas, SDI was effective in integrating and quantifying dose and combination chemotherapy. For classical AAs, the implication of SDI for the construct and analysis of clinical trials was emphasized. In addition to new drug development, emphasis should be given to reducing or eliminating DLTs, such as those of the marrow, now and, in the future, those of the gastrointestinal tract toxicity and other DLTs. The above was derived from and applies to the classical AAs. Whether they will apply to, with appropriate adjustment, agents with significantly different dose-response curves, such as biotherapeutics and hormonal agents, remains to be determined. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Univ Calif San Diego, Ctr Canc, Dept Med Oncol, La Jolla, CA 92093 USA. RP Frei, E (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 79 TC 60 Z9 60 U1 1 U2 3 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 SEP PY 1998 VL 4 IS 9 BP 2027 EP 2037 PG 11 WC Oncology SC Oncology GA 116TY UT WOS:000075742000001 PM 9748116 ER PT J AU Bates, DW Parsonnet, J Ketchum, PA Miller, EB Novitsky, TJ Sands, K Hibberd, PL Graman, PS Lanken, PN Schwartz, JS Kahn, K Snydman, DR Moore, R Black, E Platt, R AF Bates, DW Parsonnet, J Ketchum, PA Miller, EB Novitsky, TJ Sands, K Hibberd, PL Graman, PS Lanken, PN Schwartz, JS Kahn, K Snydman, DR Moore, R Black, E Platt, R CA AMCC Sepsis Project Working Grp TI Limulus amebocyte lysate assay for detection of endotoxin in patients with sepsis syndrome SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID GRAM-NEGATIVE SEPSIS; ANTIENDOTOXIN MONOCLONAL-ANTIBODIES; LIVER-TRANSPLANTATION; SEPTIC SHOCK; BACTEREMIA; BLOOD; METAANALYSIS; DEFINITIONS; MORTALITY; THERAPY AB Clinical predictions alone are insufficiently accurate to identify patients with specific types of bloodstream infection; laboratory assays might improve such predictions. Therefore, we performed a prospective cohort study of 356 episodes of sepsis syndrome and did Limulus amebocyte lysate (LAL) assays for endotoxin. The main outcome measures were bacteremia and infection due to gram-negative organisms; other types of infection were secondary outcomes. Assays were defined as positive if the result was greater than or equal to 0.4 enzyme-linked immunosorbent assay units per milliliter. There were positive assays in 119 (33%) of 356 episodes. Assay positivity correlated with the presence of fungal bloodstream infection (P < .003) but correlated negatively with the presence of gram-negative organisms in the bloodstream (P = .04). A trend toward higher rates of mortality in the LAL assay-positive episodes was no longer present after adjusting for severity. Thus, results of LAL assay did not correlate with the presence of bacteremia due to gram-negative organisms or with mortality after adjusting for severity but did correlate with the presence of fungal bloodstream infection. C1 Brigham & Womens Hosp, Dept Med, Div Gen Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Associates Cape Cod Inc, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. New England Med Ctr, Dept Med & Pathol, Div Infect Dis, Boston, MA 02111 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Hosp Univ Penn, Div Pulm & Crit Care, Philadelphia, PA 19104 USA. Hosp Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Rochester, Sch Med, Dept Med, Div Gen Internal Med, Rochester, NY USA. Univ Rochester, Sch Med, Dept Med, Infect Dis Unit, Rochester, NY USA. Univ Calif Los Angeles, Med Ctr, Div Gen Internal Med, Los Angeles, CA USA. Dartmouth Hitchcock Med Ctr, Infect Dis Sect, Lebanon, NH 03766 USA. Johns Hopkins Hosp, Div Infect Dis, Baltimore, MD 21287 USA. RP Bates, DW (reprint author), Brigham & Womens Hosp, Dept Med, Div Gen Med, 75 Francis St, Boston, MA 02115 USA. RI Snydman, David/O-3889-2014 OI Snydman, David/0000-0003-0119-3978 NR 43 TC 43 Z9 44 U1 1 U2 7 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP PY 1998 VL 27 IS 3 BP 582 EP 591 DI 10.1086/514713 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 119VD UT WOS:000075917900028 PM 9770160 ER PT J AU Pierce, TD Herndon, HJ AF Pierce, TD Herndon, HJ TI The triceps preserving approach to total elbow arthroplasty SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID REPLACEMENT; EXPERIENCE AB Elbow arthroplasty most commonly is performed through a posterior approach by detaching or reflecting the triceps off the olecranon. Surgical approaches to the elbow joint that dissociate the triceps from the olecranon have distinct disadvantages. Triceps avulsion, triceps weakness, and wound healing problems have been reported. Such complications necessitate more surgery and predispose the joint to an infection. To avoid these complications a modified posterior approach to the elbow joint that preserves the triceps muscle insertion on the olecranon was used in 10 consecutive elbow arthroplasties, This method provides adequate exposure, allows early rehabilitation, and avoids triceps weakness. C1 Bone & Joint Ctr Excellence, Bismarck, ND 58201 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Pierce, TD (reprint author), Bone & Joint Ctr Excellence, 310 N 9th St, Bismarck, ND 58201 USA. NR 30 TC 38 Z9 41 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD SEP PY 1998 IS 354 BP 144 EP 152 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 119LP UT WOS:000075898000017 PM 9755773 ER PT J AU Rao, PM Boland, GWL AF Rao, PM Boland, GWL TI Imaging of acute right lower abdominal quadrant pain SO CLINICAL RADIOLOGY LA English DT Review ID UNENHANCED HELICAL CT; ACUTE APPENDICITIS; SUSPECTED APPENDICITIS; BARIUM ENEMA; MESENTERIC ADENITIS; APPENDECTOMY RATE; UNITED-STATES; DIAGNOSIS; SONOGRAPHY; DIVERTICULITIS AB This article reviews the clinical diagnosis of appendicitis, indications and options for appendiceal imaging, compares appendiceal CT techniques, and describes the imaging findings with appendicitis and alternative conditions that can clinically mimic appendicitis. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Rao, PM (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 60 TC 41 Z9 41 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD SEP PY 1998 VL 53 IS 9 BP 639 EP 649 DI 10.1016/S0009-9260(98)80290-0 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 121PQ UT WOS:000076022900003 PM 9766717 ER PT J AU Centeno, BA AF Centeno, BA TI Fine needle aspiration biopsy of the pancreas SO CLINICS IN LABORATORY MEDICINE LA English DT Article ID CYST FLUID ANALYSIS; ISLET-CELL TUMORS; DIFFERENTIAL-DIAGNOSIS; ENDOSCOPIC ULTRASONOGRAPHY; SEROUS CYSTADENOCARCINOMA; PREOPERATIVE ASSESSMENT; CYTOLOGIC DIAGNOSIS; PERITONEAL CYTOLOGY; CLINICAL UTILITY; CARCINOMA AB This article covers basic topics such as indications, contraindications, techniques and complications. Individual sections focus on the differential diagnosis between adenocarcinoma and benign or reactive processes, diagnosis of pancreatic endocrine tumors, and the diagnosis of cystic lesions using pancreatic cyst fluid analysis including cytopathology. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Centeno, BA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Warren 831B, Boston, MA 02114 USA. NR 82 TC 16 Z9 16 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD SEP PY 1998 VL 18 IS 3 BP 401 EP + PG 29 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 119LA UT WOS:000075896500004 PM 9742377 ER PT J AU Pitman, MB AF Pitman, MB TI Fine needle aspiration biopsy of the liver - Principal diagnostic challenges SO CLINICS IN LABORATORY MEDICINE LA English DT Article ID CELL NUCLEAR ANTIGEN; HEPATOCELLULAR-CARCINOMA; CYTOLOGIC CRITERIA; ABDOMINAL-TUMORS; HEPATIC-TUMORS; CORE BIOPSY; FEATURES; CANCER; LESIONS; DIFFERENTIATION AB Fine needle aspiration biopsy (FNAB) is the diagnostic procedure of choice for evaluation of liver lesions. Although primarily applied to malignant disease, it is also used in the evaluation of benign conditions. Improvements in imaging techniques and advances in cytologic interpretations, as well as production of new biopsy needles, have all contributed to the rapid increase in radiologically guided liver FNAB. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Pitman, MB (reprint author), Massachusetts Gen Hosp, Dept Pathol, Fruit St, Boston, MA 02114 USA. NR 64 TC 17 Z9 17 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 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD SEP PY 1998 VL 18 IS 3 BP 483 EP + PG 25 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 119LA UT WOS:000075896500007 PM 9742380 ER PT J AU Holdwick, DJ Hilsenroth, MJ Castlebury, FD Blais, MA AF Holdwick, DJ Hilsenroth, MJ Castlebury, FD Blais, MA TI Identifying the unique and common characteristics among the DSM-IV antisocial, borderline, and narcissistic personality disorders SO COMPREHENSIVE PSYCHIATRY LA English DT Article; Proceedings Paper CT 1997 Midwinter Meeting of the Society-for-Personality-Assessment CY MAR 15, 1997 CL SAN DIEGO, CALIFORNIA SP Soc Personal Assessment ID AXIS-II DISORDERS; PROTOTYPICAL ANALYSIS; DIAGNOSTIC INTERVIEW; CRITERIA; VALIDITY AB A clinical chart-review study of the Cluster B personality disorders (PDs) was conducted to evaluate the specificity of DSM-IV criteria for the Antisocial Personality Disorder (ANPD), Borderline Personality Disorder (BPD), and Narcissistic Personality Disorder (NPD). Eighty-six outpatients meeting DSM-IV criteria for a PD were identified through a retrospective chart-review procedure. Records of these 86 patients were independently rated on all of the ANPD, BPD, and NPD symptom criterion for the DSM-IV. High interrater reliabilities were obtained for the presence or absence of a PD and symptom criteria for ANPD, BPD, and NPD (all kappa greater than or equal to.80). The sample consisted of ANPD (n = 20), BPD (n = 25), NPD (n = 15), and other personality disorders (OPD; Cluster A and C; n = 26). Five ANPD criteria reliably differentiated ANPD patients from BPD and NPD patients (1, 2, 3, 6, 7), and two criteria did not differentiate this group from either intracluster category (4, 5). BPD criteria also differentiated BPD patients from ANPD and NPD patients; however, the specific criteria that effectively differentiated categories were dependent on the group comparisons. BPD criteria (1, 2, 3, 6,7) differentiated BPD and ANPD patients. BPD and NPD patients could be discriminated on other BPD criteria (2, 3, 5, 6, 7, 8). NPD criteria showed a similar ability to differentiate patients. NPD criteria differentiated NPD and BPD patients on DSM-IV criteria of 1, 3, 4, 5, 7, and 9. NPD and ANPD patients could be differentiated on other NPD criteria (1, 2, 3, 4, 5, 9). The results of this study provide general support for the use of specific criteria for these three disorders in the differential comparison of related and unrelated PDs. The utility of items that describe essential features are discussed. Copyright (C) 1998 by W.B. Saunders Company. C1 Univ Arkansas, Dept Psychol, Fayetteville, AR 72701 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Tennessee, Knoxville, TN USA. RP Holdwick, DJ (reprint author), Univ Arkansas, Dept Psychol, 316 Mem Hall, Fayetteville, AR 72701 USA. NR 33 TC 23 Z9 24 U1 2 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD SEP-OCT PY 1998 VL 39 IS 5 BP 277 EP 286 DI 10.1016/S0010-440X(98)90036-0 PG 10 WC Psychiatry SC Psychiatry GA 119UQ UT WOS:000075916600006 PM 9777280 ER PT J AU Golier, J Yehuda, R AF Golier, J Yehuda, R TI Neuroendocrine activity and memory-related impairments in posttraumatic stress disorder SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID DEXAMETHASONE SUPPRESSION TEST; PITUITARY-ADRENAL AXIS; CHILDHOOD SEXUAL ABUSE; HIPPOCAMPAL VOLUME; PLASMA-CORTISOL; GLUCOCORTICOID RECEPTORS; MAJOR DEPRESSION; URINARY CORTISOL; TRAUMATIC STRESS; COMBAT VETERANS AB This article reviews memory-related impairments in trauma survivors with posttraumatic stress disorder and their possible association to neuroendocrine alterations seen in this disorder. The neuroendocrine profile in PTSD first described in chronically ill combat veterans is characterized by lower basal cortisol levels, higher glucocorticoid receptor number, enhanced sensitivity to exogenous steroids, and increased variation in basal cortisol levels over the diurnal cycle. The generalizability and time course of these neuroendocrine alterations are explored in longitudinal studies and studies in other traumatized populations. These studies suggest that at least some aspects of this neuroendocrine profile can also be seen in other populations, including women, children, and victims of childhood trauma. Additionally, the alterations may be present early in the course of illness, perhaps even in the immediate aftermath of trauma, and may continue to be manifest in elderly trauma survivors. The mechanisms by which these neuroendocrine alterations may influence the formation and processing of traumatic memories are discussed. C1 Bronx Vet Affairs Med Ctr, Bronx, NY 10468 USA. Mt Sinai Sch Med, New York, NY 10029 USA. RP Golier, J (reprint author), Bronx Vet Affairs Med Ctr, 00MH,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM golier.julia@bronx.va.gov NR 63 TC 47 Z9 51 U1 9 U2 13 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD FAL PY 1998 VL 10 IS 4 BP 857 EP 869 DI 10.1017/S0954579498001904 PG 13 WC Psychology, Developmental SC Psychology GA 152BL UT WOS:000077755500014 PM 9886230 ER PT J AU Morgan, BA Orkin, RW Noramly, S Perez, A AF Morgan, BA Orkin, RW Noramly, S Perez, A TI Stage-specific effects of Sonic hedgehog expression in the epidermis SO DEVELOPMENTAL BIOLOGY LA English DT Article DE feather bud; pattern formation; Sonic hedgehog; basal cell carcinoma ID TERMINAL CLEAVAGE PRODUCT; GENE CUBITUS-INTERRUPTUS; SIGNALING PATHWAY; FEATHER MORPHOGENESIS; TRANSCRIPTION FACTOR; HUMAN HOMOLOG; NEURAL-TUBE; INDUCTION; DROSOPHILA; POLARITY AB Sonic hedgehog (Shh) is expressed in the ectoderm of the forming hair follicle and feather bud during normal development. However, inappropriate activation of the Shh signal transduction cascade in human epidermis can cause basal cell carcinoma. Here we show that during normal development of avian skin, Shh is first expressed only after the responsiveness to this protein has been suppressed in most of the surrounding ectodermal cells. Forced expression of Shh in avian skin prior to this time causes a disorganized ectodermal proliferation. However, as skin begins to differentiate, the forced expression of Shh causes feather bud formation. Subsequently, expression of Shh in interfollicular epidermis has little or no morphological effect. Restricted responsiveness to Shh in developing skin has functional consequences for morphogenesis and may have important implications for cutaneous pathologies as well. (C) 1998 Academic Press. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Cornell Univ, Grad Sch Med Sci, New York, NY 10021 USA. RP Morgan, BA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. NR 49 TC 80 Z9 82 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD SEP 1 PY 1998 VL 201 IS 1 BP 1 EP 12 DI 10.1006/dbio.1998.8969 PG 12 WC Developmental Biology SC Developmental Biology GA 119VH UT WOS:000075918500001 PM 9733569 ER PT J AU Vicent, D Piper, M Gammeltoft, S Maratos-Flier, E Kahn, CR AF Vicent, D Piper, M Gammeltoft, S Maratos-Flier, E Kahn, CR TI Alterations in skeletal muscle gene expression of ob/ob mice by mRNA differential display SO DIABETES LA English DT Article ID GERANYLGERANYL-DIPHOSPHATE SYNTHASE; DEPENDENT DIABETES-MELLITUS; PEROXISOMAL MEMBRANE-PROTEIN; ALPHA-TROPOMYOSIN GENE; PHOSPHOLIPASE-D; MESSENGER-RNA; ATP SYNTHASE; DNA-BINDING; CLONING; NIDDM AB To identify molecules that contribute to insulin resistance, we compared the patterns of gene expression in skeletal muscle of the obese ob/ob mouse, a genetic model of obesity and severe insulin resistance, with that of its thin Littermate (ob/+) using the mRNA differential display method. From about 9,000 cDNAs displayed, me found 12 differentially expressed in ob/ob mice skeletal muscle that could be recovered from the differential display gels and confirmed by Northern blot analysis and sequenced. Eight mRNAs were overexpressed in ob/ob muscle: Id2 (a negative regulator of the basic helix-loop-helix family of transcription factors), fast skeletal muscle troponin T, ribosomal protein L3, the integral protein of the peroxisomal membrane 22PMP, the mammalian homolog of geranylgeranyl pyrophosphate synthase, an mRNA related to phosphatidylinositol-glycan-specific phospholipase D, and two unknown mRNAs. The level of overexpression of these mRNAs in skeletal muscle varied from a 500% increase to as little as a 25% increase. Two mRNAs were underexpressed 20-35%, including the f-subunit of mitochondrial ATP synthase and a retrovirus-related DNA. Two proteins with multiple transcripts, skeletal muscle alpha-tropomyosin and one for a repetitive sequence, showed a change in mRNA pattern of expression in the muscle of the ob/ob mouse. Because the primary genetic defect in the ob/ob mouse is known to be in the leptin gene, these data indicate how acquired alterations in gene expression of multiple classes of proteins may play a role in the complex pathogenesis of insulin resistance in obesity and diabetes. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM kahnr@joslab.harvard.edu RI Vicent, David/O-2255-2014 OI Vicent, David/0000-0002-6663-0350 FU NIDDK NIH HHS [DK-45935, P30-DK-36836] NR 54 TC 21 Z9 22 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 1998 VL 47 IS 9 BP 1451 EP 1458 DI 10.2337/diabetes.47.9.1451 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 113FD UT WOS:000075539000011 PM 9726234 ER PT J AU Takagi, H King, GL Aiello, LP AF Takagi, H King, GL Aiello, LP TI Hypoxia upregulates glucose transport activity through an adenosine-mediated increase of GLUT1 expression in retinal capillary endothelial cells SO DIABETES LA English DT Article ID FACTOR MESSENGER-RNA; GROWTH-FACTOR GENE; DIABETIC COMPLICATIONS; INDUCIBLE FACTOR-1; PROTEIN-BINDING; MUSCLE-CELLS; ACTIVATION; INDUCTION; RECEPTORS; ERYTHROPOIETIN AB Elevation of intracellular glucose within retinal vascular cells is believed to be an important causal factor in the development of diabetic retinopathy. The intracellular glucose concentration is regulated by both the rate of glucose metabolism and glucose transport. Because retinal hypoxia often precedes proliferative diabetic retinopathy, we have studied the regulation of the glucose transport system by hypoxia in cultured bovine retinal endothelial cells (BRECs). Because retinal ischemia is known to increase intracellular adenosine levels, which subsequently regulate hypoxia-inducible genes, such as vascular endothelial growth factor and erythropoietin, the role of adenosine and its receptor-mediated pathways has also been evaluated. Hypoxia (0.5% O(2), 5% CO(2), and 94.5% N(2)) stimulated GLUT1 mRNA expression in BRECs in a time-dependent manner with an 8.9 +/- 1.5-fold (P < 0.01) increase observed after 12 h. GLUT1 mRNA expression returned to baseline (1.4 +/- 0.3-fold of control) within 12 h after reinstitution of normoxia. N(6)-Cyclopentyl adenosine (adenosine A(1) receptor agonist, K(d) = 1 nmol/l) did not affect GLUT1 mRNA expression at concentrations up to 1 pmol/l, while 2-p-(2-carboxyethyl)-phenethyl-amino-5'-N-ethylcarboxamidoadenosine and 5'-(N-ethylcalboxamido)-adenosine (adenosine A(2) receptor [A(2)R] agonists, K(d) = 15 and 16 nmol/l, respectively) increased mRNA levels at concentrations as low as 10 nmol/l. Maximal stimulation was 2.3 +/- 0.2- and 2.1 +/- 0.2-fold, respectively (P < 0.01). The adenosine A,, receptor antagonist 8-(3-chlorostyryl)caffeine (CSC) (K(d) = 100 nmol/l for A(2)R) inhibited hypoxia-stimulated GLUT1 mRNA expression by 40 +/- 8% at 100 nmol/l. Hypoxia upregulated GLUT1 protein expression by 3.0 +/- 0.3-fold after 12 h (P < 0.01), but this response was attenuated by CSC (P < 0.05). Hypoxia increased glucose transport activity by 2.1 +/- 0.3-fold (P < 0.001) after 12 h, a response inhibited 65% by CSC (P < 0.01). A protein kinase A (PKA) inhibitor (H89, 20 mu mol/l) suppressed hypoxia-induced GLUT1 mRNA expression by 42 +/- 9% (P < 0.01). These data suggest that hypoxia in BRECs upregulates glucose transport activity through an increase of GLUT1 expression that is partially mediated by adenosine, A(2)R, and the cAMP-PKA pathway. C1 Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Aiello, LP (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM aiellol@joslab.harvard.edu FU NEI NIH HHS [EY09178, EY10827]; PHS HHS [36836] NR 49 TC 51 Z9 53 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 1998 VL 47 IS 9 BP 1480 EP 1488 DI 10.2337/diabetes.47.9.1480 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 113FD UT WOS:000075539000015 PM 9726238 ER PT J AU Larme, AC Pugh, JA AF Larme, AC Pugh, JA TI Attitudes of primary care providers toward diabetes - Barriers to guideline implementation SO DIABETES CARE LA English DT Article; Proceedings Paper CT 55th Annual Meeting and Scientific Sessions of the American-Diabetes-Association CY JUN 10-13, 1995 CL ATLANTA, GEORGIA SP Amer Diabet Assoc ID STAGE RENAL-DISEASE; PRACTICE BEHAVIORS; MANAGEMENT; PATIENT; NIDDM; ORGANIZATION; PHYSICIANS; MELLITUS AB OBJECTIVE - Primary care providers have been slow to adopt standards of care for diabetes, and continuing medical education (CME) programs have been minimally effective in changing provider behavior. The objective of this study was to explore the previously reported finding that attitudes, rather than knowledge, may impede primary care provider adherence to standards of care. RESEARCH DESIGN AND METHODS - Study participants included 31 primary care providers attending an eight-session CME program on diabetes. Providers rated on a 10-point scale how the treatment of diabetes compared with that of five other chronic conditions (hypertension, hyperlipidemia, angina, arthritis, and heart failure; 1 = easier to 10 = harder; midpoint 5.5). In a subsequent open-ended qualitative interview providers explained their scale ratings. RESULTS - Diabetes was rated as significantly harder to treat than hypertension (24 of 30 >5.5; P < 0.001) and angina (20 of 30 >5.5; P = 0.03). A majority also rated hyperlipidemia (18 of 30) and arthritis (18 of 30) as easier to treat than diabetes. Explanatory themes underlying provider frustrations with diabetes include characteristics of the disease itself and the complexity of its management, and a perceived lack of support from society and the health care system for their efforts to control diabetes. CONCLUSIONS - CME that addresses provider attitudes toward diabetes in addition to updating knowledge may be more effective than traditional CME in promoting adherence to standards of care. Additional changes are needed in our health care system to shift from an acute to a chronic disease model to effectively support diabetes care efforts. C1 Univ Texas, Hlth Sci Ctr, Dept Orthodont, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Larme, AC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Orthodont, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM larme@uthscsa.edu OI Pugh, Jacqueline/0000-0003-4933-141X FU AHRQ HHS [HS07397] NR 29 TC 160 Z9 163 U1 2 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 1998 VL 21 IS 9 BP 1391 EP 1396 DI 10.2337/diacare.21.9.1391 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 113MZ UT WOS:000075556800003 PM 9727882 ER PT J AU Horton, ES Whitehouse, F Ghazzi, MN Venable, TC Whitcomb, RW AF Horton, ES Whitehouse, F Ghazzi, MN Venable, TC Whitcomb, RW CA Troglitazone Study Grp TI Troglitazone in combination with sulfonylurea restores glycemic control in patients with type 2 diabetes SO DIABETES CARE LA English DT Article ID ORAL HYPOGLYCEMIC AGENT; INSULIN-RESISTANCE; MELLITUS; NIDDM; CS-045; ABNORMALITIES; THERAPY AB OBJECTIVE - To determine if the combination of troglitazone (a peroxisome proliferator-activated receptor-gamma activator) and sulfonylurea will provide efficacy not attainable by either medication alone. RESEARCH DESIGN AND METHODS - There were 552 patients inadequately controlled on maximum doses of sulfonylurea who participated in a 52-week randomized active-controlled multicenter study. Patients were randomized to micronized glyburide 12 mg q.d. (G12); troglitazone monotherapy 200, 400, or 600 mg q.d. (T200, T400, T600); or combined troglitazone and glyburide q.d. (T200/G12, T400/G12, T600/G12). Efficacy measures included HbA(1c), fasting serum glucose (FSG), insulin, and C-peptide. Effects on lipids and safety were also assessed. RESULTS - Patients on T600/G12 had significantly lower mean (+/- SEM) FSG (9.3 +/- 0.4 mmol/l; 167.4 +/- 6.6 mg/dl) compared with control subjects (13.7 +/- 0.4 mmol/l; 246.5 +/- 6.8 mg/dl; P < 0.0001) and significantly lower mean HbA(1c) (7.79 +/- 0.2 vs. 10.58 +/- 0.18%, P < 0.0001). Significant dose-related decreases were also seen with T200/G12 and T400/G12. Among patients on T600/G12, 60% achieved HbA(1c) less than or equal to 8%, 42% achieved HbA(1c) less than or equal to 7%, and 40% achieved FSG less than or equal to 7.8 mmol/l (140 mg/dl). Easting insulin and C-peptide decreased with all treatments. Overall, triglycerides and free fatty acids decreased, whereas HDL cholesterol increased. LDL cholesterol increased slightly, with no change in apolipoprotein B. Adverse events were similar across treatments. Hypoglycemia occurred in 3% of T600/G12 patients compared with <1% on G12 or troglitazone monotherapy. CONCLUSIONS - Patients with type 2 diabetes inadequately controlled on sulfonylurea can be effectively managed with a combination of troglitazone and sulfonylurea that is safe, well tolerated, and represents a new approach to achieving the glycemic targets recommended by the American Diabetes Association. C1 Parke Davis Pharmaceut Res, Clin Res Diabet & Metab Dis, Ann Arbor, MI 48105 USA. Henry Ford Hosp, Detroit, MI 48202 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Ghazzi, MN (reprint author), Parke Davis Pharmaceut Res, Clin Res Diabet & Metab Dis, 2800 Plymouth Rd, Ann Arbor, MI 48105 USA. NR 26 TC 99 Z9 100 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 1998 VL 21 IS 9 BP 1462 EP 1469 DI 10.2337/diacare.21.9.1462 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 113MZ UT WOS:000075556800013 PM 9727892 ER PT J AU Furuta, GT Wang, ZS Wershil, BK AF Furuta, GT Wang, ZS Wershil, BK TI Gastric inflammation during systemic anaphylaxis - Neutrophil recruitment in stomach wall of mice does not require mast cell participation SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE anaphylaxis; mast cell; neutrophil; mucosa; submucosa; cromolyn; stomach; degranulation ID INDUCED INTESTINAL ANAPHYLAXIS; DEFICIENT W/WV MICE; FC-GAMMA-RIII; DISODIUM-CROMOGLYCATE; RAT; SECRETION; MOUSE; IGE; HYPERSENSITIVITY; DEGRANULATION AB We determined whether neutrophil infiltration into the stomach wall occurred during systemic anaphylaxis in mice and assessed the participation of mast cells in the response. Normal mice sensitized and challenged with antigen exhibited significant neutrophil infiltration in the gastric mucosa and submucosa compared with saline-challenged mice. The development of clinical signs of anaphylaxis and extent of gastric neutrophil infiltration was similar in mast cell-deficient Kit(W)/Kit(W-v) or Mgf(Sl)/Mgf(Sl-d) mice and the respective normal congenic mice. Pretreatment with sodium cromoglycate prevented the clinical signs of anaphylaxis and significantly diminished the infiltration of neutrophils in +/+ or kit(W)/Kit(W-v) mice. Systemic anaphylaxis is associated with neutrophil infiltration into the stomach wall in mice, and mast cells are not required for the development of either the clinical manifestations or gastric neutrophil infiltration observed in the response. C1 Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. Childrens Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Expt Pathol, Boston, MA USA. Harvard Med Sch, Boston, MA USA. RP Wershil, BK (reprint author), Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, 149 13th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK40561, DK46819, DK33506] NR 34 TC 4 Z9 5 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD SEP PY 1998 VL 43 IS 9 BP 2021 EP 2027 DI 10.1023/A:1018851012940 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 121DP UT WOS:000075997300016 PM 9753268 ER PT J AU Adams, JC Seed, B Lawler, J AF Adams, JC Seed, B Lawler, J TI Muskelin, a novel intracellular mediator of cell adhesive and cytoskeletal responses to thrombospondin-1 SO EMBO JOURNAL LA English DT Article DE cell adhesion; extracellular matrix; fascin microspike; kelch motif ID ACTIN-BUNDLING PROTEIN; PLATELET THROMBOSPONDIN; EXTRACELLULAR-MATRIX; SIGNAL-TRANSDUCTION; NUCLEOTIDE-SEQUENCE; FASCIN MICROSPIKES; SURFACE RECEPTORS; MOLECULAR-CLONING; DROSOPHILA KELCH; TENASCIN AB We have used an expression cloning strategy based on a cell-attachment assay screen to seek identification of molecules required in cellular responses to thrombospondin-1, a regulated macromolecular component of extracellular matrix. We report the identification and functional characterization of a novel, widely expressed, intracellular protein, named muskelin, which contains dispersed motifs with homology to the tandem repeats first identified in the Drosophila kelch ORF1 protein. In adherent C2C12 cells, muskelin localizes in the cytoplasm and at cell margins. Overexpression of muskelin in C2C12 cells promotes cell attachment to the thrombospondin-1 C-terminal domain, alters the mechanisms of attachment to intact thrombospondin-1 and correlates with decreased formation of fascin microspikes and increased assembly of focal contacts by cells adherent on thrombospondin-1, Reciprocally, cell attachment, spreading and cytoskeletal organization are specifically reduced in TSP-1-adherent cells after antisense depletion of muskelin, These results establish a requirement for muskelin in cell responses to thrombospondin-1 and demonstrate that such responses involve a novel process which is integrated into the regulation of cell-adhesive behaviour and cytoskeletal organization. C1 UCL, MRC, Mol Cell Biol Lab, London WC1E 6BT, England. UCL, Dept Biochem & Mol Biol, London WC1E 6BT, England. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Adams, JC (reprint author), UCL, MRC, Mol Cell Biol Lab, Gower St, London WC1E 6BT, England. EM dmcbjca@ucl.ac.uk RI Adams, Josephine/B-1121-2009 FU NHLBI NIH HHS [HL 28749, HL 49081]; Wellcome Trust NR 58 TC 56 Z9 59 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD SEP 1 PY 1998 VL 17 IS 17 BP 4964 EP 4974 DI 10.1093/emboj/17.17.4964 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 119PG UT WOS:000075904700007 PM 9724633 ER PT J AU Daniel, PB Habener, JF AF Daniel, PB Habener, JF TI Cyclical alternative exon splicing of transcription factor cyclic adenosine monophosphate response element-binding protein (CREB) messenger ribonucleic acid during rat spermatogenesis SO ENDOCRINOLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; STAGE-SPECIFIC EXPRESSION; SERTOLI-CELLS; SEMINIFEROUS EPITHELIUM; GENE-TRANSCRIPTION; FSH RECEPTOR; MODULATOR; ISOFORMS; TESTIS; RNA AB During spermatogenesis, the levels of cAMP in seminiferous tubules undergo stage-dependent cyclical fluctuations. We show that changes in cAMP levels are accompanied by alternative exon splicing of the RNA encoding the cAMP-responsive transcription factor CREB (cAMP response element-binding protein), expressed in both the Sertoli and germ cells. Exons Y and W are expressed exclusively in the testis, and they introduce stop codons into the normal protein coding frame of CREB. The splicing in of W was shown earlier to activate the internal translation of two alternative products of the CREB messenger RNA (mRNA) containing the DNA-binding domain (I-CREBs). The I-CREBs act as potent inhibitors of activator isoforms of CREB. The functions of the alternatively spliced exon Y are unknown. To investigate whether the splicing of exons W and Y is regulated during spermatogenesis, seminiferous tubules, isolated from adult rats, were dissected into segments representing different stages of the spermatogenic cycle and were analyzed by RT-PCR. The analyses of pooled-tubule segments revealed stage-dependent splicing of both exons W and Y in the CREB transcripts. Single tubules were dissected into smaller segments for greater staging accuracy and were analyzed by RT-PCR for CREB mRNAs containing either exons W or Y, as well as for FSH receptor mRNA. This analysis confirmed that a marked, cycle-dependent variation in CREB mRNA levels was occurring. Maximal splicing of exons W and Y occurs independently at different stages of the spermatogenic cycle, stages II-VI and IX, respectively. The distinct spermatogenic cycle-dependent regulation of the splicing of exons W and Y provides further evidence in support of a functional relevance for CREB-W and Y mRNA isoforms in spermatogenesis. C1 Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Habener, JF (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, 55 Fruit St,WEL320, Boston, MA 02114 USA. EM habenej@a1.mgh.harvard.edu FU NIDDK NIH HHS [DK-25532] NR 23 TC 16 Z9 16 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 SEP PY 1998 VL 139 IS 9 BP 3721 EP 3729 DI 10.1210/en.139.9.3721 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 112NK UT WOS:000075500500007 PM 9724023 ER PT J AU Martinez, V Wu, SV Tache, Y AF Martinez, V Wu, SV Tache, Y TI Intracisternal antisense oligodeoxynucleotides to the thyrotropin-releasing hormone receptor blocked vagal-dependent stimulation of gastric emptying induced by acute cold in rats SO ENDOCRINOLOGY LA English DT Article ID DORSAL MOTOR NUCLEUS; CENTRAL-NERVOUS-SYSTEM; RAPHE PALLIDUS; SECRETORY RESPONSE; LESION FORMATION; TRH; ACID; NEURONS; COMPLEX; RESTRAINT AB Cold exposure increases TRK gene expression in hypothalamic and raphe nuclei and results in a vagal activation of gastric function. We investigated the role of medullary TRH receptors in cold (4-6 C, 90 min)-induced stimulation of gastric motor function in fasted conscious rats using intracisternal injections of TRH receptor (TRHr) antisense oligodeoxynucleotides (100 mu g twice, -48 and - 24 h). The gastric emptying of a methyl-cellulose solution was assessed by the phenol red method. TRH (0.1 mu g) or the somatostatin subtype 5-preferring analog, BIM-23052 (1 mu g), injected intracisternally increased basal gastric emptying by 34% and 47%, respectively. TRHr antisense, which had no effect on basal emptying, blocked TRH action but did not influence that of BIM-23052. Cold exposure increased gastric emptying by 64%, and the response was inhibited by vagotomy, atropine (0.1 mg/kg, ip), and TRHr antisense (intracisternally). Saline or mismatched oligodeoxynucleotides, injected intracisternally under similar conditions, did not alter the enhanced gastric emptying induced by cold or intracisternal injection of TRH or BIM-23052. These results indicate that TRH receptor activation in the brain stem mediates acute cold-induced vagal cholinergic stimulation of gastric transit, and that medullary TRH may play a role in the autonomic visceral responses to acute cold. C1 W Los Angeles Vet Affairs Med Ctr, Digest Dis Res Ctr, CURE, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), W Los Angeles Vet Affairs Med Ctr, Digest Dis Res Ctr, CURE, Bldg 115,Room 203,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@uda.edu RI Martinez, Vicente/N-1189-2014 NR 45 TC 32 Z9 32 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1998 VL 139 IS 9 BP 3730 EP 3735 DI 10.1210/en.139.9.3730 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 112NK UT WOS:000075500500008 PM 9724024 ER PT J AU Li, GD Segu, VBG Rabaglia, ME Luo, RH Kowluru, A Metz, SA AF Li, GD Segu, VBG Rabaglia, ME Luo, RH Kowluru, A Metz, SA TI Prolonged depletion of guanosine triphosphate induces death of insulin-secreting cells by apoptosis SO ENDOCRINOLOGY LA English DT Article ID GTP-BINDING PROTEINS; LOVASTATIN-INDUCED APOPTOSIS; CEREBELLAR GRANULE NEURONS; HUMAN PANCREATIC-ISLETS; INTACT RAT ISLETS; BETA-CELLS; MYCOPHENOLATE-MOFETIL; DNA-SYNTHESIS; MACROMOLECULAR-SYNTHESIS; NUCLEOTIDE PRECURSORS AB Inhibitors of IMP dehydrogenase, such as mycophenolic acid (MPA) and mizoribine, which deplete cellular GTP, are used clinically as immunosuppressive drugs. The prolonged effect of such agents on insulin-secreting beta-cells (HIT-T15 and INS-1) was investigated. Both MPA and mizoribine inhibited mitogenesis, as reflected by [H-3]thymidine incorporation. Cell number, DNA and protein contents, and cell (metabolic) viability were decreased by about 30%, 60%, and 80% after treatment of HIT cells with clinically relevant concentrations (e.g. 1 mu g/ml) of MPA for 1, 2, and 4 days, respectively. Mizoribine (48 h) similarly induced the death of HIT cells. INS-1 cells also were damaged by prolonged MPA treatment. MPA-treated HIT cells displayed a strong and localized staining with a DNA-binding dye (propidium iodide), suggesting condensation and fragmentation of DNA, which were confirmed by detection of DNA laddering in multiples of about 180 bp. DNA fragmentation was observed after 24-h MPA treatment and was dose dependent (29%, 49%, and 70% of cells were affected after 48-h exposure to 1, 3, and 10 mu g/ml MPA, respectively). Examination of MPA-treated cells by electron microscopy revealed typical signs of apoptosis: condensed and marginated chromatin, apoptotic bodies, cytosolic vacuolization, and loss of microvilli, MPA-induced cell death was almost totally prevented by supplementation with guanosine, but not with adenosine or deoxyguanosine, indicating a specific effect of GTP depletion. An inhibitor of protein isoprenylation (lovastatin, 10-100 mu M for 2-3 days) induced cell death and DNA degradation similar to those induced by sustained GTP depletion, suggesting a mediatory role of posttranslationally modified GTP-binding proteins. Indeed, impeding the function of G proteins of the Rho family (via glucosylation using Clostridium difficile toxin B), although not itself inducing apoptosis, potentiated cell death induced by MPA or lovastatin. These findings indicate that prolonged depletion of GTP induces beta-cell death compatible with apoptosis; this probably involves a direct impairment of GTP-dependent RNA-primed DNA synthesis, but also appears to be modulated by small GTP-binding proteins. Treatment of intact adult rat islets (the beta-cells of which replicate slowly) induced a modest, but definite, death by apoptosis over 1- to 3-day periods. Thus, more prolonged use of the new generation of immunosuppressive agents exemplified by MPA might have deleterious effects on the survival of islet or pancreas grafts. C1 Natl Univ Singapore, Natl Univ Med Inst, Singapore 119260, Singapore. William S Middleton Mem Vet Adm Med Ctr, Endocrinol Sect, Med Serv, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Dept Med, Div Endocrinol, Madison, WI 53792 USA. RP Li, GD (reprint author), Natl Univ Singapore, Natl Univ Med Inst, MD 11 02-01,10 Kent Ridge Crescent, Singapore 119260, Singapore. EM nmiligd@med2.nusstf.nus.sg FU NIDDK NIH HHS [DK-37312] NR 76 TC 51 Z9 52 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 SEP PY 1998 VL 139 IS 9 BP 3752 EP 3762 DI 10.1210/en.139.9.3752 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 112NK UT WOS:000075500500011 PM 9724027 ER PT J AU Fisher, JS Turner, KJ Fraser, HM Saunders, PTK Brown, D Sharpe, RM AF Fisher, JS Turner, KJ Fraser, HM Saunders, PTK Brown, D Sharpe, RM TI Immunoexpression of Aquaporin-1 in the efferent ducts of the rat and marmoset monkey during development, its modulation by estrogens, and its possible role in fluid resorption SO ENDOCRINOLOGY LA English DT Article ID CHIP28 WATER CHANNELS; RECEPTOR GENE; AROMATASE DEFICIENCY; REPRODUCTIVE-SYSTEM; SEXUAL DEVELOPMENT; EXCURRENT DUCTS; EPIDIDYMIS; TESTIS; LOCALIZATION; CELLS AB Recent data suggest that estrogens play a role in regulating fluid resorption from the efferent ducts, though the biochemical mechanisms involved are unknown. The present study has used immunocytochemistry to localize a water channel protein, Aquaporin-1 (AQP-1), to the efferent ducts of male rats and marmoset monkeys from perinatal life through to adulthood and has then investigated its potential hormonal regulation in neonatal/peripubertal life, via administration of a GnRH antagonist (GnRHa) or diethylstilbestrol (DES) to rats. AQP-1 was immunoexpressed intensely in the apical brush border of the epithelium lining the efferent ducts at all ages studied, from late fetal life through puberty to adulthood. In the marmoset, but not the rat, AQP-1 was also expressed in the epithelium of the rete testis. Once the cell types within the efferent duct epithelium had differentiated, it was clear that only nonciliated cells of the rat localized AQP-1. When gonadotropin secretion was suppressed in rats by neonatal administration of GnRHa, immunoexpression of AQP-1 at age 18 and 25 days was virtually unchanged in intensity, though the efferent ducts were reduced in size. In contrast, when DES was administered neonatally to rats (up to day 12), immunoexpression of AQP-1 was reduced at day 10, virtually abolished at day 18, reduced markedly at day 25 and to a small extent at day 35; these findings were confirmed by Western blot analysis at day 18. The DES-induced decrease in immunoexpression of AQP-1 was accompanied by pronounced distension of the efferent ducts and rete, consistent with reduced fluid resorption. The epithelial cells of the efferent ducts in DES-treated rats were cuboidal rather than columnar in shape as in controls and were reduced significantly in height compared with controls at all ages through to adulthood. These findings suggest that estrogens may play a role in regulating fluid resorption from the efferent ducts during fetal/neonatal development and/or a role in the gross and functional development of the efferent ducts and rete testis. The present data also suggest that AQP-1 is one of the elements involved in the regulation of fluid resorption in the efferent ducts. The importance of fluid flow in fetal/neonatal development of the excurrent duct system of the male is also suggested by these observations. C1 Univ Edinburgh, Ctr Reprod Biol, Reprod Biol Unit, Edinburgh EH3 9EW, Midlothian, Scotland. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02129 USA. RP Sharpe, RM (reprint author), Univ Edinburgh, Ctr Reprod Biol, Reprod Biol Unit, Edinburgh EH3 9EW, Midlothian, Scotland. RI Saunders, Philippa/C-7489-2013; Sharpe, Richard/D-2725-2013 OI Saunders, Philippa/0000-0001-9051-9380; Sharpe, Richard/0000-0003-1686-8085 FU NIDDK NIH HHS [DK-38452] NR 40 TC 90 Z9 93 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1998 VL 139 IS 9 BP 3935 EP 3945 DI 10.1210/en.139.9.3935 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 112NK UT WOS:000075500500034 PM 9724049 ER PT J AU Yip, RGC Boylan, MO Kieffer, TJ Wolfe, MM AF Yip, RGC Boylan, MO Kieffer, TJ Wolfe, MM TI Functional GIP receptors are present on adipocytes SO ENDOCRINOLOGY LA English DT Article ID GASTRIC-INHIBITORY POLYPEPTIDE; DEPENDENT INSULINOTROPIC POLYPEPTIDE; RAT ADIPOSE-TISSUE; TEST MEAL; GLUCOSE; OBESE; FAT; STIMULATION; LIPOLYSIS; METABOLISM AB In addition to its important role in maintaining glucose homeostasis, it has recently become apparent that glucose-dependent insulinotropic polypeptide (GIP) is also involved in different steps of lipid metabolism. GIP has been shown to stimulate the release of lipoprotein lipase from fat, as well as increase the rate of fat incorporation into adipose tissue. Moreover, GIP has been shown to increase the clearance rate of chylomicrons in the circulation and to inhibit the action of glucagon. Despite evidence for GIP effects on fat tissue, GIP receptors have not been identified in fat cells or tissues. The present study was undertaken to identify GIP receptors in isolated adipocytes, as well as to identify GD? receptors in the established fat cell line, differentiated 3T3-L1. RNAse protection analysis demonstrated the presence of GIP receptor transcripts in rat adipocytes. A polyclonal GIP receptor antiserum directed at the N-terminus of the receptor detected the presence of GIP receptors in both rat fat and differentiated 3T3-L1 cells by Western blot analysis. Moreover, [I-125] GIP binding assays revealed both specific and displaceable GIP binding sites in differentiated 3T3-L1 cells (IC50 = 10(-9) M). When undifferentiated 3T3-L1 cells, which appear to express relatively few GIP receptors, were incubated in the presence of GIP, no effect on intracellular cAMP accumulation was detected. In contrast, the inclusion of 10 nM GIP in the incubation medium increased cAMP accumulation in rat fat cells and differentiated 3T3-L1 cells. This increase in cAMP accumulation was abolished with the specific GIP receptor antagonist GIP(7-30)NH2. The results of these studies indicate that GTP receptors are present in fat cells and are up-regulated when 3T3-L1 cells undergo differentiation to become adipocytes. Furthermore, the increase in intracellular cAMP accumulation detected upon ligand binding indicates that these receptors are functional. C1 Boston Med Ctr, Gastroenterol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Wolfe, MM (reprint author), Boston Med Ctr, Gastroenterol Sect, Boston, MA 02118 USA. FU NIDDK NIH HHS [R01-DK53158] NR 22 TC 132 Z9 138 U1 0 U2 4 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 SEP PY 1998 VL 139 IS 9 BP 4004 EP 4007 DI 10.1210/en.139.9.4004 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 112NK UT WOS:000075500500042 PM 9724057 ER PT J AU David, D Bani, L Moreau, JL Treilhou, MP Demaison, C Sun, K Fevrier, M Salvucci, O Cayota, A Nakarai, T Chouaib, S de Montalembert, M Joussemet, M Sugamura, K Ritz, J Dupont, B Pialoux, G Theze, J AF David, D Bani, L Moreau, JL Treilhou, MP Demaison, C Sun, K Fevrier, M Salvucci, O Cayota, A Nakarai, T Chouaib, S de Montalembert, M Joussemet, M Sugamura, K Ritz, J Dupont, B Pialoux, G Theze, J TI Dysregulation of interleukin-2 receptor beta and interleukin-2 receptor gamma expression during HIV infection SO EUROPEAN CYTOKINE NETWORK LA English DT Article; Proceedings Paper CT Vth International Workshop on Cytokines at the Joint Meeting of the Ares-Sereno Foundation / European-Cytokine-Society CY MAR 16-18, 1998 CL FLORENCE, ITALY SP Ares-Sereno Fdn, European Cytokine Soc ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACQUIRED IMMUNE-DEFICIENCY; IL-2 RECEPTOR; CHAIN EXPRESSION; T-LYMPHOCYTES; ALPHA-CHAIN; CELLS; INDIVIDUALS; GENE; AIDS C1 Inst Pasteur, Unite Immunogenet Cellulaire, Dept Immunol, F-75724 Paris 15, France. Hop Inst Pasteur, Paris, France. Inst Pasteur, Unite Virol Immunol Cellulaire, Dept SIDA & Retrovirus, Paris, France. Inst Gustave Roussy, Immunol Lab, Villejuif, France. Inst Pasteur, Unite Immunol & Immunopathol, Dept Physiolpathol, F-75724 Paris, France. Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. Hop Necker Enfants Malad, Paris, France. Ctr Transfus Sanguine Jean Julliard, Clamart, France. Tohoku Univ, Sch Med, Dept Microbiol, Sendai, Miyagi 980, Japan. RP Theze, J (reprint author), Inst Pasteur, Unite Immunogenet Cellulaire, Dept Immunol, 25-28 Rue Dr Roux, F-75724 Paris 15, France. EM jtheze@pasteur.fr RI Chouaib, Salem/F-7939-2016; OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA41619] NR 38 TC 2 Z9 2 U1 0 U2 1 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1148-5493 J9 EUR CYTOKINE NETW JI Eur. Cytokine Netw. PD SEP PY 1998 VL 9 SU 3 BP 97 EP 101 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 136YD UT WOS:000076885900018 PM 9831196 ER PT J AU Bani, L David, D Fevrier, M Moreau, JL Cayota, A Nakarai, T Sugamura, K Ritz, J Theze, J AF Bani, L David, D Fevrier, M Moreau, JL Cayota, A Nakarai, T Sugamura, K Ritz, J Theze, J TI Interleukin-2 gamma chain: Intracellular expression on resting CD4 T cells and dysregulation by HIV-1 GP120 in activated CD4 T lymphocytes. SO EUROPEAN CYTOKINE NETWORK LA English DT Meeting Abstract C1 Inst Pasteur, Paris, France. Dana Farber Canc Inst, Div Hematol Malignancies & Tumor Immunol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1148-5493 J9 EUR CYTOKINE NETW JI Eur. Cytokine Netw. PD SEP PY 1998 VL 9 IS 3 MA 181 BP 396 EP 396 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 136CD UT WOS:000076839700216 ER PT J AU David, D Bani, L Moreau, JL Treilhou, MP Nakarai, T Joussemet, M Ritz, J Dupont, B Pialoux, G Theze, J AF David, D Bani, L Moreau, JL Treilhou, MP Nakarai, T Joussemet, M Ritz, J Dupont, B Pialoux, G Theze, J TI Impact of triple combination therapy on the IL-2 reactivity of CD4 and CD8 T lymphocytes from HIV-infected patients SO EUROPEAN CYTOKINE NETWORK LA English DT Meeting Abstract C1 Inst Pasteur, Paris, France. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1148-5493 J9 EUR CYTOKINE NETW JI Eur. Cytokine Netw. PD SEP PY 1998 VL 9 IS 3 MA 202 BP 396 EP 396 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 136CD UT WOS:000076839700215 ER PT J AU Hussain, MA AF Hussain, MA TI A biological function for glucagon-like peptide-2 SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID GENE-EXPRESSION; RAT; RELEASE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Endocrinol Lab, Boston, MA 02114 USA. RP Hussain, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Endocrinol Lab, Wellman 320,50 Blossom St, Boston, MA 02114 USA. NR 25 TC 2 Z9 3 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD SEP PY 1998 VL 139 IS 3 BP 265 EP 267 DI 10.1530/eje.0.1390265 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 123YQ UT WOS:000076153600005 PM 9758434 ER PT J AU Litvan, I Jankovic, J Goetz, CG Wenning, GK Sastry, N Jellinger, K McKee, A Lai, EC Brandel, JP Verny, M Ray-Chaudhuri, K Pearce, RKB Bartko, JJ Agid, Y AF Litvan, I Jankovic, J Goetz, CG Wenning, GK Sastry, N Jellinger, K McKee, A Lai, EC Brandel, JP Verny, M Ray-Chaudhuri, K Pearce, RKB Bartko, JJ Agid, Y TI Accuracy of the clinical diagnosis of postencephalitic parkinsonism: a clinicopathologic study SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE accuracy; diagnosis; postencephalitic parkinsonism; pathology ID PROGRESSIVE SUPRANUCLEAR PALSY; POST-ENCEPHALITIC PARKINSONISM; RICHARDSON-OLSZEWSKI SYNDROME; ALZHEIMERS-DISEASE; LETHARGICA; INFLUENZA; CRITERIA; OVERLAP AB The accuracy of the clinical diagnosis of postencephalitic parkinsonism (PEP) is unknown. We determined the validity of the clinical diagnosis of PEP by presenting 105 records with neuropathologic diagnoses of PEP (n = 7), progressive supranuclear palsy (n = 24), Parkinson's disease (n = 15), dementia with Lewy bodies (n = 14), multiple system atrophy (n = 16), corticobasal degeneration (n = 10), Creutzfeldt-Jakob disease (n = 4), and other dementia disorders (n = 15), as clinical vignettes to six neurologists unaware of the autopsy findings. The neurologists' own clinical diagnoses were compared with neuropathologic diagnoses for measures of diagnostic accuracy, including reliability (kappa statistics), sensitivity and positive predictive values for the first and last visits. The group reliability for the diagnosis of PEP was almost perfect (kappa = 0.91, 0.9). The mean sensitivity at the first visit was 86% (range, 71-100%) with minimal change at the last visit (83%; range, 71-100%). Positive predictive values remained unchanged (100%). The high reliability, sensitivity and positive predictive values of the clinical diagnosis of PEP indicate that neurologists identify this disorder even when they report that they have never evaluated a case. In our data set, the best predictors for the diagnosis of PEP included onset below middle age; symptom duration lasting more than 10 years, and the presence of oculogyric crisis. History of encephalitis lethargica, present in most PEP cases, was an important individual diagnostic predictor. (C) 1998 Lippincott Williams & Wilkins. C1 NINDS, Neuroepidemiol Branch, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Rush Med Coll, Dept Neurol, Chicago, IL 60612 USA. Inst Neurol, London WC1N 3BG, England. Lainz Hosp, Ludwig Boltzmann Inst Clin Neurobiol, A-1130 Vienna, Austria. Massachusetts Gen Hosp, Dept Neuropathol, Boston, MA 02114 USA. Hop La Pitie Salpetriere, INSERM, Raymond Escourolle Neuropathol Lab, U360, Paris, France. Inst Psychiat, Dept Neurol, London SE5 8AF, England. Inst Neurol, Parkinsons Dis Soc Brain Tissue Bank, London WC1N 3BG, England. NIMH, Div Epidemiol & Res Studies, Bethesda, MD 20892 USA. Hop La Pitie Salpetriere, Federat Neurol, Paris, France. Hop La Pitie Salpetriere, INSERM, U289, Paris, France. RP Litvan, I (reprint author), NINDS, Neuroepidemiol Branch, NIH, Bethesda, MD 20892 USA. OI Litvan, Irene/0000-0002-3485-3445; Ray Chaudhuri, K/0000-0003-2815-0505 NR 37 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 1998 VL 5 IS 5 BP 451 EP 457 DI 10.1046/j.1468-1331.1998.550451.x PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 128DL UT WOS:000076389900004 ER PT J AU Jacobson, AF Fogelman, I AF Jacobson, AF Fogelman, I TI Bone scanning in clinical oncology: does it have a future? SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material ID BREAST-CANCER; FOLLOW-UP; METASTASES; ABNORMALITIES; REAPPRAISAL; SCANS C1 VA Puget Sound Hlth Care Syst, Dept Radiol, Nucl Med Sect, Seattle, WA 98108 USA. United Med & Dent Sch Guys & St Thomas, Div Radiol Sci, London SE1 9RT, England. Guys Hosp, Div Radiol Sci, London SE1 9RT, England. RP Jacobson, AF (reprint author), VA Puget Sound Hlth Care Syst, Dept Radiol, Nucl Med Sect, Seattle, WA 98108 USA. NR 19 TC 43 Z9 44 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6997 J9 EUR J NUCL MED JI Eur. J. Nucl. Med. PD SEP PY 1998 VL 25 IS 9 BP 1219 EP 1223 DI 10.1007/s002590050287 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 121QW UT WOS:000076025700001 PM 9724368 ER PT J AU Pratt, H Polyakov, A Aharonson, V Korczyn, AD Tadmor, R Fullerton, BC Levine, RA Furst, M AF Pratt, H Polyakov, A Aharonson, V Korczyn, AD Tadmor, R Fullerton, BC Levine, RA Furst, M TI Effects of localized pontine lesions on auditory brain-stem evoked potentials and binaural processing in humans SO EVOKED POTENTIALS-ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE binaural interaction components; auditory brain-stem; evoked potential; generator; human; stroke ID SUPERIOR OLIVARY COMPLEX; INDUCED NEURONAL LOSS; MULTIPLE-SCLEROSIS; CLICK LATERALIZATION; INTERAURAL TIME; RESPONSES ABRS; GUINEA-PIG; INTENSITY DIFFERENCES; TRAPEZOID BODY; CAT AB Objectives and methods: Four sets of measurements were obtained from 11 patients (44-80 years old) with small, localized pontine lesions due to vascular disease: (1) Monaural auditory brain-stem evoked potentials (ABEPs; peaks I to VI); (2) Binaural ABEPs processed for their binaural interaction components (BICs) in the latency range of peaks IV to VI; (3) magnetic resonance imaging (MRI) of the brainstem; and (4) psychoacoustics of interaural time disparity measures of binaural localization. ABEPs and BICs were analyzed for peak latencies and interpeak latency differences. Three-channel Lissajous' trajectories (3-CLTs) were derived for ABEPs and BICs and the latencies and orientations of the equivalent dipoles of ABEP and BICs were inferred from them. Results: Intercomponent latency measures of monaurally evoked,ABEPs were abnormal in only 3 of the 11 patients. Consistent correlations between sites of lesion and neurophysiological abnormality were obtained in 9 of the 11 patients using 3-CLT measures of BICs. Six of the 11 patients had absence of one or more BIC components. Seven of the 11 had BICs orientation abnormality and 3 had latency abnormalities, Trapezoid body (TB) lesions (6 patients) were associated with an absent (two patients with ventral-caudal lesions) or abnormal tone patient with ventral-rostral lesions) dipole orientation of the first component (at the time of ABEPs IV), and sparing of this component with midline ventral TB lesions (two patients). A deviant orientation of the second BICs component tar the time of ABEPs V) was observed with ventral TB lesions. Psychoacoustic lateralization in these patients was biased toward the center. Rostral lateral lemniscus (LL) lesions (3 patients) were associated with absent tone patient) or abnormal (two patients) orientation of the third BICs component (at the time of ABEPs VI); and a side-biased lateralization with behavioral testing. Conclusions: These results indicate that: (I) the BICs component occurring at the time of ABEPs peak IV is dependent on ventral-caudal TB integrity; (2) the ventral TB contributes to the BICs component at the time of ABEPs peak V; and (3) the rostral LL is a contributing generator of the BICs component occurring at the time of ABEP peak VI. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Technion Israel Inst Technol, Evoked Potentials Lab, IL-32000 Haifa, Israel. Tel Aviv Univ, Fac Engn, Dept Elect Engn Syst, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Sch Med, Dept Neurol, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Sch Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Sch Med, Dept Radiol, IL-69978 Tel Aviv, Israel. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Pratt, H (reprint author), Technion Israel Inst Technol, Evoked Potentials Lab, Gutwirth Bldg, IL-32000 Haifa, Israel. EM hillel@tx.technion.ac.il RI Korczyn, Amos/C-3461-2017; OI Korczyn, Amos/0000-0003-0125-2579; Aharonson, Vered/0000-0002-4406-6525 NR 62 TC 22 Z9 22 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0168-5597 J9 EVOKED POTENTIAL JI Evoked Potential.-Electroencephalogr. Clin. Neurophysiol. PD SEP PY 1998 VL 108 IS 5 BP 511 EP 520 DI 10.1016/S0168-5597(98)00029-X PG 10 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA 123QY UT WOS:000076136900012 PM 9780022 ER PT J AU Ljubimov, AV Alba, SA Burgeson, RE Ninomiya, Y Sado, Y Sun, TT Nesburn, AB Kenney, MC Maguen, E AF Ljubimov, AV Alba, SA Burgeson, RE Ninomiya, Y Sado, Y Sun, TT Nesburn, AB Kenney, MC Maguen, E TI Extracellular matrix changes in human corneas after radial keratotomy SO EXPERIMENTAL EYE RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 11-17, 1997 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol DE human cornea; extracellular matrix; basement membrane; radial keratotomy; refractive surgery; type IV collagen chains; tenascin-C; fibrillin-1; immunofluorescence ID LASER PHOTOREFRACTIVE KERATECTOMY; BASEMENT-MEMBRANE HETEROGENEITY; IMMUNOHISTOCHEMICAL ANALYSIS; KERATOCONUS CORNEAS; RABBIT CORNEA; LONG-TERM; EXPRESSION; SURGERY; FIBRONECTIN; TENASCIN AB Extracellular matrix and basement membrane alterations were identified in human corneas after radial keratotomy. Ten normal and five radial keratotomy autopsy corneas (two at 6 months post surgery, and three at 3 years post surgery) were studied by immunofluorescence with antibodies to 28 extracellular matrix and basement membrane components. Outside of radial keratotomy scars, an studied components had a normal distribution. Of stromal extracellular matrix, only type III collagen accumulated around the. scars. The basement membrane around epithelial plugs had a normal composition except for type TV collagen. Its alpha 1-alpha 2 chains, normally present only in the limbal basement membrane, appeared around all plugs. alpha 3 and alpha 4 chains were very weak or absent in these areas, contrary to nonscarred areas. This basement membrane pattern was similar to the normal limbal but not to the central corneal pattern. Keratin 3 also had a limbal-like, suprabasal expression in the plug epithelium. The stroma around the scars accumulated tenascin-C, fibrillin-1, types Vm and XIV collagen, all of which were absent from normal corneal basement membrane and extracellular matrix. Only tenascin-C showed less staining in anterior scars 3 years post surgery than 6 months post surgery, but still persisted in posterior scars. Incomplete scar healing was evident even 3 years post radial keratotomy. It was manifested by the accumulation of abnormal extracellular matrix in the anterior and posterior scars and by the limbal-lilte pattern of type IV collagen isoforms in the basement membrane around epithelial plugs. (C) 1998 Academic Press. C1 Cedars Sinai Med Ctr, Ophthalmol Res Labs, Burns & Allen Res Inst, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. Shigei Med Res Inst, Okayama, Japan. Okayama Univ, Sch Med, Okayama 700, Japan. NYU, Sch Med, Dept Dermatol, Epithelial Biol Unit, New York, NY USA. NYU, Sch Med, Dept Pharmacol, New York, NY USA. NYU, Sch Med, Dept Urol, New York, NY USA. RP Ljubimov, AV (reprint author), Cedars Sinai Med Ctr, Ophthalmol Res Labs, Burns & Allen Res Inst, Davis 5069,8700 Beverly Blvd, Los Angeles, CA 90048 USA. RI Ljubimov, Alexander/E-5883-2013 NR 42 TC 40 Z9 40 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD SEP PY 1998 VL 67 IS 3 BP 265 EP 272 DI 10.1006/exer.1998.0511 PG 8 WC Ophthalmology SC Ophthalmology GA 131VL UT WOS:000076595900002 PM 9778407 ER PT J AU Gardner, JP Rosenzweig, M Marks, DF Harper, D Gaynor, K Fallon, RJ Wall, DA Johnson, RP Scadden, DT AF Gardner, JP Rosenzweig, M Marks, DF Harper, D Gaynor, K Fallon, RJ Wall, DA Johnson, RP Scadden, DT TI T-lymphopoietic capacity of cord blood-derived CD34(+) progenitor cells SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE T lymphopoiesis; cord blood; stem cells; CD34 ID ADULT BONE-MARROW; IN-VITRO; V(D)J RECOMBINATION; PLACENTAL BLOOD; ORGAN-CULTURE; FETAL THYMUS; STEM-CELLS; DIFFERENTIATION; TRANSPLANTATION; REPERTOIRE AB Umbilical cord blood contains an abundance of CD34(+) hematopoietic progenitor cells and has been used in transplantation as an alternative to adult bone marrow or mobilized peripheral blood. Although efficient myelomonocytic, erythroid, and B lymphoid differentiation has been shown in highly purified cord blood CD34(+) mononuclear cells lacking expression of lineage-specific antigens, generation of functional T cells has not been previously documented. Exploiting two recently developed, complementary thymic stromal monolayer systems, we show here that immature hematopoietic progenitor cells (CD34(+)lineage(-)) from human and rhesus monkey cord blood mononuclear cells undergo T lymphopoiesis in a manner that recapitulates T cell ontogeny in vivo. After 2 weeks of proliferation, cultures contained geloid cells and discrete populations of CD4(+)CD8(+) (double-positive) immature T lymphocytes, followed after an additional 2 weeks by the appearance of single-positive CD4(+)CD8(-) and CD4(-)CD8(+) T cells that coexpressed CD3. The T lymphoid phenotype was confirmed at the transcriptional level by the presence of the lymphoid-restricted genes RAG-2 and T cell receptor. T cells generated from cord blood progenitors in these systems exhibited immunofunction as assessed by alloreactive responses in mixed lymphocyte reactions. These findings were comparable between human and rhesus progenitor cells and closely resemble previous data using adult bone marrow CD34(+) cells in these models. Together, these observations demonstrate that cord blood contains abundant lymphoid progenitors that undergo T lymphopoiesis in vitro, suggesting the full multipotentiality of this stem cell source and its validity in investigating T lymphoid differentiation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Expt Hematol,AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Immunol, Southborough, MA 01772 USA. St Louis Univ, St Louis, MO 63103 USA. RP Scadden, DT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Expt Hematol,AIDS Res Ctr, Boston, MA 02114 USA. FU NCRR NIH HHS [RR00168]; NHLBI NIH HHS [HL55718, HL44851] NR 35 TC 10 Z9 10 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 1998 VL 26 IS 10 BP 991 EP 999 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 115FV UT WOS:000075653600010 PM 9728935 ER PT J AU Dubois, RN Abramson, SB Crofford, L Gupta, RA Simon, LS Van De Putte, LBA Lipsky, PE AF Dubois, RN Abramson, SB Crofford, L Gupta, RA Simon, LS Van De Putte, LBA Lipsky, PE TI Cyclooxygenase in biology and disease SO FASEB JOURNAL LA English DT Review DE prostaglandins; inflammation ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PROSTAGLANDIN-G/H SYNTHASE; HUMAN COLON-CANCER; PERIIMPLANTATION MOUSE UTERUS; MESSENGER-RNA EXPRESSION; ALZHEIMERS-DISEASE; COLORECTAL-CANCER; SELECTIVE-INHIBITION; GENE-EXPRESSION; ASPIRIN USE AB Cyclooxygenase (COX), the key enzyme required for the conversion of arachidonic acid to prostaglandins was first identified over 20 years ago. Drugs, like aspirin, that inhibit cyclooxygenase activity have been available to the public for about 100 years. In the past decade, however, more progress has been made in understanding the role of cyclooxygenase enzymes in biology and disease than at any other time in history. Two cyclooxygenase isoforms have been identified and are referred to as COX-1 and COX-2, Under many circumstances the COX-1 enzyme is produced constitutively (i.e,, gastric mucosa) whereas COX-2 is inducible (i,e,, sites of inflammation). Here, we summarize the current understanding of the role of cyclooxygenase-l and -2 in different physiological situations and disease processes ranging from inflammation to cancer. We have attempted to include all of the most relevant material in the field, but due to the rapid progress in this area of research we apologize that certain recent findings may have been left out. C1 Vanderbilt Univ, Med Ctr, Dept Med GI, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Cell Biol, Nashville, TN 37232 USA. NYU, Sch Med, Dept Rheumatol, Hosp Joint Dis, New York, NY 10003 USA. Univ Michigan, Med Ctr, Div Rheumatol, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Beth Israel Deaconness Med Ctr, Div Rheumatol, Boston, MA 02215 USA. Univ Nijmegen Hosp, Div Rheumatol, NL-6500 HB Nijmegen, Netherlands. Univ Texas, SW Med Ctr, Harold C Simmons Arthritis Res Ctr, Div Rheumat Dis, Dallas, TX 75235 USA. RP Dubois, RN (reprint author), Vanderbilt Univ, Med Ctr, Dept Med GI, 221 Kirkland Hall,MCN C-2104, Nashville, TN 37232 USA. EM duboisrn@ctrvax.vanderbilt.edu RI Crofford, Leslie/J-8010-2013 NR 117 TC 1694 Z9 1773 U1 17 U2 111 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 SEP PY 1998 VL 12 IS 12 BP 1063 EP 1073 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 116RN UT WOS:000075738500002 PM 9737710 ER PT J AU Jackson, RM Parish, G Helton, ES AF Jackson, RM Parish, G Helton, ES TI Peroxynitrite modulates MnSOD gene expression in lung epithelial cells SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE peroxynitrite; superoxide dismutase; epithelial cells; nitric oxide ID TUMOR-NECROSIS-FACTOR; MANGANESE SUPEROXIDE-DISMUTASE; NITRIC-OXIDE; MAMMALIAN-CELLS; NITRATION; INTERLEUKIN-1; SEQUENCES; INJURY AB Peroxynitrite (ONOO-) is a strong oxidant derived from nitric oxide ((NO)-N-.) and superoxide (O-2(.-)), reactive nitrogen (RNS) and oxygen species (ROS) present in inflamed tissue. Other oxidant stresses, e.g., TNF-alpha and hyperoxia, induce mitochondrial, manganese-containing superoxide dismutase (MnSOD) gene expression. These experiments tested whether ONOO- regulated MnSOD gene expression in human lung epithelial (A549) cells. 3-morpholinosydnonimine HCl (SIN-1) (10 or 1000 mu M) increased MnSOD mRNA, but did not change hypoxanthine guanine phosphoribosyl transferase (HPRT) mRNA. Authentic peroxynitrite (ONOO-) (100-500 mu M) also increased MnSOD mRNA but did not change constitutive HPRT mRNA expression. ONOO- stimulated luciferase gene expression driven by a 2.5 kb fragment of the rat MnSOD gene 5' promoter region. MnSOD gene induction due to ONOO- was inhibited effectively by L-cysteine (10 mM) and partially inhibited by N-acetyl cysteine (50 mM) or pyrrole dithiocarbamate (10 mM). (NO)-N-. from 1-propanamine, 3-(2-hydroxy-2-nitroso-1-propylhydrazine) (PAPA NONOate) (100 or 1000 mu M) did not change MnSOD or HPRT mRNA. Neither H2O2 nor NO2-, breakdown products of SIN-1 and ONOO-, had any effect on MnSOD mRNA expression; however, ONOO- and SIN-1 did not increase MnSOD protein content detectable by western blots, nor did they increase MnSOD enzymatic activity. Increased steady state [O-2(.-)] in the presence of (NO)-N-. yields ONOO-, and ONOO- has direct, stimulatory effects on MnSOD transcript expression. (C) 1998 Elsevier Science Inc. C1 Univ Alabama, Div Pulm & Crit Care Med, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL USA. RP Jackson, RM (reprint author), Univ Alabama, Div Pulm & Crit Care Med, Room 215 Tinsley Harrison Tower, Birmingham, AL 35294 USA. EM rjackson@uab.edu FU NHLBI NIH HHS [HL 57801] NR 27 TC 23 Z9 23 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD SEP PY 1998 VL 25 IS 4-5 BP 463 EP 472 DI 10.1016/S0891-5849(98)00101-4 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 113ET UT WOS:000075538000008 PM 9741582 ER PT J AU Polidori, MC Frei, B Cherubini, A Nelles, G Rordorf, G Keaney, JF Schwamm, L Mecocci, P Koroshetz, WJ Beal, MF AF Polidori, MC Frei, B Cherubini, A Nelles, G Rordorf, G Keaney, JF Schwamm, L Mecocci, P Koroshetz, WJ Beal, MF TI Increased plasma levels of lipid hydroperoxides in patients with ischemic stroke SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article ID HUMAN-BLOOD-PLASMA; CHOLESTERYL ESTER HYDROPEROXIDES; CEREBRAL-ARTERY OCCLUSION; FREE-RADICAL SCAVENGER; NERVOUS-SYSTEM TRAUMA; BUTYL NITRONE PBN; REPERFUSION INJURY; SUPEROXIDE-DISMUTASE; PHOSPHOLIPASE A(2); BRAIN ISCHEMIA AB A large body of experimental research indicates that the generation of free radicals leading to oxidative stress plays a role in the pathogenesis of ischemic brain injury, but evidence in humans is limited. We examined plasma levels of lipid hydroperoxides (measured as cholesteryl ester hydroperoxides, CEOOH) and ascorbic acid in 32 patients with cortical stroke, as compared with 13 patients with lacunar infarct. Patients with cortical stroke had significantly increased levels of CEOOH, which peaked on Day 5 after the ictus. Small decreases in ascorbic acid concentrations were not significant. There was a significant positive correlation of CEOOH with the NM stroke scale, and a significant negative correlation with the Glasgow coma scale. Concentrations of CEOOH were significantly higher in patients with total anterior cerebral syndrome as compared with patients with partial anterior cerebral syndrome or posterior cerebral syndrome. Stroke volumes computed from CT or MRI scans were significantly correlated with plasma CEOOH levels. These findings implicate oxidative stress in ischemic brain injury in humans and suggest that measurements of CEOOH in plasma may be useful both prognostically as well as in monitoring therapeutic interventions. (C) 1998 Elsevier Science Inc. C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. Oregon State Univ, Linus Pauling Inst, Cornelius, OR USA. RP Beal, MF (reprint author), Massachusetts Gen Hosp, Neurol Serv, WRN 408,32 Fruit St, Boston, MA 02114 USA. EM beal@helix.mgh.harvard.edu FU NHLBI NIH HHS [HL49954, HL56170]; NIA NIH HHS [P01 AG12992] NR 57 TC 75 Z9 75 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD SEP PY 1998 VL 25 IS 4-5 BP 561 EP 567 DI 10.1016/S0891-5849(98)00085-9 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 113ET UT WOS:000075538000019 PM 9741593 ER PT J AU Schoen, RE Corle, D Cranston, L Weissfeld, JL Lance, P Burt, R Iber, F Shike, M Kikendall, JW Hasson, M Lewin, KJ Appelman, HD Paskett, E Selby, JV Lanza, E Schatzkin, A AF Schoen, RE Corle, D Cranston, L Weissfeld, JL Lance, P Burt, R Iber, F Shike, M Kikendall, JW Hasson, M Lewin, KJ Appelman, HD Paskett, E Selby, JV Lanza, E Schatzkin, A CA Polyp Prevent Trial TI Is colonoscopy needed for the nonadvanced adenoma found on sigmoidoscopy? SO GASTROENTEROLOGY LA English DT Article ID OCCULT BLOOD-TESTS; RISK ASYMPTOMATIC PATIENTS; DIMINUTIVE COLONIC POLYPS; COLORECTAL-CANCER; FLEXIBLE SIGMOIDOSCOPY; SCREENING COLONOSCOPY; HYPERPLASTIC POLYPS; RECTOSIGMOID POLYPS; LARGE BOWEL; FIBEROPTIC SIGMOIDOSCOPY AB Background & Aims: The need for colonoscopy when small tubular adenomas with low-grade dysplasia are found on sigmoidoscopy is uncertain. The aim of this study was to examine the prevalence and characteristics of proximal adenomas in patients with distal adenomas, Methods: We studied 981 subjects with distal adenomas found on the index colonoscopy before randomization in the Polyp Prevention Trial. Results: Four hundred sixty patients (46.9%) had greater than or equal to 1 distal adenoma that was pathologically advanced (villous component, high-grade dysplasia, or greater than or equal to 1 cm); 21.5% (211 of 981) had any proximal adenoma; and 4.3% (42 of 981) (95% confidence interval [CI], 3.0-5.5) had an advanced proximal adenoma. A greater percentage of patients with an advanced distal adenoma (5.9%) (95% CI, 3.7-8.0) had an advanced proximal adenoma compared with those with a nonadvanced distal adenoma (2.9%) (95% CI, 1.4-4.3) (OR, 2.1; 95% CI, 1.1-4.3; P = 0.03). Not performing a colonoscopy in patients with a nonadvanced distal adenoma would have missed 36% (15 of 42) of the advanced proximal adenomas, Conclusions: Patients with an advanced distal adenoma are twice as likely to have an advanced proximal adenoma as patients with a nonadvanced distal adenoma. However, eschewing a colonoscopy in patients with a nonadvanced distal adenoma would result in not detecting a sizeable percentage of the prevalent advanced proximal adenomas. These data support performance of a colonoscopy in patients with a nonadvanced distal adenoma, Confirmation of these results in asymptomatic subjects undergoing screening sigmoidoscopy is advisable. C1 Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. NCI, Biometry Branch, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. WESTAT Corp, Comp Syst & Applicat, Rockville, MD 20850 USA. SUNY Buffalo, Div Gastroenterol, Buffalo, NY 14260 USA. Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Gastroenterol Sect, Hines, IL 60141 USA. Mem Sloan Kettering Canc Ctr, Div Gastroenterol, New York, NY 10021 USA. Walter Reed Army Med Ctr, Gastroenterol Sect, Bethesda, MD USA. Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA USA. Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA. Kaiser Fdn, Res Inst, Div Res, Oakland, CA USA. RP Schoen, RE (reprint author), Pittsburgh Univ Hosp, Div Gastroenterol & Hepatol, Mezzanine Level,C Wing,200 Lothrop St, Pittsburgh, PA 15213 USA. RI Lance, Peter/I-2196-2014 OI Lance, Peter/0000-0003-2944-1881 NR 71 TC 69 Z9 70 U1 2 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 1998 VL 115 IS 3 BP 533 EP 541 DI 10.1016/S0016-5085(98)70132-5 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 113PQ UT WOS:000075560800007 PM 9721149 ER PT J AU Putlitz, JZ Wieland, S Blum, HE Wands, JR AF Putlitz, JZ Wieland, S Blum, HE Wands, JR TI Antisense RNA complementary to hepatitis B virus specifically inhibits viral replication SO GASTROENTEROLOGY LA English DT Article ID ANTI-SENSE RNA; GENE-EXPRESSION; REVERSE TRANSCRIPTION; CELLS; TYPE-1; DNA; ENCAPSIDATION; POLYMERASE; INFECTION; INVITRO AB Background & Aims: Chronic infection with the hepatitis B virus (HBV) is a major public health problem, and currently available therapies have limited efficacy, Gene therapy strategies for HBV infection are under active investigation. We evaluated the potential of antisense RNA transcribed from antisense genes to interfere with HBV replication. Methods: Subgenomic fragments of the HBV genome were studied with respect to the property of inhibiting HBV replication when intracellularly expressed in the antisense orientation. Results: Antisense RNAs derived from the HBV genome specifically inhibited HBV replication and antigen expression in human hepatocellular carcinoma cells by 60%-75%, DNA sequences corresponding to the identified RNAs had no effect on HBV replication, indicating that inhibitory effects are mediated by RNA. Transcripts corresponding to the inhibitory subgenomic fragments were present at high levels. One antisense RNA was found to reduce the amount of pregenomic RNA encapsidated into core particles as a molecular mechanism of antiviral effects. Conclusions: Certain antisense RNA molecules will have substantial antiviral effects against HBV. Antisense RNAs derived from the HBV genome are promising candidates as antiviral agents and may serve as novel tools to identify functionally important regions of HBV transcripts. C1 Massachusetts Gen Hosp, Ctr Canc, Mol Hepatol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Freiburg, Dept Internal Med 2, Freiburg, Germany. RP Wands, JR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Mol Hepatol Lab, 149 13th St, Charlestown, MA 02129 USA. NR 65 TC 8 Z9 11 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 SEP PY 1998 VL 115 IS 3 BP 702 EP 713 DI 10.1016/S0016-5085(98)70150-7 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 113PQ UT WOS:000075560800025 ER PT J AU Warshaw, AL Banks, PA Castillo, CFD AF Warshaw, AL Banks, PA Castillo, CFD TI AGA technical review: Treatment of pain in chronic pancreatitis SO GASTROENTEROLOGY LA English DT Review ID QUALITY-OF-LIFE; DUODENUM-PRESERVING RESECTION; SHOCK-WAVE LITHOTRIPSY; ALCOHOLIC CHRONIC-PANCREATITIS; LONG-TERM; TOTAL PANCREATECTOMY; DISTAL PANCREATECTOMY; ENDOSCOPIC TREATMENT; FEEDBACK-REGULATION; DUCTAL MORPHOLOGY AB This literature review and the recommendations therein were prepared for the American Gastroenterological Association Clinical Practice and Practice Economics Committee. Following external review, the paper was approved by, the Committee on March 8, 1998. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Clin Gastroenterol Serv, Boston, MA 02115 USA. RP Warshaw, AL (reprint author), Amer Gastroenterol Assoc, Natl Off, Clin Practice & Practice Econ Comm, 7910 Woodmont Ave,7th Floor, Bethesda, MD 20814 USA. NR 91 TC 178 Z9 189 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 1998 VL 115 IS 3 BP 765 EP 776 DI 10.1016/S0016-5085(98)70157-X PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 113PQ UT WOS:000075560800032 PM 9721175 ER PT J AU Wang, TC Fox, JG AF Wang, TC Fox, JG TI Helicobacter pylori and gastric cancer: Koch's postulates fulfilled? SO GASTROENTEROLOGY LA English DT Editorial Material ID INFECTION; CARCINOMA; RISK; MUSTELAE; MODEL C1 Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. MIT, Div Comparat Med, Cambridge, MA 02139 USA. RP Wang, TC (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, GRJ 724,32 Fruit St, Boston, MA 02114 USA. NR 24 TC 21 Z9 23 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 1998 VL 115 IS 3 BP 780 EP 783 DI 10.1016/S0016-5085(98)70159-3 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 113PQ UT WOS:000075560800034 PM 9742001 ER PT J AU Carapeti, M Aguiar, RCT Chase, A Goldman, JM Cross, NCP AF Carapeti, M Aguiar, RCT Chase, A Goldman, JM Cross, NCP TI Assignment of the steroid receptor coactivator-1 (SRC-1) gene to human chromosome band 2p23 SO GENOMICS LA English DT Article ID ACTIVATION FUNCTION AF-2; NUCLEAR RECEPTORS; MEDIATOR C1 Hammersmith Hosp, Imperial Coll, Sch Med, Dept Haematol, London W12 0NN, England. Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Cross, NCP (reprint author), Hammersmith Hosp, Imperial Coll, Sch Med, Dept Haematol, Du Cane Rd, London W12 0NN, England. RI Cross, Nicholas/B-4817-2009 OI Cross, Nicholas/0000-0001-5481-2555 NR 12 TC 8 Z9 8 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 SEP 1 PY 1998 VL 52 IS 2 BP 242 EP 244 DI 10.1006/geno.1998.5446 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 128TD UT WOS:000076421700021 PM 9782096 ER PT J AU Strong, R AF Strong, R TI Neurochemical changes in the aging human brain: Implications for behavioral impairment and neurodegenerative disease SO GERIATRICS LA English DT Article; Proceedings Paper CT Conference on the Aging Brain in Health and Disease CY APR, 1998 CL MINNEAPOLIS, MINNESOTA SP Geriatr Res Educ & Clin Ctr (GRECC) ID AGE AB Neurotransmission is impaired in age-related disorders, such as Alzheimer's and Parkinson's diseases, which has prompted many investigations into the neurochemistry of the aging human brain. Of all the neurotransmitter systems studied, age-related changes in parameters of the serotonergic, cholinergic, and dopaminergic systems are the most reliably measured. The association of these neurotransmitters, respectively, with mood, memory, and motor function has fueled interest in hole changes in neurochemistry may contribute to age-associated behavioral changes and possibly predispose older persons to diseases of Late life. The evidence suggests that impaired neurotransmission may be responsible for at feast some of the behavioral abnormalities associated with aging. Moreover, age-related neurodegenerative diseases may evolve from the interaction between defects in specific neurochemical mechanisms and as-yet undefined pathophysiologic processes. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Aging Res & Educ Ctr, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. RP Strong, R (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 10 TC 21 Z9 21 U1 1 U2 3 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 0016-867X J9 GERIATRICS JI Geriatrics PD SEP PY 1998 VL 53 SU 1 BP S9 EP S12 PG 4 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 120ET UT WOS:000075942700003 PM 9745628 ER PT J AU Messmer, EM Raizman, MB Foster, CS AF Messmer, EM Raizman, MB Foster, CS TI Lepromatous uveitis diagnosed by iris biopsy SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article ID LEPROSY AB Ocular leprosy is rarely seen in developed countries. We report the long-term follow-up of a patient with bilateral uveitis, glaucoma, and keratitis. Skin, iris and aqueous humor biopsies disclosed abundant Wade-Fite-positive organisms consistent with Mycobacterium leprae. Leprosy must be considered in the differential diagnosis of keratitis and uveitis. C1 Univ Eye Hosp Munich, D-80336 Munich, Germany. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Immunol & Uveitis Serv, Boston, MA USA. Tufts Univ, Sch Med, Dept Ophthalmol,New England Eye Ctr, Cornea & Anterior Segment Serv, Boston, MA 02111 USA. RP Messmer, EM (reprint author), Univ Eye Hosp Munich, Mathildenstr 8, D-80336 Munich, Germany. NR 13 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD SEP PY 1998 VL 236 IS 9 BP 717 EP 719 DI 10.1007/s004170050147 PG 3 WC Ophthalmology SC Ophthalmology GA 119DH UT WOS:000075880200013 PM 9782435 ER PT J AU Motherwell, L Prudent, S AF Motherwell, L Prudent, S TI Childlessness and group psychotherapy: Psychological and sociological perspectives SO GROUP LA English DT Article DE childlessness; childfree; group therapy; women's development ID SHAME; WOMEN AB Women's developmental theory and sociocultural expectations typically link feminine identity to motherhood. This can lead to internal conflict for women who remain childless, whether by choice or by circumstance. Group psychotherapy can be useful in that it is a place where the intrapsychic and social interact. As an arena for personal change, group therapy is a place where childless women can heal the grief; shame, and guilt associated with their childlessness, and explore other ways to express femininity, creativity, and generativity. As a form of psychosocial therapy, group is a setting where both men and women can closely examine their sociocultural expectations regarding childlessness and debunk stereotypes. C1 Massachusetts Gen Hosp, Ctr Psychoanalyt Studies, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Motherwell, L (reprint author), 1180 Beacon St,Suite 4B, Brookline, MA 02446 USA. NR 37 TC 1 Z9 1 U1 0 U2 1 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0362-4021 J9 GROUP JI Group PD SEP PY 1998 VL 22 IS 3 BP 145 EP 157 DI 10.1023/A:1023085424322 PG 13 WC Psychology, Clinical SC Psychology GA 152EE UT WOS:000077762500003 ER PT J AU Tanaka, S Akiba, Y Kaunitz, JD AF Tanaka, S Akiba, Y Kaunitz, JD TI Pentagastrin gastroprotection against acid is related to H-2 receptor activation but not acid secretion SO GUT LA English DT Article DE gastric injury; gastric defence mechanisms; omeprazole; pyrilamine; ranitidine; intracellular pH ID MUCOSAL BLOOD-FLOW; INDUCED GASTRIC DAMAGE; CELL INTRACELLULAR PH; RAT STOMACH; 16,16-DIMETHYL PROSTAGLANDIN-E2; HEMORRHAGIC-SHOCK; GEL THICKNESS; NITRIC-OXIDE; IN-VIVO; HISTAMINE AB Background - Pentagastrin enhances gastric mucosal defence mechanisms against acid and protects the gastric mucosa from experimental injury. Aims - To investigate whether this gastroprotection is mediated by histamine receptors or occurs as a secondary effect of acid secretion stimulation. Methods - The effects of omeprazole (100 mu mol/kg), ranitidine (20 mg/kg), and pyrilamine (10 mg/kg) on pentagastrin (80 mu g/kg/h) induced gastroprotection against acidified aspirin injury were examined in a luminal pH controlled model. The effects of these compounds on pentagastrin enhanced gastroprotective mechanisms were investigated using intravital microscopy, in which intracellular pH of gastric surface cells (pH(i)), mucus gel thickness, gastric mucosal blood flow, and acid output were measured simultaneously. Results - Pentagastrin protected rat gastric mucosa from acidified aspirin injury. This gastroprotection was abolished by ranitidine, but not omeprazole or pyrilamine. Pentagastrin induced a hyperaemic response to luminal acid challenge, increased mucus gel thickness, and elevated pH(i) during acid challenge. Ranitidine reversed these enhanced defence mechanisms, whereas omeprazole and pyrilamine preserved these effects. Conclusions - These data indicate that pentagastrin associated gastroprotection and enhanced defence mechanisms against acid result mainly from activation of histamine H-2 receptors, and not as an effect of the stimulation of acid secretion. C1 W Los Angeles Vet Affairs Med Ctr, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, W Los Angeles Vet Affairs Med Ctr, Med Serv, Los Angeles, CA 90024 USA. RP Kaunitz, JD (reprint author), W Los Angeles Vet Affairs Med Ctr, CURE Digest Dis Res Ctr, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 49 TC 13 Z9 13 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD SEP PY 1998 VL 43 IS 3 BP 334 EP 341 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 115AY UT WOS:000075642400012 PM 9863477 ER PT J AU Harraf, F Schmulson, M Saba, L Niazi, N Fass, R Munakata, J Diehl, D Mertz, H Naliboff, B Mayer, EA AF Harraf, F Schmulson, M Saba, L Niazi, N Fass, R Munakata, J Diehl, D Mertz, H Naliboff, B Mayer, EA TI Subtypes of constipation predominant irritable bowel syndrome based on rectal perception SO GUT LA English DT Article DE visceral sensation; colonic transit ID SEVERE IDIOPATHIC CONSTIPATION; SENSITIVITY; MOTILITY AB Background - Patients who complain of constipation can be divided into those who have lost the natural call to stool, but develop abdominal discomfort after several days without a bowel movement (no urge); and those who experience a constant sensation of incomplete evacuation (urge). Aims - To determine whether the two groups differ in symptoms, colonic transit, and perceptual responses to controlled rectal distension. Methods - Forty four patients with constipation were evaluated with a bowel symptom questionnaire, colonic transit (radiopaque markers), and rectal balloon distension. Stool (S) and discomfort (D) thresholds to slow ramp (40 ml/min) and rapid phasic distension (870 ml/min) were determined with an electronic distension device. Fifteen healthy controls were also studied. Results - All patients had Rome positive irritable bowel syndrome (IBS); 17 were no urge and 27 urge. Mean D threshold to phasic rectal distensions was 28 (3) mm Hg in no urge, 27 (3) mm Hg in urge (NS), but higher in the control group (46 (2) mm Hg; p < 0.01). Sixty seven per cent of no urge and 69% of urge were hypersensitive for D. Slow ramp distension thresholds were higher in no urge (S: 26 (3); D: 45 (4) mm Hg) compared with urge (S: 16 (2); D: 31 (3) mm Hg; p < 0.01), or with controls (S: 15 (1); D: 30 (3); p < 0.01). Conclusions - Hyposensitivity to slow rectal distension is found in patients with IBS who complain of constipation and have lost the call to stool even though their sensitivity to phasic distension is increased. C1 W Los Angeles Vet Affairs Med Ctr, CURE, Digest Dis Res Ctr, Neuroenter Dis Program,Dept Med, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, CURE, Digest Dis Res Ctr, Neuroenter Dis Program,Dept Psychiat, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA 90095 USA. RP Mayer, EA (reprint author), W Los Angeles Vet Affairs Med Ctr, CURE, Digest Dis Res Ctr, Neuroenter Dis Program,Dept Med, Bldg 115, Los Angeles, CA 90073 USA. OI Diehl, David/0000-0003-4128-3839 FU NIDDK NIH HHS [DK 48351] NR 25 TC 46 Z9 47 U1 0 U2 3 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD SEP PY 1998 VL 43 IS 3 BP 388 EP 394 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 115AY UT WOS:000075642400020 PM 9863485 ER PT J AU Werner, J Fernandez-delCastillo, C Rivera, JA Kollias, N Lewandrowski, KB Rattner, DW Warshaw, AL AF Werner, J Fernandez-delCastillo, C Rivera, JA Kollias, N Lewandrowski, KB Rattner, DW Warshaw, AL TI On the protective mechanisms of nitric oxide in acute pancreatitis SO GUT LA English DT Article DE acute pancreatitis; nitric oxide; microcirculation; leucocytes; pancreatic secretion ID TRYPSINOGEN-ACTIVATION PEPTIDES; NECROTIZING PANCREATITIS; BLOOD-FLOW; L-ARGININE; RAT; SECRETION; SUPEROXIDE; CERULEIN; ACINI; PROGRESSION AB Background - Ectopic protease activation, microcirculatory changes, and leucocyte activation are the main events in the pathogenesis of acute pancreatitis. Nitric oxide (NO) is known to be a key mediator in the normal and inflamed pancreas. Aims - To investigate the targets on which NO exerts its effect in caerulein induced pancreatitis. Methods - Acute pancreatitis was induced in rats which additionally received either the NO synthase substrate, L-arginine; the NO donor, sodium nitroprusside; or the NO synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME). At six hours, pancreatic injury (oedema, leucocyte content, ectopic trypsinogen activation) was analysed and pancreatic oxygenation and perfusion were determined. A direct influence of NO on amylase secretion and trypsinogen activation was evaluated separately in vitro. Results - Both NO donors reduced the grade of inflammation. L-NAME increased the severity of inflammation, while decreasing pancreatic tissue oxygenation. Although neither amylase secretion nor intracellular trypsinogen activation in caerulein stimulated pancreatic acini was influenced by either NO donors or inhibitors, both NO donors decreased intrapancreatic trypsinogen activation peptide (TAP) and pancreatic oedema in vivo, and L-NAME increased TAP. Conclusions - NO protects against injury caused by pancreatitis in the intact animal but has no discernible effect on isolated acini. It is likely that in pancreatitis NO acts indirectly via microcirculatory changes, including inhibition of leucocyte activation and preservation of capillary perfusion. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 47 TC 52 Z9 55 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD SEP PY 1998 VL 43 IS 3 BP 401 EP 407 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 115AY UT WOS:000075642400022 PM 9863487 ER PT J AU Dangler, CA Taylor, NS Wang, T Fox, JG AF Dangler, CA Taylor, NS Wang, T Fox, JG TI High salt diet increases Helicobacter pylori colonization in C57B1/6 mice SO GUT LA English DT Meeting Abstract C1 MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD SEP PY 1998 VL 43 SU 2 BP A29 EP A29 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 126TJ UT WOS:000076309500104 ER PT J AU Dore, MP Leandro, G Realdi, G Sepulveda, AR Graham, DY AF Dore, MP Leandro, G Realdi, G Sepulveda, AR Graham, DY TI Understanding the effect of metronidazole resistance on outcome of H-pylori therapy SO GUT LA English DT Meeting Abstract C1 IRCCS S De Bellis, Bari, Italy. Univ Sassari, I-07100 Sassari, Italy. Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD SEP PY 1998 VL 43 SU 2 BP A84 EP A84 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 126TJ UT WOS:000076309500299 ER PT J AU Dore, MP Graham, DY Sepulveda, AR AF Dore, MP Graham, DY Sepulveda, AR TI A novel penicillin-binding protein(PBP-D) is involved in amoxicillin resistance in Helicobacter pylori SO GUT LA English DT Meeting Abstract C1 VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD SEP PY 1998 VL 43 SU 2 BP A7 EP A7 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 126TJ UT WOS:000076309500023 ER PT J AU Fox, JG Shen, Z Feng, E Dufour, JE Kaplan, MM Dewhi, F AF Fox, JG Shen, Z Feng, E Dufour, JE Kaplan, MM Dewhi, F TI Enterohepatic Helicobacter spp. identified from humans with primary sclerosing cholangitis SO GUT LA English DT Meeting Abstract C1 MIT, Cambridge, MA 02139 USA. Forsyth Dent Ctr, Boston, MA 02115 USA. Tufts Univ, Boston, MA 02111 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD SEP PY 1998 VL 43 SU 2 BP A3 EP A3 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 126TJ UT WOS:000076309500011 ER PT J AU Fox, JG Shen, Z Feng, F Dufour, JF Kaplan, MM Dewhi, F AF Fox, JG Shen, Z Feng, F Dufour, JF Kaplan, MM Dewhi, F TI Enterohepatic Helicobacter spp. identified from humans with primary sclerosing cholangitis SO GUT LA English DT Meeting Abstract C1 MIT, Cambridge, MA 02139 USA. Forsyth Dent Ctr, Boston, MA 02115 USA. Tufts Univ, Boston, MA 02111 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD SEP PY 1998 VL 43 SU 2 BP A115 EP A115 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 126TJ UT WOS:000076309500401 ER PT J AU Keates, S Keates, AC Peek, RM Warny, M Fatimi, A Michetti, P Kelly, CP AF Keates, S Keates, AC Peek, RM Warny, M Fatimi, A Michetti, P Kelly, CP TI H-pylori produces a soluble anti-inflammatory factor which blocks ENA-78 chemokine production in AGS gastric epithelial cells SO GUT LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD SEP PY 1998 VL 43 SU 2 BP A25 EP A25 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 126TJ UT WOS:000076309500088 ER PT J AU Kwon, DH Graham, DY El-Zaatari, FAK AF Kwon, DH Graham, DY El-Zaatari, FAK TI Transcriptional repression of multiple genes involved in Helicobacter pylori metronidazole resistance SO GUT LA English DT Meeting Abstract C1 VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD SEP PY 1998 VL 43 SU 2 BP A6 EP A6 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 126TJ UT WOS:000076309500016 ER PT J AU Malaty, HM AF Malaty, HM TI High incidence of Helicobacter pylori infection among children attending day care centers in the United States SO GUT LA English DT Meeting Abstract C1 Ctr Vet Med, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD SEP PY 1998 VL 43 SU 2 BP A45 EP A46 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 126TJ UT WOS:000076309500165 ER PT J AU Negraszus, N Yamaoka, Y Osato, M Gutierrez, O Kim, JG Graham, DY Sepulveda, AR AF Negraszus, N Yamaoka, Y Osato, M Gutierrez, O Kim, JG Graham, DY Sepulveda, AR TI Geographic distribution of genotypes of the H-pylori vacA gene from gastric cancer and duodenal ulcer isolates SO GUT LA English DT Meeting Abstract C1 Otto Von Guericke Univ, Magdeburg, Germany. VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Nacl Colombia, Bogota, Colombia. Korea Univ, Coll Med, Guru Hosp, Seoul 136701, South Korea. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD SEP PY 1998 VL 43 SU 2 BP A22 EP A22 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 126TJ UT WOS:000076309500079 ER PT J AU Realdi, G Dore, MP Atzei, A Carta, M Piana, A Manca, A Cugia, L Idda, M Are, BM Massarelli, G Mura, I Maida, A Graham, DY AF Realdi, G Dore, MP Atzei, A Carta, M Piana, A Manca, A Cugia, L Idda, M Are, BM Massarelli, G Mura, I Maida, A Graham, DY TI Importance of antibiotic resistance for choosing the best therapy for H-pylori SO GUT LA English DT Meeting Abstract C1 Univ Med, Sassari, Italy. Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD SEP PY 1998 VL 43 SU 2 BP A83 EP A83 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 126TJ UT WOS:000076309500294 ER PT J AU Saunders, KE Shen, Z Dewhirst, FE Paster, BJ Dangler, CA Fox, JG AF Saunders, KE Shen, Z Dewhirst, FE Paster, BJ Dangler, CA Fox, JG TI A novel Helicobacter sp. isolated from cotton-top tamarins (Saguinus oedipus) with colitis SO GUT LA English DT Meeting Abstract C1 MIT, Cambridge, MA 02139 USA. Forsyth Dent Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD SEP PY 1998 VL 43 SU 2 BP A117 EP A117 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 126TJ UT WOS:000076309500408 ER PT J AU Yamoka, Y Kodama, T Graham, DY Kita, M Imanishi, J Kashima, K AF Yamoka, Y Kodama, T Graham, DY Kita, M Imanishi, J Kashima, K TI No association between the presence of cagA, vacA genotype, age, or clinical outcome: Gastritis, ulcer, or cancer SO GUT LA English DT Meeting Abstract C1 VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Kyoto Prefectural Univ Med, Kyoto, Japan. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD SEP PY 1998 VL 43 SU 2 BP A20 EP A20 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 126TJ UT WOS:000076309500072 ER PT J AU Burt, VK Altshuler, LL Rasgon, N AF Burt, VK Altshuler, LL Rasgon, N TI Depressive symptoms in the perimenopause: Prevalence, assessment, and guidelines for treatment SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID ESTROGEN REPLACEMENT THERAPY; QUALITY-OF-LIFE; POSTMENOPAUSAL WOMEN; PSYCHOLOGIC DISTRESS; MENOPAUSAL WOMEN; DOUBLE-BLIND; HEALTH; EXPERIENCE; IMIPRAMINE; DISORDERS AB This review describes the biological changes occurring in perimenopause and analyzes epidemiological studies that shed light on the relationship between perimenopause and mood. The role of estrogen as a treatment for depressive symptoms is also examined. We found that a positive association may exist between depressive symptoms and the perimenopause, and that a prior history of depression may be associated with such symptoms. In most of the studies reviewed, the use of estrogen in replacement doses' appears to improve depressive symptoms in perimenopausal patients who do not have major depression. We suggest an approach to the treatment of middle-aged women presenting with such symptoms. No careful study of the incidence of DSM-IV major depression associated with perimenopause has been done, and the efficacy of estrogen as a primary or adjunctive treatment for the disorder during perimenopause is unclear. C1 Univ Calif Los Angeles, Neuropsychiat Hosp, Los Angeles, CA USA. Ctr Behav Sci, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Burt, VK (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, 300 UCLA Med Plaza,Suite 2337, Los Angeles, CA 90095 USA. NR 55 TC 43 Z9 43 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD SEP-OCT PY 1998 VL 6 IS 3 BP 121 EP 132 DI 10.3109/10673229809000320 PG 12 WC Psychiatry SC Psychiatry GA 116RW UT WOS:000075739200001 PM 10372280 ER PT J AU Rosal, MC Ockene, JK Ma, YS Hebert, JR Ockene, IS Merriam, P Hurley, TG AF Rosal, MC Ockene, JK Ma, YS Hebert, JR Ockene, IS Merriam, P Hurley, TG TI Coronary artery smoking intervention study (CASIS): 5-year follow-up SO HEALTH PSYCHOLOGY LA English DT Article DE smoking intervention; cardiac patients ID ACUTE MYOCARDIAL-INFARCTION; SELF-CHANGE; CESSATION; DISEASE; SEVERITY; TRIAL AB The authors compared the effect of a behavioral multicomponent smoking cessation special intervention (SI) to an advice-only intervention (AO) on smoking status at 5 years for smokers with coronary disease (n = 160). Regression analyses revealed an interaction between intervention type and disease severity such that patients in the SI group with greater degrees of coronary artery disease showed significantly higher cessation rates (odds ratio = 344 for 3-vessel disease in the SI vs. AO, p =.01). Factors predicting maintained abstinence included having 12 or more years of education, contemplating quitting smoking or being ready to begin action to quit at baseline, and having a higher self-efficacy score. C1 Univ Massachusetts, Sch Med, Dept Med, Div Prevent & Behav Med, Worcester, MA 01655 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Dept Med, Div Cardiovasc Med, Worcester, MA 01655 USA. RP Rosal, MC (reprint author), Univ Massachusetts, Sch Med, Dept Med, Div Prevent & Behav Med, 55 Lake Ave N, Worcester, MA 01655 USA. OI Ma, Yunsheng/0000-0003-2317-3716 FU NHLBI NIH HHS [HL 35110] NR 18 TC 35 Z9 35 U1 0 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD SEP PY 1998 VL 17 IS 5 BP 476 EP 478 DI 10.1037//0278-6133.17.5.476 PG 3 WC Psychology, Clinical; Psychology SC Psychology GA 123QV UT WOS:000076136600011 PM 9776007 ER PT J AU Armoundas, AA Rosenbaum, DS Ruskin, JN Garan, H Cohen, RJ AF Armoundas, AA Rosenbaum, DS Ruskin, JN Garan, H Cohen, RJ TI Prognostic significance of electrical alternans versus signal averaged electrocardiography in predicting the outcome of electrophysiological testing and arrhythmia-free survival SO HEART LA English DT Article DE electrophysiological testing; electrical alternans; signal averaged electrocardiography; arrhythmias ID MYOCARDIAL-INFARCTION; VENTRICULAR ARRHYTHMIAS; EJECTION FRACTION; LATE POTENTIALS; TACHYCARDIA; VULNERABILITY; PERIOD; MODEL; TIME AB Objective-To investigate the accuracy of signal averaged electrocardiography (SAECG) and measurement of microvolt level T wave alternans as predictors of susceptibility to ventricular arrhythmias. Design-Analysis of new data from a previously published prospective investigation. Setting-Electrophysiology laboratory of a major referral hospital. Patients and interventions-43 patients, not on class I or class III antiarrhythmic drug treatment, undergoing invasive electrophysiological testing had SAECG and T wave alternans measurements. The SAECG was considered positive in the presence of one (SAECG-I) or two (SAECG-II) of three standard criteria. T wave alternans was considered positive if the alternans ratio exceeded 3.0. Main outcome measures-Inducibility of sustained ventricular tachycardia or fibrillation during electrophysiological testing, and 20 month arrhythmia-free survival. Results-The accuracy of T wave alternans in predicting the outcome of electrophysiological testing was 84% (p < 0.0001). Neither SAECG-I (accuracy 60%; p < 0.29) nor SAECG-II (accuracy 71%; p < 0.10) was a statistically significant predictor of electrophysiological testing. SAECG, T wave alternans, electrophysiological testing, and follow up data were available in 36 patients while not on class I or III antiarrhythmic agents. The accuracy of T wave alternans in predicting the outcome of arrhythmia-free survival was 86% (p < 0.030). Neither SAECG-I (accuracy 65%; p < 0.21) nor SAECG-II (accuracy 71%; p < 0.48) was a statistically significant predictor of arrhythmia-free survival. Conclusions-T wave alternans was a highly significant predictor of the outcome of electrophysiological testing and arrhythmia-free survival, while SAECG was not a statistically significant predictor. Although these results need to be confirmed in prospective clinical studies, they suggest that T wave alternans may serve as a non-invasive probe for screening high risk populations for malignant ventricular arrhythmias. C1 Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. RP Cohen, RJ (reprint author), Harvard Univ, MIT, Div Hlth Sci & Technol, 77 Massachusetts Ave,E25-335, Cambridge, MA 02139 USA. FU NHLBI NIH HHS [HL-54807] NR 22 TC 47 Z9 48 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD SEP PY 1998 VL 80 IS 3 BP 251 EP 256 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 118MF UT WOS:000075841700013 PM 9875084 ER PT J AU French, CA Bieber, FR Bing, DH Genest, DR AF French, CA Bieber, FR Bing, DH Genest, DR TI Twins, placentas, and genetics: Acardiac twinning in a dichorionic diamniotic, monozygotic twin gestation SO HUMAN PATHOLOGY LA English DT Article DE acardia; twins; placenta; malformation; zygosity AB We describe a human acardiac twin with associated vascular anastomoses in a dichorionic diamniotic fused twin placenta. A 22-year-old woman delivered a healthy 3,554 g male infant and a fused diamniotic dichorionic twin placenta with a 230g umbilical cord-attached, skin-covered, ovoid mass, consistent with acardiac amorphus. By gross and histological examination, the placental dividing membranes comprised four leaves, one amnion from each placenta, and two centrally fused chorions, diagnostic of dichorionicity. Placental barium injection of the normal twin's umbilical vein showed an anastomosis with the acardiac twin which traversed the dividing membranes, then supplied major vessels of the acardiac mass via its 5.5 cm umbilical cord. DNA-typing studies of the normal twin's placenta and of the acardiac twin's tissues revealed identical alleles at II distinct genetic polymorphic loci, consistent with monozygosity. Our findings demonstrate that vascular anastomoses can occur in dichorionic twin placentas, and that human acardiac twinning is not, as heretofore believed, restricted to monochorionic placentas. Copyright (C) 1998 by W.B. Saunders Company. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Ctr Blood Res, CBR Labs, Boston, MA 02115 USA. RP Genest, DR (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 20 TC 11 Z9 12 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD SEP PY 1998 VL 29 IS 9 BP 1028 EP 1031 DI 10.1016/S0046-8177(98)90213-1 PG 4 WC Pathology SC Pathology GA 119DN UT WOS:000075880700023 PM 9744324 ER PT J AU Gao, YJ Chaudhuri, J Zhu, CM Davidson, L Weaver, DT Alt, FW AF Gao, YJ Chaudhuri, J Zhu, CM Davidson, L Weaver, DT Alt, FW TI A targeted DNA-PKcs-null mutation reveals DNA-PK-independent functions for KU in V(D)J recombination SO IMMUNITY LA English DT Article ID DEPENDENT PROTEIN-KINASE; STRAND-BREAK-REPAIR; SEVERE COMBINED IMMUNODEFICIENCY; HUMAN CELL-LINE; CATALYTIC SUBUNIT; SACCHAROMYCES-CEREVISIAE; SCID MUTATION; CODING ENDS; MOUSE; MICE AB The DNA-dependent protein kinase (DNA-PK) consists of Ku70, Ku80, and a large catalytic subunit, DNA-PKcs. Targeted inactivation of the Ku70 or Ku80 genes results in elevated ionizing radiation (IR) sensitivity and inability to perform both V(D)J coding-end and signal (RS)-end joining in cells, with severe growth retardation plus immunodeficiency in mice. In contrast, we now demonstrate that DNA-PKcs-null mice generated by gene-targeted mutation, while also severely immunodeficient, exhibit no growth retardation. Furthermore, DNA-PKcs-null cells are blocked for V(D)J coding-end joining, but retain normal RS-end joining. Finally, while DNA-PK-null fibroblasts exhibited increased IR sensitivity, DNA-PKcs-deficient ES cells did not. We conclude that Ku70 and Ku80 may have functions in V(D)J recombination and DNA repair that are independent of DNA-PKcs. C1 Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst,Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst,Ctr Blood Res, Boston, MA 02115 USA. FU NIAID NIH HHS [AI20047, AI35714] NR 64 TC 308 Z9 311 U1 0 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 SEP PY 1998 VL 9 IS 3 BP 367 EP 376 DI 10.1016/S1074-7613(00)80619-6 PG 10 WC Immunology SC Immunology GA 124VA UT WOS:000076202300009 PM 9768756 ER PT J AU McCormick, BA Siber, AM Maurelli, AT AF McCormick, BA Siber, AM Maurelli, AT TI Requirement of the Shigella flexneri virulence plasmid in the ability to induce trafficking of neutrophils across polarized monolayers of the intestinal epithelium SO INFECTION AND IMMUNITY LA English DT Article ID POLYMORPHONUCLEAR LEUKOCYTE TRANSMIGRATION; IPA INVASINS; SALMONELLA-TYPHIMURIUM; CELLS; SECRETION; ANTIGENS; PROTEIN; COLITIS; 2A; SHIGELLA-FLEXNERI-2A AB Attachment of an array of enteric pathogens to epithelial surfaces is accompanied by recruitment of polymorphonuclear leukocytes (PMN) across the intestinal epithelium. In this report, we examine how Shigella-intestinal epithelium interactions evoke the mucosal inflammatory response. We modeled these interactions in vitro by using polarized monolayers of the human intestinal epithelial cell line, T84, isolated human PMNs, and Shigella flexneri. We show that Shigella attachment to T84-cell basolateral membranes was a necessary component in the signaling cascade for induction of basolateral-to-apical directed transepithelial PMN migration, the direction of PMN transepithelial migration in vivo. In contrast, attachment of Shigella to the T84-cell apical membrane failed to stimulate a directed PMN transepithelial migration response. Importantly, the ability of Shigella to induce PMN migration across epithelial monolayers was dependent on the presence of the 220-kb virulence plasmid, Moreover. examination of Shigella genes necessary to signal subepithelial neutrophils established the requirement of a functional type III secretion system. Our results indicate that the ability of Shigella to elicit transepithelial signaling to neutrophils from the basolateral membrane of epithelial cells represents a mechanism involved in Shigella-elicited enteritis in humans. C1 Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02129 USA. Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Immunol & Microbiol, Bethesda, MD 20814 USA. RP McCormick, BA (reprint author), Massachusetts Gen Hosp E, Dept Pediat Gastroenterol & Nutr, Charlestown Navy Yard Bldg 149 1493404, Charlestown, MA 02129 USA. EM mccormic@helix.mgh.harvard.edu FU NIAID NIH HHS [AI24656, R01 AI024656]; NIDDK NIH HHS [DK50989] NR 57 TC 38 Z9 38 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 1998 VL 66 IS 9 BP 4237 EP 4243 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 113RF UT WOS:000075564500034 PM 9712773 ER EF