FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Lindberg, G Rastam, L Lundblad, A Sorlie, PD Folsom, AR AF Lindberg, G Rastam, L Lundblad, A Sorlie, PD Folsom, AR CA Atherosclerosis Risk Communities ARIC Study In TI The association between serum sialic acid and asymptomatic carotid atherosclerosis is not related to antibodies to Herpes type viruses or Chlamydia pneumoniae SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE sialic acid; carotid atherosclerosis; Herpes virus antibodies; Chlamydia pneumoniae antibodies ID CORONARY HEART-DISEASE; B-MODE ULTRASOUND; STRAIN TWAR; CYTOMEGALOVIRUS; CHOLESTEROL; INFECTIONS; MORTALITY AB Background. Total serum sialic acid is a recently investigated marker for cardiovascular mortality and carotid atherosclerosis. This study tested the hypothesis that past infection by Herpes simplex type 1 or type 2 viruses or Cytomegalovirus or Chlamydia pneumoniae accounts for the association between serum total sialic acid and atherosclerosis. Methods. Population-based samples of men and women living in four US communities were used in a cross-sectional study. Cases and matched controls were defined by B-mode ultrasound measurements of carotid and popliteal arterial wall thickness. In all, there were 267 case control pairs with information about antibody titres to viruses and 256 pairs with information about antibody titres to Chlamydia pneumoniae. Results. Serum total sialic acid (S-TSA) level was significantly higher in cases with carotid atherosclerosis compared to their controls. The odds ratio for carotid atherosclerosis associated with sialic acid level above 75th percentile was 1.73 (95% confidence interval [CI] : 1.02-2.95) in the sample with information about antibodies to viruses and 1.70 (95% CI : 1.00-2.93) in the sample with information about antibodies to C. pneumoniae. Adjustment for titres of antibodies to viruses and C. pneumoniae had no impact on the relation between sialic acid and carotid atherosclerosis. Conclusions. From these results, it seems unlikely that previous infection by any of these micro-organisms accounts for the relation between S-TSA level and carotid atherosclerosis. C1 Malmo Univ Hosp, Med Res Ctr, NEPI Fdn, S-20502 Malmo, Sweden. Univ Lund, Dept Hlth Sci, Malmo, Sweden. Linkoping Univ, Dept Clin Chem, S-58183 Linkoping, Sweden. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. RP Lindberg, G (reprint author), Malmo Univ Hosp, Med Res Ctr, NEPI Fdn, S-20502 Malmo, Sweden. FU NHLBI NIH HHS [HC-55016, HC-55018, HC-55015] NR 25 TC 5 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD DEC PY 1997 VL 26 IS 6 BP 1386 EP 1391 DI 10.1093/ije/26.6.1386 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YP308 UT WOS:000071263900031 PM 9447421 ER PT J AU Chen, ZQ Fisher, RJ Li, BQ Kamata, T Kung, HF Lautenberger, JA Rhim, JS AF Chen, ZQ Fisher, RJ Li, BQ Kamata, T Kung, HF Lautenberger, JA Rhim, JS TI Elevated expression of ETS-1 gene in a metastatic, tumorigenic human prostate epithelial cell line transformed by the v-Ki-ras oncogene SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE prostate; ETS-1 gene; metastasis; v-Ki-ras; epithelial cells ID TRANSCRIPTION FACTOR; MUTATIONS; C-ETS1; TRANSACTIVATION; ACTIVATION; CARCINOMA; PROTEINS; FAMILY; CANCER; DNA AB A suitable in vitro model system to investigate mechanisms of human prostate carcinogenesis is much needed. We have previously demonstrated that an immortal, but non-tumorigenic, human prostate epithelial cell line (267B(1)) can be malignantly transformed by the v-Ki-ras oncogene, and it can serve as a useful model for investigation of the progression steps of prostate carcinogenesis. In this study, we report for the first time the invasive/metastatic phenotype of the v-Ki-ras transformed 267B, cells (267B(1)/Ki-ras). In addition, comparing non-tumorigenic 267B, and metastatic tumorigenic 267B(1)/Ki-ras human prostate epithelial cell lines, we have found that expression of ETS-1 and ERGB mRNA was elevated to 2-5 fold in the metastatic and tumorigenic 267B(1)/Ki-ras cell line. A specific ETS-1 monoclonal antibody E44 also revealed that the expression of ETS-1 protein level in 267B(1)/Ki-ras cell line was higher than those in 267B, cell line. However, other members of the ETS gene family such as ETS-2, GABP alpha and their mRNA expression levels were similar in both cell lines. The activation of MAP kinase, a downstream target for Ki-ras, was also shown. The expression of urokinase plasminogen activator (u-PA) was also increased in the metastatic 267B(1)/Ki-ras line. An obvious capability of invasion was observed in the 267B(1)/Ki-ras cell line, but not in the 267B(1) line using BioCoat Matrigel invasion chamber assay system. The present study has provided evidence that the v-Ki-ras oncogene may activate the nuclear target gene, ETS-1 gene, to mediate tumorigenic and metastatic capacity of the v-Ki-ras transformed prostate epithelial cells. C1 NCI,LAB BIOCHEM PHYSIOL,FREDERICK,MD 21702. NCI,LAB GENOM DIVERS,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,IRSP,SAIC FREDERICK,FREDERICK,MD 21702. RI Fisher, Robert/B-1431-2009 NR 25 TC 9 Z9 9 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD DEC PY 1997 VL 11 IS 6 BP 1179 EP 1184 PG 6 WC Oncology SC Oncology GA YJ141 UT WOS:A1997YJ14100003 PM 21528319 ER PT J AU Arif, JM Gairola, CG Glauert, HP Kelloff, GJ Lubet, RA Gupta, RC AF Arif, JM Gairola, CG Glauert, HP Kelloff, GJ Lubet, RA Gupta, RC TI Effects of dietary supplementation of N-acetylcysteine on cigarette smoke-related DNA adducts in rat tissues SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE N-acetylcysteine; DNA adducts; P-32-postlabeling; tobacco smoke; cigarette smoke ID POLYCYCLIC AROMATIC-HYDROCARBONS; LUNG; EXPOSURE; NONSMOKERS; CHEMOPREVENTION; BIOMARKERS; DAMAGE; ASSAY; CELLS; MICE AB Cigarette smoking plays a major role in the etiology of several human cancers. It is believed that formation of DNA adducts is an initial step in the carcinogenic process. In this study, we have examined the ability of dietary N-acetylcysteine (NAG) to inhibit the formation of cigarette smoke-related DNA adducts in various tissues of rats. Female Sprague-Dawley rats were exposed to cigarette smoke (10 mg TPM/m(3)) in a whole-body exposure chamber for 6 h per day, seven days a week for four weeks. The smoke-exposed groups were provided either an unrefined diet or diets supplemented with low (5,000 ppm) or high (20,000 ppm) dose of NAG. A sham group was given control diet and maintained on filtered ambient air. Tissue DNA analysis of smoke-exposed rats by nuclease P1-version of the P-32-postlabeling assay showed up to 6 adducts in the following descending order expressed as total adducts/10(10) nucleotides: 1 predominant (no. 5) and 4 (no. 1-no. 4) minor adducts in the (219 +/- 36), 6 minor adducts in the heart (93 +/- 11), 5 adducts in the trachea (50 +/- 16), and 4 adducts in the bladder (50 +/- 3.5); sham-treated animals showed 2 or 3 adducts in each tissue but at 4-20-fold lower levels. Dietary intervention with either high or low dose of NAC did not affect the levels of most adducts, except for the following: a 30-40% increase (P<0.05) for adducts 3 and 4 in the lung; a 40-50% decrease (P<0.05) for adduct 2 in the trachea; and a 30% increase (P<0.05) for adduct 2 in the bladder. In a second experiment conducted under identical conditions, most major and minor adducts remained unaffected with NAC intervention, except for adduct 2 in the trachea which was somewhat diminished. These results suggest that dietary NAC intervention does not significantly influence the levels of most major and minor adducts. However, some minor adducts in the lung, trachea and bladder were modulated differentially. C1 UNIV KENTUCKY,MED CTR,DEPT PREVENT MED & ENVIRONM HLTH,LEXINGTON,KY 40536. UNIV KENTUCKY,TOBACCO & HLTH RES INST,LEXINGTON,KY 40536. UNIV KENTUCKY,DEPT NUTR & FOOD SCI,LEXINGTON,KY 40536. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. NR 47 TC 14 Z9 14 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD DEC PY 1997 VL 11 IS 6 BP 1227 EP 1233 PG 7 WC Oncology SC Oncology GA YJ141 UT WOS:A1997YJ14100011 PM 21528327 ER PT J AU Pham, D Prince, JL Xu, CY Dagher, AP AF Pham, D Prince, JL Xu, CY Dagher, AP TI An automated technique for statistical characterization of brain tissues in magnetic resonance imaging SO INTERNATIONAL JOURNAL OF PATTERN RECOGNITION AND ARTIFICIAL INTELLIGENCE LA English DT Article DE magnetic resonance imaging; pulse sequence optimization; image segmentation; fuzzy c-means; parameter estimation; relaxation times ID MULTISPECTRAL ANALYSIS; RELAXATION-TIMES; PULSE SEQUENCES; IMAGES; T1; T2; OPTIMIZATION; SEGMENTATION; DENSITY AB A procedure for estimating the joint probability density function (pdf) of T-1, T-2 and proton spin density (P-D) for gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) in the brain is presented. The pdf's have numerous applications, including the study of tissue parameter variability in pathology and across populations. The procedure requires a multispectral, spin echo magnetic resonance imaging (MRI) data set of the brain. It consists of five automated steps: (i) preprocess the data to remove extracranial tissue using a sequence of image processing operators; (ii) estimate T-1, T-2 and P-D by fitting the preprocessed data to an imaging equation; (iii) perform a fuzzy c-means clustering on the same preprocessed data to obtain a spatial map representing the membership value of the three tissue classes at each pixel location; (iv) reject estimates which are not from pure tissue or have poor fits in the parameter estimation, and classify the remaining estimates as either GM, WM or CSF; (v) compute statistics on the classified estimates to obtain a probability mass function and a Gaussian joint pdf of the tissue parameters for each tissue class. Some preliminary results are shown comparing computed pdf's of young, elderly and Alzheimer's subjects. Two brief examples applying the joint pdf's to pulse sequence optimization and generation of computational phantoms are also provided. C1 Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. NIA, GRC, LPC, NIH, Baltimore, MD 21224 USA. Thomas Jefferson Univ Hosp, Dept Radiol, Philadelphia, PA 19107 USA. RI Prince, Jerry/A-3281-2010 OI Prince, Jerry/0000-0002-6553-0876 NR 20 TC 29 Z9 30 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA JOURNAL DEPT PO BOX 128 FARRER ROAD, SINGAPORE 9128, SINGAPORE SN 0218-0014 J9 INT J PATTERN RECOGN JI Int. J. Pattern Recognit. Artif. Intell. PD DEC PY 1997 VL 11 IS 8 BP 1189 EP 1211 DI 10.1142/S021800149700055X PG 23 WC Computer Science, Artificial Intelligence SC Computer Science GA YY662 UT WOS:000072171000003 ER PT J AU Huerta, MF AF Huerta, MF TI Special issue - Processing of MR images of the human brain - Commentary SO INTERNATIONAL JOURNAL OF PATTERN RECOGNITION AND ARTIFICIAL INTELLIGENCE LA English DT Editorial Material C1 NIMH, Div Basic & Clin Neurosci Res, NIH, Rockville, MD 20857 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA JOURNAL DEPT PO BOX 128 FARRER ROAD, SINGAPORE 9128, SINGAPORE SN 0218-0014 J9 INT J PATTERN RECOGN JI Int. J. Pattern Recognit. Artif. Intell. PD DEC PY 1997 VL 11 IS 8 BP 1399 EP 1401 PG 3 WC Computer Science, Artificial Intelligence SC Computer Science GA YY662 UT WOS:000072171000012 ER PT J AU Boinski, S Mitchell, CL AF Boinski, S Mitchell, CL TI Chuck vocalizations of wild female squirrel monkeys (Saimiri sciureus) contain information on caller identity and foraging activity SO INTERNATIONAL JOURNAL OF PRIMATOLOGY LA English DT Article DE primate vocal communication; Saimiri sciureus; acoustic structure; foraging behavior; individual identity ID GOLDEN LION TAMARINS; VOCAL BEHAVIOR; ACOUSTIC STRUCTURE; RECOGNITION; COMMUNICATION; ADVERTISEMENT; INDIVIDUALITY; VARIABILITY; REPERTOIRE; SEQUENCES AB Analysis of the acoustic signal of the chuck vocalizations of adult female squirrel monkeys (Saimiri sciureus) in Parque Nacional de Manu, Peru, revealed consistent differences within and between individuals. We quantified four peak frequency parameters: (a) the peak frequency of single chucks, (b) the first and (c) the second peak frequencies of double chuck, and (d) the peak difference: the difference between the first and the second double chuck peaks. One-way ANOVAs and a posteriori comparisons of these variables revealed that each distinguished more than 70% of all possible pairs of females. When all double chuck measures were included in a discriminant analysis, 57% of double chuck were correctly assigned to the caller. Another category of information potentially encoded in the acoustic structure of chuck vocalizations is foraging activity. When the chuck of squirrel monkeys during foraging and nonforaging activities were compared, the single chuck peak frequency, and the first peak frequency and the peak difference of double chucks, were significantly reduced during foraging contexts. Previously Boinski and Mitchell (1992) concluded that chuck facilitate group cohesion among widely dispersed troop members by providing information of the location of callers; the rate of chuck produced by an adult female increases as she becomes more spatially and visually separated from other adult females. The additional information potentially conveyed by chucks on caller identity and foraging activity documented in these new analyses further emphasizes the role chuck serve to enhance group coordination and cohesion. C1 Univ Florida, Dept Anthropol, Gainesville, FL 32611 USA. Univ Florida, Div Comparat Med, Gainesville, FL 32611 USA. NIH, NIH Anim Ctr, Comparat Ethol Lab, Poolesville, MD USA. Amazonian Biodivers Project, Cusco, Peru. RP Boinski, S (reprint author), Univ Florida, Dept Anthropol, 1350 Turlington, Gainesville, FL 32611 USA. NR 55 TC 26 Z9 26 U1 0 U2 10 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0164-0291 J9 INT J PRIMATOL JI Int. J. Primatol. PD DEC PY 1997 VL 18 IS 6 BP 975 EP 993 DI 10.1023/A:1026300314739 PG 19 WC Zoology SC Zoology GA YR742 UT WOS:000071525700008 ER PT J AU Kirkbride, P Gelmon, K Eisenhauer, E Fisher, B Dulude, H AF Kirkbride, P Gelmon, K Eisenhauer, E Fisher, B Dulude, H TI A phase I/II study of paclitaxel (TAXOL(R)) and concurrent radiotherapy in advanced nonsmall cell lung cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE lung carcinoma; paclitaxel; radical radiotherapy; radiosensitiser ID RADIATION; TRIAL AB Purpose: The addition of chemotherapy to radical radiotherapy (XRT) has been shown to improve survival in locally advanced nonsmall cell lung cancer (9), Consequently, different chemotherapeutic regimens in combination with XRT are being evaluated in the treatment of this disease, Paclitaxel (TAXOL(R)) may be a valuable drug in this situation as, in addition to a demonstrated activity in NSCLC, it has been shown to enhance the effect of radiation on cell lines in vitro. Methods and Materials: Seventeen patients were enrolled onto a Phase I/II trial to determine the maximum tolerated dose of paclitaxel given by a 3-h infusion every 2 weeks throughout a 6-week course of XRT, 60 Gy in 30 daily fractions, in patients with Stage III NSCLC and then to describe the response rate of this combination in an expanded cohort of patients treated at the recommended phase II dose, Three patients were entered at each dose level (45, 90, 120, and 135 mg/m(2)), except for the 120 mg/m(2) dose level, which was expanded to nine patients. Results: The dose limiting toxicity was neutropenia-two of three patients treated at the 135 mg/m(2) level experienced Grade 3 neutropenia on day 15, which precluded administration of scheduled chemotherapy, Esophagitis was mild to moderate, and although profound lymphopenia was observed at all dose levels, there was no evidence of associated opportunistic infections, Of the nine patients treated at the recommended Phase II dose of 120 mg/m(2), there were one complete and six partial responses (response rate 78%). Conclusion: The combination of XRT, 60 Gy in 6 weeks and paclitaxel, 120 mg/m(2)q 2 weeks, can be safely given to patients with NSCLC, and although it demonstrates activity in this situation, consideration should be given to the addition of other agents, such as platinum compounds. (C) 1997 Elsevier Science Inc. C1 BRITISH COLUMBIA CANC AGCY,VANCOUVER,BC V5Z 4E6,CANADA. QUEENS UNIV,NCI,CANADA CLIN TRIALS GRP,KINGSTON,ON K7L 3N6,CANADA. BRISTOL MYERS SQUIBB,MONTREAL,PQ,CANADA. RP Kirkbride, P (reprint author), PRINCESS MARGARET HOSP,DEPT RADIAT ONCOL,OCI,ROOM 4-912,610 UNIV AVE,TORONTO,ON M5G 2M9,CANADA. NR 13 TC 17 Z9 18 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD DEC 1 PY 1997 VL 39 IS 5 BP 1107 EP 1111 DI 10.1016/S0360-3016(97)00548-8 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA YG838 UT WOS:A1997YG83800022 PM 9392551 ER PT J AU Vickers, A Cassileth, B Ernst, E Fisher, P Goldman, P Jonas, W Kang, SK Lewith, G Schulz, K Silagy, C AF Vickers, A Cassileth, B Ernst, E Fisher, P Goldman, P Jonas, W Kang, SK Lewith, G Schulz, K Silagy, C TI How should we research unconventional therapies? A panel report from the conference on complementary and alternative medicine research methodology, national institutes of health SO INTERNATIONAL JOURNAL OF TECHNOLOGY ASSESSMENT IN HEALTH CARE LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; FOLLOW-UP; CANCER-CHEMOTHERAPY; ATOPIC ECZEMA; ACUPUNCTURE; ACUPRESSURE; SURVIVAL; PLANTS; BACK AB Research in unconventional medicine requires a number of different questions to build up a ''mosaic'' of evidence. Choice of research design depends on the question being asked and is independent of the therapy under investigation. Despite the doubts of some practitioners, randomized trials are of value for determining certain questions in alternative medicine. C1 UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC. UNIV EXETER,CTR COMPLEMENTARY HLTH STUDIES,EXETER EX2 4NT,DEVON,ENGLAND. ROYAL LONDON HOMEOPATH HOSP,LONDON WC1N 3HR,ENGLAND. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. NIH,OFF ALTERNAT MED,ROCKVILLE,MD 20892. KYUNG HEE UNIV,COLL ORIENTAL MED,TONGDAEMUN KU,SEOUL 130702,SOUTH KOREA. UNIV SOUTHAMPTON,SOUTHAMPTON GEN HOSP,SCH MED,DEPT MED,SOUTHAMPTON SO16 6YD,HANTS,ENGLAND. CTR DIS CONTROL & PREVENT,DIV STD HIV,ATLANTA,GA 30333. FLINDERS UNIV S AUSTRALIA,DEPT GEN PRACTICE,ADELAIDE,SA 5001,AUSTRALIA. RP Vickers, A (reprint author), RES COUNCIL COMPLEMENTARY MED,60 GREAT ORMOND ST,LONDON WC1N 3JF,ENGLAND. OI Lewith, George/0000-0002-2364-3960 NR 29 TC 72 Z9 72 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0266-4623 J9 INT J TECHNOL ASSESS JI Int. J. Technol. Assess. Health Care PD WIN PY 1997 VL 13 IS 1 BP 111 EP 121 PG 11 WC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics GA WQ130 UT WOS:A1997WQ13000010 PM 9119619 ER PT J AU Koh, SWM Yeh, TH Morris, SM Leffler, M Higginbotham, EJ Brenneman, DE Yue, BYJT AF Koh, SWM Yeh, TH Morris, SM Leffler, M Higginbotham, EJ Brenneman, DE Yue, BYJT TI Vasoactive intestinal peptide stimulation of human trabecular meshwork cell growth SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE argon laser trabeculoplasty; cell proliferation; proliferating cell nuclear antigen; trabecular meshwork cells; vasoactive intestinal peptide ID RETINAL-PIGMENT EPITHELIUM; INTRACELLULAR CYCLIC-AMP; OPEN-ANGLE GLAUCOMA; LASER TRABECULOPLASTY; IL-6 SECRETION; DIFFERENTIATION; ARGON; VIP; NEUROPEPTIDES; CELLULARITY AB Purpose. To demonstrate that vasoactive intestinal peptide (VIP), a 28-amino acid neuropeptide, is a growth factor of human trabecular meshwork (TM) cells in culture and in a corneoscleral explant organ culture treated with laser trabeculoplasty (LTP). Methods. Proliferating human TM cells in cell cultures were incubated with VIP for 20 hours, followed by total cell number determination, using a Coulter counter. The percentage of proliferating TM cells was assessed, using an antibody against the proliferating cell nuclear antigen (PCNA). To test the growth effect of VIP on TM cells in situ, corneoscleral explants in organ cultures were first treated with argon LTP to initiate TM-cell proliferation and then were exposed to VIP for 48 hours. The mitotic TM cells were demonstrated immunocytochemically,using anti-PCNA in paraffin sections of the explants; and the total number of TM cells was determined after paraffin sections were counterstained by hematoxylin. Results. Vasoactive intestinal peptide dose-dependently stimulated the proliferation of TM cells in cell culture. Treatment with 5 X 10(-10) M VIP resulted in a maximal increase of 40% in cell number. The effect of VIP was blocked by a VIP antagonist. The number of PCNA-stained TM cells and the total cell number in the TM in LTP-treated corneoscleral explants were increased by VIP. Conclusions. Exogenously applied VIP stimulated the proliferation of human TM cells in subconfluent cultures and in LTP-treated corneoscleral explants. In that LTP has been shown to increase the number of TM cells in situ, the growth stimulatory effect of VIP may help enhance this therapy. C1 Univ Maryland, Dept Ophthalmol, Baltimore, MD 21201 USA. NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Univ Illinois, Dept Ophthalmol, Chicago, IL 60680 USA. RP Koh, SWM (reprint author), Univ Maryland, Dept Ophthalmol, Room 5-00C,10 S Pine St, Baltimore, MD 21201 USA. FU NEI NIH HHS [R01EY03890, EY05628] NR 49 TC 10 Z9 11 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 1997 VL 38 IS 13 BP 2781 EP 2789 PG 9 WC Ophthalmology SC Ophthalmology GA YM109 UT WOS:000071029300012 PM 9418731 ER PT J AU Wiener, EC Konda, S Shadron, A Brechbiel, M Gansow, O AF Wiener, EC Konda, S Shadron, A Brechbiel, M Gansow, O TI Targeting dendrimer-chelates to tumors and tumor cells expressing the high-affinity folate receptor SO INVESTIGATIVE RADIOLOGY LA English DT Article DE folate; contrast agents; gadolinium; dendrimer; cancer ID BINDING-PROTEIN; OVARIAN-CANCER; TROPHOBLAST; TISSUES; LINES AB RATIONALE AND OBJECTIVES, The authors developed a new method for delivering contrast agents to tumors and tumor cells, Gadolinium complexes of folate-conjugated dendrimer-chelates increased the longitudinal relaxation rate of tumor cells expressing the high-affinity folate receptor, hFR, The coupling of folate to polymeric chelates, composed of a dendrimer backbone, targets these chelates to endogenous folate binding proteins, These proteins exist in both the serum of patients with cancer and on the cell surface of many human cancers of epithelial origin, METHODS. The authors attached folic acid to a generation four ammonia core polyamidoamine dendrimer, The folate-dendrimer was reacted with 2-(4-isothiocyanatobenzyl)-6-methyl-diethylenetriaminepentaacetic acid to form the polymeric chelate f-PAMAM-TU-DTPA. For fluorescent studies, the generation four dendrimer was reacted with fluorescein-5-isothiocyanate and carboxytetramethylrhodamine succinimidyl ester, followed by capping the remaining amines with succinic anhydride, RESULTS. The study results show that cells accumulate the folate-conjugated dendrimer in a receptor specific manner, Tumor cells expressing the high-affinity folate receptor showed a 650% increase in the mean fluorescence. This increase occurred with a rapid rise to 325%, followed by a slow increase to 650%, It required both the expression of the hFR and the coupling of folic acid to the dendrimer, Excess free folic acid inhibited the binding of the folate conjugated polymer, Fluorescent microscopic study showed that the folate-conjugated dendrimer binds to the cell surface and is accumulated within the cells, Treatment of tumor cells that express the hFR with gadolinium complexes of the folate-conjugated polymeric chelate increases the longitudinal relaxation rate by 110%, This increase was inhibited by an excess of free folic acid. CONCLUSIONS. These data demonstrate that folate-conjugated magnetic resonance imaging contrast agents represent a promising new approach to tumor targeting. C1 UNIV ILLINOIS,DEPT NUCL ENGN,URBANA,IL 61801. NCI,NIH,BETHESDA,MD 20892. RP Wiener, EC (reprint author), UNIV ILLINOIS,COLL MED,BIOMED MAGNET RESONANCE LAB,ZIOU S GOODWIN,URBANA,IL 61801, USA. FU NCI NIH HHS [1-R29-CA61918]; NCRR NIH HHS [2-P41-RR05964-06, 5-P41-RR05964] NR 14 TC 167 Z9 185 U1 0 U2 22 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD DEC PY 1997 VL 32 IS 12 BP 748 EP 754 DI 10.1097/00004424-199712000-00005 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA YH542 UT WOS:A1997YH54200005 PM 9406015 ER PT J AU Bleyer, WA Tejeda, H Murphy, SB Robison, LL Ross, JA Pollock, BH Severson, RK Brawley, OW Smith, MA Ungerleider, RS AF Bleyer, WA Tejeda, H Murphy, SB Robison, LL Ross, JA Pollock, BH Severson, RK Brawley, OW Smith, MA Ungerleider, RS TI National cancer clinical trials: Children have equal access; Adolescents do not SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE national cancer trials; Children's Cancer Group; Pediatric Oncology Group; adolescents; cancer ID LYMPHOBLASTIC-LEUKEMIA; PEDIATRIC CANCER; UNITED-STATES; YOUNG-ADULTS; SURVIVAL; DIAGNOSIS; PLACE AB Purpose. To determine whether adolescents with cancer, who in comparison to younger patients have a higher cancer incidence and lower mortality reduction, have equal access to national cancer clinical trials. Methods. The ethnic/racial distribution of 29,859 subjects < 20 years of age entered onto National Cancer Institute-sponsored clinical trials between January 1, 1991, and June 30, 1994, was compared with the expected distribution of patients of the same age in the United States. Results. The Children's Cancer Group and Pediatric Oncology Group had 29,134 (97.6%) of the total study entries among < 20-year-old subjects during the 3.5 years of surveillance. The adult cooperative groups accounted for < 3% of the clinical trials entries in the 15-19-year age range. When analyzed nationally by region, the under-representation of the older adolescent subjects was universal. From other analyses, the two pediatric cooperative groups were estimated to have registered > 94% of the children < 15 years of age who were expected to have been diagnosed to have cancer, but only 21% of the cancer patients in the 15-19-year age group. Conclusions. The national pediatric cancer cooperative groups allow the majority of American children < 15 years of age and their families equal opportunity to access clinical cancer trials, regardless of pace or ethnicity. Among patients 15-19 years of age, however, > 75% are not being enrolled by any cooperative group sponsored by the National Cancer institute. Thus, older adolescents are disadvantaged with respect to access to the national clinical trials, regardless of their race or ethnicity. (C) Society for Adolescent Medicine, 1997. C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT & DIAGNOSIS & CTR,BETHESDA,MD 20892. NCI,PEDIAT ONCOL GRP,BETHESDA,MD 20892. RP Bleyer, WA (reprint author), CCG GRP,OPERAT CTR,441 E HUNTINGTON DR,POB 60012,ARCADIA,CA 91066, USA. FU NCI NIH HHS [CA 30969, CA13539] NR 17 TC 104 Z9 104 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD DEC PY 1997 VL 21 IS 6 BP 366 EP 373 DI 10.1016/S1054-139X(97)00110-9 PG 8 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA YH517 UT WOS:A1997YH51700004 PM 9401854 ER PT J AU Rogers, AS AF Rogers, AS TI Adolescent under enrollment in national clinical research: It is time to ask why SO JOURNAL OF ADOLESCENT HEALTH LA English DT Editorial Material RP Rogers, AS (reprint author), NICHHD,CTR RES MOTHERS & CHILDREN,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,BETHESDA,MD 20892, USA. NR 4 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD DEC PY 1997 VL 21 IS 6 BP 374 EP 375 DI 10.1016/S1054-139X(97)00173-0 PG 2 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA YH517 UT WOS:A1997YH51700005 PM 9401855 ER PT J AU Fee, E AF Fee, E TI Chicago's war on syphilis, 1937-1940: The times, the Trib, and the clap doctor SO JOURNAL OF AMERICAN HISTORY LA English DT Book Review C1 NIH, Natl Lib Med, Bethesda, MD 20892 USA. RP Fee, E (reprint author), NIH, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ORGANIZATION AMER HISTORIANS PI BLOOMINGTON PA 112 N BRYAN ST, BLOOMINGTON, IN 47408 USA SN 0021-8723 J9 J AM HIST JI J. Am. Hist. PD DEC PY 1997 VL 84 IS 3 BP 1093 EP 1094 DI 10.2307/2953173 PG 2 WC History SC History GA YN842 UT WOS:000071213500093 ER PT J AU Groll, AH Just-Nuebling, G Kurz, M Mueller, C Nowak-Goettl, U Schwabe, D Shah, PM Kornhuber, B AF Groll, AH Just-Nuebling, G Kurz, M Mueller, C Nowak-Goettl, U Schwabe, D Shah, PM Kornhuber, B TI Fluconazole versus nystatin in the prevention of candida infections in children and adolescents undergoing remission induction or consolidation chemotherapy for cancer SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article ID BONE-MARROW TRANSPLANTATION; FUNGAL-INFECTIONS; ACUTE-LEUKEMIA; OROPHARYNGEAL CANDIDIASIS; NEUTROPENIC PATIENTS; RISK-FACTORS; IMMUNOCOMPROMISED CHILDREN; ANTIFUNGAL PROPHYLAXIS; ORAL FLUCONAZOLE; AMPHOTERICIN-B AB An open, prospective, randomized pilot study was performed to assess the efficacy and safety of oral fluconazole 3 mg/kg once daily compared with oral nystatin 50,000 units/kg/day in four divided doses in preventing candida infections in 50 children undergoing remission induction or consolidation therapy for cancer. In 21 of 25 fluconazole-treated and 20 of 25 nystatin-treated patients the overall outcome of prophylaxis was clearly successful. Mild and transient oropharyngeal candidosis was observed in two and three patients in the fluconazole and nystatin groups respectively. One patient randomized to fluconazole and two patients randomized to nystatin required empirical treatment with amphotericin B and one patient assigned to fluconazole developed tissue-proven candida colitis. Initially noncolonized patients remained yeast-free throughout treatment with no differences between the two study arms. Initially colonized patients stayed colonized throughout treatment although at the end of the study, more patients randomized to nystatin were still harbouring yeasts (P = 0.05). Almost exclusively, Candida albicans (95%) was isolated. A change in species was observed in one patient in each arm of the study. Candida krusei or Candida glabrata were not encountered. Transient elevations of hepatic transaminases were more common in the fluconazole group, although not statistically significant (28% vs 12%, P = 0.15). Reversible grade I gastrointestinal and skin symptoms were observed in four patients randomized to fluconazole (16 vs 0%, P < 0.05). Fluconazole was as safe and effective as nystatin in controlling yeast colonization and in preventing superficial and invasive candida infections and the empirical use of amphotericin B in children and adolescents undergoing intensive chemotherapy for cancer. C1 Johann Wolfgang Goethe Univ Hosp, Dept Paediat, Div Haematol Oncol, Frankfurt, Germany. Johann Wolfgang Goethe Univ Hosp, Dept Med, Div Haematol Oncol, Infect Dis Sect, Frankfurt, Germany. RP Groll, AH (reprint author), NCI, Pediat Oncol Branch, Bldg 10,Room 13N240,10 Ctr Dr, Bethesda, MD 20892 USA. NR 34 TC 26 Z9 28 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 DEC PY 1997 VL 40 IS 6 BP 855 EP 862 DI 10.1093/jac/40.6.855 PG 8 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA YQ345 UT WOS:000071376000014 PM 9462438 ER PT J AU Cohen, GH AF Cohen, GH TI ALIGN: a program to superimpose protein coordinates, accounting for insertions and deletions SO JOURNAL OF APPLIED CRYSTALLOGRAPHY LA English DT Article ID RELATE 2 SETS; GENERAL METHOD; RESOLUTION; REFINEMENT; SIMILARITY; ROTATION; VECTORS; DOMAINS AB The alignment and superposition of protein structures are sometimes complicated by the presence of insertions or deletions in one structure or the other. The program ALIGN [Satow, Cohen, Padlan & Davies (1986). J. Mol. Biol. 190, 593-604] was written to address this problem. The program provides information in its analysis of results ro facilitate the understanding of transformations between structurally homologous subunits of protein structures. C1 NIDDKD, Mol Biol Lab, Bethesda, MD 20892 USA. RP Cohen, GH (reprint author), NIDDKD, Mol Biol Lab, Bethesda, MD 20892 USA. NR 21 TC 334 Z9 338 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0021-8898 J9 J APPL CRYSTALLOGR JI J. Appl. Crystallogr. PD DEC 1 PY 1997 VL 30 BP 1160 EP 1161 DI 10.1107/S0021889897006729 PN 6 PG 2 WC Chemistry, Multidisciplinary; Crystallography SC Chemistry; Crystallography GA ZA971 UT WOS:000072421300042 ER PT J AU Galliven, EA Singh, A Michelson, D Bina, S Gold, PW Deuster, PA AF Galliven, EA Singh, A Michelson, D Bina, S Gold, PW Deuster, PA TI Hormonal and metabolic responses to exercise across time of day and menstrual cycle phase SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE adrenocorticotropic hormone; circadian variation; cortisol; estrogen; eumenorrheic; glucose; running ID CORTICOTROPIN-RELEASING-FACTOR; ESTROGEN-INDUCED ALTERATIONS; ANTERIOR-PITUITARY GLAND; PLASMA ADRENOCORTICOTROPIN; CORTICOSTERONE SECRETION; INTRAVENOUS-INJECTION; TREADMILL EXERCISE; CORTISOL RESPONSES; ADRENAL RESPONSES; DIURNAL-VARIATION AB Two studies, each utilizing short-term treadmill exercise of a different intensity, assessed the metabolic and hormonal responses of women to exercise in the morning (AM) and late afternoon (PM). In study I, plasma concentrations of growth hormone, arginine vasopressin, catecholamines, adrenocorticotropic hormone, cortisol, lactate, and glucose were measured before, during, and after high-intensity exercise (90% maximal O-2 uptake) in the AM and PM. In study 2, plasma concentrations of adrenocorticotropic hormone, cortisol, lactate, and glucose were measured before, during, and after moderate-intensity exercise (70% maximal O-2 uptake) in the AM and PM in the follicular (days 3-9), midcycle (clays 10-16), and luteal (days 18-26) phases of the menstrual cycle. The results of studies 1 and 2 revealed no significant diurnal differences in the magnitude of responses for any measured variable. In addition, study 2 revealed a significant time-by-phase interaction for glucose (P = 0.014). However, net integrated responses were similar across cycle phases. These data suggest that metabolic and hormonal responses to short-term, high-intensity exercise can be assessed with equal reliability in the AM and PM and that there are subtle differences in blood glucose responses to moderate-intensity exercise across menstrual cycle phase. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT MIL & EMERGENCY MED,BETHESDA,MD 20814. UNIFORMED SERV UNIV HLTH SCI,DEPT ANESTHESIOL,BETHESDA,MD 20814. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. RI Deuster, Patricia/G-3838-2015 OI Deuster, Patricia/0000-0002-7895-0888 NR 34 TC 66 Z9 66 U1 0 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD DEC PY 1997 VL 83 IS 6 BP 1822 EP 1831 PG 10 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA YK807 UT WOS:A1997YK80700006 PM 9390951 ER PT J AU Martin, RG Rosner, JL AF Martin, RG Rosner, JL TI Fis, an accessorial factor for transcriptional activation of the mar (multiple antibiotic resistance) promoter of Escherichia coli in the presence of the activator MarA, SoxS, or Rob SO JOURNAL OF BACTERIOLOGY LA English DT Article ID SUPEROXIDE RESPONSE REGULON; DNA INTERACTIONS; INDUCIBLE GENES; BINDING-PROTEIN; RNA-POLYMERASE; STRESS GENES; OPERON; REPRESSOR; PURIFICATION; LOCUS AB Transcription of the multiple antibiotic resistance marRAB operon increases when one of the sequence-related activators, MarA, SoxS, or Rob, binds to the ''marbox'' centered at -61.5 relative to the transcriptional start site. Previous deletion analyses showed that an adjacent upstream ''accessory region'' was needed to augment the marbox-dependent activation. To analyze the roles of the marbox and accessory regions on mar transcription, thirteen promoters, each with a different 5-bp transversion of the -96 to -32 sequence, were synthesized, fused to lacZ, and assayed for beta-galactosidase production in single copy lysogens with appropriate genotypes. The accessory region is shown here to be a binding site for Fis centered at -81 and to bind Fis, a small DNA-binding and -bending protein, with a K-d of approximate to 5 nM. The binding of MarA to the marbox and that of Fis to its site were independent of each other. MarA, SoxS, and Rob each activated the mar promoter 1.5- to 2-fold when it had a wild-type marbox but Fis was absent. In the presence of MarA, SoxS, or Rob, Fis further enhanced the activity of the promoter twofold provided the promoter was also capable of binding Fis. However, in the absence of MarA, SoxS, or Rob or in the absence of a wild-type marbox, Fis nonspecifically lowered the activity of the mar promoter about 25% whether or not a wild-type Fis site was present. Thus, Fis acts as an accessory transcriptional activates at the mar promoter. RP Martin, RG (reprint author), NIDDKD,MOL BIOL LAB,NIH,BLDG 5,RM 333,BETHESDA,MD 20892, USA. NR 48 TC 56 Z9 56 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 1997 VL 179 IS 23 BP 7410 EP 7419 PG 10 WC Microbiology SC Microbiology GA YJ682 UT WOS:A1997YJ68200026 PM 9393706 ER PT J AU Fijalkowska, IJ Dunn, RL Schaaper, RM AF Fijalkowska, IJ Dunn, RL Schaaper, RM TI Genetic requirements and mutational specificity of the Escherichia coli SOS mutator activity SO JOURNAL OF BACTERIOLOGY LA English DT Article ID DNA-POLYMERASE-III; SINGLE-STRANDED-DNA; UV MUTAGENESIS; MISMATCH REPAIR; BACTERIOPHAGE-LAMBDA; ANTIMUTATOR ALLELES; REPLICATION ERRORS; ULTRAVIOLET-LIGHT; ADAPTIVE MUTATION; ALPHA-SUBUNIT AB To better understand the mechanisms of SOS mutagenesis in the bacterium Escherichia coli, we have undertaken a genetic analysis of the SOS mutator activity. The SOS mutator activity results from constitutive expression of the SOS system in strains carrying a constitutively activated RecA protein (RecA730). We show that the SOS mutator activity is not enhanced in strains containing deficiencies in the uvr ABC nucleotide excision-repair system or the xth and nfo base excision-repair systems. Further, recA730-induced errors are shown to be corrected by the MutHLS-dependent mismatch-repair system as efficiently as the corresponding errors in the rec(+) background. These results suggest that the SOS mutator activity does not reflect mutagenesis at so-called cryptic lesions but instead represents an amplification of normally occurring DNA polymerase errors. Analysis of the base-pair-substitution mutations induced by recA730 in a mismatch repair-deficient background shows that both transition and transversion errors are amplified, although the effect is much larger for transversions than for transitions. Analysis of the mutator effect in various dnaE strains, including dnaE antimutators, as well as in proofreading-deficient dnaQ (mutD) strains suggests that in recA730 strains, two types of replication errors occur in parallel: (i) normal replication errors that are subject to both exonucleolytic proofreading and dnaE antimutator effects and (ii) recA730-specific errors that are not susceptible to either proofreading or dnaE antimutator effects. The combined data are consistent with a model suggesting that in recA730 cells error-prone replication complexes are assembled at sites where DNA polymerization is temporarily stalled, most likely when a normal polymerase insertion error has created a poorly extendable terminal mismatch. The modified complex forces extension of the mismatch largely at the exclusion of proofreading and polymerase dissociation pathways. SOS mutagenesis targeted at replication-blocking DNA lesions likely proceeds in the same manner. C1 NIEHS,MOL GENET LAB,E301,RES TRIANGLE PK,NC 27709. RI Fijalkowska, Iwona/I-7796-2016 NR 80 TC 85 Z9 86 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 1997 VL 179 IS 23 BP 7435 EP 7445 PG 11 WC Microbiology SC Microbiology GA YJ682 UT WOS:A1997YJ68200029 PM 9393709 ER PT J AU Wehr, TA AF Wehr, TA TI Melatonin and seasonal rhythms SO JOURNAL OF BIOLOGICAL RHYTHMS LA English DT Article DE light; photoperiod; scotoperiod; season; pineal gland; circadian rhythm; reproductive function; seasonal affective disorder ID RAT SUPRACHIASMATIC NUCLEUS; HUMAN-REPRODUCTION; PINEAL MELATONIN; PHOTOPERIOD; CLOCK; HAMSTERS AB The pineal hormone melatonin plays a ubiquitous role in biology as a chemical mediator of the effects of season on animal physiology and behavior. Seasonal changes in night length (scotoperiod) induce parallel changes in the duration of melatonin secretion (which occurs exclusively at night), so that it is longer in winter and shorter in summer. These changes in duration of nocturnal melatonin secretion, in turn, trigger seasonal changes in behavior. The retinohypothalamic-pineal (RHP) axis's responses to light are highly conserved in humans. Like other animals, humans secrete melatonin exclusively at night, and they interrupt its secretion when they are exposed to light during the nocturnal period of its secretion. In many individuals, the RHP axis also is capable of detecting changes in the length of the night and making proportional adjustments in the duration of nocturnal melatonin secretion, producing the type of melatonin message that animals use to trigger seasonal changes in their behavior. This has been shown both in naturalistic studies in which melatonin profiles were compared in summer and winter and in experimental studies in which melatonin profiles were compared after chronic exposure to long and short artificial ''nights.'' Individuals who live in modern urban environments differ in the degree to which, or even whether, the intrinsic duration of melatonin secretion (the duration measured in constant dim Light) responds to seasonal changes in the length of the solar night. Changes in the intrinsic duration of melatonin secretion that are induced by changes in the scotoperiod are highly correlated with changes in the intrinsic timing of the morning offset of secretion and are only weakly correlated with changes in the intrinsic timing of evening onset of secretion. This finding suggests that differences in the way in which individuals are exposed to, or process, morning light may explain differences in their responsiveness to changes in duration of natural and experimental scotoperiods. Although the human RHP axis clearly is capable of detecting changes in the length of the night and in producing the melatonin message that other animals use to trigger seasonal changes in their behavior, it is not yet known whether or how the human reproductive system or other systems respond to this message. RP Wehr, TA (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,ROOM 4S-239,BLDG 10,10 CTR DR MSC 1390,BETHESDA,MD 20892, USA. NR 28 TC 66 Z9 69 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0748-7304 J9 J BIOL RHYTHM JI J. Biol. Rhythms PD DEC PY 1997 VL 12 IS 6 BP 518 EP 527 DI 10.1177/074873049701200605 PG 10 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA YJ449 UT WOS:A1997YJ44900005 PM 9406025 ER PT J AU Werner, MH Clore, GM Fisher, CL Fisher, RJ Trinh, L Shiloach, J Gronenborn, AM AF Werner, MH Clore, GM Fisher, CL Fisher, RJ Trinh, L Shiloach, J Gronenborn, AM TI Correction of the NMR structure of the ETS1/DNA complex SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE ETS1/DNA complex; solution structure; Pu.1/DNA complex ID DNA-BINDING MOTIF; 3-DIMENSIONAL SOLUTION STRUCTURE; PROTEIN-STRUCTURE DETERMINATION; ETS-DOMAIN; TRANSCRIPTION FACTORS; MURINE ETS-1; SECONDARY STRUCTURE; MAGNETIC-RESONANCE; DIRECT REFINEMENT; HELIX AB The ETS family of transcription factors consists of a group of proteins that share a highly conserved 85 amino acid DNA-binding domain (DBD). This family recognizes a consensus sequence rich in purine bases with a central GGAA motif. A comparison of the published three-dimensional structures of the DBD/DNA complexes of ETS1 by NMR [Werner et al. (1995) Cell, 83, 761-771] and the related Pu.l by X-ray crystallography [Kodandapani et al. (1996) Nature, 380, 456-460] reveals an apparent discrepancy in which the protein domains bind with opposite polarity to their target sequences. This surprising and highly unlikely result prompted us to reexamine our NMR structure. Additional NMR experiments now reveal an error in the original interpretation of the spectra defining the orientation of the ETS1-DBD on DNA. It was originally reported that the ETS1-DBD bound to DNA with a bipartite motif involving major groove recognition via a helix-turn-helix element and minor groove recognition via protein side-chain intercalation. The presence of intercalation was deduced on the basis of numerous NOEs between several amino acids in the protein and a resonance at 12.33 ppm originally assigned to a DNA imino proton. New NMR experiments now conclusively demonstrate that this resonance, which is located within the DNA imino proton region of the spectrum, arises from the hydroxyl proton of Tyr(86). Realization of this error necessitated reanalysis of the intermolecular NOEs. This revealed that the orientation of the ETS1-DBD in he complex is opposite to that originally reported and that a tryptophan residue does not intercalate into the DNA. The calculation of a new ensemble of structures based on the corrected data indicates that the structure of the ETS1-DBD/DNA complex is indeed similar to the X-ray structure of the Pu.l-DBD/DNA complex. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21707 USA. NIDDKD, Cellular & Dev Biol Lab, Bethesda, MD 20895 USA. RP Clore, GM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 48 TC 49 Z9 50 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD DEC PY 1997 VL 10 IS 4 BP 317 EP 328 DI 10.1023/A:1018399711996 PG 12 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA YR476 UT WOS:000071499100001 PM 9460239 ER PT J AU Giuliano, KA DeBiasio, RL Dunlay, RT Gough, A Volosky, JM Zock, J Pavlakis, GN Taylor, DL AF Giuliano, KA DeBiasio, RL Dunlay, RT Gough, A Volosky, JM Zock, J Pavlakis, GN Taylor, DL TI High-content screening: A new approach to easing key bottlenecks in the drug discovery process SO JOURNAL OF BIOMOLECULAR SCREENING LA English DT Article ID LIVING CELLS; MOLECULAR-DYNAMICS; TRANSLOCATION; ORGANIZATION; MICROSCOPY; PROTEINS; ARRAYS; DNA AB Recent improvements in target discovery and high throughput screening (HTS) have increased the pressure at key points along the drug discovery pipeline. High-content screening (HCS) was developed to ease bottlenecks that have formed at target validation and lead optimization points in the pipeline. HCS defines the role of targets in cell functions by combining fluorescence-based reagents with the ArrayScan((TM)) System to automatically extract temporal and spatial information about target activities within cells. The ArrayScan System is a tabletop instrument that includes optics for subcellular resolution of fluorescence signals from many cells in a field within a well of a microtiter plate. One demonstrated application is a high-content screen designed to measure the drug-induced transport of a green fluorescent protein-human glucocorticoid receptor chimeric protein from the cytoplasm to the nucleus of human tumor cells. A high-content screen is also described for the multiparametric measurement of apoptosis. This single screen provides measurements of nuclear size and shape changes, nuclear DNA content, mitochondrial potential, and actin-cytoskeletal rearrangements during drug-induced programmed cell death. The next generation HCS system is a miniaturized screening platform, the CellChip((TM)) System, that will increase the throughput of HCS, while integrating HCS with HTS on the same platform. C1 BioDx Inc, Pittsburgh, PA 15238 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP BioDx Inc, 635 William Pitt Way, Pittsburgh, PA 15238 USA. OI Gough, Albert/0000-0001-6456-0195 NR 25 TC 130 Z9 143 U1 0 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0571 EI 1552-454X J9 J BIOMOL SCREEN JI J. Biomol. Screen PD WIN PY 1997 VL 2 IS 4 BP 249 EP 259 DI 10.1177/108705719700200410 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry GA YM293 UT WOS:000071049100011 ER PT J AU Chanturiya, AN AF Chanturiya, AN TI Fast two dimensional computer simulation of bilayer hemifusion SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article ID MEMBRANE-FUSION; INTERMEDIATE; MECHANISMS AB Computer simulation of model membranes was used to evaluate the possible mechanism of lipid bilayer fusion. The simplified two dimensional model of the membrane cross section was used as an analog of three dimensional reality. Lipid molecules were represented by rodlike structures, and forces between them were limited to attraction/repulsion interactions described by a simple energy function with a minimum: 300-400 molecules were modeled in every simulation. Using the energy minimization procedure, it was possible to obtain stable linear or circular bilayer structures (two dimensional analogs of planar membranes and liposomes). In response to changes in attraction/repulsion equilibrium between molecules these bilayers were able to reorganize via cooperative process. By increasing the headgroup attraction parameter for contacting monolayers, it was possible to induce formation of a zone of hemifusion in the area of bilayer contact. The possible correlation between cooperative bilayer rearrangement in the model and in real bilayers is discussed. C1 NICHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Inst Biochem, Dept Neurochem, Kiev, Ukraine. RP Chanturiya, AN (reprint author), NICHD, Lab Cellular & Mol Biophys, NIH, Bldg 10,Rm 10D04, Bethesda, MD 20892 USA. NR 20 TC 1 Z9 1 U1 0 U2 0 PU ADENINE PRESS INC PI GUILDERLAND PA PO BOX 355/340, GUILDERLAND, NY 12084 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD DEC PY 1997 VL 15 IS 3 BP 547 EP 553 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YQ219 UT WOS:000071362700010 PM 9440001 ER PT J AU DSouza, RN Cavender, A Sunavala, G Alvarez, J Ohshima, T Kulkarni, AB MacDougall, M AF DSouza, RN Cavender, A Sunavala, G Alvarez, J Ohshima, T Kulkarni, AB MacDougall, M TI Gene expression patterns of murine dentin matrix protein 1 (Dmp1) and dentin sialophosphoprotein (DSPP) suggest distinct developmental functions in vivo SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT 75th General Session of the International-Association-for-Dental-Research CY 1997 CL ORLANDO, FL SP Int Assoc Dental Res ID ACIDIC PHOSPHOPROTEIN; COLLAGEN; SIALOPROTEIN; BIOMINERALIZATION; DENTINOGENESIS; PHOSPHOPHORYN; BINDING; PROTEOGLYCANS; ODONTOBLASTS; INDUCTION AB Although the precise mechanisms of the conversion of predentin to dentin are not well understood, several lines of evidence implicate the noncollagenous proteins (NCPs) as important regulators of dentin biomineralization. Here we compared the in vivo temporospatial expression patterns of two dentin NCP genes, dentin matrix protein 1 (Dmp1), and dentin sialophosphoprotein (DSPP) in developing molars, Reverse transcription-polymerase chain reaction was performed on embryonic day 13 to 1-day-old first molars using Dmp1- and DSPP-specific primer sets, Dmp1 transcripts appeared at the late bud stage, while DSPP mRNA was seen at the cap stage, Expression of both genes was sustained throughout odontogenesis, In situ hybridization analysis revealed interesting differences in the expression patterns of these genes, While Dmp1 and DSPP showed coexpression fn young odontoblasts before the start of mineralization, the expression of these genes was notably distinct at later stages, Dmp1 expression decreased in secretory odontoblasts after the appearance of mineral, while high levels of DSPP were sustained hi odontoblasts. In early secretory ameloblasts, DSPP expression was transient and down-regulated with the appearance of dentin matrix, Interestingly, Dmp1 expression became evident in ameloblasts during the maturative Dbase of amelogenesis. In contrast to Dspp expression that was tooth-specific, Dmp1 was expressed by osteoblasts throughout ossification in the skeleton, Probes directed to the ''DSP'' and ''DPP'' regions of the DSPP gene showed identical patterns of mRNA expression, These data show that the developmental expression patterns of Dmp1 and DSPP are distinct, implying that these molecules serve different biological functions in vivo. C1 UNIV TEXAS,HLTH SCI CTR,DEPT PEDIAT DENT,SAN ANTONIO,TX 78284. NIDR,GENE TARGETING RES & CORE FACIL,NIH,BETHESDA,MD 20892. RP DSouza, RN (reprint author), UNIV TEXAS,HLTH SCI CTR,DENT BRANCH,DEPT BASIC SCI,ROOM 4133,6516 JOHN FREEMAN AVE,HOUSTON,TX 77030, USA. OI D'Souza, Rena/0000-0002-1505-5173 FU NIDCR NIH HHS [DE-10517, DE-11658] NR 38 TC 222 Z9 229 U1 4 U2 11 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD DEC PY 1997 VL 12 IS 12 BP 2040 EP 2049 DI 10.1359/jbmr.1997.12.12.2040 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YJ698 UT WOS:A1997YJ69800009 PM 9421236 ER PT J AU Heegaard, AM Robey, PG Vogel, W Just, W Widom, RL Scholler, J Fisher, LW Young, MF AF Heegaard, AM Robey, PG Vogel, W Just, W Widom, RL Scholler, J Fisher, LW Young, MF TI Functional characterization of the human biglycan 5'-flanking DNA and binding of the transcription factor c-Krox SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID GROWTH-FACTOR-BETA; I COLLAGEN; PROTEOGLYCANS BIGLYCAN; NEGATIVE REGULATION; X-CHROMOSOME; GENE; EXPRESSION; PROMOTER; DECORIN; REGION AB The transcriptional regulation of human biglycan expression under normal and pathological conditions nas studied, The 5'-flanking regions of the human and mouse genes mere isolated and analyzed; the two promoter regions share 81% identity, Both promoters are without a TATA and CAT box and contain multiple Spl sites, Human dermal fibroblasts were transiently transfected with progressive deletional human biglycan 5'-flanking DNA-CAT constructs, and a significant variation in activity among the individual constructs was found, A small deletion in several cases caused a more than 2-fold increase or decrease in promoter activity, thereby mapping the target sites for repressors or activators, Human biglycan expression is reduced in females with Ullrich-Turner syndrome (45,X) and increased in individuals with supernumerary sex chromosomes, and it has been speculated that biglycan plays a role in the short stature phenotype of Turner syndrome, Analysis of the transcriptional regulation of biglycan in individuals with sex chromosome anomalies showed that a -262 to -218 region of the biglycan promoter was differentially regulated, This region was extensively analyzed by DNAse footprinting and electrophoretic mobility shift assays, and a putative binding site for the transcription factor c-Krox was discovered, The binding of c-Krox to a site located at approximately -248 to -230 in the human biglycan promoter was confirmed by using extracts from COS cells expressing recombinant human c-Krox. The expression of c-Krox in bone was then examined by reverse-transcribed polymerase chain reaction and Northern blotting analysis; an similar to 3.4 kb transcript was detected in primary osteoblastic cells, in MG-63 cells, and in human bone marrow stromal cells, This is the first detection of c-Krox in bane cells, and it suggests that c-Krox, like another member of the Krox family, Krox-20, might play a regulatory role in bone. C1 NIDR, BONE RES BRANCH, NIH, BETHESDA, MD 20892 USA. UNIV ULM, ABT MED GENET, ULM, GERMANY. BOSTON UNIV, SCH MED, CTR ARTHRITIS, BOSTON, MA 02118 USA. RP Heegaard, AM (reprint author), CTR CLIN & BASIC RES, BALLERUP BYVEJ 22, DK-2750 BALLERUP, DENMARK. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 36 TC 25 Z9 26 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD DEC PY 1997 VL 12 IS 12 BP 2050 EP 2060 DI 10.1359/jbmr.1997.12.12.2050 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YJ698 UT WOS:A1997YJ69800010 PM 9421237 ER PT J AU Czerwiec, FS Collins, M Feuillan, P Shenker, A AF Czerwiec, FS Collins, M Feuillan, P Shenker, A TI Further study of the therapy for fibrous dysplasia is necessary SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Letter ID BONE C1 CHILDRENS MEM HOSP,CHICAGO,IL 60614. RP Czerwiec, FS (reprint author), NICHHD,NIH,BETHESDA,MD 20892, USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD DEC PY 1997 VL 12 IS 12 BP 2128 EP 2129 DI 10.1359/jbmr.1997.12.12.2128 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YJ698 UT WOS:A1997YJ69800022 PM 9421248 ER PT J AU Sciaky, N Presley, J Smith, C Zaal, KJM Cole, N Moreira, JE Terasaki, M Siggia, E LippincottSchwartz, J AF Sciaky, N Presley, J Smith, C Zaal, KJM Cole, N Moreira, JE Terasaki, M Siggia, E LippincottSchwartz, J TI Golgi tubule traffic and the effects of Brefeldin A visualized in living cells SO JOURNAL OF CELL BIOLOGY LA English DT Article ID ADP-RIBOSYLATION FACTOR; FLUORESCENT CERAMIDE ANALOG; GTP-BINDING PROTEIN; ENDOPLASMIC-RETICULUM; ELECTRON-MICROSCOPY; ORGANELLE STRUCTURE; PHOSPHOLIPASE-D; 3-DIMENSIONAL ARCHITECTURE; DEPENDENT FORMATION; GUANINE-NUCLEOTIDE AB The Golgi complex is a dynamic organelle engaged in both secretory and retrograde membrane traffic. Here, we use green fluorescent protein-Golgi protein chimeras to study Golgi morphology in vivo. In untreated cells, membrane tubules were a ubiquitous, prominent feature of the Golgi complex, serving both to interconnect adjacent Golgi elements and to carry membrane outward along microtubules after detaching from stable Golgi structures. Brefeldin A treatment, which reversibly disassembles the Golgi complex, accentuated tubule formation without tubule detachment. A tubule network extending throughout the cytoplasm was quickly generated and persisted for 5-10 min until rapidly emptying Golgi contents into the ER within 15-30 s. Both lipid and protein emptied from the Golgi at similar rapid rates, leaving no Golgi structure behind, indicating that Golgi membranes do not simply mix but are absorbed into the ER in BFA-treated cells. The directionality of redistribution implied Golgi membranes are at a higher free energy state than ER membranes. Analysis of its kinetics suggested a mechanism that is analogous to wetting or adsorptive phenomena in which a tension-driven membrane flow supplements diffusive transfer of Golgi membrane into the ER. Such nonselective, flow-assisted transport of Golgi membranes into ER suggests that mechanisms that regulate retrograde tubule formation and detachment from the Golgi complex are integral to the existence and maintenance of this organelle. C1 NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. NINCDS,NIH,BETHESDA,MD 20892. UNIV CONNECTICUT,CTR HLTH,DEPT PHYSIOL,FARMINGTON,CT 06032. CORNELL UNIV,DEPT PHYS,ITHACA,NY 14853. NR 78 TC 347 Z9 354 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 1 PY 1997 VL 139 IS 5 BP 1137 EP 1155 DI 10.1083/jcb.139.5.1137 PG 19 WC Cell Biology SC Cell Biology GA YK658 UT WOS:A1997YK65800007 PM 9382862 ER PT J AU Wolter, KG Hsu, YT Smith, CL Nechushtan, A Xi, XG Youle, RJ AF Wolter, KG Hsu, YT Smith, CL Nechushtan, A Xi, XG Youle, RJ TI Movement of Bax from the cytosol to mitochondria during apoptosis SO JOURNAL OF CELL BIOLOGY LA English DT Article ID FLUORESCENT PROTEIN GFP; PROGRAMMED CELL-DEATH; LIVING CELLS; BCL-2 ONCOPROTEIN; MEMBRANE PROTEIN; DIPHTHERIA-TOXIN; PRODUCT; BLOCKS; TRANSLOCATION; CYTOPLASM AB Bax, a member of the Bcl-2 protein family, accelerates apoptosis by an unknown mechanism. Bax has been recently reported to be an integral membrane protein associated with organelles or bound to or ganelles by Bcl-2 or a soluble protein found in the cytosol. To explore Bcl-2 family member localization in living cells, the green fluorescent protein (GFP) was fused to the NH2 termini of Bax, Bcl-2, and Bcl-X-L. Confocal microscopy performed on living Cos-7 kidney epithelial cells and L929 fibroblasts revealed that GFP-Bcl-2 and GFP-Bcl-X-L had a punctate distribution and colocalized with a mitochondrial marker, whereas GFP-Bax was found diffusely throughout the cytosol. Photobleaching analysis confirmed that GFP-Bax is a soluble protein, in contrast to organelle-bound GFP-Bcl-2. The diffuse localization of GFP-Bax did not change with coexpression of high levels of Bcl-2 or Bcl-X-L. However, upon induction of apoptosis, GFP-Bax moved intracellularly to a punctate distribution that partially colocalized with mitochondria. Once initiated, this Bax movement was complete within 30 min, before cellular shrinkage or nuclear condensation. Removal of a COOH-terminal hydrophobic domain from GFP-Bax inhibited redistribution during apoptosis and inhibited the death-promoting activity of both Bax and GFP-Bax. These results demonstrate that in cells undergoing apoptosis, an early, dramatic change occurs in the intracellular localization of Bax, and this redistribution of soluble Bax to organelles appears important for Bax to promote cell death. C1 NINCDS,BIOCHEM SECT,SURG NEUROL BRANCH,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NINCDS,LIGHT MICROSCOPY FACIL,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 41 TC 1334 Z9 1379 U1 5 U2 39 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 1 PY 1997 VL 139 IS 5 BP 1281 EP 1292 DI 10.1083/jcb.139.5.1281 PG 12 WC Cell Biology SC Cell Biology GA YK658 UT WOS:A1997YK65800018 PM 9382873 ER PT J AU Kim, YR Peterkofsky, B AF Kim, YR Peterkofsky, B TI Differential effects of ascorbate depletion and alpha,alpha'-dipyridyl treatment on the stability, but not on the secretion, of type IV collagen in differentiated F9 cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE basement membrane; vitamin C; degradation; proline hydroxylation; teratocarcinoma cells ID BASEMENT-MEMBRANE PROCOLLAGEN; TERATOCARCINOMA STEM-CELLS; HUMAN LUNG FIBROBLASTS; PARIETAL YOLK SACS; RETINOIC ACID; OSTEOGENESIS IMPERFECTA; PROLINE HYDROXYLATION; ENDOPLASMIC-RETICULUM; III PROCOLLAGEN; PROTEIN AB Ascorbic acid stimulates secretion of type I collagen because of its role in 4-hydroxyproline synthesis, but there is some controversy as to whether secretion of type IV collagen is similarly affected. This question was examined in differentiated F9 cells, which produce only type IV collagen, by labeling proteins with [C-14]proline and measuring collagen synthesis and secretion. Hydroxylation of proline residues in collagen was inhibited to a greater extent in cells treated with the iron chelator alpha,alpha'-dipyridyl (97.7%) than in cells incubated without ascorbate (63.1%), but both conditions completely inhibited the rate of collagen secretion after 2-4 h, respectively Neither treatment affected laminin secretion. Collagen synthesis was not stimulated by ascorbate even after treatment for 2 days. On SDS polyacrylamide gels, collagen produced by alpha,alpha'-dipyridyl-treated cells consisted mainly of a single band that migrated faster than either fully (+ ascorbate) or partially (- ascorbate) hydroxylated alpha 1(IV) or alpha 2(IV) chains. It did not contain interchain disulfide bonds or asn-linked glycosyl groups, and was completely digested by pepsin at 15 degrees C. These results suggested that it was a degraded product lacking the 7 S domain and that it could not form a triple helical structure. In contrast, the partially hydroxylated molecule contained interchain disulfide bonds and it was cleaved by pepsin to collagenous fragments similar in size to those obtained from the fully hydroxylated molecule, but at a faster rate. Kinetic experiments and monensin treatment suggested that completely unhydroxylated type IV collagen was degraded intracellularly in the endoplasmic reticulum or cis Golgi. These studies indicate that partial hydroxylation of type IV collagen confers sufficient helical structure to allow interchain disulfide bond formation and resistance to pepsin and intracellular degradation, but not sufficient for optimal secretion. (C) 1997 Wiley-Liss, Inc. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 46 TC 8 Z9 8 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD DEC 1 PY 1997 VL 67 IS 3 BP 338 EP 352 DI 10.1002/(SICI)1097-4644(19971201)67:3<338::AID-JCB6>3.0.CO;2-X PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YF524 UT WOS:A1997YF52400006 PM 9361189 ER PT J AU Shankavaram, UT DeWitt, DL Funk, SE Sage, EH Wahl, LM AF Shankavaram, UT DeWitt, DL Funk, SE Sage, EH Wahl, LM TI Regulation of human monocyte matrix metalloproteinases by SPARC SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID MACROPHAGE COLLAGENASE PRODUCTION; HUMAN MONONUCLEAR PHAGOCYTES; PROSTAGLANDIN-H SYNTHASE-2; EXTRACELLULAR-MATRIX; NONMINERALIZED TISSUES; ENDOTHELIAL-CELLS; GENE-EXPRESSION; BINDING; DIFFERENTIATION; RECEPTOR AB SPARC (secreted protein, acidic and rich in cysteine), also called osteonectin or BM-40, is a collagen-binding glycoprotein secreted by a variety of cells and is associated with functional responses involving tissue remodeling, cell movement and proliferation. Because SPARC and monocytes/macrophages are prevalent at sites of inflammation and remodeling in which there is connective tissue turnover, we examined the effect of SPARC on monocyte matrix metalloproteinase (MMP) production. Treatment of human peripheral blood monocytes with SPARC stimulated the production of gelatinase B (MMP-9) and interstitial collagenase (MMP-1). Experiments with synthetic peptides indicated that peptide 3.2, belonging to the alpha helical domain III of SPARC, is the major peptide mediating the MMP production by monocytes. SPARC and peptide 3.2 were also shown to induce prostaglandin synthase (PGHS)-2 as determined by Western and Northern blot analyses. The increase in PGHS-2 stimulated by SPARC or peptide 3.2 correlated with substantially elevated levels of prostaglandin E-2 (PGE(2)) and other arachidonic acid metabolites as measured by radioimmunoassay and high performance liquid chromatography (HPLC), respectively. Moreover, the synthesis of MMP was dependent on the generation of PGE(2) by PGHS-2, since indomethacin inhibited the production of these enzymes and their synthesis was restored by addition of exogenous PGE(2) or dibutyryl cAMP (Bt(2)cAMP). These results demonstrate that SPARC might play a significant role in the modulation of connective tissue turnover due to its stimulation of PGHS-2 and the subsequent release of PGE(2), a pathway that leads to the production of MMP by monocytes. (C) 1997 Wiley-Liss, Inc.(+) C1 NIDR,NIH,IMMUNOPATHOL SECT,BETHESDA,MD 20892. MICHIGAN STATE UNIV,DEPT BIOCHEM,E LANSING,MI 48824. UNIV WASHINGTON,DEPT BIOL STRUCT,SEATTLE,WA 98195. FU NHLBI NIH HHS [HL 18645]; NIGMS NIH HHS [GM 40711] NR 64 TC 88 Z9 89 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD DEC PY 1997 VL 173 IS 3 BP 327 EP 334 DI 10.1002/(SICI)1097-4652(199712)173:3<327::AID-JCP4>3.0.CO;2-P PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA YE619 UT WOS:A1997YE61900004 PM 9369945 ER PT J AU Winkles, JA Alberts, GF Chedid, M Taylor, WG DeMartino, S Rubin, JS AF Winkles, JA Alberts, GF Chedid, M Taylor, WG DeMartino, S Rubin, JS TI Differential expression of the keratinocyte growth factor (KGF) and KGF receptor genes in human vascular smooth muscle cells and arteries SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID ATHEROSCLEROTIC HUMAN ARTERIES; IMMUNOGLOBULIN DOMAIN; INTIMAL HYPERPLASIA; MESSENGER-RNA; ACIDIC FGF; SPECIFICITY; LIGAND; INTERLEUKIN-1; PROLIFERATION; FIBROBLASTS AB Keratinocyte growth factor (KGF) is a secreted member of the fibroblast growth factor (FGF) family of heparin-binding proteins. Studies reported to date indicate that it functions primarily as an important paracrine mediator of epithelial cell growth and differentiation. KGF appears to act via binding to a specific FGF receptor-2 isoform generated by an alternative splicing mechanism. To determine whether KGF may play a role in vascular smooth muscle cell (SMC) biology, we investigated KGF and KGF receptor gene expression in human SMC cultured in vitro as well as in several human nonatherosclerotic artery and atheroma specimens. KGF mRNA but not KGF receptor mRNA was expressed by SMCs, as determined by Northern blot hybridization analysis or reverse transcription-polymerase chain reaction assays, respectively. Additional experiments demonstrated that 1) human SMCs produce and secrete mitogenically active KGF and that 2) the cytokine interleukin-1 increases KGF mRNA and protein levels in human SMCs. We also found that KGF transcripts but not KGF receptor transcripts were expressed in control and atherosclerotic human arteries. Taken together, these results indicate that KGF is unlikely to be involved in SMC growth regulation unless ii can function intracellularly or interact with a presently unidentified KGF receptor. (C) 1997 Wiley-Liss, Inc.(dagger). C1 GEORGE WASHINGTON UNIV,MED CTR,DEPT BIOCHEM & MOL BIOL,WASHINGTON,DC 20037. GEORGE WASHINGTON UNIV,MED CTR,INST BIOMED SCI,WASHINGTON,DC 20037. NCI,CELLULAR & MOL BIOL LAB,NIH,BETHESDA,MD 20892. RP Winkles, JA (reprint author), AMER RED CROSS,HOLLAND LAB,DEPT MOL BIOL,15601 CRABBS BRANCH WAY,ROCKVILLE,MD 20855, USA. NR 44 TC 32 Z9 35 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD DEC PY 1997 VL 173 IS 3 BP 380 EP 386 DI 10.1002/(SICI)1097-4652(199712)173:3<380::AID-JCP10>3.0.CO;2-G PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA YE619 UT WOS:A1997YE61900010 PM 9369951 ER PT J AU Horinaka, N Kuang, TY Pak, H Wang, RB Jehle, J Kennedy, C Sokoloff, L AF Horinaka, N Kuang, TY Pak, H Wang, RB Jehle, J Kennedy, C Sokoloff, L TI Blockade of cerebral blood flow response to insulin-induced hypoglycemia by caffeine and glibenclamide in conscious rats SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 02-06, 1996 CL PHILADELPHIA, PA SP Amer Soc Neurochem DE adenosine receptors; ATP; sensitive K+ channels; [C-14]iodoantipyrine ID SENSITIVE POTASSIUM CHANNELS; DEPENDENT PROTEIN-KINASE; ARTERIAL SMOOTH-MUSCLE; K+ CHANNELS; ADENOSINE CONCENTRATION; OXIDATIVE-METABOLISM; VASCULAR-RESISTANCE; UNANESTHETIZED RATS; CORONARY-ARTERY; CYCLIC-AMP AB The possibility that adenosine and ATP-sensitive potassium channels (K-ATP) might be involved in the mechanisms of the increases in cerebral blood flow (CBF) that occur in insulin-induced hypoglycemia was examined. Cerebral blood flow was measured by the [C-14]iodoantipyrine method in conscious rats during insulin-induced, moderate hypoglycemia (2 to 3 mmol/L glucose in arterial plasma) after intravenous injections of 10 to 20 mg/kg of caffeine, an adenosine receptor antagonist, or intracisternal infusion of 1 to 2 mu mol/L glibenclamide, a K-ATP channel inhibitor. Cerebral blood flow was also measured in corresponding normoglycemic and drug-free control groups. Cerebral blood flow was 51% higher in untreated hypoglycemic than in untreated normoglycemic rats (P < 0.01). Caffeine had a small, statistically insignificant effect on CBF in normoglycemic rats, but reduced the CBF response to hypoglycemia in a dose-dependent manner, i.e., 27% increase with 10 mg/kg and complete elimination with 20 mg/kg. Chemical determinations by HPLC in extracts of freeze-blown brains showed significant increases in the levels of adenosine and its degradation products, inosine and hypoxanthine, during hypoglycemia (P < 0.05). Intracisternal glibenclamide had little effect on CBF in normoglycemia, but, like caffeine, produced dose-dependent reductions in the magnitude of the increases in CBF during hypoglycemia, i.e., +66% with glibenclamide-free artificial CSF administration, +25% with 1 mu mol/L glibenclamide, and almost complete blockade (+5%) with 2 mu mol/L glibenclamide. These results suggest that adenosine and K-ATP channels may play a role in the increases in CBF during hypoglycemia. C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. NR 62 TC 20 Z9 20 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD DEC PY 1997 VL 17 IS 12 BP 1309 EP 1318 PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA YJ686 UT WOS:A1997YJ68600006 PM 9397030 ER PT J AU Cassorla, F Mericq, V Eggers, M Avila, A Garcia, C Fuentes, A Rose, SR Cutler, GB AF Cassorla, F Mericq, V Eggers, M Avila, A Garcia, C Fuentes, A Rose, SR Cutler, GB TI Effects of luteinizing hormone-releasing hormone analog-induced pubertal delay in growth hormone (GH)-deficient children treated with GH: Preliminary results SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LONG-TERM TREATMENT; TRUE PRECOCIOUS PUBERTY; FINAL HEIGHT; ADULT HEIGHT; SEXUAL PRECOCITY; DEFICIENCY; AGONIST; GIRLS; THERAPY; DESLORELIN AB To study the effect of delaying epiphyseal fusion on the growth of GH-deficient children, we studied 14 pubertal, treatment naive, GH-deficient patients (6 girls and 8 boys) in a prospective, randomized, placebo-controlled trial. Chronological age was 14.5 +/- 0.5 yr, and bone age was 11.6 +/- 0.3 yr (mean +/- SEM) at the beginning of the study. Patients were assigned randomly to receive GH and LH-releasing hormone (LHRH) analog (n = 8) or GH and placebo (n = 6) during 3 yr, with planned continuation of GH treatment until epiphyseal fusion. Patients were measured with a stadiometer and had serum LHRH tests, serum testosterone (boys), serum estradiol (girls), and bone age performed every 6 months. Patients treated with GH and LHRH analog showed a clear suppression of their pituitary-gonadal axis and a marked delay in bone age progression. We observed a greater gain in height prediction in these patients than in the patients treated with GH and placebo after 3 yr of treatment (mean +/- SEM, 14.0 +/- 1.6 vs. 8.0 +/- 2.4 cm; P < 0.05). These preliminary findings suggest that delaying epiphyseal fusion with LHRH analog in pubertal GH-deficient children treated with GH increases height prediction and may increase final height compared to treatment with GH alone. C1 Univ Chile, Inst Invest Materno Infantil, Santiago, Chile. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Cassorla, F (reprint author), Univ Chile, Inst Invest Materno Infantil, Casilla 226-3, Santiago, Chile. RI Mericq, Veronica/F-3927-2010 NR 30 TC 21 Z9 21 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1997 VL 82 IS 12 BP 3989 EP 3992 DI 10.1210/jc.82.12.3989 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YL869 UT WOS:000071002000016 PM 9398701 ER PT J AU Kohn, LD Suzuki, K Hoffman, WH Tombaccini, D Marcocci, C Shimojo, N Watanabe, Y Amino, N Cho, BY Kohno, Y Hirai, A Tahara, K AF Kohn, LD Suzuki, K Hoffman, WH Tombaccini, D Marcocci, C Shimojo, N Watanabe, Y Amino, N Cho, BY Kohno, Y Hirai, A Tahara, K TI Characterization of monoclonal thyroid-stimulating and thyrotropin binding-inhibiting autoantibodies from a Hashimoto's patient whose children had intrauterine and neonatal thyroid disease SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID IDIOPATHIC MYXEDEMA PATIENTS; ANTI-TSH RECEPTOR; GRAVES-DISEASE; BLOCKING ANTIBODIES; IMMUNOGLOBULIN-G; TRANSIENT HYPOTHYROIDISM; CYTOCHEMICAL BIOASSAY; CLINICAL ASSAY; CELLS; LYMPHOCYTES AB A multiplicity of TSH receptor autoantibodies (TSHRAbs) have been characterized after subcloning heterohybridomas produced from the lymphocytes of a patient who has Hashimoto's thyroiditis and had three children with intrauterine or neonatal hyperthyroidism. Twelve clones produced stimulating TSHRAbs that increased cAMP levels and iodide uptake in rat FRTL-5 thyroid cells and increased cAMP levels in Chinese hamster ovary (CHO) cells transfected with the human TSHR; like 95% of Graves' stimulating TSHRAbs, all 12 have their functional epitope on the N-terminus of the TSHR extracellular domain, requiring residues 90-165 for activity. All 12 bind to human thyroid membranes in the absence, but not the presence, of TSH, but are only weak inhibitors of TSH binding in assays measuring TSH binding-inhibiting Igs (TBIIs). In contrast, 8 different clones produced TSHRAbs that did not increase cAMP levels, but, instead, exhibited significant TBII activity. Four inhibited the ability of TSH or a stimulating TSHRAb to increase cAMP levels and had their functional epitope on the C-terminal portion of the TSHR external domain, residues 261-370, mimicking the properties of blocking TSHRAbs that cause hypothyroidism in patients with idiopathic myxedema. The 4 other TBIIs inhibited the ability of TSH, but not that of a stimulating TSHRAb, to increase cAMP levels, like TBIIs in Graves' patients. The functional epitope for 3 of these Graves'-like TBIIs was residues 90-165; the functional epitope for the fourth was residues 24-89. The fourth also increased arachidonic acid release and inositol phosphate levels in FRTL-5 thyroid cells and exhibited conversion activity, i.e. the ability to increase cAMP levels in the presence of an anti-human IgG. Thus, this TBII exhibited signal transduction activity, unlike the other 3 Graves'-like TBIIs. The patient, therefore, has stimulating TSHRAbs and 3 different types of TBIIs, each with different functional properties and different epitopes on the TSHR. C1 NIDDKD, Cell Regulat Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Med Coll Georgia, Dept Pediat, Sect Pediat Endocrinol, Augusta, GA 30912 USA. Chiba Univ, Sch Med, Dept Pediat, Chiba 260, Japan. SRL Inc, Hachioji, Tokyo 192, Japan. Osaka Univ, Sch Med, Dept Lab Med, Suita, Osaka 565, Japan. Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 110744, South Korea. Chiba Univ, Sch Med, Dept Internal Med 2, Div Endocrinol & Metab, Chiba 280, Japan. RP Kohn, LD (reprint author), NIDDKD, Cell Regulat Sect, Metab Dis Branch, NIH, Bldg 10,Room 9C101B,10 Ctr DR MSC 1800, Bethesda, MD 20892 USA. EM lenk@bdg10.NIDDK.nih.gov NR 56 TC 35 Z9 35 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1997 VL 82 IS 12 BP 3998 EP 4009 DI 10.1210/jc.82.12.3998 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YL869 UT WOS:000071002000018 PM 9398703 ER PT J AU Tsigos, C Papanicolaou, DA Kyrou, I Defensor, R Mitsiadis, CS Chrousos, GP AF Tsigos, C Papanicolaou, DA Kyrou, I Defensor, R Mitsiadis, CS Chrousos, GP TI Dose-dependent effects of recombinant human interleukin-6 on glucose regulation SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PITUITARY-ADRENAL AXIS; INSULIN-SECRETION; INHIBITION; METABOLISM; ENDOCRINE; CYTOKINES; RECEPTOR; ISLETS; ALPHA; TNF AB Inflammatory cytokines have metabolic actions that probably contribute to the general adaptation of the organism during infectious or inflammatory stress. To examine the effects of interleukin 6 (IL-6), the main circulating cytokine, on glucose metabolism in man, we performed dose-response studies of recombinant human IL-6 in normal volunteers. Increasing single doses of IL-6 (0.1, 0.3, 1.0, 3.0, and 10.0 mg/Kg BW) were injected sc in 15 healthy male volunteers (3 in each dose) after a 12-h fast. All IL-6 doses were tolerated well and produced no significant adverse effects. We measured the circulating levels of glucose, insulin, C-peptide, and glucagon at baseline and half-hourly over 4 h after the IL-6 injection. Mean peak plasma levels of IL-6 were achieved between 120 and 240 min and were 8, 22, 65, 290, and 4050 pg/mL, respectively, for the 5 doses. After administration of the 2 smaller IL-6 doses, we observed no significant changes in plasma glucose levels, which, because of continued fasting, decreased slightly over time. By 60 min after the 3 higher IL-6 doses, however, the decline in fasting;blood glucose was arrested, and glucose levels increased in a dose-dependent fashion. The concurrent levels of plasma insulin and C-peptide were not affected by any IL-6 dose. In contrast, IL-6 caused significant increases in plasma glucagon levels, which peaked between 120 and 150 min after the IL-6 injection. In conclusion, sc IL-6 administration induced dose-dependent increases in fasting blood glucose, probably by stimulating glucagon release and other counteregulatory hormones and/or by inducing peripheral resistance to insulin action. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Hellen Natl Ctr Res Prevent & Treatment Diabet Me, Athens 10675, Greece. RP Tsigos, C (reprint author), Hellen Natl Diabet Ctr, 3 Ploutarchou St, Athens 10675, Greece. NR 19 TC 194 Z9 199 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1997 VL 82 IS 12 BP 4167 EP 4170 DI 10.1210/jc.82.12.4167 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YL869 UT WOS:000071002000049 PM 9398733 ER PT J AU Imai, Y Philippe, N Sesti, G Accili, D Taylor, SI AF Imai, Y Philippe, N Sesti, G Accili, D Taylor, SI TI Expression of variant forms of insulin receptor substrate-1 identified in patients with noninsulin-dependent diabetes mellitus SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GENE-MUTATIONS; ALPHA-GENE; IRS-1 GENE; PROTEIN; RESISTANCE; NIDDM; OBESITY; MICE; POLYMORPHISMS; ASSOCIATION AB Several polymorphisms have been identified in the amino acid sequence of human insulin receptor substrate-1 (IRS-1). Some of the variant sequences have been reported to be increased in prevalence among patients with noninsulin-dependent diabetes mellitus (NIDDM). This observation led to the hypothesis that these amino acid substitutions may impair the function of IRS-1, thereby causing the insulin resistance seen in patients with NIDDM. To address this question, we have designed studies to evaluate the effects of three variant sequences identified in our laboratory: Gly(819)-->Arg, Gly(972)-->Arg, and Arg(1221)-->Cys. We constructed four IRS-1 expression vectors for transfection in COS-7 cells: wild-type, single mutant (Gly(819)-->Arg), double mutant (Gly(819)-->Arg; Gly(972)-->Arg), and triple mutant (Glys(819)-->Arg; Gly(972)-->Arg; Arg(1221)-->Cys) IRS-1. The mutations did not alter the level of expression or the extent of insulin receptor-mediated tyrosine phosphorylation of recombinant IRS-1. Moreover, the mutations did not lead to a detectable impairment in the association of recombinant IRS-1 with important downstream effecters, including the p85 subunit of phosphatidylinositol 3-kinase and growth factor receptor-binding protein-2. We conclude that these amino acid substitutions do not appear to cause a major defect in the function of IRS-1, as judged by our assays. However, this type of assay probably lacks the sensitivity to detect subtle functional defects. In light of the suggestive associations observed in epidemiological studies, it is premature to totally discard the hypothesis that variant sequences of IRS-1 may contribute to the pathogenesis of NIDDM. Nevertheless, our studies cannot be interpreted as lending support to that hypothesis. C1 NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. Univ Roma Tor Vergata, Dipartimento Med Interna, Rome, Italy. RP Taylor, SI (reprint author), NIDDKD, Diabet Branch, NIH, Bldg 10,Room 9S-213,10 Ctr Dr, Bethesda, MD 20892 USA. EM Simeon_Taylor@nih.gov RI Sesti, Giorgio/B-1509-2012; OI Sesti, Giorgio/0000-0002-1618-7688 FU Telethon [E.0327] NR 34 TC 35 Z9 35 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1997 VL 82 IS 12 BP 4201 EP 4207 DI 10.1210/jc.82.12.4201 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YL869 UT WOS:000071002000056 PM 9398740 ER PT J AU Yamaguchi, KI Shimojo, N Kikuoka, S Hoshioka, A Hirai, A Tahara, K Kohn, LD Kohno, Y Niimi, H AF Yamaguchi, KI Shimojo, N Kikuoka, S Hoshioka, A Hirai, A Tahara, K Kohn, LD Kohno, Y Niimi, H TI Genetic control of anti-thyrotropin receptor antibody generation in H-2(K) mice immunized with thyrotropin receptor transfected fibroblasts SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID AUTOIMMUNE THYROID-DISEASE; GRAVES-DISEASE; EXTRACELLULAR DOMAIN; IMMUNOGLOBULIN-G; NOD MICE; INDUCTION; EXPRESSION; LYMPHOCYTES; ANTIGEN; STRAINS AB We recently showed that immunization of AKR/N mice with murine fibroblasts transfected with the thyrotropin receptor (TSHR) and a murine major histocompatibility complex (MHC) class II molecule having the same H-2(k) haplotype, but not either alone, induces immune thyroid disease with the humoral and histological features of human Graves', including the presence of two different TSHR antibodies (TSHRAbs): stimulating TSHRAbs which cause hyperthyroidism and thyrotropin-binding-inhibiting immunoglobulins (TBIIs). Immunization of 5 different mouse strains that share the H-2(k) haplotype, but differ in their genetic background, results in different TBII titers, indicating non-MHC genetic effect on TSHRAb formation. In addition, immunization of C3H/He mice induced TBII formation even in the absence of aberrant class II, unlike AKR/N mice. However, the mice did not develop hyperthyroxinemia characteristic of the presence of stimulating TSHRAbs. Aberrant class II expression is, therefore, necessary for the development of a full Graves' syndrome with stimulating TSHRAbs; and immune recognition mechanisms by which TBIIs and stimulating TSHRAbs develop are differently regulated. C1 Chiba Univ, Sch Med, Dept Pediat, Chiba 260, Japan. Chiba Univ, Sch Med, Dept Internal Med 2, Chiba 260, Japan. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Yamaguchi, KI (reprint author), Chiba Univ, Sch Med, Dept Pediat, Chiba 260, Japan. NR 21 TC 41 Z9 42 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1997 VL 82 IS 12 BP 4266 EP 4269 DI 10.1210/jc.82.12.4266 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YL869 UT WOS:000071002000067 PM 9398751 ER PT J AU Bornstein, SR Torpy, DJ Chrousos, GP Licinio, J Engelmann, L AF Bornstein, SR Torpy, DJ Chrousos, GP Licinio, J Engelmann, L TI Leptin levels are elevated despite low thyroid hormone levels in the "euthyroid sick" syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Letter ID EXPRESSION C1 NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIMH, NIH, Bethesda, MD 20892 USA. Univ Leipzig, Dept Internal Med 3, D-7010 Leipzig, Germany. RP Bornstein, SR (reprint author), NICHD, Dev Endocrinol Branch, NIH, Bldg 10 Rm 10N-26Z,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Licinio, Julio/0000-0001-6905-5884 NR 14 TC 13 Z9 14 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1997 VL 82 IS 12 BP 4278 EP 4279 DI 10.1210/jc.82.12.4278 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YL869 UT WOS:000071002000077 PM 9398759 ER PT J AU Sternberg, EM AF Sternberg, EM TI Neural-immune interactions in health and disease SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID CORTICOTROPIN-RELEASING HORMONE; CENTRAL-NERVOUS-SYSTEM; NEURONAL SURVIVAL; INDUCED ARTHRITIS; GENE-EXPRESSION; RATS; CYTOKINES; BRAIN; CELL; SUSCEPTIBILITY C1 NIMH, Sect Neuroendocrine Immunol & Behav, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Sternberg, EM (reprint author), NIMH, Sect Neuroendocrine Immunol & Behav, Clin Neuroendocrinol Branch, NIH, Bldg 10,Rm 2D-46,10 Ctr Dr,MSC 1284, Bethesda, MD 20892 USA. NR 31 TC 215 Z9 220 U1 1 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC 1 PY 1997 VL 100 IS 11 BP 2641 EP 2647 DI 10.1172/JCI119807 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA YL912 UT WOS:000071007300001 PM 9389725 ER PT J AU Welsh, LE Quinn, TC Gaydos, CA AF Welsh, LE Quinn, TC Gaydos, CA TI Influence of endocervical specimen adequacy on PCR and direct fluorescent-antibody staining for detection of Chlamydia trachomatis infections SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID LIGASE CHAIN-REACTION; FIRST-VOID URINE; REACTION ASSAY; CERVICAL INFECTION; ASYMPTOMATIC MEN; DIAGNOSIS; WOMEN; QUALITY; DNA AB The cellular quality of the endocervical swab specimen used for the detection of Chlamydia trachomatis may dramatically impact the sensitivity of the diagnostic assay used, An evaluation of the adequacy of 319 endocervical swab specimens from women attending two inner-city sexually transmitted disease and family planning clinics, as well as five high school-based family planning clinics, was performed, and the resulting data were compared with the diagnostic results obtained by both Amplicor PCR and Microtrak direct fluorescent-antibody (DFA) staining. The swab from each patient was rolled across the open circular area of a DFA slide and then used to inoculate a transport tube for PCR (Roche), after which the swab was discarded, The slides were stained and examined by epifluorescence microscopy for the presence of C., trachomatis elementary bodies and for the presence and number of cell types to determine specimen adequacy. Cellular adequacy for a cervical swab specimen was defined as the presence of one or more columnar epithelial or metaplastic epithelial cells or the presence of more than 100 erythrocytes per high-power microscopic field. Of the 319 specimens read by DFA, 204 (63.9%) were determined to be adequate. There were 34 (10.7%) positive specimens by DFA and/or PCR. Twenty-nine (9.1%) specimens were positive by PCR, 20 (6.3%) specimens were DFA positive, and 15 (4.7%) were concordantly positive by both tests, The prevalence of chlamydia among adequate specimens was 14.2% (29/204), compared to 4.3% (5/115) for inadequate specimens (P < 0.0001), Variations in specimen quality and the sensitivity of the diagnostic assay used have a significant impact on determining the prevalence of C. trachomatis in a population. C1 JOHNS HOPKINS UNIV,DIV INFECT DIS,BALTIMORE,MD 21205. NIAID,NIH,BETHESDA,MD 20892. RI Gaydos, Charlotte/E-9937-2010 NR 30 TC 27 Z9 29 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 1997 VL 35 IS 12 BP 3078 EP 3081 PG 4 WC Microbiology SC Microbiology GA YG967 UT WOS:A1997YG96700012 PM 9399497 ER PT J AU Navarro, EE Almario, JS Schaufele, RL Bacher, J Walsh, TJ AF Navarro, EE Almario, JS Schaufele, RL Bacher, J Walsh, TJ TI Quantitative urine cultures do not reliably detect renal candidiasis in rabbits SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID TRACT INFECTIONS; CLINICAL-SIGNIFICANCE; CANDIDURIA; ALBICANS; DIAGNOSIS AB The significance of quantitative urine cultures in patients at risk for hematogenous disseminated candidiasis is controversial, While various concentrations of Candida spp. in urine have been suggested as critical cutoff points in the diagnosis of renal candidiasis, other investigators consider quantitative cultures less critical in diagnosing upper tract infections, To determine the significance of quantitative urine cultures in renal candidiasis, we studied serial quantitative urinary cultures of Candida albicans in a rabbit model of hematogenous infection, Of 197 urine samples from 34 infected animals, 144 were culture positive, with a sensitivity of 73.1% for urine cultures and a lower limit of detection of 10 CFU/ml, The yield of urine cultures varied according to severity and duration of infection, The mean renal and urinary concentrations of C. albicans from rabbits with subacute candidiasis differed significantly from those from rabbits with acute candidiasis (P = 0.013 and P less than or equal to 0.001, respectively), During the first 4 days of subacute renal candidiasis, more than one-half of all urine cultures were negative for C. albicans, Only 12 (8.1%) of 148 urine cultures in animals with subacute renal candidiasis had concentrations of >10(3) CFU/ml, 2.7% had concentrations of >10(4) CFU/ml, and none were greater than or equal to 10(5) CFU/ml, By comparison, all urine cultures from the animals dth lethal acute renal candidiasis had higher concentrations of C. albicans and were positive throughout the course of infection, Urinary concentrations of C. albicans were not predictive of the amount of Candida in the kidney (r less than or equal to 0.49) and did not correlate with survival (r = 0.0232), However, the renal concentration of C. albicans (in CFU/gram) inversely correlated with the duration of survival (in days) of rabbits with renal candidiasis (r = 0.76; P < 0.001), These findings indicate that a negative urine culture in rabbits does not preclude the presence of renal candidiasis, The interpretation of a urine culture positive at any concentration, on the other hand, must involve an analysis of the risk factors for renal candidiasis, for any urinary concentration of C. albicans may reflect kidney infection. C1 NCI,PEDIAT BRANCH,IMMUNOCOMPROMISED HOST SECT,BETHESDA,MD 20892. NIH,VET RESOURCE PROGRAM,DIV RES RESOURCES,BETHESDA,MD 20892. GEORGETOWN UNIV HOSP,DEPT INTERNAL MED,NEPHROL SECT,WASHINGTON,DC 20007. NR 43 TC 12 Z9 13 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 1997 VL 35 IS 12 BP 3292 EP 3297 PG 6 WC Microbiology SC Microbiology GA YG967 UT WOS:A1997YG96700052 PM 9399537 ER PT J AU Moreno, C Alvarado, M Balcazar, H Lane, C Newman, E Ortiz, G Forrest, M AF Moreno, C Alvarado, M Balcazar, H Lane, C Newman, E Ortiz, G Forrest, M TI Heart disease education and prevention program targeting immigrant Latinos: Using focus group responses to develop effective interventions SO JOURNAL OF COMMUNITY HEALTH LA English DT Article ID ACCULTURATION AB Although research has provided considerable knowledge concerning the positive effects of behavioral change on morbidity and mortality from heart disease and related risk factors, some segments of the population have not benefited equitably from this information. In April 1995, the National Heart, Lung, and Blood Institute (NHLBI) conducted seven focus groups to determine knowledge and attitudes about heart disease and associated risk factors, identify media usage and preferences, and assess publications usage and preferences among Spanish-speaking Latino immigrants residing in the Washington, D.C., metropolitan al ea. This information was gathered to assist in the development of key messages and strategies for the NHLBI Latino Community Cardiovascular Disease Prevention and Outreach Initiative, Salud para su Corazon-a heart disease prevention and education campaign. Findings from these focus groups indicate that Latinos may not benefit from heart disease prevention messages developed for the general population because of language and cultural differences. The researchers concluded that health education and disease prevention programs targeting the Latino community should develop educational materials and interventions that addresss language preferences and cultural values. Furthermore, to be effective, these programs should show people how to make positive behavioral changes based on their current circumstances, while remaining sensitive to the fact that Latino immigrants face major life adjustments and many are still greatly influenced by their country of origin. C1 NHLBI,BETHESDA,MD 20892. ARIZONA STATE UNIV,TEMPE,AZ 85287. NR 6 TC 29 Z9 30 U1 0 U2 5 PU HUMAN SCI PRESS INC PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 SN 0094-5145 J9 J COMMUN HEALTH JI J. Community Health PD DEC PY 1997 VL 22 IS 6 BP 435 EP 450 DI 10.1023/A:1025128615666 PG 16 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA YH681 UT WOS:A1997YH68100003 PM 9403401 ER PT J AU Thall, PF Russell, KE Simon, RM AF Thall, PF Russell, KE Simon, RM TI Variable selection in regression via repeated data splitting SO JOURNAL OF COMPUTATIONAL AND GRAPHICAL STATISTICS LA English DT Article DE cross validation; data splitting; Monte Carlo simulation; regression; variable selection ID CROSS-VALIDATION; PREDICTION ERROR; BOOTSTRAP; MODELS AB A new algorithm-backward elimination via repeated data splitting (BERDS)-is proposed for variable selection in regression. Initially, the data are partitioned into two sets {E, V}, and an exhaustive backward elimination (BE) is performed in E. For each p value cutoff alpha used in BE, the corresponding fitted model from E is validated in V by computing the sum of squared deviations of observed from predicted values. This is repeated m times, and the ct minimizing the sum of the m sums of squares is used as the cutoff in a final BE on the entire data set. BERDS is a modification of the algorithm BECV proposed by Thall, Simon, and Grier (1992). An extensive simulation study shows that, compared to BECV, BERDS has a smaller model error and higher probabilities of excluding noise variables, of selecting each of several uncorrelated true predictors, and of selecting exactly one of two or three highly correlated true predictors. BERDS is also superior to standard BE with cutoffs .05 or .10, and this superiority increases with the number of noise variables in the data and the degree of correlation among true predictors. An application is provided for illustration. C1 RICE UNIV,DEPT USER SERV,HOUSTON,TX 77005. NCI,BIOMETR RES BRANCH,CANC THERAPY EVALUAT PROGRAM,ROCKVILLE,MD 20892. RP Thall, PF (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,DEPT BIOMATH,1515 HOLCOMBE BLVD,BOX 237,HOUSTON,TX 77030, USA. NR 27 TC 8 Z9 8 U1 1 U2 2 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 SN 1061-8600 J9 J COMPUT GRAPH STAT JI J. Comput. Graph. Stat. PD DEC PY 1997 VL 6 IS 4 BP 416 EP 434 DI 10.2307/1390744 PG 19 WC Statistics & Probability SC Mathematics GA YK837 UT WOS:A1997YK83700004 ER PT J AU Vidal, NOA Ekberg, S Enerback, S Lindahl, A Ohlsson, C AF Vidal, NOA Ekberg, S Enerback, S Lindahl, A Ohlsson, C TI The CCAAT/enhancer-binding protein-alpha is expressed in the germinal layer of the growth plate: colocalisation with the growth hormone receptor SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID RAT EPIPHYSEAL CHONDROCYTES; FACTOR-I GENE; SUSPENSION-CULTURE; COLONY FORMATION; RABBIT EAR; CELLS; DIFFERENTIATION; PROLIFERATION; CARTILAGE; TIBIA AB The transcription factor C/EBP alpha, a member of the CCAAT/enhancer-binding protein family, is highly expressed in the liver and in adipose tissue. The aim of this study was to determine if C/EBP alpha is expressed in rat growth cartilage. The expression pattern of C/EBP alpha in monolayer-cultured growth plate chondrocytes was similar to that of C/EBP alpha during hepatocyte and preadipocyte differentiation. Immunohistochemistry with a polyclonal antibody for C/EBP alpha revealed that the C/EBP alpha protein is present in the perichondrial ring, in the germinal layer of the growth plate and on the surface of the articular cartilage. The growth hormone (GH) receptor has a similar distribution in the rat tibial growth plate, and hypophysectomised rats were used to investigate a possible connection between C/EBP alpha and GH. C/EBP alpha mRNA levels were decreased in rib cartilage after hypophysectomy. However, GH treatment did not counteract this effect, indicating that other pituitary hormones regulate the C/EBP alpha mRNA levels in growth plate cartilage. We thus demonstrate, for the first time, that C/EBP alpha is expressed in cartilage. The finding that C/EBP alpha, like the GH receptor, is predominantly expressed in stem cell areas of the rat growth plate indicates a possible functional role for C/EBP alpha during early chondrogenic differentiation. C1 UNIV GOTHENBURG,SAHLGRENS UNIV HOSP,DEPT INTERNAL MED,RES CTR ENDOCRINOL & METAB,S-41345 GOTHENBURG,SWEDEN. DEPT MOL BIOL,GOTHENBURG,SWEDEN. NIDDK,DIABET BRANCH,NATL INST HLTH,BETHESDA,MD 20892. RP Vidal, NOA (reprint author), UNIV GOTHENBURG,SAHLGRENS UNIV HOSP,DEPT CLIN CHEM,RES CTR ENDOCRINOL & METAB,BRUNA STRAKET 16,S-41345 GOTHENBURG,SWEDEN. RI Lindahl, Anders/H-9550-2014 OI Lindahl, Anders/0000-0003-2871-5166 NR 33 TC 9 Z9 9 U1 0 U2 0 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD DEC PY 1997 VL 155 IS 3 BP 433 EP 441 DI 10.1677/joe.0.1550433 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YK176 UT WOS:A1997YK17600004 PM 9487988 ER PT J AU Sousa, CRE Hieny, S SchartonKersten, T Jankovic, D Charest, H Germain, RN Sher, A AF Sousa, CRE Hieny, S SchartonKersten, T Jankovic, D Charest, H Germain, RN Sher, A TI In vivo microbial stimulation induces rapid CD40 ligand-independent production of interleukin 12 by dendritic cells and their redistribution to T cell areas SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TUMOR-NECROSIS-FACTOR; INTERFERON-GAMMA PRODUCTION; IFN-GAMMA; TOXOPLASMA-GONDII; PHENOTYPE DEVELOPMENT; MONOCLONAL-ANTIBODY; LANGERHANS CELLS; IL-12 PRODUCTION; ACUTE INFECTION; UP-REGULATION AB The early induction of interleukin (IL)-12 is a critical event in determining the development of both innate resistance and adaptive immunity to many intracellular pathogens. Previous in vitro studies have suggested that the macrophage (M Phi) is a major source of the initial IL-12 produced upon microbial stimulation and that this response promotes the differentiation of protective T helper cell 1 (Th1) CD4(+) lymphocytes from precursors that are primed on antigen-bearing dendritic cells (DC). Here, we demonstrate by immunolocalization experiments and flow cytometric analysis that, contrary to expectation, DC and not M Phi are the initial cells to synthesize IL-12 in the spleens of mice exposed in vivo to an extract of Toxoplasma gondii or to lipopolysaccharide, two well characterized microbial stimulants of the cytokine. importantly, this production of IL-12 occurs very rapidly and is independent of interferon gamma priming or of signals from T cells, such as CD40 ligand. IL-12 production by splenic DC is accompanied by an increase in number of DCs, as well as a redistribution to the T cell areas and the acquisition of markers characteristic of interdigitating dendritic cells. The capacity of splenic DC but not M Phi to synthesize de novo high levels of IL-12 within hours of exposure to microbial products in vivo, as well as the ability of the same stimuli to induce migration of DC to the T cell areas, argues that DC function simultaneously as both antigen-presenting cells and IL-12 producing accessory cells in the initiation of cell-mediated immunity to intracellular pathogens. This model avoids the need to invoke a three-cell interaction for Th1 differentiation and points to the DC as both a sentinel for innate recognition and the dictator of class selection in the subsequent adaptive response. C1 NIAID,IMMUNOBIOL SECT,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. RP Sousa, CRE (reprint author), NIAID,LBS,LI,DIR,NIH,BLDG 10,RM 11N311,10 CTR DR,MSC 1892,BETHESDA,MD 20892, USA. NR 44 TC 486 Z9 491 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 1 PY 1997 VL 186 IS 11 BP 1819 EP 1829 DI 10.1084/jem.186.11.1819 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA YK681 UT WOS:A1997YK68100004 PM 9382881 ER PT J AU Oravecz, T Pall, M Roderiquez, G Gorrell, MD Ditto, M Nguyen, NY Boykins, R Unsworth, E Norcross, MA AF Oravecz, T Pall, M Roderiquez, G Gorrell, MD Ditto, M Nguyen, NY Boykins, R Unsworth, E Norcross, MA TI Regulation of the receptor specificity and function of the chemokine RANTES (regulated on activation, normal T cell expressed and secreted) by dipeptidyl peptidase IV (CD26)-mediated cleavage SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID STIMULATING FACTOR; MOLECULAR-CLONING; HIV-1 ENTRY; CD26; IDENTIFICATION; INFECTION; FUSION; CHEMOATTRACTANT; 7-TRANSMEMBRANE; PROTEINS AB CD26 is a leukocyte activation marker that possesses dipeptidyl peptidase IV activity but whose natural substrates and immunological functions have not been clearly defined. Several chemokines, including RANTES (regulated on activation, normal T cell expressed and secreted), have now been shown to be substrates for recombinant soluble human CD26. The truncated RANTES(3-68) lacked the ability of native RANTES(1-68) to increase the cytosolic calcium concentration in human monocytes, but still induced this response in macrophages activated with macrophage colony-stimulating factor. Analysis of chemokine receptor messenger RNAs and patterns of desensitization of chemokine responses showed that the differential activity of the truncated molecule results from an altered receptor specificity. RANTES(3-68) showed a reduced activity, relative to that of RANTES(1-68), with cells expressing the recombinant CCR1 chemokine receptor, but retained the ability to stimulate CCR5 receptors and to inhibit the cytopathic effects of HIV-1. Our results indicate that CD26-mediated processing together with cell activation-induced changes in receptor expression provides an integrated mechanism for differential cell recruitment and for the regulation of target cell specificity of RANTES, and possibly other chemokines. C1 NIH,DIV HEMATOL PROD,CTR BIOL EVALUAT & RES,FDA,BETHESDA,MD 20892. US FDA,DIV ALLERGEN PROD & PARASITOL,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. US FDA,FACIL BIOTECHNOL RESOURCES,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. ROYAL PRINCE ALFRED HOSP,AW MORROW GASTROENTEROL & LIVER CTR,NEWTOWN,NSW 2042,AUSTRALIA. UNIV SYDNEY,CENTENARY INST CANC MED & CELL BIOL,NEWTOWN,NSW 2042,AUSTRALIA. OI Gorrell, Mark/0000-0002-0528-2604 NR 36 TC 296 Z9 298 U1 0 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 1 PY 1997 VL 186 IS 11 BP 1865 EP 1872 DI 10.1084/jem.186.11.1865 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA YK681 UT WOS:A1997YK68100008 PM 9382885 ER PT J AU Punt, JA Havran, W Abe, R Sarin, A Singer, A AF Punt, JA Havran, W Abe, R Sarin, A Singer, A TI T cell receptor (TCR)-induced death of immature CD4(+)CD8(+) thymocytes by two distinct mechanisms differing in their requirement for CD28 costimulation: Implications for negative selection in the thymus SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TUMOR-NECROSIS-FACTOR; FAS-LIGAND; PHOSPHATIDYLINOSITOL 3-KINASE; INDUCED APOPTOSIS; CLONAL DELETION; TRANSGENIC MICE; CD4+CD8+ CELLS; ACTIVATION; ANTIGEN; EXPRESSION AB Negative selection is the process by which the developing lymphocyte receptor repertoire rids itself of autoreactive specificities. One mechanism of negative selection in developing T cells is the induction of apoptosis in immature CD4(+)CD8(+) (DP) thymocytes, referred to as clonal deletion. Clonal deletion is necessarily T cell receptor (TCR) specific, but TCR signals alone are not lethal to purified DP thymocytes. Here, we identify two distinct mechanisms by which TCR-specific death of DP thymocytes can be induced. One mechanism requires simultaneous TCR and costimulatory signals initiated by CD28. The other mechanism is initiated by TCR signals in the absence of simultaneous costimulatory signals and is mediated by subsequent interaction with antigen-presenting cells. We propose that these mechanisms represent two distinct clonal deletion strategies that are differentially implemented during development depending on whether immature thymocytes encounter antigen in the thymic cortex or thymic medulla. C1 NCI, EXPT IMMUNOL BRANCH, NIH, BETHESDA, MD 20892 USA. USN, MED RES INST, IMMUNE CELL BIOL DEPT, BETHESDA, MD 20889 USA. Scripps Res Inst, DEPT IMMUNOL, LA JOLLA, CA 92037 USA. NR 79 TC 90 Z9 90 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 1 PY 1997 VL 186 IS 11 BP 1911 EP 1922 DI 10.1084/jem.186.11.1911 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA YK681 UT WOS:A1997YK68100012 PM 9382889 ER PT J AU Miller, DS Pritchard, JB AF Miller, DS Pritchard, JB TI Dual pathways for organic anion secretion in renal proximal tubule SO JOURNAL OF EXPERIMENTAL ZOOLOGY LA English DT Article; Proceedings Paper CT Symposium on Cellular and Molecular Membrane Transport in Honor of Arnost Kleinzeller CY AUG 01-03, 1996 CL MT DESERT ISL BIOL LAB, SALSBURY COVE, ME HO MT DESERT ISL BIOL LAB ID CANALICULAR MEMBRANE; INHIBITION; MECHANISMS; TRANSPORT; CATIONS AB Transport on the ''classical'' organic anion system in renal proximal tubule is specific, active, Na-dependent, and ouabain sensitive. Here we review recent studies using intact teleost proximal tubules and laser scanning confocal microscopy which show that the secretion of large organic anions, such as, fluorescein-methotrexate (FL-MTX, Mw 923 Da) is handled by a separate and distinct organic anion transport system. In contrast to the classical system, FL-MTX uptake into cells and secretion into the tubular lumen was ouabain insensitive and largely Na-independent. KCN did not affect cellular uptake but abolished secretion into the lumen. PAH and probenecid, potent inhibitors of transport on the classical system, were weak inhibitors of FL-MTX transport. Uptake and secretion of FL-MTX were inhibited by micromolar concentrations of other organic anions (MTX, folate, bromocresol green, bromosulfonphthalein). FL-MTX secretion into the lumen was inhibited by leukotriene C-4 and cyclosporine A, neither of which affected transport of the model substrate for the classical system, fluorescein. Thus, FL-MTX secretion is specific, but largely Na-independent and ouabain-insensitive. Both the basolateral and luminal steps in FL-MTX transport differ from those associated with fluorescein and P-aminohippurate secretion. (C) 1997 Wiley-Liss, Inc. RP Miller, DS (reprint author), NIEHS,LAB PHARMACOL & CHEM,NIH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 14 TC 22 Z9 23 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0022-104X J9 J EXP ZOOL JI J. Exp. Zool. PD DEC 1 PY 1997 VL 279 IS 5 BP 462 EP 470 DI 10.1002/(SICI)1097-010X(19971201)279:5<462::AID-JEZ8>3.0.CO;2-M PG 9 WC Zoology SC Zoology GA YH746 UT WOS:A1997YH74600008 PM 9392867 ER PT J AU Sekhar, M Yu, JM Soma, T Dunbar, CE AF Sekhar, M Yu, JM Soma, T Dunbar, CE TI Murine long-term repopulating ability is compromised by ex vivo culture in serum-free medium despite preservation of committed progenitors SO JOURNAL OF HEMATOTHERAPY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; UMBILICAL-CORD BLOOD; BONE-MARROW CELLS; PERIPHERAL-BLOOD; EXVIVO EXPANSION; GROWTH-FACTORS; CD34+ CELLS; IN-VITRO; COMPETITIVE REPOPULATION; ENGRAFTMENT AB Hematopoietic progenitor cells can be maintained and expanded ex vivo in standard or serum-free culture medium supplemented with a variety of stimulatory cytokines, The use of serum-free medium allows specification of reproducible and precise growth conditions optimal for various applications and is more acceptable from a safety and regulatory point of view, Human and murine committed progenitor cells have been shown to be equivalently or better supported by serum-free culture conditions in the presence of multicytokine combinations, but there is little information on the effects of such culture conditions on repopulating stem cells, We used a murine competitive repopulation model to assess the effect of serum-free versus serum-containing ex vivo culture on long-term reconstituting cells, Despite equivalent numbers of committed CFU-C and day 12 CFU-S present after 4 days of culture of murine marrow in serum-free or serum-containing conditions in the presence of IL-3, IL-6, and SCF, long-term reconstituting activity was significantly impaired by serum-free culture, These findings may have important implications for transplantation and gene therapy applications. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Dunbar, CE (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,73103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 44 TC 17 Z9 19 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1061-6128 J9 J HEMATOTHER JI J. Hematother. PD DEC PY 1997 VL 6 IS 6 BP 543 EP 549 DI 10.1089/scd.1.1997.6.543 PG 7 WC Hematology; Medicine, Research & Experimental; Transplantation SC Hematology; Research & Experimental Medicine; Transplantation GA YP410 UT WOS:000071274000004 PM 9483189 ER PT J AU Jamur, MC Grodzki, ACG Moreno, AN Swaim, WD Siraganian, RP Oliver, C AF Jamur, MC Grodzki, ACG Moreno, AN Swaim, WD Siraganian, RP Oliver, C TI Immunomagnetic isolation of rat bone marrow-derived and peritoneal mast cells SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE mast cell; maturation; peritoneal cavity; bone marrow; immunomagnetic; immunocytochemistry; electron microscopy ID BASOPHILIC LEUKEMIA-CELLS; MONOCLONAL-ANTIBODIES; IGE; BINDING; IDENTIFICATION; MACS AB Mast cells are difficult to purify from heterogeneous cell populations and to preserve, especially for pre-embedding immunostaining at the ultrastructural level. We have developed a technique that permits the isolation of a pure population of mast cells suitable for immunocytochemical studies. A rat mast cell-specific monoclonal antibody (MAb AA4) conjugated to tosylactivated Dynabeads 450 was used to immunomagnetically separate mast cells from rat bone marrow and peritoneal cell suspensions. Approximately 85% of the mast cells were recovered in the positive population that comprised virtually pure mast cells. After microwave fixation, morphological examination showed that the cells were intact and retained their ultrastructural detail. Mast cells in all stages of maturation were immunolabeled with a panel of antibodies after immunomagnetic separation. The combination of immunomagnetic separation followed by immunostaining should prove useful for the study of mast cell maturation and for the characterization of other specific cell types that are present in tissues in only limited numbers. C1 OFF NAVAL RES,ARLINGTON,VA 22217. UNIV FED PARANA,DEPT BIOL CELULAR,BR-80060000 CURITIBA,PARANA,BRAZIL. NIDR,IMMUNOL LAB,NIH,BETHESDA,MD 20892. RI Jamur, Maria Celia/L-5520-2016 OI Jamur, Maria Celia/0000-0001-7065-8543 NR 28 TC 13 Z9 13 U1 0 U2 2 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD DEC PY 1997 VL 45 IS 12 BP 1715 EP 1722 PG 8 WC Cell Biology SC Cell Biology GA YK686 UT WOS:A1997YK68600015 PM 9389775 ER PT J AU Youn, BS Zhang, SM Lee, EK Park, DH Broxmeyer, HE Murphy, PM Locati, M Pease, JE Kim, KK Antol, K Kwon, BS AF Youn, BS Zhang, SM Lee, EK Park, DH Broxmeyer, HE Murphy, PM Locati, M Pease, JE Kim, KK Antol, K Kwon, BS TI Molecular cloning of leukotactin-1: A novel human beta-chemokine, a chemoattractant for neutrophils, monocytes, and lymphocytes, and a potent agonist at CC chemokine receptors 1 and 3 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY FORMATION; IDENTIFICATION; SEQUENCE; GENES; MIP-1-ALPHA; MIP-1-BETA; EXPRESSION; PROTEINS; RANTES; FAMILY AB A new member of human beta-chemokine cDNA was isolated and named leukotactin-1 (Lkn-1). Lkn-1, along with murine macrophage inflammatory protein-related protein-1 and -2, defines a subgroup of beta-chemokines based on two conserved cysteines in addition to the four others conserved in all beta-chemokines. The putative mature Lkn-1 is composed of 92 amino acids with a calculated m.w. of 10,162. The Lkn-1 gene was mapped to human chromosome 17, region q12. Recombinant Lkn-1 was a potent chemoattractant for neutrophils, monocytes, and lymphocytes and induced calcium flux in these cells, Lkn-1 specifically induced calcium flux in CCR1- and CCR3-expressing HOS cell lines. Lkn-1 suppressed colony formation by human granulocyte-macrophage, erythroid, and multipotential progenitor cells stimulated by combinations of growth factors. Hence, we have isolated and characterized a human C6 beta-chemokine that is a potent agonist at CCR1 and CCR3 and shows broad biologic activities, including leukocyte chemoattraction. C1 Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Walther Oncol Ctr, Indianapolis, IN 46202 USA. Mogam Biotechnol Res Inst, KyungKi Do, South Korea. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Univ Sheffield, Krebs Inst, Dept Mol Biol & Biotechnol, Sheffield S10 2TN, S Yorkshire, England. St Marys Coll, Dept Chem Phys, Notre Dame, IN 46556 USA. RP Kwon, BS (reprint author), Indiana Univ, Sch Med, Dept Microbiol & Immunol, 635 Barnhill Dr, Indianapolis, IN 46202 USA. RI Kim, Kack-Kyun/C-5031-2012; Locati, Massimo/H-8404-2015 OI Kim, Kack-Kyun/0000-0002-1279-5387; Locati, Massimo/0000-0003-3077-590X FU NHLBI NIH HHS [HL56416]; NIAID NIH HHS [AI28125]; NIDCR NIH HHS [DE12156] NR 24 TC 93 Z9 95 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1997 VL 159 IS 11 BP 5201 EP 5205 PG 5 WC Immunology SC Immunology GA YW263 UT WOS:000071914800005 PM 9548457 ER PT J AU Page, DM Tokugawa, Y Silver, J Stewart, CL AF Page, DM Tokugawa, Y Silver, J Stewart, CL TI Role of Thy-1 in T cell development SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASES; CLASS-II MHC; THYMIC MEDULLARY EPITHELIUM; MONOCLONAL-ANTIBODY; NEGATIVE SELECTION; CLONAL DELETION; ANTIGEN RECEPTOR; POSITIVE SELECTION; LYMPHOCYTES-T; SIGNAL TRANSDUCTION AB Tolerance to self proteins is accomplished in part by elimination of autoreactive immature T cells as they develop in the thymus. Although many investigators have studied the cellular interactions that regulate this important process, the specific molecules involved in negative selection are still not well understood, Thy-1 is a glycosyl-phosphatidylinositol-linked protein that is expressed at high levels on immature thymocytes, and recent evidence suggests that it is involved in thymocyte apoptosis. Correspondingly, we have found that Abs to Thy-1 block Ag-dependent thymocyte deletion in an in vitro culture system. Thus, we investigated the role of Thy-1 in T cell development by using Thy-1-deficient mice containing a TCR transgene specific for a class II MHC-restricted Ag, With this system, the role of Thy-1 in Ag-specific self-restriction and self-tolerance could be analyzed, Thy-1-null mice were found to undergo normal negative selection in three different models: the in vitro culture system, anti-CD3-induced thymocyte deletion in vivo, and Ag-induced thymocyte deletion in vivo. Self-restriction to MHC class II also appeared to occur normally in Thy-1-null mice, These results therefore suggest that Thy-1 is not essential for either self-restriction or self-tolerance to MHC class II-restricted Ags, This finding is discussed in light of recent data regarding the role of other glycosyl-phosphatidylinositol-linked proteins in thymocyte development. C1 Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA. Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA. N Shore Univ Hosp, Cornell Univ Med Coll, Div Mol Med, Manhasset, NY 11030 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Lab Canc & Dev Biol, Frederick, MD 21702 USA. RP Page, DM (reprint author), Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA. FU NIAID NIH HHS [AI36976] NR 76 TC 17 Z9 17 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1997 VL 159 IS 11 BP 5285 EP 5292 PG 8 WC Immunology SC Immunology GA YW263 UT WOS:000071914800015 PM 9548467 ER PT J AU Moriuchi, H Moriuchi, M Fauci, AS AF Moriuchi, H Moriuchi, M Fauci, AS TI Cloning and analysis of the promoter region of CCR5, a coreceptor for HIV-1 entry SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHEMOKINE RECEPTOR GENE; MOLECULAR-CLONING; T-LYMPHOCYTES; TROPIC HIV-1; EXPRESSION; INFECTION; PROTEIN; MIP-1-ALPHA; INDIVIDUALS; MIP-1-BETA AB The chemokine receptor CCR5 is a cofactor for cellular entry of macrophage-tropic strains of HIV-1. Expression of CCR5 is restricted to T cells, macrophages, and certain cell lines; however, the mechanisms controlling its expression remain largely unknown. To delineate these mechanisms, approximately 1.0 kb of DNA from the immediate 5' upstream region of CCR5 was cloned and characterized. CCR5 promoter activity was up-regulated by PMA, and a region spanning -417 to +61 relative to the transcription start site was sufficient for the basal and induced activity. DNase I footprinting assays demonstrated several protected areas within this region, and gel shift assays determined binding sites for transcriptional factors Oct-1, Oct-2, T cell factor 1 alpha, and GATA1, CCR5 promoter activity was also induced by IL-2 or anti-CD3 Ab, while stimulation with anti-CD28 Ab markedly reduced CD3-mediated up-regulation of the CCR5 promoter. Flow cytometry confirmed the findings at the level of cell surface expression, Further delineation of the regulation of the CCR5 promoter will be important for a more comprehensive understanding of the pathogenesis of HIV disease. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Moriuchi, H (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 6A11,10 Ctr Dr,MSC-1576, Bethesda, MD 20892 USA. NR 31 TC 63 Z9 63 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1997 VL 159 IS 11 BP 5441 EP 5449 PG 9 WC Immunology SC Immunology GA YW263 UT WOS:000071914800032 PM 9548484 ER PT J AU Karron, RA Wright, PF Crowe, JE ClementsMann, ML Thompson, J Makhene, M Casey, R Murphy, BR AF Karron, RA Wright, PF Crowe, JE ClementsMann, ML Thompson, J Makhene, M Casey, R Murphy, BR TI Evaluation of two live, cold-passaged, temperature-sensitive respiratory syncytial virus vaccines in chimpanzees and in human adults, infants, and children SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID YOUNG-CHILDREN; SERONEGATIVE CHIMPANZEES; SURFACE GLYCOPROTEINS; RSV; IMMUNOGENICITY; MUTANT; IMMUNIZATION; RECOMBINANTS; SAFETY; INFECTIONS AB Two live-attenuated, cold-passaged (cp), temperature-sensitive (ts) candidate vaccines, designated cpts530/1009 and cpts248/955, were attenuated, genetically stable, and immunogenic in chimpanzees and were highly attenuated for human adults, In respiratory syncytial virus (RSV)-seropositive children, cpts530/1009 was more restricted in replication than cpts248/955. In seronegative children, 10(4) pfu of cpts248/955 was insufficiently attenuated, and a high titer of vaccine virus was shed (mean peal; titer, 10(4.4) pfu/mL), whereas 10(4) pfu of cpts530/1009 was relatively attenuated and restricted in replication (mean peak titer, 10(4) pfu/mL), At a dose of 10(5) pfu, cpts530/1009 was immunogenic in seronegative children (geometric mean titer of RSV neutralizing antibodies, 1:724), Transmission of either vaccine to seronegative placebo recipients occurred at a frequency of 20%-25%. Of importance, vaccine viruses recovered from chimpanzees and humans were ts, In contrast to previous studies, this study indicates that live attenuated RSV vaccines that are immunogenic and phenotypically stable can he developed, Additional studies are being conducted to identify a live RSV vaccine that is slightly more attenuated and less transmissible than cpts530/1009. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. NIAID,INFECT DIS LAB,NIH,BETHESDA,MD 20892. VANDERBILT UNIV,SCH MED,VANDERBILT VACCINE CTR,DEPT PEDIAT,NASHVILLE,TN 37212. RP Karron, RA (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,CTR IMMUNIZAT RES,DEPT INT HLTH,HAMPTON HOUSE 117,BALTIMORE,MD 21205, USA. RI Crowe, James/B-5549-2009 OI Crowe, James/0000-0002-0049-1079 FU NIAID NIH HHS [AI-15095] NR 39 TC 137 Z9 145 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1997 VL 176 IS 6 BP 1428 EP 1436 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YH160 UT WOS:A1997YH16000003 PM 9395351 ER PT J AU Murphy, EL Glynn, SA Fridey, J Sacher, RA Smith, JW Wright, DJ Newman, B Gibble, JW Ameti, DI Nass, CC Schreiber, GB Nemo, GJ AF Murphy, EL Glynn, SA Fridey, J Sacher, RA Smith, JW Wright, DJ Newman, B Gibble, JW Ameti, DI Nass, CC Schreiber, GB Nemo, GJ TI Increased prevalence of infectious diseases and other adverse outcomes in human T lymphotropic virus types I- and II-infected blood donors SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 49th Annual Congress of the American-Association-of-Blood-Banks CY OCT 12-16, 1996 CL ORLANDO, FL SP Amer Assoc Blood Banks ID INTRAVENOUS-DRUG-USERS; CELL LEUKEMIA-LYMPHOMA; NON-HODGKIN-LYMPHOMA; HTLV-I; NEUROLOGICAL DISEASE; SPASTIC PARAPARESIS; JAMAICA; MYELOPATHY; AIDS; PROGRESSION AB Disease associations of human T lymphotropic virus types I and II (HTLV-I and -II) infection were studied in 154 HIV-I-infected, 387 HTLV-II-infected, and 799 uninfected blood donors. Adjusted odds ratios (ORs) and 99% confidence intervals (CIs) were derived from logistic regression models controlling for demographics and relevant confounders. All subjects were human immunodeficiency virus type l-seronegative, HTLV-II was significantly associated with a history of pneumonia (OR, 26; 99% CI, 1.2-5.3), minor fungal infection (OR, 2.9; 99% CI, 1.2-7.1), and bladder or kidney infection (OR, 1.6; 99% CI, 1.0-2.5) within the past 5 years and with a lifetime history of tuberculosis (OR, 3.9; 99% CI, 1.3-11.6) and arthritis (OR, 1.8; 99% CI, 1.2-2.9). Lymphadenopathy (greater than or equal to 1 cm) was associated with both HTLV-I (OR, 6.6; 99% CI, 2.2-19.2) and HTLV-II (OR, 2.8; 99% CI, 1.1-7.1) infection, although no case of adult T cell leukemia/lymphoma was diagnosed. Urinary urgency and gait disturbance were associated with both viruses. This new finding of increased prevalence of a variety of infections in HTLV-II-positive donors suggests immunologic impairment. C1 UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT EPIDEMIOL BIOSTAT,SAN FRANCISCO,CA 94143. BLOOD BANK SAN BERNARDINO & RIVERSIDE COUNTIES,SAN BERNARDINO,CA. WESTAT CORP,ROCKVILLE,MD. NHLBI,NIH,BETHESDA,MD 20892. GEORGETOWN UNIV HOSP,WASHINGTON,DC 20007. OKLAHOMA BLOOD INST,OKLAHOMA CITY,OK. AMER RED CROSS,BLOOD SERV,DETROIT,MI. RP Murphy, EL (reprint author), UNIV CALIF SAN FRANCISCO,DEPT LAB MED,BOX 0884,SAN FRANCISCO,CA 94143, USA. FU NHLBI NIH HHS [HB-97077, HB-97078, HB-47114] NR 45 TC 52 Z9 52 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1997 VL 176 IS 6 BP 1468 EP 1475 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YH160 UT WOS:A1997YH16000008 PM 9395356 ER PT J AU Bobo, LD Novak, N Munoz, B Hsieh, YH Quinn, TC West, S AF Bobo, LD Novak, N Munoz, B Hsieh, YH Quinn, TC West, S TI Severe disease in children with trachoma is associated with persistent Chlamydia trachomatis infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 3rd Meeting of the European-Society-for-Chlamydia-Research CY SEP 11-14, 1996 CL VIENNA, AUSTRIA SP Eur Soc Chlamydia Res ID OUTER-MEMBRANE PROTEIN; POLYMERASE CHAIN-REACTION; ENZYME-IMMUNOASSAY; RISK-FACTORS; OMP1 GENE; RESPONSES; TANZANIA; AMPLIFICATION; PATHOGENESIS; ADENOVIRUSES AB The immediate study objective was to determine if variable disease severity in children with trachoma could be attributable in part to host variation in the ability to clear Chlamydia trachomatis infection, Identification of sibling cohorts with these variant phenotypes would be useful for immunogenetic studies. A weekly survey far 3 months in a trachoma-hyperendemic village using detection of chlamydial DNA and grading of disease severity indicated that 62% (33/53) of children had at least one infection episode. DE those, 64% (21/33) who were persistently infected had both significantly higher mean chlamydial DNA loads and more severe trachoma than did sporadically infected children, Of importance, duration of infection differed between siblings in 60% (6/10) of families, The results suggest that chlamydial load and duration of infection determine the chronic nature of severe disease in trachoma and that host variable efficiency for chlamydial clearance between siblings is in part determined by host variation. C1 JOHNS HOPKINS UNIV,SCH MED,DANA CTR INVEST OPHTHALMOL,BALTIMORE,MD. NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. FU NEI NIH HHS [EY-09954-01A2] NR 37 TC 48 Z9 50 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1997 VL 176 IS 6 BP 1524 EP 1530 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YH160 UT WOS:A1997YH16000016 PM 9395364 ER PT J AU Shah, KV Daniel, RW Strickler, HD Goedert, JJ AF Shah, KV Daniel, RW Strickler, HD Goedert, JJ TI Investigation of human urine for genomic sequences of the primate polyomaviruses simian virus 40, BK virus, and JC virus SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT CBER/NCI/NICHD/NIP/NVPO Workshop on Simian Virus 40 (SV40) - a Possible Human Polyomavirus CY JAN 27-28, 1997 CL BETHESDA, MD SP CBER, NCI, NICHD, NIP, NVPO ID HUMAN IMMUNODEFICIENCY VIRUS; PLEURAL MESOTHELIOMA; CHOROID-PLEXUS; DNA-SEQUENCES; TUMORS; SIMIAN-VIRUS-40 AB Recent reports of the detection of simian virus 40 (SV40) nucleotide sequences in ependymomas, choroid plexus tumors, osteosarcomas, and mesotheliomas have raised the possibility that SV40, which naturally infects Asian macaques, is circulating among humans. This possibility was examined by performing polymerase chain reaction assays on urine samples of 166 homosexual men, 88 of them human immunodeficiency virus (HIV)-seropositive, for genomic sequences of SV40 as well as of human polyomaviruses BK virus (BKV) and JC virus (JCV). Tests with masked urine specimens spiked with SV40-transformed cells were included to monitor the SV40 assay. SV40, BKV, and JCV sequences mere identified, respectively, in 0, 14%, and 34% of the urine specimens. JCV viruria was far more common (37%) than BKV viruria (5%) in HIV-seronegative persons. HIV infection and more severe immunosuppression were associated with a higher frequency of BKV viruria. In summary, SV40 viruria mas not detected among homosexual men who shed human polyomaviruses at a high frequency. C1 NCI,VIRAL EPIDEMIOL BRANCH,NIH,BETHESDA,MD 20892. RP Shah, KV (reprint author), JOHNS HOPKINS UNIV,SCH PUBL HLTH,DEPT MOL MICROBIOL & IMMUNOL,615 N WOLFE ST,BALTIMORE,MD 21205, USA. FU NCI NIH HHS [CP-40521] NR 15 TC 67 Z9 67 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1997 VL 176 IS 6 BP 1618 EP 1621 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YH160 UT WOS:A1997YH16000029 PM 9395377 ER PT J AU Blaser, MJ Allos, BM Lang, D AF Blaser, MJ Allos, BM Lang, D TI Development of Guillain-Barre syndrome following Campylobacter infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material C1 VET ADM MED CTR,NASHVILLE,TN. NIAID,NIH,BETHESDA,MD 20892. RP Blaser, MJ (reprint author), VANDERBILT UNIV,SCH MED,DIV INFECT DIS,MED CTR N A3310,DEPT MED,NASHVILLE,TN 37232, USA. NR 0 TC 6 Z9 6 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1997 VL 176 SU 2 BP S91 EP S91 DI 10.1086/513790 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YH506 UT WOS:A1997YH50600001 ER PT J AU Lang, DR Allos, BM Blaser, MJ AF Lang, DR Allos, BM Blaser, MJ TI Workshop summary and recommendations regarding the development of Guillain-Barre syndrome following Campylobacter infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material C1 VANDERBILT UNIV,SCH MED,DEPT MED,NASHVILLE,TN 37212. VET ADM MED CTR,NASHVILLE,TN. RP Lang, DR (reprint author), NIAID,NIH,SOLAR BLDG,ROOM 3A21,6003 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1997 VL 176 SU 2 BP S198 EP S200 DI 10.1086/513792 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YH506 UT WOS:A1997YH50600024 PM 9396711 ER PT J AU Wilfond, BS Rothenberg, KH Thomson, EJ Lerman, C AF Wilfond, BS Rothenberg, KH Thomson, EJ Lerman, C TI Cancer genetic susceptibility testing: Ethical and policy implications for future research and clinical practice SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article ID BREAST-OVARIAN-CANCER; BRCA1; MUTATIONS; RELATIVES; FAMILIES; REFORM AB Authors examine the ethical and health policy implications in the Cancer Genetic Studies Consortium projects, which attempt to collect data on the clinical benefits and harms of cancer genetic testing. They suggest that more data are needed on the long-term physical and psychosocial effects of testing and that further examination is needed of the ethical issues raised by testing. C1 Univ Arizona, Dept Pediat, Tucson, AZ 85721 USA. Univ Maryland, Sch Law, Law & Hlth Care Program, Baltimore, MD 21201 USA. NIH, Natl Human Genome Res Inst, Bethesda, MD USA. Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Washington, DC USA. RP Wilfond, BS (reprint author), Univ Arizona, Dept Pediat, Tucson, AZ 85721 USA. FU AHRQ HHS [R29-HS08570] NR 44 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC LAW MEDICINE ETHICS PI BOSTON PA 765 COMMONWEALTH AVE, 16TH FL, BOSTON, MA 02215 USA SN 0277-8459 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD WIN PY 1997 VL 25 IS 4 BP 243 EP + DI 10.1111/j.1748-720X.1997.tb01406.x PG 10 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA ZD314 UT WOS:000072672800002 PM 11066506 ER PT J AU Naccache, PH Gilbert, C Barabe, F AlShami, A Mahana, W Bourgoin, SG AF Naccache, PH Gilbert, C Barabe, F AlShami, A Mahana, W Bourgoin, SG TI Agonist-specific tyrosine phosphorylation of Cbl in human neutrophils SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE phagocytic particles; chemotactic factors ID COLONY-STIMULATING FACTOR; TUMOR-NECROSIS-FACTOR; ELECTROPERMEABILIZED HUMAN-NEUTROPHILS; METHIONYL-LEUCYL-PHENYLALANINE; RABBIT PERITONEAL NEUTROPHILS; HUMAN INTERLEUKIN-8 RECEPTOR; ACTIVATED PROTEIN-KINASES; EPIDERMAL GROWTH-FACTOR; FC-GAMMA RECEPTORS; C-CBL AB The effects of soluble and particulate agonists on the tyrosine phosphorylation levels of the proto-oncogene Cbl in human neutrophils were examined, Experimental conditions allowing the maintenance of Cbl as well as of its tyrosine phosphorylation status were first established, Their use allowed us to observe that Cbl was tyrosine phosphorylated in response to some (Fc gamma RII ligation, opsonized bacteria and zymosan, granulocyte-macrophage colony-stimulating factor, monosodium urate, and calcium pyrophosphate microcrystals), but not all (fMet-Leu-Phe, interleukin-8) neutrophil agonists, Cbl was also shown to account for a varying proportion of the 120-kDa phosphoprotein(s) observed In response to the above stimuli, These data establish that Cbl is present in human neutrophils and that its level of tyrosine phosphorylation is modulated by some of these cells' agonists, and in particular by phagocytic particles, Furthermore, the signaling pathways activated by chemotactic factors and the other neutrophil stimuli tested in this investigation diverge at or downstream from the tyrosine phosphorylation of Cbl. C1 UNIV LAVAL,FAC MED,DEPT MED,ST FOY,PQ G1K 7P4,CANADA. UNIV LAVAL,FAC MED,DEPT PHYSIOL,ST FOY,PQ G1K 7P4,CANADA. NIAID,IMMUNOGENET LAB,BETHESDA,MD 20892. RP Naccache, PH (reprint author), CHUL,CTR RECH,CTR RECH RHUMATOL & IMMUNOL,2705 BLVD LAURIER,ST FOY,PQ G1V 4G2,CANADA. RI Al-Shami, Amin/D-3889-2009 NR 74 TC 21 Z9 21 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD DEC PY 1997 VL 62 IS 6 BP 901 EP 910 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA YJ991 UT WOS:A1997YJ99100025 PM 9400833 ER PT J AU Shamburek, RD Pentchev, PG Zech, LA Blanchette-Mackie, J Carstea, ED VandenBroek, JM Cooper, PS Neufeld, EB Phair, RD Brewer, HB Brady, RO Schwartz, CC AF Shamburek, RD Pentchev, PG Zech, LA Blanchette-Mackie, J Carstea, ED VandenBroek, JM Cooper, PS Neufeld, EB Phair, RD Brewer, HB Brady, RO Schwartz, CC TI Intracellular trafficking of the free cholesterol derived from LDL cholesteryl ester is defective in vivo in Niemann-Pick C disease: insights on normal metabolism of HDL and LDL gained from the NP-C mutation SO JOURNAL OF LIPID RESEARCH LA English DT Article DE cholesterol metabolism; intracellular transport; bile; kinetic model; lipoprotein ID HIGH-DENSITY-LIPOPROTEIN; LYSOSOMAL ACCUMULATION; CULTURED FIBROBLASTS; PLASMA-MEMBRANE; BILE FISTULA; CELLS; RAT; IDENTIFICATION; TRANSPORT; SECRETION AB Niemann-Pick C disease (NP-C) is a rare inborn error of metabolism with hepatic involvement and neurological sequelae that usually manifest in childhood. Although in vitro studies have shown that the lysosomal distribution of LDL-derived cholesterol is defective in cultured cells of NP-C subjects, no unusual characteristics mark the plasma lipoprotein profiles. We set out to determine whether anomalies exist in vivo in the cellular distribution of newly synthesized, HDL-derived or LDL-derived cholesterol under physiologic conditions in NP-C subjects. Three affected and three normal male subjects were administered [C-14] mevalonate as a tracer of newly synthesized cholesterol and [H-3] cholesteryl linoleate in either HDL or LDL to trace the distribution of lipoprotein-derived free cholesterol. The rate of appearance of free [C-14]- and free [H-3] cholesterol in the plasma membrane was detected indirectly by monitoring their appearance in plasma and bile. The plasma disappearance of [H-3] cholesterol linoleate was slightly faster in NP-C subjects regardless of its lipoprotein origin. Appearance of free [C-14] cholesterol in the plasma (and in bile) was essentially identical in normal and affected individuals as was the initial appearance of free [H-3] cholesterol derived from HDL, observed before extensive exchange occurred of the [H-3] cholesteryl linoleate among lipoproteins. In contrast, the rate of appearance of LDL-derived free [H-3] cholesterol in the plasma membrane of NP-C subjects, as detected in plasma and bile, was retarded to a similar extent that LDL cholesterol metabolism was defective in cultured fibroblasts of these affected subjects. These findings show that intracellular distribution of both newly synthesized and HDL-derived cholesterol are essentially unperturbed by the NP-C mutation, and therefore occur by lysosomal-independent paths. In contrast, in NP-C there is defective trafficking of LDL-derived cholesterol to the plasma membrane in vivo as well as in vitro. The in vivo assay of intracellular cholesterol distribution developed herein should prove useful to quickly evaluate therapeutic interventions for NP-C. C1 NIH, Mol Dis Branch, Bethesda, MD 20892 USA. NIH, Math Biol Lab, Bethesda, MD 20892 USA. NIH, Dev & Metab Neurol Branch, Bethesda, MD 20892 USA. NIH, Lipid Cell Biol Sect, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Med, Richmond, VA 23298 USA. Bioinformat Serv, Rockville, MD 20854 USA. RP Shamburek, RD (reprint author), NIH, Mol Dis Branch, Bethesda, MD 20892 USA. FU NCRR NIH HHS [M01 RR00065] NR 36 TC 35 Z9 35 U1 0 U2 1 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD DEC PY 1997 VL 38 IS 12 BP 2422 EP 2435 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YP442 UT WOS:000071277200004 PM 9458266 ER PT J AU Brousseau, ME Santamarina-Fojo, S Vaisman, BL Applebaum-Bowden, D Berard, AM Talley, GD Brewer, HB Hoeg, JM AF Brousseau, ME Santamarina-Fojo, S Vaisman, BL Applebaum-Bowden, D Berard, AM Talley, GD Brewer, HB Hoeg, JM TI Overexpression of human lecithin : cholesterol acyltransferase in cholesterol-fed rabbits: LDL metabolism and HDL metabolism are affected in a gene dose-dependent manner SO JOURNAL OF LIPID RESEARCH LA English DT Article DE apolipoprotein A-I; cholesterol; lecithin : cholesterol acyltransferase; low density lipoproteins; metabolism ID ESTER TRANSFER PROTEIN; LOW-DENSITY LIPOPROTEINS; APOLIPOPROTEIN-A-I; LIPID TRANSFER PROTEINS; FISH EYE DISEASE; TRANSGENIC RABBITS; HUMAN-PLASMA; ALPHA-LCAT; RECEPTOR; DEFICIENCY AB Lecithin:cholesterol acyltransferase (LCAT) is an enzyme well known for its involvement in the intravascular metabolism of high density lipoproteins; however, its role in the regulation of apolipoprotein (apo) B-containing lipoproteins remains elusive. The present study was designed to investigate the metabolic mechanisms responsible for the differential lipoprotein response observed between cholesterol-fed hLCAT transgenic and control rabbits. I-131-labeled HDL apoA-I and I-125-labeled LDL kinetics were assessed in age- and sex-matched groups of rabbits with high (HE), low (LE), or no hLCAT expression after 6 weeks on a 0.3% cholesterol diet. In HE, the mean total cholesterol concentration on this diet, mg/dl (230 +/- 50), was not significantly different from that of either LE (313 +/- 46) or controls (332 +/- 52) due to the elevated level of HDL-C observed in HE (127 +/- 19), as compared with both LE (100 +/- 33) and controls (31 +/- 4). In contrast, the mean nonHDL-C concentration for HE (103 +/- 33) was much lower than that for either LE (213 +/- 39) or controls (301 +/- 55). FPLC analysis of plasma confirmed that HDL was the predominant lipoprotein class in HE on the cholesterol diet, whereas cholesteryl ester-rich, apoB-containing lipoproteins characterized the plasma of LE and, most notably, of controls. In vivo kinetic experiments demonstrated that the differences in HDL levels noted between the three groups were attributable to distinctive rates of apoA-I catabolism, with the mean fractional catabolic rate (FCR, d(-1)) of apoA-I slowest in HE (0.282 +/- 0.03), followed by LE (0.340 +/- 0.01) and controls (0.496 +/- 0.04). A similar, but opposite, pattern was observed for nonHDL-C levels and LDL metabolism (h(-1)), such that HE had the lowest nonHDL-C levels with the fastest rate of clearance (0.131 +/- 0.027), followed by LE (0.057 +/- 0.009) and controls (0.031 +/- 0.001). Strong correlations were noted between LCAT activity and both apoA-I (r = -0.868, P < 0.01) and LDL (r = 0.670, P = 0.06) FCR, indicating that LCAT activity played a major role in the mediation of lipoprotein metabolism. In summary, these data are the first to show that LCAT overexpression can regulate both LDL and HDL metabolism in cholesterol-fed rabbits and provide a potential explanation for the prevention of diet-induced atherosclerosis observed in our previous study. C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. RP Brousseau, ME (reprint author), NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. NR 43 TC 45 Z9 45 U1 0 U2 0 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD DEC PY 1997 VL 38 IS 12 BP 2537 EP 2547 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YP442 UT WOS:000071277200015 PM 9458277 ER PT J AU Yang, YH Xu, S Dawson, MJ Lauterbur, PC AF Yang, YH Xu, S Dawson, MJ Lauterbur, PC TI Diffusion measurement in phantoms and tissues using SLIM localization SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article ID MOLECULAR SELF-DIFFUSION; WATER DIFFUSION; NMR; SPECTROSCOPY; BRAIN; METABOLITES; MUSCLE AB A new approach to efficient localized diffusion measurements has been developed and evaluated on phantoms and isolated tissues. The combination of a diffusion-sensitive pulse sequence with SLIM (spectral localization by imaging) makes efficient and accurate localized water and metabolite diffusion measurements possible with a substantial improvement in spatial or time resolution compared to standard methods. Phantom experiments showed that diffusion of substances present in relatively low concentration within small compartments can be measured accurately by this method, suggesting potential applications for diffusion measurements of metabolites in vivo, Experiments on excised rat uterine horns demonstrated the ability of this method to measure localized diffusion of water within irregularly shaped regions of biological samples, Accurate diffusion measurements were achieved in the localized regions with acquisition times less than would have been required by standard diffusion imaging methods. (C) 1997 Academic Press. C1 Univ Illinois, Biomed Magnet Resonance Lab, Urbana, IL 60801 USA. RP Yang, YH (reprint author), NIH, Lab Diagnost Radiol Res, OIR, Bldg 10,Room B1N-256, Bethesda, MD 20892 USA. FU NCI NIH HHS [1 R01 CA51430]; NCRR NIH HHS [5P41 RR05964, 1S10RR06243] NR 22 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD DEC PY 1997 VL 129 IS 2 BP 161 EP 164 DI 10.1006/jmre.1997.1257 PG 4 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA YV259 UT WOS:000071805300007 PM 9441880 ER PT J AU McNellis, D AF McNellis, D TI A view from Bethesda: Recent changes in grant policies and procedures at the National Institutes of Health (NIH) SO JOURNAL OF MATERNAL-FETAL INVESTIGATION LA English DT Editorial Material RP McNellis, D (reprint author), NICHHD,OBSTET PREGNANCY & PERINATOL BRANCH,NIH,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0939-6322 J9 J MATERN-FETAL INVES JI J. Matern.-Fetal Invest. PD WIN PY 1997 VL 7 IS 1 BP 2 EP 2 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA WK741 UT WOS:A1997WK74100002 ER PT J AU Noel, JS Ando, T Leite, JP Green, KY Dingle, KE Estes, MK Seto, Y Monroe, SS Glass, RI AF Noel, JS Ando, T Leite, JP Green, KY Dingle, KE Estes, MK Seto, Y Monroe, SS Glass, RI TI Correlation of patient immune responses with genetically characterized small round-structured viruses involved in outbreaks of nonbacterial acute gastroenteritis in the united states, 1990 to 1995 SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE small round-structured viruses; Norwalk virus; Toronto virus; Lordsdale virus; Hawaii virus immune response; genetic diversity; calicivirus ID NORWALK-LIKE VIRUSES; HUMAN ENTERIC CALICIVIRIDAE; MOLECULAR CHARACTERIZATION; CAPSID PROTEIN; ELECTRON-MICROSCOPY; ENZYME-IMMUNOASSAY; GENOMIC DIVERSITY; SNOW MOUNTAIN; HAWAII VIRUS; SEQUENCE AB Small round-structured viruses (SRSVs) are a genetically and antigenically diverse group of caliciviruses that are the most common cause of outbreaks of acute nonbacterial gastroenteritis. We have applied both molecular techniques to characterize SRSVs in fecal specimens and serologic assays using four different expressed SRSV antigens to examine the distribution of outbreak strains in the United States and determine if the immune responses of patients were strain specific. Strains from 23 outbreaks of SRSV gastroenteritis were characterized by reverse transcription-PCR and nucleotide sequencing of a 277-base region of the capsid gene. These strains segregated into two distinct genogroups, I and II, comprising four and six clusters of strains respectively, each representing a distinct phylogenetic lineage. Serum IgG responses in patients were measured by enzyme immunoassay using expressed capsid antigens of Norwalk virus (NV), Toronto virus (TV), Hawaii virus (HV), and Lordsdale virus (LV), representing four of the 10 clusters. While strains in genogroups I and II were antigenically distinct, within genogroups, the specificity of the immune response varied greatly. Patients infected with genogroup I strains which had as much as 38.5% aa divergence from NV demonstrated relatively homologous seroresponses to the single NV antigen. In contrast, in genogroup II, homologous seroresponses to TV and HV were only present when the infecting strains showed less than 6.5% aa divergence from these antigens. These results suggest that TV and HV represent not only separate genetic clusters in genogroup II but also separate antigenic groups, each of which is related but distinguishable. In addition, two genetically distinct SRSV strains were identified for which we have no homologous antigen. This study suggests that while current molecular diagnostics are capable of detecting the full range of SRSVs, additional expressed antigens will be required to detect an immune response to SRSV infection caused by all the antigenically diverse strains. (C) 1997 Wiley-Liss, Inc. C1 INST OSWALDO CRUZ,DEPT VIROL,BR-20001 RIO JANEIRO,BRAZIL. NIAID,INFECT DIS LAB,NIH,BETHESDA,MD 20892. UNIV SOUTHAMPTON,SOUTHAMPTON GEN HOSP,SCH MED,MOL MICROBIOL GRP,SOUTHAMPTON,HANTS,ENGLAND. BAYLOR COLL MED,DIV MOL VIROL,HOUSTON,TX 77030. OSAKA CITY INST PUBL HLTH & ENVIRONM SCI,DEPT HLTH & EPIDEMIOL,OSAKA 543,JAPAN. RP Noel, JS (reprint author), CTR DIS CONTROL & PREVENT,VIRAL GASTROENTERITIS UNIT G04,VIRAL GASTROENTERITIS SECT,ATLANTA,GA 30333, USA. OI Monroe, Stephan/0000-0002-5424-716X NR 37 TC 149 Z9 154 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD DEC PY 1997 VL 53 IS 4 BP 372 EP 383 DI 10.1002/(SICI)1096-9071(199712)53:4<372::AID-JMV10>3.0.CO;2-H PG 12 WC Virology SC Virology GA YJ685 UT WOS:A1997YJ68500010 PM 9407386 ER PT J AU Santos, A De Solorzano, CO Vaquero, JJ Pena, JM Malpica, N Del Pozo, F AF Santos, A De Solorzano, CO Vaquero, JJ Pena, JM Malpica, N Del Pozo, F TI Evaluation of autofocus functions in molecular cytogenetic analysis SO JOURNAL OF MICROSCOPY-OXFORD LA English DT Article DE analytical cytometry; autofocus; FISH; focusing algorithms ID MICROSCOPY AB This work describes a systematic evaluation of several autofocus functions used for analytical fluorescent image cytometry studies of counterstained nuclei. Focusing is the first step in the automatic fluorescence in situ hybridization analysis of cells. Thirteen functions have been evaluated using qualitative and quantitative procedures, For the last of these procedures a figure-of-merit (FOM) is defined and proposed. This new FOM takes into account five important features of the focusing function. Our results show that functions based on correlation measures have the best performance for this type of image. C1 ETSI Telecomun, Grp Bioingn & Telemed, E-28040 Madrid, Spain. Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA. NIH, Dept Nucl Med, Bethesda, MD 20892 USA. RP Santos, A (reprint author), ETSI Telecomun, Grp Bioingn & Telemed, Ciudad Univ, E-28040 Madrid, Spain. RI Ortiz de Solorzano, Carlos/G-3278-2010; Vaquero, Juan Jose/D-3033-2009; Santos, Andres/C-4012-2009; DEL POZO GUERRERO, FRANCISCO/H-6668-2015; Malpica, Norberto/I-2090-2015 OI Ortiz de Solorzano, Carlos/0000-0001-8720-0205; Vaquero, Juan Jose/0000-0001-9200-361X; Santos, Andres/0000-0001-7423-9135; DEL POZO GUERRERO, FRANCISCO/0000-0001-9919-9125; Malpica, Norberto/0000-0003-4618-7459 NR 10 TC 151 Z9 165 U1 2 U2 18 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-2720 J9 J MICROSC-OXFORD JI J. Microsc.-Oxf. PD DEC PY 1997 VL 188 BP 264 EP 272 DI 10.1046/j.1365-2818.1997.2630819.x PN 3 PG 9 WC Microscopy SC Microscopy GA YQ336 UT WOS:000071375100008 PM 9450330 ER PT J AU Wang, Y Kole, HK Montrose-Rafizadeh, C Perfetti, R Bernier, M Egan, JM AF Wang, Y Kole, HK Montrose-Rafizadeh, C Perfetti, R Bernier, M Egan, JM TI Regulation of glucose transporters and hexose uptake in 3T3-L1 adipocytes: glucagon-like peptide-1 and insulin interactions SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Article ID MESSENGER-RNA; ADIPOSE-TISSUE; GLUT4 GENE; RAT; CELLS; TRANSCRIPTION; EXPRESSION; RECEPTOR; INCRETIN; HORMONE AB Glucagon-like peptide-1 (7-36 amide) (GLP-1) is known to increase insulin release when given as a bolus in the fasted and fed state. GLP-1 also increases glucose uptake and lipid synthesis in cultured adipocytes. In this study we investigated the effects of GLP-1 on glucose uptake and on the levels of expression of the facilitative glucose transporters, GLUT1 and GLUT4, in fully differentiated 3T3-L1 adipocytes. Cells were incubated with GLP-1 (10 nM) with or without insulin (10 and 100 nM) for 24 h. Under these conditions, GLP-1 alone caused an increase in basal and acute insulin-stimulated glucose uptake along with an increase in GLUT1 and GLUT4 protein levels. However, there was no change in the expression of GLUT1 and GLUT4 mRNAs. In the absence of GLP-1, prolonged exposure to insulin caused a marked reduction in the levels of GLUT4 mRNA and protein, and an inhibition of glucose uptake after an acute exposure to insulin. This insulin-induced down-regulation of GLUT4 was prevented when GLP-1 was present during the 24-h treatment. In contrast, the acute insulin-stimulated glucose uptake could not be restored by GLP-1. GLP-1 is therefore the first gut hormone shown to be capable of modulating glucose transporter levels in cultured adipocytes. C1 NIA, Gerontol Res Ctr, Diabet Sect 23, Baltimore, MD 21224 USA. RP Egan, JM (reprint author), NIA, Gerontol Res Ctr, Diabet Sect 23, 4940 Eastern Ave, Baltimore, MD 21224 USA. OI Bernier, Michel/0000-0002-5948-368X NR 28 TC 35 Z9 35 U1 0 U2 4 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL BS12 4NQ, ENGLAND SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD DEC PY 1997 VL 19 IS 3 BP 241 EP 248 DI 10.1677/jme.0.0190241 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YQ871 UT WOS:000071432800003 PM 9460645 ER PT J AU Jahnke, GD Miller, MJ Martinez, A Montuenga, L Cuttitta, F AF Jahnke, GD Miller, MJ Martinez, A Montuenga, L Cuttitta, F TI Adrenomedullin expression in the mouse mammary gland: evidence for the mature form in milk SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Article ID SMOOTH-MUSCLE CELLS; EPIDERMAL GROWTH-FACTOR; NORMAL HUMAN LUNG; HYPOTENSIVE PEPTIDE; VASODILATORY PEPTIDE; RAT ADRENOMEDULLIN; CLONING; CDNA; PRECURSOR; CAMP AB Adrenomedullin (AM) is a recently identified amidated peptide produced by a variety of tissue types. We have investigated the involvement of AM and its receptor (AM-R) in developing mouse mammary glands and have examined what influence ovarian hormones have on AM and AM-R expression in this system. Tissues from ductal morphogenesis, virgin adult, pregnancy, and lactation stages were assessed for AM and AM-R by molecular, biochemical and immunohistochemical techniques. Results from these studies indicated that messenger RNA for AM and AM-R and immunoreactivity for AM were expressed in the luminal epithelium of small and large ducts and in terminal end buds. Immunoreactive AM was identified as a cytoplasm component of ductal cells, with some cells also having nuclear staining. Western blot analysis of mammary gland tissues yielded two molecular mass species (M-r 14 000 and 18 500) of AM immunoreactivity in the mammary gland for the above developmental stages, consistent with processed intermediate and prohormone forms respectively. Ovariectomy alone or followed by hormonal treatments did not alter the expression pattern for these two proteins. By Western blot, the fully processed AM form (M-r 6000) was identified in milk extracts from lactating glands. These data suggest a potential role for AM and its receptor in the maintenance of mammary gland homeostasis and suggests a potential role for AM in development of the newborn. C1 NIEHS, Toxicol Lab, Reprod Toxicol Workgrp, Res Triangle Pk, NC 27709 USA. NCI, Biomarkers & Prevent Res Branch, Div Canc Prevent & Control, NIH, Rockville, MD 20850 USA. RP Jahnke, GD (reprint author), NIEHS, Reprod Toxicol Grp, Bldg 101,MD B3-05, Res Triangle Pk, NC 27709 USA. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 42 TC 20 Z9 23 U1 0 U2 1 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL BS12 4NQ, ENGLAND SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD DEC PY 1997 VL 19 IS 3 BP 279 EP 289 DI 10.1677/jme.0.0190279 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YQ871 UT WOS:000071432800007 PM 9460649 ER PT J AU Shigeta, H Zuo, W Yang, N DiAugustine, R Teng, CT AF Shigeta, H Zuo, W Yang, N DiAugustine, R Teng, CT TI The mouse estrogen receptor-related orphan receptor alpha 1 molecular cloning and estrogen responsiveness SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Article ID COUP-TF; NUCLEAR RECEPTOR; LACTOFERRIN GENE; RETINOIC ACID; MESSENGER-RNA; GROWTH-FACTOR; GAMMA GENE; PROMOTER; EXPRESSION; BINDING AB Estrogen receptor-related orphan receptor alpha 1 is a member of the steroid/thyroid nuclear receptor superfamily. We have previously cloned the human estrogen receptor-related orphan receptor alpha 1 (hERR alpha 1) cDNA and demonstrated that it enhances estrogen responsiveness of the lactoferrin gene promoter in transfected human endometrial carcinoma cells. In the present study, we used the hERR alpha 1 cDNA as a probe and isolated the mouse homologue of ERR alpha 1 from the cDNA libraries of the brain and kidney. Sequence comparison between human and mouse ERR alpha 1 (mERR alpha 1) revealed that the homologies are 89% in nucleotides and 97% in amino acids. By electrophoresis mobility shift assay, we showed that the glutathione S-transferase-mERR alpha 1 fusion protein produced in a bacterial system bound to the human ERR alpha 1 DNA-binding element. Mouse uterine nuclear extract also interacted with this DNA element and produced three complexes in the mobility shift assay, one of which was supershifted by the hERR alpha 1 antiserum. A 2.2 kbp transcript was detected by Northern analysis in all adult mouse tissues tested; however, large variations in the amount alpha 1 mRNA were among them. Multiple immunoreactive forms of mouse ERR alpha 1 were detected by Western analysis in non-reproductive tissues, whereas a major 53 kDa protein was found in reproductive tissues such as uterus, cervix and vagina. Diethylstilbestrol (DES) stimulated the expression of ERR alpha 1 mRNA in the uterus of 19-day-old mouse. We showed that DES estradiol, but not progesterone or dexamethasone, enhanced the level of immunoreactive ERR alpha 1 in the mouse uterus. These results demonstrated that the ERR alpha 1 is an estrogen-responsive gene in the mouse uterus and provides a model system with which to study the biological roles of this nuclear orphan receptor. C1 NIEHS, Gene Regulat Grp, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Hormones & Canc Grp, NIH, Res Triangle Pk, NC 27709 USA. RP Teng, CT (reprint author), NIEHS, Gene Regulat Grp, Reprod & Dev Toxicol Lab, NIH, POB 12233,MD E201, Res Triangle Pk, NC 27709 USA. NR 49 TC 61 Z9 64 U1 1 U2 1 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL BS12 4NQ, ENGLAND SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD DEC PY 1997 VL 19 IS 3 BP 299 EP 309 DI 10.1677/jme.0.0190299 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YQ871 UT WOS:000071432800009 PM 9460651 ER PT J AU Huang, NY Strakhova, M Layer, RT Skolnick, P AF Huang, NY Strakhova, M Layer, RT Skolnick, P TI Chronic antidepressant treatments increase cytochrome b mRNA levels in mouse cerebral cortex SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE imipramine; electroconvulsive shock (ECS); cytochrome b; differential display PCR ID RNA DIFFERENTIAL DISPLAY; MESSENGER-RNA; GENE-EXPRESSION; NMDA RECEPTORS; RAT-BRAIN; DEPRESSION; ADAPTATION; DISEASE; SYSTEM; DRUGS AB Antidepressant therapies include drugs with a remarkable structural diversity and nonpharmacological interventions, such as electroconvulsive shock. Although the primary neurochemical effects of these treatments may differ, the greater than or equal to 2- to 3-wk lag in therapeutic onset has led to the hypothesis that adaptive changes in a final common pathway are required for an antidepressant action. Based on this hypothesis, we sought to identify and characterize common changes in gene expression following chronic antidepressant treatments. We utilized a differential display strategy to identify genes that were differentially expressed in mice following chronic treatment with imipramine and electroconvulsive shock. Differential display PCR followed by subcloning, screening by reverse Northern blot, and confirmation by Northern blot revealed a significant increase in the expression of one gene candidate from mouse cortex following antidepressant treatments. The sequence of this 193-bp gene candidate was an exact match to the DNA sequence of mouse mitochondrial cytochrome b. In contrast to the increased mRNA levels of cytochrome b found in cortex, chronic treatment with these antidepressants did not alter mRNA levels in hippocampus, cerebellum, or liver. Moreover, no differences in cortical levels of cytochrome b mRNA were observed after either acute antidepressant treatments or chronic treatment with nonantidepressant drugs (haloperidol and morphine). The observation that chronic, but not acute treatment with imipramine and electroconvulsive shock produces a region-specific change in the levels of mRNA encoding cytochrome b suggests that this enzyme may be involved in the sequence of events resulting in an antidepressant action. C1 NIDDK, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Huang, NY (reprint author), NIDDK, Neurosci Lab, NIH, Room 111,Bldg 8, Bethesda, MD 20892 USA. NR 39 TC 17 Z9 18 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD DEC PY 1997 VL 9 IS 3 BP 167 EP 176 DI 10.1007/BF02800499 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA YU389 UT WOS:000071712200003 PM 9481618 ER PT J AU Granja, R Gunnersen, D Wong, G Valeyev, A Skolnick, P AF Granja, R Gunnersen, D Wong, G Valeyev, A Skolnick, P TI Diazepam enhancement of GABA-gated currents in binary and ternary GABA(A) receptors - Relationship to benzodiazepine binding site density SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE GABA(A) receptor; benzodiazepines; diazepam; beta-subunit; flunitrazepam; Ro 15-4513 ID AMINOBUTYRIC ACID(A) RECEPTORS; A RECEPTORS; PHARMACOLOGY; SUBUNITS; STOICHIOMETRY; ANTAGONIST; MODULATION; SUBTYPES; LIGANDS; BRAIN AB Although the predominant GABA(A) receptor isoform in the adult rodent central nervous system is a ternary complex composed of alpha(1) beta(2/3)gamma(2)-subunits, small populations of binary receptors lacking beta-subunits (i.e., complexes containing alpha gamma-subunits) have also been identified. When expressed in HEK 293 cells, recombinant GABA(A) receptors composed of either alpha(1) beta(2/3)gamma(2)- or alpha(1) gamma(2)-subunits subunits form benzodiazepine-responsive, GABA-gated chloride channels. The objective of this study was to compare the ability of a prototypic benzodiazepine (diazepam) to augment GABA-gated chloride currents in these binary and ternary receptor isoforms. The potency of GABA was characteristically increased by diazepam (1 mu M) in both receptor isoforms, but this increase was significantly greater (p < 0.05) in receptors composed of alpha(1) beta(2) gamma(2)-subunits (approximately five- to sixfold) compared to alpha(1) gamma(2)-subunits (similar to 2.2-fold). At GABA concentrations approximating its EC50 value (5 mu M), the greater augmentation observed in ternary receptors was attributable to a higher efficacy of diazepam. Radioligand binding studies revealed that the B-max of [H-3]flunitrazepam was increased similar to 1.8- and 3.5-fold in cells expressing alpha(1) beta(2) gamma(2)- and alpha(1) beta(3) gamma(2)-subunits, respectively, compared to cells expressing alpha(1) gamma(2)-subunits. A similar increase (similar to 3.8-fold) in the B-max of [H-3]Ro 15-4513 was observed in HEK 293 cells transiently transfected with cDNAs encoding alpha(6) beta(3) gamma(2)-compared to alpha(6) gamma(2)-subunits. The K-d values of these radioligands were not different in binary and ternary receptor isoforms. It is hypothesized that the greater efficacy of diazepam in alpha(1) beta(2) gamma(2) compared to alpha(1) gamma(2) GABA(A) receptors results from the higher benzodiazepine binding site density produced by the formation of a ternary complex. C1 NIDDK, Neurosci Lab, NIH, Bethesda, MD 20892 USA. NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Skolnick, P (reprint author), Eli Lilly & Co, Lilly Res Labs, Drop Code 0510, Indianapolis, IN 46285 USA. NR 37 TC 5 Z9 5 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD DEC PY 1997 VL 9 IS 3 BP 187 EP 195 DI 10.1007/BF02800501 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA YU389 UT WOS:000071712200005 PM 9481620 ER PT J AU Ashur-Fabian, O Giladi, E Brenneman, DE Gozes, I AF Ashur-Fabian, O Giladi, E Brenneman, DE Gozes, I TI Identification of VIP/PACAP receptors on rat astrocytes using antisense oligodeoxynucleotides SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE antisense oligodeoxynucleotides; vasoactive intestinal peptide (VIP); pituitary adenylate cyclase-activating peptide (PACAP); neuronal survival; receptor binding; mRNA; polymerase chain reaction (PCR) ID VASOACTIVE-INTESTINAL-PEPTIDE; DIFFERENTIAL SIGNAL-TRANSDUCTION; FUNCTIONAL EXPRESSION; NEURONAL SURVIVAL; GENE-EXPRESSION; NEUROTROPHIC FACTOR; SPLICE VARIANTS; CEREBRAL-CORTEX; PACAP RECEPTOR; VIP AB Vasoactive intestinal peptide (VIP) has been shown to be a potent promoter of neuronal survival. Pituitary adenylate cyclase-activating peptide (PACAP), a homologous peptide, shares activity and receptor molecules with VIP. The neuroprotective effects of VIP have been shown to be mediated via astroglial-derived molecules. Utilizing a battery of antisense oligodeoxynucleotides directed against the multiple cloned VIP-preferring (VIP receptors 1 and 2) or PACAP-preferring receptors (six splice variants derived from the same gene transcript), the authors have demonstrated the existence of a specific PACAP receptor splice variant (PACAP4 or hop2) on astrocytes as well as a VIP type2 receptor. The identification of the receptors was achieved by incubation of the cells in the presence of the specific antisense oligodeoxynucleotide followed by radiolabeled VIP binding and displacement. Polymerase chain reaction (PCR) coupled to direct sequencing identified the expression of the PACAP4-hop2 receptor splice variant in astrocytes. Neuronal survival assays were conducted in mixed neuronal-glial cultures derived from newborn rat cerebral cortex. When these cultures were exposed to the battery of the antisense oligodeoxynucleotides, in serum-free media, only the PACAP-specific ones (e.g., hop2-specific) had an effect in decreasing neuronal cell counts. Thus, the VIP neuronal survival effect is mediated, at least in part, via a specific PACAP receptor (containing a unique insertion of 27 amino acids-the hop2 cassette). These data indicate that a hop2-like PACAP/VIP receptor is the receptor that mediates neurotropism. C1 Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. NICHHD, Sect Dev & Mol Pharmacol, Dev Neurobiol Lab, Bethesda, MD 20892 USA. RP Gozes, I (reprint author), Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. NR 50 TC 60 Z9 63 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD DEC PY 1997 VL 9 IS 3 BP 211 EP 222 DI 10.1007/BF02800503 PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA YU389 UT WOS:000071712200007 PM 9481622 ER PT J AU Hahm, SH Chen, LB Patel, C Erickson, J Bonner, TI Weihe, E Schafer, MKH Eiden, LE AF Hahm, SH Chen, LB Patel, C Erickson, J Bonner, TI Weihe, E Schafer, MKH Eiden, LE TI Upstream sequencing and functional characterization of the human cholinergic gene locus SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE vesicular acetylcholine transporter, VAChT; cholinergic gene locus; choline acetyltransferase, ChAT; neuron-specific gene transcription ID VESICULAR ACETYLCHOLINE TRANSPORTER; TISSUE-SPECIFIC EXPRESSION; INTESTINAL-PEPTIDE VIP; ACETYLTRANSFERASE GENE; PROMOTER REGION; RAT; IDENTIFICATION; LOCALIZATION; ELEMENTS AB The 5' flanking region of the human VAChT gene was sequenced to approx 5350 bases upstream of the initiating methionine codon of the VAChT open reading frame (orf). The 5' flanks of the human and rat cholinergic gene loci were compared to identify regions of local sequence conservation, and therefore of potential regulatory importance. Several discrete domains of high homology, including a cluster of far-upstream cis-active consensus motifs, a neuronally restrictive silencer element consensus sequence, and additional conserved sequences within the putative nerve growth factor response domain of the locus, were identified. The probable start of transcription of the VAChT gene was deduced from mapping of sequences of rat and human VAChT cDNAs onto the 5' flanking regions of the human and rat cholinergic gene loci. The actual utilization of a putative 5' VAChT exon in rat central nervous system (CNS) tissue was assessed by in situ hybridization histochemistry. RNA transcripts containing both VAChT and ChAT protein-coding sequences were abundant in spinal cord motoneurons, sympathetic preganglionic cells, basal forebrain, striatum, and cranial motor nuclei. R-exon-containing transcripts could be detected only at low levels in these cell groups, implying that most transcription of VAChT proceeds from a promoter downstream of the R-exon. To assess the structural requirements for expression of the VAChT gene without bias regarding the actual start of transcription, a 5' fragment of the human gene corresponding to similar to 3 kb of sequence extending upstream from within the presumed 5' untranslated region of VAChT itself was fused to a luciferase-encoding reporter and transfected into VAChT-expressing and nonexpressing human and rat cell lines. This portion of the VAChT gene provided strong promoter expression in both cholinergic and noncholinergic cell lines. Deletion of the putative neuronally restrictive silencer element (NRSE) resulted in enhanced transcription in all cell lines. Lack of differential expression of VAChT transcription in VAChT-expressing vs non-VAChT-expressing cell lines suggested that additional enhancer elements controlling cell-specific expression of the VAChT gene exist further upstream in the cholinergic locus 5' flank, Conservation of potential cis-active elements within a 1.4 kb sequence immediately upstream of the NRSE in both rat and human cholinergic gene loci suggests that this domain is required for cholinergic-specific regulation of VAChT and ChAT gene transcription. C1 NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. NIMH, Genet Sect, NIH, Bethesda, MD 20892 USA. Univ Marburg, Dept Anat & Cell Biol, D-3550 Marburg, Germany. RP Eiden, LE (reprint author), 36 Convent Dr,MSC-4090, Bethesda, MD 20892 USA. OI Eiden, Lee/0000-0001-7524-944X NR 32 TC 28 Z9 29 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD DEC PY 1997 VL 9 IS 3 BP 223 EP 236 DI 10.1007/BF02800504 PG 14 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA YU389 UT WOS:000071712200008 PM 9481623 ER PT J AU Ozaki, N Chuang, DM AF Ozaki, N Chuang, DM TI Lithium increases transcription factor binding to AP-1 and cyclic AMP-responsive element in cultured neurons and rat brain SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE lithium; AP-1; cyclic AMP-responsive element binding protein; cerebellar granule cells ID PROTEIN-KINASE-C; CEREBELLAR GRANULE CELLS; RECEPTOR MESSENGER-RNA; SIGNAL-TRANSDUCTION; ADENYLATE-CYCLASE; PHOSPHOLIPASE-C; NERVOUS-SYSTEM; ALPHA-SUBUNIT; EXPRESSION; FOS AB We have investigated whether lithium has effects on transcription factor binding to consensus DNA sequences of AP-1 and cyclic AMP-responsive element (CRE) in cultured rat neurons and in vivo. Treatment of rat cerebellar granule cells (CGC) with lithium chloride induced a concentration-dependent increase in AP-1 and CRE binding activities with maximal effects at therapeutically relevant concentrations of 0.5 and 1.0 mM. Time-course studies show that lithium's effects on AP-1 and CRE binding were biphasic within the first 24 h of treatment in immature CGC in culture and persistent in mature CGC, lasting as long as 7 days. These actions were concurrent with an increase in the mRNA levels of c-fos and c-jun, as well as the protein levels of c-Fos, c-Jun, and phosphorylated CRE binding protein (p-CREB). Gel supershift assays using transcription factor-specific antibodies revealed that p-CREB, Jun D, and a Fos family protein(s) are components of the AP-1 binding complex in untreated and lithium-treated CGC. Chronic dietary treatment of rats with lithium carbonate for 4 weeks also significantly increased AP-1 and CRE binding activity in the frontal cortex, hippocampus, amygdala, and cerebellum. Similar to the results obtained in CGC, p-CREB, Jun D, and Fos family proteins are present in the AP-1 binding sites in the frontal cortex and hippocampus of untreated and lithium-treated rats. Lithium-induced activation of transcription factor binding to AP-1 and CRE sites in vivo and in vitro provides a new avenue to study the mechanisms of action of lithium in the treatment of manic depressive illness. C1 NIMH,MOL NEUROBIOL SECT,BIOL PSYCHIAT BRANCH,NIH,BETHESDA,MD 20892. NR 42 TC 153 Z9 155 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 1997 VL 69 IS 6 BP 2336 EP 2344 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA YG275 UT WOS:A1997YG27500012 PM 9375664 ER PT J AU Holtzman, DA Brooks, PJ Pfaff, DW Schwartz-Giblin, S AF Holtzman, DA Brooks, PJ Pfaff, DW Schwartz-Giblin, S TI Preproenkephalin mRNA is regulated by an interaction between steroid hormones and nociceptive stimulation SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE preproenkephalin; dorsal horn; ventromedial nucleus of the hypothalamus; steroid hormones; noxious stimulus; in situ hybridization; spinal cord ID SPINAL-CORD DYNORPHIN; DORSAL HORN NEURONS; MESSENGER-RNA; FEMALE RAT; GENE-EXPRESSION; SPINOHYPOTHALAMIC TRACT; REPRODUCTIVE-BEHAVIOR; NUCLEUS CAUDALIS; PREGNANCY; PROGESTERONE AB The expression of preproenkephalin (PPE) mRNA has previously been shown to be regulated by steroid hormones in the ventromedial nucleus of the hypothalamus (VMH) and to be regulated by noxious stimuli in the dorsal horn of the spinal cord (DH), The present in situ hybridization study in ovariectomized rats showed that PPE mRNA expression in both the VMH and the lumbar DH, responds to the interaction between a noxious peripheral stimulus and ovarian steroid hormones. In the VMH, either estradiol or estradiol + progesterone increased the mean PPE mRNA content per cell by 100% compared with vehicle-treated rats, Unilateral hindpaw injection of 5% formalin, as compared to saline, significantly increased mean PPE mRNA content per VMH cell in rats treated with vehicle or estradiol but not those treated with estradiol + progesterone. Regression analysis for mean PPE mRNA content per VMH cell as a function of intensity of hindpaw inflammation showed a significant positive correlation coefficient after vehicle and estradiol treatment (P<0.02) but a strong trend towards a negative correlation coefficient after estradiol + progesterone treatment (P<0.06), ANOVA for homogeneity of regression coefficients showed a significant difference across hormone groups (P<0.01). In the lumbar DH, mean PPE mRNA content per cell was greater in rats injected with formalin than with saline and was greatest in rats given steroids + formalin, Mean PPE mRNA content per DH cell was greater ipsilateral than contralateral to the formalin injection in estradiol-treated rats, but no laterality difference was seen in the other hormone groups. No significant differences in mean PPE mRNA levels per DH cell were found among the rats treated with saline + hormone, saline + vehicle, formalin + vehicle, or uninjected rats, For all hormone groups combined, mean PPE mRNA per DH cell showed a significant positive regression on intensity of hindpaw inflammation (P<0.05). Taken together these data are consistent with reports of increased pain threshold during pregnancy, descending control of antinociception from the basomedial hypothalamus and positive correlations between VMH levels of PPE mRNA and lordosis, a behavior evoked by somatosensory stimulation below nociceptive threshold. C1 Univ Rochester, Dept Brain & Cognit Sci, Rochester, NY 14627 USA. NIAAA, Neurogenet Lab, NIH, Rockville, MD USA. Rockefeller Univ, Neurobiol & Behav Lab, New York, NY 10021 USA. Allegheny Univ Hlth Sci, MCP Hahnemann Med Sch, Dept Physiol, Philadelphia, PA 19102 USA. RP Schwartz-Giblin, S (reprint author), SUNY Hlth Sci Ctr, Dept Neurol, Box 41,450 Clarkson Ave, Brooklyn, NY 11203 USA. FU NICHD NIH HHS [HD25543]; NINDS NIH HHS [NS09170] NR 41 TC 16 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 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD DEC PY 1997 VL 9 IS 12 BP 913 EP 922 DI 10.1046/j.1365-2826.1997.00658.x PG 10 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA YR854 UT WOS:000071537600005 PM 9468016 ER PT J AU Recanzone, GH Wurtz, RH Schwarz, U AF Recanzone, GH Wurtz, RH Schwarz, U TI Responses of MT and MST neurons to one and two moving objects in the receptive field SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID TEMPORAL VISUAL AREA; PURSUIT EYE-MOVEMENTS; MACAQUE MONKEY; DIRECTION SELECTIVITY; EXPANSION CONTRACTION; TRANSPARENT MOTION; ROTATION CELLS; DORSAL PART; LESIONS; MECHANISMS AB To test the effects of complex visual motion stimuli on the responses of single neurons in the middle temporal visual area (MT) and the medial superior temporal area (MST) of the macaque monkey, we compared the response elicited by one object in motion through the receptive field with the response of two simultaneously presented objects moving in different directions through the receptive field. There was an increased response to a stimulus moving in a direction other than the best direction when it was paired with a stimulus moving in the best direction. This increase was significant for all directions of motion of the non-best stimulus and the magnitude of the difference increased as the difference in the directions of the two stimuli increased. Similarly, there was a decreased response to a stimulus moving in a non-null direction when it was paired with a stimulus moving in the null direction. This decreased response in MT did not reach significance unless the second stimulus added to the null direction moved in the best direction, whereas in MST the decrease was significant when the second stimulus direction differed from the null by 90 degrees or more. Further analysis showed that the two-object responses were better predicted by taking the averaged response of the neuron to the two single-object stimuli than by summation, multiplication, or vector addition of the responses to each of the two single-object stimuli. Neurons in MST showed larger modulations than did neurons in MT with stimuli moving in both the best direction and in the null direction and the average better predicted the two-object response in area MST than in area MT. This indicates that areas MT and MST probably use a similar integrative mechanisms to create their responses to complex moving visual stimuli, but that this mechanism is further refined in MST. These experiments show that neurons in both MT and MST integrate the motion of all directions in their responses to complex moving stimuli. These results with the motion of objects were in sound agreement with those previously reported with the use of random dot patterns for the study of transparent motion in MT and suggest that these neurons use similar lar computational mechanisms in the processing of object and global motion stimuli. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. Univ Calif Davis, Ctr Neurosci, Sect Neurobiol Physiol & Behav, Davis, CA 95616 USA. RP Wurtz, RH (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 44 TC 120 Z9 120 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 1997 VL 78 IS 6 BP 2904 EP 2915 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA YP840 UT WOS:000071320900009 PM 9405511 ER PT J AU Kjaer, TW Gawne, TJ Hertz, JA Richmond, BJ AF Kjaer, TW Gawne, TJ Hertz, JA Richmond, BJ TI Insensitivity of V1 complex cell responses to small shifts in the retinal image of complex patterns SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID PRIMARY VISUAL-CORTEX; CORTICAL-NEURONS; STRIATE CORTEX; SINGLE UNITS; 2-DIMENSIONAL PATTERNS; INFORMATION; STABILIZATION; RECOGNITION; FIXATION; MACAQUE AB An important role for neurons in the early visual system is to convey information about the structure of visual stimuli. However, neuronal responses show substantial variation across presentations of the same stimulus. In awake monkeys, it has been assumed that a great deal of this variation is related to the scatter in eye position (inducing scatter in the retinal position of the stimulus). Here we investigate the implied consequence of this assumption, i.e., that the scatter variation in eye position degrades the decodability of the neural response. We recorded from 50 complex cells in primary visual cortex of fixating monkeys while different complex stimuli were presented. Three types of retinal shifts were considered: natural scatter in the fixation, systematic fixation point shift, and systematic stimulus position shift. The stimulus pattern accounts for >50% of the response variance, always six times that accounted for by the scatter in eye position during fixation. The retinal location of a stimulus had to be shifted by 10-12 min of are, an amount almost two times larger than the smallest picture element, before the responses changed systematically. Nonetheless, changes of the stimulus at the single pixel level often gave rise to discriminable responses. Thus complex cells convey information about the spatial structure of a stimulus, independent of rigid stimulus displacements on the order of the receptive field size or smaller. C1 NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. NORDITA, DK-2100 Copenhagen, Denmark. RP Richmond, BJ (reprint author), NIMH, Neuropsychol Lab, 49 Convent Dr, Bethesda, MD 20892 USA. NR 24 TC 17 Z9 17 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 1997 VL 78 IS 6 BP 3187 EP 3197 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA YP840 UT WOS:000071320900036 PM 9405538 ER PT J AU Booth, V Rinzel, J Kiehn, O AF Booth, V Rinzel, J Kiehn, O TI Compartmental model of vertebrate motoneurons for Ca2+-dependent spiking and plateau potentials under pharmacological treatment SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID RAT HYPOGLOSSAL MOTONEURONS; PERSISTENT INWARD CURRENT; CRUSTACEAN MOTOR-NEURON; CAT SPINAL MOTONEURONS; IN-VITRO; CALCIUM CONDUCTANCES; ALPHA-MOTONEURONES; FIRING PROPERTIES; SEROTONIN; TURTLE AB In contrast to the limited response properties observed under normal experimental conditions, spinal motoneurons generate complex firing patterns, such as Ca2+-dependent regenerative spiking and plateaus, in the presence of certain neurotransmitters and ion-channel blockers. We have developed a quantitative motoneuron model, based on turtle motoneuron data, to investigate the roles of specific ionic currents and the effects of their soma and dendritic distribution in generating these complex firing patterns. In addition, the model is used to explore the effects of multiple ion channel blockers and neurotransmitters that are known to modulate motoneuron firing patterns. To represent the distribution of ionic currents across the soma and dendrites, the model contains two compartments. The soma compartment, representing the soma and proximal dendrites, contains Hodgkin-Huxley-like sodium (I-Na) and delayed rectifier K+ (IK-dr) currents, an N-like Ca2+ current (ICn-N), and a calcium-dependent K+ current [I-K(Ca)]. The dendritic compartment, representing the lumped distal dendrites, contains, in addition to ICa-N and I-K(Ca) as in the soma, a persistent L-Iike calcium current (ICa-L) We determined kinetic parameters for I-Na, IK-dr, ICa-N, and I-K(Ca) in order to reproduce normal action-potential firing observed in turtle spinal motoneurons, including fast and slow afterhyperpolarizations (AHPs) and a linear steady-state frequency-current relation. With this parameter set as default, a sequence of pharmacological manipulations were systematically simulated. A small reduction of IK-dr [mimicking the experimental effect of tetraethylammonium (TEA) in low concentration] enhanced the slow AHP and caused calcium spiking (mediated by ICa-N) when I-Na was blocked. Firing patterns observed experimentally in high TEA [and tetrodotoxin (TTX)], namely calcium spikes riding on a calcium plateau, were reproduced only when both IK-dr and I-K(Ca), were reduced. Dendritic plateau potentials, mediated by ICa-L, were reliably unmasked when I-K(Ca) was reduced, mimicking the experimental effect of the bee venom apamin. The effect of 5-HT, which experimentally induces the ability to generate calcium-dependent plateau potentials but not calcium spiking, was reproduced in the model by reducing IK(Cn) alone. The plateau threshold current level, however, was reduced substantially if a simultaneous increase in ICa-L was simulated, suggesting that serotonin (5-HT) induces plateau potentials by regulating more than one conductance. The onset of the plateau potential showed significant delays in response to near-threshold, depolarizing current steps. In addition, the delay times were sensitive to the current step amplitude. The delay and its sensitivity were explained by examining the model's behavior near the threshold for plateau onset. This modeling study thus accurately accounts for the basic firing behavior of vertebrate motoneurons as well as a range of complex firing patterns invoked by ion-channel blockers and 5-HT. In addition, our computational results support the hypothesis that the electroresponsiveness of motoneurons depends on a nonuniform distribution of ionic conductances, and they predict modulatory effects of 5-HT and properties of plateau activation that have yet to be tested experimentally. C1 NIDDKD, Math Res Branch, NIH 9190, Bethesda, MD 20814 USA. Panum Inst, Dept Physiol, Sect Neurophysiol, DK-2200 Copenhagen, Denmark. RP Booth, V (reprint author), New Jersey Inst Technol, Dept Math, Univ Hts, Newark, NJ 07102 USA. RI Kiehn, Ole/C-4679-2008 NR 52 TC 110 Z9 112 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 1997 VL 78 IS 6 BP 3371 EP 3385 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA YP840 UT WOS:000071320900049 PM 9405551 ER PT J AU Pare, M Wurtz, RH AF Pare, M Wurtz, RH TI Monkey posterior parietal cortex neurons antidromically activated from superior colliculus SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID SACCADE-RELATED ACTIVITY; FRONTAL EYE FIELDS; LATERAL INTRAPARIETAL AREA; HORSERADISH-PEROXIDASE; CORTICAL PROJECTIONS; ASSOCIATION CORTEX; SPATIAL PROPERTIES; MACAQUE MONKEY; RHESUS-MONKEYS; MICROSTIMULATION AB The connection between the posterior parietal cortex (PPC) and the superior colliculus (SC) was investigated by antidromically activating neurons within the lateral intraparietal(LIP) area with single-pulse stimulation delivered to the intermediate layers of the SC. To dissociate visual and saccade-related responses, the discharge properties of the identified efferent neurons were studied in the delayed visually guided saccade task and the memory guided saccade task. We found that the great majority (74%) of the identified LIP efferent neurons have a peripheral visual receptive field, typically with a broad spatial tuning. About two-thirds (64%) exhibited sustained activity during the delay period of the behavioral tasks, during which the monkeys had to withhold eye movements, and 80% of these increased their activity just before the onset of saccades. Both delay and presaccadic discharges in the delayed visually guided saccade task were higher than in the memory guided saccade task. These results establish that the neuronal signal sent by LIP to the SC carries both visual and saccade-related information. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Pare, M (reprint author), NEI, Sensorimotor Res Lab, NIH, 9000 Rockville Pike,Bldg 49,Room 2A50, Bethesda, MD 20892 USA. NR 36 TC 120 Z9 121 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 1997 VL 78 IS 6 BP 3493 EP 3497 PG 5 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA YP840 UT WOS:000071320900066 PM 9405568 ER PT J AU George, MS Ketter, TA Parekh, PI Rosinsky, N Ring, HA Pazzaglia, PJ Marangell, LB Callahan, AM Post, RM AF George, MS Ketter, TA Parekh, PI Rosinsky, N Ring, HA Pazzaglia, PJ Marangell, LB Callahan, AM Post, RM TI Blunted left cingulate activation in mood disorder subjects during a response interference task (the stroop) SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID SLEEP-DEPRIVATION; EMISSION TOMOGRAPHY; GLUCOSE-METABOLISM; BLOOD-FLOW; DEPRESSION; PERFORMANCE; CORTEX; SPECT AB Functional neuroimaging studies have found abnormal anterior cingulate activity in depressed subjects, and other studies have shown that the cingulate gyrus becomes active in healthy subjects during interference tasks. The authors hypothesized that subjects with mood disorder might show blunted cingulate activation during the standard Stroop interference task or during a modified version involving sadness-laden wards. In contrast to 11 age- and sex-matched healthy control subjects who activated the left cingulate during the standard Stroop, 11 mood-disordered subjects activated the right anterior cingulate gyrus only slightly and instead showed increased activity in the left dorso-lateral prefrontal and visual cortex. This study supports theories of blunted limbic and paralimbic activation and abnormal cingulate activity in depression and adds to the growing knowledge of the functional neuroanatomy of depression. C1 MED UNIV S CAROLINA,DEPT PSYCHIAT,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT NEUROL,CHARLESTON,SC 29425. RALPH H JOHNSON VET AFFAIRS HOSP,DEPT PSYCHIAT,CHARLESTON,SC. NEUROL INST,RAYMOND WAY NEUROPSYCHIAT RES GRP,LONDON,ENGLAND. NIMH,BIOL PSYCHIAT BRANCH,NIH,BETHESDA,MD 20892. RP George, MS (reprint author), MED UNIV S CAROLINA,DEPT RADIOL,171 ASHLEY AVE,CHARLESTON,SC 29425, USA. RI Ring, Howard/G-6684-2011 NR 62 TC 188 Z9 193 U1 0 U2 10 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD WIN PY 1997 VL 9 IS 1 BP 55 EP 63 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WD688 UT WOS:A1997WD68800007 PM 9017529 ER PT J AU Ketter, TA Malow, BA Post, RM Theodore, WH AF Ketter, TA Malow, BA Post, RM Theodore, WH TI Psychiatric effects of felbamate SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Letter C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NINCDS,EPILEPSY RES BRANCH,BETHESDA,MD 20892. NINCDS,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. RP Ketter, TA (reprint author), STANFORD UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,STANFORD,CA 94305, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD WIN PY 1997 VL 9 IS 1 BP 118 EP 118 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WD688 UT WOS:A1997WD68800016 PM 9017538 ER PT J AU Liebl, DJ Tessarollo, L Palko, ME Parada, LF AF Liebl, DJ Tessarollo, L Palko, ME Parada, LF TI Absence of sensory neurons before target innervation in brain-derived neurotrophic factor-, neurotrophin 3-, and TrkC-deficient embryonic mice SO JOURNAL OF NEUROSCIENCE LA English DT Article DE BDNF; NT-3; Trk; gene targeting; neurotrophins; sensory neurons ID NERVE GROWTH-FACTOR; DORSAL-ROOT GANGLION; SYMPATHETIC NEURONS; SPINAL GANGLIA; RECEPTOR GENE; SYSTEM; DEPENDENCE; BDNF; SURVIVAL; NT-3 AB Gene-targeting experiments of Trk receptors and neurotrophins has confirmed the expectation that embryonic sensory and sympathetic neurons require neurotrophin function for survival. They have further revealed correlation between a specific neurotrophin requirement and eventual sensory modality. We have analyzed embryonic and neonatal mice with mutations in the BDNF, neurotrophin 3 (NT-3), and TrkC genes. Our data confirm an unexpectedly high proportion of sensory neuron losses in NT-3 (>70%), BDNF (>20%), and TrkC (>30%) mutants, which encompass populations thought to be NGF-dependent. Direct comparison of TrkC and NT-3 mutants indicates that only a subset of the NT-3-dependent neurons also requires TrkC. The observed losses in our TrkC mutant, which is null for all proteins encoded by the gene, are more severe than those previously reported for the kinase-negative TrkC mutation, implicating additional and important functions for the truncated receptors. Our data further indicate that mature NGF-requiring neurons undergo precocious and transitory requirements for NT-3 and/or BDNF. We suggest that neurotrophins may function in creating early heterogeneity that would enable ganglia to compensate for diverse modality requirements before the period of naturally occurring death. C1 UNIV TEXAS,SW MED CTR,CTR DEV BIOL,DALLAS,TX 75235. NCI,ADV BIOSCI LAB,BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. RI Parada, luis/B-9400-2014 FU NCI NIH HHS [N01-CO-4600]; NINDS NIH HHS [NS33199] NR 45 TC 166 Z9 170 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 1 PY 1997 VL 17 IS 23 BP 9113 EP 9121 PG 9 WC Neurosciences SC Neurosciences & Neurology GA YG470 UT WOS:A1997YG47000019 PM 9364058 ER PT J AU Drew, PD Gado, AM Canning, RD Nagle, JW Dehejia, AM Polymeropoulos, MH Biddison, WE Jacobson, S Becker, KG AF Drew, PD Gado, AM Canning, RD Nagle, JW Dehejia, AM Polymeropoulos, MH Biddison, WE Jacobson, S Becker, KG TI C2H2-546: A zinc finger protein differentially expressed in HTLV-1 infected T cells SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE HTLV-1; transcription factor; zinc finger; molecular pathogenesis ID GENE; LEUKEMIA; RETROVIRUS; LYMPHOMA; KRUPPEL; PATIENT; REGION; LINE; CHROMOSOME-10; ABNORMALITIES AB We report the cloning and characterization of a novel cDNA termed C2H2-546 which encodes a C2H2-type zinc finger protein. C2H2-546 RNA is expressed in the HTLV-1 infected T cells examined which were derived from HAM-TSP patients, but not in T cells derived from ATL patients. The C2H2-546 gene is conserved in humans and primates and maps to chromosome 10q11.2, a site associated with a variety of cancers. Thus, C2H2-546 is a candidate regulatory molecule important in the formation of these tumors, and may serve as an important marker to distinguish HTLV-1 infected ATL versus HAM-TSP T cell lineages. C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Neurogenet Lab, Bethesda, MD 20892 USA. NCHGR, Gene Mapping Unit, Lab Genet Dis Res, NIH, Bethesda, MD 20892 USA. RP Drew, PD (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 10,Rm 5B16, Bethesda, MD 20892 USA. OI Becker, Kevin/0000-0002-6794-6656 NR 30 TC 1 Z9 2 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD DEC PY 1997 VL 3 IS 6 BP 455 EP 459 PG 5 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA YR640 UT WOS:000071515500009 PM 9475118 ER PT J AU Horak, E Hartmann, F Garmestani, K Wu, CC Brechbiel, M Gansow, OA Landolfi, NF Waldmann, TA AF Horak, E Hartmann, F Garmestani, K Wu, CC Brechbiel, M Gansow, OA Landolfi, NF Waldmann, TA TI Radioimmunotherapy targeting of HER2/neu oncoprotein on ovarian tumor using lead-212-DOTA-AE1 SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE HER2; neu proto-oncogene; alpha-emitting radionuclides; monoclonal antibody therapy; ovarian tumor ID HUMAN-BREAST CANCER; MONOCLONAL-ANTIBODIES; ANTI-TAC; THERAPY; CELLS; RECEPTOR; PROTOONCOGENE; COMPLEXES; EXPRESSION; APOPTOSIS AB The specificity, toxicity and efficacy of lead (Pb-212) radioimmunotherapy were evaluated in nude mice bearing the SK-OV-3 human ovarian tumor cell line expressing the HER2/neu proto-oncogene. Methods: The therapeutic agent used was the tumor-specific anti-HER2/neu monoclonal antibody AE1 conjugated to Pb-212, Bi-212 being the daughter and thus the source of the alpha-particle and beta emissions. A bifunctional derivative of tetraazacyclododecanetetraacetic acid (p-SCN-Bz-DOTA) was used to couple Pb-212 to the anti-HER2/neu monoclonal antibody AE1. The chelating agent did not alter the binding affinity to its antigenic target or the pharmacokinetics and tissue distribution of the AE1 antibody, Toxicity and therapeutic efficacy of Pb-212-AE1 were evaluated in nude mouse ascites or solid tumor models, wherein SK-OV-3 cells were administered i.p. or s.c., respectively. Results: The dose-limiting acute toxicity after i.v. administration of Pb-212-AE1 was bone marrow suppression, which was observed at doses above 25 mu Ci. Therefore, doses of 10 and 20 mu Ci were used in efficacy trials. The i.p. administration of Pb-212-AE1 3 days after i.p. tumor inoculation led to a significant (p(2) = 0.015) prolongation of tumor-free survival. In a second model, i.v. treatment with Pb-212-AE1 3 days after s.c. tumor inoculation prevented subsequent tumor development in all animals treated with 10 or 20 mu Ci of Pb-212-AE1 (p(2) = 0.002 compared to control groups). This efficacy in the adjuvant setting was antibody specific because treatments with equivalently labeled control antibody or unlabeled AE1 antibody or no treatment were less effective. The rate of growth of small (mean tumor volume, 15 mm(3)) SK-OV-3 tumors was modestly inhibited. However, tumor growth was not inhibited in mice bearing larger (mean tumor volume, 146 mm(3)) SK-OV-3 tumors by the administration of a single dose of 10 or 20 mu Ci of Pb-212-AE1. Conclusion: Lead-212-AE1 as an intact radiolabeled monoclonal antibody may be of only modest value in the therapy of bulky solid tumors due to the short physical half-life of Pb-212 and time required to achieve a useful tumor-to-normal tissue ratio of radionuclide after administration. However, the radiolabeled monoclonal antibody may be useful in therapy of tumors in the adjuvant setting. Furthermore, Pb-212 may be of value in select situations, including treatment of leukemia, intercavitary therapy or strategies that target vascular endothelial cells of tumors. C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Inorgan & Radioimmune Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. Prot Design Labs Inc, Mt View, CA USA. RP Waldmann, TA (reprint author), NCI, Metab Branch, NIH, Bldg 10,Room 4N115, Bethesda, MD 20892 USA. NR 37 TC 72 Z9 77 U1 0 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD DEC PY 1997 VL 38 IS 12 BP 1944 EP 1950 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA YP202 UT WOS:000071252800031 PM 9430475 ER PT J AU Kishimoto, R Ueda, M Kawakami, M Goda, K Park, SS Nakata, Y AF Kishimoto, R Ueda, M Kawakami, M Goda, K Park, SS Nakata, Y TI Effect of chronic administration of alcoholic beverages and seasoning containing alcohol on hepatic ethanol metabolism in mice SO JOURNAL OF NUTRITIONAL SCIENCE AND VITAMINOLOGY LA English DT Article DE C3H/He mice; alcoholic beverages; mirin; CYP2E1; CYP1A1 ID RAT-LIVER CYTOCHROME-P-450; MONOCLONAL-ANTIBODIES; OXIDIZING SYSTEM; ALDEHYDE DEHYDROGENASES; CONSUMPTION; OXIDATION; BEER; CARCINOGENESIS; IDENTIFICATION; NITROSAMINES AB Five-week-old male mice, C3H/HeNCrj (C3H/He), were given a 5% (v/v) ethanol solution, commercial alcoholic beverages (Japanese sake (sake) or red wine) or a Japanese seasoning (mirin [containing ethanol and a large amount of glucose]) ad libitum for 45 d, and were then examined for changes in the hepatic enzymes related to ethanol metabolism 2 h after oral administration of 5 g of ethanol/kg body weight. The specific activity of aniline hydroxylase (ANH) in the hepatic microsome increased significantly in all groups chronically administered ethanol solution, sake, red wine or mirin, and the greatest increase was in the hepatic microsome of mirin-administered mice. The cytochrome P-450 (CYP) 2E1 increased in the hepatic microsome of the mice administered ethanol solution, red wine or mirin where accompanied by high ANH activity. The immunoreactive band for CYP1A1 showed high specificity in the microsome of mice given sake, red wine or mirin. It was assumed that CYP1A1 was induced by unknown component(s) other than ethanol in these solutions, In the cytosolic fraction, following the chronic administration of sake and mirin, the total aldehyde dehydrogenase (AlDH) activity with high-Km decreased significantly. In the mitochondrial fraction, the activity of high-Km AlDH increased significantly in the mirin-administered mice which drank a large amount of ethanol, whereas that in the red wine-administered group tended to decrease. These results indicate that the enzyme activities related to the oxidation of both ethanol and acetaldehyde in the cytosolic, mitochondrial and microsomal fractions of the liver were affected by either the action of ethanol or its interaction with other constituents of sake, red wine and mirin. C1 Kobe Gakuin Univ, Fac Nutr, Nishi Ku, Kobe, Hyogo 65121, Japan. NCI, Comparat Carcinogenesis Lab, NIH, Frederick, MD 21702 USA. Osaka Univ, Sch Med Sci, Suita, Osaka 565, Japan. RP Kishimoto, R (reprint author), Kobe Gakuin Univ, Fac Nutr, Nishi Ku, Kobe, Hyogo 65121, Japan. NR 33 TC 6 Z9 6 U1 0 U2 2 PU CENTER ACADEMIC PUBL JAPAN PI TOKYO PA 4-16 YAYOI 2-CHOME, BUNKYO-KU, TOKYO, 113, JAPAN SN 0301-4800 J9 J NUTR SCI VITAMINOL JI J. Nutr. Sci. Vitaminol. PD DEC PY 1997 VL 43 IS 6 BP 613 EP 626 PG 14 WC Nutrition & Dietetics SC Nutrition & Dietetics GA YN610 UT WOS:000071187200002 PM 9530614 ER PT J AU Neuenschwander, H Takahashi, Y Kador, PF AF Neuenschwander, H Takahashi, Y Kador, PF TI Dose-dependent reduction of retinal vessel changes associated with diabetic retinopathy in galactose-fed dogs by the aldose reductase inhibitor M79175 SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID MURAL CELLS; CAPILLARIES; PERICYTES; LOCALIZATION; PREVENTION; GROWTH AB The onset and progression of retinal vascular changes associated with early diabetic retinopathy has been delayed in beagles fed 30% galactose diet for 38 months by treatment with the aldose reductase inhibitor M79175 (2-methyl-6-fluoro-spirochroman-4-5'-imidazolidine-2',4'-dione). Forty 9-month old male beagles were fed a daily diet containing either 30% non-nutrient filler or 30% galactose. One group of galactose-fed dogs was untreated while the others received M79175 at an average group dose of either 10 or 16 mg/kg/day. After 38 months one eye from 4 dogs from each group was enucleated and the isolated retinal vasculatures were objectively evaluated using an Olympus Cue-3 color image analysis system. Measurements of endothelium/pericyte (E/P) ratios, pericyte ghosts/1000 cells, pericytes and endothelial densities, and % acellularity per area and % acellularity per capillary length were conducted on a 0.1 mm square area surrounding the midpoints of 12 previously defined subregions. With the exception of endothelial densities which were not changed in galactose-fed dogs, M79175 treatment resulted in smaller changes in all parameters examined with the E/P ratio in dogs treated with 16 mg/kg/day M79175 not significantly different from that of age-matched non-galactose-fed dogs. These studies indicate that aldose reductase inhibitors provide dose-dependent protection against pericyte degeneration and subsequent microaneurysms formation. C1 NEI, Lab Ocular Therapeut, NIH, Bethesda, MD 20892 USA. RP Kador, PF (reprint author), NEI, Lab Ocular Therapeut, NIH, Bldg 10,Room 10B11,10 Ctr Dr,MSC 1850, Bethesda, MD 20892 USA. NR 29 TC 37 Z9 38 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1080-7683 J9 J OCUL PHARMACOL TH JI J. Ocular Pharmacol. Ther. PD DEC PY 1997 VL 13 IS 6 BP 517 EP 528 DI 10.1089/jop.1997.13.517 PG 12 WC Ophthalmology; Pharmacology & Pharmacy SC Ophthalmology; Pharmacology & Pharmacy GA YL902 UT WOS:000071006000004 PM 9436155 ER PT J AU Martin, R Boyer, P Hammill, H Peavy, H Platzker, A Settlage, R Shah, A Sperling, R Tuomala, R Wu, M AF Martin, R Boyer, P Hammill, H Peavy, H Platzker, A Settlage, R Shah, A Sperling, R Tuomala, R Wu, M TI Incidence of premature birth and neonatal respiratory disease in infants of HIV-positive mothers SO JOURNAL OF PEDIATRICS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SEROPOSITIVE WOMEN; DISTRESS SYNDROME; MATERNAL SMOKING; GESTATIONAL-AGE; WEIGHT OUTCOMES; COCAINE USE; TO-CHILD; INFECTION; TRANSMISSION AB Objective: We sought to determine the prematurity rate in infants of HIV-positive mothers and to characterize the incidence and severity of neonatal respiratory disease in this population. Study design: From 1990 to 1994, 600 live-born infants of HIV-infected mothers were enrolled prenatally (73%) or postnatally (27%) from five U.S. centers. Logistic regression was used to determine the association of HIV status in the infant with prematurity (less than or equal to 37 weeks), low birth weight (less than or equal to 2.5 kg), and very low birth weight (less than or equal to 1.5 kg) rates. The incidence of respiratory distress syndrome (RDS), bronchopulmonary dysplasia, meconium aspiration syndrome, and neonatal pneumonia was compared with anticipated rates for gestational age and birth weight. Results: Very high rates of prematurity (19%), low birth weight (18.3%), and very low birth weight (3.3%) were found in the infants of HIV-positive mothers; and HIV infection in the infant was associated with younger gestational age. The overall incidence of RDS was 3% (17/600), which coincided with the anticipated rate, after adjusting for prematurity and birth weight. Only five infants (all less than or equal to 1.5 kg) had bronchopulmonary dysplasia, and none required assisted ventilation beyond 14 days. Three term infants had mild meconium aspiration syndrome, and there were no cases of documented neonatal pneumonia. Conclusion: Infants born to HIV-positive mothers exhibited high prematurity and low birth weight rates, and the odds of prematurity were higher in infants who were infected with HIV. Despite the high incidence of prematurity and perinatal risk of this population, incidence and severity of neonatal respiratory disease were not higher than would be expected from available neonatal data in populations not exposed to HIV. C1 Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Baylor Coll Med, Houston, TX 77030 USA. NHLBI, Bethesda, MD 20892 USA. Childrens Hosp, Los Angeles, CA 90027 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Mt Sinai Sch Med, New York, NY USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Martin, R (reprint author), Rainbow Babies & Childrens Hosp, Div Neonatol, 11100 Euclid Ave, Cleveland, OH 44106 USA. FU NHLBI NIH HHS [N01-HR-96039, N01-HR-96037, N01-HR-96038] NR 27 TC 34 Z9 42 U1 1 U2 1 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 DEC PY 1997 VL 131 IS 6 BP 851 EP 856 DI 10.1016/S0022-3476(97)70032-5 PG 6 WC Pediatrics SC Pediatrics GA YN402 UT WOS:000071165100014 PM 9427889 ER PT J AU Stratakis, CA Mastorakos, G Magiakou, MA Papavasiliou, E Oldfield, EH Chrousos, GP AF Stratakis, CA Mastorakos, G Magiakou, MA Papavasiliou, E Oldfield, EH Chrousos, GP TI Thyroid function in children with Cushing's disease before and after transsphenoidal surgery SO JOURNAL OF PEDIATRICS LA English DT Article ID SURGICAL CURE; THYROTROPIN; GLUCOCORTICOIDS; DEXAMETHASONE; SECRETION; HORMONE; STATURE; GROWTH; AXIS AB The degree of thyroid impairment and the effects on growth have not been investigated in children with Cushing's disease. We followed the thyroid function of 24 children and adolescents (12 males and 12 females) with CD (age, 12.9 +/- 3.2 years; mean +/-; SD), who were successfully treated by transsphenoidal surgery. Patients were evaluated before, and 3, 6, and 12 months after TSS. Analysis of variance and linear correlation were performed between thyroid function tests and body weight and mass index and bone age. Preoperative free thyroxine levels (1.37 +/- 0.03 ng/dl) were significantly higher than those at 3 months (1.17 +/- 0.05 ng/dl, p < 0.05), but similar to those at 6 and 12 months postoperatively. Preoperative T3 (114.2 +/- 7.7 ng/dl) and TSH (1.36 +/- 0.2 IU/ml) were significantly lower than the postoperative values at 3 (158.9 +/- 6.8 and 2.3 +/- 0.3, respectively), 6 (159.1 +/- 10.8 and 2.5 +/- 0.3, respectively), and 12 months (136 +/- 6.5 and 2.2 +/- 0.3, respectively) (all p < 0.05). One patient had frank hypothyroidism (fT4 < 1 ng/dl) before surgery. Five additional patients had secondary hypothyroidism in the immediate postsurgical period; two of them had normal thyroid function 2 and 3 years postoperatively. One patient has remained hypothyroid for more than 5 years since surgery. No significant correlation was found between thyroid function and body weight, BMI, or BA. We conclude that hypothyroidism was an infrequent complication of CD and TSS. Mild suppression of thyroid function occurs in most children and adolescents with CD before and in the first few months after TSS, but it fully resolves after 6 months and does not correlate with the growth delay and obesity of these patients. C1 NINDS, Dev Endocrinol Branch, NICHHD, Surg Neurol Branch,NIH, Bethesda, MD 20892 USA. Georgetown Univ, Childrens Med Ctr, Div Pediat Endocrinol, Washington, DC 20007 USA. Georgetown Univ, Childrens Med Ctr, Div Genet, Washington, DC 20007 USA. RP Stratakis, CA (reprint author), NICHHD, NIH, Bldg 10,Room 10N262,10 Ctr Dr MSC 1928, Bethesda, MD 20892 USA. NR 27 TC 16 Z9 16 U1 0 U2 1 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 DEC PY 1997 VL 131 IS 6 BP 905 EP 909 DI 10.1016/S0022-3476(97)70041-6 PG 5 WC Pediatrics SC Pediatrics GA YN402 UT WOS:000071165100023 PM 9427898 ER PT J AU Wiggins, JS AF Wiggins, JS TI Circumnavigating dodge Morgan's interpersonal style SO JOURNAL OF PERSONALITY LA English DT Article ID PERSONALITY-SCALES; CLASSIFICATION; CIRCUMPLEX; TAXONOMY; MODEL AB The Interpersonal Circumplex Model provides a third perspective on Dodge Morgan's personality that clarifies and extends the perspectives provided by the five-factor and life-story models. Classification of Morgan as a prototypical autonomous personality "type" allows for nomothetic interpretations based on an extensive empirical literature. An explicit structural representation of agency and communion served to reveal the diversity of substantive interpretations that have been made with respect to these metaconcepts. Agreement on a structural representation of agency and communion might lead to more uniform interpretations of their dynamic relations with each another. C1 NIA, Gerontol Res Ctr, Lab Personal & Cognit, Baltimore, MD 21224 USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. RP Wiggins, JS (reprint author), NIA, Gerontol Res Ctr, Lab Personal & Cognit, 4940 Eastern Ave, Baltimore, MD 21224 USA. NR 42 TC 10 Z9 11 U1 1 U2 1 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0022-3506 J9 J PERS JI J. Pers. PD DEC PY 1997 VL 65 IS 4 BP 1069 EP 1086 DI 10.1111/j.1467-6494.1997.tb00544.x PG 18 WC Psychology, Social SC Psychology GA YV895 UT WOS:000071874900010 PM 9483819 ER PT J AU Ullrich, KJ Rumrich, G Burke, TR Shirazi-Beechey, SP Lang, HJ AF Ullrich, KJ Rumrich, G Burke, TR Shirazi-Beechey, SP Lang, HJ TI Interaction of alkyl/arylphosphonates, phosphonocarboxylates and diphosphonates with different anion transport systems in the proximal renal tubule SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CONTRALUMINAL SULFATE TRANSPORT; PARA-AMINOHIPPURATE TRANSPORT; BRUSH-BORDER MEMBRANE; RAT-KIDNEY; DICARBOXYLIC-ACIDS; PHOSPHATE-TRANSPORT; PAH TRANSPORT; SPECIFICITY; NA+; CONVOLUTION AB Luminal and contraluminal stop-flow microperfusion was applied, and the apparent K-i values (mmol/l) against the luminal phosphate and the contraluminal p-aminohippurate (PAH), sulfate and dicarboxylate transport systems were evaluated. Luminal phosphate transporter: Among the 20 compounds tested only phosphonoformate (foscarnet), etidronate, and clodronate have a good affinity (app.K-i, < 1 mmol/l), whereas the 2-naphthylphosphonates, phosphonoacetate, pamidronate, alendronate and aminomethanediphosphonates have a moderate affinity (app.K-i, 1.6-6.0 mmol/l). The other compounds tested had a. low (app.K-i > 6 mmol/l) or no affinity. Contraluminal PAH transporter: The hydrophobic phenyl-, benzyl- or 2-naphthylphosphonates have good to moderate affinity, whereas the less hydrophobic alkylphosphonates, the phosphonocarboxylates (except 4-phosphonobutyrate) and all tested diphosphonates show no interaction. Sulfate transportee 2-Naphthylmethylphosphonate and 2-naphthylmethyldifluorophosphonate have a good affinity (app.K-i less than or equal to 0.5 mmol/l), whereas Cl-F-methylphosphonate, 20H-5NO(2)-benzyl-phosphonate, 2-naphthylhydroxymethylphosphonate, phosphonoacetate etidonate and clodronate have only a moderate affinity (app.K-i approximate to 3 mmol/l). The other tested compounds have a low or no affinity. Dicarboxylate transporter: Among the tested compounds only 3-phosphonopropionate (app.K-i, 4.2 mmol/l) and 4 phosphonobutyrate (app.K-i, 7.0 mmol/l) interact with this transporter. Thus, we might conclude that in the submillimolar range only phosphonoformate (foscarnet), etidronate and clodronate inhibit luminal phosphate transport. As predictable from previous structure-activity studies for the contraluminal PAH, sulfate and dicarboxylate transporters the alkyl/arylphosphonates and the phosphonocarboxylates interact with these transporters according to their hydrophobicity and charge distribution. Among the seven diphosphonates tested, only etidronate and clodronate have a moderate affinity to the sulfate transporter, whereas the aminodiphosphonates have no (or low) affinity to any of the contraluminal anion transporters. C1 Max Planck Inst Biophys, D-60596 Frankfurt, Germany. NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Wales, Inst Biol Sci, Aberystwyth, Dyfed, Wales. HMR Hoechst AG, Synthet Res, Frankfurt, Germany. RP Ullrich, KJ (reprint author), Max Planck Inst Biophys, Kennedyallee 70, D-60596 Frankfurt, Germany. RI Burke, Terrence/N-2601-2014 NR 39 TC 22 Z9 22 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 1997 VL 283 IS 3 BP 1223 EP 1229 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YM806 UT WOS:000071102900031 PM 9399997 ER PT J AU Caudle, RM Mannes, AJ Iadarola, MJ AF Caudle, RM Mannes, AJ Iadarola, MJ TI GR89,696 is a kappa-2 opioid receptor agonist and a kappa-1 opioid receptor antagonist in the guinea pig hippocampus SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID LONG-TERM POTENTIATION; MOSSY FIBER SYNAPSES; UNILATERAL INFLAMMATION; BEHAVIORAL HYPERALGESIA; NMDA RECEPTORS; DENTATE GYRUS; RAT; BRAIN; TOLERANCE; DYNORPHIN AB Receptor binding studies and electrophysiological studies demonstrated the existence of at least two kappa opioid receptors, which have been designated ka,apa-l and kappa-2, Several agonists and antagonists are selective for the kappa-1 receptor whereas no known ligands are selective for the kappa-2 receptor. In this study, the kappa opioid GR89,696 was tested in the guinea pig hippocampal slice preparation for kappa-l versus kappa-2 activity, The perforant path-evoked population spike in the dentate was use to evaluate activity at the kappa-l receptor, and the Schaffer collateral-evoked N-methyl-D-aspartate (NMDA) receptor-mediated synaptic current in CA3 pyramidal cells was used to measure kappa-2 receptor activation. GR89,696 had no effect on the perforant path-evoked dentate population spike; however, it did reverse the effects of the selective kappa-l agonist U69,593 when co-perfused over the slices. In the CA3, GR89,696 inhibited the NMDA receptor-mediated synaptic current. The inhibition was antagonized by naloxone. The EC50 for GR89,696 on the NMDA current was 41.7 nM (95% CL, 7.0-248 nM). These findings indicate that GR89,696 is an agonist for kappa-2 opioid receptors and an antagonist at kappa-l receptors in the guinea pig hippocampus. C1 NIDR, PNMB, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Dept Anesthesia, Philadelphia, PA 19104 USA. RP Caudle, RM (reprint author), NIDR, PNMB, NIH, Bldg 49,Room 1W26,49 Convent Dr,MSC 4410, Bethesda, MD 20892 USA. NR 28 TC 20 Z9 20 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 1997 VL 283 IS 3 BP 1342 EP 1349 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YM806 UT WOS:000071102900043 PM 9400009 ER PT J AU Bovetto, S Boyer, PA Skolnick, P Fossom, LH AF Bovetto, S Boyer, PA Skolnick, P Fossom, LH TI Chronic administration of a glycine partial agonist alters the expression of N-methyl-D-aspartate receptor subunit mRNAs SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID HETEROMERIC NMDA RECEPTORS; EXCITATORY AMINO-ACIDS; 1-AMINOCYCLOPROPANECARBOXYLIC ACID; PARKINSONS-DISEASE; GLOBAL-ISCHEMIA; MODULATORY SITE; GLUTAMATE; RAT; ANTAGONIST; COMPLEX AB Both acute and chronic treatments with the glycine partial agonist 1-aminocyclopropanecarboxylic acid (ACPC) are neuroprotective in animal models of focal, global and spinal ischemia. After a chronic regimen of ACPC, brain and plasma levels were undetectable at the time of ischemic insult, which suggests that the neuroprotective effects of acute and chronic ACPC are mediated by different mechanisms. To investigate the possibility that chronic administration of ACPC alters N-methyl-D-aspartate (NMDA) receptor composition, the levels of mRNAs encoding xi and epsilon subunits were quantified by in situ hybridization histochemistry with S-35-labeled riboprobes. Chronic ACPC administered to mice (200 mg/kg for 14 days) increased the level of epsilon-l mRNA in the hippocampus (particularly CA1 and CA2 regions) and cerebral cortex (frontal, parietal and occipital regions), without altering levels in cerebellum. In contrast, this regimen decreased epsilon-3 subunit mRNA levels in the hippocampus (especially CAI and dentate gyrus) and frontal and occipital cortices. Decreases in epsilon-2 subunit mRNA levels in cerebral cortex (especially frontal and parietal cortices) were also observed without accompanying alterations in the cerebellum, hippocampus or dentate gyrus. The levels of zeta subunit mRNA (determined with a probe that detects all splice variants) were not altered in any brain areas examined. Based an studies in recombinant receptors, these region-specific changes in mRNAs produced by a chronic reg imen of ACPC could result in NMDA receptors with reduced affinities for glycine and glutamate. It is hypothesized that such alterations in NMDA receptor subunit composition may explain the neuroprotective effects produced by chronic ACPC. C1 NIDDKD, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Fossom, LH (reprint author), NIDDK, Neurosci Lab, NIH, Bldg 8,Room 1A15, Bethesda, MD 20892 USA. NR 40 TC 7 Z9 7 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 1997 VL 283 IS 3 BP 1503 EP 1508 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YM806 UT WOS:000071102900061 PM 9400027 ER PT J AU Albertini, TF Kingman, A Brown, LJ AF Albertini, TF Kingman, A Brown, LJ TI Prevalence and distribution of dental restorative materials in US Air Force veterans SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE dental restorations; dental materials; dental epidemiology; health services; oral health; adults; United States ID CLASS-III; RESIN; REPLACEMENT AB Objectives: Millions of restorative procedures are performed annually in the United States, yet very little is known about their distribution in the general population. With increasing concern about potential adverse health effects of some restorative materials, a better understanding of the extent of exposure to these materials in the population is important. The purpose of this study is to report the prevalence, patterns, and distribution of dental restorative materials in a population of male veterans. Methods: This collaborative study with the US Air Force examined 1,166 male veterans to assess exposure to dental amalgam and other restorative materials. An inventory of dental materials in the study population was obtained through oral examinations. Dental materials were classified into five categories: (1) amalgam; (2) resin; (3) porcelain, cement, or temporary, including ionomer (PCT); (4) cast gold alloys/direct filling gold; and (5) other metals (OM). The mean age of the study participants was 52.9 years. Over 94 percent of the study participants were dentate. Results: The study participants averaged 45.8 restored/replaced surfaces. Restored/replaced surfaces increased with age while the number of teeth decreased with age. The most frequently used restorative material was amalgam, averaging 19.89 surfaces per subject, followed by PCT (9.38), resins (8.99), OM (5.52), and gold (4.91). The distributions of restorative materials varied by age, arch type, and location in the mouth. Conclusions: The study population experienced substantial exposure to dental materials. RP Albertini, TF (reprint author), NIDR,DIV INTRAMURAL RES,NIH,NATCHER BLDG,ROOM 4AS-13E,45 CTR DR MSC 6401,BETHESDA,MD 20892, USA. FU NIDCR NIH HHS [N01DE-22595, 1YO1-DE-20037] NR 23 TC 3 Z9 3 U1 0 U2 0 PU AAPHD NATIONAL OFFICE PI RICHMOND PA J PUBLIC HEALTH DENT 10619 JOUSTING LANE, RICHMOND, VA 23235 SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD WIN PY 1997 VL 57 IS 1 BP 5 EP 10 DI 10.1111/j.1752-7325.1997.tb02467.x PG 6 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA WW556 UT WOS:A1997WW55600002 PM 9150058 ER PT J AU Brooks, WM Sabet, A Sibbitt, WL Barker, PB vanZijl, PCM Duyn, JH Moonen, CTW AF Brooks, WM Sabet, A Sibbitt, WL Barker, PB vanZijl, PCM Duyn, JH Moonen, CTW TI Neurochemistry of brain lesions determined by spectroscopic imaging in systemic lupus erythematosus SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE systemic lupus erythematosus; spectroscopy; nuclear magnetic resonance; neurochemistry; brain injuries ID MAGNETIC-RESONANCE SPECTROSCOPY; PROTON NMR-SPECTROSCOPY; MULTIPLE-SCLEROSIS LESIONS; CENTRAL-NERVOUS-SYSTEM; WHITE-MATTER LESIONS; NEUROPSYCHIATRIC LUPUS; CEREBRAL-ISCHEMIA; N-ACETYLASPARTATE; ACUTE STROKE; INVOLVEMENT AB Objective. The significance and etiology of focal brain lesions in systemic lupus erythematosus (SLE) are unknown. Our purpose was to determine whether the neurochemistry of focal lesions and normal appearing brain tissues in SLE were consistent with neuronal loss, demyelination, or ischemia. Methods. Patients with SLE (n = 14) and controls (n = 13) were studied using magnetic resonance imaging (MRI) and spectroscopic imaging (SI) at 1.5 Tesla. Results. MRI detected fixed focal brain lesions (n = 16) and SI measured brain metabolites, including N-acetylaspartate (NAA), creatine (Cre), choline (Cho), and lactate (Lac). NAA/Cre of normal appearing brain was decreased in patients with SLE compared to controls: grey matter (1.74 +/- 0.16 vs 1.92 +/- 0.18; p = 0.01), occipital white matter (1.98 +/- 0.22 vs 2.23 +/- 0.16; p = 0.004), and periventricular white matter (2.00 +/- 0.23 vs 2.33 +/- 0.23; p = 0.001). Lesions were characterized by markedly decreased NAA/Cre relative to normal appearing tissues in the same patient (1.67 +/- 0.22 vs 1.88 +/- 0.14; p = 0.0002). Elevated Cho/Cre was observed in 25% of focal lesions and 21% of normal appearing tissues. No elevation of lactate was observed in lesions or normal appearing tissues. Conclusion. SI detects focal and generalized brain abnormalities in SLE characterized by decreased NAA, elevated choline, and normal lactate. These findings are consistent with widespread neuronal injury and demyelination, but are not consistent with anaerobic metabolism. C1 UNIV NEW MEXICO,HLTH SCI CTR,DEPT INTERNAL MED,DIV CLIN IMMUNOL & RHEUMAT DIS,ALBUQUERQUE,NM 87131. UNIV NEW MEXICO,HLTH SCI CTR,DEPT NEUROSCI,ALBUQUERQUE,NM 87131. UNIV NEW MEXICO,HLTH SCI CTR,CTR NONINVAS DIAG,ALBUQUERQUE,NM 87131. HENRY FORD HOSP,DEPT NEUROL,DETROIT,MI 48202. JOHNS HOPKINS UNIV,SCH MED,DEPT RADIOL,BALTIMORE,MD 21205. NIH,BETHESDA,MD 20892. RI van Zijl, Peter/B-8680-2008; Duyn, Jozef/F-2483-2010; Moonen, Chrit/K-4434-2016; OI Moonen, Chrit/0000-0001-5593-3121; brooks, william/0000-0001-6227-7636 NR 46 TC 67 Z9 69 U1 0 U2 4 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD DEC PY 1997 VL 24 IS 12 BP 2323 EP 2329 PG 7 WC Rheumatology SC Rheumatology GA YJ242 UT WOS:A1997YJ24200011 PM 9415636 ER PT J AU Jensen, PS Mrazek, D Knapp, PK Steinberg, L Pfeffer, C Schowalter, J Shapiro, T AF Jensen, PS Mrazek, D Knapp, PK Steinberg, L Pfeffer, C Schowalter, J Shapiro, T TI Evolution and revolution in child psychiatry: ADHD as a disorder of adaptation SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE evolution; attention-deficit/hyperactivity disorder; adaptation; behavioral ecology ID HARMFUL DYSFUNCTION; HYPERACTIVE BOYS; CONDUCT DISORDER; MENTAL DISORDER; METHYLPHENIDATE; COMPREHENSION; ATTENTION AB Current knowledge about early plasticity and children's responsiveness to environmental modifications as well as the atheoretical nature of current nosological systems necessitate alternative models to explain the phenomena of childhood behavioral and emotional disturbances. Evolutionary biology provides one such framework. It organizes data from the behavioral and cognitive sciences and parallels similar efforts in other areas of medicine and biology. Through an evolutionary biological lens, some mental disorders are better viewed as an adaptive response to early pathogenic environments and/or reflect the optimization of brain function to same environments at the cost of poorer response to the demands of other environments. As an example, the authors examine attention-deficit/hyperactivity disorder (ADHD) in relation to evolutionary theories of psychology and biology and clarify the potentially adaptive nature of characteristics of inattention, impulsivity and motoric hyperactivity, depending on the nature of child's environments. Reframing ADHD characteristics according to evolutionary theory has important treatment implications for clinicians and offers researchers opportunities for novel scientific discoveries. C1 GEORGE WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,WASHINGTON,DC 20052. UNIV CALIF DAVIS,DEPT PSYCHIAT,DIV CHILD & ADOLESCENT PSYCHOL,DAVIS,CA. TEMPLE UNIV,DEPT PSYCHOL,PHILADELPHIA,PA 19122. CORNELL UNIV,SCH MED,NEW YORK,NY 10021. YALE UNIV,YALE CHILD STUDY CTR,NEW HAVEN,CT. RP Jensen, PS (reprint author), NIMH,CHILD & ADOLESCENT DISORDERS RES BRANCH,PARKLAWN BLDG,ROOM 18C-17,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. OI Jensen, Peter/0000-0003-2387-0650 NR 30 TC 104 Z9 106 U1 6 U2 27 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD DEC PY 1997 VL 36 IS 12 BP 1672 EP 1679 DI 10.1097/00004583-199712000-00015 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA YJ171 UT WOS:A1997YJ17100015 PM 9401328 ER PT J AU Sollitto, RB Kraemer, KH DiGiovanna, JJ AF Sollitto, RB Kraemer, KH DiGiovanna, JJ TI Normal vitamin D levels can be maintained despite rigorous photoprotection: Six years' experience with xeroderma pigmentosum SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID SUNSCREEN USE; SKIN-CANCER; ISOTRETINOIN; PHOTOSYNTHESIS; ULTRAVIOLET; DECREASES; SUNLIGHT; THERAPY AB Background: Although sun protection is advocated for skin cancer prevention, sunlight is also important in generation of vitamin D in the skin. There is concern that sun protection may result in an abnormally low level of vitamin D. Objective: To assess the risk of vitamin D deficiency in a sunlight-deprived population, we studied eight ambulatory patients with xeroderma pigmentosum (XP) who practiced intensive sun protection during a chemoprevention study of oral isotretinoin. Methods: We surveyed the patients to determine the extent of sun protection and vitamin D intake and measured the serum levels of two vitamin D metabolites (25-hydroxyvitamin D [25-OHD] and 1,25-dihydroxyvitamin D [1,25-(OH)(2)D]), calcium, and parathyroid hormone during 6 years, Results: The patients all wore protective clothing and sunscreens when outdoors, Estimated mean vitamin D intake was normal. The mean values of serum 25-OHD were low normal, but 1,25-(OH)(2)D, calcium, ionized calcium and parathyroid hormone levels were normal. Lack of seasonal variation in serum 25-OHD indicated rigorous photoprotection. Conclusion: Despite rigorous sun protection normal vitamin D levels can be maintained in ambulatory patients with XP. C1 NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NIAMSD, Dermatol Clin Res Unit, NIH, Bethesda, MD 20892 USA. RP Kraemer, KH (reprint author), NCI, Mol Carcinogenesis Lab, NIH, Bldg 37,Room 3E24, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 BC004517-31] NR 25 TC 55 Z9 56 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD DEC PY 1997 VL 37 IS 6 BP 942 EP 947 DI 10.1016/S0190-9622(97)70069-0 PG 6 WC Dermatology SC Dermatology GA YM517 UT WOS:000071072700005 PM 9418761 ER PT J AU Kikuchi, A Okamoto, S Takahashi, S Asano, S Nishikawa, T AF Kikuchi, A Okamoto, S Takahashi, S Asano, S Nishikawa, T TI Linear chronic cutaneous graft-versus-host disease SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article C1 Keio Univ, Sch Med, Dept Dermatol, Keio, Japan. Keio Univ, Sch Med, Dept Internal Med, Div Hematol Oncol, Keio, Japan. Univ Tokyo, Inst Med Sci, Tokyo, Japan. RP Kikuchi, A (reprint author), NCI, Dermatol Branch, Bldg 10,Room 12N238, Bethesda, MD 20892 USA. NR 10 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 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD DEC PY 1997 VL 37 IS 6 BP 1004 EP 1006 DI 10.1016/S0190-9622(97)70086-0 PG 3 WC Dermatology SC Dermatology GA YM517 UT WOS:000071072700021 PM 9418777 ER PT J AU Dolan, TA McGorray, SP GrinsteadSkigen, CL Mecklenburg, R AF Dolan, TA McGorray, SP GrinsteadSkigen, CL Mecklenburg, R TI Tobacco control activities in US dental practices SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID CIGARETTE-SMOKING; DENTISTS AB The authors surveyed general dentists, periodontists, pediatric dentists and dental hygienists in three U.S. geographical regions to estimate the percentage who practiced tobacco use cessation activities in their dental offices. A total of 1,746 dentists and 723 dental hygienists completed either a long or short version of a mailed survey or telephone interview. The authors found that tobacco cessation activities are not a routine part of dental practice and that tobacco control activities and training vary by dentist type and geographical region. C1 DUVAL CTY HLTH DEPT,IM SULZBACHER CTR HOMELESS,JACKSONVILLE,AL. NCI,SMOKING & TOBACCO CONTROL PROGRAM,BETHESDA,MD 20892. UNIV FLORIDA,DEPT STAT,GAINESVILLE,FL 32611. RP Dolan, TA (reprint author), UNIV FLORIDA,COLL DENT,DIV PUBL HLTH SERV & RES,JHMHC BOX 100405,GAINESVILLE,FL 32610, USA. NR 27 TC 77 Z9 78 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD DEC PY 1997 VL 128 IS 12 BP 1669 EP 1679 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YJ866 UT WOS:A1997YJ86600021 PM 9415764 ER PT J AU Slavkin, HC AF Slavkin, HC TI Reflections on taste for oral health professionals SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article RP Slavkin, HC (reprint author), NIDR,31 CTR DR,MSC 2290,BLDG 31,ROOM 2C39,BETHESDA,MD 20892, USA. NR 3 TC 3 Z9 3 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD DEC PY 1997 VL 128 IS 12 BP 1697 EP 1701 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YJ866 UT WOS:A1997YJ86600024 PM 9415767 ER PT J AU Pennington, JAT Hubbard, VS AF Pennington, JAT Hubbard, VS TI Derivation of daily values used for nutrition labeling SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Review AB Daily Values (DVs) are the daily dietary intake standards used for nutrition labeling. Information on the derivation of DVs is important for dietetics professionals and nutrition educators who use DVs to educate and instruct patients and students about diet planning and evaluation and about adherence to modified diets. The first daily intake standards for nutrition labeling were established in 1973 and were referred to as the US Recommended Daily Allowances (US RDAs). They were based on the 1968 Recommended Dietary Allowances (RDAs) developed by the National Academy of Sciences. These intake standards were mandatory for 8 and optional for 12 food components on nutrition labels. Regula tions revising the daily intake standards for nutrition labeling were published in 1993. The new standards included Reference Daily Intakes (RDIs) for 19 food components and Daily Reference Values (DRVs) for 8 food components. The RDIs were based on the 1973 US RDAs, and the DRVs were based on consensus recommendations. On the nutrition label, the RDIs and DRVs are referred to as DVs. Percent DVs are mandatory on nutrition labels for 10 food components and optional for 16 food components. In 1995, DVs were established by regulation for 6 additional food components; these DVs are optional for nutrition labels. The DVs established in 1995 were based on information from the 1980 and 1989 revisions of the RDAs and Estimated Safe and Adequate Daily Dietary Intakes. Currently, percent DVs are mandatory on nutrition labels far 19 food components and optional for 22. Optional percent: DVs become mandatory if claims are made about the food components or if the food components are added to the food through fortification or as food additives. C1 NIDDKD,DIV DIGEST DIS & NUTR,NUTR SCI BRANCH,BETHESDA,MD 20892. RP Pennington, JAT (reprint author), NIDDKD,DIV NUTR RES COORDINAT,NATCHER BLDG,RM 5AN32,45 CTR DR,MSC 6600,BETHESDA,MD 20892, USA. NR 6 TC 10 Z9 11 U1 0 U2 1 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD DEC PY 1997 VL 97 IS 12 BP 1407 EP 1412 DI 10.1016/S0002-8223(97)00340-4 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA YJ872 UT WOS:A1997YJ87200019 PM 9404338 ER PT J AU Rantanen, T Era, P Heikkinen, E AF Rantanen, T Era, P Heikkinen, E TI Physical activity and the changes in maximal isometric strength in men and women from the age of 75 to 80 years SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID 75-YEAR-OLD MEN; ANTHROPOMETRY AB OBJECTIVE: To research the natural changes in maximal isometric strength, over a period of 5 years, in men and women aged 75 at baseline, and to study the effect of everyday physical activity on strength alterations. DESIGN: A 5-year longitudinal study. SETTING: Exercise laboratory PARTICIPANTS: The target group in 1989 was the total 75-year-old population of Jyvaskyla. One hundred one men (81%) and 186 women (75%) participated in baseline strength tests, and after 5 years, 55 men and 111 women (70% and 72% of the survivors) took part in the follow-up measurements. METHODS: Maximal isometric hand grip, arm flexion, knee extension, trunk flexion, and trunk extension forces were measured using dynamometers. Self-rated physical activity was recorded using a scale by Grimby (1986). Strength changes were compared between groups based on the amount of everyday physical activity: (1) remained active (AA, 24 men, 24 women); (2) remained sedentary (SS, 11 men, 43 women); (3) decreased activity (AS, 11 women); and (4) increased activity (SA, 32 women). AS and SA could be formed for women only because of the small number of men. All analyses were stratified by gender. MAIN RESULTS: The average percentage change in strength over 5 years among survivors varied from a 4% increase in knee extension strength observed in men and women to a 16% decrease in grip strength in women. The grip strength decrease was greater in women than men. the AA men maintained their trunk extension strength at a higher level than the SS men. Time by group interactions in men were not significant. In women, the rate of decline in AS was 32% in grip and 27% in elbow flexion strength, which was greater than in the other activity groups. The AA women retained their knee extension strength at a higher level than the other groups. Those who died before follow-up tests exhibited poorer strength test results at baseline. Physical activity decreased over follow-up. CONCLUSIONS: Strength alterations with age differed between muscle groups. Undertaking everyday physical activities such as household work, walking, and gardening, which are also the most common physically demanding activities of older people, may play an important role in maintaining strength at an adequate level for independent living. C1 UNIV JYVASKYLA,FINNISH CTR INTERDISCIPLINARY GERONTOL,JYVASKYLA,FINLAND. UNIV JYVASKYLA,DEPT HLTH SCI,JYVASKYLA,FINLAND. RP Rantanen, T (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,NIH,GATEWAY BLDG,ROOM 3C309,7201 WISCONSIN AVE,MSC920,BETHESDA,MD 20892, USA. RI Rantanen, Taina/O-6579-2016 OI Rantanen, Taina/0000-0002-1604-1945 NR 23 TC 155 Z9 158 U1 1 U2 11 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 1997 VL 45 IS 12 BP 1439 EP 1445 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA YK263 UT WOS:A1997YK26300003 PM 9400552 ER PT J AU Sharp, DS Burchfiel, CM Curb, JD Rodriguez, BL Enright, PL AF Sharp, DS Burchfiel, CM Curb, JD Rodriguez, BL Enright, PL TI The synergy of low lung function and low body mass index predicting all-cause mortality among older Japanese-American men SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; CORONARY HEART-DISEASE; EXPIRATORY FLOW-RATE; MUCUS HYPERSECRETION; ELDERLY POPULATION; CHRONIC-BRONCHITIS; REFERENCE VALUES; NATIONAL COHORT; WEIGHT; ADULTS AB OBJECTIVE: To assess the joint characteristics of low standardized weight and compromised pulmonary function in predicting all-cause morrality. DESIGN: A population-based, prospective cohort study. SETTING: Oahu Island, Hawaii. PARTICIPANTS: Surviving Japanese-American men of the Honolulu Heart Program cohort, 71 to 93 years of age (N = 3059). MEASUREMENTS: Body mass index (BMI - weight in kilograms/square of height in meters) and I-second forced expiratory volume (FEV1) as a percentage of age-and height-predicted FEV1 from the 1991 to 1993 examination of the cohort. Mortality data derived from the ongoing tracking of deaths of the cohort. Relations of selected risk factors among joint levels of BMI (less than or equal to 21, > 21 to < 25, greater than or equal to 25 kg/m(2)) and pet-tent predicted FEV1 (less than or equal to 70%, > 70%) were determined, The impact of these covariates on relations between joint BMI/percent predicted FEV1 levels and subsequent all-cause mortality was assessed. RESULTS: The highest age-adjusted mortality rate (91.9 deaths per 1000 person-years) was noted among men characterized by the joint conditions of percent predicted FEV1 less than or equal to 70% and BMI less than or equal to 21 kg/m.(2) This rate was 4.0 times the mortality rate of a ''healthy'' reference group characterized by percent predicted FEV1 > 70% and 21 < BMI < 25 kg/m(2). This rate ratio is attenuated to 3.2 upon statistical control for measures of current and past smoking behavior. Among the three strata of BMI, statistical interaction is reflected in a heterogeneity of mortality rate differences (49.7, 21.8, - 9.6 deaths/person-year, respectively) and rate ratios (2.18, 1.98, .66, respectively) comparing men with percent predicted FEV1 less than or equal to 70% to > 70%. CONCLUSION: Joint loss of pulmonary function and relative weight is predictive of subsequent all-cause mortality in excess of additive or multiplicative effects of each condition separately. Smoking behavior may contribute to this observation. C1 KUAKINI MED CTR, HONOLULU HEART PROGRAM, HONOLULU, HI USA. UNIV HAWAII, JOHN A BURNS SCH MED, HONOLULU, HI 96822 USA. UNIV ARIZONA, RESP SCI CTR, TUCSON, AZ 85721 USA. RP Sharp, DS (reprint author), NHLBI, DIV EPIDEMIOL & CLIN APPLICAT, EBP, HONOLULU EPIDEMIOL RES UNIT, ROCKLEDGE CTR 2, BETHESDA, MD 20892 USA. FU NHLBI NIH HHS [N01-HC-05102] NR 39 TC 14 Z9 14 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 1997 VL 45 IS 12 BP 1464 EP 1471 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA YK263 UT WOS:A1997YK26300007 PM 9400556 ER PT J AU Leveille, SG LaCroix, AZ Newton, KM Keenan, NL AF Leveille, SG LaCroix, AZ Newton, KM Keenan, NL TI Older women and hormone replacement therapy: Factors influencing late life initiation SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID POSTMENOPAUSAL ESTROGEN THERAPY; CORONARY HEART-DISEASE; MIDDLE-AGED WOMEN; ELDERLY WOMEN; OSTEOPOROSIS; ATTITUDES AB OBJECTIVE: To describe factors associated with initiation of hormone replacement therapy (HRT) by older women, DESIGN: A cross-sectional study of 671 randomly selected women aged 65 to 80 who participated in a larger telephone survey on preventive health behaviors. SETTING: A large health maintenance organization (HMO) in Seattle, Washington. PARTICIPANTS: Of the 521 women who responded (78%), 51 had begun taking HRT at age 60 or older and were identified as initiators. Women who had never used HRT or past users who had begun HRT before age 60 were classified as noninitiators (n = 362). Current users who started HRT before age 60 (n = 108) were excluded. MEASUREMENTS: Sources included the telephone survey, automated HMO pharmacy data, and HMO utilization and provider databases. RESULTS: Initiators were similar to noninitiators with respect to age, marital status, education, and health status. Initiators were more likely to have had a hysterectomy at age 60 or later than noninitiators. Sixty-two percent of the noninitiators said they had received no information about the benefits of HRT from their providers compared with 18% of initiators. HRT initiation was associated with belief in prevention benefits of HRT for fractures and cardiovascular disease and with reported encouragement from the physician to use HRT. CONCLUSIONS: Other than hysterectomy status, there were few sociodemographic or health characteristics that markedly distinguished older initiators from noninitiators. Our findings show the importance of physician counseling in an older woman's decision to initiate HRT. C1 UNIV WASHINGTON,SCH PUBL HLTH & COMMUNITY MED,NW PREVENT EFFECTIVENESS CTR,SEATTLE,WA 98195. UNIV WASHINGTON,CTR HLTH STUDIES,GRP HLTH COOPERAT PUGET SOUND,SEATTLE,WA 98195. FRED HUTCHINSON CANC RES CTR,DIV PUBL HLTH SCI,SEATTLE,WA 98104. CTR DIS CONTROL & PREVENT,ATLANTA,GA. RP Leveille, SG (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,7201 WISCONSIN AVE,SUITE 3C-309,BETHESDA,MD 20892, USA. FU PHS HHS [U48/CCU009654] NR 28 TC 23 Z9 23 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 1997 VL 45 IS 12 BP 1496 EP 1500 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA YK263 UT WOS:A1997YK26300011 PM 9400560 ER PT J AU Havlik, RJ AF Havlik, RJ TI Antihypertensive drugs, brain structure, and cognitive function: More research is necessary SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material ID WHITE MATTER LESIONS; HYPERTENSION RP Havlik, RJ (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,NIH,BETHESDA,MD 20892, USA. NR 20 TC 4 Z9 6 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 1997 VL 45 IS 12 BP 1529 EP 1531 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA YK263 UT WOS:A1997YK26300018 PM 9400567 ER PT J AU Mennitt, PA Wade, JB Ecelbarger, CA Palmer, LG Frindt, G AF Mennitt, PA Wade, JB Ecelbarger, CA Palmer, LG Frindt, G TI Localization of ROMK channels in the rat kidney SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CORTICAL COLLECTING TUBULE; CONDUCTANCE K+ CHANNEL; THICK ASCENDING LIMB; APICAL MEMBRANE; HENLES LOOP; HETEROGENEITY AB Renal potassium secretion occurs in the distal segments of the nephron through apically located secretory potassium (SK) channels. SK may correspond to the ROMK channels cloned from rat kidney. In this study, the localization of ROMK at the cellular level in the rat kidney was examined using an affinity-purified polyclonal antibody raised against a C-terminal peptide of ROMK. The specificity of the antibody was demonstrated by immunoblots of membranes of Xenopus oocytes expressing ROMK2. Immunoblots of homogenates from rat renal outer medulla and cortex revealed predominant bands of 70 to 75 kD, which were ablated by preadsorption with an excess of peptide. These bands were specific for the rat kidney. Immunolocalization studies revealed that ROMK is expressed in specific nephron segments in both the cortex and medulla. In the cortex, ROMK was found in the apical domain of the thick ascending limb of Henle's loop, the connecting tubule, and in some, but not all, cells of cortical collecting tubules. In the medulla, expression in the apical membrane of the thick ascending limbs of Henle's loop was strong, whereas outer medullary collecting ducts were weakly stained. Expression in the thick ascending Limb was also heterogeneous; some cells that expressed the Na-K-CI cotransporter were weakly stained with the anti-ROMK antibody. No staining of glomeruli, proximal tubules, or inner medullary collecting ducts was found. The localization of ROMK agrees well with the findings of SK in patch-clamp studies and supports the view that ROMK is the SK channel of the distal segments of the nephron. C1 CORNELL UNIV,COLL MED,DEPT PHYSIOL & BIOPHYS,NEW YORK,NY. UNIV MARYLAND,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21201. NHLBI,KIDNEY & ELECTROLYTE METAB LAB,NIH,BETHESDA,MD 20892. FU NIDDK NIH HHS [DK 32839, DK45829, DK27847] NR 22 TC 71 Z9 71 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 1997 VL 8 IS 12 BP 1823 EP 1830 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA YH761 UT WOS:A1997YH76100002 PM 9402083 ER PT J AU Albert, PS Hunsberger, SA Biro, FM AF Albert, PS Hunsberger, SA Biro, FM TI Modeling repeated measures with monotonic ordinal responses and misclassification, with applications to studying maturation SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE diagnostic error; EM algorithm; longitudinal data; Markov chains; Markov mixture models ID MEASUREMENT ERROR; MARKOV-CHAINS; DISEASE AB Many longitudinal studies of children are concerned with the modelling of monotonic responses such as growth and sexual maturation. The National Heart, Lung, and Blood Institute Growth and Health Study (NGHS) is a longitudinal study designed to examine the effect of growth and maturation on the development of obesity and related cardiovascular risk factors among black and white adolescent girls. Sexual maturation is measured with an ordinal outcome and is known to be measured with sizable diagnostic error. Of interest is examining the effects of race and age on the sexual maturation process. Here we propose a class of models for analyzing repeated monotonic ordinal responses with diagnostic misclassification in which we separately model the underlying monotonic response and misclassification processes. We develop an EM algorithm for maximum likelihood estimation that incorporates covariates and randomly missing data. We use the method to analyze the NGHS sexual maturation data. C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. Univ Cincinnati, Cincinnati, OH 45228 USA. RP Albert, PS (reprint author), NHLBI, Off Biostat Res, Bldg 10, Bethesda, MD 20892 USA. NR 22 TC 21 Z9 21 U1 0 U2 2 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD DEC PY 1997 VL 92 IS 440 BP 1304 EP 1311 DI 10.2307/2965400 PG 8 WC Statistics & Probability SC Mathematics GA YN091 UT WOS:000071132200011 ER PT J AU Soderstrom, CA Smith, GS Kufera, JA Dischinger, PC Hebel, JR McDuff, DR Gorelink, DA Ho, SM Kerns, TJ Read, KM AF Soderstrom, CA Smith, GS Kufera, JA Dischinger, PC Hebel, JR McDuff, DR Gorelink, DA Ho, SM Kerns, TJ Read, KM TI The accuracy of the CAGE, the Brief Michigan Alcoholism Screening Test, and the alcohol use disorders identification test in screening trauma center patients for alcoholism SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 19th Annual Meeting of the Association-for-Medical-Education-and-Research-in-Substance-Abuse CY NOV 10, 1995 CL WASHINGTON, D.C. SP Assoc Med Educ & Res Substance Abuse ID UNITED-STATES; COLLABORATIVE PROJECT; DSM-IV; DEPENDENCE; EMERGENCY; INJURIES; ABUSE; CARE; INTERVENTIONS; QUESTIONNAIRE AB Objective: To evaluate the accuracy of questionnaire screening instruments to identify lifetime alcohol dependence among trauma center patients, Methods: The study was conducted at a Level I trauma center between September 1994 and November 1996, Patients meeting eligibility requirements (greater than or equal to 18 years old, admission from injury scene, greater than or equal to 2 days of hospitalization, intact cognition) were evaluated for alcohol abuse and dependence. Screening instruments consisted of the CAGE, the Brief Michigan Alcoholism Screening Test, and the Alcohol Use Disorders Identification Test, Screening results were compared with lifetime alcohol dependence diagnoses made using the in-depth Psychoactive Substance Use Disorders section of the Structured Clinical Interview. Accuracy was quantified as sensitivity, specificity, positive/negative predictive values, and receiver operating characteristic curves (used to calculate area under the curve), Results: Of the 1,118 patients studied, lifetime alcohol dependence was diagnosed by Structured Clinical Interview in 397 (35.5%), and abuse was diagnosed in 90 (8.1%) others, The CAGE,vas the best predictor of lifetime alcohol dependence, i.e., had the largest area under the curve (93%) and the highest sensitivity (84%), specificity (90%), positive predictive value (82%), and negative predictive value (91%), Among patients testing positive for alcohol, 63% had a lifetime alcohol dependence diagnosis, Conclusion: The CAGE is an efficient screening test to detect alcohol dependence in trauma center populations, It should be used in combination with alcohol testing to identify patients at risk of alcohol use problems. C1 Univ Maryland, Med Syst, R Adams Cowley Shock Trauma Ctr, Baltimore, MD 21201 USA. Natl Study Ctr Trauma & Emergency Med Syst, Baltimore, MD USA. Univ Maryland, Sch Med, Dept Epidemiol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. NIDA, Div Intramural Res, Baltimore, MD USA. RP Soderstrom, CA (reprint author), Univ Maryland, Med Syst, R Adams Cowley Shock Trauma Ctr, 22 S Greene St, Baltimore, MD 21201 USA. OI Smith, Gordon/0000-0002-2911-3071 FU NIAAA NIH HHS [R01 AA09050] NR 54 TC 62 Z9 64 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD DEC PY 1997 VL 43 IS 6 BP 962 EP 969 DI 10.1097/00005373-199712000-00017 PG 8 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA YN398 UT WOS:000071164700021 PM 9420113 ER PT J AU Wingfield, PT Stahl, SJ Thomsen, DR Homa, FL Booy, FP Trus, BL Steven, AC AF Wingfield, PT Stahl, SJ Thomsen, DR Homa, FL Booy, FP Trus, BL Steven, AC TI Hexon-only binding of VP26 reflects differences between the hexon and penton conformations of VP5, the major capsid protein of herpes simplex virus SO JOURNAL OF VIROLOGY LA English DT Article ID RECOMBINANT BACULOVIRUSES; SECONDARY STRUCTURE; SIMIAN VIRUS-40; TYPE-1; LOCALIZATION; CELLS; RECONSTRUCTION; VISUALIZATION; MICROGRAPHS; MICROSCOPY AB VP26 is a 12-kDa capsid protein of herpes simplex virus 1. Although VP26 is dispensable for assembly, the native capsid (a T=16 icosahedron) contains 900 copies: six on each of the 150 herons of VP5 (149 kDa) but none on the 12 VP5 pentons at its vertices. We have investigated this interaction by expressing VP26 in Escherichia coli and studying the properties of the purified protein in solution and its binding to capsids. Circular dichroism spectroscopy reveals that the conformation of purified VP26 consists mainly of beta-sheets (similar to 80%), with a small alpha-helical component (similar to 15%). Its state of association was determined by analytical ultracentrifugation to be a reversible monomer-dimer equilibrium, with a dissociation constant of similar to 2 x 10(-5) M. Bacterially expressed VP26 binds to capsids in the normal amount, as determined by quantitative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Cryoelectron microscopy shows that the protein occupies its usual sites on herons but does not bind to pentons, even when available in 100-fold molar excess. Quasi-equivalence requires that penton VP5 must differ in conformation from hexon VP5: our data show that in mature capsids, this difference is sufficiently pronounced to abrogate its ability to bind VP26. C1 NIAMSD,STRUCT BIOL LAB,NIH,BETHESDA,MD 20892. NIAMSD,PROT EXPRESS LAB,NIH,BETHESDA,MD 20892. NIAMSD,COMPUTAT BIOSCI & ENGN LAB,DIV COMP RES & TECHNOL,NIH,BETHESDA,MD 20892. PHARMACIA & UPJOHN INC,KALAMAZOO,MI 49007. NR 43 TC 46 Z9 48 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1997 VL 71 IS 12 BP 8955 EP 8961 PG 7 WC Virology SC Virology GA YF896 UT WOS:A1997YF89600001 PM 9371551 ER PT J AU Bukreyev, A Whitehead, SS Murphy, BR Collins, PL AF Bukreyev, A Whitehead, SS Murphy, BR Collins, PL TI Recombinant respiratory syncytial virus from which the entire SH gene has been deleted grows efficiently in cell culture and exhibits site-specific attenuation in the respiratory tract of the mouse SO JOURNAL OF VIROLOGY LA English DT Article ID SMALL HYDROPHOBIC PROTEIN; TRANSCRIPTION ELONGATION-FACTOR; EXTENSIVE SEQUENCE DIVERGENCE; MESSENGER-RNA; NUCLEOTIDE-SEQUENCE; INTERGENIC REGIONS; MEMBRANE-PROTEIN; SUBGROUP-A; IDENTIFICATION; GLYCOPROTEIN AB The small hydrophobic protein SH of human respiratory syncytial virus (RSV) is a short transmembrane surface protein of unknown function. A full length cDNA of RSV strain A2 (subgroup A) antigenomic RNA was modified such that the entire SH gene, including the transcription signals and the complete mRNA-encoding sequence, was deleted and replaced by a synthetic intergenic region. This reduced the length of the antigenome by 398 nucleotides and ablated expression of 1 of the 10 RSV mRNAs. Recombinant virus containing this engineered deletion was recovered, and the absence of the SH gene was confirmed by reverse transcription in conjunction with PCR Northern blot analysis of intracellular RNAs and gel electrophoresis of labeled intracellular proteins confirmed the lack of expression of the SH mRNA and protein. The absence of the SH gene did not noticeably affect RNA replication, but two effects on transcription were noted. First, synthesis of the G, F, and M2 mRNAs was increased, presumably due to their being one position closer to the promoter in the gene order. Second, transcription of genes downstream of the engineered site exhibited a steeper gradient of polarity, On monolayers of HEp-2 cells, the SK-minus virus produced syncytia which were at least equivalent in size to those of the wild type and produced plaques which were 70% larger. Furthermore, the SH-minus virus grew somewhat better (up to 12.6-fold) than wild-type recombinant RSV in certain cell lines. While the function of the SH protein remains to be determined, it seems to be completely dispensable for growth in tissue culture and fusion function, When inoculated intranasally into mice, the SII-minus virus resembled the wild-type recombinant virus in its efficiency of replication in the lungs, whereas it replicated 10-fold less efficiently in the upper respiratory tract. In mice, the SH-minus and wild-type recombinant viruses were similarly immunogenic and effective in inducing resistance to virus challenge. C1 NIAID,INFECT DIS LAB,NIH,BETHESDA,MD 20892. NR 41 TC 159 Z9 166 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1997 VL 71 IS 12 BP 8973 EP 8982 PG 10 WC Virology SC Virology GA YF896 UT WOS:A1997YF89600003 PM 9371553 ER PT J AU Zheng, ZM He, PJ Baker, CC AF Zheng, ZM He, PJ Baker, CC TI Structural, functional, and protein binding analyses of bovine papillomavirus type 1 exonic splicing enhancers SO JOURNAL OF VIROLOGY LA English DT Article ID PRE-MESSENGER-RNA; SPLICEOSOME ASSEMBLY PATHWAY; T ALTERNATIVE EXON; SR-PROTEINS; PREMESSENGER RNA; CONSERVED FAMILY; SITE SELECTION; POLYMERASE-II; BRANCH POINT; SERINE-RICH AB Alternative splicing plays an important role in regulation of bovine papillomavirus type 1 (BPV-1) gene expression, We have recently identified in BPV-1 late pre-mRNAs two purine-rich exonic splicing enhancers (SE1 and SE2) which also stimulate splicing of a Drosophila doublesex (dsx) pre-mRNA containing a suboptimal 3' splice site. In vivo studies now demonstrate that both SE1 and SE2 are required for preferential use of the BPV-1 nucleotide (nt) 3225 3' splice site in nonpermissive cells, Deletion or mutation of either element in a BPV-1 late pre-mRNA switches splicing to the late-specific alternative 3' splice site at nt 3605. To investigate the sequence specificity of these exonic splicing enhancers, various mutant SE1 or SE2 elements were connected to dsx pre-mRNAs and tested for their stimulatory effects on dsx pre-mRNA splicing in vitro, Substitution of U residues for either A or G residues in and around potential ASF/SF2 binding sites in SE1 or SE2 resulted in a significant reduction of splicing enhancer activity, However, the G-to U substitutions in both enhancers had the largest effect, reducing splicing to near control levels, Further in vitro analyses showed that splicing enhancement by SE2 could be competed with excess unlabeled SE2 RNA, indicating that SE2 activity in HeLa nuclear extracts is mediated by trans-acting factors. UV cross-linking plus immunoprecipitation assays showed that both wild-type SE1 and SE2 RNAs could bind directly to purified HeLa SR proteins SRp30a (ASF/SF2), SRp55, and SRp75, UV cross-linking experiments also identified a 23-kDa protein which binds to SE2 but not SE1. This protein is present in both HeLa nuclear extracts and S100 extracts but absent from SR protein preparations, suggesting that it is not a classical SR protein. Mutant SE elements (containing G-to U-mutations) which had minimal splicing enhancer activity also had very weak binding capacity for these proteins, strongly suggesting that the binding of these proteins is required for splicing enhancer function. RP Zheng, ZM (reprint author), NCI,BASIC RES LAB,DIV BASIC SCI,NIH,BLDG 41,ROOM C111,41 LIB DR,MSC 5055,BETHESDA,MD 20892, USA. NR 58 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1997 VL 71 IS 12 BP 9096 EP 9107 PG 12 WC Virology SC Virology GA YF896 UT WOS:A1997YF89600016 PM 9371566 ER PT J AU Mendez, E Kawanishi, T Clemens, K Siomi, H Soldan, SS Calabresi, P Brady, J Jacobson, S AF Mendez, E Kawanishi, T Clemens, K Siomi, H Soldan, SS Calabresi, P Brady, J Jacobson, S TI Astrocyte-specific expression of human T-cell lymphotropic virus type 1 (HTLV-1) tax: Induction of tumor necrosis factor alpha and susceptibility to lysis by CD8(+) HTLV-1-specific cytotoxic T cells SO JOURNAL OF VIROLOGY LA English DT Article ID I-ASSOCIATED MYELOPATHY; TROPICAL SPASTIC PARAPARESIS; ACQUIRED IMMUNODEFICIENCY SYNDROME; CEREBROSPINAL-FLUID; LEUKEMIA-VIRUS; NEUROLOGICAL DISEASE; ELEVATED LEVELS; LYMPHOCYTES-T; PROVIRAL DNA; SPINAL-CORD AB Human T-cell lymphotropic virus type 1 (HTLV-1) is associated with a chronic neurological disease termed HTLV-1-associated myelopathy/tropical spastic paraperesis (HAM/TSP). Although the pathogenesis of this disease remains to be elucidated, the evidence suggests that immunopathological mechanisms are involved. Since HTLV-1 tax mRNA was colocalized with glial acidic flibrillary protein, a marker for astrocytes, we developed an in vitro model to assess whether HTLV-1 infection activates astrocytes to secrete cytokines or present viral immunodominant epitopes to virus-specific T cells. Two human astrocytic glioma cell lines, U251 and U373, were transfected with the 3' portion of the HTLV-1 genome and with the HTLV-1 fax gene under astrocyte-specific promoter control. In this study, we report that Tax-expressing astrocytic glioma transfectants activate the expression of tumor necrosis factor alpha mRNA in vitro. Furthermore, these Tax-expressing glioma transfectants can serve as immunological targets for HTLV-1-specific cytotoxic T lymphocytes (CTL). We propose that these events could contribute to the neuropathology of HAM/TSP, since infected astrocytes can become a source for inflammatory cytokines upon HTLV-1 infection and serve as targets for HTLV-1-specific CTL, resulting in parenchymal damage by direct lysis and/or cytokine release. C1 NINCDS,VIRAL IMMUNOL SECT,NEUROIMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NCI,NIH,BETHESDA,MD 20892. UNIV PENN,SCH MED,HOWARD HUGHES MED INST,RES LABS,PHILADELPHIA,PA 19104. RI Siomi, Haruhiko/A-7020-2015 OI Siomi, Haruhiko/0000-0001-8690-3822 NR 54 TC 23 Z9 23 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1997 VL 71 IS 12 BP 9143 EP 9149 PG 7 WC Virology SC Virology GA YF896 UT WOS:A1997YF89600021 PM 9371571 ER PT J AU Yang, CC Xiao, X Zhu, X Ansardi, DC Epstein, ND Frey, MR Matera, AG Samulski, RJ AF Yang, CC Xiao, X Zhu, X Ansardi, DC Epstein, ND Frey, MR Matera, AG Samulski, RJ TI Cellular recombination pathways and viral terminal repeat hairpin structures are sufficient for adeno-associated virus integration in vivo and in vitro SO JOURNAL OF VIROLOGY LA English DT Article ID SITE-SPECIFIC INTEGRATION; ADENOASSOCIATED VIRUS; GENE-TRANSFER; HUMAN-CELLS; DETROIT-6 CELLS; DNA FRAGMENTS; AAV; TYPE-2; SEQUENCE; INVITRO AB The human parvovirus adeno-associated virus (AAV) is unique in its ability to target viral integration to a specific site on chromosome 19 (ch-19). Recombinant AAV (rAAV) vectors retain the ability to integrate but have apparently lost this ability to target. In this report, we characterize the terminal-repeat-mediated integration for wild-type (wt), rAAV, and in vitro systems to gain a better understanding of these differences. Cell lines latent for either wt or rAAV were characterized by a variety of techniques, including PCR, Southern hybridization, and fluorescence in situ hybridization analysis. More than 40 AAV-rAAV integration junctions were cloned, sequenced, and then subjected to comparison and analysis. In both immortalized and normal diploid human cells, wt AAV targeted integration to ch-19. Integrated provirus structures consisted of head-to-tail tandem arrays with the majority of the junction sequences involving the AAV inverted terminal repeats (ITRs). No complete viral ITRs were directly observed. In some examples, the AAV p5 promoter sequence was found to be fused at the virus-cell junction. Data from dot blot analysis of PCR products were consistent with the occurrence of inversions of genomic and/or viral DNA sequences at the wt integration site. Unlike wt provirus junctions, rAAV provirus junctions mapped to a subset of non-ch-19 sequences. Southern analysis supported the integration of proviruses from two independent cell lines at the same locus on ch-2. In addition, provirus terminal repeat sequences existed in both the flip and hop orientations, with microhomology evident at the junctions. In all cases with the exception of the ITRs, the vector integrated intact. rAAV junction sequence data were consistent with the occurrence of genomic rearrangement by deletion and/or rearrangement-translocation at the integration locus. Finally, junctions formed in an in vitro system between several AAV substrates and the ch-19 target site were isolated and characterized. Linear AAV substrates typically utilized the end of the virus DNA substrate as the point of integration, whereas products derived from AAV terminal repeat hairpin structures in the presence or absence of Rep protein resembled AAV-ch-19 junctions generated in vivo. These results describing wt AAV, rAAV, and in vitro integration junctions suggest that the viral integration event itself is mediated by terminal repeat hairpin structures via nonviral cellular recombination pathways, with specificity for ch-19 in vivo requiring additional viral components. These studies should have an important impact on the use of rAAV vectors in human gene therapy. C1 UNIV N CAROLINA,GENE THERAPY CTR,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT PHARMACOL,CHAPEL HILL,NC 27599. NHLBI,NIH,BETHESDA,MD 20829. CASE WESTERN RESERVE UNIV,DEPT GENET,CLEVELAND,OH 44106. FU NHLBI NIH HHS [HL51818]; NIDDK NIH HHS [DK51880] NR 49 TC 123 Z9 125 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1997 VL 71 IS 12 BP 9231 EP 9247 PG 17 WC Virology SC Virology GA YF896 UT WOS:A1997YF89600032 PM 9371582 ER PT J AU Lifson, JD Nowak, MA Goldstein, S Rossio, JL Kinter, A Vasquez, G Wiltrout, TA Brown, C Schneider, D Wahl, L Lloyd, AL Williams, J Elkins, WR Fauci, AS Hirsch, VM AF Lifson, JD Nowak, MA Goldstein, S Rossio, JL Kinter, A Vasquez, G Wiltrout, TA Brown, C Schneider, D Wahl, L Lloyd, AL Williams, J Elkins, WR Fauci, AS Hirsch, VM TI The extent of early viral replication is a critical determinant of the natural history of simian immunodeficiency virus infection SO JOURNAL OF VIROLOGY LA English DT Article ID PRIMARY HIV-1 INFECTION; CD8(+) T-CELLS; IMMUNE-RESPONSES; RHESUS-MONKEYS; POPULATION-DYNAMICS; TYPE-1 INFECTION; LYMPHOID-TISSUE; CD4 LYMPHOCYTES; IN-VIVO; PLASMA AB Different patterns of viral replication correlate with the natural history of disease progression in humans and macaques infected with human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV), respectively. However, the viral and host factors influencing these patterns of viral replication in vivo are poorly understood. We intensively studied viral replication in macaques receiving identical inocula of SIV. Marked differences in viral replication patterns were apparent within the first week following inoculation, a time prior to the development of measurable specific immune effector responses to viral antigens. Plasma viral RNA levels measured on day 7 postinoculation correlated with levels measured in the postacute phase of infection. Differences in the susceptibility of host cells from different animals to in vitro SIV infection correlated with the permissiveness of the animals for early in vivo viral replication and hence with the postacute set point level of plasma viremia. These results suggest that host factors that exert their effects prior to full development of specific immune responses are critical in establishing the in vivo viral replication pattern and associated clinical course in subjects infected with SIV and, by extension, with HIV-1. C1 UNIV OXFORD,DEPT ZOOL,OXFORD OX1 3PS,ENGLAND. NIAID,INFECT DIS LAB,ROCKVILLE,MD 20852. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20852. MAGAININ PHARMACEUT INC,PLYMOUTH MEETING,PA 19462. RP Lifson, JD (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,AIDS VACCINE PROGRAM,FREDERICK,MD 21702, USA. RI Nowak, Martin/A-6977-2008; Lloyd, Alun/H-4944-2012 FU Wellcome Trust NR 68 TC 207 Z9 208 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1997 VL 71 IS 12 BP 9508 EP 9514 PG 7 WC Virology SC Virology GA YF896 UT WOS:A1997YF89600063 PM 9371613 ER PT J AU Patton, JT Jones, MT Kalbach, AN He, YW Xiaobo, J AF Patton, JT Jones, MT Kalbach, AN He, YW Xiaobo, J TI Rotavirus RNA polymerase requires the core shell protein to synthesize the double-stranded RNA genome SO JOURNAL OF VIROLOGY LA English DT Article ID MESSENGER-RNA; GUANYLYLTRANSFERASE ACTIVITY; 3-DIMENSIONAL STRUCTURE; REPLICASE ACTIVITY; BINDING; IDENTIFICATION; MORPHOGENESIS; PARTICLES; VP3; TRANSCRIPTION AB Rotavirus cores contain the double-stranded RNA (dsRNA) genome, RNA polymerase VP1, and guanylyltransferase VP3 and are enclosed within a lattice formed by the RNA-binding protein VP2. Analysis of baculovirus-expressed core-like particles (CLPs) has shown that VP1 and VP2 assemble into the simplest core-like structures with replicase activity and that VP1, but not VP3, is essential for replicase activity. To further define the role of VP1 and VP2 in the synthesis of dsRNA from viral mRNA, recombinant baculoviruses containing gene 1 (rBVg1) and gene 2 (rBVg2) of SA11 rotavirus were generated and used to express recombinant VP1 (rVP1) and rVP2, respectively, After purification, the proteins were assayed individually and together for the ability to catalyze the synthesis of dsRNA in a cell-free replication system. The results showed that dsRNA was synthesized only in assays containing rVP1 and rVP2, thus establishing that both proteins are essential for replicase activity, Even in assays containing a primer-linked mRNA template, neither rVP1 nor rVP2 alone directed RNA synthesis. Characterization of the cis-acting replication signals in mRNA recognized by the replicase of rVP1 and rVP2 showed that they were the same as those recognized by the replicase of virion-derived cores, thus excluding a role for VP3 in recognition of the mRNA template by the replicase, Analysis of RNA-protein interactions indicated that the mRNA template binds strongly to VP2 in replicase assays but that the majority of the dsRNA product neither is packaged nor stably associates with VP2. The results of replicase assays performed with mutant VP2 containing a deletion in its RNA-binding domain suggests that the essential role for VP2 in replication is linked to the protein's ability to bind the mRNA template for minus-strand synthesis. C1 UNIV MIAMI,SCH MED,DEPT MICROBIOL & IMMUNOL,MIAMI,FL 33101. RP Patton, JT (reprint author), NIAID,INFECT DIS LAB,NIH,7 CTR DR,MSC 0720,ROOM 117,BETHESDA,MD 20892, USA. NR 50 TC 78 Z9 88 U1 2 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1997 VL 71 IS 12 BP 9618 EP 9626 PG 9 WC Virology SC Virology GA YF896 UT WOS:A1997YF89600076 PM 9371626 ER PT J AU Moriuchi, H Moriuchi, M Arthos, J Hoxie, J Fauci, AS AF Moriuchi, H Moriuchi, M Arthos, J Hoxie, J Fauci, AS TI Promonocytic U937 subclones expressing CD4 and CXCR4 are resistant to infection with and cell-to-cell fusion by T-cell-tropic human immunodeficiency virus type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 ENTRY; MONONUCLEAR PHAGOCYTES; FUNCTIONAL EXPRESSION; FACILITATE INFECTION; MOLECULAR-CLONING; RECEPTOR; MIP-1-ALPHA; PROGRESSION; MIP-1-BETA; DISEASE AB Different strains of human immunodeficiency virus type 1 (HIV-1) vary markedly in the ability to infect cells of the monocyte/macrophage (M/M) lineage. M/M are generally resistant to infection with T-cell-tropic (T-tropic) strains of HIV-1. Recently, the chemokine receptors CCR5 and CXCR4 were identified as cofactors for fusion/entry of macrophage- and T-tropic strains of HIV-1, respectively. To investigate the mechanisms of resistance of M/M to T-tropic HIV-1 infection, we examined a number of subclones of the U937 promonocytic cell line. We found that certain subclones of U937 (plus clones) could, while others (minus clones) could not, support replication of T-tropic strains of HIV-1. We demonstrate that (i) both minus and plus clones support HIV-1 replication when transfected with an infectious molecular cDNA clone of a T-tropic HIV-1; (ii) minus clones do not, but plus clones do, efficiently support fusion with cells expressing HIV-1 IIIB Env; (iii) both plus and minus clones (with the exception of one clone) express physiologically functional CXCR4 protein as well as CD4 on the cell surface; (iv) introduction of CXCR4 into the CXCR4-negative clone does not restore fusogenicity with or susceptibility to T-tropic HIV-1; and (v) a ligand (stromal cell-derived factor 1) for or a monoclonal antibody (12G5) to CXCR4 does not effectively inhibit HIV-mediated cell-to-cell fusion of U937 cells. These data indicate that resistance to T-tropic HIV-1 infection of U937 minus clones occurs at fusion/entry events and that expression of functional CXCR4 and CD4 is not a sole determinant for susceptibility to T-tropic HIV-1 infection; furthermore, they suggest that other factors are positively or negatively involved in HIV-mediated cell-to-cell fusion in U937 promonocytic cells. C1 UNIV PENN,DIV HEMATOL ONCOL,PHILADELPHIA,PA 19104. RP Moriuchi, H (reprint author), NIAID,IMMUNOREGULAT LAB,NIH,BLDG 10,ROOM 6A11,10 CTR DR,MSC-1576,BETHESDA,MD 20892, USA. NR 46 TC 41 Z9 41 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1997 VL 71 IS 12 BP 9664 EP 9671 PG 8 WC Virology SC Virology GA YF896 UT WOS:A1997YF89600081 PM 9371631 ER PT J AU Smith, SM Maldarelli, F Jeang, KT AF Smith, SM Maldarelli, F Jeang, KT TI Efficient expression by an alphavirus replicon of a functional ribozyme targeted to human immunodeficiency virus type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID ANTI-RAS RIBOZYME; GENE-EXPRESSION; HAMMERHEAD RIBOZYME; THERAPEUTIC AGENTS; RNA; VECTORS; ANTISENSE; SUPPRESSION; REPLICATION; SEQUENCES AB Intracellular applications of ribozymes have been limited partly by the availability of suitable high-expression systems. For RNA effecters, consideration of an RNA virus vector system for delivery and expression is reasonable. We show that alphavirus replicons can be highly efficient nonintegrating ribozyme-expressing vectors. Using a hammerhead ribozyme targeted to a highly conserved sequence in the U5 region of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat, we demonstrate that a full-length 8.3-kb Semliki Forest virus ribozyme (SFVRz) chimeric RNA maintains catalytic activity. SFVRz is packaged into viral particles, and these particles transduce mammalian cells efficiently. SFVRz-transduced BHK cells were found to produce large amounts of genomic and subgenomic forms of ribozyme-containing RNAs that are functional in cleaving a U5-tagged mRNA. The RNase protection assay shows that HIV-1 U5-chloramphenicol acetyltransferase mRNA expressed intracellularly from an RNA polymerase II promoter is quantitatively eliminated in SFVRz-transduced BHK cells. C1 NIAID,MOL MICROBIOL LAB,BETHESDA,MD 20892. RI Jeang, Kuan-Teh/A-2424-2008 NR 27 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1997 VL 71 IS 12 BP 9713 EP 9721 PG 9 WC Virology SC Virology GA YF896 UT WOS:A1997YF89600087 PM 9371637 ER PT J AU Kolesnitchenko, V King, L Riva, A Tani, Y Korsmeyer, SJ Cohen, DI AF Kolesnitchenko, V King, L Riva, A Tani, Y Korsmeyer, SJ Cohen, DI TI A major human immunodeficiency virus type 1-initiated killing pathway distinct from apoptosis SO JOURNAL OF VIROLOGY LA English DT Article ID PROGRAMMED CELL-DEATH; TUMOR-NECROSIS-FACTOR; FAS-MEDIATED APOPTOSIS; HIV-1 TAT PROTEIN; T-CELLS; ENVELOPE GLYCOPROTEINS; INFECTED INDIVIDUALS; MONOCLONAL-ANTIBODY; VPR ARRESTS; ACTIVATION AB We have investigated the relative contribution of apoptosis or programmed cell death (PCD) to cell killing during acute infection with T-cell-tropic, cytopathic human immunodeficiency virus type 1 (HIV-1), by employing diverse strategies to inhibit PCD or to detect its common end-stage sequelae. When Bcl-2-transfected cell lines were infected with HIV-1, their viability was only slightly higher than that of control infections. Although the adenovirus E1B 19-kDa protein has been reported to be a stronger competitor of apoptosis than Bcl-2, it did not inhibit HIV-mediated cell death better than Bcl-2 protein. Competition for Fas ligand or inactivation of the Fas pathway secondary to intracellular mutation (MOLT-4 T cells) also had modest effects an overall cell death during acute HIV infection. In contrast to these observations with HIV infection or with HIV envelope-initiated cell death, Tat-expressing cell lines were much more susceptible (200% enhancement) to Fas-induced apoptosis than controls and Bcl-2 overexpression strongly (75%) inhibited this apoptotic T-cell death. PCD associated with FasR ligation resulted in the cleavage of common interleukin-1 beta-converting enzyme (ICE)-protease targets, poly(ADP-ribose) polymerase (PARP) and pro-ICE, whereas cleaved products were not readily detected during HIV infection of peripheral blood mononuclear cells or T-cell lines even during periods of extensive cell death. These results indicate that one important form of HIV-mediated cell killing proceeds by a pathway that lacks the characteristics of T-cell apoptosis. Our observations support the conclusion that at least two HIV genes (env and tat) can kill T cells by distinct pathways and that an envelope-initiated process of T-cell death can be discriminated from apoptosis by many of the properties most closely associated with apoptotic cell death. C1 NCI,BASIC RES LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NCI,LAB IMMUNE CELL BIOL,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. WASHINGTON UNIV,SCH MED,HOWARD HUGHES MED INST,ST LOUIS,MO 63110. NR 84 TC 42 Z9 42 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1997 VL 71 IS 12 BP 9753 EP 9763 PG 11 WC Virology SC Virology GA YF896 UT WOS:A1997YF89600091 PM 9371641 ER PT J AU Jun, HS Kang, Y Notkins, AL Yoon, JW AF Jun, HS Kang, Y Notkins, AL Yoon, JW TI Gain or loss of diabetogenicity resulting from a single point mutation in recombinant encephalomyocarditis virus SO JOURNAL OF VIROLOGY LA English DT Article ID INDUCED DIABETES-MELLITUS; NONDIABETOGENIC VARIANTS; CAPSID PROTEIN; AMINO-ACID; CELLS; MICE; RNA; VP1 AB Molecular pathogenic mechanisms for virus-induced disease have received considerable attention. Encephalomyocarditis (EMC) virus-induced diabetes in mice has been extensively studied to elucidate the cellular and molecular mechanisms involved in the development of this disease. In this study, we report for the first time that a single point mutation at nucleotide position 3155 or 3156 of the recombinant EMC viral genome, located on the major capsid protein VP1, which causes an amino acid change, results in the gain or loss of viral diabetogenicity. A G base at nucleotide position 3155 (alanine at amino acid position 776 of the EMC virus polyprotein [Ala(776)]; <(G)under bar CC>) results in viral diabetogenicity, whereas the substitution of other bases at the same or next position results in a loss of viral diabetogenicity. This finding provides clear evidence that a point mutation at a critical site in a viral genome affects the ability of the virus to cause a cell-specific disease. C1 UNIV CALGARY,FAC MED,DEPT MICROBIOL & INFECT DIS,JULIA MCFARLANE DIABET RES CTR,CALGARY,AB T2N 4N1,CANADA. AJOU UNIV,SCH MED,DEPT ENDOCRINOL & METAB,INST MED SCI,LAB ENDOCRINOL,SUWON 441749,SOUTH KOREA. NIDR,ORAL INFECT & IMMUN BRANCH,NIH,BETHESDA,MD 20892. NR 25 TC 26 Z9 29 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1997 VL 71 IS 12 BP 9782 EP 9785 PG 4 WC Virology SC Virology GA YF896 UT WOS:A1997YF89600095 PM 9371645 ER PT J AU Valentin, A Aldrovandi, G Zolotukhin, AS Cole, SW Zack, JA Pavlakis, GN Felber, BK AF Valentin, A Aldrovandi, G Zolotukhin, AS Cole, SW Zack, JA Pavlakis, GN Felber, BK TI Reduced viral load and lack of CD4 depletion in SCID-hu mice infected with Rev-independent clones of human immunodeficiency virus type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID SIMIAN RETROVIRUS TYPE-1; PERIPHERAL-BLOOD; HIV-1 INFECTION; REPLICATION; ELEMENT; EXPRESSION; PATHOGENICITY; THYMUS; CELLS; MOUSE AB The posttranscriptional control element CTE of the simian type D retrovirus has been shown to support replication of Rev-Rev-responsive-element (RRE)-deficient molecular clones of human immunodeficiency virus type 1 (HIV-1). Upon infection of peripheral blood mononuclear cells in vitro, these CTE-containing Rev-independent viruses that are nef(+) or nef-minus showed lower replicative capacity and infectivity than the wild-type HIV-1. We studied the effects of Rev-RRE replacement by the CTE on HIV-1 expression with SCID-hu mice. The nef(+) and nef-minus Rev-independent viruses established infection with kinetics slower than that of the nef-minus NL4-3. Most importantly, no depletion of CD4-bearing thymocytes was observed after 6 weeks for mice infected with these Rev-independent viruses. This is in contrast to the infection with both wild-type and nef-minus viruses, which led to varying depletion of thymocytes. These data suggest an attenuated phenotype for growth and cytotoxicity of the Rev-independent HIV-1 clones in SCID-hu mice, independent of the presence of Nef. The mutant viruses, which have the essential Rev-RRE regulatory system eliminated, display a distinct phenotype not previously observed with HIV mutant viruses having deletions of accessory genes. Therefore, replacement of the Rev-RRE regulatory axis may generate viruses with altered biological properties in vivo. C1 NCI,HUMAN RETROVIRUS PATHOGENESIS GRP,ABL BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NCI,HUMAN RETROVIRUS SECT,ABL BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,DIV HEMATOL ONCOL,LOS ANGELES,CA 90024. JONSSON COMPREHENS CANC CTR,LOS ANGELES,CA 90024. FU NIAID NIH HHS [AI36059] NR 26 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1997 VL 71 IS 12 BP 9817 EP 9822 PG 6 WC Virology SC Virology GA YF896 UT WOS:A1997YF89600103 PM 9371653 ER PT J AU Agodoa, L Eknoyan, G Ingelfinger, J Keane, W Mauer, M Mitch, W Striker, G Wilcox, C AF Agodoa, L Eknoyan, G Ingelfinger, J Keane, W Mauer, M Mitch, W Striker, G Wilcox, C TI Assessment of structure and function in progressive renal disease SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT Symposium on Progression of Renal Disease - Clinical Patterns, Therapeutic Options and What We Have Learned from Clinical Trials CY MAY 31-JUN 03, 1997 CL COOLUM, AUSTRALIA SP Takeda Chem Ind Ltd, Tokyo, Novartis Pharma AG, Basel, PMSI Japan Ltd, ICMS Australasia PTY Ltd DE progression of renal disease; end-stage renal disease; measurement of renal function; imaging ID GLOMERULAR-FILTRATION RATE; INJURY AB The incidence and prevalence rates of end-stage renal disease (ESRD) in the United States continue to increase. In 1995, the incidence rate was 262 per million population, with a point prevalence rate of 975 per million population. The exact number of individuals with abnormal renal function but not yet at end stage is difficult to assess. Crude estimates suggest that approximately 0.4% of the U.S. population has serum creatinine values greater than 2.0 mg/dl. In some sub-populations, such as African Americans, the estimate is+ as high as 1.0%. The rate of progression, likewise, is difficult to assess. In general. renal manifestations of certain systemic diseases such as diabetes mellitus and systemic lupus erythematosus, and those with significant proteinuria (usually greater that 3.0 g/24 hr) seem to have a more rapid progressive course to end stage. If intervention is expected to be successful in halting or slowing down progression, accurate assessment of the early manifestations of renal disease, structure, and function need to be established. Currently accepted methods of assessment of renal disease include measurement of renal function such as serum creatinine and glomerular filtration rate, measurement of proteinuria, assessment of tubular function, glomerular sieving and permselectivity, radiologic imaging techniques, and evaluation of histo-morphometry. Interventions that have been shown to slow progression include control of hypertension, and treatment modalities that reduce proteinuria, such as, the use of angiotensin converting enzyme inhibitors. Further clinical and basic science studies are needed to accurately define the important predictors of progression, and interventions that are effective in slowing or halting progression. C1 BAYLOR COLL MED, DEPT MED, HOUSTON, TX 77030 USA. MASSACHUSETTS GEN HOSP, DEPT PEDIAT NEPHROL, BOSTON, MA 02114 USA. HENNEPIN CTY MED CTR, DEPT MED, MINNEAPOLIS, MN 55415 USA. UNIV MINNESOTA, SCH MED, DEPT PEDIAT, MINNEAPOLIS, MN 55455 USA. EMORY UNIV, SCH MED, DIV RENAL, ATLANTA, GA 30322 USA. GEORGETOWN UNIV, MED CTR, DIV NEPHROL, WASHINGTON, DC 20007 USA. RP Agodoa, L (reprint author), NIDDK, END STAGE RENAL DIS PROGRAM, DIV KIDNEY UROL & HEMATOL DIS,NIH,BLDG 45, ROOM 6AS13B, BETHESDA, MD 20392 USA. NR 29 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD DEC PY 1997 SU 63 BP S144 EP S150 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA YJ605 UT WOS:A1997YJ60500036 ER PT J AU Nelson, RG Meyer, TW Myers, BD Bennett, PH AF Nelson, RG Meyer, TW Myers, BD Bennett, PH TI Course of renal disease in Pima Indians with non-insulin-dependent diabetes mellitus SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT Symposium on Progression of Renal Disease - Clinical Patterns, Therapeutic Options and What We Have Learned from Clinical Trials CY MAY 31-JUN 03, 1997 CL COOLUM, AUSTRALIA SP Takeda Chem Ind Ltd, Tokyo, Novartis Pharma AG, Basel, PMSI Japan Ltd, ICMS Australasia PTY Ltd ID GLOMERULAR-FILTRATION RATE; OVERT NEPHROPATHY; ALBUMIN EXCRETION; PROGRESSION; PROTEINURIA; PREVALENCE; RISK AB The course of renal disease attributable to non-insulin-dependent diabetes mellitus (NIDDM) has been characterized extensively in the Pima Indians of Arizona. Studies in this population indicate that the glomerular filtration rate often increases at the onset of NIDDM and remains elevated as long as normal urinary albumin excretion (< 30 mg albumin/g creatinine) or microalbuminuria (30-299 mg albumin/g creatinine) persist. After the development of macroalbuminuria (greater than or equal to 300 mg albumin/g creatinine), the glomerular filtration rate declines at least as rapidly as reported in subjects with insulin-dependent diabetes. Morphologic examination of kidney tissue reveals extensive glomerular sclerosis, mesangial expansion, and widening of epithelial cell fool processes and the glomerular basement membrane in the subjects with macroalbuminuria, but not in those with normo-or microalbuminuria. These findings suggest that substantial structural damage to the kidney occurs al or about the time that macroalbuminuria develops, and the decline in glomerular function in those with macroalbuminuria is due to a loss of ultrafiltration surface area and a reduction in glomerular hydraulic permeability. C1 VA PALO ALTO HEALTHCARE SYST,DEPT MED,STANFORD,CA. STANFORD UNIV,DIV NEPHROL,SCH MED,STANFORD,CA. RP Nelson, RG (reprint author), NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,NIH,1550 E INDIAN SCH RD,PHOENIX,AZ 85014, USA. RI Nelson, Robert/B-1470-2012 NR 26 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 1997 SU 63 BP S45 EP S48 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA YJ605 UT WOS:A1997YJ60500012 ER PT J AU Striker, GE Lupia, E Elliot, S Zheng, F McQuinn, C Blagg, C Selim, S Vilar, J Striker, LJ AF Striker, GE Lupia, E Elliot, S Zheng, F McQuinn, C Blagg, C Selim, S Vilar, J Striker, LJ TI Glomerulosclerosis, arteriosclerosis, and vascular graft stenosis: Treatment with oral heparinoids SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT Symposium on Progression of Renal Disease - Clinical Patterns, Therapeutic Options and What We Have Learned from Clinical Trials CY MAY 31-JUN 03, 1997 CL COOLUM, AUSTRALIA SP Takeda Chem Ind Ltd, Tokyo, Novartis Pharma AG, Basel, PMSI Japan Ltd, ICMS Australasia PTY Ltd DE pentosan polysulfate; heparinoid therapy; glomerulosclerosis; atherosclerosis ID SMOOTH-MUSCLE CELLS; EXTRACELLULAR-MATRIX; GROWTH-FACTOR; DIABETIC NEPHROPATHY; GENE-EXPRESSION; PROLIFERATION; PROTEOGLYCAN; COLLAGENASE; INHIBITION; MODEL AB At present there is no known treatment for established glomerulosclerosis or atherosclerosis. Since the principal lesion in glomerulosclerosis involves mesangial cells, a vascular smooth muscle cell, we searched for new therapeutic approaches affecting vascular smooth muscle function, especially with respect to modifying the turnover of extracellular matrix. We used mice transgenic for bovine growth hormone (bGH), since these mice develop end-stage renal disease due to progressive glomerulosclerosis. We previously showed that the subcutaneous injection of a non-anticoagulant heparin reduced glomerulosclerosis in bGH mice. Since injectable drugs are not a practical means of controlling glomerulosclerosis in humans, we assessed oral heparin-like compounds and found that oral pentosan polysulfate (PPS) reduced glomerulosclerosis in bGH mice at non-toxic doses. Because the positive therapeutic response in the bGH model could have been principally hormone-mediated, we examined other models of non-immune mediated glomerulosclerosis, including ROP Os/+ non-diabetic and diabetic mice. We found that an oral PPS (Elmiron), which is approved for other indications in humans, reduced sclerosis in all of these forms of chronic, progressive glomerulosclerosis. Based on the similarity of the cellular events in glomerulosclerosis and arteriosclerosis, we assessed the effect(s) of PPS in congenital (Watanabe rabbits) and induced (New Zealand White lipid-fed rabbits) models of arteriosclerosis. The extent and severity of the lesions was significantly reduced in both models by PPS treatment. Finally, we asked whether the proliferative and sclerotic lesion, which is the cause of vascular graft stenosis, might also respond to PPS treatment. To do this we cultured cells from the materials removed from stenotic arteriovenous grafts in hemodialysis patients. We found that PPS inhibits the proliferation and matrix production in a dose-dependent manner. C1 UNIV WASHINGTON,DEPT MED,SEATTLE,WA. UNIV WASHINGTON,DEPT SURG,SEATTLE,WA. IVAX CORP,MIAMI,FL. UNIV PARIS 07,INSERM,U319,PARIS,FRANCE. RP Striker, GE (reprint author), NIDDK,RENAL CELL BIOL SECT,MDB,NIH,BLDG 10,ROOM 3N110,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 22 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 1997 SU 63 BP S120 EP S123 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA YJ605 UT WOS:A1997YJ60500030 ER PT J AU van der Pluijm, G Vloedgraven, H Papapoulos, S Lowik, C Grzesik, W Kerr, J Robey, PG AF van der Pluijm, G Vloedgraven, H Papapoulos, S Lowik, C Grzesik, W Kerr, J Robey, PG TI Attachment characteristics and involvement of integrins in adhesion of breast cancer cell lines to extracellular bone matrix components SO LABORATORY INVESTIGATION LA English DT Article ID FIBRONECTIN RECEPTOR; MONOCLONAL-ANTIBODIES; IN-VITRO; MAMMARY CARCINOMAS; SIALOPROTEIN; EXPRESSION; METASTASIS; MOLECULES; TUMORS; GLYCOPROTEINS AB Evidence is mounting that changes in the ability of cancer cells to adhere to extracellular matrices play a decisive role in metastatic spread. The mechanism underlying the preference of breast cancer cells to metastasize to bone is, however, poorly understood. We investigated the expression and involvement of integrin adhesion receptors in the adhesion of breast cancer cells to bone matrix (constituents) in two in vitro attachment assays using RGD peptides and anti-integrin antibodies. Breast cancer cells adhered rapidly to extracellular bone matrix. Adhesion of most cells to vitronectin, fibronectin, thrombospondin, osteopontin, and the fairly bone-specific bone sialoprotein was inhibited by the 200 mu g/ml GRGDS peptide. These data suggest that integrin adhesion receptors can modulate the attachment of breast cancer cells to bone matrix molecules. In accordance with these findings, we found that alpha(1)-alpha(5)(beta(1)) and alpha(v)(beta(3)) integrins were expressed by mammary carcinoma cells. Highly tumorigenic MDA-MB-231 cells, which form osteolytic metastases in vivo, expressed relatively high levels of alpha(2) beta(1), alpha(3) beta(1), alpha(5) beta(1), alpha(v) beta(3) integrins, when compared to MCF-7, T47D, and ZR75-1 breast cancer cells. Addition of function-blocking anti-alpha(2) beta(1), -alpha(3) beta(1), -alpha(5) beta(1) and -alpha(v) beta(3) antibodies significantly inhibited the adhesion of MDA-MB-231 breast cancer cells to bone matrices. In conclusion, our data suggest a possible role for beta(1) and beta(3) integrin subfamily members in the establishment of skeletal metastases in advanced breast cancer patients. Clearly, functional evidence is required; to understand the mechanisms involved in the development of skeletal metastases in breast cancer patients. C1 Leiden Univ Hosp, Dept Endocrinol C4 89, NL-2333 AA Leiden, Netherlands. NIDR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP van der Pluijm, G (reprint author), Leiden Univ Hosp, Dept Endocrinol C4 89, Albinusdreef 2, NL-2333 AA Leiden, Netherlands. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 59 TC 50 Z9 50 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD DEC PY 1997 VL 77 IS 6 BP 665 EP 675 PG 11 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA YN189 UT WOS:000071142000015 ER PT J AU Sandor, V Wilson, W Fojo, T Bates, SE AF Sandor, V Wilson, W Fojo, T Bates, SE TI The role of MDR-1 in refractory lymphoma SO LEUKEMIA & LYMPHOMA LA English DT Review DE MDR-1; refractory lymphoma; lymphoma; multidrug resistance; P-glycoprotein; chemotherapy ID GLUTATHIONE-S-TRANSFERASE; MULTIDRUG RESISTANCE GENE; P-GLYCOPROTEIN EXPRESSION; NON-HODGKINS-LYMPHOMA; MONOCLONAL-ANTIBODIES; DRUG-RESISTANCE; IMMUNOHISTOCHEMICAL DETECTION; CYCLOSPORINE-A; HUMAN CANCERS; CELL-LINES AB Although lymphoma is one of the few solid tumours for which chemotherapy can be curative, the treatment of refractory lymphoma remains a major clinical problem. P-glycoprotein (Pgp), the drug efflux pump encoded by the MDR-1 gene is associated with multidrug resistance in several laboratory models of drug resistance, and a number of investigators have attempted to establish a role for Pgp in refractory lymphoma. Despite a considerable variability in the results of these studies investigating Pgp expression in lymphoma, the preponderance of the data suggests that Pgp may at least in part account for drug resistance in this disease. Several clinical trials using Pgp modulating compounds have attempted to reverse the drug resistant phenotype of refractory lymphoma. These studies, although difficult to interpret because of the effect of Pgp modulators on chemotherapeutic drug pharmacokinetics, also suggest a role for Pgp in mediating drug resistance in a subset of patients with refractory lymphoma. Studies with newer Pgp modulating agents with phase III designs will be needed before Pgp modulation can be considered for incorporation into routine oncologic practice. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Bates, SE (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 44 TC 21 Z9 21 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD DEC PY 1997 VL 28 IS 1-2 BP 23 EP 31 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA YU068 UT WOS:000071677900003 PM 9498700 ER PT J AU Jiang, YZ Barrett, J AF Jiang, YZ Barrett, J TI The allogeneic CD4(+) T-cell-mediated graft-versus-leukemia effect SO LEUKEMIA & LYMPHOMA LA English DT Review DE BMT; CML; GVL; GVHD; CD4(+) T-cell; CD8(+) T-cell ID BONE-MARROW TRANSPLANTATION; CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; TUMOR-NECROSIS-FACTOR; MINOR HISTOCOMPATIBILITY ANTIGENS; HOST DISEASE; IN-VITRO; INTERFERON-GAMMA; DONOR LEUKOCYTES; DENDRITIC CELLS AB CD4(+) T-cells have emerged as important cells in the initiation and delivery of the GVL response. Nevertheless it seems likely that they act in concert with other T-cells and NK cell effecters to produce the full in vivo effect of GVL. How they interact with other effecters is yet to be determined, Furthermore it is very likely that different hematological malignancies have different susceptibility to attack by various lymphocyte subsets, depending upon their MHC expression, nature of the antigens presented and other properties not yet defined, Here we specifically focus on the role of CD4(+) T-cells in mediating GVL, particularly in chronic myeloid leukemia, Candidate antigens recognised by CD4(+) cells are described and new approaches to GVL modulation in clinical bone marrow transplantation are discussed. C1 NHLBI, Bone Marrow Transplantat Unit, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Jiang, YZ (reprint author), NHLBI, Bone Marrow Transplantat Unit, Hematol Branch, NIH, Bldg 10,Room 7e103,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jiangy@gwgate.nhlbi.nih.gov NR 98 TC 13 Z9 14 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD DEC PY 1997 VL 28 IS 1-2 BP 33 EP 42 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA YU068 UT WOS:000071677900004 PM 9498701 ER PT J AU Leiter, EH Tsumura, H Serreze, DV Chapman, HD Rabin, DU Lan, MS Notkins, AL AF Leiter, EH Tsumura, H Serreze, DV Chapman, HD Rabin, DU Lan, MS Notkins, AL TI Mapping to Chromosomes 1 and 12 of mouse homologs of human protein tyrosine phosphatase, receptor-type, related genes encoding pancreatic beta cell autoantigens SO MAMMALIAN GENOME LA English DT Article ID IA-2; IDENTIFICATION; IA-2-BETA; IDDM; MICE C1 BAYER RES CTR,W HAVEN,CT 06516. NIDR,ORAL MED LAB,NIH,BETHESDA,MD 20892. RP Leiter, EH (reprint author), JACKSON LAB,600 MAIN ST,BAR HARBOR,ME 04609, USA. FU NIDDK NIH HHS [DK46266, DK36175, DK27722] NR 13 TC 7 Z9 8 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD DEC PY 1997 VL 8 IS 12 BP 949 EP 950 DI 10.1007/s003359900619 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA YH381 UT WOS:A1997YH38100022 PM 9383296 ER PT J AU Chidambaram, A Allikmets, R Chandrasekarappa, S Guru, SC Modi, W Gerrard, B Dean, M AF Chidambaram, A Allikmets, R Chandrasekarappa, S Guru, SC Modi, W Gerrard, B Dean, M TI Characterization of a human homolog (OVOL1) of the Drosophila ovo gene, which maps to Chromosome 11q13 SO MAMMALIAN GENOME LA English DT Article ID LINKAGE MAP; LOCUS; MELANOGASTER; SHAVENBABY; SEQUENCES; GERMLINE C1 NCI,FREDERICK CANC RES & DEV CTR,HUMAN GENET SECT,INTRAMURAL RES SUPPORT PROGRAM,SAIC,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,HUMAN GENET SECT,LAB GENOME DIVERS,FREDERICK,MD 21702. NHGRI,LAB GENE TRANSFER,NIH,BETHESDA,MD 20892. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 18 TC 16 Z9 18 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD DEC PY 1997 VL 8 IS 12 BP 950 EP 951 DI 10.1007/s003359900620 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA YH381 UT WOS:A1997YH38100023 PM 9383297 ER PT J AU Roth, GS AF Roth, GS TI Age changes in signal transduction and gene expression SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article; Proceedings Paper CT 1st International NILS Workshop on Longevity Sciences - The Role of Molecular Genetics in Longevity Sciences CY NOV 29, 1996 CL OBU, JAPAN SP Natl Inst Longev Sci ID CULTURED RAT HEPATOCYTES; MESSENGER-RNA; DNA-SYNTHESIS; RECEPTOR CDNA; DOPAMINE D-2; IN-SITU; STRIATUM; BRAIN; CLONING RP Roth, GS (reprint author), NIA,CELLULAR & MOL BIOL LAB,MOL PHYSIOL & GENET SECT,NIH,GERONTOL RES CTR,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 35 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing. Dev. PD DEC PY 1997 VL 98 IS 3 BP 231 EP 238 DI 10.1016/S0047-6374(97)00110-3 PG 8 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA YB781 UT WOS:A1997YB78100005 PM 9352492 ER PT J AU Greene, JF Morgan, CD Rao, A Amoss, MS Arguello, F AF Greene, JF Morgan, CD Rao, A Amoss, MS Arguello, F TI Regression by differentiation in the Sinclair swine model of cutaneous melanoma SO MELANOMA RESEARCH LA English DT Article DE cancer therapy; differentiation; macrophage; melanoma; regression; swine ID MALIGNANT-MELANOMA; MINIATURE SWINE; CELLS; MELANOCYTES; EXPRESSION; MOUSE; HISTOPATHOLOGY; MELANOSOMES; MATURATION; LYSOSOMES AB The spontaneous regression of melanoma in Sinclair miniature swine involves the replacement of tumours by pigmented cells, hitherto interpreted as pigment-laden macrophages (PLMs). We hypothesized that these residual cells are terminally differentiated melanoma cells, not monocyte-derived macrophages. Swine melanoma explants with no regression were transplanted into severe combined immunodeficient (SCID) mice. Harvested transplant sites were examined by routine light and electron microscopy techniques. Paraffin sections were also stained with Hoeschst dye and examined by fluorescence microscopy. All but one site had completely regressed and were replaced by PLM-like cells. Hoeschst staining indicated they were of swine, not mouse, origin. The ultrastructural features of the single, partially regressed lesion demonstrated many premelanosomes in these cells. We conclude that tumour differentiation is an important mechanism of regression in the Sinclair swine melanoma model. C1 Texas A&M Univ, Hlth Sci Ctr, Coll Med,Scott Sherwood & Brindley Fdn, Scott & White Clin & Mem Hosp,Dept Pathol, Temple, TX 76508 USA. Texas A&M Univ, Coll Vet Med, Dept Physiol & Pharmacol, College Stn, TX 77843 USA. NCI, Div Canc Treatment, Lab Drug Discovery Res & Dev, Dev Therapeut Program,NIH, Frederick, MD USA. RP Greene, JF (reprint author), Texas A&M Univ, Hlth Sci Ctr, Coll Med,Scott Sherwood & Brindley Fdn, Scott & White Clin & Mem Hosp,Dept Pathol, 2401 S 31st St, Temple, TX 76508 USA. FU NCI NIH HHS [P01 CA 9488] NR 33 TC 16 Z9 16 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD DEC PY 1997 VL 7 IS 6 BP 471 EP 477 DI 10.1097/00008390-199712000-00005 PG 7 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA YM801 UT WOS:000071102200005 PM 9464619 ER PT J AU Stubbs, L Carver, EA Cacheiro, NLA Shelby, M Generoso, W AF Stubbs, L Carver, EA Cacheiro, NLA Shelby, M Generoso, W TI Generation and characterization of heritable reciprocal translocations in mice SO METHODS LA English DT Article ID BALANCED TRANSLOCATION; DOMINANT LETHAL; MUTATIONS; GENE; IDENTIFICATION; BREAKPOINT; LOCUS; MODEL AB Reciprocal translocations have provided crucial tools for the localization of genes associated with a variety of human cancers and hereditary diseases. Although heritable translocations are relatively rare in humans, they can be easily induced in mice through exposure of male germ cells at specific spermatogenic stages to different types of radiation and chemicals. Mutagenesis schemes that produce translocations at high frequencies in the progeny of treated males are summarized, and the use of these valuable mutations for analyzing developmental consequences of partial aneuploidy, for identification of mutant genes, and for other purposes is reviewed. Preliminary studies of a large collection of translocation mutants, including several stocks that display dominantly or recessively inherited phenotypes caused by the disruption of critical genes are described. These combined studies demonstrate that several mutagenesis protocols can be used to generate easily mapped, novel mouse mutations with high efficiency and highlight the unique value of reciprocal translocations as tools for gaining access to the biological functions of mammalian genes. (C) 1997 Academic Press. C1 Univ Tennessee, Div Life Sci, Grad Sch Biomed Sci, Oak Ridge, TN 37831 USA. Oak Ridge Natl Lab, Div Life Sci, Oak Ridge, TN 37831 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Stubbs, L (reprint author), Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, 7000 East Ave,L-452, Livermore, CA 94550 USA. EM Stubbs5@llnl.gov OI Stubbs, Lisa/0000-0002-9556-1972 FU NIEHS NIH HHS [Y01-ES-20085] NR 50 TC 11 Z9 12 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD DEC PY 1997 VL 13 IS 4 BP 397 EP 408 DI 10.1006/meth.1997.0546 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YZ446 UT WOS:000072254900007 PM 9480784 ER PT J AU Fend, F AF Fend, F TI Almasri NM, Zaer FS, Iturraspe JA, Braylan RC. Contribution of flow cytometry to the diagnosis of gastric lymphomas in endoscopic biopsy specimens. Mod Pathol 1997;10 : 650-6. SO MODERN PATHOLOGY LA English DT Letter ID POLYMERASE CHAIN-REACTION C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Fend, F (reprint author), NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD DEC PY 1997 VL 10 IS 12 BP 1265 EP 1266 PG 2 WC Pathology SC Pathology GA YM640 UT WOS:000071085000014 PM 9436974 ER PT J AU Joseph, GT McCarthy, JS Huima, T Mair, KF Kass, PH Boussinesq, M Goodrick, L Bradley, JE Lustigman, S AF Joseph, GT McCarthy, JS Huima, T Mair, KF Kass, PH Boussinesq, M Goodrick, L Bradley, JE Lustigman, S TI Onchocerca volvulus: Characterization of a highly immunogenic Gln-rich protein SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Onchocerca volvulus; larvae; putatively immune individuals; polyglutamine tract; IgG subclasses; T-cell proliferation ID GUATEMALAN HUMAN ONCHOCERCIASIS; PUTATIVELY IMMUNE INDIVIDUALS; PROTECTIVE IMMUNITY; 3RD-STAGE LARVAE; INFECTIVE LARVAE; ANTIGEN PRESENT; CROSS-LINKING; IDENTIFICATION; RESPONSES; PARASITE AB A pool of sera from individuals classified as putatively immune (PI) to Onchocerca volvulus infection was employed in the screening of a fourth-stage larval cDNA expression library. A highly immunogenic clone, encoding the Ov 53/80 protein, was identified. The full length cDNA of clone 4.21 contained 2527 nucleotides encoding 769 amino acids of which 100 are glutamine residues (13%). Antibodies raised against recombinant protein encoded by a partial cDNA sequence (clone 73-k) recognized a 53 and 80 kDa protein in O. volvulus larval and adult parasite extracts, respectively. The antibodies localized the native protein in the cuticle, hypodermis, secretory vesicles and in granules of the glandular esophagus of larvae and in the hypodermis and the cuticle of adult worms. The recombinant 73-k polypeptide (r73) was recognized by 90-100% of sera from PI and infected individuals from Liberia, but only by 67% of similar groups from Ecuador. r73 specific IgG2 and IgG3 levels in the PI from Liberia and Ecuador, respectively, were significantly lower than in the infected, whereas the r73 specific IgG1/IgG3 or IgG1/IgG2 in the PI and the infected individuals from Liberia or Ecuador, respectively, were similar. The IgG4 specific antibody response in the PI from Liberia and Ecuador were lower than in the infected. The T-cell proliferative responses to r73 in infected individuals from Cameroon were found to be inversely correlated with their levels of microfilariae. (C) 1997 Elsevier Science B.V. C1 New York Blood Ctr, Lindsley F Kimball Res Inst, New York, NY 10021 USA. NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. Univ Calif Davis, Sch Vet Med, Davis, CA USA. Univ Calif Davis, Sch Vet Med, Paris, France. ORSTOM, F-75010 Paris, France. Univ Salford, Dept Biol Sci, Manchester, Lancs, England. RP Lustigman, S (reprint author), New York Blood Ctr, Lindsley F Kimball Res Inst, 310 E 67th St, New York, NY 10021 USA. EM slustigm@server.nybc.org RI Boussinesq, Michel/J-7256-2016 OI Boussinesq, Michel/0000-0001-6312-0681 NR 35 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD DEC 1 PY 1997 VL 90 IS 1 BP 55 EP 68 DI 10.1016/S0166-6851(97)00132-1 PG 14 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA YU428 UT WOS:000071716100006 PM 9497032 ER PT J AU Guinet, F Wellems, TE AF Guinet, F Wellems, TE TI Physical mapping of a defect in Plasmodium falciparum male gametocytogenesis to an 800 kb segment of chromosome 12 SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE malaria; gametes; gametocytes; chromosome mapping ID MALE GAMETOGENESIS; GENETIC CROSS; INFECTIVITY; CLONES; MAP C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Wellems, TE (reprint author), NIAID, NIH, Bethesda, MD 20892 USA. NR 15 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD DEC 1 PY 1997 VL 90 IS 1 BP 343 EP 346 DI 10.1016/S0166-6851(97)00144-8 PG 4 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA YU428 UT WOS:000071716100032 PM 9497058 ER PT J AU Templeton, TJ Fujioka, H Aikawa, M Parker, KC Kaslow, DC AF Templeton, TJ Fujioka, H Aikawa, M Parker, KC Kaslow, DC TI Plasmodium falciparum Pfs40, renamed Pf39, is localized to an intracellular membrane-bound compartment and is not sexual stage-specific SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Plasmodium falciparum; endoplasmic reticulum; gamete; zygote; Pfs40; Pf39 ID ANTIGENS; IMMUNITY; VACCINE; PROTEIN C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA. Tokai Univ, Res Inst Med Sci, Kanagawa 25911, Japan. NIAID, Mol Struct Lab, NIH, Bethesda, MD 20892 USA. RP Kaslow, DC (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. OI Parker, Kenneth/0000-0002-6282-2478 FU NIAID NIH HHS [AI-35827] NR 7 TC 22 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD DEC 1 PY 1997 VL 90 IS 1 BP 359 EP 365 DI 10.1016/S0166-6851(97)00164-3 PG 7 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA YU428 UT WOS:000071716100035 PM 9497061 ER PT J AU Blomberg, LA Wu, SM Dirami, G Dym, M Chou, JY Chan, WY AF Blomberg, LA Wu, SM Dirami, G Dym, M Chou, JY Chan, WY TI Characterization and cellular localization of PSG in rat testis SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE pregnancy-specific beta 1-glycoprotein; cDNA; rat; Sertoli; Leydig; myoid ID PREGNANCY-SPECIFIC BETA-1-GLYCOPROTEIN; ANTIGEN GENE FAMILY; PROTEIN-KINASE-C; CARCINOEMBRYONIC ANTIGEN; SUBSTRATE-SPECIFICITY; SYNTHETIC PEPTIDES; CDNA CLONING; FETAL LIVER; GLYCOPROTEIN; EXPRESSION AB In order to establish the rat testis as a model system for studying the human pregnancy-specific beta 1-glycoprotein (PSG), expression and cellular distribution of PSG in rat testis were examined. Three partial PSG cDNAs, namely, rnCGM6, rnGCM7, and rnCGM8 were obtained when rat testis cDNA Libraries were screened with a human placental PSG cDNA probe. Unlike the human PSGs, the rat PSGs show less nucleotide and amino acid sequence homology among family members. The rat PSGs also have multiple truncated leader sequences followed by immunoglobulin variable-like N domains while human PSGs have a single N domain. Examination of the testis, intestine, kidney, liver, lung, and muscle of male rats by reverse transcription-polymerase chain reaction (RT-PCR) with nested gene-specific primers showed that rnCGM6 was present only in the testis, while rnCGM8 was present in the testis, intestine and lung. On the other hand rnCMG7 was found in all tissues examined. Furthermore, rnCGM7 transcript was present in all somatic cells examined whereas rnCGM6 was predominantly in myoid cells and rnCMG8 in Leydig cells. These results suggest that there is cell-specificity in the expression of PSGs in the rat testis and that the rat testis is a good model for studying the biological activities of the PSGs. C1 Georgetown Univ, Childrens Med Ctr, Dept Pediat, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Cell Biol, Washington, DC 20007 USA. NIH, NICHHD, Heritable Disorders Branch, Bethesda, MD 20892 USA. RP Chan, WY (reprint author), Georgetown Univ, Childrens Med Ctr, Dept Pediat, 3800 Reservoir Rd,NW, Washington, DC 20007 USA. FU NICHD NIH HHS [P01HD32644] NR 46 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD DEC PY 1997 VL 177 IS 1-2 BP 229 EP 237 DI 10.1023/A:1006811305616 PG 9 WC Cell Biology SC Cell Biology GA YP132 UT WOS:000071245900030 PM 9450667 ER PT J AU Xiao, H Lis, JT Jeang, KT AF Xiao, H Lis, JT Jeang, KT TI Promoter activity of Tat at steps subsequent to TATA-binding protein recruitment SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RNA-POLYMERASE-II; HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; TRANSCRIPTIONAL ACTIVATION DOMAIN; IN-VIVO; MAMMALIAN-CELLS; 2 STEPS; ELONGATION; HIV-1; HOLOENZYME AB Artificial recruitment of TATA-binding protein (TBP) to many eukaryotic promoters bypasses DNA-bound activator function. The human immunodeficiency virus type 1 (HIV-1) Tat is an unconventional activator that up-regulates transcription from the HIV-1 long terminal repeat (LTR) through binding to a nascent RNA sequence, TAR. Because this LTR and its cognate activator have atypical features compared to a standard RNA polymerase II (RNAP II) transcriptional unit, the precise limiting steps for HIV-1 transcription and how Tat resolves these limitations remain incompletely understood. We thus constructed human TBP fused to the DNA-binding domain of GAL4 to determine whether recruitment of TBP is one rate-limiting-step in HIV-1 LTR transcription and whether Tat functions to recruit TBP. As a control, we compared the activity of the adenovirus E1b promoter. Our findings indicate that TBP tethering to the E1b promoter fully effected transcription to the same degree achievable with the potent GAL4-VP16 activator. By contrast, TBP recruitment to the HIV-1 LTR, although necessary for conferring Tat responsiveness, did not bypass a physical need for Tat in achieving activated transcription. These results document that the HIV-1 and the E1b promoters are transcriptionally limited at different steps; the major rate-limiting step for E1b is recruitment of TBP, while activation of the HIV-1 LTR requires steps in addition to TBP recruitment. We suggest that Tat acts to accelerate rate-limiting steps after TBP recruitment. C1 CORNELL UNIV,BIOCHEM MOL & CELL BIOL SECT,ITHACA,NY 14853. RP Xiao, H (reprint author), NIAID,MOL VIROL SECT,MOL MICROBIOL LAB,NIH,BLDG 4,ROOM 306,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 62 TC 46 Z9 46 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1997 VL 17 IS 12 BP 6898 EP 6905 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YG441 UT WOS:A1997YG44100014 PM 9372921 ER PT J AU Kurumizaka, H Wolffe, AP AF Kurumizaka, H Wolffe, AP TI Sin mutations of histone H3: Influence on nucleosome core structure and function SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Review ID YEAST SWI/SNF COMPLEX; RNA-POLYMERASE-II; TRANSCRIPTION FACTOR-IIIA; TATA-BINDING PROTEIN; SILENT MATING LOCI; SACCHAROMYCES-CEREVISIAE; LINKER HISTONES; 5S RNA; NEGATIVE REGULATOR; XENOPUS-LAEVIS AB Sin mutations in Saccharomyces cerevisiae alleviate transcriptional defects that result from the inactivation of the yeast SWI/SNF complex. We have investigated the structural and functional consequences for the nucleosome of Sin mutations in histone H3. We directly test the hypothesis that mutations in histone H3 leading to a SWI/SNF-independent (Sin) phenotype in yeast lead to nucleosomal destabilization. In certain instances this is shown to be true; however, nucleosomal destabilization does not always occur. Topoisomerase I-mediated relaxation of minichromosomes assembled with either mutant histone H3 or wild-type H3 together with histones H2A, H2B, and H4 indicates that DNA is constrained into nucleosomal structures containing either mutant or wild-type proteins. However, nucleosomes containing particular mutant H3 molecules (R116-H and T118-I) are more accessible to digestion by micrococcal nuclease and do not constrain DNA in a precise rotational position, as revealed by digestion with DNase I. This result establishes that Sin mutations in histone H3 located close to the dyad axis can destabilize histone-DNA contacts at the periphery of the nucleosome core. Other nucleosomes containing a distinct mutant H3 molecule (E105-K) associated with a Sin phenotype show very little change in nucleosome structure and stability compared to wild-type nucleosomes. Both mutant and wild-type nucleosomes continue to restrict the binding of either TATA-binding protein/transcription factor IIA (TFIIA) or the RNA polymerase III transcription machinery. Thus, different Sin mutations in histone H3 alter the stability of histone-DNA interactions to various extents in the nucleosome while maintaining the fundamental architecture of the nucleosome and contributing to a common Sin phenotype. C1 NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892. NR 110 TC 60 Z9 60 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1997 VL 17 IS 12 BP 6953 EP 6969 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YG441 UT WOS:A1997YG44100021 PM 9372928 ER PT J AU Yoon, JH Whalen, WA Bharathi, A Shen, RL Dhar, R AF Yoon, JH Whalen, WA Bharathi, A Shen, RL Dhar, R TI Npp106p, a Schizosaccharomyces pombe nucleoporin similar to Saccharomyces cerevisiae Nic96p, functionally interacts with Rae1p in mRNA export SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NUCLEAR-PORE COMPLEX; MESSENGER-RNA TRANSPORT; POLY(A)(+) RNA; NUCLEOCYTOPLASMIC TRANSPORT; BINDING-PROTEIN; CONDITIONAL ALLELE; ENVELOPE STRUCTURE; FISSION YEAST; GENE; CYTOPLASM AB To identify components of the mRNA export machinery in Schizosaccharomyces pombe, a screen was developed to identify mutations that were synthetically lethal with the conditional mRNA export allele rae1-167. Mutations defining three complementation groups were isolated, and here we report the characterization of npp106 (for nuclear pore protein of 106 kDa) This gene encodes a predicted protein that has significant similarity to the Nic96p nucleoporin of Saccharomyces cerevisiae. Consistent with Npp106p being a nucleoporin, a functional green fluorescent protein (GFP)-tagged Npp106p localized to the nuclear periphery. In contrast to NIC96, the npp106 gene is not essential. Moreover, a Delta npp106 mutant did not show cytoplasmic mislocalization of a simian virus 40 nuclear localization signal-GFP-LacZ reporter protein, and a fraction of cells had accumulation of poly(A)(+) RNA in the nucleus. A consequence of the synthetic lethality between rae1-167 and npp106-1 was the accumulation of poly(A)(+) RNA in the nucleus when cells were grown under synthetic lethal conditions. In addition to npp106-1, which is a nonsense mutation that truncates the protein at amino acid 292, the Delta npp106 mutation was synthetically lethal with rae1-167, suggesting that the synthetic lethality is a consequence of the loss of a function of npp106. We further demonstrate that a region between amino acids 74 end 348 of Npp106p is required for complementation of the synthetic lethality. These results uncover a potential direct or indirect involvement of Npp106p in mRNA export. C1 NCI, LAB BASIC SCI, NIH, BETHESDA, MD 20892 USA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. RI Shen, Rulong/E-4079-2011 NR 78 TC 25 Z9 26 U1 0 U2 0 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 DEC PY 1997 VL 17 IS 12 BP 7047 EP 7060 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YG441 UT WOS:A1997YG44100029 PM 9372936 ER PT J AU Nielsen, KH Papageorge, AG Vass, WC Willumsen, BM Lowy, DR AF Nielsen, KH Papageorge, AG Vass, WC Willumsen, BM Lowy, DR TI The Ras-specific exchange factors mouse Sos1 (mSos1) and mSos2 are regulated differently: mSos2 contains ubiquitination signals absent in mSos1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GUANINE-NUCLEOTIDE EXCHANGE; SACCHAROMYCES-CEREVISIAE; TYROSINE KINASE; PROTEOLYTIC PATHWAY; CYCLIN DESTRUCTION; PROTEASOME PATHWAY; SEVENLESS PROTEIN; ADAPTER PROTEIN; IN-VIVO; M-PHASE AB We have compared aspects of the mouse sos1 (msos1) and msos2 genes, which encode widely Expressed, closely related Ras-specific exchange factors, Although an msos1 plasmid did not induce phenotypic changes in MB 3T3 cells, addition of a 15-codon myristoylation signal to its 5' end enabled the resulting plasmid, myr-sos1, to induce approximately one-half as many foci of transformed cells as a v-H-ras control, By contrast, an isogenic myr-sos2 plasmid, which was made by fusing the first 102 codons from myr-sos1 at homologous sequences to an intact msos2 cDNA, did not induce focal transformation directly, although it could form foci in cooperation with c-H-ras. Pulse-chase experiments indicated that the half-life of Sos1 in NIH 3T3 cells was greater than 18 h, while that of Sos2 was less than 3 h, While in vitro-translated Sos1 was stable in a rabbit reticulocyte lysate, Sos2 was degraded in the lysate, as were each of two reciprocal chimeric Sos1-Sos2 proteins, albeit at a slower rate. In the lysate, Sos2 and the two chimeric proteins could be stabilized by ATP gamma S. Unlike Sos1, Sos2 was specifically immunoprecipitated by antiubiquitin antibodies. In a myristoylated version, the chimeric gene encoding Sos2 at its C terminus made a stable protein in NIH 3T3 cells and induced focal transformation almost as efficiently as myr-msos1, while the myristoylated protein encoded by the other chimera was unstable and defective in the transformation assay. We conclude that mSos2 is much less stable than mSos1 and is degraded by a ubiquitin-dependent process. A second mSos2 degradation signal, mapped to the C terminus in the reticulocyte lysate, does not seem to function under the growth conditions of the NIH 3T3 cells. C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. UNIV COPENHAGEN,DEPT MOL CELL BIOL,DK-1353 COPENHAGEN,DENMARK. RI Willumsen, Berthe/H-1903-2012 OI Willumsen, Berthe/0000-0002-2277-6999 NR 53 TC 22 Z9 23 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1997 VL 17 IS 12 BP 7132 EP 7138 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YG441 UT WOS:A1997YG44100038 PM 9372945 ER PT J AU Grigoriev, M Hsieh, P AF Grigoriev, M Hsieh, P TI A histone octamer blocks branch migration of a Holliday junction SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SITE-SPECIFIC RECOMBINATION; BACTERIOPHAGE-T7 ENDONUCLEASE-I; CHROMATIN STRUCTURE; MEIOTIC RECOMBINATION; NUCLEOSOME CORE; SACCHAROMYCES-CEREVISIAE; TRANSCRIBING POLYMERASE; HYPERSENSITIVE SITES; DNA-SEQUENCE; DUPLEX DNA AB The Holliday junction is a key intermediate in genetic recombination, Here, we examine the effect of a nucleosome core on movement of the Holliday junction in vitro by spontaneous branch migration. Histone octamers consisting of H2A, H2B, H3, and H4 are reconstituted onto DNA duplexes containing an artificial nucleosome-positioning sequence consisting of a tandem array of an alternating AT-GC sequence motif, Characterization of the reconstituted branch migration substrates by micrococcal nuclease mapping and exonuclease III and hydroxyl radical footprinting reveal that 70% of the reconstituted octamers are positioned near the center of the substrate and the remaining 30% are located at the distal end, although in both cases some translational degeneracy is observed. Branch migration assays with the octamer-containing substrates reveal that the Holliday junction cannot migrate spontaneously through DNA organized into a nucleosomal core unless DNA-histone interactions are completely disrupted, Similar results are obtained with branch migration substrates containing an octamer positioned on a naturally occurring sequence derived from the yeast GLN3 locus, Digestion of Holliday junctions with T7 endonuclease I establishes that the junction is not trapped by the octamer but can branch migrate in regions free of histone octamers, Our findings suggest that migration of Holliday junctions during recombination and the recombinational repair of DNA damage requires proteins not only to accelerate the intrinsic rate of branch migration but also to facilitate the passage of the Holliday junction through a nucleosome. C1 NIDDKD,GENET & BIOCHEM BRANCH,NIH,BETHESDA,MD 20892. NR 60 TC 12 Z9 13 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1997 VL 17 IS 12 BP 7139 EP 7150 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YG441 UT WOS:A1997YG44100039 PM 9372946 ER PT J AU Weirich, G Hornauer, MA Bruning, T Hofler, H Brauch, H AF Weirich, G Hornauer, MA Bruning, T Hofler, H Brauch, H TI Fixed archival tissue - Purify DNA and primers for good PCR yield! SO MOLECULAR BIOTECHNOLOGY LA English DT Article DE fixation; DNA-extraction; PCR-HPLC ID POLYMERASE CHAIN-REACTION; FIXATION AB The analysis of archival formalin-fixed, paraffin-embedded tissue samples becomes increasingly important for molecular biology studies. As fixation and paraffin-embedding cause alterations of proteins and nucleic acids, archival sources of DNA must be handled with care. To address the need for specificity and reproducibility, we developed an improved protocol for semi-automated DNA extraction adapted to fixed, embedded tissue samples, and a PCR approach using HPLC-purified primers. C1 NCI, Immunobiol Lab, Frederick, MD 21702 USA. Tech Univ Munich, Sch Med, Inst Pathol, Dept Mol Pathol, D-8000 Munich, Germany. Univ Dortmund, Inst Occupat Physiol, Dept Occupat Toxicol & Occupat Med, Dortmund, Germany. Univ Hamburg, Sch Med, Dept Gynecol, Lab Oncol, Hamburg, Germany. EM weirichg@mail.ncifcrf.gov NR 7 TC 25 Z9 27 U1 2 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1073-6085 J9 MOL BIOTECHNOL JI Mol. Biotechnol. PD DEC PY 1997 VL 8 IS 3 BP 299 EP 301 DI 10.1007/BF02760783 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA YQ982 UT WOS:000071444700011 PM 9438264 ER PT J AU Dobi, A Palkovits, M Ring, MA Eitel, A Palkovits, CG Lim, F Agoston, DV AF Dobi, A Palkovits, M Ring, MA Eitel, A Palkovits, CG Lim, F Agoston, DV TI Sample and probe: a novel approach for identifying development-specific cis-elements of the enkephalin gene SO MOLECULAR BRAIN RESEARCH LA English DT Article DE enkephalin gene; regulation; development; microdissection; protein-DNA interaction ID CENTRAL-NERVOUS-SYSTEM; PREPROENKEPHALIN MESSENGER-RNA; ENDOGENOUS OPIOID SYSTEM; DNA-BINDING PROTEINS; PROENKEPHALIN GENE; IKAROS GENE; RAT; TRANSCRIPTION; EXPRESSION; BRAIN AB We have developed a novel 'sample and probe' approach as a means to identifying specific DNA elements of the enkephalin gene that control differentiation of the enkephalinergic phenotype during neurodevelopment. The approach is a systematic spatiotemporal analysis of protein-DNA interactions; soluble nuclear proteins ('samples') prepared from microdissected regions of the developing brain are 'probed' with radiolabeled DNA fragments representing various regulatory regions of the enkephalin gene. The resulting spatiotemporal 'molecular maps', i.e. characteristic patterns of protein-DNA complexes showed DNA regions that harbor potential cis-elements regulating differentiation of the enkephalin phenotype at various stages of neurodevelopment. DNase I footprint analysis of such a DNA region identified a binding site (GACGGGAGATCGCTCGT) which is similar to the moth for a lymphoid-specific, developmentally regulated transcription factor, Ikaros, suggesting that the developing brain expresses Ikaros-like transcription factor(s) in a spatiotemporally defined manner. In summary, our approach offers a unique view into the chronology of coordinated protein-DNA interactions and will greatly facilitate identifying DNA elements and isolating development-specific transcription factors. (C) 1997 Elsevier Science B.V. C1 NIMH,UNIT MOL CONTROL NEURODIFFERENTIAT,LDN,NICHD,NIH,BETHESDA,MD 20892. NIMH,GENET SECT,NIH,BETHESDA,MD 20892. RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 55 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD DEC 1 PY 1997 VL 52 IS 1 BP 98 EP 111 DI 10.1016/S0169-328X(97)00238-6 PG 14 WC Neurosciences SC Neurosciences & Neurology GA YL458 UT WOS:A1997YL45800011 ER PT J AU SunayashikiKusuzaki, K Kikuchi, T Wawrousek, EF Shinohara, T AF SunayashikiKusuzaki, K Kikuchi, T Wawrousek, EF Shinohara, T TI Arrestin and phosducin are expressed in a small number of brain cells SO MOLECULAR BRAIN RESEARCH LA English DT Article DE arrestin; phosducin; pinealocyte; brain; transgenic mouse; beta-Gal expression ID RETINOID-BINDING PROTEIN; S-ANTIGEN; PINEAL-GLAND; PHOTORECEPTOR CELLS; GENE-EXPRESSION; MELATONIN; MOUSE; PROMOTER; COMPLEX; LOCALIZATION AB Retinal photoreceptor rods and pinealocytes contain well-characterized proteins such as arrestin and phosducin whose expression is highly restricted to these cell types. Transgenic mice having a LacZ gene under the control of an arrestin promoter expressed beta-galactosidase (beta-Gal) in the photoreceptor rods and pinealocytes. In addition, it was expressed in very small numbers of discrete cells in the habenular commissura, amygdala, ventral tegmental area and superior colliculus of the brain. Immunocytochemical studies with antibody probes revealed that high level of arrestin and phosducin were also found in the same cell types. Furthermore melatonin was found in those cells of the habenula commissura. The results indicate that novel cell types are present in the brain tissues. Since high levels of arrestin and phosducin expression are generally restricted to photoreceptor rod cells and pinealocytes, these data suggest that certain brain cells may have functions similar to pinealocytes. (C) 1997 Elsevier Science B.V. C1 BRIGHAM & WOMENS HOSP,CTR OPHTHALM RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02115. NEI,SECT MOL & DEV BIOL,NIH,BETHESDA,MD 20892. RI Wawrousek, Eric/A-4547-2008; OI Shinohara, Toshimichi/0000-0002-7197-9039 NR 36 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD DEC 1 PY 1997 VL 52 IS 1 BP 112 EP 120 DI 10.1016/S0169-328X(97)00247-7 PG 9 WC Neurosciences SC Neurosciences & Neurology GA YL458 UT WOS:A1997YL45800012 ER PT J AU Dumaz, N Duthu, A Ehrhart, JC Drougard, C Appella, E Anderson, CW May, P Sarasin, A Daya-Grosjean, L AF Dumaz, N Duthu, A Ehrhart, JC Drougard, C Appella, E Anderson, CW May, P Sarasin, A Daya-Grosjean, L TI Prolonged p53 protein accumulation in trichothiodystrophy fibroblasts dependent on unrepaired pyrimidine dimers on the transcribed strands of cellular genes SO MOLECULAR CARCINOGENESIS LA English DT Article DE DNA repair; p53; WAF1; GADD45; ultraviolet light ID TUMOR-SUPPRESSOR PROTEIN; DNA-DAMAGING AGENTS; C-TERMINAL DOMAIN; WILD-TYPE P53; XERODERMA-PIGMENTOSUM; ATAXIA-TELANGIECTASIA; NUCLEAR ACCUMULATION; G(1) ARREST; SKIN TUMORS; REPAIR AB Trichothiodistrophy (TTD), xeroderma pigmentosum (XP), and Cockayne's syndrome (CS) are three distinct human diseases with sensitivity to ultraviolet (UV) radiation affected by mutations in genes involved in nucleotide excision repair (NER). Among the many responses of human cells to UV irradiation, both nuclear accumulation of p53, a tumor suppressor protein, and alterations in cell-cycle checkpoints play crucial roles. The purpose of this study was to define the signals transmitted after UV-C-induced DNA damage, which activates p53 accumulation in TTD/XP-D fibroblasts, and compare this with XP-D cell lines that carry different mutations in the same gene, XPD. Our results showed that p53 was rapidly induced in the nuclei of TTD/XP-D and XP-D fibroblasts in a dose-dependent manner after UV-C irradiation, as seen in XP-A and CS-A fibroblasts, much lower doses being required for the protein accumulation than in normal human fibroblasts, XP variant cells, and XP-C cells. The kinetics of accumulation of p53 and two effector proteins involved in cell-cycle arrest, WAF1 a nd GAD D45, were also directly related to the repair potential of the cells, as in normal human fibroblasts the ir levels declined after 24 h, the time required for repair of UV-induced lesions, whereas NER-deficient TTD/XP-D cells showed p53, WAF1, and GADD45 accumulation for over 72 h after irradiation. Our results indicate that p53 accumulation followed by transcriptional activation of genes implicated in growth arrest is triggered in TTD/XP-D cells by the persistence of cyclobutane pyrimidine dimers, which are known to block transcription, on the transcribed strands of active genes. (C) 1997 Wiley-Liss, Inc. C1 Inst Rech Canc, Genet Mol Lab, Inst Federat, CNRS 1, F-94801 Villejuif, France. NCI, Cell Biol Lab, Bethesda, MD 20892 USA. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. RP Daya-Grosjean, L (reprint author), Inst Rech Canc, Genet Mol Lab, Inst Federat, CNRS 1, IFC1,7 Rue Guy Moquet, F-94801 Villejuif, France. RI Dumaz, Nicolas/B-5907-2008 OI Dumaz, Nicolas/0000-0003-3511-2160 NR 49 TC 59 Z9 60 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD DEC PY 1997 VL 20 IS 4 BP 340 EP 347 DI 10.1002/(SICI)1098-2744(199712)20:4<340::AID-MC3>3.0.CO;2-N PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA YQ402 UT WOS:000071383200003 PM 9433478 ER PT J AU Roberts-Thomson, SJ Snyderwine, EG AF Roberts-Thomson, SJ Snyderwine, EG TI Effect of dietary fat on codon 12 and 13 Ha-ras gene mutations in 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced rat mammary gland tumors SO MOLECULAR CARCINOGENESIS LA English DT Article DE heterocyclic amine; dietary fat; mammary gland; rat ID NITROSO-N-METHYLUREA; SPRAGUE-DAWLEY RATS; HETEROCYCLIC AMINES; EPITHELIAL-CELLS; COOKED FOODS; CARCINOMAS; CARCINOGENESIS; ACTIVATION; INDUCTION; ONCOGENES AB Activating mutations in and expression of the Ha-ras gene were examined in benign and malignant female Sprague-Dawley rat mammary gland tumors induced by the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhlP) and promoted by a diet high in polyunsaturated fat. Ha-ras mutations were detected in codons 12 and 13 by selective polymerase chain reaction amplification of mutated sequences and nucleotide sequencing. The percentage of Ha-ras mutations in carcinomas from PhlP-treated rats was significantly higher in rats on a low-fat diet than in rats on a high-fat diet (82% (nine of 11) vs 26% (seven of 27), respectively, P < 0.01). In addition, whereas 56% of the carcinomas with Ha-ras mutations from rats on a low-fat diet carried double Ha-ras mutations, none of the carcinomas from rats on a high-fat diet had double mutations. Ha-ras mutations were also detected in benign tumors (largely adenomas) induced by PhlP in rats on different diets; two of eight and three of four benign tumors examined from rats on low-fat and high-fat diets, respectively, had Ha-ras mutations, suggesting that activating Ha-ras mutations alone are not sufficient for PhlP-induced tumors to become malignant. No differences were observed in the level of Ha-ras mRNA expression in the different groups. In our animal model, a high-fat diet increased the incidence and percentage of malignant PhlP-induced mammary gland tumors yet decreased the percentage of carcinomas showing Ha-ras mutations. Thus, the complement of genetic alterations associated with PhlP-induced mammary gland carcinogenesis is probably altered by the level of dietary fat. (C) 1997 Wiley-Liss, Inc. C1 NCI, Chem Carcinogenesis Sect, LEC, Div Basic Sci, Bethesda, MD 20892 USA. RP Snyderwine, EG (reprint author), NCI, Chem Carcinogenesis Sect, LEC, Div Basic Sci, Bldg 37,Room 3C28, Bethesda, MD 20892 USA. RI Roberts-Thomson, Sarah/B-4282-2011 OI Roberts-Thomson, Sarah/0000-0001-8202-5786 NR 37 TC 26 Z9 26 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD DEC PY 1997 VL 20 IS 4 BP 348 EP 354 DI 10.1002/(SICI)1098-2744(199712)20:4<348::AID-MC4>3.0.CO;2-F PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA YQ402 UT WOS:000071383200004 PM 9433479 ER PT J AU Puri, PL Sartorelli, V Yang, XJ Hamamori, Y Ogryzko, VV Howard, BH Kedes, L Wang, JYJ Graessmann, A Nakatani, Y Levrero, M AF Puri, PL Sartorelli, V Yang, XJ Hamamori, Y Ogryzko, VV Howard, BH Kedes, L Wang, JYJ Graessmann, A Nakatani, Y Levrero, M TI Differential roles of p300 and PCAF acetyltransferases in muscle differentiation SO MOLECULAR CELL LA English DT Article ID RNA-POLYMERASE-II; LARGE T-ANTIGEN; ADENOVIRUS E1A; HISTONE ACETYLTRANSFERASE; RETINOBLASTOMA PROTEIN; SKELETAL-MUSCLE; BHLH PROTEINS; UP-REGULATION; CELL-CYCLE; TRANSCRIPTION AB PCAF is a histone acetyltransferase that associates with p300/CBP and competes with E1A for access to them. While exogenous expression of PCAF potentiates both MyoD-directed transcription and myogenic differentiation, PCAF inactivation by anti-PCAF antibody microinjection prevents differentiation. MyoD interacts directly with both p300/CBP and PCAF, forming a multimeric protein complex on the promoter elements. Viral transforming factors that interfere with muscle differentiation disrupt this complex without affecting the MyoD-DNA interaction, indicating functional significance of the complex formation. Exogenous expression of PCAF or p300 promotes p21 expression and terminal cell-cycle arrest. Both of these activities are dependent on the histone acetyltransferase activity of PCAF, but not on that of p300. These results indicate that recruitment of histone acetyltransferase activity of PCAF by MyoD, through p300/ CBP, is crucial for activation of the myogenic program. C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. Univ Rome La Sapienza, Gene Express Lab, Fdn Andrea Cesalpino, Policlin Umberto 1,Ist Clin Med 1, I-00161 Rome, Italy. Univ So Calif, Sch Med, Inst Med Genet, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA. Univ Brescia, Sch Med, Inst Chem, I-25100 Brescia, Italy. Free Univ Berlin, Inst Biochem & Mol Biol, Berlin 33, Germany. Univ Cagliari, Ist Med Interna, I-09124 Cagliari, Italy. Univ Calif San Diego, Ctr Mol Genet, Dept Biol, La Jolla, CA 92093 USA. RP Nakatani, Y (reprint author), NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RI Ogryzko, Vasily/M-6665-2015 OI Ogryzko, Vasily/0000-0002-8548-1389 FU NCI NIH HHS [R01 CA058320, CA59318]; NHLBI NIH HHS [HL52771, HL55005]; Telethon [A.064] NR 49 TC 317 Z9 321 U1 2 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD DEC PY 1997 VL 1 IS 1 BP 35 EP 45 DI 10.1016/S1097-2765(00)80005-2 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZG142 UT WOS:000072970300005 PM 9659901 ER PT J AU Mizuguchi, G Tsukiyama, T Wisniewski, J Wu, C AF Mizuguchi, G Tsukiyama, T Wisniewski, J Wu, C TI Role of nucleosome remodeling factor NURF in transcriptional activation of chromatin SO MOLECULAR CELL LA English DT Article ID RNA-POLYMERASE-II; SOLUBLE NUCLEAR FRACTION; DNA-BINDING DOMAIN; HEAT-SHOCK FACTOR; CELL-FREE SYSTEM; DROSOPHILA EMBRYOS; IN-VITRO; PREINITIATION COMPLEXES; MULTISUBUNIT COMPLEX; GENE-PRODUCTS AB The Drosophila nucleosome remodeling factor (NURF) is a protein complex of four subunits that assists transcription factor-mediated perturbation of nucleosomes in an ATP-dependent manner. We have investigated the role of NURF in activating transcription from a preassembled chromatin template and have found that NURF is able to facilitate transcription mediated by a GAL4 derivative carrying both a DNA binding and an activator domain. Interestingly, once nucleosome remodeling by the DNA binding factor is accomplished, a high level of NURF activity is not continuously required for recruitment of the general transcriptional machinery and transcription for at least 100 nucleotides. Our results provide direct evidence that NURF is able to assist gene activation in a chromatin context, and identify a stage of NURF dependence early in the process leading to transcriptional initiation. C1 NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wu, C (reprint author), NCI, Mol Cell Biol Lab, NIH, Bldg 37,Room 5E-26, Bethesda, MD 20892 USA. NR 70 TC 106 Z9 107 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD DEC PY 1997 VL 1 IS 1 BP 141 EP 150 DI 10.1016/S1097-2765(00)80015-5 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZG142 UT WOS:000072970300015 PM 9659911 ER PT J AU Cong, LN Chen, H Li, YH Zhou, LX McGibbon, MA Taylor, SI Quon, MJ AF Cong, LN Chen, H Li, YH Zhou, LX McGibbon, MA Taylor, SI Quon, MJ TI Physiological role of Akt in insulin-stimulated translocation of GLUT4 in transfected rat adipose cells SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PROTEIN-KINASE-B; PHOSPHATIDYLINOSITOL 3-KINASE; C-AKT; RECEPTOR SUBSTRATE-1; SIGNAL-TRANSDUCTION; SER/THR KINASE; GLUCOSE-UPTAKE; EXPRESSION; ACTIVATION; PATHWAYS AB Stimulation of glucose transport is among the most important metabolic actions of insulin. Studies in adipose cells have demonstrated that insulin stimulates its receptor to phosphorylate tyrosine residues in IRS-1, leading to activation of phosphatidylinositol 3-kinase, which plays a necessary role in mediating the translocation of the insulin-responsive glucose transporter GLUT4 to the cell surface. Akt is a serine-threonine kinase recently identified as a direct downstream target of phosphatidylinositol 3-kinase. A previous study in 3T3-L1 cells showed that overexpression of a constitutively active mutant of Akt is sufficient to recruit GLUT4 to the cell surface. Since effects of overexpression of signaling molecules in tissue culture models do not always reflect physiological function, we have overexpressed a dominant inhibitory mutant of Akt in rat adipose cells to investigate the effects of inhibiting endogenous Akt in a physiologically relevant insulin target cell. Cells were transfected with either wild type (Akt-WT), constitutively active (Akt-myr), or dominant inhibitory (Akt-K179A) forms of Akt, and effects of overexpression of these constructs on insulin-stimulated translocation of a cotransfected epitope-tagged GLUT4 were studied. Overexpression of Akt-WT resulted in significant translocation of GLUT4 to the cell surface even in the absence of insulin. Interestingly, overexpression of Akt-myr resulted in an even larger effect that was independent of insulin. More importantly, overexpression of Akt-K179A (kinase-inactive mutant) significantly inhibited insulin-stimulated translocation of GLUT4. Taken together, our data suggest that Akt is not only capable of stimulating the translocation of GLUT4 but that endogenous Akt is likely to play a significant physiological role in insulin-stimulated glucose uptake in insulin targets such as muscle and adipose tissue. C1 NHLBI,HYPERTENS ENDOCRINE BRANCH,NIH,BETHESDA,MD 20892. NIDDKD,DIABET BRANCH,NIH,BETHESDA,MD 20892. RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 40 TC 265 Z9 271 U1 1 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC PY 1997 VL 11 IS 13 BP 1881 EP 1890 DI 10.1210/me.11.13.1881 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YK065 UT WOS:A1997YK06500001 PM 9415393 ER PT J AU Zhou, J Kumar, TR Matzuk, MM Bondy, C AF Zhou, J Kumar, TR Matzuk, MM Bondy, C TI Insulin-like growth factor I regulates gonadotropin responsiveness in the murine ovary SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; RAT GRANULOSA-CELLS; GENE-EXPRESSION; IGF-I; RECEPTORS; INVIVO; MICE AB The present study shows that insulin-like growth factor I(IGF-I) and FSH receptor (FSHR) mRNAs are selectively coexpressed in a subset of healthy-appearing follicles in murine ovaries, irrespective of cycle stage. Aromatase gene expression, a prime marker for FSH effect, is found only in IGF-I/FSHR-positive follicles, showing that these are healthy, gonadotropin-responsive follicles. Given the striking coexpression of FSHR and IGF-I, we hypothesized that FSH was responsible for follicular IGF-I expression. We found, however, that granulosa cell IGF-I mRNA levels are not reduced in hypophysectomized (+/-PMSG) or FSH knockout mice, indicating that FSH does not have a major role in regulation of granulosa cell IGF-I gene expression. To test the alternative hypothesis that IGF-I regulates FSHR gene expression, we studied ovaries from IGF-I knockout mice. FSHR mRNA was significantly reduced in ovaries from homozygous IGF-I knockout compared with wild type mice and was restored to control values by exogenous IGF-I treatment. The functional significance of the reduced FSHR gene expression in IGF-I knockout ovaries is suggested by reduced aromatase expression and by the failure of their follicles to develop normally beyond the early antral stage. in fact, IGF-I knockout and FSH knockout ovaries appear very similar in terms of arrested follicular development. In summary, we have shown that IGF-I and FSHR are selectively coexpressed in healthy, growing murine follicles and that FSH does not affect IGF-I expression but that IGF-I augments granulosa cell FSHR expression. These data suggest that ovarian IGF-I expression serves to enhance granulosa cell FSH responsiveness by augmenting FSHR expression. C1 BAYLOR COLL MED, DEPT PATHOL, HOUSTON, TX 77030 USA. RP Zhou, J (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, NIH, BLDG 10, ROOM 10N262, BETHESDA, MD 20892 USA. FU NCI NIH HHS [CA60651] NR 27 TC 154 Z9 161 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC PY 1997 VL 11 IS 13 BP 1924 EP 1933 DI 10.1210/me.11.13.1924 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YK065 UT WOS:A1997YK06500005 PM 9415397 ER PT J AU Fraefel, C Jacoby, DR Lage, C Hilderbrand, H Chou, JY Alt, FW Breakefield, XO Majzoub, JA AF Fraefel, C Jacoby, DR Lage, C Hilderbrand, H Chou, JY Alt, FW Breakefield, XO Majzoub, JA TI Gene transfer into hepatocytes mediated by helper virus-free HSV/AAV hybrid vectors SO MOLECULAR MEDICINE LA English DT Article ID GLYCOGEN-STORAGE-DISEASE; ADENOASSOCIATED VIRUS; IN-VIVO; TRANSGENIC MICE; FACTOR-IX; EXPRESSION; THERAPY; LIVER; TYPE-1; CELLS AB Background: Vectors based on herpes simplex virus type 1 (HSV-1) can efficiently transduce hepatocytes in the mouse Liver, and vector genomes can persist for at least 2 months. However, 24 hr after gene transfer, the number of cells that express the transgene decreases rapidly and no transduced cells are detectable after 7 days. Ln this study, we examined the capability of a helper virus-free HSV/AAV hybrid amplicon vector to extend transgene expression in hepatocytes in vivo. Materials and Methods: HSV-1 amplicon or HSV/ AAV hybrid amplicon vectors that express reporter genes from different transcriptional regulatory sequences were packaged into HSV-1 virions using a helper virus-free packaging system. To determine relative transduction efficiencies, vector stocks were titered on four different cell lines, including hamster kidney (BHK21) and human lung (Hs913T) fibroblasts, and mouse (G6Pase-/-) and human (NPLC) hepatocytes. After in vivo injection of vector stocks into mouse liver, tissue sections were examined for reporter gene expression and cellular inflammatory response. Blood samples were collected to measure serum transaminase levels as a biochemical index of liver toxicity. Results: Expression of a reporter gene from liver-specific promoter sequences was consistently more effective in hepatic cells compared with fibroblasts, whereas the opposite was true when using an HSV-1 immediate-early promoter. Expression in hepatocytes in vivo was markedly longer from HSV/AAV hybrid vector compared with traditional HSV-1 amplicon vector: the number of transduced cells (similar to 2% of all hepatocytes) remained stable over 7 days after injection of HSV/AAV hybrid vector, whereas no transduced cells were detected 7 days after gene transfer with standard HSV-1 amplicon vector. The rapid decline in reporter gene expression from standard amplicons was not solely caused by a B or T lymphocyte-mediated immune response, as it also occurred in RAG2-/- mice. Hepatocyte toxicity and cellular inflammatory effects associated with HSV/ AAV hybrid vector-mediated gene transfer were minimal, and readministration of vector stock proved equally effective in naive mice and in animals that received a first vector dose 4 weeks earlier. Conclusions: HSV/AAV hybrid amplicon vectors support gene expression in vivo for considerably longer than do traditional HSV-1 amplicon vectors. Moreover, expression from these vectors does not provoke an overt inflammatory or immune response, allowing efficacious expression following repeated in vivo dosing. These characteristics suggest that such vectors may hold future promise for hepatic gene replacement therapy. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Harvard Univ, Childrens Hosp, Sch Med, Div Endocrinol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Fraefel, C (reprint author), Univ Zurich, Inst Virol, Winterthurerstr 266A, CH-8057 Zurich, Switzerland. FU NCI NIH HHS [CA69246]; NIDCD NIH HHS [DC002281]; NINDS NIH HHS [NS24279] NR 45 TC 71 Z9 73 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD DEC PY 1997 VL 3 IS 12 BP 813 EP 825 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA YN075 UT WOS:000071130600003 PM 9440115 ER PT J AU Jarvis, WD Fornari, FA Auer, KL Freemerman, AJ Szabo, E Birrer, MJ Johnson, CR Barbour, SE Dent, P Grant, S AF Jarvis, WD Fornari, FA Auer, KL Freemerman, AJ Szabo, E Birrer, MJ Johnson, CR Barbour, SE Dent, P Grant, S TI Coordinate regulation of stress- and mitogen-activated protein kinases in the apoptotic actions of ceramide and sphingosine SO MOLECULAR PHARMACOLOGY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the American-Association-for-Cancer-Research CY APR 20-24, 1996 CL WASHINGTON, D.C. SP Amer Assoc Canc Res ID PROGRAMMED CELL-DEATH; NECROSIS-FACTOR-ALPHA; C-JUN; HL-60 CELLS; PHARMACOLOGICAL INHIBITORS; SIGNAL-TRANSDUCTION; DNA FRAGMENTATION; LEUKEMIA-CELLS; INDUCTION; PATHWAY AB We characterized participation of the stress-activated protein kinase (SAPK) cascade in the lethal actions of the cytotoxic lipid messengers ceramide and sphingosine in U937 human monoblastic leukemia cells. Acute exposure of U937 cells to either lipid resulted in loss of proliferative capacity, degradation of genomic DNA, and manifestation of apoptotic cytoarchitecture. Ceramide robustly stimulated p46-JNK1/p54-JNK2 activity and increased expression of c-jun mRNA and c-Jun protein; in contrast, sphingosine moderately stimulated p46-JNK1/p54-JNK2 and failed to modify c-jun/c-Jun expression. Dominant-negative blockade of normal c-Jun activity by transfection with the TAM-67 c-Jun NH2-terminal deletion mutant abolished the lethal actions of ceramide but was without effect on those of sphingosine, indicating that ceramide-related apoptosis is directly dependent on activation of c-Jun, whereas sphingosine-induced cell death proceeds via an unrelated downstream mechanism. Characterization of the mitogen-activated protein kinase (MAPK) cascade in these responses revealed a further functional disparity between the two lipids: basal p42-ERK1/p44-ERK2 activity was gradually reduced by ceramide but immediately and completely suppressed by sphingosine. Moreover, blockade of the MAPK cascade by the aminomethoxyflavone MEK1 inhibitor PD-98059 unexpectedly activated p46-JNK1/p54-JNK2 and induced apoptosis in a manner qualitatively resembling that of sphingosine. Both lipids sharply increased p38-RK activity; selective pharmacological inhibition of p38-RK by the pyridinyl imidazole SE-203580 failed to mitigate the cytotoxicity associated with either ceramide or sphingosine, suggesting that p38-RK is not essential for lipid-induced apoptosis. These findings demonstrate that reciprocal alterations in the SARK and MAPK cascades are associated with the apoptotic influence of either lipid inasmuch as (i) ceramide-mediated lethality is primarily associated with strong stimulation of SARK and weak inhibition of MAPK, whereas (ii) sphingosine-mediated lethality is primarily associated with weak stimulation of SAPK and strong inhibition of MAPK. We therefore propose that leukemic cell survival depends on the maintenance of an imbalance of the outputs from the MAPK and SAPK systems such that the dominant basal influence of the MAPK cascade allows sustained proliferation, whereas acute redirection of this balance toward the SAPK cascade initiates apoptotic cell death. C1 Virginia Commonwealth Univ, Med Coll Virginia, MED HEM ONC, Dept Med, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Med Chem, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Radiat Oncol, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Immunol Microbiol, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol Toxicol, Richmond, VA 23298 USA. NCI, Biomarkers & Prevent Res Branch, NIH, Bethesda, MD 20850 USA. RP Jarvis, WD (reprint author), Virginia Commonwealth Univ, Med Coll Virginia, MED HEM ONC, Dept Med, Box 980230,MCV Stn, Richmond, VA 23298 USA. FU NCI NIH HHS [CA63753, CA09380]; NHLBI NIH HHS [HL09241] NR 40 TC 123 Z9 129 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 1997 VL 52 IS 6 BP 935 EP 947 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YM055 UT WOS:000071023400003 PM 9415703 ER PT J AU Horton, JK Thimmaiah, KN Altenberg, GA Castro, AF Germain, GS Gowda, GK Houghton, PJ AF Horton, JK Thimmaiah, KN Altenberg, GA Castro, AF Germain, GS Gowda, GK Houghton, PJ TI Characterization of a novel bisacridone and comparison with PSC 833 as a potent and poorly reversible modulator of P-glycoprotein SO MOLECULAR PHARMACOLOGY LA English DT Article ID RESISTANCE-MODIFYING AGENTS; MULTIDRUG-RESISTANCE; CELL-LINES; CYCLOSPORINE-A; EXTRACELLULAR PH; PLASMA-MEMBRANE; BINDING SITE; SDZ PSC-833; EXPRESSION; VERAPAMIL AB Novel compounds, composed of two acridone moieties connected by a propyl or butyl spacer, were synthesized and tested as potential modulators of P-glycoprotein (P-gp)-mediated multidrug resistance. The propyl derivative 1,3-bis(9-oxoacridin-10-yl)-propane (PBA) was extremely potent and, at a concentration of 1 mu M, increased steady state accumulation of vinblastine (VLB) approximate to 9-fold in the multidrug-resistant cell line KB8-5. In contrast to the readily reversible effects of VRP and cyclosporin A on VLB uptake and similar to the effects of the cyclosporin analog PSC 833, this modulation by PBA was not fully reversed 6-8 hr after transfer of cells to PBA-free medium. Continuous exposure to 3 mu M PBA was nontoxic and could completely reverse VLB resistance in KB8-5 cells. Consistent with its effects on VLB transport, the drug resistance-modulating effect of PSC 833 was significantly more persistent than that of VRP. However, the effect of PEA was, like that of VRP, rapidly reversed once the modulator was removed from the extracellular environment. PEA was able to compete with radiolabeled azidopine for binding to P-gp and to stimulate P-gp ATPase activity, However, both the steady state accumulation of PEA and the rate of efflux of PBA were similar in drug-sensitive KB3-1 and drug-resistant KB8-5 cells, suggesting that this compound is not efficiently transported by P-gp. These results indicate that PEA represents a new class of potent and poorly reversible synthetic modulators of P-gp-mediated VLB transport. C1 Univ Texas, Med Branch, Sealy Ctr Mol Sci, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Physiol & Biophys, Galveston, TX 77555 USA. Univ Mysore, Dept Studies Chem, Mysore 570006, Karnataka, India. St Jude Childrens Res Hosp, Dept Mol Pharmacol, Memphis, TN 38101 USA. RP Horton, JK (reprint author), NIEHS, Struct Biol Lab, MD F301, POB 12233,TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM hortonl@niehs.nih.gov FU NCI NIH HHS [CA21675, CA23099, CA72783] NR 39 TC 15 Z9 15 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 1997 VL 52 IS 6 BP 948 EP 957 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YM055 UT WOS:000071023400004 PM 9415704 ER PT J AU Spivak, CE Beglan, CL Seidleck, BK Hirshbein, LD Blaschak, CJ Uhl, GR Surratt, CK AF Spivak, CE Beglan, CL Seidleck, BK Hirshbein, LD Blaschak, CJ Uhl, GR Surratt, CK TI Naloxone activation of mu-opioid receptors mutated at a histidine residue lining the opioid binding cavity SO MOLECULAR PHARMACOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; SITE-DIRECTED MUTAGENESIS; PHARMACOLOGICAL CHARACTERIZATION; FUNCTIONAL EXPRESSION; OPIATE RECEPTOR; LIGAND-BINDING; AMINO-ACIDS; CLONING; BACTERIORHODOPSIN; ACETYLCHOLINE AB The mu-opioid receptor is the principal site of action in the brain by which morphine, other opiate drugs of abuse, and endogenous opioid peptides effect analgesia and alter mood. A member of the seven-transmembrane domain (TM) G protein-coupled receptor (GPCR) superfamily, the mu-opioid receptor modulates ion channels and second messenger effecters in an opioid agonist-dependent fashion that is reversible by the classic opiate antagonist naloxone. Mutation of a histidine residue (His297) in TM 6 afforded agonist-like G protein-coupled signal transduction mediated by naloxone and other alkaloid antagonists and enhanced the intrinsic activity of documented alkaloid partial agonists, including buprenorphine. The intrinsic activities of all opioid peptide agonists and antagonists tested were not altered at the His297 mutant receptors. Consistent with a role for the TM 6 histidine in maintaining high affinity binding sites for opioid agonists and antagonists, opioid ligand-dependent protection of this residue from a histidine-specific alkylating agent indicated that the His297 side chain is positioned in or very near the binding cavity. The TM 6 His297 mutants identify a discrete region of the receptor critical for determining whether a specific drug pharmacophore triggers receptor activation. Because many GPCRs possess a similarly positioned TM histidine residue, our findings with the mu-opioid receptor may extend to these receptors and potentially serve as a model for rational design of therapeutic GPCR partial agonists and antagonists. C1 NIDA, Cellular Neurobiol Branch, Intramural Res Program, Baltimore, MD 21224 USA. NIDA, Mol Neurobiol Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Surratt, CK (reprint author), NIDA, Cellular Neurobiol Branch, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 40 TC 44 Z9 44 U1 0 U2 7 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 1997 VL 52 IS 6 BP 983 EP 992 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YM055 UT WOS:000071023400008 PM 9415708 ER PT J AU Neamati, N Hong, HX Sunder, S Milne, GWA Pommier, Y AF Neamati, N Hong, HX Sunder, S Milne, GWA Pommier, Y TI Potent inhibitors of human immunodeficiency virus type 1 integrase: Identification of a novel four-point pharmacophore and tetracyclines as novel inhibitors SO MOLECULAR PHARMACOLOGY LA English DT Article ID DRUG INFORMATION-SYSTEM; ACID PHENETHYL ESTER; CATALYTIC DOMAIN; METAL-BINDING; DNA CLEAVAGE; SITE; TRANSCRIPTION; REPLICATION; DERIVATIVES; RESIDUES AB A four-point pharmacophore was constructed from energy-minimized structures of chicoric acid and dicaffeoylquinic acid. The search of 206,876 structures in the National Cancer Institute 3D database yielded 179 compounds that contain this pharmacophore. Thirty-nine of these compounds were tested in an in vitro assay specific for human immunodeficiency virus type 1 integrase (IN). Each retrieved structure was fit to the pharmacophore, and the conformation that afforded the best fit was identified. Twenty of the 39 compounds tested exhibited IC50 values of <20 mu M. Among the most potent inhibitors, tetracyclines emerged as a new class of inhibitors. Although the parent tetracycline exhibited marginal potency against purified IN, all substituted tetracyclines tested showed 5-100-fold increased potency. Disintegration assays with truncated IN mutants indicated that tetracyclines inhibit the IN catalytic core domain. To investigate whether chelation of divalent metals is implicated in differential potency of tetracyclines, enzyme assays were performed in the presence of both Mn2+ or Mg2+; no significance difference in potency was observed. Rolitetracycline inhibited IN/DNA complex formation in the presence of EDTA, which suggests that inhibition was metal independent. Rolitetracycline reversed DNA binding of IN after the complex was allowed to form before the addition of drug. Selectivity of tetracyclines was also examined in an assay specific for topoisomerase I, and none of the tetracyclines tested induced topoisomerase I-mediated cleavable complex or inhibited camptothecin-induced cleavable complex, Remarkable potency against the IN in the absence of divalent metals and the core enzyme-coupled with water solubility makes tetracyclines potential candidates for X-ray crystal structure determination with IN. C1 NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Med Chem Lab, Div Basic Sci, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bldg 37,Room 5DO2, Bethesda, MD 20892 USA. NR 39 TC 86 Z9 88 U1 1 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 1997 VL 52 IS 6 BP 1041 EP 1055 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YM055 UT WOS:000071023400015 PM 9415714 ER PT J AU Jiang, JJ Jordan, SJ Barr, DP Gunther, MR Maeda, H Mason, RP AF Jiang, JJ Jordan, SJ Barr, DP Gunther, MR Maeda, H Mason, RP TI In vivo production of nitric oxide in rats after administration of hydroxyurea SO MOLECULAR PHARMACOLOGY LA English DT Article ID ELECTRON-SPIN-RESONANCE; SICKLE-CELL DISEASE; RIBONUCLEOTIDE REDUCTASE; DERIVATIVES; INHIBITION; COMPLEXES; RADICALS; ISCHEMIA; THERAPY; EPR AB The metabolism of nitrovasodilators such as glyceryl trinitrate and nitroprusside provides the active moiety of these drugs (that is, nitric oxide). This process is not limited to the known nitrovasodilators, but also occurs with nitroaromatic antimicrobials. Here we report that the administration of hydroxyurea, an antitumor drug, to rats at pharmacological doses formed detectable nitrosyl hemoglobin, which increased with dose. At higher doses, nitrosyl hemoprotein complexes could also be detected in liver tissue. [(15)N]hydroxyurea was synthesized and compared with [(14)N]hydroxyurea. These observations verified that nitric oxide detected as nitrosyl hemoglobin or nitrosyl hemoprotein complexes in rats was the result of the metabolism of hydroxyurea. The time course and dose-dependence of nitric oxide generation were also investigated. Hydroxyurea's antineoplastic activity is caused by its direct action on ribonucleotide reductase, the rate-limiting enzyme in DNA synthesis. Because nitric oxide also inhibits ribonucleotide reductase, this metabolite may supplement this action of hydroxyurea. In addition, the known ability of hydroxyurea to ease the pain of sickle cell anemia patients may be the result of vasodilation by the drug-derived nitric oxide. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Kumamoto Univ Med, Dept Microbiol, Kumamoto 860, Japan. RP Mason, RP (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233,MD F0-01, Res Triangle Pk, NC 27709 USA. EM mason4@niebs.nih.gov RI Maeda, Hiroshi/N-4471-2016 NR 40 TC 81 Z9 85 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 1997 VL 52 IS 6 BP 1081 EP 1086 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YM055 UT WOS:000071023400019 PM 9415718 ER PT J AU Cannon, RE Tennant, RW AF Cannon, RE Tennant, RW TI Shock toxicology with transgenics SO NATURE BIOTECHNOLOGY LA English DT News Item ID CARCINOGENS RP Cannon, RE (reprint author), NIEHS,LAB ENVIRONM CARCINOGENESIS & MUTAGENESIS,PO BOX 12233,RES TRIANGLE PK,NC 27709, USA. NR 5 TC 5 Z9 5 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD DEC PY 1997 VL 15 IS 13 BP 1349 EP 1349 DI 10.1038/nbt1297-1349 PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA YK361 UT WOS:A1997YK36100024 PM 9415885 ER PT J AU Warner, HR Johnson, TE AF Warner, HR Johnson, TE TI Parsing age, mutations and time SO NATURE GENETICS LA English DT Editorial Material ID OXIDATIVE DAMAGE; DNA; ACCUMULATION; REPAIR; MICE C1 UNIV COLORADO,INST BEHAV GENET,BOULDER,CO 80309. RP Warner, HR (reprint author), NCI,BIOL AGING PROGRAM,BETHESDA,MD 20892, USA. NR 15 TC 6 Z9 6 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 1997 VL 17 IS 4 BP 368 EP 370 DI 10.1038/ng1297-368 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA YJ924 UT WOS:A1997YJ92400004 PM 9398828 ER PT J AU Everett, LA Glaser, B Beck, JC Idol, JR Buchs, A Heyman, M Adawi, F Hazani, E Nassir, E Baxevanis, AD Sheffield, VC Green, ED AF Everett, LA Glaser, B Beck, JC Idol, JR Buchs, A Heyman, M Adawi, F Hazani, E Nassir, E Baxevanis, AD Sheffield, VC Green, ED TI Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS) SO NATURE GENETICS LA English DT Article ID HORMONE RECEPTOR-BETA; CONGENITAL CHLORIDE DIARRHEA; PROTEIN-CODING REGIONS; THYROID-HORMONE; HUMAN GENOME; WAARDENBURG SYNDROME; HEARING-LOSS; SEQUENCE; LINKAGE; MAPS AB Pendred syndrome is a recessively inherited disorder with the hallmark features of congenital deafness and thyroid goitre, By some estimates, the disorder may account for upwards of 10% of hereditary deafness, Previous genetic linkage studies localized the gene to a broad interval on human chromosome 7q22-31.1. Using a positional cloning strategy, we have identified the gene (PDS) mutated in Pendred syndrome and found three apparently deleterious mutations, each segregating with the disease in the respective families in which they occur. PDS produces a transcript of approximately 5 kb that was found to be expressed at significant levels only in the thyroid. The predicted protein, pendrin, is closely related to a number of known sulphate transporters. These studies provide compelling evidence that defects in pendrin cause Pendred syndrome thereby launching a new area of investigation into thyroid physiology, the pathogenesis of congenital deafness and the role of altered sulphate transport in human disease. C1 NATL HUMAN GENOME RES INST,GENOME TECHNOL BRANCH,NIH,BETHESDA,MD 20892. HADASSAH UNIV HOSP,DEPT ENDOCRINOL & METAB,IL-91120 JERUSALEM,ISRAEL. UNIV IOWA,DEPT PEDIAT,DIV MED GENET,IOWA CITY,IA 52242. RIVKA ZEEV HOSP,DEPT ENDOCRINOL,IL-16950 ZAFAD,ISRAEL. WESTERN GALILEE NAHARIYA HOSP,DEPT INTERNAL MED,IL-22100 NAHARIYYA,ISRAEL. FU NHGRI NIH HHS [R01-HG00457] NR 74 TC 696 Z9 750 U1 0 U2 22 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 1997 VL 17 IS 4 BP 411 EP 422 DI 10.1038/ng1297-411 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA YJ924 UT WOS:A1997YJ92400021 PM 9398842 ER PT J AU Barlow, C Brown, KD Deng, CX Tagle, DA WynshawBoris, A AF Barlow, C Brown, KD Deng, CX Tagle, DA WynshawBoris, A TI Atm selectively regulates distinct p53-dependent cell-cycle checkpoint and apoptotic pathways SO NATURE GENETICS LA English DT Article ID RADIATION-INDUCED APOPTOSIS; ATAXIA-TELANGIECTASIA; IONIZING-RADIATION; P53 PROTEIN; DNA-DAMAGE; MICE; INSTABILITY; SUPPRESSION; INDUCTION; PARADIGM AB Atm is part of a pathway that responds to DNA damage from ionizing radiation (IR). This pathway involves p53, as Atm-deficient cell lines and mice are defective in p53 induction after IR1-5. p53 is a multi-functional protein that simultaneously regulates distinct downstream pathways controlling cell-cycle progression and apoptosis(6,7). However, the mechanisms by which p53 differentially activates downstream pathways are unknown. To determine the relationship between Atm and p53, we examined cell-cycle and apoptotic responses in Atm-, p53- (ref. 8) and p21-deficient(9) mice after IR in the whole animal, As expected, p53 protein levels were not induced by IR in thymus of Atm-deficient mice. IR-induced cell-cycle checkpoint function was also defective, and induction of p21 was attenuated in thymus from Atm-deficient mice, However, IR-induced apoptosis and Bar induction were completely normal; both of which are mediated by p53. IR-induced thymic apoptosis was suppressed in Atm/p53 double-mutant mice but not in Atm/p21 double mutants, demonstrating p53 dependence and Atm independence. Thus, Atm deficiency results in lack of p53 induction by IR, but only selective disruption of p53-dependent functions, Our results support a model in which upstream effecters such as Atm selectively activate p53 to regulate specific downstream pathways, providing a mechanism for controlling distinct cell-cycle and apoptotic responses. C1 NIDDKD,LAB GENET DIS RES,NATL HUMAN GENOME RES INST,NIH,BETHESDA,MD 20892. NIDDKD,LAB GENE TRANSFER,NATL HUMAN GENOME RES INST,NIH,BETHESDA,MD 20892. NIDDKD,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20892. RI deng, chuxia/N-6713-2016 NR 31 TC 167 Z9 168 U1 0 U2 3 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 1997 VL 17 IS 4 BP 453 EP 456 DI 10.1038/ng1297-453 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA YJ924 UT WOS:A1997YJ92400028 PM 9398849 ER PT J AU Barlow, C Liyanage, M Moens, PB Deng, CX Ried, T WynshawBoris, A AF Barlow, C Liyanage, M Moens, PB Deng, CX Ried, T WynshawBoris, A TI Partial rescue of the prophase I defects of Atm-deficient mice by p53 and p21 null alleles SO NATURE GENETICS LA English DT Article ID ATAXIA-TELANGIECTASIA; PARADIGM AB Patients with the human disorder ataxia-telangiectasia (A-T; refs 1,2) and Atm-deficient mice(3-5) have a pleiotropic phenotype that includes infertility, Here we demonstrate that male gametogenesis is severely disrupted in Atm-deficient mice in the earliest stages of meiotic prophase I, resulting in apoptotic degeneration. Atm is required for proper assembly of Rad51 onto the chromosomal axial elements during meiosis. In addition, p53, p21 and Bar are elevated in testes from Atm-deficient mice. To determine whether these elevated protein levels are important factors in the meiotic disruption of Atm-deficient mice, we analysed the meiotic phenotype of Atm/p53 or Atm/p21 double mutants. In these double mutants, meiosis progressed to later stages but was only partly rescued. Assembly of Rad51 foci on axial elements remained defective, and gametogenesis proceeded only to pachytene of prophase I. Previous results demonstrated that mice homozygous for a null mutation in Rad51 (ref. 6) display an early embryonic lethal phenotype that can be partly rescued by removing p53 and/or p21. Because Atm-deficient mice are viable but completely infertile, our studies suggest that the Rad51 assembly defects and elevated levels of p53, p21 and Bar represent tissue-specific responses to the absence of Atm. C1 NIDDKD,LAB GENET DIS RES,NATL HUMAN GENOME RES INST,NIH,BETHESDA,MD 20892. NIDDKD,GENOME TECHNOL BRANCH,NATL HUMAN GENOME RES INST,NIH,BETHESDA,MD 20892. NIDDKD,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20892. YORK UNIV,DEPT BIOL,DOWNSVIEW,ON M3J 1P3,CANADA. RI deng, chuxia/N-6713-2016 NR 23 TC 98 Z9 99 U1 3 U2 3 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 1997 VL 17 IS 4 BP 462 EP 466 DI 10.1038/ng1297-462 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA YJ924 UT WOS:A1997YJ92400030 PM 9398851 ER PT J AU Jhappan, C Morse, HC Fleischmann, RD Gottesman, MM Merlino, G AF Jhappan, C Morse, HC Fleischmann, RD Gottesman, MM Merlino, G TI DNA-PKcs: a T-cell tumour suppressor encoded at the mouse scid locus SO NATURE GENETICS LA English DT Article ID DEPENDENT PROTEIN-KINASE; SEVERE COMBINED IMMUNODEFICIENCY; STRAND-BREAK-REPAIR; ATAXIA-TELANGIECTASIA GENE; V(D)J RECOMBINATION; CATALYTIC SUBUNIT; TRANSGENIC MICE; MUTATION; PHOSPHODIESTERASE; REQUIREMENT AB Severe combined immunodeficiency (SCID) mice(1) are defective in their ability to rearrange their variable (V), diversity (D) and joining (J) genetic elements to generate functional immuno-globulin tig) and T-cell receptor (TCR) molecules; as a result, they lack mature B and T cells(2). These mice are highly sensitive to ionizing radiation, suggesting that the product of the scid gene plays a critical role in both V(D)I recombination and DNA double-strand break repair(3-5). Recent studies suggest that the SCID defect lies in the gene encoding the catalytic subunit of DNA-dependent protein kinase (DNA-PK; refs 6-8), a nuclear protein made up of the Ku 70 and Ku 86 subunits as well as the large catalytic subunit, DNA-PKcs(9,10). Other reports have implied that the SCID phenotype correlates with nonsense mutations at the extreme 3' end of Prkdc, the DNA-PKcs gene(11-14). The identity of the gene remains in doubt, however, because the consequences of genetic inactivation of Prkdc have not been determined. This study shows that complete inactivation of Prkdc in a novel insertional mouse mutant recapitulates the SCID phenotype and that Prkdc and scid are allelic, Significantly, DNA-PKcs null mice demonstrate complete penetrance of thymic lymphoblastic lymphomas, strongly suggesting that Prkdc functions in mice as a T-cell tumour suppressor and, by virtue of its association with DNA repair and recombination, belongs to the 'caretaker' class of tumour-suppressor genes that includes ATM, BRCA1 and BRCA2 (ref. 15). C1 NIAID,IMMUNOPATHOL LAB,NIH,BETHESDA,MD 20892. NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. RP Jhappan, C (reprint author), NCI,MOL BIOL LAB,NIH,37 CONVENT DR,BETHESDA,MD 20892, USA. OI Morse, Herbert/0000-0002-9331-3705 NR 30 TC 105 Z9 105 U1 0 U2 1 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 1997 VL 17 IS 4 BP 483 EP 486 DI 10.1038/ng1297-483 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA YJ924 UT WOS:A1997YJ92400035 PM 9398856 ER PT J AU Ram, Z Culver, KW Oshiro, EM Viola, JJ DeVroom, HL Otto, E Long, ZF Chiang, Y McGarrity, GEJ Muul, LM Katz, D Blaese, RM Oldfield, EH AF Ram, Z Culver, KW Oshiro, EM Viola, JJ DeVroom, HL Otto, E Long, ZF Chiang, Y McGarrity, GEJ Muul, LM Katz, D Blaese, RM Oldfield, EH TI Therapy of malignant brain tumors by intratumoral implantation of retroviral vector-producing cells SO NATURE MEDICINE LA English DT Article ID THYMIDINE KINASE GENE; EXPERIMENTAL GLIOMAS; RAT-BRAIN; IN-VIVO; TRANSDUCTION; REGRESSION; GANCICLOVIR; INVIVO AB Intratumoral implantation of murine cells modified to produce retroviral vectors containing the herpes simplex virus-thymidine kinase (HSV-TK) gene induces regression of experimental brain tumors in rodents after ganciclovir (GCV) administration. We evaluated this approach in 15 patients with progressive growth of recurrent malignant brain tumors. Antitumor activity was detected in five of the smaller tumors (1.4 +/- 0.5 ml). In situ hybridization for HSV-TK demonstrated survival of vector-producing cells (VPCs) at 7 days but indicated limited gene transfer to tumors, suggesting that indirect, "bystander," mechanisms provide local antitumor activity in human tumors. However, the response of only very small tumors in which a high density of vector-producing cells had been placed suggests that techniques to improve delivery and distribution of the therapeutic gene will need to be developed if clinical utility is to be achieved with this approach. C1 NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA. NCI, Metab Branch, Bethesda, MD 20892 USA. Genet Therapy Inc, Gaithersburg, MD USA. Natl Ctr Human Genome Res, Clin Gene Therapy Branch, Bethesda, MD 20892 USA. NINDS, Off Clin Director, Bethesda, MD 20892 USA. NINDS, Pathol Lab, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), NINDS, Surg Neurol Branch, Bldg 36,Rm 4D04,10-5D37,10 Ctr Dr, Bethesda, MD 20892 USA. NR 29 TC 532 Z9 540 U1 0 U2 3 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 1997 VL 3 IS 12 BP 1354 EP 1361 DI 10.1038/nm1297-1354 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA YZ389 UT WOS:000072249500031 PM 9396605 ER PT J AU Laske, DW Youle, RJ Oldfield, EH AF Laske, DW Youle, RJ Oldfield, EH TI Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors SO NATURE MEDICINE LA English DT Article ID TRANSFERRIN RECEPTOR; MONOCLONAL-ANTIBODY; NATIONAL SURVEY; NERVOUS-SYSTEM; PROTEIN TOXINS; CELL LYMPHOMA; RICIN; IMMUNOTOXIN; CARCINOMA; DELIVERY AB We investigated regional therapy of recurrent malignant brain tumors with transferrin-CRM107, a conjugate of human transferrin (Tf) and a genetic mutant of diphtheria toxin (CRM107) that lacks native toxin binding. Physiological barriers to delivering proteins to tumor and surrounding infiltrated brain were circumvented with high-flow interstitial microinfusion. At least a 50% reduction in tumor volume on magnetic resonance imaging (MRI) occurred in 9 of 15 patients who could be evaluated (60%), including two complete responses. Peritumoral toxicity developed 1-4 weeks after treatment in three of three patients at 1.0 mu g/ml, but in zero of nine patients treated at lower concentrations. No symptomatic systemic toxicity occurred. Regional perfusion with Tf-CRM107 produces tumor responses without systemic toxicity in patients with malignant brain tumors refractory to conventional therapy. Direct interstitial infusion can be used successfully to distribute a large protein in the tumor and infiltrated brain surrounding the tumor. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,10-5D37, Bethesda, MD 20892 USA. NR 42 TC 357 Z9 366 U1 4 U2 12 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 1997 VL 3 IS 12 BP 1362 EP 1368 DI 10.1038/nm1297-1362 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA YZ389 UT WOS:000072249500032 PM 9396606 ER PT J AU Zaitseva, M Blauvelt, A Lee, S Lapham, CK Klaus-Kovtun, V Mostowski, H Manischewitz, J Golding, H AF Zaitseva, M Blauvelt, A Lee, S Lapham, CK Klaus-Kovtun, V Mostowski, H Manischewitz, J Golding, H TI Expression and function of CCR5 and CXCR4 on human Langerhans cells and macrophages: Implications for HIV primary infection SO NATURE MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; DENDRITIC CELLS; RHESUS MACAQUES; LYMPHOCYTE SUBSETS; GENITAL-TRACT; TRANSMISSION; ANTIGEN; BLOOD; REPLICATION; VARIANTS AB Transmission of HIV-1 is predominantly restricted to macrophage (M Phi)-tropic strains. Langerhans cells (LCs) in mucosal epithelium, as well as macrophages located in the submucosal tissues, may be initial targets for HIV-1. This study was designed to determine whether restricted transmission of HIV-1 correlates with expression and function of HIV-1 co-receptors on LCs and macrophages. Using polyclonal rabbit IgGs specific for the HIV co-receptors cytokines CXCR4 and CCR5, we found that freshly isolated epidermal LCs (resembling resident mucosal LCs) expressed CCR5, but not CXCR, on their surfaces. In concordance with surface expression, fresh LCs fused with M Phi-tropic but not with T-tropic HIV-1 envelopes. However, fresh LCs did contain intracellular CXCR4 protein that was transported to the surface during in vitro culture. Macrophages expressed high levels of both co-receptors on their surfaces, but only CCR5 was functional in a fusion assay. These data provide several possible explanations for the selective transmission of M Phi-tropic HIV variants and for the resistance to infection conferred by the CCR5 deletion. C1 US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Cell & Gene Therapy, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NCI, Dermatol Branch, Bethesda, MD 20892 USA. RP Golding, H (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bldg 29B,Room 4NN04,HFM 454,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 43 TC 287 Z9 291 U1 1 U2 6 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 1997 VL 3 IS 12 BP 1369 EP 1375 DI 10.1038/nm1297-1369 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA YZ389 UT WOS:000072249500033 PM 9396607 ER PT J AU Soldan, SS Berti, R Salem, N Secchiero, P Flamand, L Calabresi, PA Brennan, MB Maloni, HW McFarland, HF Lin, HC Patnaik, M Jacobson, S AF Soldan, SS Berti, R Salem, N Secchiero, P Flamand, L Calabresi, PA Brennan, MB Maloni, HW McFarland, HF Lin, HC Patnaik, M Jacobson, S TI Association of human herpes virus 6 (HHV-6) with multiple sclerosis: Increased IgM response to HHV-6 early antigen and detection of serum HHV-6 DNA SO NATURE MEDICINE LA English DT Article ID HUMAN HERPESVIRUS-6; INFECTION; EXACERBATIONS; ANTIBODIES AB Viruses have long been suggested to be involved in the etiology of multiple sclerosis (MS)(1). This suggestion is based on (1) epidemiological evidence of childhood exposure to infectious agents and increase in disease exacerbations with viral infection(1,2); (2) geographic association of disease susceptibility with evidence of MS clustering(3-4); (3) evidence that migration to and from high-risk areas influences the likelihood of developing MS (refs. 2, 5); (4) abnormal immune responses to a variety of viruses(6,7); and (5) analogy with animal models and other human diseases in which viruses can cause diseases with long incubation periods, a relapsing-remitting course, and demyelination(1,2). Many of these studies involve the demonstration of increased antibody titers to a particular virus, whereas some describe isolation of virus from MS material. However, no virus to date has been definitively associated with this disease. Recently, human herpesvirus 6 (HHV-6), a newly described beta-herpes virus that shares homology with cytomegalovirus (CMV)(8), has been reported to be present in active MS plaques(9). In order to extend these observations, we have demonstrated increased IgM serum antibody responses to HHV-6 early antigen (p41/38) in patients with relapsing-remitting MS (RRMS), compared with patients with chronic progressive MS (CPMS), patients with other neurologic disease (OND), patients with other autoimmune disease (OID), and normal controls. Given the ubiquitous nature of this virus and the challenging precedent of correlating antiviral antibodies with disease association(10), these antibody studies have been supported by the detection of HHV-6 DNA from samples of MS serum as a marker of active viral infection. C1 NINDS, Viral Immunol Sect, Bethesda, MD 20892 USA. Specialty Labs Inc, Santa Monica, CA 90404 USA. Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. RP Jacobson, S (reprint author), NINDS, Viral Immunol Sect, Bldg 10,Room 5B-16,9000 Rockville Pike, Bethesda, MD 20892 USA. RI secchiero, paola/G-9689-2015 OI secchiero, paola/0000-0003-4101-7987 NR 20 TC 307 Z9 309 U1 1 U2 8 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 1997 VL 3 IS 12 BP 1394 EP 1397 DI 10.1038/nm1297-1394 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA YZ389 UT WOS:000072249500037 PM 9396611 ER PT J AU Khan, AR Cherney, MM Tarasova, NI James, MNG AF Khan, AR Cherney, MM Tarasova, NI James, MNG TI Structural characterization of activation 'intermediate 2' on the pathway to human gastricsin SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID AMINO-ACID-SEQUENCE; PEPSINOGEN-A; ANGSTROM RESOLUTION; ASPARTIC PROTEINASE; NUCLEOTIDE-SEQUENCE; HUMAN PROGASTRICSIN; PORCINE PEPSINOGEN; CYSTEINE PROTEASE; CRYSTAL-STRUCTURE; PROCATHEPSIN-B AB The crystal structure of an activation intermediate of human gastricsin has been determined at 2.4 Angstrom resolution. The human digestive enzyme gastricsin (pepsin C) is an aspartic proteinase that is synthesized as the inactive precursor (zymogen) progastricsin (pepsinogen C or hPGC), In the zymogen, a positively-charged N-terminal prosegment of 43 residues (Ala 1p-Leu 43p; the suffix 'p' refers to the prosegment) sterically prevents the approach of a substrate to the active site. Zymogen conversion occurs in an autocatalytic and stepwise fashion at low pH through the formation of intermediates. The structure of the non-covalent complex of a partially-cleaved peptide of the prosegment (Ala 1p-Phe 26p) with mature gastricsin (Ser l-Ala 329) suggests an activation pathway that may be common to all gastric aspartic proteinases. C1 UNIV ALBERTA, DEPT BIOCHEM, MRC, GRP PROT STRUCT & FUNCT, EDMONTON, AB T6G 2H7, CANADA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, MOL ASPECTS DRUG DESIGN SECT, FREDERICK, MD 21702 USA. NR 45 TC 28 Z9 30 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD DEC PY 1997 VL 4 IS 12 BP 1010 EP 1015 DI 10.1038/nsb1297-1010 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA YK578 UT WOS:A1997YK57800014 PM 9406551 ER PT J AU Resnick, SM Metter, EJ Zonderman, AB AF Resnick, SM Metter, EJ Zonderman, AB TI Estrogen replacement therapy and longitudinal decline in visual memory - A possible protective effect? SO NEUROLOGY LA English DT Article ID DENDRITIC SPINE DENSITY; DEMENTIA-ALZHEIMERS TYPE; OLDER WOMEN; POSTMENOPAUSAL WOMEN; GLUCOSE-UTILIZATION; MENSTRUAL-CYCLE; BASAL FOREBRAIN; FEMALE RATS; DISEASE; ESTRADIOL AB Estrogen replacement therapy (ERT) is increasingly recommended for postmenopausal women due to its beneficial effects on physical health in older women. Recent studies have suggested that ERT may have a protective effect on cognitive function and may reduce the risk of Alzheimer's disease. In the present study we test the hypothesis that ERT may have a protective effect on memory in nondemented women. Data on hormonal status and memory were examined in 288 postmenopausal women in the Baltimore Longitudinal Study of Aging. One hundred sixteen women who reported that they were receiving ERT during a cognitive assessment were compared with 172 women who had never received ERT. Women who were receiving ERT had fewer errors on the Benton Visual Retention Test (BVRT), a measure of short-term visual memory, visual perception, and constructional skills. Furthermore, ERT appeared to protect against age changes in BVRT performance in a subgroup of 18 women for whom BVRT data were available before and during treatment with ERT. These findings suggest that ERT may protect against memory decline in nondemented postmenopausal women and offer further support for a beneficial role of estrogen on cognitive function in aging women. C1 NIA, Gerontol Res Ctr, Lab Personal & Cognit, Baltimore, MD 21224 USA. NIA, Longitudinal Studies Branch, Baltimore, MD 21224 USA. RP Resnick, SM (reprint author), NIA, Gerontol Res Ctr, Lab Personal & Cognit, 4940 Eastern Ave,Box 03, Baltimore, MD 21224 USA. OI Zonderman, Alan B/0000-0002-6523-4778 NR 55 TC 207 Z9 211 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 1997 VL 49 IS 6 BP 1491 EP 1497 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA YL495 UT WOS:000070961600002 PM 9409335 ER PT J AU Higgins, JJ Morton, H Patronas, N Nee, LE AF Higgins, JJ Morton, H Patronas, N Nee, LE TI An autosomal recessive disorder with posterior column ataxia and retinitis pigmentosa SO NEUROLOGY LA English DT Article ID DEGENERATION AB We report an autosomal recessive form of ataxia that is not allelic to Friedreich's disease in six individuals from a large kindred with family origins traced to a common founder of German-Swiss descent. The disorder begins during early childhood with a concentric contraction of the visual fields and proprioceptive loss. Eventually blindness, a severe sensory ataxia, achalasia, scoliosis, and inanition develop by the third decade. Inversion recovery MRIs of the spinal cord in affected individuals demonstrate a hyperintense signal in the posterior columns. Finding the gene responsible for this disorder may aid in our understanding of the mechanisms that cause sensory neuronal degeneration. C1 New York State Dept Hlth, Wadsworth Ctr Labs & Res, Albany, NY 12201 USA. NINDS, Clin Neurogenet Unit, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. Clin Special Children, Strasburg, PA USA. NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Higgins, JJ (reprint author), New York State Dept Hlth, Wadsworth Ctr Labs & Res, Pob 509, Albany, NY 12201 USA. NR 9 TC 17 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 1997 VL 49 IS 6 BP 1717 EP 1720 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA YL495 UT WOS:000070961600044 PM 9409377 ER PT J AU McCann, UD Morgan, CM Geraci, M Slate, SO Murphy, DL Post, RM AF McCann, UD Morgan, CM Geraci, M Slate, SO Murphy, DL Post, RM TI Effects of the 5-HT3 antagonist, ondansetron, on the behavioral and physiological effects of pentagastrin in patients with panic disorder and social phobia SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE cholecystokinin (CCK); neuropeptides; anxiety disorders; serotonin ID ELEVATED PLUS-MAZE; CHOLECYSTOKININ-TETRAPEPTIDE; ENHANCED SENSITIVITY; RECEPTOR ANTAGONIST; HEALTHY-VOLUNTEERS; ANXIETY; ATTACKS; RELEASE; RAT; NEUROPEPTIDES AB Pentagastrin, a cholecystokinin (CCK) agonist, produces anxiety and panic in patients with panic disorder and social phobia. Preclinical data suggests that pentagastrin-induced anxiogenesis may be mediated via 5-HT3 receptors. In the present study, 14 patients with panic disorder or social phobia underwent pharmacological challenge in three conditions: (1) pretreatment with saline followed by pentagastrin infusion; (2) pretreatment with ondansetron followed by pentagastrin infusion; and (3) pretreatment with saline followed by saline infusion. As expected, pentagastrin administration led to increased anxiety, physical symptoms of panic attacks, pulse, plasma adrenocorticotropic hormone (ACTH), and cortisol. Pentagastrin's behavioral effects were not blocked by ondansetron, and in fact, tended to be exaggerated, Ondansetron pretreatment did not alter the pentagastrin-induced cortisol increase but significantly prolonged the pentagastrin-induced increase in ACTH. These findings suggest that pentagastrin's behavioral effects are not mediated by 5HT(3) receptors. Mechanisms by which peripherally administered CCK agonists lead to anxiety remain to be elucidated. Published by Elsevier Science Inc. C1 NIMH,CLIN SCI LAB,NIH,BETHESDA,MD 20892. RP McCann, UD (reprint author), NIMH,UNIT ANXIETY DISORDERS,BIOL PSYCHIAT BRANCH,NIH,BLDG 10,ROOM 3N-212,MSC 1272,10 CTR DR,BETHESDA,MD 20892, USA. NR 47 TC 22 Z9 23 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 1997 VL 17 IS 6 BP 360 EP 369 DI 10.1016/S0893-133X(97)00085-7 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA YG564 UT WOS:A1997YG56400002 PM 9397424 ER PT J AU Ernst, M Zametkin, AJ Matochik, J Schmidt, M Jones, PH Liebenauer, LL Hardy, KK Cohen, RM AF Ernst, M Zametkin, AJ Matochik, J Schmidt, M Jones, PH Liebenauer, LL Hardy, KK Cohen, RM TI Intravenous dextroamphetamine and brain glucose metabolism SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE stimulant; PET; dextroamphetamine; attention; FDG; imaging ID POSITRON-EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT; COGNITIVE ACTIVATION; NEURONAL-ACTIVITY; D-AMPHETAMINE; TEST-RETEST; DOPAMINE; SCHIZOPHRENIA AB This study reports the effects of intravenous dextroamphetamine on cerebral glucose metabolism assayed by positron emission tomography (PET) and [fluorine-18]fluorodeoxyglucose (FDG) in 13 healthy adults during the performance of a continuous visual attention task. Two FDG PET scans were performed within a single experimental session. The first scan was preceded by the injection of placebo and the second scan by the injection of 0.15 mg/kg dextroamphetamine. Global and normalized regional glucose metabolic rates (rCMRglc) were examined as a function of pharmacological challenge and subjective experience. Subcortical, limbic, frontal, and cerebellar rCMRglc significantly increased after dextroamphetamine, whereas rCMRglc of the temporal cortex significantly decreased. Physiological and self-report measures of subjective states showed the expected alterations. These rCMRglc changes reflect both the direct pharmacological effect of dextroamphetamine on monoaminergic neurotransmitter systems as well as enhancement of the activation of the neural network mediating the performance of the continuous attention task. Published by Elsevier Science Inc. C1 NIMH,CEREBRAL METAB LAB,NIH,BETHESDA,MD 20892. RI Schmidt, Mark/I-5052-2016; OI Schmidt, Mark/0000-0003-3417-8977; Hardy, Kristina/0000-0002-5479-5043 NR 55 TC 32 Z9 32 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 1997 VL 17 IS 6 BP 391 EP 401 DI 10.1016/S0893-133X(97)00088-2 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA YG564 UT WOS:A1997YG56400005 PM 9397427 ER PT J AU Wang, H Moriwaki, A Wang, JB Uhl, GR Pickel, VM AF Wang, H Moriwaki, A Wang, JB Uhl, GR Pickel, VM TI Ultrastructural immunocytochemical localization of mu-opioid receptors in dendritic targets of dopaminergic terminals in the rat caudate-putamen nucleus SO NEUROSCIENCE LA English DT Article DE extrasynaptic site; morphine; nigrostriatal afferent; stereotyped behaviour; tyrosine hydroxylase; ultrastructural localization ID PROENKEPHALIN MESSENGER-RNA; DELTA-OPIATE AGONISTS; TYROSINE-HYDROXYLASE; BASAL GANGLIA; CORTICOSTRIATAL AFFERENTS; IMMUNOREACTIVE STRUCTURES; STRIATONIGRAL NEURONS; STEREOTYPED BEHAVIOR; LOCOMOTOR ACTIVITIES; VOLUME TRANSMISSION AB Many motor effects of opiates acting at mu-opioid receptors are thought to reflect functional interactions with dopaminergic inputs to the caudate-putamen nucleus. We examined the cellular and subcellular bases for this interaction in the rat caudate-putamen nucleus by dual immunocytochemical labelling for mu-opioid receptors and tyrosine hydroxylase, a marker mainly for dopamine in this region. mu-Opioid receptor-like immunoreactivity showed a patchy distribution by light microscopy. Within the patches, electron microscopy revealed that immunogold labelling for mu-opioid receptors was mainly distributed along extrasynaptic plasma membranes of medium spiny neurons. In contrast, immunoperoxidase labelling for tyrosine hydroxylase was exclusively located in axons and axon terminals without detectable mu-opioid receptor-like immunoreactivity. Forty-six percent of the total mu-opioid receptor-labelled neuronal profiles (n=1441) were in contact with tyrosine hydroxylase-immunoreactive axons and terminals. These contacts were characterized by closely apposed parallel plasma membrane segments, without well-defined synaptic junctions, or with punctate symmetric specializations. From 639 noted appositions, over 90% were between mu-opioid receptor-labelled dendrites and/or dendritic spines and tyrosine hydroxylase-containing terminals. The dendritic spines containing mu-opioid receptor-like immunoreactivity often received asymmetric synapses characteristic of excitatory inputs from unlabelled terminals. Axon terminals containing mu-opioid receptor-like immunoreactivity formed asymmetric synapses with dendritic spines, or apposed tyrosine hydroxylase-labelled terminals. Our results suggest that, in striatal patch compartments, mu-agonists and dopamine dually modulate the activity of single spiny neurons mainly through changes in their postsynaptic responses to excitatory inputs. In addition, our findings implicate mu-opioid receptors and dopamine in the presynaptic regulation of excitatory neurotransmitter release within the striatal patch compartments. (C) 1997 IBRO. Published by Elsevier Science Ltd. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. RP Wang, H (reprint author), NIDA,MOL NEUROBIOL BRANCH,INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224, USA. FU NIDA NIH HHS [DA 04600]; NIMH NIH HHS [MH 00078] NR 74 TC 34 Z9 34 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD DEC PY 1997 VL 81 IS 3 BP 757 EP 771 DI 10.1016/S0306-4522(97)00253-4 PG 15 WC Neurosciences SC Neurosciences & Neurology GA XX982 UT WOS:A1997XX98200015 PM 9316027 ER PT J AU Maeda, K Kaneda, H Whetsell, WO Tamminga, CA AF Maeda, K Kaneda, H Whetsell, WO Tamminga, CA TI Neurochemical and metabolic consequences of elevated cerebrospinal fluid quinolinic acid concentrations in rat brain SO NEUROSCIENCE RESEARCH LA English DT Article DE quinolinic acid; choline acetyltransferase; somatostatin; local cerebral glucose utilization; cerebrospinal fluid; 2-deoxyglucose ID CEREBRAL GLUCOSE-UTILIZATION; D-ASPARTATE RECEPTOR; HUNTINGTONS-DISEASE; STIMULATION; ACTIVATION; STRIATUM; INFUSION; LESIONS; NEURONS; CORTEX AB Quinolinic acid (QUIN) is an endogenous excitatory amino acid, which is elevated in brain tissues or cerebrospinal fluid (CSF) in several acute and chronic inflammatory central nervous system (CNS) diseases. The functional significance of this elevation is unknown but speculations of excitotoxicity have been raised. We have begun to address the pathologic consequences of elevated CSF QUIN by studying the effects of intracerebroventricular (icy) administration of QUIN on regional choline acetyltransferase (ChAT) activity, somatostatin content and glucose metabolism in the rat brain. QUIN (12 and 60 nmol) icy administration once a day for 7 days (total dose; 84 and 420 nmol, respectively) had minimal effect on somatostatin content and no effect on ChAT activity. In contrast, following continuous icy infusion of QUIN for 14 days using an osmotic minipump (480 nmol), ChAT activity dropped in the hippocampus and the striatum and somatostatin content was reduced in the frontal cortex, hippocampus, striatum and amygdala. Moreover, following the QUIN infusion, glucose utilization decreased in the basal nucleus of Meynert, frontal cortex, and portions of the basal ganglia and the limbic system. These results indicate that subchronic icy infusion of QUIN to rats results in selective regional neurochemical and metabolic changes distributed throughout the CNS. These results suggest target brain areas and transmitter systems which may be associated with neurologic syndromes characterized by elevated CSF QUIN levels. (C) 1997 Elsevier Science Ireland Ltd. C1 Univ Maryland, Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. NINDS, NIH, Baltimore, MD 20892 USA. Vanderbilt Univ, Dept Pathol, Nashville, TN 37232 USA. RP Maeda, K (reprint author), Hyogo Inst Aging Brain & Cognit Disorders, Himeji, Hyogo 670, Japan. NR 36 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PD DEC PY 1997 VL 29 IS 4 BP 303 EP 309 DI 10.1016/S0168-0102(97)00102-8 PG 7 WC Neurosciences SC Neurosciences & Neurology GA YV008 UT WOS:000071779300004 PM 9527621 ER PT J AU Somogyi, R Fuhrman, S Askenazi, M Wuensche, A AF Somogyi, R Fuhrman, S Askenazi, M Wuensche, A TI The gene expression matrix: Towards the extraction of genetic network architectures SO NONLINEAR ANALYSIS-THEORY METHODS & APPLICATIONS LA English DT Article; Proceedings Paper CT 2nd World Congress of Nonlinear Analysis CY JUL 10-17, 1996 CL ATHENS, GREECE SP Int Federat Nonlinear Analysts DE parallel distributed processing networks; genetic networks; gene expression; PCR; molecular biology; functional genomics; differentiation; Boolean networks; states; trajectories; attractors; cluster analysis; reverse engineering C1 NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. Santa Fe Inst, Santa Fe, NM 87501 USA. RP Somogyi, R (reprint author), NINDS, Neurophysiol Lab, NIH, Bldg 36,Rm 2C02, Bethesda, MD 20892 USA. NR 14 TC 27 Z9 27 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0362-546X J9 NONLINEAR ANAL-THEOR JI Nonlinear Anal.-Theory Methods Appl. PD DEC PY 1997 VL 30 IS 3 BP 1815 EP 1824 DI 10.1016/S0362-546X(97)00217-4 PG 10 WC Mathematics, Applied; Mathematics SC Mathematics GA YV497 UT WOS:000071831000055 ER PT J AU Fowler, MG Melnick, SL Mathieson, BJ AF Fowler, MG Melnick, SL Mathieson, BJ TI Women and HIV - Epidemiology and global overview SO OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN PAPILLOMAVIRUS INFECTION; SEXUALLY-TRANSMITTED DISEASES; INJECTING DRUG-USERS; MALE-TO-FEMALE; CERVICAL INTRAEPITHELIAL NEOPLASIA; RISK-FACTORS; KAPOSIS-SARCOMA; NATURAL-HISTORY; UNITED-STATES AB The epidemiology of HIV-1 in women is presented, including global estimates of the epidemic through the mid 1990s. Risk factors for acquisition of HIV infection and disease progression in women are reviewed, as well as clinical manifestations. C1 NCI,EXTRAMURAL EPIDEMIOL AIDS & RETROVIRAL ASSOCIATED,DIV CANC EPIDEMIOL & GENET,NIH,BETHESDA,MD 20892. NIH,OFF AIDS RES,OFF DIRECTOR,BETHESDA,MD 20892. RP Fowler, MG (reprint author), NIAID,EFFICACY TRIALS BRANCH,DIV AIDS,NIH,ROOM 2A09,SOLAR BLDG,6003 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 137 TC 28 Z9 31 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8545 J9 OBSTET GYN CLIN N AM JI Obstet. Gynecol. Clin. N. Am. PD DEC PY 1997 VL 24 IS 4 BP 705 EP & DI 10.1016/S0889-8545(05)70340-5 PG 26 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA YL296 UT WOS:A1997YL29600002 PM 9430163 ER PT J AU Mofenson, LM AF Mofenson, LM TI Mother-child HIV-2 transmission - Timing and determinants SO OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; VITAMIN-A-DEFICIENCY; T-CELL ACTIVITY; VERTICAL TRANSMISSION; PERINATAL TRANSMISSION; BREAST-MILK; ZIDOVUDINE TREATMENT; P24 ANTIGEN; VIRAL LOAD; CERVICOVAGINAL SECRETIONS AB Prevention of mother-to-child transmission of HIV is a significant public health priority. A regimen of zidovudine administered during pregnancy, intrapartum, and to the newborn significantly reduces transmission, and incorporation of this regimen into clinical practice has been associated with significant decreases in perinatal transmission in industrialized countries. This regimen, however, is not applicable in the developing world (where most perinatal transmission occurs), and simpler, shorter, less costly regimens are urgently needed. An understanding of the pathogenesis of perinatal transmission is crucial for the design of new preventive and therapeutic regimens, and current knowledge is reviewed in this article, with an emphasis on relevance to prevention. C1 NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,CTR RES MOTHERS & CHILDREN,NIH,BETHESDA,MD 20892. NR 99 TC 45 Z9 45 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8545 J9 OBSTET GYN CLIN N AM JI Obstet. Gynecol. Clin. N. Am. PD DEC PY 1997 VL 24 IS 4 BP 759 EP & DI 10.1016/S0889-8545(05)70343-0 PG 27 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA YL296 UT WOS:A1997YL29600005 PM 9430166 ER PT J AU Brady, RO Murray, GJ Oliver, KL Leitman, SF Sneller, MC Fleisher, TA Barton, NW AF Brady, RO Murray, GJ Oliver, KL Leitman, SF Sneller, MC Fleisher, TA Barton, NW TI Management of neutralizing antibody to ceredase in a patient with type 3 Gaucher disease SO PEDIATRICS LA English DT Article DE Gaucher disease; neutralizing antibody; Ceredase ID MACROPHAGE-TARGETED GLUCOCEREBROSIDASE; ENZYME REPLACEMENT THERAPY; INTRAVENOUS INFUSIONS; DEFICIENCY AB Objectives. The beneficial effects of macrophage-targeted glucocerebrosidase (Ceredase) in patients with Gaucher disease are well established. A minority of recipients develop transient nonneutralizing antibodies to the exogenous enzyme. A 7-year-old patient with type 3 Gaucher disease whose clinical course began to deteriorate while receiving Ceredase developed a progressively increasing titer of IgG antibody that blocked the catalytic activity of Ceredase. We sought to develop a strategy that would restore the benefit of enzyme replacement therapy in this patient. Methods. The patient was treated with two courses of a combination of plasma exchange, cydophosphamide, intravenous IgG, and large doses of Ceredase. Results. After the second course of this regimen, the titer of the neutralizing antibody in the blood gradually declined to negligible levels. Clinical parameters that had been deteriorating (reduction of hemoglobin level, increased serum acid phosphates activity, repeated skeletal infarctions, progressive enlargement and infarction of the spleen) all improved. There has been no recurrence of the neutralizing antibody in this patient. Conclusions. Very few patients with Gaucher disease who are treated with Ceredase develop a neutralizing antibody to the exogenous enzyme. In the rare instances where this phenomenon occurs, it is likely that the strategy we have used (plasma exchange, cyclophosphamide, intravenous IgG, and large doses of enzyme) may provide benefit to such individuals. It is also likely that this technique may be helpful when enzyme replacement therapy is attempted in patients with other disorders in which the genetic mutation abrogates the production of the protein (CRIM-negative individuals). C1 NIAID, IMMUNOREGULAT LAB, BETHESDA, MD 20892 USA. NIAID, DEPT TRANSFUS MED, CTR CLIN, BETHESDA, MD 20892 USA. NIH, DEPT CLIN PATHOL, CTR CLIN, BETHESDA, MD 20892 USA. RP Brady, RO (reprint author), NINCDS, DEV & METAB NEUROL BRANCH,NIH,BLDG 10,ROOM 3D04, 10 CTR DR MSC 1260, BETHESDA, MD 20852 USA. NR 20 TC 27 Z9 28 U1 0 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD DEC PY 1997 VL 100 IS 6 BP art. no. EP e11 DI 10.1542/peds.100.6.e11 PG 4 WC Pediatrics SC Pediatrics GA YJ314 UT WOS:A1997YJ31400031 PM 9382912 ER PT J AU Clemens, JD Rao, MR Chakraborty, J Yunus, M Ali, M Kay, B vanLoon, FPL Naficy, A Sack, DA AF Clemens, JD Rao, MR Chakraborty, J Yunus, M Ali, M Kay, B vanLoon, FPL Naficy, A Sack, DA TI Breastfeeding and the risk of life-threatening enterotoxigenic Escherichia coli diarrhea in Bangladeshi infants and children SO PEDIATRICS LA English DT Article DE enterotoxigenic Escherichia coli; breastfeeding; diarrhea ID ORAL CHOLERA VACCINES; RURAL BANGLADESH; FIELD TRIAL; YOUNG-CHILDREN; BREAST-MILK; ANTIBODIES; DISEASES; PROTECTION; INTERVENTIONS; TRANSMISSION AB Objective. To assess the relationship between breastfeeding and the risk of life-threatening enterotoxigenic Escherichia coli (ETEC) diarrhea among Bangladeshi infants and young children < 36 months of age. Design. Case-control study. Setting. A rural Bangladesh community. Participants. A total of 168 cases with clinically severe ETEC diarrhea detected in a treatment center-based surveillance system during 1985 to 1986 and 3679 controls selected in three surveys of the same community during the same calendar interval. Outcomes. Cases and controls were compared for the frequency of antecedent breastfeeding patterns. Results. Compared with other feeding modes, exclusive breastfeeding of infants was associated with significant protection against severe ETEC diarrhea (relative risk [RR] = 0.51; 95% confidence interval [CI]: 0.28,0.96). However, during the second and third years of life, the risk of this outcome was similar in both breastfed and nonbreastfed children (RR = 0.98; 95% CI: 0.45,2.12), and no significant overall protective association between breastfeeding and severe ETEC diarrhea was evident during the first 3 years of life (RR = 0.86; 95% CI: 0.43,1.74). Conclusions. Exclusive breastfeeding appeared to protect infants against severe ETEC diarrhea, but breastfeeding was not associated with protection after infancy, nor was it associated with a major overall reduction of severe ETEC disease during the first 3 years of life. Although not diminishing the importance of breastfeeding, our findings suggest that other interventions, such as immunization and education about proper food hygiene, may also be required in efforts to prevent this major pediatric disease. C1 INT CTR DIARRHOEAL DIS RES, DHAKA 1000, BANGLADESH. JOHNS HOPKINS UNIV, SCH PUBL HLTH, BALTIMORE, MD 21218 USA. CTR DIS CONTROL & PREVENT, ATLANTA, GA USA. RP Clemens, JD (reprint author), NICHHD, DIV EPIDEMIOL STAT & PREVENT RES, 6100 EXECUT BLVD, BETHESDA, MD 20892 USA. RI Ali, Mohammad/E-2365-2017 OI Ali, Mohammad/0000-0003-1410-388X NR 36 TC 19 Z9 20 U1 2 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD DEC PY 1997 VL 100 IS 6 BP art. no. EP e2 DI 10.1542/peds.100.6.e2 PG 7 WC Pediatrics SC Pediatrics GA YJ314 UT WOS:A1997YJ31400022 PM 9374580 ER PT J AU Plotz, PH AF Plotz, PH TI Deconstructing disease: An anatomy of illness in the age of molecular biology SO PERSPECTIVES IN BIOLOGY AND MEDICINE LA English DT Editorial Material ID GENE RP Plotz, PH (reprint author), NIAMSD,NIH,CLIN CTR 9N244,BETHESDA,MD 20892, USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0031-5982 J9 PERSPECT BIOL MED JI Perspect. Biol. Med. PD WIN PY 1997 VL 40 IS 2 BP 160 EP 164 PG 5 WC History & Philosophy Of Science; Medicine, Research & Experimental SC History & Philosophy of Science; Research & Experimental Medicine GA WK489 UT WOS:A1997WK48900001 PM 9058949 ER PT J AU Gelboin, HV Krausz, KW Shou, M Gonzalez, FJ Yang, TJ AF Gelboin, HV Krausz, KW Shou, M Gonzalez, FJ Yang, TJ TI A monoclonal antibody inhibitory to human P450 2D6: a paradigm for use in combinatorial determination of individual P450 role in specific drug tissue metabolism SO PHARMACOGENETICS LA English DT Article DE bufuralol; dextromethorphan; human P450 2D6; inhibitory monoclonal antibodies; P450 2C8/9/19; P450 function in human tissue ID CDNA-EXPRESSED HUMAN; CYTOCHROME-P450; HYDROXYLATION; BACULOVIRUS; MICROSOMES; BUFURALOL AB Human cytochrome P450 2D6 metabolizes more than 50 common drugs and is polymorphically expressed, with 5-10% of the population lacking expression caused by mutant genes. This may result in a defective and toxic response in deficient individuals treated with 2D6 drug substrates. Baculovirus-expressed 2D6 was used to immunize mice for hybridoma production and two clones yielded monoclonal antibodies, that were positive against 2D6 by ELISA and inhibited 2D6 catalysed metabolism of bufuralol, dextromethorphan and phenanthrene by more than 90%. The inhibitory activity was highly specific to 2D6 and the monoclonal antibodies did not bind to 11 other P450s, nor inhibit seven human P450s tested. Analysis of eight human liver microsome samples showed that their basal bufuralol 1'-hydroxylase activity varied from 6.7-83.5 pmol min(-1) nmol(-1) P450. The monoclonal antibody 512-1-8 inhibited 2D6-dependent bufuralol 1'-hydroxylase in these samples by 10-70% indicating a widely variable role for 2D6 in human liver bufuralol 1'-hydroxylase activity and a role for other P450s in bufuralol metabolism. Independent analysis of several recombinant human P450s showed that 2D6, 2C8, 2C9, 2C19 and 1A2 exhibited bufuralol 1'-hydroxylase activity with 2D6 and 2C19 being the most active. Further analysis of three liver samples was made with individual inhibitory monoclonal antibodies. Inhibitory antibodies to 2D6, 2B6, 2E1, 2C8/9/19, 3A4 and 1A2 were added to the microsomes either singly or additively. Inhibitory activity of bufuralol 1'-hydroxylase was observed with antibodies to 2D6 (14-76%), 2C8/9/19 (24-69%) and 1A2 (2-25%) indicating a variable and different role for each of these P450s in the bufuralol 1'-hydroxylase of human liver. The monoclonal antibodies to 2B6, 2E1 and 3A4 were not inhibitory, indicating that these enzymes play no role in bufuralol 1'-hydroxylase metabolism. When the three antibodies to 2D6, 2C8/9/19 and 1A2, respectively, were all added, the total bufuralol 1'-hydroxylase of the liver samples was inhibited by more than 90%, indicating that the latter P450s catalyse all of liver bufuralol 1'-hydroxylase metabolism. These studies demonstrate that inhibitory monoclonal antibodies offer a simple and precise method for assessing the quantitative role of each P450 in the metabolism of a P450 substrate in a tissue, which include drugs, carcinogens, mutagens, toxic chemicals and endobiotics. C1 NCI,LAB METAB,NIH,BETHESDA,MD 20892. RP Gelboin, HV (reprint author), NCI,MOL CARCINOGENESIS LAB,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 17 TC 27 Z9 28 U1 0 U2 1 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD DEC PY 1997 VL 7 IS 6 BP 469 EP 477 DI 10.1097/00008571-199712000-00005 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA YK802 UT WOS:A1997YK80200005 PM 9429232 ER PT J AU Ciotti, M Marrone, A Potter, C Owens, IS AF Ciotti, M Marrone, A Potter, C Owens, IS TI Genetic polymorphism in the human UGT1A6 (planar phenol) UDP-glucuronosyltransferase: pharmacological implications SO PHARMACOGENETICS LA English DT Article DE experimental drugs; phenol UDP-glucuronosyltransferase; pKa values; polymorphism; therapeutic drugs ID SYNDROME TYPE-I; SUBSTRATE-SPECIFICITY; COS-1 CELLS; BILIRUBIN; PATIENT; TRANSFERASE; CLONING; IDENTIFICATION; DEFICIENCY; EXPRESSION AB Two missense mutations were uncovered in the UGT1A6 (HLUG P1) cDNA which codes for a human phenol-metabolizing UDP-glucuronosyltransferase. The mutant and a wild-type UGT1A6 cDNAs were isolated from a custom synthesized human liver lambda Zap cDNA library. Both an A to G transition at nucleotide 541 (T181 A) and an A to C transversion at nucleotide 552 (R184S) occurred in exon 1 of the UGT1A6 (UGT1F) gene at the UGT1 locus. The two mutations on a single allele created a heterozygous genotype. Newly created BsmI and BsoFI sites at the T181 A and R184S locations, respectively, were confirmed by endonuclease treatment of PCR-generated DNA using the donor-liver genomic DNA as template. Screens with endonuclease treatment showed that 33/98 DNA samples were heterozygous with both mutations on one allele. One other individual also carried the R184S mutation on the second allele. Wild-type UGT1A6 generated a broad plateau of activity from pH 5.0 to pH 8.0 with certain experimental phenols, while activity was 1.3-2.5-fold higher at pH 6.4 than at pH 7.2 for others. UGT1A6*2 (181 A+ and 184S+) metabolized 4-nitrophenol, 4-tert-butylphenol, 3-ethylphenol/4-ethylphenol, 4-hydroxycoumarin, butylated hydroxy anisole and butylated hydroxy toluene, with the pH 6.4 preference, at only 27-75% of the rate of the wild-type isozyme whereas 1-naphthol, 3-iodophenol, 7-hydroxycoumarin, and 7-hydroxy-4-methylcoumarin were metabolized at essentially the normal level. Furthermore, UGT1A6*2 metabolized 3-O-methyl-dopa and methyl salicylate at 41-74% of that of the wild-type, and a series of beta-blockers at 28-69% of the normal level. This evidence suggests that the UGT1A6 enzyme activity is affected by different amino acids depending upon the substrate selection. C1 NICHHD,HERITABLE DISORDERS BRANCH,NIH,BETHESDA,MD 20892. NIDDK,DIGEST DIS BRANCH,NIH,BETHESDA,MD 20892. NR 27 TC 143 Z9 154 U1 2 U2 3 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD DEC PY 1997 VL 7 IS 6 BP 485 EP 495 DI 10.1097/00008571-199712000-00007 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA YK802 UT WOS:A1997YK80200007 PM 9429234 ER PT J AU Lerman, C Shields, PG Main, D Audrain, J Roth, J Boyd, NR Caporaso, NE AF Lerman, C Shields, PG Main, D Audrain, J Roth, J Boyd, NR Caporaso, NE TI Lack of association of tyrosine hydroxylase genetic polymorphism with cigarette smoking SO PHARMACOGENETICS LA English DT Article DE genetics; hydroxylase; nicotine; smoking; tyrosine ID NICOTINE; MECHANISMS; DISEASE C1 NCI,HUMAN CARCINOGENESIS LAB,MOL EPIDEMIOL SECT,BETHESDA,MD 20892. FOX CHASE CANC CTR,DIV POPULAT SCI,CHELTENHAM,PA 19012. NCI,PHARMACOGENET SECT,ROCKVILLE,MD 20852. RP Lerman, C (reprint author), GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,2233 WISCONSIN AVE NW,SUITE 535,WASHINGTON,DC 20007, USA. RI Shields, Peter/I-1644-2012 NR 14 TC 28 Z9 28 U1 0 U2 1 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD DEC PY 1997 VL 7 IS 6 BP 521 EP 524 DI 10.1097/00008571-199712000-00012 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA YK802 UT WOS:A1997YK80200012 PM 9429239 ER PT J AU Gram, TE AF Gram, TE TI Chemically reactive intermediates and pulmonary xenobiotic toxicity SO PHARMACOLOGICAL REVIEWS LA English DT Review ID CLARA CELL CYTOTOXICITY; BUTYLATED HYDROXYTOLUENE BHT; INDUCED LUNG INJURY; A/J MOUSE LUNG; POLYCYCLIC AROMATIC-HYDROCARBONS; MURINE STRAIN DIFFERENCES; INVITRO COVALENT BINDING; TARGET ORGAN ALKYLATION; ACUTE PARAQUAT TOXICITY; MIXED-FUNCTION OXIDASE C1 NCI, Sect Drug Interact, Dev Therapeut Program, NIH, Bethesda, MD 20892 USA. RP Gram, TE (reprint author), 1036 Welsh Dr, Rockville, MD 20852 USA. NR 282 TC 82 Z9 82 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0031-6997 J9 PHARMACOL REV JI Pharmacol. Rev. PD DEC PY 1997 VL 49 IS 4 BP 297 EP 341 PG 45 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YP452 UT WOS:000071278200001 PM 9443161 ER PT J AU Bienkowski, P Iwinska, K Stefanski, R Kostowski, W AF Bienkowski, P Iwinska, K Stefanski, R Kostowski, W TI Discriminative stimulus properties of ethanol in the rat: Differential effects of selective and nonselective benzodiazepine receptor agonists SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE ethanol; GABA(A) receptor complex; benzodiazepine receptor; drug discrimination; rat ID GATED ION CHANNELS; DRUG DISCRIMINATION; NMDA ANTAGONISTS; SUBSTITUTION; ABECARNIL; SUBTYPES; LIGANDS AB Rats were trained to discriminate between ethanol (1.0 g/kg; 10% v/v) and saline under a fixed ratio 10 schedule of sweetened milk reinforcement. Both diazepam [nonselective, full benzodiazepine (BZ) receptors agonist] and bretazenil (nonselective, partial BZ receptor agonist) produced dose-dependent ethanol-appropriate responding (>75%). Neither diazepam nor bretazenil affected the response rate at the doses producing maximal generalisation from ethanol. In contrast, zolpidem (full BZ1 receptor agonist) and abecarnil (full BZ1/full or partial BZ2 receptor agonist) produced only moderate (<50%) ethanol-appropriate responding when tested up to doses that markedly decreased the overall re sponse rate. These results suggest that: 1) there are no major differences between full and partial, nonselective BZ receptor agonists in their ability to substitute for 1.0 g/kg dose of ethanol; 2) stimulation of BZ1 receptors alone is not sufficient to produce ethanol-like discriminative stimulus effects in the rat. (C) 1997 Elsevier Science Inc. C1 INST PSYCHIAT & NEUROL,DEPT PHARMACOL & PHYSIOL NERVOUS SYST,PL-02957 WARSAW,POLAND. WARSAW MED UNIV,DEPT EXPT & CLIN PHARMACOL,PL-00927 WARSAW,POLAND. NIDA,PRECLIN PHARMACOL LAB,BEHAV PHARMACOL & GENET SECT,BALTIMORE,MD 21224. NR 28 TC 13 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD DEC PY 1997 VL 58 IS 4 BP 969 EP 973 DI 10.1016/S0091-3057(97)00034-8 PG 5 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA YH611 UT WOS:A1997YH61100020 PM 9408202 ER PT J AU Bicout, DJ AF Bicout, DJ TI Green's functions and first passage time distributions for dynamic instability of microtubules SO PHYSICAL REVIEW E LA English DT Article ID SELF-ORGANIZED CRITICALITY; TELEGRAPHERS EQUATION; KINETICS; GROWTH AB It is shown that the dynamic instability process describing the self-assembly and/or disassembly of microtubules is a continuous version of a variant of persistent random walks described by the generalized telegrapher's equation. That is to say, a microtubule is likely to undergo stochastic traveling waves in which catastrophe and rescue events cannot propagate faster than upsilon(-) and upsilon(+), respectively. For this stochastic process, analytic expressions for Green's functions of position and velocity of a microtubule and exact solutions for the first passage time distributions of a microtubule to the nucleating site are obtained. It is shown that, in the omega-->infinity limit, where omega(-1) is the persistence time, the dynamic instability process can be described by a diffusion process in the presence of a drift term that, in fact, is the steady-stare velocity of the microtubule. As a result, the catastrophe time distribution (i.e., the distribution of microtubule lifetimes to the nucleating site) exhibits a power law with an exponential cutoff as F(t\x(0))similar to t(-3/2)e(-t/tau c), where tau(c) is the time scale at which the drift term and the diffusive term are comparable. C1 NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP NIDDKD, Phys Chem Lab, NIH, Bldg 5,Room 136, Bethesda, MD 20892 USA. EM bicout@speck.niddk.nih.gov NR 23 TC 33 Z9 33 U1 1 U2 3 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 2470-0045 EI 2470-0053 J9 PHYS REV E JI Phys. Rev. E PD DEC PY 1997 VL 56 IS 6 BP 6656 EP 6667 DI 10.1103/PhysRevE.56.6656 PG 12 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA YM237 UT WOS:000071043500058 ER PT J AU Parsegian, VA AF Parsegian, VA TI How should physicists, biologists work together? The 'Harness the Hubris' debate continues SO PHYSICS TODAY LA English DT Letter RP Parsegian, VA (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0031-9228 J9 PHYS TODAY JI Phys. Today PD DEC PY 1997 VL 50 IS 12 BP 14 EP 14 PG 1 WC Physics, Multidisciplinary SC Physics GA YJ169 UT WOS:A1997YJ16900004 ER PT J AU Page, WF Braun, MM Partin, AW Caporaso, N Walsh, P AF Page, WF Braun, MM Partin, AW Caporaso, N Walsh, P TI Heredity and prostate cancer: A study of World War II veteran twins SO PROSTATE LA English DT Article DE genetics; twin concordance; epidemiology ID FAMILY HISTORY; RISK; POPULATION AB BACKGROUND. Increased risk of prostate cancer among men with a family history of the disease has been observed in several epidemiological studies, and family studies have identified hereditary prostate cancer characterized by early onset and autosomal dominant inheritance. METHODS. In this study, we examine prostate cancer heritability among twins in the NAS-NRC Twin Registry, with cases ascertained from a number of sources: recent telephone interviews, Medicare and Department of Veterans Affairs hospitalizations, previous mail questionnaires, and death certificates. A total of 1,009 prostate cancer cases were identified among the cohort of 31,848 veteran twins born in the years 1917-1927. RESULTS. Probandwise concordance for prostate cancer was substantially higher among monozygous twin pairs, 27.1%, than among dizygous twin pairs, 7.1% (P < 0.001). CONCLUSIONS. These data suggest that genetic influences account for approximately 57%, and environmental influences for 43%, of the variability in twin liability for prostate cancer. (C) 1997 Wiley-Liss, Inc. C1 US FDA,CTR BIOL EVALUAT & RES,DIV BIOSTAT & EPIDEMIOL,WASHINGTON,DC 20204. JOHNS HOPKINS MED INST,JAMES BUCHANAN BRADY UROL INST,BALTIMORE,MD 21205. NCI,GENET EPIDEMIOL BRANCH,NIH,BETHESDA,MD. RP Page, WF (reprint author), NATL ACAD SCI,MED FOLLOW UP AGCY,INST MED,2101 CONSTITUT AVE NW,WASHINGTON,DC 20418, USA. NR 23 TC 98 Z9 102 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0270-4137 J9 PROSTATE JI Prostate PD DEC 1 PY 1997 VL 33 IS 4 BP 240 EP 245 PG 6 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA YJ508 UT WOS:A1997YJ50800003 PM 9397195 ER PT J AU Smith, MBK Michejda, CJ Hughes, SH Boyer, PL Janssen, PAJ Andries, K Buckheit, RW Smith, RH AF Smith, MBK Michejda, CJ Hughes, SH Boyer, PL Janssen, PAJ Andries, K Buckheit, RW Smith, RH TI Molecular modeling of HIV-1 reverse transcriptase drug-resistant mutant strains: implications for the mechanism of polymerase action SO PROTEIN ENGINEERING LA English DT Article DE AIDS; computer; inhibitor; resistance; reverse transcriptase ID IMMUNODEFICIENCY-VIRUS TYPE-1; NONNUCLEOSIDE INHIBITORS; ANGSTROM RESOLUTION; MUTATION; THERAPY; SENSITIVITY; POLYMERIZATION; DNA AB A computer model of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) either alone, or complexed with a non-nucleoside inhibitor (NNI), was constructed using crystal coordinate data from a subset of the protein surrounding the binding pocket region. Molecular mechanics calculations were carried out on solvated wild-type RT and RT that contained modifications corresponding to resistance-engendering mutations. Results from the calculations revealed that the r.m.s. difference between 12 modified proteins and that of wild-type RT could be qualitatively correlated with the measured polymerase activity of the enzyme in the presence of these mutations. In addition, the level of activity was related to the measured distance between the primer grip and dNTP binding regions of the protein. These data suggest a direct correlation between RT structure and function. Complexes of RT-8-C1 TIBO and RT-alpha-APA were also minimized in models containing modifications corresponding to key drug-resistant mutants. The variant complexes all showed weaker binding than wild-type RT, while giving rise to similar, but critical changes in the protein. Therefore, the design of new inhibitors should center on obtaining stronger binding drugs to key drug-resistant RT variants. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. Janssen Res Fdn, Ctr Mol Design, B-2350 Vosselaar, Belgium. So Res Inst, Virol Res Grp, Frederick, MD 21701 USA. Western Maryland Coll, Dept Chem, Westminster, MD 21157 USA. RP Smith, MBK (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, POB B, Frederick, MD 21702 USA. NR 28 TC 11 Z9 11 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD DEC PY 1997 VL 10 IS 12 BP 1379 EP 1383 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA ZC099 UT WOS:000072539800005 ER PT J AU Rajagopal, V Pastan, I Kreitman, RJ AF Rajagopal, V Pastan, I Kreitman, RJ TI A form of anti-Tac(Fv) which is both single-chain and disulfide stabilized: comparison with its single-chain and disulfide-stabilized homologs SO PROTEIN ENGINEERING LA English DT Article DE anti-Tac(Fv); disulfide stabilized; single chain ID FV FRAGMENT; ESCHERICHIA-COLI; RECOMBINANT IMMUNOTOXINS; PSEUDOMONAS EXOTOXIN; COMPLETE REGRESSION; ANTITUMOR-ACTIVITY; IMPROVED BINDING; NUDE-MICE; ANTIBODY; PROTEINS AB Disulfide-stabilized Fvs (dsFvs) are recombinant proteins composed of a heavy-chain variable domain (V-H) of an antibody connected via a disulfide bond to the light-chain variable domain (V-L). In single-chain Fvs (scFvs), a peptide connector links V-H and V-L. The dsFv form of the anti-Tac monoclonal antibody which reacts with the alpha subunit of the IL2 receptor was recently reported to be more stable and to aggregate less during renaturation than anti-Tac(scFv). In addition, it could be produced in a better yield owing to less aggregation. However, the yields are still too low to permit the production of material for clinical trials in which the dsFv will be used to image or treat IL2 receptor (CD25)-containing tumors. To increase the efficiency by which V-H and V-L associate and form a disulfide bond during renaturation, we have prepared an Fv form of anti-Tac which is both single chain and disulfide stabilized (scdsFv). The recombinant protein is expressed in Escherichia coli, where it accumulates in inclusion bodies. Using inclusion body protein as the reference point, the yield of purified anti-Tac(scdsFv) was 13% compared with 2% for anti-Tac(dsFv). Anti-Tac(scdsFv) has equivalent binding affinity, immunoreactivity after radiolabeling and stability. The results show that a linker between V-H and V-L facilitates heterodimer formation and leads to disulfide bond formation in a higher percentage of the molecules renatured. Thus anti-Tac(scdsFv) is the preferred form of anti-Tac(Fv) to be used for clinical studies. We anticipate that scdsFvs will be the optimum recombinant form of Fv to produce from bacteria. C1 NCI, Div Canc Biol, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kreitman, RJ (reprint author), NCI, Div Canc Biol, Mol Biol Lab, NIH, 37-4E16,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 22 TC 24 Z9 29 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD DEC PY 1997 VL 10 IS 12 BP 1453 EP 1459 DI 10.1093/protein/10.12.1453 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA ZC099 UT WOS:000072539800013 PM 9543007 ER PT J AU Tsao, KL Waugh, DS AF Tsao, KL Waugh, DS TI Balancing the production of two recombinant proteins in Escherichia coli by manipulating plasmid copy number: High-level expression of heterodimeric Ras farnesyltransferase SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID ALPHA-SUBUNIT; SACCHAROMYCES-CEREVISIAE; SIGNAL-TRANSDUCTION; METAL REQUIREMENTS; PEPTIDE-BINDING; DNA-REPLICATION; RNA-POLYMERASE; BETA-SUBUNIT; CDNA CLONING; PROMOTER AB The native Ras farnesyltransferase heterodimer (cup) and a heterodimer with a truncated a subunit (alpha'beta) were overproduced at a high level and in a soluble form in Escherichia coli. The alpha, alpha', and beta subunits were synthesized from individual plasmid vectors under the control of bacteriophage T7 promoters. Although each subunit could be expressed at a high level by itself, when either the alpha or alpha' and the beta plasmid were present in cells at the same time, the alpha and alpha' subunits were preferentially expressed to such a degree that little or none of the beta subunit accumulated, A satisfactory balance between both combinations of subunits (alpha beta and alpha'beta) was achieved by making incremental adjustments in the copy number of the beta-encoding plasmid, As the copy number of the beta plasmid increased, so did the ratio of beta:alpha or beta:alpha', but there was little difference in the total amount of recombinant protein (alpha + beta or alpha' + beta) that was produced, This may be a generally useful method for balancing the production of two recombinant polypeptides in E. coli, A noteworthy advantage of this approach is that it can be undertaken without first determining the cause of the imbalance. (C) 1997 Academic Press. C1 Hoffmann La Roche Inc, Roche Res Ctr, Dept Phys Chem, Nutley, NJ 07110 USA. RP Waugh, DS (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, POB B, Frederick, MD 21702 USA. NR 50 TC 10 Z9 10 U1 1 U2 4 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 DEC PY 1997 VL 11 IS 3 BP 233 EP 240 DI 10.1006/prep.1997.0794 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA YM739 UT WOS:000071096000002 PM 9425626 ER PT J AU Geetha, V Munson, PJ AF Geetha, V Munson, PJ TI Linkers of secondary structures in proteins SO PROTEIN SCIENCE LA English DT Article DE catalytic triad of serine proteases; clustering conformational analysis; linkers, orthogonal mainly alpha proteins ID GLOBULAR-PROTEINS; BETA-HAIRPINS; CLASSIFICATION; FEATURES; MOTIFS; LOOPS; DIVERSITY; SEQUENCE; TAXONOMY; FAMILIES AB Linkers that connect repeating secondary structures fall into conformational classes based on distance and main-chain torsion clustering. A data set of 300 unique plot-in chains with low pairwise sequence identity was clustered into only a few groups representing the preferred motifs. The linkers of two to eight residues for the nonredundant data set are designated H-Ln-H, H-Ln-E, E-Ln-H, B-Ln-E, where n is the length, H stands for n helices, and E for beta-strands. Most of the clusters identified here corroborate earlier findings. However, 19 new clusters are identified in this paper, with many of them having seven and eight residue linkers. In our first analysis, the secondary structures nanking the linkers are: both interacting and noninteracting and there is no precise angle of orientation between them. A second analysis was performed on a set of proteins with restricted orientations for the flanking elements, namely, mainly alpha class of proteins with orthogonal architecture, Two definite clusters are identified, one corresponding to linkers of orthogonal helices and the other to Linkers of antiparallel helices. Loops forming binding sites or involved in catalytic activity ars important determinants of the function of proteins. Although the structural conservation of the residues around the catalytic triad of serine proteases has been studied widely, there has not been a systematic analysis of the conformation of the loops that contain them. Residues of the catalytic triad reside in the linkers of beta-strands, with varying lengths of more than eight residues, Here, we analyze the structural conservation of such linkers by superposition, and observe a conserved structural feature of the linkers incorporating each of the three residues of the catalytic triad. RP Geetha, V (reprint author), NIH,DIV COMP RES & TECHNOL,STRUCT BIOL LAB,ANALYT BIOSTAT SECT,BLDG 12A,RM 2041,BETHESDA,MD 20892, USA. NR 36 TC 12 Z9 12 U1 0 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD DEC PY 1997 VL 6 IS 12 BP 2538 EP 2547 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YK912 UT WOS:A1997YK91200006 PM 9416603 ER PT J AU Nosworthy, NJ Ginsburg, A AF Nosworthy, NJ Ginsburg, A TI Thermal unfolding of dodecameric glutamine synthetase: Inhibition of aggregation by urea SO PROTEIN SCIENCE LA English DT Article DE calorimetry; glutamine synthetase; protein unfolding; subunit dissociation; urea denaturation ID ESCHERICHIA-COLI; SUBUNIT INTERACTIONS; SITE; TRANSITIONS; ADENYLYLATION; PROTEINS; DOMAINS; BINDING; STATE; ATP AB Thermal unfolding of dodecameric manganese.glutamine synthetase (622,000 M-r) at pH 7 and similar to 0.02 ionic strength occurs in two observable steps: a small reversible transition (T-m similar to 42 degrees C; Delta H congruent to 0.9 J/g) followed by a large irreversible transition (T-m similar to 81 degrees C; Delta H congruent to 23.4 J/g) in which secondary structure is lost and soluble aggregates form. Secondary structure, hydrophobicity, and oligomeric structure of the equilibrium intermediate are the same as for the native protein, whereas some aromatic residues are more exposed. Urea (3 M:) destabilizes the dodecamer (with a tertiary structure similar to that without urea at 55 degrees C) and inhibits aggregation accompanying un folding at less than or equal to 0.2 mg protein/ml. With increasing temperature (30-70 degrees C) or incubation times at 25 degrees C: (5-35h) in 3 Pn urea, only dodecamer and unfolded monomer are detected. In addition, the loss in enzyme secondary structure is pseudo-first-order (t(1/2) = 1,030 s at 20.0 degrees C in 4.5 M urea). Differential scanning calorimetry of the enzyme in 3 M urea shows one endotherm (T-max similar to 64 degrees C; Delta H = 17 +/- 2 J/g). The enthalpy change for dissociation and unfolding agrees with that determined by urea titrations by isothermal calorimetry (Delta H = 57 +/- 15 J/g; Zolkiewski M, Nosworthy NJ, Ginsburg A, 1995, Protein Sci 4:1544-1552), after correcting for the binding of urea to protein sites exposed during unfolding (-42 J/g). Refolding and assembly to active enzyme occurs upon dilution of urea after thermal unfolding. C1 NHLBI,SECT PROT CHEM,BIOCHEM LAB,NIH,BETHESDA,MD 20892. NR 37 TC 12 Z9 12 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD DEC PY 1997 VL 6 IS 12 BP 2617 EP 2623 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YK912 UT WOS:A1997YK91200013 PM 9416610 ER PT J AU Galperin, MY Koonin, EV AF Galperin, MY Koonin, EV TI A diverse superfamily of enzymes with ATP-dependent carboxylate-amine/thiol ligase activity SO PROTEIN SCIENCE LA English DT Article DE ATP binding site; ATP-grasp fold; biotin carboxylase; glutathione synthetase; purine biosynthesis; succinate thiokinase; tubuline-tyrosine ligase ID SUCCINYL-COA SYNTHETASE; D-ALANINE LIGASE; ESCHERICHIA-COLI; GLUTATHIONE SYNTHETASE; 3-DIMENSIONAL STRUCTURE; BIOTIN CARBOXYLASE; ALIGNMENT; RESOLUTION; SEQUENCE; PROTEIN AB The recently developed PSI-BLAST method for sequence database search and methods for motif analysis were used to define and expand a superfamily of enzymes with an unusual nucleotide-binding fold, referred to as palmate, or ATP-grasp fold. In addition to D-alanine-D-alanine ligase, glutathione synthetase, biotin carboxylase, and carbamoyl phosphate synthetase, enzymes with known three-dimensional structures, the ATP-grasp domain is predicted in the ribosomal protein S6 modification enzyme (RimK), urea amidolyase, tubulin-tyrosine ligase, and three enzymes of purine biosynthesis. All these enzymes possess ATP-dependent carboxylate-amine ligase activity, and their catalytic mechanisms are likely to include acylphosphate intermediates. The ATF-grasp superfamily also includes succinate-CoA ligase (both ADP-forming and GDP-forming variants), malate-CoA ligase, and ATP-citrate lyase, enzymes with a carboxylate-thiol ligase activity, and several uncharacterized proteins. These findings significantly extend the variety of the substrates of ATP-grasp enzymes and the range of biochemical pathways in which they are involved, and demonstrate the complementarity between structural comparison and powerful methods for sequence analysis. RP Galperin, MY (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20894, USA. RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 NR 37 TC 205 Z9 211 U1 2 U2 17 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD DEC PY 1997 VL 6 IS 12 BP 2639 EP 2643 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YK912 UT WOS:A1997YK91200018 PM 9416615 ER PT J AU Schooler, C Neumann, E Caplan, LJ Roberts, BR AF Schooler, C Neumann, E Caplan, LJ Roberts, BR TI Continued inhibitory capacity throughout adulthood: Conceptual negative priming in younger and older adults SO PSYCHOLOGY AND AGING LA English DT Article ID SELECTIVE ATTENTION; PERSISTENCE; MECHANISMS; STIMULI; AGE AB Two negative priming experiments in older and younger adults are reported. Participants in Experiment 1, involving both positive and negative priming conditions, showed both types of priming. There were no significant differences between age groups. If anything, older participants showed more negative priming. In Experiment 2, involving only negative priming conditions, similar results were obtained. Our findings rule out possible effects of experimental conditions that episodic retrieval theorists have suggested might account for negative priming in older adults. Although our results may be consistent with an explanation of negative riming in older adults by an expansively specified theory of episodic retrieval, they are at least as consistent with the view that inhibitory processes are intact in older adults. In light of these findings: conflicting empirical results and alternative views of negative priming in older adults are examined. RP Schooler, C (reprint author), NIMH,SECT SOCIOENVIRONM STUDIES,NIH,FED BLDG ROOM B1A-14,BETHESDA,MD 20892, USA. NR 43 TC 39 Z9 39 U1 2 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0882-7974 J9 PSYCHOL AGING JI Psychol. Aging PD DEC PY 1997 VL 12 IS 4 BP 667 EP 674 DI 10.1037//0882-7974.12.4.667 PG 8 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA YK918 UT WOS:A1997YK91800011 PM 9416634 ER PT J AU Leshner, AI AF Leshner, AI TI Introduction to the special issue: The National Institute on Drug Abuse's (NIDA's) Drug Abuse Treatment Outcome Study (DATOS) SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Editorial Material ID FOLLOW-UP C1 NIDA, Rockville, MD 20857 USA. NIH, Bethesda, MD 20892 USA. RP Leshner, AI (reprint author), NIDA, 5600 Fishers Lane,Room 10-05, Rockville, MD 20857 USA. NR 23 TC 18 Z9 20 U1 1 U2 3 PU EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD DEC PY 1997 VL 11 IS 4 BP 211 EP 215 DI 10.1037/0893-164X.11.4.211 PG 5 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA YM928 UT WOS:000071115900001 ER PT J AU Fletcher, BW Tims, FM Brown, BS AF Fletcher, BW Tims, FM Brown, BS TI Drug Abuse Treatment Outcome Study (DATOS): Treatment evaluation research in the United States SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Review ID METHADONE-MAINTENANCE TREATMENT; FOLLOW-UP; THERAPEUTIC-COMMUNITY; COMPULSORY TREATMENT; OPIOID ADDICTS; COCAINE ABUSE; TIME SPENT; NEW-YORK; RETENTION; USERS AB Much of what is known about typical drug abuse treatment outcomes comes from a series of large-scale national prospective longitudinal treatment evaluation studies supported by the National Institute on Drug Abuse over the past 3 decades. An overview of the historical context, research design, and findings from the Drug Abuse Reporting Program (DARP) and the Treatment Outcome Prospective Study (TOPS) is presented. The Drug Abuse Treatment Outcome Study (DATOS), a multisite cooperative agreement, is the latest and most advanced in this research designed to understand drug abuse treatment. DATOS investigators are conducting analyses in 4 thematic areas: health services research, retention and engagement in treatment, the life course of treated addicts, and policy-relevant treatment outcome studies. C1 NIDA, Serv Res Branch, Rockville, MD 20857 USA. Univ S Florida, Tampa, FL 33620 USA. RP Fletcher, BW (reprint author), NIDA, Serv Res Branch, 5600 Fishers Lane,Room 10A-30, Rockville, MD 20857 USA. EM bf31v@nih.gov NR 109 TC 73 Z9 74 U1 1 U2 4 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD DEC PY 1997 VL 11 IS 4 BP 216 EP 229 PG 14 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA YM928 UT WOS:000071115900002 ER PT J AU Choyke, PL Walther, MM Wagner, JR Rayford, W Lyne, JC Linehan, WM AF Choyke, PL Walther, MM Wagner, JR Rayford, W Lyne, JC Linehan, WM TI Renal cancer: Preoperative evaluation with dual-phase three-dimensional MR angiography SO RADIOLOGY LA English DT Article DE kidney, MR; kidney neoplasms, staging; magnetic resonance (MR), vascular studies; renal arteries, MR; renal veins, MR ID ABDOMINAL AORTIC-ANEURYSMS; SINGLE-BREATH-HOLD; SPARING SURGERY; CARCINOMA; AORTOGRAPHY; EXTENSION; ECHO AB PURPOSE: To evaluate the use of dual-phase three-dimensional magnetic resonance (MR) angiography in the preoperative staging of renal cancer. MATERIALS AND METHODS: MR angiography was performed in 18 patients before performance of partial (n = 7), radical (n = 10), or laparoscopic (n = 1) nephrectomy to treat renal canter. Dynamic, three-dimensional MR angiograms were obtained with gadoteridol enhancement breath holding, and a three-dimensional spoiled gradient-echo sequence. Images were obtained at 15-second intervals to achieve opacification of arteries and veins. Source, maximum intensity projection, and multiplanar reconstruction images were evaluated. Imaging results were compared with surgical findings. RESULTS: Renal arterial phase MR angiograms depicted 30 of 31 (97%) surgically confirmed renal arteries, with one false-positive result (an artery that arose from an early-branching single main renal artery, interpreted as a separate accessory artery). Renal venous phase MR angiograms depicted all seven instances of renal vein involvement, including extension to the inferior vena cava in two patients. Collateral vessels around the tumor, including prominent gonadal veins in three patients, were demonstrated. Additional findings included adenopathy and adrenal and pulmonary metastases. CONCLUSION: Dual-phase MR angiography of the kidney may be a useful technique in depicting renal vessels before nephrectomy. C1 NCI,UROL ONCOL BRANCH,DIV CLIN SCI,NIH,BETHESDA,MD 20892. RP Choyke, PL (reprint author), NCI,DEPT DIAGNOST RADIOL,WARREN GRANT MAGNUSON CLIN CTR,NIH,BLDG 10,RM 1C660,10 CTR DR,MSC 1182,BETHESDA,MD 20892, USA. NR 20 TC 46 Z9 46 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 1997 VL 205 IS 3 BP 767 EP 771 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA YG850 UT WOS:A1997YG85000023 PM 9393533 ER PT J AU Brown, KE Young, NS AF Brown, KE Young, NS TI The simian parvoviruses SO REVIEWS IN MEDICAL VIROLOGY LA English DT Review ID B19 PARVOVIRUS; INFECTION; GENOME; CLONING; ANEMIA AB Autonomous parvoviruses with tropism for erythroid cells have recently been reclassified in a new genus, erythrovirus. Although B19 is the type member, and presently the only internationally accepted member of the erythrovirus genus, we have identified three new simian viruses, all of which have the molecular features of parvoviruses, and are highly tropic for erythroid progenitor cells. This review describes the identification of these new animal parvoviruses and summarises current knowledge of their molecular, clinical and epidemiological features. Most studies have been performed with the first virus discovered, simian parvovirus (SPV), which was isolated from anaemic cynomolgus monkeys. SPV is currently under investigation as an animal model for B19 parvovirus infection. Clinical similarities and molecular homology to parvovirus B19 justify the inclusion of these novel viruses as new members of the erythrovirus genus. (C) 1997 by John Wiley & Sons, Ltd. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Brown, KE (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Room 7C218,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 22 TC 14 Z9 15 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1052-9276 J9 REV MED VIROL JI Rev. Med. Virol. PD DEC PY 1997 VL 7 IS 4 BP 211 EP 218 DI 10.1002/(SICI)1099-1654(199712)7:4<211::AID-RMV204>3.3.CO;2-W PG 8 WC Virology SC Virology GA YP668 UT WOS:000071302000003 ER PT J AU Cohn, M AF Cohn, M TI Some thoughts on the response to antigens that are effector T-helper independent ('thymus independence') SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Review ID MODEL AB The Self-Non-Self discrimination is germline-selected for defence mechanisms ('innate immune systems') whereas it is somatically learned for immune systems ('adaptive immune systems'). It is proposed that immune systems evolved from defence mechanisms by adding large recognitive repertoires that, by aggregating with antigens, were able to trigger the already existent effector functions of defence mechanisms. Thus today there are two pathways to triggering each class of effector function (macrophage opsonization, complement lysis or natural killer/-natural cytotoxic cell activity). The antigen-antibody complex and the T-cell antigen-receptor interaction trigger the immune pathway; the receptors of the defence mechanism trigger the 'alternate' or 'innate' pathway. The evolutionary selection pressure on defence mechanisms was to increase the size of the recognitive repertoire, which in turn, necessitated the emergence of a somatically learned Self-Non-Self discrimination. By contrast with defence mechanisms that are triggered effector T-helper (eTh) independently by polymers (Signal[3]), immune systems can be activated by monomers, a pathway that requires associative recognition of monomer and the reading of two Signals, Signal[1] resulting from the binding of an epitope to the antigen-receptor complex, Signal[2] delivered by an eTh cell. The evolving immune system hijacked part of this eTh-independent pathway (Signal[3]) into which Signal([1]+[2]) merged. A model of these relationships is proposed. C1 NIH, Fogarty Int Ctr Adv Study Hlth Sci, Bethesda, MD 20892 USA. Salk Inst Biol Studies, Conceptual Immunol Grp, San Diego, CA 92138 USA. RP Cohn, M (reprint author), Salk Inst Biol Studies, Conceptual Immunol Grp, San Diego, CA 92138 USA. FU NCRR NIH HHS [R01 RR007716, RR07716] NR 5 TC 15 Z9 15 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD DEC PY 1997 VL 46 IS 6 BP 565 EP 571 DI 10.1046/j.1365-3083.1997.d01-172.x PG 7 WC Immunology SC Immunology GA YN864 UT WOS:000071216000006 PM 9420619 ER PT J AU Lenhoff, HM Wang, PP Greenberg, F Bellugi, U AF Lenhoff, HM Wang, PP Greenberg, F Bellugi, U TI Williams syndrome and the brain SO SCIENTIFIC AMERICAN LA English DT Article C1 UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD. SALK INST BIOL STUDIES,COGNIT NEUROSCI LAB,SAN DIEGO,CA 92138. RP Lenhoff, HM (reprint author), UNIV CALIF IRVINE,IRVINE,CA 92717, USA. NR 3 TC 71 Z9 73 U1 0 U2 3 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 0036-8733 J9 SCI AM JI Sci.Am. PD DEC PY 1997 VL 277 IS 6 BP 68 EP 73 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YG852 UT WOS:A1997YG85200026 PM 9388834 ER PT J AU Ferrucci, L Guralnik, JM Pahor, M Harris, T Corti, MC Hyman, BT Wallace, RB Havlik, RJ AF Ferrucci, L Guralnik, JM Pahor, M Harris, T Corti, MC Hyman, BT Wallace, RB Havlik, RJ TI Apolipoprotein E epsilon 2 allele and risk of stroke in the older population SO STROKE LA English DT Article DE aging; apolipoproteins; risk factors; stroke ID CORONARY HEART-DISEASE; ONSET ALZHEIMERS-DISEASE; E POLYMORPHISM; EUROPEAN POPULATIONS; LIPOPROTEIN-LIPASE; VASCULAR DEMENTIA; ARTERY DISEASE; E GENE; MEN; CHOLESTEROL AB Background and Purpose There is evidence for a role of apolipoprotein E (apoE) in atherosclerosis. Coronary heart disease morbidity is higher in persons carrying an epsilon 4 allele and lower in those carrying an epsilon 2 allele, but the effect on cerebrovascular disease is controversial. We estimated the risk of stroke associated with different apoE genotypes in older persons. Methods At the sixth annual follow-up of the Iowa cohort of the Established Populations for Epidemiologic Studies of the Elderly, 1664 persons aged greater than or equal to 71 years and free of stroke were genotyped for apo E Occurrence of ischemic strokes was prospectively assessed from subsequent hospital discharge records and death certificates. Results One hundred fifty persons had an ischemic stroke over the subsequent 5 years (21.2 per 1000 person-years). The presence of epsilon 3 and epsilon 4 did not influence stroke risk. Among persons aged < 80 years at the time of genotyping, epsilon 2 carriers had lower risk of incident stroke, while no effect was detected in the older group, Compared with epsilon 2 carriers aged 70 to 79 years (reference group), those in the same age group and not carrying an epsilon 2 had 2.6-fold higher risk of incident stroke, and those aged greater than or equal to 80 years had even higher risks of stroke but without any difference according to presence/absence of epsilon 2 (relative risks 3.6 and 3.3). Results remained substantially unchanged when adjusted for potential confounders and in models estimating the effect of apoE polymorphism on the risk of developing a stroke at ages between 70 and 79 years (56 events) and separately at ages greater than or equal to 80 years (94 events). Conclusions The conditioning influence of age on the protection conferred by the apoE epsilon 2 allele on stroke risk may account for previous controversies. This hypothesis should be verified in a population with a wider age range. C1 I FRATICINI NATL RES INST,DEPT GERIATR,INRCA,FLORENCE,ITALY. UNIV TENNESSEE,DEPT PREVENT MED,MEMPHIS,TN. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. UNIV IOWA,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA 52242. RP Ferrucci, L (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,NIH,7201 WISCONSIN AVE,GATEWAY BLDG,SUITE 3C-309,BETHESDA,MD 20892, USA. FU NIA NIH HHS [N01-AG-0 TO 2105] NR 53 TC 44 Z9 45 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 1997 VL 28 IS 12 BP 2410 EP 2416 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA YL157 UT WOS:A1997YL15700013 PM 9412623 ER PT J AU Gueyffier, F Boissel, JP Boutitie, F Pocock, S Coope, J Cutler, J Ekbom, T Fagard, R Friedman, L Kerlikowske, K Perry, M Prineas, R Schron, E AF Gueyffier, F Boissel, JP Boutitie, F Pocock, S Coope, J Cutler, J Ekbom, T Fagard, R Friedman, L Kerlikowske, K Perry, M Prineas, R Schron, E TI Effect of antihypertensive treatment in patients having already suffered from stroke - Gathering the evidence SO STROKE LA English DT Editorial Material DE antihypertensive agents; clinical trials; hypertension; meta-analysis; stroke prevention ID HIGH BLOOD-PRESSURE; HYPERTENSION; TRIALS; METAANALYSIS AB Background and Purpose Drug treatment of high blood pressure has been shown to reduce the associated cardiovascular risk. Stroke represents the type of event more strongly linked with high blood pressure, responsible for a high rate of death or invalidity, and with the highest proportion of events that can be avoided by treatment. Hypertensive patients with a history of cerebrovascular accident are at particularly high risk of recurrence. Specific trials of blood pressure lowering drugs in stroke survivors showed inconclusive results in the past. Methods We performed a meta-analysis using all available randomized controlled clinical trials assessing the effect of blood pressure lowering drugs on clinical outcomes (recurrence of stroke, coronary events, cause-specific, and overall mortality) in patients with prior stroke or transient ischemic attack. Results We identified 9 trials, including a total of 6752 patients: 2 trials included 551 hypertensive stroke survivors; 6 trials of hypertensive patients included a small proportion of stroke survivors (536 patients); 1 trial included stroke survivors, whether hypertensive or not (5665 patients). The recurrence of stroke, fatal and nonfatal, was significantly reduced in active groups compared with control groups consistently across the different sources of data (relative risk of 0.72, 95% confidence interval: 0.61 to 0.85). There was no evidence that this intervention induced serious adverse effect. Conclusions Blood pressure lowering drug interventions reduced the risk of stroke recurrence in stroke survivors. Available data did not allow to verify whether such benefit depends on initial blood pressure level. More data are needed before considering antihypertensive therapy in normotensive patients at high cerebrovascular risk. C1 UNIV LYON 1,LYON HOSP,DEPT CLIN PHARMACOL,LYON,FRANCE. UNIV LONDON LONDON SCH HYG & TROP MED,LONDON WC1E 7HT,ENGLAND. NHLBI,BETHESDA,MD 20892. HYPERTENS & CARDIOVASC REHABIL UNIT,LOUVAIN,BELGIUM. VET ADM MED CTR,SAN FRANCISCO,CA 94121. DEPT COMMUNITY HLTH SCI,DALBY,LUND,SWEDEN. UNIV MIAMI,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,MIAMI,FL. WASHINGTON UNIV,SCH MED,ST LOUIS,MO. RI Gueyffier, Francois/B-8545-2008 OI Gueyffier, Francois/0000-0002-9921-0977 NR 19 TC 175 Z9 178 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 1997 VL 28 IS 12 BP 2557 EP 2562 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA YL157 UT WOS:A1997YL15700042 PM 9412649 ER PT J AU Wu, PC Alexander, HR Bartlett, DL Doppman, JL Fraker, DL Norton, JA Gibril, F Fogt, F Jensen, RT AF Wu, PC Alexander, HR Bartlett, DL Doppman, JL Fraker, DL Norton, JA Gibril, F Fogt, F Jensen, RT TI A prospective analysis of the frequency, location, and curability of ectopic (nonpancreaticoduodenal, nonnodal) gastrinoma SO SURGERY LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the American-Association-of-Endocrine-Surgeons CY APR 06-08, 1997 CL BALTIMORE, MARYLAND SP Amer Assoc Endocrine Surgeons ID ZOLLINGER-ELLISON SYNDROME; EXTRAPANCREATIC GASTRINOMAS; RESECTION; SURGERY; LIVER AB Background. Extrapancreatic, extraduodenal, and extralymphatic (ectopic) gastrinomas have been reported only rarely. The frequency, locations, and surgical outcome of these lesions are unknown. Methods. From 1982 to 1997, 215 patients with Zollinger-Ellison syndrome were evaluated prospectively at the National Institutes of Health and 142 patients (66 %) underwent standardized surgical exploration and resection. Eight patients (5.6 %) (six men and two women; mean age, 41 years) had primary gastrinoma located in ectopic sites. Long-term follow-up, was derived from a prospective database. Results. Ectopic gastrinoma tissue was identified and resected in the liver (three patients), common bile duct (one patient), jejunum (one patient), omentum (one patient), pylorus (one patient), and ovary (one patient). Seven patients (88 %) were cured biochemically after resection and five patients (63 %) have sustained cures, with a mean follow-up of 7.5 years (range, 0.4 to 11.7 years). One patient with a jejunal primary gastrinoma had a biochemical recurrence at 2 years, and another with a primary hepatic gastrinoma had a recurrence 6 years after resection. A patient with a pyloric primary gastrinoma was not cured. Conclusions. Extraduodenal, extrapancreatic, and extranodal gastrinomas are encountered in 5.6% of patients who undergo exploration with curative Intent. If no gastrinoma is found in the usual locations, other ectopic sites should be examined carefully. Resection of these primary ectopic tumors can lead to durable biochemical cures. C1 NCI, Surg Metab Sect, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Alexander, HR (reprint author), NCI, Surg Metab Sect, Surg Branch, NIH, Bldg 10,Room 2B07, Bethesda, MD 20892 USA. NR 25 TC 32 Z9 33 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1997 VL 122 IS 6 BP 1176 EP 1182 DI 10.1016/S0039-6060(97)90224-5 PG 7 WC Surgery SC Surgery GA YM682 UT WOS:000071089200049 PM 9426435 ER PT J AU Libutti, SK Bartlett, DL Jaskowiak, NT Skarulis, M Marx, SJ Speigel, AM Fraker, DL Doppman, JL Shawker, TJ Alexander, HR AF Libutti, SK Bartlett, DL Jaskowiak, NT Skarulis, M Marx, SJ Speigel, AM Fraker, DL Doppman, JL Shawker, TJ Alexander, HR TI The role of thyroid resection during reoperation for persistent or recurrent hyperparathyroidism SO SURGERY LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the American-Association-of-Endocrine-Surgeons CY APR 06-08, 1997 CL BALTIMORE, MARYLAND SP Amer Assoc Endocrine Surgeons ID PARATHYROID-GLANDS; MANAGEMENT; ADENOMAS; SURGERY; ANATOMY AB Background. The role of "bind" thyroid lobectomy in the surgical management of patients with persistent or recurrent primary hyperparathyroidism is not known. We reviewed our experience with reoperation for hyperparathyroidism to determine the utility of blind thyroid resection in this setting. Methods. From 1982 to 1995, 269 patients underwent reoperation for hyperparathyroidism at our institution. All patients had biochemical confirmation of hyperparathyroidism and underwent noninva sive and if necessary invasive localization studies. Patients who underwent thyroid lobectomy in an attempt to extirpate the hyperfunctioning parathyroid gland form the basis of this report. Results. Thirty-two of 269 patients (12 %) underwent thyroid lobectomy to remove a parathyroid gland. Intrathyroidal parathyroids were confirmed in 19 of 32 patients (59%). In 18 of 19 patients (94 %), preoperative or intraoperative ultrasonography correctly identified an intrathyroidal lesion suspicious for a parathyroid. Only 1 of 6 patients (17 %) undergoing a blind thyroidectomy had an intrathyroidal gland identified. Ultrasonography had a sensitivity of 95 % and a negative predictive value of 99.5 % in detecting an intrathyroidal parathyroid gland. Conclusions. The prevalence of an intrathyrodal parathyroid gland in our series is low (19 of 269, 7 %). Ultrasonography can be used reliably to select patients for thyroid resection, reducing the need to perform a blind thyroid lobectomy and avoiding the potential morbidity of thyroid resection in this clinical setting. C1 NIDDKD, Surg Branch, NCI, Metab Dis Branch, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Alexander, HR (reprint author), NCI, Surg Metab Sect, Surg Branch, NIH, Bldg 10,Room 2B07, Bethesda, MD 20892 USA. NR 14 TC 5 Z9 5 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1997 VL 122 IS 6 BP 1183 EP 1187 DI 10.1016/S0039-6060(97)90225-7 PG 5 WC Surgery SC Surgery GA YM682 UT WOS:000071089200051 PM 9426436 ER PT J AU Brown, CK Bartlett, DL Doppman, JL Gorden, P Libutti, SK Fraker, DL Shawker, TH Skarulis, MC Alexander, HR AF Brown, CK Bartlett, DL Doppman, JL Gorden, P Libutti, SK Fraker, DL Shawker, TH Skarulis, MC Alexander, HR TI Intraarterial calcium stimulation and intraoperative ultrasonography in the localization and resection of insulinomas SO SURGERY LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the American-Association-of-Endocrine-Surgeons CY APR 06-08, 1997 CL BALTIMORE, MARYLAND SP Amer Assoc Endocrine Surgeons ID PANCREAS; TUMORS AB Background. Standard imaging studies (computed tomography, magnetic resonance imaging somatostatin receptor scintigraphy, ultrasonography, and angiography) correctly localize insulinomas in less than 50 % of patients and provide no information about the feasibility of enucleation based on proximily of tumor to pancreatic duct. We reviewed our experience with intraarterial calcium stimulation (Ca-Stim) and intraoperative ultrasonography (IOUS) to localize and guide management of insulinomas. Methods. Thirty-six patients (14 men, 22 women, median age 44 years) with insulinomas were treated between August 1989 and June 1996. Preoperative imaging studies were obtained. Patients underwent abdominal exploration with IOUS. Fourteen were evaluated by a surgeon blinded to preoperative imaging results. Results. Tumors (4 to 50 mm) were resected by enucleation (67 %) or partial pancreatectomy (33 %); all were cured. Sensitivities of computed tomography, magnetic resonance imaging somatostatin receptor scintigraphy, ultrasonography, angiography, and Ca-Stim in localizing insulinomas were 24 %, 45 %, 17%, 13 %, 43 %, and 94 %, respectively. Tumors were identified by blinded surgical exploration with IOUS in 12 of 14 patients (86 %). Conclusions. All insulinomas were identified before operation; however, sensitivity of individual noninvasive tests was low (less than 50 %). In contrast, Ca-Stim was correct in 94 % of cases, thus allowing a focused pancreatic exploration and obviating-use of blind distal pancreatectomy. IOUS can then De used to guide safe enucleation. C1 NCI, Surg Metab Sect, Surg Branch, NIH, Bethesda, MD 20892 USA. Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD USA. NIDDKD, Clin & Cellular Biol Sect, Diabet Branch, Bethesda, MD 20892 USA. NIDDKD, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Alexander, HR (reprint author), NCI, Surg Metab Sect, Surg Branch, NIH, Bldg 10,Room 2B07,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 8 TC 65 Z9 70 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1997 VL 122 IS 6 BP 1189 EP 1193 DI 10.1016/S0039-6060(97)90226-9 PG 5 WC Surgery SC Surgery GA YM682 UT WOS:000071089200053 PM 9426437 ER PT J AU Liu, X Musachio, JL Wagner, HN Mochizuki, T Dannals, RF London, ED AF Liu, X Musachio, JL Wagner, HN Mochizuki, T Dannals, RF London, ED TI External monitoring of cerebral nicotinic acetylcholine receptors in living mice SO SYNAPSE LA English DT Article ID EPIBATIDINE; BRAIN; AGONIST; RAT C1 NIDA,BRAIN IMAGING CTR,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,DIV NUCL MED & RADIAT HLTH SCI,BALTIMORE,MD 21205. NR 8 TC 3 Z9 4 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD DEC PY 1997 VL 27 IS 4 BP 378 EP 380 PG 3 WC Neurosciences SC Neurosciences & Neurology GA YE826 UT WOS:A1997YE82600011 PM 9372560 ER PT J AU Sarlis, NJ Brucker-Davis, F Swift, JP Tahara, K Kohn, LD AF Sarlis, NJ Brucker-Davis, F Swift, JP Tahara, K Kohn, LD TI Graves' disease following thyrotoxic painless thyroiditis. Analysis of antibody activities against the thyrotropin receptor in two cases SO THYROID LA English DT Article ID LYMPHOCYTIC THYROIDITIS; SILENT THYROIDITIS; STIMULATING ANTIBODIES; IDIOPATHIC MYXEDEMA; IMMUNOGLOBULINS; CELLS; HETEROGENEITY; TSH AB The exact immunologic mechanisms that lead to the emergence and progression of painless ("silent") thyroiditis remain unclear. We report two cases of painless postpartum thyroiditis followed by Graves' disease, where extensive immunologic evaluation supported a possible pathogenetic association. The time course of changes in thyroid function tests, I-123 thyroidal uptake values, and thyrotropin receptor antibodies (TSHRAbs) were documented. The existence of stimulating TSHRAbs (TSAbs) activating the cyclic adenosine monophosphate (cAMP) and phosphatidylinositol 4,5-bisphosphate (PIP2) signal cascades and their functional epitopes, as well as two different thyrotropin-binding inhibitory immunoglobulins (TBII) were documented in both patients at the time of diagnosis of Graves' disease. We suggest that susceptible persons may develop an immunologic response that can trigger the appearance of a mixture of species of TSHRAbs, which in turn may lead to the sequential occurrence of painless thyroiditis and Graves' disease. Additionally, the multiple phases of hyperthyroidism and hypothyroidism that can occur in these patients may reflect the existence and changing spectrum of TSHRAbs in their sera. C1 NIDDK, SHS, LMCB, NIH, Bethesda, MD 20892 USA. NIDDK, Mol & Cellular Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Cell Regulat Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Internal Med Ctr PA, Chevy Chase, MD USA. Chiba Univ, Sch Med, Dept Internal Med 2, Div Endocrinol & Metab,Chuo Ku, Chiba 260, Japan. RP NIDDK, SHS, LMCB, NIH, Bldg 8,Rm B2 A11,8 Ctr Dr, Bethesda, MD 20892 USA. NR 30 TC 15 Z9 15 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD DEC PY 1997 VL 7 IS 6 BP 829 EP 836 DI 10.1089/thy.1997.7.829 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YP949 UT WOS:000071332200003 PM 9459624 ER PT J AU Schuppert, F Rambusch, E Kirchner, H Atzpodien, J Kohn, LD von zur Muhlen, A AF Schuppert, F Rambusch, E Kirchner, H Atzpodien, J Kohn, LD von zur Muhlen, A TI Patients treated with interferon-alpha, interferon-beta, and interleukin-2 have a different thyroid autoantibody pattern than patients suffering from endogenous autoimmune thyroid disease SO THYROID LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the German-Society-of-Endocrinology CY 1997 CL LUBECK, GERMANY SP German Soc Endocrinol ID CHRONIC HEPATITIS-C; CYTOKINE GENE-EXPRESSION; COMPLEX CLASS-I; GRAVES-DISEASE; THYROTROPIN RECEPTOR; EPITHELIAL-CELLS; HUMAN THYROCYTES; GAMMA; HLA; ANTIGEN AB Cytokines are believed to mediate the induction and perpetuation of autoimmune thyroid disease (ATD) in humans. However, this concept is mainly based on in vitro findings and to date, concrete in vivo evidence is still lacking. This prompted us to compare serum thyroid parameters of patients treated with cytokines with patients suffering from ATD. The cytokine group (n = 61) consisted of patients suffering from chronic hepatitis (n = 27) and from hemato-oncological diseases (n = 34). Patients were treated with interferon-alpha (IFN-alpha) or IFN-beta, either alone (n = 31) or in combination with interleukin-2 (IL-2) (n = 15) or with antineoplastic agents (n = 15). The ATD group (n = 105) consisted of 51 patients with Graves' disease, 26 with euthyroid ATD, 18 with Hashimoto's disease, and 10 with atrophic thyroiditis. Only 6 of 61 patients (10%) from the cytokine-treated group had thyroid peroxidase antibody (TPOAb) titers equal to or greater than 100 U/mL, whereas 82 of 87 patients (94%) suffering from ATD had TPOAb titers equal to or greater than 100 U/mL (p = 0.0001). In contrast, the percentage of patients who had thyroglobulin antibody (TgAb) serum titers equal to or greater than 100 U/mL were identical in both groups: 25 of 61 patients (41%) treated with cytokines versus 40 of 87 patients (46%) suffering from ATD (p = 0.789). Thus, patients with ATD had significantly higher TPOAb titers (p = 0.0001) whereas TgAb titers were not significantly different compared with patients from the cytokine group. The substantial difference in autoantibody response raises the possibility that thyroid abnormalities associated with ATD reflect genetic susceptibility and/or an independent stimulus or incident aside from cytokine dysfunction and that cytokines may play a secondary, rather than primary role in disease expression. C1 Hannover Med Sch, Dept Clin Endocrinol, D-30625 Hannover, Germany. Hannover Med Sch, Dept Gastroenterol & Hepatol, D-30625 Hannover, Germany. Hannover Med Sch, Dept Hematol & Oncol, D-30625 Hannover, Germany. Siloah Hosp, Dept Oncol, Hannover, Germany. NIDDK, Metab Dis Branch, NIH, Bethesda, MD USA. RP Schuppert, F (reprint author), Hannover Med Sch, Dept Clin Endocrinol, Carl Neuberg Str 1, D-30625 Hannover, Germany. NR 26 TC 13 Z9 13 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 DEC PY 1997 VL 7 IS 6 BP 837 EP 842 DI 10.1089/thy.1997.7.837 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YP949 UT WOS:000071332200004 PM 9459625 ER PT J AU Tahara, K Ishikawa, N Yamamoto, K Hirai, A Ito, K Tamura, Y Yoshida, S Saito, Y Kohn, LD AF Tahara, K Ishikawa, N Yamamoto, K Hirai, A Ito, K Tamura, Y Yoshida, S Saito, Y Kohn, LD TI Epitopes for thyroid stimulating and blocking autoantibodies on the extracellular domain of the human thyrotropin receptor SO THYROID LA English DT Article ID IDIOPATHIC MYXEDEMA PATIENTS; HIGH-AFFINITY BINDING; AMINO-ACIDS 268-304; N-TERMINAL REGION; TSH RECEPTOR; GONADOTROPIN RECEPTORS; SIGNAL-TRANSDUCTION; DIFFERENT SITES; IDENTIFICATION; ANTIBODIES AB The majority (97%) of functional epitopes for stimulating thyrotropin receptor (TSHR) antibodies (stimulating TSHRAbs) in a large cohort (n = 59) of Japanese Graves' patients exists on the N-terminal region of the extracellular domain of TSHR, between residues 25 and 165 numbering from the methionine start site. This was determined by measuring the loss of stimulating activity in the Cos-7 cells transfected with TSHR/lutropin-choriogonadotropin receptor (LH-CGR) chimeras wherein TSHR residues 89-165 (Mc2) or 8-165 (Mc1 + 2) are replaced by comparable LH-CGR residues. There is no comparable loss when stimulating TSHRAb activity is measured in an Mc4 chimera, wherein TSHR residues 261 to 370 are replaced. In contrast, immunoglobulin (IgG) preparations from 35 patients with Hashimoto's disease or idiopathic myxedema, who have blocking TSHRAbs causing hypothyroidism, loose blocking TSHRAb activity in the Mc4 chimera, but not the Mc2 or Mc1 + 2 chimeras. Thus, in a large population of Japanese patients with autoimmune thyroid disease caused by TSHR autoantibodies, the major functional epitope for stimulating TSHRAbs is on the N-terminal portion of the TSHR extracellular domain, whereas that for blocking TSHRAbs is on the C-terminal portion of the extracellular domain. To further evaluate the nature of the critical functional epitope between residues 90 to 165, we divided this region approximately in half, creating chimeras Mc2a and Mc2b with, respectively, residues 90-124 or 125-165 replaced by comparable LH-CGR residues. IgGs from all patients tested lost significant stimulating activity using the Mc2a and Mc2b chimeras; however, when present, residual stimulating TSHRAb activity was evident on one or the other half of the region or on both halves, indicating that both segments are required for expression of the stimulating TSHRAb epitope within residues 90-165. Finally, we have identified a complex epitope involving both the N- and C-terminal portion of the extracellular domain that appears to account for the small fraction of stimulating TSHRAbs whose activity is not solely dependent on residues 25 to 165. Thus, using chimeras Mc1 + 2 + 4, with TSHR residues 8-165 and 261-370 substituted, or chimera Mc1 + 2 + 3 + 4, with residues 8-370 substituted, as well as Mc2, Mc1 + 2, and Mc4, we show that the Graves' IgGs which maintain stimulating TSHRAb activity when residues 8-165 of the TSHR are replaced by LH-CGR residues have an epitope involving residues 90-165 and the immunogenic 15mer peptide (YYVFFEEQEDEIIGF), residues, 352-366. Because that peptide can decrease the stimulating TSHRAb activity of these Graves IgGs in assays with the Mc2 chimera alone, we speculate that this complex epitope may be important in an epitope spreading process involved in the formation of stimulating TSHRAbs. C1 NIDDK, Cell Regulat Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Chiba Univ, Sch Med, Dept Internal Med 2, Chiba 280, Japan. Ito Hosp, Tokyo 150, Japan. RP Tahara, K (reprint author), NIDDK, Cell Regulat Sect, Metab Dis Branch, NIH, Bldg 10,Room 9C101B,10 Ctr Dr MSC 1800, Bethesda, MD 20892 USA. NR 29 TC 40 Z9 41 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 DEC PY 1997 VL 7 IS 6 BP 867 EP 877 DI 10.1089/thy.1997.7.867 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YP949 UT WOS:000071332200009 PM 9459630 ER PT J AU Zimmerman, PA Wieseman, M Spalding, T Boatin, BA Nutman, TB AF Zimmerman, PA Wieseman, M Spalding, T Boatin, BA Nutman, TB TI A new intercellular adhesion molecule-1 allele identified in west Africans is prevalent in African-Americans in contrast to other North American racial groups SO TISSUE ANTIGENS LA English DT Article DE ICAM-1; allele; West Africa ID ICAM-1; IMMUNOGLOBULIN C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland Med Syst, Amer Red Cross, Natl Histocompatibil Lab, Baltimore, MD USA. Onchocerciasis Control Programme, Ouagadougou, Burkina Faso. RP Zimmerman, PA (reprint author), Case Western Reserve Univ, Sch Med, Div Geog Med, W147D, 2109 Adelbert Rd, Cleveland, OH 44106 USA. NR 5 TC 6 Z9 6 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD DEC PY 1997 VL 50 IS 6 BP 654 EP 656 DI 10.1111/j.1399-0039.1997.tb02926.x PG 3 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA YL733 UT WOS:000070987400014 PM 9458121 ER PT J AU Morgan, DL Shines, CJ Jeter, SP Blazka, ME Elwell, MR Wilson, RE Ward, SM Price, HC Moskowitz, PD AF Morgan, DL Shines, CJ Jeter, SP Blazka, ME Elwell, MR Wilson, RE Ward, SM Price, HC Moskowitz, PD TI Comparative pulmonary absorption, distribution, and toxicity of copper gallium diselenide, copper indium diselenide, and cadmium telluride in Sprague-Dawley rats SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID MACROPHAGE FIBRONECTIN RELEASE; ALVEOLAR MACROPHAGE; LUNG INJURY; FIBROSIS; RESPONSES; AEROSOL; CELLS AB Copper gallium diselenide (CGS), copper indium diselenide (CIS), and cadmium telluride (CdTe) are novel compounds used in the photovoltaic and semiconductor industries. This study was conducted to characterize the relative toxicities of these compounds and to evaluate the pulmonary absorption and distribution after intratracheal instillation. Female Sprague-Dawley rats were administered a single equimolar dose (70 mM) of CGS (21 mg/kg), CIS (24 mg/kg), CdTe (17 mg/kg), or saline by intratracheal instillation. Bronchoalveolar lavage fluid (BALF) protein, fibronectin, inflammatory cells, lung hydroxyproline, and tissue distribution were measured 1, 3, 7, 14, and 28 days after instillation. Relative lung weights were significantly increased in CIS- and CdTe-treated rats at most time points. Inflammatory lesions in the lungs consisting of an influx of macrophages, lymphocytes, and PMNs were most severe in CdTe-treated rats, intermediate in CIS-treated rats, and minimal in rats receiving CGS. Hyperplasia of alveolar type 2 cells was present in CIS-and CdTe-treated rats and was greatest in CdTe-treated rats. Pulmonary interstitial fibrosis was observed in CdTe-treated rats at all time points. All three compounds caused marked increases in total BALF cell numbers, with the greatest increase observed in CIS-treated rats. BALF protein, fibronectin, and lung hydroxyproline were significantly increased in all treated animals and were highest in CdTe-treated animals. There was no apparent pulmonary absorption or tissue distribution of CGS. Indium levels increased in extrapulmonary tissues of CIS-treated rats, although Cu and Se levels remained unchanged. CdTe was absorbed from the lung to a greater extent than CGS and CIS. Cd and Te levels decreased in the lung and increased in extrapulmonary tissues. Of these compounds CdTe presents the greatest potential health risk because it causes severe pulmonary inflammation and fibrosis and because it is readily absorbed from the lung may potentially cause extrapulmonary toxicity. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Mantech Environm Technol Inc, Res Triangle Pk, NC 27709 USA. Brookhaven Natl Lab, Upton, NY 11973 USA. RP Morgan, DL (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 27 TC 24 Z9 25 U1 0 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD DEC PY 1997 VL 147 IS 2 BP 399 EP 410 DI 10.1006/taap.1997.8267 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA YR553 UT WOS:000071506800024 PM 9439735 ER PT J AU Kohn, MC AF Kohn, MC TI The importance of anatomical realism for validation of physiological models of disposition of inhaled toxicants SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID INHALATION PHARMACOKINETICS; RISK ASSESSMENT; SPECIES-DIFFERENCES; BUTADIENE MONOXIDE; RATS; MICE; METABOLISM; 1,3-BUTADIENE; HUMANS; MOUSE AB The goodness of fit of three PBPK models to data for inhalation uptake of 1,3-butadiene by mice from closed chambers were compared. These models included a classical flow-limited model with blood consolidated into arterial and venous compartments, a flow-limited model with implicit blood and alveolar compartments, and a model with an actual alveolar compartment and blood distributed among compartments for arterial, venous, and capillary spaces. Using physiological and biochemical parameters from the literature, all three models reproduced observed steady-state blood butadiene concentrations. However, the first two models predicted more rapid uptake of butadiene than was observed. Assumptions such as ignoring extrahepatic metabolism or reducing the ventilation rate by 75% were required to enable these models to fit the butadiene uptake data. The behavior of the third model resembled that of the other two models when the single-pass extraction ratio of butadiene for all tissues was close to 1, but the model did reproduce observed butadiene uptake when an extraction ratio of 0.5 was used. The difference in predictions of the three models was traced to smaller computed blood:tissue gradients and tissue butadiene concentrations, hence reduced rates of metabolic clearance, when the blood is distributed. These results suggest that the common assumption of flow limitation in the disposition of an inhaled gas may not always be appropriate. Because structurally different models can reproduce the same uptake data and all these models cannot be correct, the assumptions on which these models were based must be investigated experimentally to ensure that they are physiologically realistic. C1 NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. RP Kohn, MC (reprint author), NIEHS, Lab Computat Biol & Risk Anal, POB 12233,Mail Drop A3-06, Res Triangle Pk, NC 27709 USA. NR 38 TC 31 Z9 32 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD DEC PY 1997 VL 147 IS 2 BP 448 EP 458 DI 10.1006/taap.1997.8289 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA YR553 UT WOS:000071506800029 PM 9439740 ER PT J AU Matzinger, P AF Matzinger, P TI The immune system's role in graft loss: Theoretic considerations SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT Symposium on Individualizing Immunosuppression - Strategies for the Next Decade CY OCT 25-26, 1996 CL TUCSON, ARIZONA ID NONSELF; SELF C1 NIAID, Div Intramural Res, Bethesda, MD 20892 USA. RP Matzinger, P (reprint author), NIAID, Div Intramural Res, Bldg 4,Room 111, Bethesda, MD 20892 USA. NR 6 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD DEC PY 1997 VL 29 IS 8A SU S BP 11S EP 12S DI 10.1016/S0041-1345(97)00848-8 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA YN007 UT WOS:000071123700002 PM 9414667 ER PT J AU Zachary, AA Leffell, MS Johnson, A Rose, SM Bias, WB AF Zachary, AA Leffell, MS Johnson, A Rose, SM Bias, WB TI HLA antigens, alleles, and haplotypes among African-Americans SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 4th International Samuel L Kountz Symposium on Renal Disease and Transplantation in African Americans CY JUL 08-09, 1997 CL WASHINGTON, D.C. SP Sandoz, Fujisawa, Biotrin, Hoffman LaRoche, Ortho Biotech, Sang Stat, Trans-Med Corp, Waters Instruments, Wyeth-Ayerst Lab ID UNOS REGISTRY; DONORS C1 Johns Hopkins Univ, Baltimore, MD 21218 USA. Georgetown Univ, Washington, DC 20057 USA. NIH, Bethesda, MD 20892 USA. RP Zachary, AA (reprint author), Johns Hopkins Univ, Baltimore, MD 21218 USA. FU PHS HHS [N01A182514] NR 2 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 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD DEC PY 1997 VL 29 IS 8 BP 3706 EP 3706 DI 10.1016/S0041-1345(97)01118-4 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA YL514 UT WOS:000070963500228 PM 9414893 ER PT J AU Burshtyn, DN Long, EO AF Burshtyn, DN Long, EO TI Regulation through inhibitory receptors: lessons from natural killer cells SO TRENDS IN CELL BIOLOGY LA English DT Review ID TYROSINE-PHOSPHATASE 1C; FC-GAMMA-RIIB; NEGATIVE REGULATION; CYTOPLASMIC DOMAIN; SH2 DOMAINS; ACTIVATION; RECOGNITION; RECRUITMENT; MOTIF; PTP1C AB Natural killer (NK) cells employ an unconventional mode of recognition: they kill target cells that lack ligands for inhibitory NK cell receptors. Activation of NK cytotoxicity is tightly controlled by inhibitory receptors that recruit and activate the tyrosine phosphatase SHP-1 through the tyrosine-phosphorylated [I/V]xYxxL amino acid sequence in their cytoplasmic tail. This sequence motif, often referred to as an immunoreceptor tyrosine-based inhibitory motif (ITIM), is found in several other receptors that deliver similar negative signals in diverse types of cells. We suggest that this kind of regulation through inhibition is a widespread mechanism for the control of various cellular responses. RP Burshtyn, DN (reprint author), NIAID,IMMUNOGENET LAB,NIH,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 58 TC 57 Z9 57 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD DEC PY 1997 VL 7 IS 12 BP 473 EP 479 DI 10.1016/S0962-8924(97)01167-7 PG 7 WC Cell Biology SC Cell Biology GA YG867 UT WOS:A1997YG86700002 PM 17709010 ER PT J AU Kolenbrander, PE AF Kolenbrander, PE TI Biofilm developmental biology SO TRENDS IN MICROBIOLOGY LA English DT Letter ID CONFOCAL LASER MICROSCOPY C1 NIH, Bethesda, MD 20892 USA. RP Kolenbrander, PE (reprint author), NIH, Bldg 30,Room 310,30 Convent Dr,MSC 4350, Bethesda, MD 20892 USA. NR 5 TC 1 Z9 3 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD DEC PY 1997 VL 5 IS 12 BP 475 EP 475 DI 10.1016/S0966-842X(97)88501-0 PG 1 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA YP245 UT WOS:000071257300005 PM 9447658 ER PT J AU Barmes, DE Enwonwu, CO Leclercq, MH Bourgeois, D Falkler, WA AF Barmes, DE Enwonwu, CO Leclercq, MH Bourgeois, D Falkler, WA TI The need for action against oro-facial gangrene (noma) SO TROPICAL MEDICINE & INTERNATIONAL HEALTH LA English DT Editorial Material DE noma; cancrum oris; oro-facial gangrene; malnutrition; infections; developing countries; measles; visceral leishmaniasis; viral infections ID CANCRUM ORIS; CHILDREN C1 NIDR, Div Extramural Res, NIH, Bethesda, MD 20892 USA. Univ Maryland, Baltimore, MD 21201 USA. WHO, Noma Project, CH-1211 Geneva, Switzerland. Univ Lyon 1, Fac Odontol, F-69622 Villeurbanne, France. RP Barmes, DE (reprint author), NIDR, Div Extramural Res, NIH, 45 Ctr Dr,Natcher Bldg,Room 4AN-24D, Bethesda, MD 20892 USA. FU FIC NIH HHS [T37TW0025] NR 20 TC 29 Z9 30 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 1360-2276 J9 TROP MED INT HEALTH JI Trop. Med. Int. Health PD DEC PY 1997 VL 2 IS 12 BP 1111 EP 1114 DI 10.1046/j.1365-3156.1997.d01-220.x PG 4 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA YR991 UT WOS:000071553200001 PM 9438464 ER PT J AU Tsarev, SA Tsareva, TS Emerson, SU Govindarajan, S Shapiro, M Gerin, JL Purcell, RH AF Tsarev, SA Tsareva, TS Emerson, SU Govindarajan, S Shapiro, M Gerin, JL Purcell, RH TI Recombinant vaccine against hepatitis E: dose response and protection against heterologous challenge SO VACCINE LA English DT Article DE hepatitis E; HEV ORF2; hepatitis E vaccine ID TRANSMITTED NON-A; NON-B HEPATITIS; E VIRUS; PAKISTAN AB Thirty-two rhesus monkeys were used to evaluate the dose response of a recombinant HEV vaccine, and the efficacy of the vaccine based on the ORF2 protein of the Pakistani strain for pre- and post-exposure vaccination against intravenous challenge with homologous or heterologous virus was examined. Post-exposure vaccination did not protect animals against hepatitis. Although primates vaccinated twice 50-mu g, 10-mu g, 2-mu g, or 0.4-mu g doses of the recombinant 55 kDa ORF-2 protein were infected, they were protected from hepatitis when they were challenged with very high doses of the homologous strain of HEV. Primates vaccinated twice with a 50 mu g does of the recombinant protein were protected from hepatitis after heterologous challenge with the Mexican strain, the strain of HEV most genetically distant from the Pakistani strain. (C) 1997 Elsevier Science Ltd. C1 NIAID,HEPATITIS VIRUSES SECT,INFECT DIS LAB,NIH,BETHESDA,MD 20892. UNIV SO CALIF,RANCHO LOS AMIGOS HOSP,PATHOL & CLIN LABS,DOWNEY,CA 90242. GEORGETOWN UNIV,SCH MED,DIV MOL VIROL & IMMUNOL,ROCKVILLE,MD 20852. FU NIAID NIH HHS [N01-AI-05069, N01-AO-45180] NR 10 TC 83 Z9 93 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD DEC PY 1997 VL 15 IS 17-18 BP 1834 EP 1838 DI 10.1016/S0264-410X(97)00145-X PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA YJ428 UT WOS:A1997YJ42800005 PM 9413090 ER PT J AU Philipp, MT Lobet, Y Bohm, RP Roberts, ED Dennis, VA Gu, Y Lowrie, RC Desmons, P Duray, PH England, JD Hauser, P Piesman, J Xu, KY AF Philipp, MT Lobet, Y Bohm, RP Roberts, ED Dennis, VA Gu, Y Lowrie, RC Desmons, P Duray, PH England, JD Hauser, P Piesman, J Xu, KY TI The outer surface protein A (OspA) vaccine against Lyme disease: efficacy in the rhesus monkey SO VACCINE LA English DT Article; Proceedings Paper CT VII LDF Annual Scientific Conference on Lyme Borreliosis CY APR 28-29, 1995 CL VANCOUVER, CANADA DE vaccine efficacy; OspA; Borrelia burgdorferi; Lyme disease ID BORRELIA-BURGDORFERI; RECOMBINANT OSPA; NERVOUS-SYSTEM; A OSPA; MICE; TRANSMISSION; MODEL; NEUROBORRELIOSIS; IMMUNOGENICITY; INOCULATION AB The efficacy of an outer surface protein A (OspA) vaccine in three different formulations was investigated in the rhesus monkey. The challenge infection was administered using Ixodes scapularis ticks that were infected with the B31 strain of Borrelia burgdorferi. Protection was assessed against both infection and disease, by a variety of procedures. Some of the animals were radically immune suppressed, as an attempt to reveal any putative low level infection in the vaccinated animals. The significant difference found between the spirochaetal infection rates of ticks that had fed on vaccinated vs. control monkeys, lack of seroconversion in the vaccinated animals, and the absence of spirochaetal DNA in the skin of vaccinated monkeys were protected against tick challenge. The post-mortem immunohistochemical and polymerase chain reaction analyses, however, suggest that these monkeys may have undergone a low-level infection that was transient. (C) 1997 Elsevier Science Ltd. C1 SMITHKLINE BEECHAM BIOL,RIXENSART,BELGIUM. NCI,NIH,BETHESDA,MD 20892. LOUISIANA STATE UNIV,DEPT NEUROL,NEW ORLEANS,LA 70112. CTR DIS CONTROL & PREVENT,DIV VECTOR BORNE INFECT DIS,FT COLLINS,CO. RP Philipp, MT (reprint author), TULANE UNIV,MED CTR,TULANE REG PRIMATE RES CTR,COVINGTON,LA 70433, USA. FU NCRR NIH HHS [RR00164] NR 37 TC 35 Z9 35 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD DEC PY 1997 VL 15 IS 17-18 BP 1872 EP 1887 DI 10.1016/S0264-410X(97)00133-3 PG 16 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA YJ428 UT WOS:A1997YJ42800012 PM 9413097 ER PT J AU Parsegian, VA Podgornik, R AF Parsegian, VA Podgornik, R TI Surface-tension suppression of lamellar swelling on solid substrates SO COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS LA English DT Article ID THERMAL-MECHANICAL FLUCTUATIONS; CHARGED PHOSPHOLIPID-BILAYERS; X-RAY; FLUID MEMBRANES; HYDRATION FORCES; ELASTICITY; FILMS AB Multilayers of charged lipids immersed in distilled water swell to whatever dilution allowed them by the available volume of solvent. Multilayers of the same lipids on a solid surface will imbibe only a small amount of water from a vapor, even from a 100% relative-humidity vapor. We argue that the essential difference is in the extra work needed to create a vapor/multilayer interface. For stiff tightly packed multilayers, this interfacial energy is an additive constant of little consequence. But, in liquid water, multilayers swell to a softness where thermal excitation creates a rippled surface; the surface energy goes as the contour area not as the flat area of projected surface. The contour area grows as the multilayer swells. Vapor/liquid surface tension creates a "hard" surface that quells ripples and, usually, pulls the multilayer back to tighter packing. Tension can act to enhance direct attractive bilayer-bilayer forces such as weak van der Waals interactions to create new energy minima at very close spacings. These new energy minima might explain the limited swelling of charged lipids on substrates. What is remarkable is the long range and the strength of surface-tension perturbation on layered systems. In our statistical-thermodynamic formulation, bilayer motion is treated as the sum of undulations or waves that can pervade the entire multilayer. Disturbance of the surface can reach inward to distances comparable to the lateral extent of the multilayers. We use measured osmotic compressibility and bending rigidity to reveal the qualitative difference in affinity for water of multilayers in liquids and those on substrates exposed to vapors of the same chemical potential. (C) 1997 Elsevier Science B.V. C1 NIDDK, Struct Biol Lab, Div Comp Res & Technol, NIH, Bethesda, MD 20892 USA. NIDDK, Off Director Intramural Res, NIH, Bethesda, MD 20892 USA. RP Parsegian, VA (reprint author), NIDDK, Struct Biol Lab, Div Comp Res & Technol, NIH, Bethesda, MD 20892 USA. RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 27 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0927-7757 EI 1873-4359 J9 COLLOID SURFACE A JI Colloid Surf. A-Physicochem. Eng. Asp. PD NOV 30 PY 1997 VL 129 BP 345 EP 364 DI 10.1016/S0927-7757(97)00052-6 PG 20 WC Chemistry, Physical SC Chemistry GA YR645 UT WOS:000071516000031 ER PT J AU Procacci, P Darden, TA Paci, E Marchi, M AF Procacci, P Darden, TA Paci, E Marchi, M TI ORAC: A molecular dynamics program to simulate complex molecular systems with realistic electrostatic interactions SO JOURNAL OF COMPUTATIONAL CHEMISTRY LA English DT Article DE molecular dynamics; biomolecules; electrostatics; software; reversible multiple time-step algorithms ID CAR-PARRINELLO EQUATIONS; MULTIPLE TIME SCALES; PARTICLE MESH EWALD; LONG-RANGE FORCES; NUCLEIC-ACIDS; ALGORITHM; PROTEINS; MACROMOLECULES; TEMPERATURE; FORMULATION AB In this study, we present a new molecular dynamics program for simulation of complex molecular systems. The program, named ORAC, combines state-of-the-art molecular dynamics (MD) algorithms with flexibility in handling different types and sizes of molecules. ORAC is intended for simulations of molecular systems and is specifically designed to treat biomolecules efficiently and effectively in solution or in a crystalline environment. Among its unique features are: (i) implementation of reversible and symplectic multiple time step algorithms (or r-RESPA, reversible reference system propagation algorithm) specifically designed and tuned for biological systems with periodic boundary conditions; (ii) availability for simulations with multiple or single time steps of standard Ewald or smooth particle mesh Ewald (SPME) for computation of electrostatic interactions; and (iii) possibility of simulating molecular systems in a variety of thermodynamic ensembles. We believe that the combination of these algorithms makes ORAC more advanced than other MD programs using standard simulation algorithms. (C) 1997 John Wiley & Sons, Inc. C1 CEA,CTR ETUD,DSV,DBCM,SECT BIOPHYS PROT & MEMBRANES,F-91191 GIF SUR YVETTE,FRANCE. ECOLE NORMALE SUPER LYON,CTR EUROPEEN CALCUL ATOM & MOL,F-69364 LYON,FRANCE. NATL INST ENVIRONM HLTH,RES TRIANGLE PK,NC. UNIV FLORENCE,DIPARTIMENTO CHIM,I-50120 FLORENCE,ITALY. RI Marchi, Massimo/E-1792-2011; Paci, Emanuele/B-1893-2010; Procacci, Piero/D-7860-2012 OI Marchi, Massimo/0000-0003-4890-6349; Paci, Emanuele/0000-0002-4891-2768; Procacci, Piero/0000-0003-2667-3847 NR 52 TC 135 Z9 136 U1 0 U2 5 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0192-8651 J9 J COMPUT CHEM JI J. Comput. Chem. PD NOV 30 PY 1997 VL 18 IS 15 BP 1848 EP 1862 DI 10.1002/(SICI)1096-987X(19971130)18:15<1848::AID-JCC2>3.0.CO;2-O PG 15 WC Chemistry, Multidisciplinary SC Chemistry GA YD622 UT WOS:A1997YD62200002 ER PT J AU Chen, MG Ing, BL Robinson, KA Feagin, AC Buse, MG Quon, MJ AF Chen, MG Ing, BL Robinson, KA Feagin, AC Buse, MG Quon, MJ TI Effects of overexpression of glutamine : fructose-6-phosphate amidotransferase (GFAT) and glucosamine treatment on translocation of GLUT4 in rat adipose cells SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE glucose toxicity; hexosamine; insulin resistance ID DEPENDENT DIABETES-MELLITUS; PRIMARY CULTURED ADIPOCYTES; INSULIN-RESISTANCE; TRANSPORT SYSTEM; INDUCED DESENSITIZATION; GLYCOGEN-SYNTHASE; FRUCTOSE-6-PHOSPHATE AMIDOTRANSFERASE; HEXOSAMINE BIOSYNTHESIS; SKELETAL-MUSCLE; MESSENGER-RNA AB Insulin resistance is associated with diabetes. Hyperglycemia per se causes insulin resistance as well as increased flux of glucose through the hexosamine biosynthetic pathway. The rate-limiting enzyme for entry of glucose into this pathway is glutamine:fructose-6-phosphate amidotransferase (GFAT). To directly evaluate the role of GFAT in modulating insulin-stimulated glucose transport, we co-transfected primary cultures of rat adipose cells with expression vectors for human GFAT as well as an epitope-tagged GLUT4 and examined the effect of overexpressed GFAT on insulin-stimulated translocation of GLUT4. When we measured cell surface tagged GLUT4 in response to insulin, cells overexpressing GFAT and tagged GLUT4 had an insulin-dose response curve that was similar to that of control cells expressing only tagged GLUT4. As an alternative means of increasing flux through the hexosamine biosynthetic pathway, we incubated adipose cells with glucosamine (a substrate of the pathway downstream from GFAT) and insulin. Interestingly, for short incubation limes (4 h) we observed a decrease in both basal and insulin-stimulated glucose transport without a detectable effect on insulin-stimulated translocation of GLUT4. However, for longer incubation times (16 h), we observed a significant decrease in the amount of GLUT4 in the plasma membrane. Our data suggest that products of the hexosamine biosynthetic pathway may cause insulin resistance, in part, by acutely decreasing intrinsic activity of GLUT4 as well as chronically altering the amount of GLUT4 at the cell surface. (C) 1997 Elsevier Science Ireland Ltd. C1 NHLBI, Hypertens Endocrine Branch, NIH, Bethesda, MD 20892 USA. Med Univ S Carolina, Dept Med, Div Endocrinol, Charleston, SC 29425 USA. RP Quon, MJ (reprint author), NHLBI, Hypertens Endocrine Branch, NIH, Bldg 10,Room 8C-103,10 Ctr Dr,MSC 1754, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 39 TC 24 Z9 24 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD NOV 30 PY 1997 VL 135 IS 1 BP 67 EP 77 PG 11 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA YM688 UT WOS:000071089900008 ER PT J AU Faraggi, D Simon, R AF Faraggi, D Simon, R TI Large sample Bayesian inference on the parameters of the proportional hazard models SO STATISTICS IN MEDICINE LA English DT Article ID COX REGRESSION-MODEL; LINEAR-REGRESSION; VARIABLE SELECTION; SUBSET REGRESSION; BOOTSTRAP; INFORMATION; EFFICIENCY; CANCER AB This paper considers large sample Bayesian analysis of the proportional hazards model when interest is in inference on the parameters and estimation of the log relative risk for specified covariate vectors rather than on prediction of the survival function. We use a normal prior distribution for the parameters and make inferences based on the derived posterior distribution. The suggested approach is much simpler than alternative Bayesian analyses previously suggested for the proportional hazards models. Using simulated data we compare estimates obtained from the Bayesian analysis with those obtained from the full proportional hazards model and the reduced model after backwards elimination. We show that under a wider range of assumptions, the Bayesian analysis provides reduced estimation errors and improved rejection of noise variables. Finally, we illustrate the methodology using data from a large study of prognostic markers in breast cancer. (C) 1997 by John Wiley & Sons, Ltd. C1 NCI,BIOMETR RES BRANCH,ROCKVILLE,MD 20852. UNIV HAIFA,DEPT STAT,IL-31999 HAIFA,ISRAEL. NR 34 TC 11 Z9 11 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 30 PY 1997 VL 16 IS 22 BP 2573 EP 2585 DI 10.1002/(SICI)1097-0258(19971130)16:22<2573::AID-SIM685>3.3.CO;2-F PG 13 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA YG248 UT WOS:A1997YG24800005 PM 9403957 ER PT J AU Tayebi, N Cushner, SR Kleijer, W Lau, EK DamschroderWilliams, PJ Stubblefield, BK DenHollander, J Sidransky, E AF Tayebi, N Cushner, SR Kleijer, W Lau, EK DamschroderWilliams, PJ Stubblefield, BK DenHollander, J Sidransky, E TI Prenatal lethality of a homozygous null mutation in the human glucocerebrosidase gene SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE Gaucher disease; glucocerebrosidase; neuronopathic; hydrops fetalis; knock-out mouse; frameshift mutation ID GAUCHER DISEASE; TARGETED DISRUPTION; BETA-GLUCOSIDASE; FIBROBLASTS; PHENOTYPE; MODEL AB The complete spectrum of clinical phenotypes resulting from glucocerebrosidase deficiency continues to evolve, While most patients with Gaucher disease have residual glucocerebrosidase activity, we describe a fetus with severe prenatal lethal type 2 (acute neuronopathic) Gaucher disease lacking glucocerebrosidase activity, This 22-week fetus was the result of a first cousin marriage and had hydrops, external abnormalities, hepatosplenomegaly, and Gaucher cells in several organs, Fetal fibroblast DNA was screened for common Gaucher mutations, none of which was detected, Southern blot analysis using the restriction enzymes SstII and SspI ruled out a fusion gene, deletion, or duplication of either allele, and quantitative studies of SspI digested genomic DNA indicated that both alleles were present, Northern blot analysis of total RNA from fetal fibroblasts demonstrated no detectable transcription, although RT-PCR successfully amplified several exons, suggesting the presence of a very unstable mRNA. Direct PCR sequencing of all exons demonstrated a homozygous frameshift mutation (deletion of a C) on codon 139 in exon 5, thereby introducing a premature termination codon in exon 6, The absence of glucocerebrosidase protein was confirmed by Western analysis. This unique case confirms the essential role of glucocerebrosidase in human development and, like the null allele Gaucher mouse, demonstrates the lethality of a homozygous null mutation, The presence of this novel mutation and the resulting unstable mRNA accounts for the severity of the phenotype observed in this fetus, and contributes to the understanding of genotype/ phenotype correlation in Gaucher disease. (C) 1997 Wiley-Liss, Inc. C1 NIMH,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. ERASMUS UNIV ROTTERDAM,UNIV HOSP,DEPT CLIN GENET,ROTTERDAM,NETHERLANDS. ERASMUS UNIV ROTTERDAM,UNIV HOSP,DEPT PATHOL,ROTTERDAM,NETHERLANDS. NR 25 TC 34 Z9 34 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 28 PY 1997 VL 73 IS 1 BP 41 EP 47 DI 10.1002/(SICI)1096-8628(19971128)73:1<41::AID-AJMG9>3.0.CO;2-S PG 7 WC Genetics & Heredity SC Genetics & Heredity GA YE636 UT WOS:A1997YE63600009 PM 9375921 ER PT J AU Su, XZ Kirkman, LA Fujioka, H Wellems, TE AF Su, XZ Kirkman, LA Fujioka, H Wellems, TE TI Complex polymorphisms in an similar to 330 kDa protein are linked to chloroquine-resistant P-falciparum in Southeast Asia and Africa SO CELL LA English DT Article ID PARASITE PLASMODIUM-FALCIPARUM; INFECTED HUMAN-ERYTHROCYTES; DRUG-RESISTANCE; CROSS-RESISTANCE; PFMDR1 GENE; MALARIA; INVITRO; AMPLIFICATION; PYRIMETHAMINE; SENSITIVITY AB Chloroquine resistance in a P. falciparum cross maps as a Mendelian trait to a 36 kb segment of chromosome 7. This segment harbors cg2, a gene encoding a unique similar to 330 kDa protein with complex polymorphisms. A specific set of polymorphisms in 20 chloroquine-resistant parasites from Asia and Africa, in contrast with numerous differences in 21 sensitive parasites, suggests selection of a cg2 allele originating in Indochina over 40 years ago. One chloroquine-sensitive clone exhibited this allele, suggesting another resistance component. South American parasites have cg2 polymorphisms consistent with a separate origin of resistance. CG2 protein is found at the parasite periphery, a site of chloroquine transport, and in association with hemozoin of the digestive vacuole, where chloroquine inhibits heme polymerization. C1 NIAID,NIH,BETHESDA,MD 20892. CASE WESTERN RESERVE UNIV,INST PATHOL,CLEVELAND,OH 44106. OI Su, Xinzhuan/0000-0003-3246-3248 FU NIAID NIH HHS [AI-35827] NR 64 TC 277 Z9 290 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD NOV 28 PY 1997 VL 91 IS 5 BP 593 EP 603 DI 10.1016/S0092-8674(00)80447-X PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YH960 UT WOS:A1997YH96000007 PM 9393853 ER PT J AU Sweet, DH Wolff, NA Pritchard, JB AF Sweet, DH Wolff, NA Pritchard, JB TI Expression closing and characterization of ROAT1 - The basolateral organic anion transporter in rat kidney SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID XENOPUS-LAEVIS OOCYTES; PARA-AMINOHIPPURATE TRANSPORT; RENAL PROXIMAL TUBULE; MEMBRANE-VESICLES; FUNCTIONAL EXPRESSION; TRANSMEMBRANE PROTEINS; P-AMINOHIPPURATE; CLONING; NA+; URATE AB Expression cloning in Xenopus laevis oocytes was used to isolate an organic anion transport protein from rat kidney, A cDNA library was constructed from size-fractionated poly(A)(+) RNA and screened for probenecid-sensitive transport of p-aminohippurate (PAH), A 2,227-base pair cDNA clone containing a 1,656-base pair open reading frame coding for a peptide 551 amino acids long was isolated and named ROAT1, ROAT1-mediated transport of 50 mu M [H-3]PAH was independent of imposed changes in membrane potential, Transport was significantly inhibited at 4 degrees C, or upon incubation with other organic anions, but nea, by the organic cation tetraethyl-ammonium, by the multidrug resistance ATPase inhibitor cyclosporin A, or by urate, External glutarate and alpha-ketoglutarate (1 mM), both counterions for basolateral PAH exchange, also inhibited transport, suggesting that ROAT1 is functionally similar to the basolateral PAH carrier. Consistent with this conclusion, PAH uptake was trans-stimulated in oocytes preloaded with glutarate, whereas the dicarboxylate methylsuccinate, which is not accepted by the basolateral exchanger, did not trans-stimulate. Finally, ROAT1-mediated PAH transport was saturable, with an estimated K-m of 70 mu M. Each of these properties is identical to those previously described for the basolateral alpha-ketoglutarate/PAH exchanger in isolated membrane vesicles or intact renal tubules. C1 NIEHS,LAB PHARMACOL & CHEM,NIH,RES TRIANGLE PK,NC 27709. RI Sweet, Douglas/H-7914-2013 OI Sweet, Douglas/0000-0002-8911-9184 NR 40 TC 351 Z9 359 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 28 PY 1997 VL 272 IS 48 BP 30088 EP 30095 DI 10.1074/jbc.272.48.30088 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YH613 UT WOS:A1997YH61300018 PM 9374486 ER PT J AU Sica, A Dorman, L Viggiano, V Cippitelli, M Ghosh, P Rice, N Young, HA AF Sica, A Dorman, L Viggiano, V Cippitelli, M Ghosh, P Rice, N Young, HA TI Interaction of NF-kappa B and NFAT with the interferon-gamma promoter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID T-CELL ACTIVATION; HUMAN INTERLEUKIN-4 GENE; DNA-BINDING SUBUNIT; IFN-GAMMA; NUCLEAR FACTOR; TRANSCRIPTIONAL ACTIVATION; REGULATORY ELEMENTS; IMMUNE INTERFERON; MESSENGER-RNA; LYMPHOCYTE-T AB Interferon-gamma (IFN-gamma) is a pleiotropic lymphokine whose production is restricted to activated T cells and NK cells. Along with other cytokines, IFN-gamma gene expression is inhibited by the immunosuppressant cyclosporin A. We have previously identified an intronic enhancer region (C3) of the IFN-gamma gene that binds the NF-kappa B protein c-Rel and that shows partial DNA sequence homology with the cyclosporin A-sensitive NFAT binding site and the 3'-half of the NF-kappa B consensus site. Sequence analysis of the IFN-gamma promoter revealed the presence of two additional C3-related elements (C3-1P and C3-3P). In addition, an NF-kappa B site (IFN-gamma kappa B) was identified within the promoter region. Based on this observation, we have analyzed the potential role of NF-kappa B and NFAT family members in regulating IFN-gamma transcription. Electrophoretic mobility shift assay analysis demonstrated that after T cell activation, the p50 and p65 NF-kappa B subunits bind specifically to the newly identified IFN-gamma kappa B and C3-related sites. In addition, we identified the NFAT proteins as a component of the inducible complexes that bind to the C3-3P site. Site-directed mutagenesis and transfection studies demonstrate that calcineurin-inducible transcriptional factors enhance the transcriptional activity of the IFN-gamma promoter through the cyclosporin-sensitive C3-3P site, whereas NF-kappa B proteins functionally interact with the C3-related sites. In addition, when located downstream to the beta-galactosidase gene driven by the IFN-gamma promoter, the intronic C3 site worked in concert with both the IFN-gamma kappa B and the C3-3P site to enhance gene transcription. These results demonstrate that the coordinate activities of NFAT and NF-kappa B proteins are involved in the molecular mechanisms controlling IFN-gamma gene transcription. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,EXPT IMMUNOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC,BIOL CARCINOGENESIS DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RP Sica, A (reprint author), IST RIC FARMACOL MARIO NEGRI,DEPT IMMUNOL & CELL BIOL,VIA ERITREA 62,MILAN,ITALY. NR 55 TC 303 Z9 308 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 28 PY 1997 VL 272 IS 48 BP 30412 EP 30420 DI 10.1074/jbc.272.48.30412 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YH613 UT WOS:A1997YH61300064 PM 9374532 ER PT J AU Habecker, BA Symes, AJ Stahl, N Francis, NJ Economides, A Fink, JS Yancopoulos, G Landis, SC AF Habecker, BA Symes, AJ Stahl, N Francis, NJ Economides, A Fink, JS Yancopoulos, G Landis, SC TI A sweat gland-derived differentiation activity acts through known cytokine signaling pathways SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LEUKEMIA INHIBITORY FACTOR; CILIARY NEUROTROPHIC FACTOR; CULTURED SYMPATHETIC NEURONS; NEUROTRANSMITTER PLASTICITY INVIVO; NEUROPEPTIDE MESSENGER-RNAS; TRIPARTITE CNTF RECEPTOR; NEUROBLASTOMA CELL-LINE; ONCOSTATIN-M; CHOLINERGIC DIFFERENTIATION; NEUROPOIETIC CYTOKINES AB The sympathetic innervation of sweat glands undergoes a target-induced noradrenergic to cholinergic/peptidergic switch during development. Similar changes are induced in cultured sympathetic neurons by sweat gland cells or by one of the following cytokines: leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), or cardiotrophin-1 (CT-1), None of these is the sweat gland-derived differentiation activity. LIF, CNTF, and CT-1 act through the known receptors LIF receptor beta (LIFR beta) and gp130 and well defined signaling pathways including receptor phosphorylation and STAT3 activation. Therefore, to determine whether the gland-derived differentiation activity was a member of the LIF/CNTF cytokine family, we tested whether it acted via these same receptors and signal cascades. Blockade of LIFR beta inhibited the sweat gland differentiation activity in neuron/gland co-cultures, and extracts of gland containing footpads stimulated tyrosine phosphorylation of LIFR beta and gp130, An inhibitor (CGX) of molecules that bind the CNTFR alpha, which is required for CNTF signaling, did not affect the gland derived differentiation activity. Soluble footpad extracts induced the same changes In NBFL neuroblastoma cells as LIF and CNTF, including increased vasoactive intestinal peptide mRNA, STAT3 dimerization, and DNA binding, and stimulation of transcription from the vasoactive intestinal peptide cytokine-responsive element. Thus, the sweat gland-derived differentiation activity uses the same signaling pathway as the neuropoietic cytokines, and is likely to be a family member. C1 CASE WESTERN RESERVE UNIV,DEPT NEUROSCI,CLEVELAND,OH 44106. MASSACHUSETTS GEN HOSP,MOL NEUROBIOL LAB,BOSTON,MA 02114. REGENERON PHARMACEUT INC,TARRYTOWN,NY 10591. UNIFORMED SERV UNIV HLTH SCI,DEPT PHARMACOL,BETHESDA,MD 20814. RP Habecker, BA (reprint author), NINCDS,NEURAL DEV SECT,NIH,BLDG 36-5A05,36 CONVENT DR,BETHESDA,MD 20892, USA. RI Symes, Aviva/S-7471-2016; OI Symes, Aviva/0000-0003-2557-9939; Habecker, Beth/0000-0002-4658-8730 FU NINDS NIH HHS [NS023678, NS27514] NR 89 TC 52 Z9 55 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 28 PY 1997 VL 272 IS 48 BP 30421 EP 30428 DI 10.1074/jbc.272.48.30421 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YH613 UT WOS:A1997YH61300065 PM 9374533 ER PT J AU Hamawy, MM Swieter, M Mergenhagen, SE Siraganian, RP AF Hamawy, MM Swieter, M Mergenhagen, SE Siraganian, RP TI Reconstitution of high affinity IgE receptor-mediated secretion by transfecting protein tyrosine kinase pp125(FAK) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FOCAL ADHESION KINASE; BASOPHILIC LEUKEMIA-CELLS; FC-EPSILON-RI; SIGNAL-TRANSDUCTION; ANTIGEN RECEPTOR; RBL-2H3 CELLS; MAST-CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; HISTAMINE-RELEASE; CALCIUM SIGNAL AB To study the role of the focal adhesion tyrosine kinase (FAK) in receptor-mediated secretion, we transfected FAK cDNA into a variant (3B6) of the RBL-2H3 mast cell line. This 3B6 cell line expressed low levels of FAK and was defective in high affinity IgE receptor (Fc epsilon RI) but not Ca2+ ionophore-mediated secretion. Fc epsilon RI-mediated secretion was reconstituted after transfection of wild-type FAK. Histamine release was also enhanced by the stable expression of two mutants of FAK: a kinase-inactive form in which the ATP binding site Lys-454 was replaced by Arg or a mutant in which the autophosphorylation site Tyr-397 was replaced by Phe. Therefore, the catalytic activity and the autophosphorylation site of FAK are not essential for secretion. Fc epsilon RI aggregation increased. the tyrosine phosphorylation of both mutants of FAK to the same extent as wild-type FAK. Therefore, tyrosine kinases activated by Fc epsilon RI aggregation are phosphorylating FAK and some of these phosphorylation sites are other than Tyr-397. These results strongly suggest that FAK plays a role in Fc epsilon RI-induced secretion by functioning as an adapter or linker molecule. RP Hamawy, MM (reprint author), NIDR,IMMUNOL LAB,NIH,BLDG 10,RM 1N106,BETHESDA,MD 20892, USA. NR 50 TC 27 Z9 27 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 28 PY 1997 VL 272 IS 48 BP 30498 EP 30503 DI 10.1074/jbc.272.48.30498 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YH613 UT WOS:A1997YH61300075 PM 9374543 ER PT J AU Gavrilova, O Barr, V MarcusSamuels, B Reitman, M AF Gavrilova, O Barr, V MarcusSamuels, B Reitman, M TI Hyperleptinemia of pregnancy associated with the appearance of a circulating form of the leptin receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OBESE GENE; BINDING-PROTEIN; WEIGHT; SERUM; MICE; EXPRESSION; RODENT; HUMANS; RNA AB Leptin is a hormone produced in adipose cells that regulates energy expenditure, food intake, and adiposity, In mice, we observed that circulating leptin levels increase 20-40-fold during pregnancy, Pregnant ob/ob females had no detectable serum leptin, demonstrating that the heterozygous conceptus was not the source of the leptin. However, leptin RNA and protein levels in maternal adipose tissue were not elevated, The circulating leptin was in a high molecular weight complex, suggesting that the rise in leptin was due to expression of a binding protein, Indeed, quantitative assays of serum leptin binding capacity revealed a 40-fold increase, coincident with the rise in serum leptin, Leptin binding activity reached a capacity of 207 +/- 15 nmol/liter of serum at day 18 of gestation, and half-maximal binding was observed with similar to 3 nM leptin, The binding protein was purified and partially sequenced, revealing sequence identity to the extracellular domain of the leptin receptor, We found that the placenta produces large amounts of the OB-Re isoform of leptin receptor mRNA, which encodes a soluble binding protein, Thus, the extreme hyperleptinemia of late pregnancy is attributable to binding of the leptin by a secreted form of the leptin receptor made by the placenta. C1 NIDDK,DIABET BRANCH,NIH,BETHESDA,MD 20892. RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 NR 37 TC 183 Z9 189 U1 2 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 28 PY 1997 VL 272 IS 48 BP 30546 EP 30551 DI 10.1074/jbc.272.48.30546 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YH613 UT WOS:A1997YH61300081 PM 9374549 ER PT J AU Hughes, FM Bortner, CD Purdy, GD Cidlowski, JA AF Hughes, FM Bortner, CD Purdy, GD Cidlowski, JA TI Intracellular K+ suppresses the activation of apoptosis in lymphocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROGRAMMED CELL-DEATH; ACID CLEAVAGE ACTIVITY; PROTEIN-SYNTHESIS; CAENORHABDITIS-ELEGANS; PROLYL OLIGOPEPTIDASE; THYMOCYTE APOPTOSIS; DNA-DEGRADATION; MICE DEFICIENT; ICE FAMILY; PROTEASES AB Little is known about the mechanisms of suppression of apoptosis. We have addressed the novel possibility that the level of intracellular K+ regulates the apoptotic process by controlling the activity of death enzymes. We show that K+, at normal intracellular levels, inhibits both apoptotic DNA fragmentation and caspase-3(CPP32)-like protease activation, suggesting that intracellular K+ loss must occur early during apoptosis. Direct measurement of K+ by inductively coupled plasma/ mass spectrometry and flow cytometry indicates a major decrease in intracellular K+ concentration in the apoptotic cell. Flow cytometric analysis revealed that caspase and nuclease activity were restricted to the subpopulation of cells with reduced K+, Disruption of the natural K+ electrochemical gradient suppressed the activity of both caspase and nuclease independent of the mode of activation of the apoptotic inducing agent, demonstrating that a decrease in intracellular K+ concentration is a necessary, early event in programmed cell death. C1 NIEHS,LAB SIGNAL TRANSDUCT,NIH,RES TRIANGLE PK,NC 27709. NR 70 TC 368 Z9 376 U1 2 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 28 PY 1997 VL 272 IS 48 BP 30567 EP 30576 DI 10.1074/jbc.272.48.30567 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YH613 UT WOS:A1997YH61300085 PM 9374553 ER PT J AU Bi, S Gavrilova, O Gong, DW Mason, MM Reitman, M AF Bi, S Gavrilova, O Gong, DW Mason, MM Reitman, M TI Identification of a placental enhancer for the human leptin gene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOUSE OBESE GENE; BINDING PROTEIN-ALPHA; OB GENE; TRANSCRIPTION FACTOR; PROMOTER ACTIVITY; HUMAN CHORIOCARCINOMA; ADIPOSE-CELLS; GROWTH-FACTOR; SUBUNIT GENE; FOOD-INTAKE AB Leptin is a hormone that regulates metabolic efficiency, energy expenditure, and food intake. Leptin is produced chiefly in adipose cells, but in humans, mRNA encoding leptin is also present in the placenta. Here we elucidate the basis for placental leptin production. The same promoter is used for adipose and placental transcription. An upstream enhancer functions in the JEG-3 and JAR choriocarcinoma cell lines but not in adipocytes or HeLa cells. The minimal positive acting region is 60 base pairs in length. This region is within a MER11 repetitive element, suggesting that human placental expression of leptin is the result of insertion of this element. Binding analyses demonstrated three protein binding sites, designated placental leptin enhancer elements (PLE)1, PLE2, and PLE3. PLE2 binds Sp1. Enhancer activity was reduced by mutation of the PLE1 or PLE3 sites but was unaffected by alteration of PLE2. Proteins binding to PLE3 were present in JEG-3 and human placental nuclear extracts but not in extracts from non-placental sources. Upon triplication, the PLE3 element was a strong enhancer in choriocarcinoma cells but not in HeLa cells. The protein binding to the PLE3 motif appears to be a novel, placenta-specific transcription factor. C1 NIDDK,DIABET BRANCH,NIH,BETHESDA,MD 20892. RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 NR 54 TC 127 Z9 129 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 28 PY 1997 VL 272 IS 48 BP 30583 EP 30588 DI 10.1074/jbc.272.48.30583 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YH613 UT WOS:A1997YH61300087 PM 9374555 ER PT J AU Collins, FS Guyer, MS Chakravarti, A AF Collins, FS Guyer, MS Chakravarti, A TI Variations on a theme: Cataloging human DNA sequence variation SO SCIENCE LA English DT Editorial Material ID DEPENDENT DIABETES-MELLITUS; POSITIONAL CLONING; HUMAN GENOME; GENE; MUTATION; CANCER; BREAST C1 CASE WESTERN RESERVE UNIV,CTR HUMAN GENET,DEPT GENET,CLEVELAND,OH 44106. RP Collins, FS (reprint author), NATL HUMAN GENOME RES INST,NIH,BETHESDA,MD 20892, USA. NR 29 TC 717 Z9 755 U1 3 U2 23 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 28 PY 1997 VL 278 IS 5343 BP 1580 EP 1581 DI 10.1126/science.278.5343.1580 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YJ874 UT WOS:A1997YJ87400028 PM 9411782 ER PT J AU Cote, TR Biggar, RJ Rosenberg, PS Devesa, SS Percy, C Yellin, FJ Lemp, G Hardy, C Geodert, JJ Blattner, WA West, D Singleton, J Young, J Kerndt, P Deapen, D Ginzberg, M AntonCulver, H Lieb, S Hopkins, R Williams, B Liff, J Morgan, D Parkin, W AF Cote, TR Biggar, RJ Rosenberg, PS Devesa, SS Percy, C Yellin, FJ Lemp, G Hardy, C Geodert, JJ Blattner, WA West, D Singleton, J Young, J Kerndt, P Deapen, D Ginzberg, M AntonCulver, H Lieb, S Hopkins, R Williams, B Liff, J Morgan, D Parkin, W TI Non-Hodgkin's lymphoma among people with AIDS: Incidence, presentation and public health burden SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; RISK; DIAGNOSES; DISEASES; CANCERS; MEN AB We describe the anatomic and histologic presentation and prognosis of non-Hodgkin's lymphoma (NHL) among people with AIDS (PWA) and determine their contribution to the NHL burden. We linked AIDS and cancer registries in selected areas of the United States and compared NHL sites and histologies in PWA and non-PWA, after adjusting for age, sex and ethnicity. Among 51,033 PWA, we found 2,156 cases of NHL (4.3%). Half of NHL cases occurring post-AIDS were not reported to AIDS registries. NHL was part of an AIDS-defining condition for 3.2% of all PWA; the relative risk of NHL with 3.5 years of another AIDS diagnosis was 165-fold compared to non-PWA within the cancer surveillance system. Of NHLs, 39% were high grade (vs. 12% among non-PWA), 60% were nodal (vs. 74% among non-PWA) and 15% had brain primaries (vs. 1% among non-PWA). Excluding brain sites, extranodal sites were still 20% more common than expected. Relative risk was elevated for all histologic types, with the risk ranging from 652-fold for high-grade diffuse immunoblastic tumors and 261-fold for Burkitt's lymphomas to 113 for intermediate-grade lymphoma to 14-fold for low-grade lymphoma. Survival among PWA with NHL was poor, and tumor grade had little impact. In high-risk AIDS areas, AIDS-related NHLs constitute a major share of the NHL burden. We conclude that NHL risk is considerably under-estimated in AIDS registry data. The major differences between PWA and non-PWA were the high frequency of brain lymphoma and the increase in high-grade lymphomas in PWA. However, the grade of NHL did not influence the prognosis among PWA with lymphoma. The increasing risk of NHL in PWA has contributed substantially to the general increase in NHL rates in the United States since 1981. (C) 1997 Wiley-Liss, Inc. C1 NCI,VIRAL EPIDEMIOL BRANCH,DIV CANC ETIOL,ROCKVILLE,MD. NCI,BIOSTAT BRANCH,DIV CANC ETIOL,ROCKVILLE,MD. NCI,CANC STAT BRANCH,DIV CANC PREVENT & CONTROL,ROCKVILLE,MD. ATLANTIC RES CORP,ROCKVILLE,MD. SAN FRANCISCO DEPT PUBL HLTH,DIV HIV AIDS,SAN FRANCISCO,CA. NR 26 TC 174 Z9 184 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 27 PY 1997 VL 73 IS 5 BP 645 EP 650 DI 10.1002/(SICI)1097-0215(19971127)73:5<645::AID-IJC6>3.0.CO;2-X PG 6 WC Oncology SC Oncology GA YJ325 UT WOS:A1997YJ32500006 PM 9398040 ER PT J AU Tsutsui, T Tamura, Y Yagi, E Hasegawa, K Tanaka, Y Uehama, A Someya, T Hamaguchi, F Yamamoto, H Barrett, JC AF Tsutsui, T Tamura, Y Yagi, E Hasegawa, K Tanaka, Y Uehama, A Someya, T Hamaguchi, F Yamamoto, H Barrett, JC TI Cell-transforming activity and genotoxicity of phenolphthalein in cultured Syrian hamster embryo cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID FREE-RADICAL FORMATION; IN-VITRO; INDUCTION; DIETHYLSTILBESTROL; ADDUCTS; INVITRO; VIOLET; MICE AB Phenolphthalein is a cathartic agent widely used in non-prescription laxatives. For the simultaneous assessment of in vitro carcinogenicity and mutagenicity of phenolphthalein, the ability of this chemical to induce cell transformation and genetic effects was examined using the Syrian hamster embryo (SHE) cell model. Cell growth was reduced by treatment with phenolphthalein at 10-40 mu M in a dose-related manner. Treatment with phenolphthalein for 48 hr induced a dose-dependent increase in morphological transformation of SHE cells. Over the dose range that resulted in cell transformation (10-40 mu M), treatment of SHE cells with phenolphthalein induced gene mutations at the hprt locus but not at the Na+/K+ ATPase locus. A statistically significant level of chromosomal aberrations was elicited in SHE cells treated with phenolphthalein at the highest dose (40 mu M). Meanwhile, neither numerical chromosomal changes nor DNA adduct formation, analyzed by the nuclease P1 enhancement version of P-32-post-labeling, were induced by treatment with phenolphthalein at any concentrations examined. We thus report cell-transforming activity and mutagenicity of phenolphthalein assessed with the same mammalian cells in culture. Our results provide evidence that phenolphthalein has cell-transforming and genotoxic activity in cultured mammalian cells. The mutagenic and clastogenic activities of phenolphthalein could be a causal mechanism for carcinogenicity in rodents. (C) 1997 Wiley-Liss, Inc. C1 NIEHS,MOL CARCINOGENESIS LAB,MD C2 15,RES TRIANGLE PK,NC 27709. NIPPON DENT UNIV TOKYO,DEPT PHARMACOL,TOKYO,JAPAN. NR 27 TC 10 Z9 10 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 27 PY 1997 VL 73 IS 5 BP 697 EP 701 PG 5 WC Oncology SC Oncology GA YJ325 UT WOS:A1997YJ32500014 PM 9398048 ER PT J AU Liaw, KL Hsing, AW Schiffman, MH You, SL Zhang, T Burk, R Chen, CJ AF Liaw, KL Hsing, AW Schiffman, MH You, SL Zhang, T Burk, R Chen, CJ TI Human papillomavirus types 52 and 58 are prevalent in cervical cancer from Chinese women SO INTERNATIONAL JOURNAL OF CANCER LA English DT Letter C1 NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. NATL TAIWAN UNIV,SCH PUBL HLTH,TAIPEI 10764,TAIWAN. ROCHE MOL SYST,ALAMEDA,CA. ALBERT EINSTEIN COLL MED,BRONX,NY 10467. RI Chen, Chien-Jen/C-6976-2008 NR 5 TC 36 Z9 40 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 27 PY 1997 VL 73 IS 5 BP 775 EP 776 DI 10.1002/(SICI)1097-0215(19971127)73:5<775::AID-IJC27>3.0.CO;2-3 PG 2 WC Oncology SC Oncology GA YJ325 UT WOS:A1997YJ32500027 PM 9398061 ER PT J AU McAnulty, J Halperin, B Kron, J Larsen, G Raitt, M Swenson, R Florek, R Marchant, C Hamlin, M Heywood, G Friedman, P Stevenson, W Swat, M Ganz, L Sweeney, M Shea, J Steinberg, J Ehlert, F Zelenkofske, S MenchavezTan, E DeStefano, M Brown, G Anderson, J Karagounis, L Crandall, B Osborn, J Rawling, D Summers, K Jacobsen, M Herre, J Bernstein, R Klevan, L Cannon, D Bhandari, A Lerman, R Firth, B Klein, R Freedman, R Marks, M Delahunty, M Spratt, C Marinchak, R Rials, S Kowey, P Filart, R Hernandez, M Scher, D Zukerman, L Farrell, S Kolk, D Criner, H Tait, B Wilkoff, B Pinski, S Cross, J Shewchik, J Epstein, A Cooper, R Dailey, S Kay, G Plumb, V Bubien, R KnottsDolson, S McKenna, P Tidwell, C Kim, S Fisher, J Ferrick, K Gross, J BenZur, U Durkin, J Ferrick, A Beckman, K McClelland, J Gonzalez, M Widman, L Lane, R Deaton, T Foster, J Straughn, G Wade, L Brodsky, M Allen, B Ehrlich, S Wolff, L MacariHinson, M Coromilas, J Bigger, T Livelli, F Reiffel, J Hickey, K Akiyama, T Daubert, J Kim, C Switzer, D Pande, P Flynn, D Keller, M Ocampo, C Wahl, K Vogt, J Kutalek, S Hessen, S Movsowitz, C Samuels, F Wilber, S Baessler, C Soto, D Schuster, M Scott, G CovelaskyRobinson, R Fletcher, S Siegl, K Finn, L Saari, C Almquist, A Baldwin, P Hauser, R Milstein, S Pritzker, M Schreiber, V Torres, V Pai, S Platt, M Timothy, P Bishop, V Zipes, D Engelstein, E Miles, W Foreman, L Love, J Cutler, J BosworthFarrell, S RizoPatron, C Belco, K Payne, J Arnold, D Zhu, W Pratt, C Martins, J Lee, H Hopson, J Hopson, R Tullo, N Irmiere, C Henry, A Wathen, M Echt, D Roden, D Lee, J Murray, K Rottman, J Crawford, D Connors, N Berns, E Lippman, N Barry, M Dalamagas, H Cook, J Kabell, G Kirchhoffer, J Warwick, D Burkott, B Tomaszewski, D Buxton, A Hsia, H Miller, J Rothman, S Adelizzi, N Gastineau, M Thome, L Whitley, D Greer, G Santoro, I Swaim, J Whittle, S Rome, M Kresge, K Tregoning, C Howard, C Carlson, M Rosenbaum, D Lewis, W Biblo, L Mackall, J Waldo, A Kandrac, J Foster, P Crevey, B Genovely, H Schutzman, J Viater, K Coyle, C Pacifico, A Nasir, N Trainor, K Sung, R Liem, B Young, C Lauer, M Peterson, J Ottoboni, L Goold, P Curtis, A Conti, J Nelson, C Mounsey, P Nath, S Haines, D Ackerman, S Bowman, L Nora, M OToole, M Collura, R Enger, E Russo, A Waxman, H Morrissey, J Raspa, D Jadonath, R Goldner, B Merkatz, K Chepurko, L Saksena, S Krol, R Munsif, A Lewis, C Luceri, R Zilo, P Weiss, D Jonas, A Vardeman, L Stamato, N Whiting, D Chilson, D Lessmeier, T Pochis, W Baxter, J Nademanee, K Weinberger, J Bailey, W Reiter, M Blankenship, M Page, R Jessen, M Canby, R Horton, R Welch, P Kessler, D Joglar, J Hamdan, M Nelson, L Erwin, G Chien, W Stevenot, R Merillat, J McPherson, M Gold, M Shorofsky, S Peters, R Kavesh, N Froman, D Scott, H Shih, HT Dougherty, A Jalal, S Naccarrelli, G Wolbrette, D Wilson, D Roth, J Gadhoke, A Mauermann, S Schwartz, K Asbell, C Scheinman, M Eisenberg, S Epstein, L Fitzpatrick, A Griffin, G Lee, R Lesh, M Wong, M Zebede, J Samet, P Tolentino, A Rubin, S Podrid, P Fuchs, T Mazur, M Wyse, G Duff, H Gillis, A Mitchell, B Rothschild, J Sheldon, R Cassidy, P Karaian, C Dorian, P Newman, D Mitchell, J Greene, M Roy, D Dubuc, M Talajic, M Thibault, B Morrissette, D Jenkins, L Connolly, S Hallstrom, A Greene, L Scholz, M Powell, J Renfroe, E Ledingham, R Morris, M Lancaster, S Moore, R Olarte, A Yao, Q Brooks, MM Hofer, B Sullivan, S Schron, E Domanski, M Follmann, D Rosenberg, Y Jennings, C Richardson, D Cobb, L Furman, S DiMarco, J Knatterud, G Levine, R Strauss, H Woosley, R Singh, B Mason, J Griffin, J Ruskin, J Yusuf, S AF McAnulty, J Halperin, B Kron, J Larsen, G Raitt, M Swenson, R Florek, R Marchant, C Hamlin, M Heywood, G Friedman, P Stevenson, W Swat, M Ganz, L Sweeney, M Shea, J Steinberg, J Ehlert, F Zelenkofske, S MenchavezTan, E DeStefano, M Brown, G Anderson, J Karagounis, L Crandall, B Osborn, J Rawling, D Summers, K Jacobsen, M Herre, J Bernstein, R Klevan, L Cannon, D Bhandari, A Lerman, R Firth, B Klein, R Freedman, R Marks, M Delahunty, M Spratt, C Marinchak, R Rials, S Kowey, P Filart, R Hernandez, M Scher, D Zukerman, L Farrell, S Kolk, D Criner, H Tait, B Wilkoff, B Pinski, S Cross, J Shewchik, J Epstein, A Cooper, R Dailey, S Kay, G Plumb, V Bubien, R KnottsDolson, S McKenna, P Tidwell, C Kim, S Fisher, J Ferrick, K Gross, J BenZur, U Durkin, J Ferrick, A Beckman, K McClelland, J Gonzalez, M Widman, L Lane, R Deaton, T Foster, J Straughn, G Wade, L Brodsky, M Allen, B Ehrlich, S Wolff, L MacariHinson, M Coromilas, J Bigger, T Livelli, F Reiffel, J Hickey, K Akiyama, T Daubert, J Kim, C Switzer, D Pande, P Flynn, D Keller, M Ocampo, C Wahl, K Vogt, J Kutalek, S Hessen, S Movsowitz, C Samuels, F Wilber, S Baessler, C Soto, D Schuster, M Scott, G CovelaskyRobinson, R Fletcher, S Siegl, K Finn, L Saari, C Almquist, A Baldwin, P Hauser, R Milstein, S Pritzker, M Schreiber, V Torres, V Pai, S Platt, M Timothy, P Bishop, V Zipes, D Engelstein, E Miles, W Foreman, L Love, J Cutler, J BosworthFarrell, S RizoPatron, C Belco, K Payne, J Arnold, D Zhu, W Pratt, C Martins, J Lee, H Hopson, J Hopson, R Tullo, N Irmiere, C Henry, A Wathen, M Echt, D Roden, D Lee, J Murray, K Rottman, J Crawford, D Connors, N Berns, E Lippman, N Barry, M Dalamagas, H Cook, J Kabell, G Kirchhoffer, J Warwick, D Burkott, B Tomaszewski, D Buxton, A Hsia, H Miller, J Rothman, S Adelizzi, N Gastineau, M Thome, L Whitley, D Greer, G Santoro, I Swaim, J Whittle, S Rome, M Kresge, K Tregoning, C Howard, C Carlson, M Rosenbaum, D Lewis, W Biblo, L Mackall, J Waldo, A Kandrac, J Foster, P Crevey, B Genovely, H Schutzman, J Viater, K Coyle, C Pacifico, A Nasir, N Trainor, K Sung, R Liem, B Young, C Lauer, M Peterson, J Ottoboni, L Goold, P Curtis, A Conti, J Nelson, C Mounsey, P Nath, S Haines, D Ackerman, S Bowman, L Nora, M OToole, M Collura, R Enger, E Russo, A Waxman, H Morrissey, J Raspa, D Jadonath, R Goldner, B Merkatz, K Chepurko, L Saksena, S Krol, R Munsif, A Lewis, C Luceri, R Zilo, P Weiss, D Jonas, A Vardeman, L Stamato, N Whiting, D Chilson, D Lessmeier, T Pochis, W Baxter, J Nademanee, K Weinberger, J Bailey, W Reiter, M Blankenship, M Page, R Jessen, M Canby, R Horton, R Welch, P Kessler, D Joglar, J Hamdan, M Nelson, L Erwin, G Chien, W Stevenot, R Merillat, J McPherson, M Gold, M Shorofsky, S Peters, R Kavesh, N Froman, D Scott, H Shih, HT Dougherty, A Jalal, S Naccarrelli, G Wolbrette, D Wilson, D Roth, J Gadhoke, A Mauermann, S Schwartz, K Asbell, C Scheinman, M Eisenberg, S Epstein, L Fitzpatrick, A Griffin, G Lee, R Lesh, M Wong, M Zebede, J Samet, P Tolentino, A Rubin, S Podrid, P Fuchs, T Mazur, M Wyse, G Duff, H Gillis, A Mitchell, B Rothschild, J Sheldon, R Cassidy, P Karaian, C Dorian, P Newman, D Mitchell, J Greene, M Roy, D Dubuc, M Talajic, M Thibault, B Morrissette, D Jenkins, L Connolly, S Hallstrom, A Greene, L Scholz, M Powell, J Renfroe, E Ledingham, R Morris, M Lancaster, S Moore, R Olarte, A Yao, Q Brooks, MM Hofer, B Sullivan, S Schron, E Domanski, M Follmann, D Rosenberg, Y Jennings, C Richardson, D Cobb, L Furman, S DiMarco, J Knatterud, G Levine, R Strauss, H Woosley, R Singh, B Mason, J Griffin, J Ruskin, J Yusuf, S TI A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HOSPITAL CARDIAC-ARREST; CARDIOVERTER-DEFIBRILLATOR; MYOCARDIAL-INFARCTION; CLINICAL-TRIALS; LEAD SYSTEMS; SURVIVORS; CLASSIFICATION; MORTALITY; DISEASE AB Background Patients who survive life-threatening ventricular arrhythmias are at risk for recurrent arrhythmias. They can be treated with either an implantable cardioverter-defibrillator or antiarrhythmic drugs, but the relative efficacy of these two treatment strategies is unknown. Methods To address this issue, we conducted a randomized comparison of these two treatment strategies in patients who had been resuscitated from near-fatal ventricular fibrillation or who had undergone cardioversion from sustained ventricular tachycardia, Patients with ventricular tachycardia also had either syncope or other serious cardiac symptoms, along with a left ventricular ejection fraction of 0.40 or less. One group of patients was treated with implantation of a cardioverter-defibrillator; the other received class III antiarrhythmic drugs, primarily amiodarone at empirically determined doses. Fifty-six clinical centers screened all patients who presented with ventricular tachycardia or ventricular fibrillation during a period of nearly four years. Of 1016 patients (45 percent of whom had ventricular fibrillation, and 55 percent ventricular tachycardia), 507 were randomly assigned to treatment with implantable cardioverter-defibrillators and 509 to antiarrhythmic-drug therapy. The primary end point was overall mortality. Results Follow-up was complete for 1013 patients (99.7 percent). Overall survival was greater with the implantable defibrillator, with unadjusted estimates of 89.3 percent, as compared with 82.3 percent in the antiarrhythmic-drug group at one year, 81.6 percent versus 74.7 percent at two years, and 75.4 percent versus 64.1 percent at three years (P<0.02). The corresponding reductions in mortality (with 95 percent confidence limits) with the implantable defibrillator were 39+/-20 percent, 27+/-21 percent, and 31+/-21 percent. Conclusions Among survivors of ventricular fibrillation or sustained ventricular tachycardia causing severe symptoms, the implantable cardioverter-defibrillator is superior to antiarrhythmic drugs for increasing overall survival. (C) 1997, Massachusetts Medical Society. C1 INDIANA UNIV, INDIANAPOLIS, IN 46204 USA. UNIV CALGARY, CALGARY, AB, CANADA. BRIGHAM & WOMENS HOSP, BOSTON, MA 02115 USA. UNIV ALABAMA, BIRMINGHAM, AL USA. NHLBI, BETHESDA, MD 20892 USA. RP McAnulty, J (reprint author), UNIV WASHINGTON, AVID CLIN TRIAL CTR, 1107 NE 45TH ST, RM 505, SEATTLE, WA 98105 USA. OI Fisher, John/0000-0003-2748-8715 NR 34 TC 1725 Z9 1756 U1 0 U2 25 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 27 PY 1997 VL 337 IS 22 BP 1576 EP 1583 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA YH521 UT WOS:A1997YH52100002 ER PT J AU Kimmelman, A Tolkacheva, T Lorenzi, MV Osada, M Chan, AML AF Kimmelman, A Tolkacheva, T Lorenzi, MV Osada, M Chan, AML TI Identification and characterization of R-ras3: a novel member of the RAS gene family with a non-ubiquitous pattern of tissue distribution SO ONCOGENE LA English DT Article DE Ras; TC21; R-ras; G-protein; transformation; MAPK ID NUCLEOTIDE DISSOCIATION STIMULATOR; GTPASE-ACTIVATING PROTEIN; NIH 3T3 CELLS; R-RAS; ONCOGENIC RAS; MALIGNANT TRANSFORMATION; SIGNALING PATHWAY; K-RAS; H-RAS; KINASE AB Members of the Ras subfamily of GTP-binding proteins, including Ras (H-, K-, and N-), TC21, and R-ras have been shown to display transforming activity, and activating lesions have been detected in human tumors. We have identified an additional member of the Ras gene family which shows significant sequence similarity to the human TC21 gene. This novel human ras-related gene, R-rad, encodes for a protein of 209 amino acids, and shows similar to 60-75% sequence identity in the N-terminal catalytic domain with members of the Ras subfamily of GTP-binding proteins. An activating mutation corresponding to the leucine 61 oncogenic lesion of the ras oncogenes when introduced into R-ras3, activates its transforming potential. R-ras3 weakly stimulates the mitogen-activated protein kinase (MAPK) activity, but this effect is greatly potentiated by the co-expression of c-raf-l. By the yeast two-hybrid system, R-rad interacts only weakly with known Ras effecters, such as Raf and RalGDS, but not with RglII. In addition, R-ras3 displays modest stimulatory effects on trans-activation from different nuclear response elements which bind transcription factors, such as SRF, ETS/TCF, Jun/Fos, and NF-kappa B/Rel. Interestingly, Northern blot analysis of total RNA isolated from various tissues revealed that the 3.8 kilobasepair (kb) transcript of R-rad is highly restricted to the brain and heart. The close evolutionary conservation between R-rad and Ras family members, in contrast to the significant differences in its biological activities and the pattern of tissue expression, raise the possibility that R-rad may control novel cellular functions previously not described for other GTP-binding proteins. C1 CUNY MT SINAI SCH MED,DERALD H RUTTENBERG CANC CTR,NEW YORK,NY 10029. NCI,CELLULAR & MOL BIOL LAB,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [CA66654] NR 54 TC 59 Z9 62 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 27 PY 1997 VL 15 IS 22 BP 2675 EP 2685 DI 10.1038/sj.onc.1201674 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA YH468 UT WOS:A1997YH46800005 PM 9400994 ER PT J AU Grasso, AW Wen, DZ Miller, CM Rhim, JS Pretlow, TG Kung, HJ AF Grasso, AW Wen, DZ Miller, CM Rhim, JS Pretlow, TG Kung, HJ TI ErbB kinases and NDF signaling in human prostate cancer cells SO ONCOGENE LA English DT Article DE ErbB3; receptor tyrosine kinase; tyrosine phosphorylation; prostate cancer ID EPIDERMAL GROWTH-FACTOR; NEU DIFFERENTIATION FACTOR; ACTIVATED PROTEIN-KINASE; MAMMARY EPITHELIAL-CELLS; PHOSPHOLIPASE C-GAMMA; FACTOR RECEPTOR FAMILY; PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE PHOSPHORYLATION; TUMOR-CELLS; MAP KINASE AB Prostate carcinoma (PCA) is the most commonly diagnosed malignancy in American men. Our knowledge of PCA growth regulation lags behind that of other cancers, such as breast and colon carcinomas. Among receptor tyrosine kinases, the ErbB family is most frequently implicated in neoplasia. We report here the expression of ErbB family kinases and their ligands in PCA cell lines and a xenograft. While ErbB1/EGFR, ErbB2/NEU, and ErbB3 were always observed in a distinct pattern, ErbB4 was not observed. Interestingly, while TGF-alpha was expressed in the majority of PCA lines, the ligand Neu Differentiation Factor/Heregulin (NDF) was expressed only in an immortalized, non-transformed prostate epithelial line. Concomitantly, there was a significant difference in biological response to these ligands, NDF inhibited LNCaP growth and induced an epithelial-like morphological change, in contrast to TGF-alpha, which accelerated cell growth. We also performed the first comprehensive analysis of NDF signaling in a prostate line, LNCaP stimulated with NDF demonstrated crosstalk between ErbB3 and ErbB2 which did not involve ErbB1. NDF also turned on several cascades, including those of PI3-K, ERK/MAPK, mHOG/p38 and JNK/SAPK, but not those of PLC gamma or the STAT family. This signaling pattern is distinct from that of TGF-alpha. The activation of mHOG by ErbB2 or ErbB3 has not been reported, and may contribute to the unusual phenotype, PI3-K activation is characterized by the formation of a striking 'activation complex' vith multiple tyrosine-phosphorylated species, including ErbB3. Our studies provide a framework in which to dissect the growth and differentiation signals of prostate cancer cells. C1 CASE WESTERN RESERVE UNIV,SCH MED,DEPT MOL BIOL & MICROBIOL,CLEVELAND,OH 44106. AMGEN INC,THOUSAND OAKS,CA 91320. CASE WESTERN RESERVE UNIV,SCH MED,DEPT PATHOL,CLEVELAND,OH 44106. NCI,BIOCHEM PHYSIOL LAB,FREDERICK,MD 21702. RI Kung, Hsing-Jien/C-7651-2013 FU NCI NIH HHS [CA39207, CA57179]; NIDDK NIH HHS [DK52659] NR 87 TC 114 Z9 116 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 27 PY 1997 VL 15 IS 22 BP 2705 EP 2716 DI 10.1038/sj.onc.1201447 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA YH468 UT WOS:A1997YH46800008 PM 9400997 ER PT J AU Merta, A Aksamit, RR Cantoni, GL AF Merta, A Aksamit, RR Cantoni, GL TI The rat S-adenosylhomocysteine hydrolase promoter SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID L-HOMOCYSTEINE HYDROLASE; GENE AB The 1,2-kb DNA sequence flanking the transcription start of the AdoHcy hydrolase gene was cloned into the luciferase reporter plasmid pGL3-basic, and promoter activity was measured in transiently transfected CHO cells. Deletion analysis showed that most promoter activity was located within a 153 bp fragment immediately upstream from the predominant transcription start. The 153 bp fragment includes sites for AP-2, glucocorticoid-responsive element, SP-1, and a TATA-like sequence TATTTAAA, Mutational analysis demonstrated that the SP-1 site nearest the start of transcription contributed significantly to promoter activity, whereas, the other elements, including the appropriately positioned TATTTAAA sequence, had little affect on promoter activity. (C) 1997 Academic Press. C1 US FDA,LAB CELLULAR HEMATOL,DIV HEMATOL,CTR BIOL EVALUAT & RES,HFM 335,BETHESDA,MD 20892. NIMH,LAB GEN & COMPARAT BIOCHEM,BETHESDA,MD 20892. NR 10 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 26 PY 1997 VL 240 IS 3 BP 580 EP 585 DI 10.1006/bbrc.1997.7704 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YK696 UT WOS:A1997YK69600012 PM 9398607 ER PT J AU McKeon, C Accili, D Chen, H Pham, T Walker, GE AF McKeon, C Accili, D Chen, H Pham, T Walker, GE TI A conserved region in the first intron of the insulin receptor gene binds nuclear proteins during adipocyte differentiation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROMOTER REGION; TRANSCRIPTION FACTOR; ENHANCER; EXPRESSION; CELLS; CHLORAMPHENICOL; ADIPOGENESIS AB The insulin receptor gene is induced 8 to 10-fold during adipocyte differentiation. Plasmids containing the promoter, exon 1 and a portion of the first intron from either the mouse or human gene are able to modulate the expression of an insulin receptor/CAT gene 3 to 7-fold during differentiation. We have shown that several nuclear proteins from both preadipocyte and adipocyte nuclear extracts bind to two discrete sites within a 278-bp region in the 5' end of the first intron. Sequence comparison between the first intron of the human gene and the mouse gene shows two regions of sequence identity which correspond to the protein binding regions detected by DNase footprinting. One of these sites binds proteins that are enriched in adipocyte nuclear extracts and can be competed by adipose regulatory element, ARE6. (C) 1997 Academic Press. RP McKeon, C (reprint author), NIDDK,METAB DIS & GENE THERAPY RES PROGRAM,NIH,DIABET BRANCH,NATCHER BLDG,RM 5AN18B,45 CTR DR,BETHESDA,MD 20892, USA. FU NIDDK NIH HHS [NIDDK 190916, NIDDK 188739] NR 20 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 26 PY 1997 VL 240 IS 3 BP 701 EP 706 DI 10.1006/bbrc.1997.7725 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YK696 UT WOS:A1997YK69600035 PM 9398630 ER PT J AU Mimnaugh, EG Chen, HY Davie, JR Celis, JE Neckers, L AF Mimnaugh, EG Chen, HY Davie, JR Celis, JE Neckers, L TI Rapid deubiquitination of nucleosomal histones in human tumor cells caused by proteasome inhibitors and stress response inducers: Effects on replication, transcription, translation, and the cellular stress response SO BIOCHEMISTRY LA English DT Article ID UBIQUITIN-ACTIVATING ENZYME; TEMPERATURE-SENSITIVE MUTANTS; HEAT-SHOCK PROTEIN; IMMUNOCHEMICAL DETECTION; CHROMATIN CONDENSATION; TS85 CELLS; DEGRADATION; DISAPPEARANCE; CYCLE; H2B AB The proteasome inhibitors, lactacystin and N-acetyl-leucyl-leucyl-norlucinal, caused a rapid and near-complete loss of similar to 22-23-kDa ubiquitinated nucleoproteins, which we have identified as monoubiquitinated nucleosomal histones H2A and H2B by immunological and two-dimensional electrophoretic techniques. In human SKBr3 breast tumor cells, depletion of monoubiquitinated histones by the proteasome inhibitors coincided with the accumulation of high molecular weight ubiquitinated proteins in both nucleoprotein and cytosolic fractions and decreased unconjugated ubiquitin in the cytosol, without changes in the nonubiquitinated core histones. Unconjugated ubiquitin was not detected in isolated tumor cell nuclei. A similar loss in monoubiquitinated histones occurred in cells harboring a defective, temperature-sensitive mutation of the ubiquitin-activating E1 enzyme, after these cells were elevated from 33 degrees C to the non-permissive temperature of 39 degrees C. DNA replication and RNA transcription were decreased by the proteasome inhibitors most strongly after 90% of the ubiquitin had been removed from ubiquitinated histones H2A and H2B, suggesting a relationship between the nucleosomal histone ubiquitin status and the processing of genetic information. interestingly, although both proteasome inhibitors caused a generalized decrease in methionine incorporation into proteins, they strongly induced the synthesis of the hsp72 and hsp90 stress proteins. Finally, treating cells with heat-shock at 43 degrees C, with stress response-provoking chemicals or with several other proteasome inhibitors caused ubiquitinated proteins to accumulate, depleted free ubiquitin, and concomitantly decreased nucleosomal monoubiquitinated histones. These results suggest that deubiquitination of nucleosomal histones H2A and H2B may play a previously unrecognized role in the cellular stress response, as well as in the processing of chromatin, and emphasize the important role of the proteasome in cellular homeostasis. C1 UNIV MANITOBA,DEPT BIOCHEM & MOL BIOL,WINNIPEG,MB R3E 0W3,CANADA. AARHUS UNIV,DANISH CTR HUMAN GENOME RES,DK-8000 AARHUS C,DENMARK. RP Mimnaugh, EG (reprint author), NCI,DEPT CANC & CELL BIOL,MED BRANCH,NIH,BETHESDA,MD 20892, USA. NR 58 TC 125 Z9 126 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 25 PY 1997 VL 36 IS 47 BP 14418 EP 14429 DI 10.1021/bi970998j PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YH566 UT WOS:A1997YH56600017 PM 9398160 ER PT J AU Hessler, JL Kreitman, RJ AF Hessler, JL Kreitman, RJ TI An early step in Pseudomonas exotoxin action is removal of the terminal lysine residue, which allows binding to the KDEL receptor SO BIOCHEMISTRY LA English DT Article ID CARBOXYPEPTIDASE-N; ANTI-TAC; FRAGMENT; TOXIN; CYTOTOXICITY; IMMUNOTOXINS; DERIVATIVES; CLEAVAGE; DOMAINS; CYTOSOL AB During the intoxication process, Pseudomonas exotoxin (PE) and immunotoxins containing PE internalize into the target cell and become processed into two fragments, and the carboxyl fragment translocates into the cytosol where it inactivates elongation factor 2. We have proposed that after internalization into cells the carboxyl-terminal fragment of PE (amino acids 280-613), which ends in REDLK, binds to the KDEL receptor (ERD2) which carries it to the endoplasmic reticulum, from which the PE fragment translocates to the cytosol. Earlier experiments showing that REDL but not REDLK binds to the KDEL receptor suggested that the terminal lysine is removed sometime during the intoxication process. To determine if and where this occurs, we exposed a peptide ending in REDLK to malignant cells in culture and found that binding to the KDEL receptor was restored. Restoration of receptor binding also occurred if a peptide or toxin ending in REDLK at its carboxyl terminus was incubated with plasma, indicating that the terminal lysine is removed prior to entry of the toxin into the cell. We conclude that plasma carboxypeptidase(s) cleave(s) the lysine residue from the carboxyl terminus of PE and PE-containing immunotoxins as an early and essential step in their cellular intoxication pathway. C1 NCI,MOL BIOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 25 TC 50 Z9 51 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 25 PY 1997 VL 36 IS 47 BP 14577 EP 14582 DI 10.1021/bi971447w PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YH566 UT WOS:A1997YH56600033 PM 9398176 ER PT J AU Dasso, JF Howell, MD AF Dasso, JF Howell, MD TI Neonatal appendectomy impairs mucosal immunity in rabbits SO CELLULAR IMMUNOLOGY LA English DT Article DE rabbit; mucosa; appendix; gut-associated lymphoid tissues (GALT); B lymphocytes; repertoire development; antibodies ID APPENDIX; PRECURSORS; GENE AB We compared the effects of neonatal appendectomy in rabbits on total Ig and antigen (Ag)-specific Ig levels in the serum and gut, and on plasma cell numbers in the small intestine in response to intraperitoneal (ip) and intraduodenal (id) immunizations with ovalbumin (OVA). Animals were sacrificed after 9 weeks. Antibodies (Abs) in the duodenum were collected and quantified by enzyme-linked immunosorbent assay (ELISA) while plasma cells were quantified by double immunofluorescent staining. Appendectomy markedly reduced total intestinal IgA (P < 0.0006), IgM (P < 0.003), and IgG (P < 0.05) relative to controls, whereas total serum Ig levels were not lowered significantly. Moreover, appendectomy nearly ablated OVA-specific IgA (P < 0.007) in the gut and severely depleted OVA-specific IgG in the gut (P < 0.03) and serum (P < 0.007). The sharp decreases in total IgA and anti-OVA IgA were paralleled by decreases in total IgA(+) plasma cells (P < 0.0005) and OVA-reactive IgA(+) plasma cells (P < 0.05). These results support a major role of the rabbit appendix in seeding the intestinal lamina propria with plasma cell precursors, especially those producing IgA. (C) 1997 Academic Press. C1 Univ No Colorado, Dept Sci Biol, Greeley, CO 80639 USA. Colorado State Univ, Dept Microbiol, Ft Collins, CO 80523 USA. RP Dasso, JF (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311, Bethesda, MD 20892 USA. NR 38 TC 34 Z9 35 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD NOV 25 PY 1997 VL 182 IS 1 BP 29 EP 37 DI 10.1006/cimm.1997.1216 PG 9 WC Cell Biology; Immunology SC Cell Biology; Immunology GA YM638 UT WOS:000071084800004 PM 9427807 ER PT J AU Kokkonen, GC Kitano, S Mock, YD Ishigami, A Reed, TD Chrest, FJ Roth, GS AF Kokkonen, GC Kitano, S Mock, YD Ishigami, A Reed, TD Chrest, FJ Roth, GS TI Aging reduces the numbers of hepatocytes synthesizing DNA in response to EGF and epinephrine SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID CULTURED RAT HEPATOCYTES; AGE AB Primary cultures of hepatocytes were prepared from young (6 month) and old (24 month) Wistar rats and exposed to epinephrine or epidermal growth factor. Incorporation of [H-3]thymidine into DNA was determined both radiochemically and autoradiographically, The numbers of responding cells and degree of response per cell were determined and the results confirmed by FACScan analysis. Such analyses clearly demonstrate a reduced number of hepatocytes capable of responding to the above stimuli in cultures obtained from old rats, Thus, changes in numbers of responding cells may be an important mechanism involved in reduced responsiveness of the aged liver to agents which stimulate DNA synthesis and cell division. (C) 1997 Academic Press. C1 NIA, Gerontol Res Ctr, Mol Physiol & Genet Sect, Lab Cellular & Mol Physiol,NIH, Baltimore, MD 21224 USA. RP Roth, GS (reprint author), NIA, Gerontol Res Ctr, Mol Physiol & Genet Sect, Lab Cellular & Mol Physiol,NIH, Baltimore, MD 21224 USA. NR 20 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD NOV 25 PY 1997 VL 237 IS 1 BP 77 EP 82 DI 10.1006/excr.1997.3763 PG 6 WC Oncology; Cell Biology SC Oncology; Cell Biology GA YN237 UT WOS:000071146800011 PM 9417869 ER PT J AU Mahalingam, H Watanabe, A Tachibana, M Niles, RM AF Mahalingam, H Watanabe, A Tachibana, M Niles, RM TI Characterization of density-dependent regulation of the tyrosinase gene promoter: Role of protein kinase C SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID MOUSE MELANOMA-CELLS; LOOP-HELIX PROTEINS; RETINOIC ACID; TRANSCRIPTION FACTOR; DNA-BINDING; MICROPHTHALMIA GENE; HUMAN MELANOGENESIS; HUMAN HOMOLOG; EXPRESSION; ACTIVATION AB The rate-limiting step in melanogenesis is catalyzed by tyrosinase, a multifunctional enzyme encoded by the albino locus. We have previously reported that depletion of protein kinase C by long-term treatment of B16 mouse melanoma cells with phorbol dibutyrate (PDBu) prevented cell density-dependent melanogenesis. This was accompanied by a lack of induction of tyrosinase protein and mRNA. We report here the effect of PDBu on the functional activity of the mouse tyrosinase promoter by reporter gene assay and its effect on the binding of nuclear proteins from B16 cells to the "M-box" region of the mouse tyrosinase promoter. Short-term PDBu treatment of B16 cells transfected with a mouse tyrosinase promoter-luciferase construct resulted in increased reporter gene activity, while long-term PDBu treatment inhibited reporter gene activity. Using an oligonucleotide containing the RI-box and its flanking residues in electrophoretic mobility shift assays, we found a density-dependent change in the pattern of DNA-protein complexes. One complex was found to be negatively regulated by longterm PDBu treatment. Competition experiments with various mutated oligonucleotides demonstrated that both the RI-box and flanking residues are important for nuclear protein binding. The complex whose formation was inhibited by long-term PDBu treatment was shown to contain the basic helix-loop-helix leucine zipper protein microphthalmia-associated transcription factor (MITF). These results suggest that chronic PDBu treatment might inhibit tyrosinase expression (and subsequent melanogenesis) by affecting the amount or function of MITF. (C) 1997 Academic Press. C1 Marshall Univ, Sch Med, Dept Biochem & Mol Biol, Huntington, WV 25755 USA. Natl Inst Deafness & Commun Disorders, Genet Mol Lab, NIH, Bethesda, MD 20850 USA. RP Niles, RM (reprint author), Marshall Univ, Sch Med, Dept Biochem & Mol Biol, Huntington, WV 25755 USA. FU NCI NIH HHS [CA-59539] NR 49 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 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD NOV 25 PY 1997 VL 237 IS 1 BP 83 EP 92 DI 10.1006/excr.1997.3773 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA YN237 UT WOS:000071146800012 PM 9417870 ER PT J AU Das, SK Taylor, JA Korach, KS Paria, BC Dey, SK Lubahn, DB AF Das, SK Taylor, JA Korach, KS Paria, BC Dey, SK Lubahn, DB TI Estrogenic responses in estrogen receptor-alpha deficient mice reveal a distinct estrogen signaling pathway SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MOUSE UTERUS; GENE; IMPLANTATION; RAT; IDENTIFICATION; TRANSCRIPTION; DISRUPTION; METABOLITES; EXPRESSION; PITUITARY AB Estrogens are thought to regulate female reproductive functions by altering gene transcription in target organs primarily via the nuclear estrogen receptor-alpha (ER-alpha). By using ER-alpha ''knock-out'' (ERKO) mice, we demonstrate herein that a catecholestrogen, 4-hydroxyestradiol-17 beta (4-OH-E-2), and an environmental estrogen, chlordecone (kepone), up-regulate the uterine expression of an estrogen-responsive gene, lactoferrin (LF), independent of ER-alpha, A primary estrogen, estradiol-17 beta (E-2), did not induce this LF response, An estrogen receptor antagonist, ICI-182,780, or E-2 failed to inhibit uterine LF gene expression induced by 4-OH-E-2 or kepone in ERKO mice, which suggests that this estrogen signaling pathway is independent of both ER-alpha and the recently cloned ER-beta, 4-OH-E-2, but not E-2, also stimulated increases in uterine water imbibition and macromolecule uptake in ovariectomized ERKO mice, The results strongly imply the presence of a distinct estrogen-signaling pathway in the mouse uterus that mediates the effects of both physiological and environmental estrogens, This estrogen response pathway will have profound implications for our understanding of the physiology and pathophysiology of female sex steroid hormone actions in target organs. C1 UNIV MISSOURI,DEPT BIOCHEM,COLUMBIA,MO 65211. UNIV MISSOURI,DEPT CHILD HLTH,COLUMBIA,MO 65211. NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. RP Das, SK (reprint author), UNIV KANSAS,MED CTR,RALPH L SMITH RES CTR,DEPT MOL & INTEGRAT PHYSIOL,KANSAS CITY,KS 66160, USA. OI Korach, Kenneth/0000-0002-7765-418X FU NICHD NIH HHS [HD 12304, R37 HD012304]; NIEHS NIH HHS [ES 07814, ES08272, R01 ES007814] NR 45 TC 134 Z9 140 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 25 PY 1997 VL 94 IS 24 BP 12786 EP 12791 DI 10.1073/pnas.94.24.12786 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YJ456 UT WOS:A1997YJ45600020 PM 9371753 ER PT J AU Michaud, NR Therrien, M Cacace, A Edsall, LC Spiegel, S Rubin, GM Morrison, DK AF Michaud, NR Therrien, M Cacace, A Edsall, LC Spiegel, S Rubin, GM Morrison, DK TI KSR stimulates Raf-1 activity in a kinase-independent manner SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ACTIVATED PROTEIN-KINASE; CYSTEINE-RICH REGION; SIGNAL-TRANSDUCTION; IN-VITRO; PLASMA-MEMBRANE; GENE ENCODES; ZETA-ISOFORM; C-ELEGANS; RAS; CERAMIDE AB Kinase suppressor of Ras (KSR) is an evolutionarily conserved component of Ras-dependent signaling pathways. Here, we find that murine KSR (mKSR1) translocates from the cytoplasm to the plasma membrane in the presence of activated Ras. At the membrane, mKSR1 modulates Ras signaling by enhancing Raf-1 activity in a kinase-independent manner, The activation of Raf-1 is mediated by the mKSR1 cysteine-rich CA3 domain and involves a detergent labile cofactor that is not ceramide, These findings reveal another point of regulation for Ras-mediated signal transduction and further define a noncatalytic role for mKSR1 in the multistep process of Raf-1 activation. C1 GEORGETOWN UNIV,MED CTR,DEPT BIOCHEM & MOL BIOL,WASHINGTON,DC 20007. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOL BASIS CARCINOGENESIS LAB,FREDERICK,MD 21702. UNIV CALIF BERKELEY,HOWARD HUGHES MED INST,DEPT MOL & CELL BIOL,BERKELEY,CA 94720. OI Rubin, Gerald/0000-0001-8762-8703 NR 45 TC 123 Z9 124 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 25 PY 1997 VL 94 IS 24 BP 12792 EP 12796 DI 10.1073/pnas.94.24.12792 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YJ456 UT WOS:A1997YJ45600021 PM 9371754 ER PT J AU Druey, KM Kehrl, JH AF Druey, KM Kehrl, JH TI Inhibition of regulator of G protein signaling function by two mutant RGS4 proteins SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GTPASE-ACTIVATING PROTEINS; ALPHA-SUBUNITS; MECHANISM; HYDROLYSIS; FAMILY; GAIP AB Regulators of G protein signaling (RGS) proteins limit the lifetime of activated (GTP-bound) heterotrimeric G protein alpha subunits by acting as GTPase-activating proteins (GAPs), Mutation of two residues in RGS4, which, based on the crystal structure of RGS4 complexed with G(i alpha 1)-GDP-AlF4-, directly contact G(i alpha 1) (N88 and L159), essentially abolished RGS4 binding and GAP activity, Mutation of another contact residue (S164) partially inhibited both binding and GAP activity, Two other mutations, one of a contact residue (R167M/A) and the other an adjacent residue (F168A), also significantly reduced RGS4 binding to G(i alpha 1)-GDP-AlF4-, but in addition redirected RGS4 binding toward the GTP gamma S-bound form, These two mutant proteins had severely impaired GAP activity, but in contrast to the others behaved as RGS antagonists in GAP and in vivo signaling assays, Overall, these results are consistent with the hypothesis that the predominant role of RGS proteins is to stabilize the transition state for GTP hydrolysis. In addition, mutant RGS proteins can be created with an altered binding preference for the G(i alpha)-GTP conformation, suggesting that efficient RGS antagonists can be developed. C1 NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. OI Kehrl, John/0000-0002-6526-159X NR 20 TC 44 Z9 44 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 25 PY 1997 VL 94 IS 24 BP 12851 EP 12856 DI 10.1073/pnas.94.24.12851 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YJ456 UT WOS:A1997YJ45600031 PM 9371764 ER PT J AU Kim, IY Stadtman, TC AF Kim, IY Stadtman, TC TI Inhibition of NF-kappa B DNA binding and nitric oxide induction in human T cells and lung adenocarcinoma cells by selenite treatment SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE selenium; human cell lines ID TRANSCRIPTION FACTOR; ACTIVATION; SYNTHASE; PROTEIN; INVOLVEMENT; AP-1; FOS; SELENODIGLUTATHIONE; MACROPHAGES; EXPRESSION AB NF-kappa B is a major transcription factor consisting of 50(p50)- and 65(p65)-kDa proteins that controls the expression of various genes, among which are those encoding cytokines, cell adhesion molecules, and inducible NO synthase (iNOS). After initial activation of NF-kappa B, which involves release and proteolysis of a bound inhibitor, essential cysteine residues are maintained in the active reduced state through the action of thioredoxin and thioredoxin reductase. In the present study, activation of NF-kappa B in human T cells and lung adenocarcinoma cells was induced by recombinant human tumor necrosis factor (alpha or bacterial lipopolysaccharide, After lipopolysaccharide activation, nuclear extracts were treated with increasing concentrations of selenite, and the effects on DNA-binding activity of NF-kappa B were examined. Binding of NF-kappa B to nuclear responsive elements was decreased progressively by increasing selenite levels and, at 7 mu M selenite, DNA-binding activity was completely inhibited, Selenite inhibition was reversed by addition of a dithiol, DTT, Proportional inhibition of iNOS activity as measured by decreased NO products in the medium (NO2- and NO3-) resulted from selenite addition to cell suspensions, This loss of iNOS activity was due to decreased synthesis of NO synthase protein, Selenium at low essential levels (nM) is required for synthesis of redox active selenoenzymes such as glutathione peroxidases and thioredoxin reductase, but in higher toxic levels (>5-10 mu 2) selenite can react with essential thiol groups on enzymes to form RS-Se-SR adducts with resultant inhibition of enzyme activity, Inhibition of NF-kappa B activity bg selenite is presumed to be the result of adduct formation with the essential thiols of this transcription factor. C1 NHLBI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. KOREA UNIV,GRAD SCH BIOTECHNOL,SEOUL 136701,SOUTH KOREA. NR 35 TC 114 Z9 126 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 25 PY 1997 VL 94 IS 24 BP 12904 EP 12907 DI 10.1073/pnas.94.24.12904 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YJ456 UT WOS:A1997YJ45600040 PM 9371773 ER PT J AU Morinaga, N Moss, J Vaughan, M AF Morinaga, N Moss, J Vaughan, M TI Cloning and expression of a cDNA encoding a bovine brain brefeldin A sensitive guanine nucleotide-exchange protein for ADP-ribosylation factor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PHOSPHOLIPASE-D; GOLGI; ARF; SEC7; ARABIDOPSIS; BINDING; CELL AB A 200-kDa guanine nucleotide-exchange protein (p200 or GEP) for ADP-ribosylation factors 1 and 3 (ARF1 and ARF3) that was inhibited by brefeldin A (BFA) was purified earlier from cytosol of bovine brain cortex. Amino acid sequences of four tryptic peptides were 47% identical to that of Sec7 from Saccharomyces cerevisiae, which is involved in vesicular trafficking in the Golgi. By using a PCR-based procedure with two degenerate primers representing sequences of these peptides, a product similar in size to Sec7 that contained the peptide sequences was generated. Two oligonucleotides based on this product were used to screen a bovine brain library, which yielded one clone that was a partial cDNA for p200. The remainder of the cDNA was obtained by 5' and 3' rapid amplification of cDNA ends (RACE). The ORF of the cDNA encodes a protein of 1,849 amino acids (approximate to 208 kDa) that is 33% identical to yeast Sec7 and 50% identical in the Sec7 domain region. On Northern blot analysis of bovine tissues, a approximate to 7.4-kb mRNA was identified that hybridized with a p200 probe; it was abundant in kidney, somewhat less abundant in lung, spleen, and brain, and still less abundant in heart. A six-His-tagged fusion protein synthesized in baculovirus-infected Sf9 cells demonstrated BFA-inhibited GEP activity, confirming that BFA sensitivity is an intrinsic property of this ARF GEP and not conferred by another protein component of the complex from which p200 was originally purified. RP Morinaga, N (reprint author), NHLBI,PULM CRIT CARE MED BRANCH,NIH,ROOM 5N-307,BLDG 10,10 CTR DR,MSC 1434,BETHESDA,MD 20892, USA. NR 23 TC 86 Z9 88 U1 2 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 25 PY 1997 VL 94 IS 24 BP 12926 EP 12931 DI 10.1073/pnas.94.24.12926 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YJ456 UT WOS:A1997YJ45600044 PM 9371777 ER PT J AU vanSchaick, HSA Smidt, MP Rovescalli, AC Luijten, M vanderKleij, AAM Asoh, S Kozak, CA Nirenberg, M Burbach, JPH AF vanSchaick, HSA Smidt, MP Rovescalli, AC Luijten, M vanderKleij, AAM Asoh, S Kozak, CA Nirenberg, M Burbach, JPH TI Homeobox gene Prx3 expression in rodent brain and extraneural tissues SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE embryo; transcription factors; OG-12; SHOX; limb ID MOUSE; TRANSCRIPTION; ORGANIZATION; PATTERNS; CLONING; TRANSLATION; LINEAGES; DOMAINS; MODEL; RAT AB Different cDNA clones encoding a rat homeobox gene and the mouse homologue OG-12 were cloned from adult rat brain and mouse embryo mRNA, respectively, The predicted amino acid sequences of the proteins belong to the paired-related subfamily of homeodomain proteins (Prx homeodomains). Hence, the gene was named Prx3 and the mouse and rat genes are indicated as mPrx3 and rPrx3, respectively, In the mouse as well as in the rat, the predicted Prx3 proteins share the homeodomain but have three different N termini, a 12-aa residue variation in the C terminus, and contain a 14-aa residue motif common to a subset of homeodomain proteins, termed the ''aristaless domain.'' Genetic mapping of Prx3 in the mouse placed this gene on chromosome 3, In situ hybridization on whole mount 12.5-day-old mouse embryos and sections of rat embryos at 14.5 and 16.5 days postcoitum revealed marked neural expression in discrete regions in the lateral and medial geniculate complex, superior and inferior colliculus, the superficial gray layer of the superior colliculus, pontine reticular formation, and inferior olive, In rat and mouse embryos, nonneuronal structures around the oral cavity and in hip and shoulder regions also expressed the Prx3 gene, In the adult rat brain, Prx3 gene expression was restricted to thalamic, tectal, and brainstem structures that include relay nuclei of the visual and auditory systems as well as other ascending systems conveying somatosensory information, Prx3 may have a role in specifying neural systems involved in processing somatosensory information, as well as in face and body structure formation. C1 UNIV UTRECHT,FAC MED,RUDOLF MAGNUS INST NEUROSCI,DEPT MED PHARMACOL,NL-3584 CG UTRECHT,NETHERLANDS. NHLBI,LAB BIOCHEM GENET,NIH,BETHESDA,MD 20892. NIAID,MOL MICROBIOL LAB,NIH,BETHESDA,MD 20892. NR 38 TC 19 Z9 21 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 25 PY 1997 VL 94 IS 24 BP 12993 EP 12998 DI 10.1073/pnas.94.24.12993 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YJ456 UT WOS:A1997YJ45600055 PM 9371788 ER PT J AU Damjanovich, S Bene, L Matko, J Alileche, A Goldman, CK Sharrow, S Waldmann, TA AF Damjanovich, S Bene, L Matko, J Alileche, A Goldman, CK Sharrow, S Waldmann, TA TI Preassembly of interleukin 2 (IL-2) receptor subunits on resting Kit 225 K6 T cells and their modulation by IL-2, IL-7, and IL-15: A fluorescence resonance energy transfer study SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE receptor assembly; cytokine binding; cell activation ID MHC CLASS-I; GAMMA-CHAIN; BETA-CHAIN; CYTOPLASMIC DOMAINS; TAC PEPTIDE; AFFINITY; SURFACE; MOLECULES; ASSOCIATION; COMPLEX AB Assembly and mutual proximities of alpha, beta, and gamma(c) subunits of the interleukin 2 receptors (IL-2R) in plasma membranes of Kit 225 K6 T lymphoma cells were investigated by fluorescence resonance energy transfer (FRET) using fluorescein isothiocyanate-and Cy3-conjugated monoclonal antibodies (mAbs) that were directed against the IL-2R alpha, IL-2R beta, and gamma(c) subunits of IL-2R. The cell-surface distribution of subunits was analyzed at the nanometer scale (2-10 nm) by FRET on a cell-by-cell basis, The cells were probed in resting phase and after coculture with saturating concentrations of IL-2, IL-7, and IL-15, FRET data from donor-and acceptor-labeled IL-2R beta-alpha, gamma-alpha, and gamma-beta pairs demonstrated close proximity of all subunits to each other in the plasma membrane of resting T cells, These mutual proximities do not appear to represent m4b-induced microaggregation, because FRET measurements with Fab fragments of the mAbs gave similar results, The relative proximities were meaningfully modulated by binding of IL-2, IL-7, and IL-15, Based on FRET analysis the topology of the three subunits at the surface of resting cells can be best described by a ''triangular model'' in the absence of added interleukins. IL-2 strengthens the bridges between the subunits, making the triangle more compact, IL-7 and IL-15 act in the opposite direction by opening the triangle possibly because they associate their private specific alpha receptors with the beta and/or gamma(c) subunits of the IL-2R complex, These data suggest that IL-2R subunits are already colocalized in resting T cells and do not require cytokine-induced redistribution, This colocalization is significantly modulated by binding of relevant interleukins in a cytokine-specific manner. C1 NCI,METAB BRANCH,NIH,BETHESDA,MD 20892. NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. DEBRECEN UNIV MED,SCH MED,DEPT BIOPHYS,H-4012 DEBRECEN,HUNGARY. RI Damjanovich, Sandor/A-9284-2011; Matko, Janos/C-9008-2013 OI Matko, Janos/0000-0001-9434-934X NR 48 TC 102 Z9 102 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 25 PY 1997 VL 94 IS 24 BP 13134 EP 13139 DI 10.1073/pnas.94.24.13134 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YJ456 UT WOS:A1997YJ45600079 PM 9371812 ER PT J AU Porgador, A Mandelboim, O Restifo, NP Strominger, JL AF Porgador, A Mandelboim, O Restifo, NP Strominger, JL TI Natural killer cell lines kill autologous beta(2)-microglobulin-deficient melanoma cells: Implications for cancer immunotherapy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HIGH-DOSE INTERLEUKIN-2; CLASS-I MOLECULES; RECOMBINANT INTERLEUKIN-2; T-LYMPHOCYTES; NK CELLS; ANTIGENS; THERAPY; EXPRESSION; METASTASES; RECEPTORS AB Cancer vaccines used to generate specific cytotoxic T lymphocytes are not effective against tumor cells that have lost or suppressed expression of their class I major histocompatibility complex proteins. This loss is common in some cancers and particularly in metastatic lesions, We show that beta(2)-microglobulin-deficient class I-negative melanoma variants derived from patients undergoing specific T cell therapy are lysed by heterologous as well as autologous natural killer (NK) lines and clones, but not by specific T cells, Moreover, the minor NK cell fraction but not the major T cell fraction derived from heterologous lymphokine activated killer cells kills those tumor cell lines. ICAM-1 expression by the different class I protein deficient tumors was correlated with their sensitivity to lysis by NK cells, Adoptive autologous NK therapy may be an important supplement to consider in the design of new cancer immunotherapies. C1 NCI,SURG BRANCH,DIV CANC TREATMENT,NIH,BETHESDA,MD 20892. HARVARD UNIV,DEPT MOL & CELLULAR BIOL,CAMBRIDGE,MA 01238. RP Porgador, A (reprint author), NIAID,LYMPHOCYTE BIOL SECT,IMMUNOL LAB,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01]; NCI NIH HHS [CA 47554] NR 41 TC 78 Z9 79 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 25 PY 1997 VL 94 IS 24 BP 13140 EP 13145 DI 10.1073/pnas.94.24.13140 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YJ456 UT WOS:A1997YJ45600080 PM 9371813 ER PT J AU Yamanaka, R Barlow, C LekstromHimes, J Castilla, LH Liu, PP Eckhaus, M Decker, T WynshawBoris, A Xanthopoulos, KG AF Yamanaka, R Barlow, C LekstromHimes, J Castilla, LH Liu, PP Eckhaus, M Decker, T WynshawBoris, A Xanthopoulos, KG TI Impaired granulopoiesis, myelodysplasia, and early lethality in CCAAT/enhancer binding protein epsilon-deficient mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID COLONY-STIMULATING FACTOR; C/EBP-BETA; TRANSCRIPTION FACTOR; TARGETED DISRUPTION; GENE; GRANULOCYTE; ALPHA; DIFFERENTIATION; EXPRESSION; LEUKEMIA AB Polymorphonuclear leukocytes are essential for host defense to infectious diseases, CCAAT/enhancer binding protein epsilon (C/EBP epsilon) is preferentially expressed in granulocytes and lymphoid cells, Mice with a null mutation in C/EBP epsilon develop normally and are fertile but fail to generate functional neutrophils and eosinophils, Opportunistic infections and tissue destruction lead to death by 3-5 months of age, Furthermore, end-stage mice develop myelodysplasia, characterized by proliferation of atypical granulocytes that efface the bone marrow and result in severe tissue destruction. Thus, C/EBP epsilon is essential for terminal differentiation and functional maturation of committed granulocyte progenitor cells. C1 NATL HUMAN GENOME RES INST,CLIN GENE THERAPY BRANCH,NIH,BETHESDA,MD 20892. NATL HUMAN GENOME RES INST,LAB GENET DIS RES,NIH,BETHESDA,MD 20892. NATL HUMAN GENOME RES INST,LAB GENE TRANSFER,NIH,BETHESDA,MD 20892. NIH,VET RESOURCES PROGRAM,NATL CTR RES RESOURCES,BETHESDA,MD 20892. VIENNA BIOCTR,INST MICROBIOL & GENET,A-1030 VIENNA,AUSTRIA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 28 TC 232 Z9 235 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 25 PY 1997 VL 94 IS 24 BP 13187 EP 13192 DI 10.1073/pnas.94.24.13187 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YJ456 UT WOS:A1997YJ45600088 PM 9371821 ER PT J AU Chun, TW Stuyver, L Mizell, SB Ehler, LA Mican, JAM Baseler, M Lloyd, AL Nowak, MA Fauci, AS AF Chun, TW Stuyver, L Mizell, SB Ehler, LA Mican, JAM Baseler, M Lloyd, AL Nowak, MA Fauci, AS TI Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PERIPHERAL-BLOOD CELLS; CD8(+) T-CELLS; INFECTED INDIVIDUALS; LIFE-SPAN; IN-VIVO; TYPE-1; EXPRESSION; LYMPHOCYTES; DISEASE AB Although highly active antiretroviral therapy (HAART) in the form of triple combinations of drugs including protease inhibitors can reduce the plasma viral load of some HIV-1-infected individuals to undetectable levels, it is unclear what the effects of these regimens are on latently infected CD4(+) T cells and what role these cells play in the persistence of HIV-1 infection in individuals receiving such treatment, The present study demonstrates that highly purified CD4(+) T cells from 13 of 13 patients receiving HAART with an average treatment time of 10 months and with undetectable (<500 copies HIV RNA/ml) plasma viremia by a commonly used bDNA assay carried integrated proviral DNA and were capable of producing infectious virus upon cellular activation in vitro. Phenotypic analysis of HIV-1 produced by activation of latently infected CD4(+) T cells revealed the presence in some patients of syncytium-inducing virus. In addition, the presence of unintegrated HIV-1 DNA in infected resting CD4(+) T cells from patients receiving HAART, even those with undetectable plasma viremia, suggests persistent active virus replication in vivo. C1 INNOGENET NV,B-9052 GHENT,BELGIUM. SCI APPLICAT INT CORP,FREDERICK,MD 21702. UNIV OXFORD,DEPT ZOOL,OXFORD OX1 3PS,ENGLAND. RP Chun, TW (reprint author), NIAID,IMMUNOREGULAT LAB,NIH,BLDG 10,ROOM 6A32,BETHESDA,MD 20892, USA. RI Nowak, Martin/A-6977-2008; Lloyd, Alun/H-4944-2012 NR 40 TC 1062 Z9 1081 U1 1 U2 28 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 25 PY 1997 VL 94 IS 24 BP 13193 EP 13197 DI 10.1073/pnas.94.24.13193 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YJ456 UT WOS:A1997YJ45600089 PM 9371822 ER PT J AU Black, HR Cohen, JD Kaplan, NM Ferdinand, KC Chobanian, AV Dustan, HP Gifford, RW Moser, M Sheps, SG Agodoa, L August, PA Bakris, GL Burt, V Busse, W Carter, BL Chesley, FD Cleeman, J Cohn, JN Cregler, LL Crespo, C Cushman, WC Cutler, J Darrow, MD DeQuattro, VL Devereux, RB Dworkin, LD Elliott, WJ Epstein, M Falkner, B Ferrario, CM Flack, JM Frishman, W Frohlich, ED Green, LA Grimm, RH Hagberg, JM Hall, WD Handler, J Havas, S Hill, MN Horan, MJ Hsueh, WA Hyman, BN Izzo, JL Jamerson, K Kiley, JP Kochar, MS Kolasa, KM Krakoff, LR Levy, D Lindheimer, MD Luepker, RV Malone, MEL Massie, B Materson, BJ Merchant, J Messerli, FH Miller, NH Moore, MA MustoneAlexander, L Oparil, S Perry, HM Pickering, TG Pratt, JH Ram, CVS Randall, OS Reed, JW Roberts, RW Roccella, EJ Rogus, SD Saunders, E Schron, E Schwartz, G Sibai, BM Snyder, D Sowers, JR Stamler, J Temple, R Textor, S Thom, T Vidt, DG Weber, M Weinberger, MH Weinshilboum, R Whelton, PK Whisnant, JP Wiebers, DO Winston, MC Wright, JT Lenfant, C Casser, L Colman, PJ Edwards, T Feeley, DM Gajewski, J Levine, D Manger, W Marshall, EC Nickey, WA Robert, RW Secrest, BG Singer, EH Whisnant, JP Wilson, GJ Young, JM Bachman, JW Campese, VM Carr, AA Hand, M Holden, DC Jamieson, MJ Julius, S Mensah, GA Prisant, M Sullivan, JM Wilson, DJ Morosco, G Anderson, DE Waugh, D AF Black, HR Cohen, JD Kaplan, NM Ferdinand, KC Chobanian, AV Dustan, HP Gifford, RW Moser, M Sheps, SG Agodoa, L August, PA Bakris, GL Burt, V Busse, W Carter, BL Chesley, FD Cleeman, J Cohn, JN Cregler, LL Crespo, C Cushman, WC Cutler, J Darrow, MD DeQuattro, VL Devereux, RB Dworkin, LD Elliott, WJ Epstein, M Falkner, B Ferrario, CM Flack, JM Frishman, W Frohlich, ED Green, LA Grimm, RH Hagberg, JM Hall, WD Handler, J Havas, S Hill, MN Horan, MJ Hsueh, WA Hyman, BN Izzo, JL Jamerson, K Kiley, JP Kochar, MS Kolasa, KM Krakoff, LR Levy, D Lindheimer, MD Luepker, RV Malone, MEL Massie, B Materson, BJ Merchant, J Messerli, FH Miller, NH Moore, MA MustoneAlexander, L Oparil, S Perry, HM Pickering, TG Pratt, JH Ram, CVS Randall, OS Reed, JW Roberts, RW Roccella, EJ Rogus, SD Saunders, E Schron, E Schwartz, G Sibai, BM Snyder, D Sowers, JR Stamler, J Temple, R Textor, S Thom, T Vidt, DG Weber, M Weinberger, MH Weinshilboum, R Whelton, PK Whisnant, JP Wiebers, DO Winston, MC Wright, JT Lenfant, C Casser, L Colman, PJ Edwards, T Feeley, DM Gajewski, J Levine, D Manger, W Marshall, EC Nickey, WA Robert, RW Secrest, BG Singer, EH Whisnant, JP Wilson, GJ Young, JM Bachman, JW Campese, VM Carr, AA Hand, M Holden, DC Jamieson, MJ Julius, S Mensah, GA Prisant, M Sullivan, JM Wilson, DJ Morosco, G Anderson, DE Waugh, D TI The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure SO ARCHIVES OF INTERNAL MEDICINE LA English DT Review ID CORONARY HEART-DISEASE; LEFT-VENTRICULAR HYPERTROPHY; ISOLATED SYSTOLIC HYPERTENSION; CONVERTING ENZYME-INHIBITION; RANDOMIZED CONTROLLED TRIALS; ACUTE MYOCARDIAL-INFARCTION; STAGE RENAL-DISEASE; FOLLOW-UP PROGRAM; ANTIHYPERTENSIVE THERAPY; CARDIOVASCULAR-DISEASE C1 NHLBI, INFORMAT CTR, NATL HIGH BLOOD PRESSURE EDUC PROGRAM, BETHESDA, MD 20894 USA. MAYO CLIN & MAYO FDN, MAYO MED SCH, ROCHESTER, MN 55905 USA. RUSH PRESBYTERIAN ST LUKES MED CTR, CHICAGO, IL 60612 USA. ST LOUIS UNIV, HLTH SCI CTR, ST LOUIS, MO 63103 USA. UNIV TEXAS, SW MED SCH, DALLAS, TX 75230 USA. HEARTBEATS LIFE CTR, NEW ORLEANS, LA USA. BOSTON UNIV, BOSTON, MA 02215 USA. UNIV VERMONT, COLL MED, BURLINGTON, VT 05405 USA. CLEVELAND CLIN FDN, CLEVELAND, OH 44195 USA. YALE UNIV, SCH MED, NEW HAVEN, CT 06520 USA. NIDDK, BETHESDA, MD USA. NEW YORK HOSP, NEW YORK, NY 10021 USA. NATL CTR HLTH STAT, HYATTSVILLE, MD 20782 USA. UNIV WISCONSIN, MADISON, WI 53706 USA. UNIV COLORADO, DENVER, CO 80202 USA. US DEPT HHS, AGCY HLTH CARE POLICY & RES, ROCKVILLE, MD 20852 USA. UNIV MINNESOTA, SCH MED, MINNEAPOLIS, MN 55455 USA. CUNY, SCH MED, NEW YORK, NY 10031 USA. UNIV TENNESSEE, COLL MED, MEMPHIS, TN USA. E CAROLINA UNIV, SCH MED, GREENVILLE, NC 27858 USA. UNIV SO CALIF, MED CTR, LOS ANGELES, CA 90089 USA. CORNELL UNIV, MED CTR, NEW YORK, NY 10021 USA. RHODE ISL HOSP, PROVIDENCE, RI USA. UNIV MIAMI, SCH MED, MIAMI, FL USA. ALLEGHENY UNIV HLTH SCI, PHILADELPHIA, PA 19102 USA. WAKE FOREST UNIV, BOWMAN GRAY SCH MED, WINSTON SALEM, NC USA. MONTEFIORE MED CTR, ALBERT EINSTEIN COLL MED, BRONX, NY 10467 USA. ALTON OCHSNER MED FDN & OCHSNER CLIN, NEW ORLEANS, LA 70121 USA. UNIV MICHIGAN, ANN ARBOR, MI 48109 USA. UNIV MARYLAND, COLLEGE PK, MD 20742 USA. EMORY UNIV, ATLANTA, GA 30322 USA. KAISER PERMANENTE, ANAHEIM, CA USA. UNIV MARYLAND, SCH MED, BALTIMORE, MD 21201 USA. JOHNS HOPKINS UNIV, BALTIMORE, MD 21218 USA. BAYLOR COLL MED, HOUSTON, TX 77030 USA. SUNY BUFFALO, BUFFALO, NY 14260 USA. MED COLL WISCONSIN, MILWAUKEE, WI 53226 USA. E CAROLINA UNIV, SCH MED, GREENVILLE, NC 27858 USA. ENGLEWOOD HOSP, ENGLEWOOD, CO USA. NHLBI, FRAMINGHAM HEART STUDY, BETHESDA, MD 20894 USA. UNIV CHICAGO HOSP, CHICAGO, IL 60637 USA. JEFFERSON COMMUNITY COLL, LOUISVILLE, KY USA. UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94143 USA. HLTH CARE FINANCING ADM, WASHINGTON, DC USA. STANFORD CARDIAC REHABIL PROGRAM, PALO ALTO, CA USA. GEORGE WASHINGTON UNIV, SCH MED & HLTH SCI, WASHINGTON, DC 20052 USA. UNIV ALABAMA, BIRMINGHAM, AL USA. VET AFFAIRS MED CTR, WASHINGTON, DC 20422 USA. WASHINGTON UNIV, SCH MED, ST LOUIS, MO 63130 USA. INDIANA UNIV, SCH MED, INDIANAPOLIS, IN USA. UNIV TEXAS, SW MED CTR, DALLAS, TX USA. HOWARD UNIV HOSP, WASHINGTON, DC USA. MOREHOUSE SCH MED, ATLANTA, GA 30310 USA. VENCOR, LOUISVILLE, KY USA. US HLTH RESOURCES & SERV ADM, ROCKVILLE, MD 20857 USA. WAYNE STATE UNIV, DETROIT, MI 48202 USA. NORTHWESTERN UNIV, SCH MED, CHICAGO, IL USA. US FDA, ROCKVILLE, MD 20857 USA. BROOKDALE HOSP, BROOKLYN, NY USA. TULANE UNIV, SCH PUBL HLTH & TROP MED, NEW ORLEANS, LA 70118 USA. AMER HEART ASSOC, DALLAS, TX USA. CASE WESTERN RESERVE UNIV, CLEVELAND, OH 44106 USA. CTR DIS CONTROL & PREVENT, NATL CTR HLTH STAT, ATLANTA, GA 30333 USA. AMER OPTOMETR ASSOC, ST LOUIS, MO USA. US DEPT HHS, AGCY HLTH CARE POLICY & RES, ROCKVILLE, MD 20852 USA. AMER COLL PHYSICIANS, PHILADELPHIA, PA USA. AMER PODIATR MED ASSOC, BETHESDA, MD USA. NATL KIDNEY FDN, NEW YORK, NY USA. AMER RED CROSS, WASHINGTON, DC 20006 USA. NHLBI, AD HOC COMM MINOR POPULAT, BETHESDA, MD 20894 USA. AMER COLL CARDIOL, BETHESDA, MD USA. AMER MED ASSOC, CHICAGO, IL 60610 USA. AMER ACAD FAMILY PHYS, KANSAS CITY, MO USA. AMER PUBL HLTH ASSOC, WASHINGTON, DC 20005 USA. AMER ACAD OPHTHALMOL, SAN FRANCISCO, CA USA. AMER NURSES ASSOC, WASHINGTON, DC 20024 USA. AMER ACAD PHYS ASSISTANTS, ALEXANDRIA, VA 22314 USA. AMER OSTEOPATH ASSOC, CHICAGO, IL 60611 USA. US DEPT VET AFFAIRS, WASHINGTON, DC USA. AMER PHARMACEUT ASSOC, WASHINGTON, DC USA. AMER DENT ASSOC, CHICAGO, IL 60611 USA. AMER COLL CHEST PHYS, NORTHBROOK, IL 60062 USA. AMER DIABET ASSOC, ALEXANDRIA, VA USA. AMER ACAD NEUROL, MINNEAPOLIS, MN USA. AMER DIETET ASSOC, CHICAGO, IL USA. AMER COLL OCCUPAT & ENVIRONM MED, ARLINGTON HTS, IL 60005 USA. AUGUSTA PREVENT CARDIOL, CIRCULATORY DIS CTR, AUGUSTA, GA USA. UNIV TEXAS, HLTH SCI CTR, SAN ANTONIO, TX USA. MED COLL GEORGIA, AUGUSTA, GA 30912 USA. ROW SCI INC, ROCKVILLE, MD USA. NR 252 TC 4448 Z9 4569 U1 4 U2 67 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 24 PY 1997 VL 157 IS 21 BP 2413 EP 2446 PG 34 WC Medicine, General & Internal SC General & Internal Medicine GA YH222 UT WOS:A1997YH22200004 ER PT J AU Okochi, M Ishii, K Usami, M Sahara, N Kametani, F Tanaka, K Fraser, PE Ikeda, M Saunders, AM Hendriks, L Shoji, SI Nee, LE Martin, JJ Van Broeckhoven, C StGeorgeHyslop, PH Roses, AD Mori, H AF Okochi, M Ishii, K Usami, M Sahara, N Kametani, F Tanaka, K Fraser, PE Ikeda, M Saunders, AM Hendriks, L Shoji, SI Nee, LE Martin, JJ Van Broeckhoven, C StGeorgeHyslop, PH Roses, AD Mori, H TI Proteolytic processing of presenilin-1 (PS-1) is not associated with Alzheimer's disease with or without PS-1 mutations SO FEBS LETTERS LA English DT Article DE Alzheimer's disease; presenilin; mutation; caspase-3; CPP32 ID IN-VIVO; MISSENSE MUTATIONS; GENE; PRECURSOR AB Cerebral presenilin-1 protein (PS-1) is normally composed of the amino-terminal fragment (NTF) with M-r 28 kDa and the carboxy-terminal fragment (CTF) with 18 kDa. We analyzed human PS-1 in brains with early-onset familial Alzheimer's disease (FAD) with and without PS-1 mutations to study whether mutated PS-1 was abnormally metabolized, Cerebral PS-1 were found to be cleaved into two fragments of NTF and CTF independently of the occurrence of PS-1 mutation in human brains, A small portion of PS-1 nas recently found to suffer another processing by caspase-3, an apoptosis-related cysteine protease. In contrast to the recent finding that the Volga-German mutation on presenilin-2 (PS-2) affects the increasing caspase-3 PS-2 fragment, the PS-1 mutation did not cause a significant change in PS-1 fragmentation. We conclude that PS-1 fragmentation and other (probably caspase-3-mediated) digestion following apoptosis occur independently of PS-1 mutations. (C) 1997 Federation of European Biochemical Societies. C1 TOKYO INST PSYCHIAT, DEPT MOL BIOL, SETAGAYA KU, TOKYO 156, JAPAN. UNIV TSUKUBA, INST CLIN MED, DEPT NEUROL, TSUKUBA, IBARAKI 305, JAPAN. UNIV TORONTO, DEPT MED NEUROL & MED BIOPHYS, CTR RES NEURODEGENERAT DIS, TORONTO, ON M5S 1A8, CANADA. TORONTO HOSP, DEPT MED, DIV NEUROL, TORONTO, ON M5S 1A8, CANADA. DUKE UNIV, MED CTR, JOSEPH & KATHLEEN BRYAN ALZHEIMER DIS RES CTR, DEPT MED NEUROL, DURHAM, NC USA. DUKE UNIV, MED CTR, JOSEPH & KATHLEEN BRYAN ALZHEIMER DIS RES CTR, DEPT NEUROBIOL, DURHAM, NC USA. UNIV ANTWERP VIB, BORN BUNGE FDN, DEPT BIOCHEM,LAB NEUROGENET, B-2020 ANTWERP, BELGIUM. NINCDS, MED NEUROL BRANCH, NIH, BETHESDA, MD 20892 USA. UNIV ANTWERP, BORN BUNGE FDN, DEPT MED, NEUROPATHOL LAB, B-2020 ANTWERP, BELGIUM. OI Okochi, Masayasu/0000-0002-2318-7651 NR 28 TC 31 Z9 31 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 EI 1873-3468 J9 FEBS LETT JI FEBS Lett. PD NOV 24 PY 1997 VL 418 IS 1-2 BP 162 EP 166 DI 10.1016/S0014-5793(97)01378-1 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA YJ818 UT WOS:A1997YJ81800037 PM 9414118 ER PT J AU Carroll, MW Moss, B AF Carroll, MW Moss, B TI Host range and cytopathogenicity of the highly attenuated MVA strain of vaccinia virus: Propagation and generation of recombinant viruses in a nonhuman mammalian cell line SO VIROLOGY LA English DT Article ID OPEN READING FRAME; HAMSTER OVARY CELLS; PROTEIN-SYNTHESIS; ENVELOPE PROTEIN; EXTRACELLULAR VIRUS; INSERTION SITE; RNA-POLYMERASE; E3L GENE; DELETION; REPLICATION AB Modified vaccinia virus Ankara (MVA), attenuated by over 500 passages in primary chick embyro fibroblasts (CEF), is presently being used as a safe expression vector. We compared the host ranges of MVA and the parental Ankara strain in CEF and 15 permanent cell lines. The cells could be grouped into three categories: permissive, semipermissive, and nonpermissive. For MVA, the permissive category consisted of primary CEF, a quail cell line derived from QT6, and the Syrian hamster cell line BHK-21. Only in BHK-21 cells did the Virus yield approach that occurring in primary CEF. The semipermissive category included two African green monkey cell lines: BS-C-1 and CV-1. The nonpermissive category for MVA consisted of three human cell lines HeLa, 293, and SW 839; one rhesus monkey cell line FRhK-4; two Chinese hamster cell lines CHO and CHL; one pig cell line PK(15); and three rabbit cell lines RK13, RAB-B, and SIRC. The grouping for MVA with a restored K1L host range gene was similar except for the inclusion of RK13 cells among permissive lines. The grouping for the Ankara strain, however, was quite different with more permissive and semipermissive cell lines. Nevertheless, in cells that were permissive for MVA, the virus replicated to higher levels than Ankara, consistent with both positive and negative growth elements associated with the adaptation of MVA. The cell lines were also characterized according to their susceptibilty to MVA-induced cytopathic effects, expression of a late promoter regulated reporter gene by an MVA recombinant, and stage at which virion morphogenesis was blocked, Finally, the permissive BHK-21 cell line was shown to be competent for constructing and propagating recombinant MVA, providing an alternative to primary CEF. (C) 1997 Academic Press. C1 NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. NR 42 TC 210 Z9 216 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 24 PY 1997 VL 238 IS 2 BP 198 EP 211 DI 10.1006/viro.1997.8845 PG 14 WC Virology SC Virology GA YK656 UT WOS:A1997YK65600004 PM 9400593 ER PT J AU Voevodin, AF Johnson, BK Samilchuk, EI Stone, GA Druilhet, R Greer, WJ Gibbs, CJ AF Voevodin, AF Johnson, BK Samilchuk, EI Stone, GA Druilhet, R Greer, WJ Gibbs, CJ TI Phylogenetic analysis of simian T-lymphotropic virus type I (STLV-I) in common chimpanzees (Pan troglodytes): Evidence for interspecies transmission of the virus between chimpanzees and humans in Central Africa SO VIROLOGY LA English DT Article DE STLV-I; chimpanzee; PCR; phylogenetic analysis ID CELL LEUKEMIA-VIRUS; NON-HUMAN PRIMATES; CLOSELY RELATED AGENT; HTLV-I; TRANSMEMBRANE GLYCOPROTEIN; SEROLOGICAL CONFIRMATION; JAPANESE MONKEYS; INFECTION; ANTIBODIES; IMMUNOBLOT AB Serum and peripheral blood leukocytes from the chimpanzees (Pan troglodytes) of the colony of the Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, NIH, were tested for the presence of STLV-1-specific antibodies and proviral DNA. Antibodies were determined by gelatin particle agglutination and Western blot (WB) assays utilizing HTLV-I antigens. Proviral DNA was detected by four PCR assays targeting three different regions of STLV-l genome: the fragments of the env and pol genes and LTR. Twenty of twenty-two DNA samples from WE-positive animals were PCR positive. None of the DNA samples from WE-negative (n = 5) and WE-indeterminate (n = 4) animals was PCR positive. The results of the nested and double nested env PCR tests were fully concordant; the seminested LTR PCR test was much less sensitive. The DNA sequences from the env (483 bp) and the pol (200 bp) genes and LTR (705 bp) were determined for six, two, and two chimpanzee STLV-l isolates, respectively. Phylogenetic analysis revealed that chimpanzee STLV-l isolates can be attributed to three clades. The first of these clades (SS-PTR1/CSA) included STLV-l isolates from the chimpanzees and West African subspecies of African green monkeys (Cercopithecus a. sabaeus). The other clades (S-PTR2 and S-PTR3) included STLV-l isolates only from chimpanzees. However, both S-PTR2 and S-PTR3 clustered together with Central African HTLV-I comprising the human/simian clade (HS-HSA/PTR). This pattern of phylogenetic clustering suggests that interspecies transmission of STLV-l occurred between chimpanzees and African green monkey subspecies as well between chimpanzees and human populations in Central Africa. (C) 1997 Academic Press. C1 NINCDS,CENT NERVOUS SYST STUDIES LAB,NIH,BETHESDA,MD 20892. KUWAIT MED GENET CTR,KUWAIT,KUWAIT. RP Voevodin, AF (reprint author), KUWAIT UNIV,FAC MED,DEPT MICROBIOL,POB 24923,SAFAT 13110,KUWAIT. NR 32 TC 31 Z9 31 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 24 PY 1997 VL 238 IS 2 BP 212 EP 220 DI 10.1006/viro.1997.8826 PG 9 WC Virology SC Virology GA YK656 UT WOS:A1997YK65600005 PM 9400594 ER PT J AU Ohno, H Aguilar, RC Fournier, MC Hennecke, S Cosson, P Bonifacino, JS AF Ohno, H Aguilar, RC Fournier, MC Hennecke, S Cosson, P Bonifacino, JS TI Interaction of endocytic signals from the HIV-1 envelope glycoprotein complex with members of the adaptor medium chain family SO VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TRANS-GOLGI NETWORK; TRANSFERRIN RECEPTOR INTERNALIZATION; CLATHRIN-ASSOCIATED PROTEINS; VARICELLA-ZOSTER VIRUS; CYTOPLASMIC DOMAIN; AMINO-ACID; TRANSMEMBRANE PROTEIN; SORTING SIGNALS; CELL-SURFACE AB The envelope glycoprotein (Env) complex of HIV-I undergoes rapid internalization from the plasma membrane of human cells by virtue of a tyrosine-based endocytic signal (RQGYSPL, residues 704-710) in the cytosolic tail of the protein (J. F. Rowell et al., J. Immunol. 155, 473-488, 1995). Here we demonstrate that this tyrosine-based signal interacts with the mu 2 (medium) chain of the AP-2 clathrin-associated adaptor, a protein complex involved in endocytosis of cell surface receptors. he same signal is also capable of interacting with two other members of the adaptor medium chain family, mu 1 and mu 3A, which are components of the AP-I and AP-3 adaptor complexes, respectively. Interactions with mu 1 and mu 3A might be responsible for the targeting of the internalized envelope glycoprotein to lysosomes or to the basolateral plasma membrane of polarized epithelial cells. A second potential tyrosine-based signal (LFSYHRL, residues 760-766) also interacts with mu 1, mu 2, and mu 3A, although it is less important for internalization in vivo probably due to its position within the cytosolic tail. Overexpression of chimeric proteins having the HIV-1 Env cytosolic tail increases expression of the transferrin receptor on the cell surface, probably due to saturation of the cellular pool of mu 2 by the overexpressed proteins. These observations suggest that HIV-I Env utilizes the protein sorting machinery of the host cells for internalization and sorting at various steps of the endocytic and biosynthetic pathways. (C) 1997 Academic Press. C1 NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. BASEL INST IMMUNOL,CH-4005 BASEL,SWITZERLAND. RI Ohno, Hiroshi/L-7899-2014; OI Ohno, Hiroshi/0000-0001-8776-9661; Bonifacino, Juan S./0000-0002-5673-6370 NR 57 TC 123 Z9 123 U1 2 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 24 PY 1997 VL 238 IS 2 BP 305 EP 315 DI 10.1006/viro.1997.8839 PG 11 WC Virology SC Virology GA YK656 UT WOS:A1997YK65600014 PM 9400603 ER PT J AU Hyman, SE AF Hyman, SE TI Regulation of transcription factors by environmental stimuli. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 21 PY 1997 VL 74 IS 6 BP 556 EP 556 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YB414 UT WOS:A1997YB41400004 ER PT J AU Goldman, D Knowler, WC Hanson, RL Robin, RW Urbanek, M Moore, E Bennett, PH Long, J AF Goldman, D Knowler, WC Hanson, RL Robin, RW Urbanek, M Moore, E Bennett, PH Long, J TI Autosome-wide scan for alcohol dependence in southwestern American Indians provides suggestive evidence for loci on chromosomes 4 and 11 SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIAAA,NEUROGENET LAB,ROCKVILLE,MD 20852. RI Hanson, Robert/O-3238-2015; Goldman, David/F-9772-2010 OI Hanson, Robert/0000-0002-4252-7068; Goldman, David/0000-0002-1724-5405 NR 0 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 21 PY 1997 VL 74 IS 6 BP 574 EP 575 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA YB414 UT WOS:A1997YB41400072 ER PT J AU Philibert, RA StJean, PL Schork, NJ Anderson, MC Dalwadi, H DamschroderWilliams, PJ Doherty, AE Dymarskaia, I Ehlert, MA Galdzicka, M Lau, E Long, RT Patel, A Paul, SP Remortel, BG Stubblefield, BK Martin, BM Allen, CR Pauls, DL Elston, RC Egeland, JA Paul, SM Ginns, EI AF Philibert, RA StJean, PL Schork, NJ Anderson, MC Dalwadi, H DamschroderWilliams, PJ Doherty, AE Dymarskaia, I Ehlert, MA Galdzicka, M Lau, E Long, RT Patel, A Paul, SP Remortel, BG Stubblefield, BK Martin, BM Allen, CR Pauls, DL Elston, RC Egeland, JA Paul, SM Ginns, EI TI A genome-wide search for chromosome regions linked to bipolar affective disorder in the Old Order Amish identifies several candidate loci. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIMH,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. CASE WESTERN RESERVE UNIV,DEPT EPIDEMIOL & BIOSTAT,CLEVELAND,OH 44106. UNIV MIAMI,SCH MED,DEPT PSYCHIAT,HERSHEY,PA. YALE UNIV,SCH MED,CTR CHILD STUDY,NEW HAVEN,CT. ELI LILLY & CO,LILLY RES LABS,INDIANAPOLIS,IN 46285. NR 0 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 21 PY 1997 VL 74 IS 6 BP 585 EP 586 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA YB414 UT WOS:A1997YB41400109 ER PT J AU Philibert, RA StJean, PL Sahbatou, M Egeland, JA Paul, SM Ginns, EI AF Philibert, RA StJean, PL Sahbatou, M Egeland, JA Paul, SM Ginns, EI TI A multivariate model using haplotype sharing: Results for bipolar affective disorder in the Old Order Amish. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIMH,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. CASE WESTERN RESERVE UNIV,DEPT EPIDEMIOL & BIOSTAT,CLEVELAND,OH 44106. CEPH,FDN JEAN DAUSSET,PARIS,FRANCE. UNIV MIAMI,SCH MED,DEPT PSYCHIAT,HERSHEY,PA. ELI LILLY & CO,LILLY RES LABS,INDIANAPOLIS,IN 46285. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 21 PY 1997 VL 74 IS 6 BP 591 EP 591 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YB414 UT WOS:A1997YB41400128 ER PT J AU Meslin, EM AF Meslin, EM TI Ethical, legal, and social implications of research in psychiatric genetics: Thoughts from the ELSI research program at the US National Human Genome Research Institute. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NATL HUMAN GENOME RES INST,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 21 PY 1997 VL 74 IS 6 BP 593 EP 593 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YB414 UT WOS:A1997YB41400133 ER PT J AU Shore, D AF Shore, D TI Ethical issues and informed consent in psychiatric genetic research. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIMH,DIV CLIN & TREATMENT RES,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 21 PY 1997 VL 74 IS 6 BP 593 EP 593 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YB414 UT WOS:A1997YB41400134 ER PT J AU Callicott, JH Bertolino, A Mattay, VS Podell, D Weschler, M Frank, JA Egan, MF Weinberger, DR AF Callicott, JH Bertolino, A Mattay, VS Podell, D Weschler, M Frank, JA Egan, MF Weinberger, DR TI H-1-MRSI abnormalities in unaffected siblings of patients with schizophrenia: A possible intermediate neurobiological phenotype. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIMH,CLIN BRAIN DISORDERS BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 21 PY 1997 VL 74 IS 6 BP 595 EP 595 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YB414 UT WOS:A1997YB41400140 ER PT J AU Egan, MF Goldberg, TE Bigelow, L Coppola, R Weschler, M Hommer, D Weinberger, DR AF Egan, MF Goldberg, TE Bigelow, L Coppola, R Weschler, M Hommer, D Weinberger, DR TI Suitability of neuropsychological parameters and saccade frequency as phenotypes for genetic studies of schizophrenia. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIMH,ST ELIZABETHS HOSP,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 21 PY 1997 VL 74 IS 6 BP 597 EP 597 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YB414 UT WOS:A1997YB41400147 ER PT J AU Knable, M Egan, MF Goldberg, T Bigelow, L CannonSpoor, E Weinberger, DR AF Knable, M Egan, MF Goldberg, T Bigelow, L CannonSpoor, E Weinberger, DR TI Relationship between adult cortical dysfunction and childhood developmental abnormalities in patients with schizophrenia: Evidence for a neurodevelopmental-cortical phenotype? SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIMH,NEUROSCI RES CTR,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 21 PY 1997 VL 74 IS 6 BP 598 EP 598 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YB414 UT WOS:A1997YB41400150 ER PT J AU Stassen, HH Coppola, R Torrey, EF Gottesman, II AF Stassen, HH Coppola, R Torrey, EF Gottesman, II TI Nongenetic pathologic developments of brain-wave patterns in monozygotic twins discordant and concordant for schizophrenia. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 PSYCHIAT UNIV HOSP ZURICH,RES DEPT,ZURICH,SWITZERLAND. NIMH,NEUROPSYCHIAT RES HOSP,WASHINGTON,DC 20032. UNIV VIRGINIA,DEPT PSYCHOL,CHARLOTTESVILLE,VA 22903. RI G, I/D-8042-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 21 PY 1997 VL 74 IS 6 BP 600 EP 600 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YB414 UT WOS:A1997YB41400156 ER PT J AU Moldin, SO AF Moldin, SO TI Mapping genes for schizophrenia with discordant sib-pair sampling. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIMH,SCHIZOPHRENIA RES BRANCH,GENET RES PROGRAM,NIH,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 21 PY 1997 VL 74 IS 6 BP 601 EP 601 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YB414 UT WOS:A1997YB41400160 ER PT J AU StJean, PL Schork, NJ Thiel, B Philibert, RA Egeland, JA Paul, SM Ginns, EI AF StJean, PL Schork, NJ Thiel, B Philibert, RA Egeland, JA Paul, SM Ginns, EI TI Haplotype sharing analysis of bipolar affective disorder in the Old Order Amish. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 CASE WESTERN RESERVE UNIV,DEPT EPIDEMIOL & BIOSTAT,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,DEPT GENET,CLEVELAND,OH 44106. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. JACKSON LAB,BAR HARBOR,ME 04609. NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. UNIV MIAMI,DEPT PSYCHIAT,MIAMI,FL 33152. ELI LILLY & CO,LILLY RES LABS,INDIANAPOLIS,IN 46285. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 21 PY 1997 VL 74 IS 6 BP 601 EP 601 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YB414 UT WOS:A1997YB41400159 ER PT J AU Sommer, S Feng, J Sobell, J Heston, L Goldman, D Cook, E Gelernter, J Kranzler, H AF Sommer, S Feng, J Sobell, J Heston, L Goldman, D Cook, E Gelernter, J Kranzler, H TI Mutation screening of candidate genes in psychiatric patients by restriction endonuclease fingerprinting. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 CITY HOPE NATL MED CTR,BECKMAN RES INST,DEPT MOL GENET,DUARTE,CA 91010. CITY HOPE NATL MED CTR,BECKMAN RES INST,DIV MOL MED,DUARTE,CA 91010. UNIV WASHINGTON,DEPT PSYCHIAT,SEATTLE,WA 98195. NATL INST ALCOHOL ABUSE & ALCOHOLISM,NEUROGENET LAB,BETHESDA,MD. UNIV CHICAGO,DEPT CHILD PSYCHIAT,CHICAGO,IL 60637. YALE UNIV,DEPT PSYCHIAT,NEW HAVEN,CT 06520. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 21 PY 1997 VL 74 IS 6 BP 603 EP 604 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA YB414 UT WOS:A1997YB41400169 ER PT J AU vanAmelsvoort, TAMJ Schapiro, MB Robertson, DMW Daly, E Xenitidis, K Critchley, H Murphy, DGM AF vanAmelsvoort, TAMJ Schapiro, MB Robertson, DMW Daly, E Xenitidis, K Critchley, H Murphy, DGM TI X-chromosome trinucleotide repeats: Effect on brain structure and metabolism. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 INST PSYCHIAT,DEPT PSYCHOL MED,LONDON SE5 8AF,ENGLAND. NIA,CTR CLIN,NEUROSCI LAB,SECT BRAIN AGING & DEMENTIA,BETHESDA,MD 20892. RI daly, eileen/B-6716-2011; critchley, hugo/G-9267-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 21 PY 1997 VL 74 IS 6 BP 606 EP 606 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YB414 UT WOS:A1997YB41400176 ER PT J AU Malhotra, AK Goldman, D Mazzanti, C Clifton, A Breier, A Pickar, D AF Malhotra, AK Goldman, D Mazzanti, C Clifton, A Breier, A Pickar, D TI A functional serotonin transporter polymorphism is associated with psychosis in neuroleptic-free schizophrenics. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIMH,EXPT THERAPEUT BRANCH,DIV INTRAMURAL RES PROGRAM,NIH,BETHESDA,MD 20892. NIAAA,NEUROGENET LAB,DIV INTRAMURAL CLIN & BIOL RES,NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 21 PY 1997 VL 74 IS 6 BP 613 EP 613 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YB414 UT WOS:A1997YB41400200 ER PT J AU Rotondo, A Mazzanti, CM Nielsen, DA Schuebel, KE Lezza, A Gemignani, A Presta, S Pfanner, C Bouanani, S Ramacciotti, C DellOsso, L Mauri, M Goldman, D Cassano, GB AF Rotondo, A Mazzanti, CM Nielsen, DA Schuebel, KE Lezza, A Gemignani, A Presta, S Pfanner, C Bouanani, S Ramacciotti, C DellOsso, L Mauri, M Goldman, D Cassano, GB TI Lack of association of promoter region variation in tryptophan hydroxylase and serotonin transporter with obsessive compulsive disorder and eating disorders. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 UNIV PISA,INST PSYCHIAT,I-56100 PISA,ITALY. NIAAA,NEUROGENET LAB,NIH,ROCKVILLE,MD 20852. RI Nielsen, David/B-4655-2009 NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 21 PY 1997 VL 74 IS 6 BP 621 EP 621 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YB414 UT WOS:A1997YB41400230 ER PT J AU Castellanos, FX Lau, E Tayebi, N Lee, P Long, RE Giedd, JN Sharp, W Marsh, WL Ginns, EI Rapoport, JL Sidransky, E AF Castellanos, FX Lau, E Tayebi, N Lee, P Long, RE Giedd, JN Sharp, W Marsh, WL Ginns, EI Rapoport, JL Sidransky, E TI Evidence that a D4DR*7R dopamine receptor polymorphism is not correlated with attention-deficit/hyperactivity disorder. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 21 PY 1997 VL 74 IS 6 BP 623 EP 623 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YB414 UT WOS:A1997YB41400237 ER PT J AU Cravchik, A Sibley, DR Gejman, PV AF Cravchik, A Sibley, DR Gejman, PV TI Functional analysis of the human dopamine: D-2 receptor variants. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. NINCDS,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 21 PY 1997 VL 74 IS 6 BP 624 EP 624 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YB414 UT WOS:A1997YB41400238 ER PT J AU Birkett, JTP Collier, DA Kerwin, RW AF Birkett, JTP Collier, DA Kerwin, RW TI A novel polymorphism in the promoter region of the N-acetyltransferase gene is not associated with schizophrenia or bipolar affective disorder. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIAAA,NEUROGENET LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 21 PY 1997 VL 74 IS 6 BP 642 EP 642 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YB414 UT WOS:A1997YB41400299 ER PT J AU Feng, J Sobell, J Heston, L Goldman, D Cook, E Gelernter, J Kranzler, H Sommer, S AF Feng, J Sobell, J Heston, L Goldman, D Cook, E Gelernter, J Kranzler, H Sommer, S TI Variants in the alpha(2A) adrenergic receptor gene in psychiatric patients. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 CITY HOPE NATL MED CTR,BECKMAN RES INST,DEPT MOL GENET,DUARTE,CA 91010. CITY HOPE NATL MED CTR,BECKMAN RES INST,DIV MOL MED,DUARTE,CA 91010. UNIV WASHINGTON,DEPT PSYCHIAT,SEATTLE,WA 98195. NIAAA,NEUROGENET LAB,BETHESDA,MD 20892. UNIV CHICAGO,DEPT CHILD PSYCHIAT,CHICAGO,IL 60637. YALE UNIV,DEPT PSYCHIAT,NEW HAVEN,CT 06520. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 21 PY 1997 VL 74 IS 6 BP 643 EP 643 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YB414 UT WOS:A1997YB41400303 ER PT J AU Moldin, SO Wynne, D Shore, D AF Moldin, SO Wynne, D Shore, D TI The NIMH genetics initiative: A new scientific resource. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIMH,GENET RES PROGRAM,SCHIZOPHRENIA RES BRANCH,NIH,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 21 PY 1997 VL 74 IS 6 BP 659 EP 659 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YB414 UT WOS:A1997YB41400353 ER PT J AU DeteraWadleigh, SD Berrettini, WH Yoshikawa, T Badner, JA Sanders, AR Goldin, LR Turner, G Rolins, DY Moses, T Nurnberger, JI Gershon, ES AF DeteraWadleigh, SD Berrettini, WH Yoshikawa, T Badner, JA Sanders, AR Goldin, LR Turner, G Rolins, DY Moses, T Nurnberger, JI Gershon, ES TI Linkage disequilibrium detects a potential susceptibility locus for bipolar disorder at 11q2-24. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIMH,CLIN NEUROGENET BRANCH,NIH,BETHESDA,MD 20892. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PSYCHIAT & HUMAN BEHAV,PHILADELPHIA,PA 19107. INDIANA UNIV,DEPT PSYCHIAT,INST PSYCHIAT RES,INDIANAPOLIS,IN 46204. NR 0 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 21 PY 1997 VL 74 IS 6 BP 669 EP 669 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YB414 UT WOS:A1997YB41400390 ER PT J AU Sanders, AR Guroff, JJ Gershon, ES Gejman, PV AF Sanders, AR Guroff, JJ Gershon, ES Gejman, PV TI Genetic linkage study of male homosexual orientation. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIMH,CLIN NEUROGENET BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 21 PY 1997 VL 74 IS 6 BP 679 EP 679 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YB414 UT WOS:A1997YB41400425 ER PT J AU Liu, JL Blakesley, VA Gutkind, JS LeRoith, D AF Liu, JL Blakesley, VA Gutkind, JS LeRoith, D TI The constitutively active mutant G(alpha 13) transforms mouse fibroblast cells deficient in insulin-like growth factor-I receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALPHA-SUBUNIT; G-PROTEINS; NEOPLASTIC TRANSFORMATION; KINASE; G-ALPHA(12); PATHWAYS; GENE; ACTIVATION; MUTATION; ANTIGEN AB Insulin-like growth factor-I (IGF-I) receptor plays an important role in normal cell cycle progression and tumor growth, and it is thought to be essential for cellular transformation, To test this hypothesis, we stably transfected a GTPase-deficient mutant human G(alpha 13), which is highly oncogenic when overexpressed in vitro, into R-fibroblasts derived from IGF-I receptor-deficient mice, Northern blots of multiple clones revealed the expression of a 1.8-kilobase pair mutant G(alpha 13) transcript in transfected cells, in addition to the 6-kilobase pair endogenous mRNA, The transfection resulted in a doubling of the expression of G(alpha 13) protein in these cells as assessed by Western blot analysis, The transforming ability of the mutant G(alpha 13) was tested using the soft agar assay, Nontransfected R-cells cultured with 10% fetal bovine serum failed to form colonies after 3 weeks, Most of the mutant G(alpha 13)-expressing clones formed significant numbers of colonies (11-50 colonies/1000 cells plated), Overexpression of the IGF-I receptor enabled R-cells to form colonies (27 colonies), and co transfection of the mutant G(alpha 13) caused a further increase in colony formation (117-153 colonies) in three of five clones analyzed, Apparently G(alpha 13) works through pathways other than mitogen-activated protein kinase and c-Jun N-terminal kinase in transforming R-cells, because their activities were not significantly altered by the mutant G(alpha 13) expression, These results demonstrate that G(alpha 13) can induce cellular transformation through pathways apparently independent of the IGF-I receptor and that activation of the IGF-I receptor signaling pathways, although not essential for the transforming phenotype, enhances the effect of other pathways. C1 NIDDK,SECT CELLULAR & MOL PHYSIOL,DIABET BRANCH,NIH,BETHESDA,MD 20892. NIDR,CELLULAR DEV & ONCOL LAB,NIH,BETHESDA,MD 20892. RI Gutkind, J. Silvio/A-1053-2009 NR 37 TC 31 Z9 32 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 21 PY 1997 VL 272 IS 47 BP 29438 EP 29441 DI 10.1074/jbc.272.47.29438 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YG647 UT WOS:A1997YG64700011 PM 9368001 ER PT J AU Garces, C RuizHidalgo, MJ deMora, JF Park, C Miele, L Goldstein, J Bonvini, E Porras, A Laborda, J AF Garces, C RuizHidalgo, MJ deMora, JF Park, C Miele, L Goldstein, J Bonvini, E Porras, A Laborda, J TI Notch-1 controls the expression of fatty acid-activated transcription factors and is required for adipogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADIPOSE CELL-DIFFERENTIATION; BINDING-PROTEIN-ALPHA; PEROXISOME PROLIFERATOR; ADIPOCYTE DIFFERENTIATION; DROSOPHILA-MELANOGASTER; RECEPTOR-GAMMA; 3T3-L1 CELLS; NEUROGENESIS; GENE; WINGLESS AB Notch, a transmembrane receptor member of the homeotic epidermal growth factor-like family of proteins, participates in cell-to-cell signaling to control cell fate during development, Activated Notch-1 constructs lacking the extracellular region prevent differentiation of several mammalian cells in vitro, This effect, however, bypasses the normal mechanisms of cell-to-cell interactions in which Notch-1 participates, We investigated the role of Notch-1. in the hormone-induced adipocyte differentiation of 3T3-L1 fibroblasts, a paradigmatic model of adipogenesis that requires cell-to-cell contact, Unlike other differentiation models, Notch-1 expression and function were necessary conditions for adipogenesis, Impaired Notch-1 expression by antisense Notch-1 constructs prevented adipocyte differentiation. Strategies aimed at blocking putative Notch/ligand interactions also blocked adipogenesis, implicating Notch as a critical molecule in cell-to-cell signaling necessary for differentiation, Inhibition of Notch-1 expression or function decreased the expression of peroxisomal proliferator-activated receptors delta and gamma, transcription factors that control adipocyte differentiation and that are up-regulated at cell confluence, These results implicate Notch in the commitment of 3T3-L1 cells to undergo adipogenesis by controlling the expression of the principal regulators of this process. C1 CTR BIOL EVALUAT & RES,DIV MONOCLONAL ANTIBODIES,IMMUNOBIOL LAB,ROCKVILLE,MD 20852. NCI,CELLULAR & MOL BIOL LAB,NIH,BETHESDA,MD 20892. RI Laborda, Jorge/L-5726-2014; Ruiz-Hidalgo, Maria/L-1956-2014; Font de Mora, Jaime/H-6304-2015; Porras, Almudena/N-2121-2015 OI Laborda, Jorge/0000-0002-9210-838X; Font de Mora, Jaime/0000-0002-6816-2095; Porras, Almudena/0000-0002-6495-3308 NR 59 TC 111 Z9 112 U1 2 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 21 PY 1997 VL 272 IS 47 BP 29729 EP 29734 DI 10.1074/jbc.272.47.29729 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YG647 UT WOS:A1997YG64700052 PM 9368042 ER PT J AU Zhou, LX Chen, H Lin, CH Cong, LN McGibbon, MA Sciacchitano, S Lesniak, MA Quon, MJ Taylor, SI AF Zhou, LX Chen, H Lin, CH Cong, LN McGibbon, MA Sciacchitano, S Lesniak, MA Quon, MJ Taylor, SI TI Insulin receptor substrate-2 (IRS-2) can mediate the action of insulin to stimulate translocation of GLUT4 to the cell surface in rat adipose cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLUCOSE-TRANSPORT ACTIVITY; PHOSPHATIDYLINOSITOL 3-KINASE; 1-PHOSPHATIDYLINOSITOL 3-KINASE; PLASMA-MEMBRANE; ACTIVATION; MICE; PROTEIN; DOMAIN; KINASE; BINDS AB Insulin receptor substrates-1 and -2 (IRS-1 and -2) are important substrates of the insulin receptor tyrosine kinase, Previous studies have focused upon the role of IRS-1 in mediating the actions of insulin, In the present study, we demonstrate that IRS-2 can mediate translocation of the insulin responsive glucose transporter GLUT4 in a physiologically relevant target cell for insulin action, Co-immunoprecipitation experiments performed on cell lysates derived from freshly isolated rat adipose cells incubated in the presence or absence of insulin indicated that twice as much phosphatidylinositol 3-kinase was associated with endogenous IRS-1 as with IRS-2 after insulin stimulation, When rat adipose cells in primary culture were transfected with expression vectors for IRS-1 or IRS-2, we observed 40-fold over-expression of human IRS-1 or murine IRS-2. In addition, anti-phosphotyrosine immunoblotting experiments confirmed that the recombinant substrates were phosphorylated in response to insulin stimulation, To examine the role of IRS-2 in insulin-stimulated translocation of GLUT4, we studied the effects of overexpression of IRS-1 and -2 on translocation of a co-transfected epitope-tagged GLUT4 (GLUT4-HA). Overexpression of IRS-1 or IRS-2 in adipose cells resulted in a significant increase in the basal level of cell surface GLUT4 (in the absence of insulin). Interestingly, at maximally effective concentrations of insulin (60 nM), the level of cell surface GLUT4 in cells overexpressing IRS-1 or -2 significantly exceeded the maximal recruitment observed in the control cells (160 and 135% of control, respectively; p < 0.003), Our data directly demonstrate that IRS-2, like IRS-1, is capable of participating in insulin signal transduction pathways leading to the recruitment of GLUT4, Thus, IRS-2 may provide an alternative pathway for critical metabolic actions of insulin. C1 NHLBI,HYPERTENS ENDOCRINE BRANCH,NIH,BETHESDA,MD 20892. RP Zhou, LX (reprint author), NIDDK,DIABET BRANCH,NIH,BETHESDA,MD 20892, USA. RI Quon, Michael/B-1970-2008 NR 38 TC 41 Z9 41 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 21 PY 1997 VL 272 IS 47 BP 29829 EP 29833 DI 10.1074/jbc.272.47.29829 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YG647 UT WOS:A1997YG64700065 PM 9368055 ER PT J AU Liu, Y Watanabe, H Nifuji, A Yamada, Y Olson, EN Noda, M AF Liu, Y Watanabe, H Nifuji, A Yamada, Y Olson, EN Noda, M TI Overexpression of a single helix-loop-helix-type transcription factor, scleraxis, enhances aggrecan gene expression in osteoblastic osteosarcoma ROS17/2.8 cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MYOD FAMILY; DNA-BINDING; PROTEIN; RNA; OSTEOPONTIN; MYOGENESIS; FRAGMENTS; SEQUENCE AB Cell differentiation is determined by a certain set of transcription factors such as MyoD in myogenesis, However, transcription factors that play a positive role in phenotypic gene expression in skeletal cells are largely unknown, except the recently identified CBFA1. Scleraxis is a helix-loop-helix-type transcription factor whose transcripts are expressed in sclerotome and in a certain set of skeletal cells; however, nothing is known about its function with regard to the regulation of cell function, To examine possible roles of scleraxis, we overexpressed scleraxis in osteoblastic ROS17/2.8 cells, which express low levels of scleraxis, Scleraxis overexpression enhanced expression of the aggrecan gene, which is not normally expressed at high levels in these osteoblastic cells, Overexpression of scleraxis also increased mRNA levels of type II collagen and osteopontin while suppressing expression of osteoblast phenotype-related genes encoding type I collagen and alkaline phosphatase, Transient transfection experiments indicated that scleraxis enhanced the chloramphenicol acetyltransferase activity of the reporter construct AgCAT-8, which contained an 8-kilobase pair (kb) fragment of the aggrecan gene including both the promoter and its first intron, Deletion analysis identified a 1-kb region that is responsive to scleraxis within the aggrecan gene, This region contains two adjacent E-box sequences, A 29-base pair DNA fragment (AgE) containing these E-box sequences bound to proteins in the ROS17/2.8 cell nuclear extracts as well as to in vitro translated scleraxis, This binding was competed with unlabeled AgE, but not with a mutated E-box DNA sequence (mAgE), indicating the specificity of the binding activity, The AgE binding activity in the ROS17/2.8 cell nuclear extracts was enhanced in the cells overexpressing scleraxis and was supershifted by the antiserum raised against scleraxis, Furthermore, AgE, but not mAgE, conferred responsiveness to scleraxis overexpression to a heterologous promoter, Finally, replacement mutation of the AgE sequence within the 2.5-kb AgCAT-1 construct significantly reduced its responsiveness to scleraxis, These results indicate that overexpression of a single helix-loop-helix-type transcription factor, scleraxis, enhances aggrecan gene expression via binding to the E box-containing AgE sequence in ROS17/2.8 cells. C1 TOKYO MED & DENT UNIV,MED RES INST,DIV FUNCT DISORDER RES,DEPT MOL PHARMACOL,CHIYODA KU,TOKYO 101,JAPAN. NIDR,MOL BIOL SECT,NIH,BETHESDA,MD 20892. UNIV TEXAS,SW MED CTR,HARMON CTR BASIC RES CANC,DALLAS,TX 75235. NR 29 TC 55 Z9 56 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 21 PY 1997 VL 272 IS 47 BP 29880 EP 29885 DI 10.1074/jbc.272.47.29880 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YG647 UT WOS:A1997YG64700072 PM 9368062 ER PT J AU Paz, K Hemi, R LeRoith, D Karasik, A Elhanany, E Kanety, H Zick, Y AF Paz, K Hemi, R LeRoith, D Karasik, A Elhanany, E Kanety, H Zick, Y TI Elevated serine/threonine phosphorylation of IRS-1 and IRS-2 inhibits their binding to the juxtamembrane region of the insulin receptor and impairs their ability to undergo insulin-induced tyrosine phosphorylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-NECROSIS-FACTOR; KAPPA-B ACTIVATION; P55 TNF-RECEPTOR; CELL-DEATH; KINASE-ACTIVITY; AMINO-ACIDS; SUBSTRATE-1; PROTEIN; SPHINGOMYELINASE; RESISTANCE AB Tumor necrosis factor alpha (TNF alpha) or chronic hyperinsulinemia that induce insulin resistance trigger increased Ser/Thr phosphorylation of the insulin receptor (Hi) and of its major insulin receptor substrates, IRS-1 and IRS-2. To unravel the molecular basis for this uncoupling in insulin signaling, we undertook to study the interaction of Ser/Thr-phosphorylated IRS-1 and IRS-2 with the insulin receptor. We could demonstrate that, similar to IRS-1, IRS-2 also interacts with the juxtamembrane (JM) domain (amino acids 943-984) but not with the carboxyl-terminal region (amino acids 1245-1331) of IR expressed in bacteria as His(6) fusion peptides, Moreover, incubation of rat hepatoma Fao cells with TNF alpha, bacterial sphingomyelinase, or other Ser(P)/Thr(P)-elevating agents reduced insulin-induced Tyr phosphorylation of IRS-I and IRS-2, markedly elevated their Ser(P)/Thr(P) levels, and significantly reduced their ability to interact with the JM region of IR. Withdrawal of TNF alpha for periods as short as 30 min reversed its inhibitory effects on IR-IRS interactions, Similar inhibitory effects were obtained when Fao cells were subjected to prolonged (20-60 min) pretreatment with insulin, Incubation of the cell extracts with alkaline phosphatase reversed the inhibitory effects of insulin. These findings suggest that insulin resistance is associated with enhanced Ser/Thr phosphorylation of IRS-1 and IRS-S, which impairs their interaction with the JIVE region of IR. Such impaired interactions abolish the ability of IRS-1 and IRS-2 to undergo insulin-induced Tyr phosphorylation and further propagate the insulin receptor signal. Moreover, the reversibility of the TNF alpha effects and the ability to mimic its action by exogenously added sphingomyelinase argue against the involvement of a proteolytic cascade in mediating the acute inhibitory effects of TNF alpha on insulin action. C1 WEIZMANN INST SCI,DEPT MOL CELL BIOL,IL-76100 REHOVOT,ISRAEL. CHAIM SHEBA MED CTR,INST ENDOCRINOL,IL-52621 TEL HASHOMER,ISRAEL. NIH,DIABET BRANCH,BETHESDA,MD 20982. ISRAEL INST BIOL RES,DEPT BIOCHEM,IL-70400 NESS ZIONA,ISRAEL. NR 44 TC 352 Z9 371 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 21 PY 1997 VL 272 IS 47 BP 29911 EP 29918 DI 10.1074/jbc.272.47.29911 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YG647 UT WOS:A1997YG64700077 PM 9368067 ER PT J AU Blough, BE Abraham, P Mills, AC Lewin, AH Boja, JW Scheffel, U Kuhar, MJ Carroll, FI AF Blough, BE Abraham, P Mills, AC Lewin, AH Boja, JW Scheffel, U Kuhar, MJ Carroll, FI TI 3 beta-(4-ethyl-3-iodophenyl)nortropane-2 beta-carboxylic acid methyl ester as a high-affinity selective ligand for the serotonin transporter SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID NOREPINEPHRINE TRANSPORTERS; I-125 RTI-55; COCAINE; DOPAMINE; BINDING; ANALOGS C1 RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NIDA,NEUROSCI BRANCH,ADDICT RES CTR,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DIV NUCL RES,DEPT RADIOL,BALTIMORE,MD 21205. FU NIDA NIH HHS [DA05477, DA-4-8308] NR 20 TC 43 Z9 43 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 21 PY 1997 VL 40 IS 24 BP 3861 EP 3864 DI 10.1021/jm970492z PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA YH537 UT WOS:A1997YH53700001 PM 9397165 ER PT J AU Addess, KJ Basilion, JP Klausner, RD Rouault, TA Pardi, A AF Addess, KJ Basilion, JP Klausner, RD Rouault, TA Pardi, A TI Structure and dynamics of the iron responsive element RNA: Implications for binding of the RNA by iron regulatory binding proteins SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE iron regulation; RNA structure; hairpin loops and bulges; IRP; NMR structure ID FERRITIN MESSENGER-RNA; ISOTOPICALLY LABELED RNA; PAIRED FLANKING REGIONS; ACTIVE-SITE RESIDUES; NMR-SPECTROSCOPY; CRYSTAL-STRUCTURE; TRANSLATIONAL REGULATION; CYTOSOLIC ACONITASE; SECONDARY STRUCTURE; COUPLING-CONSTANTS AB The iron responsive element (IRE) is a similar to 30 nucleotide RNA hairpin that is located in the 5' untranslated region of all ferritin mRNAs and in the 3' untranslated region of all transferrin receptor mRNAs. The IREs are bound by two related IRE-binding proteins (IRPs) which help control intracellular levels of iron by regulating the expression of both ferritin and transferrin receptor genes. Multi-dimensional NMR and computational approaches were used to study the structure and dynamics of the IRE RNA in solution. The NMR data are consistent with formation of A-form helical stem regions, a one-base internal bulge and a Watson-Crick C.G base-pair between the first and fifth nucleotides in the loop. A superposition of refined structures indicates that the conserved C in the internal bulge, and three residues in the six-nucleotide hairpin loop are quite dynamic in this RNA. The structural roles of the stems, the loop and the bulge in the function of the IRE RNA and in possible interactions with the iron regulatory protein are discussed. (C) 1997 Academic Press Limited. C1 UNIV COLORADO,DEPT CHEM & BIOCHEM,BOULDER,CO 80309. NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. FU NIAID NIH HHS [AI33098]; NIGMS NIH HHS [GM16577] NR 71 TC 144 Z9 145 U1 2 U2 7 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 21 PY 1997 VL 274 IS 1 BP 72 EP 83 DI 10.1006/jmbi.1997.1377 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YK495 UT WOS:A1997YK49500009 PM 9398517 ER PT J AU Hinck, AP Markus, MA Huang, SR Grzesiek, S Kustonovich, I Draper, DE Torchia, DA AF Hinck, AP Markus, MA Huang, SR Grzesiek, S Kustonovich, I Draper, DE Torchia, DA TI The RNA binding domain of ribosomal protein L11: Three-dimensional structure of the RNA-bound form of the protein and its interaction with 23 S rRNA SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE L11, heteronuclear NMR; protein-RNA; 23 S ribosomal RNA; ribosome ID CONSERVED GTPASE CENTER; SIDE-CHAIN RESONANCES; TERTIARY STRUCTURE; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; C-13/N-15-ENRICHED PROTEINS; ANTIBIOTIC THIOSTREPTON; DNA-RECOGNITION; BACKBONE AMIDE; PROTON-CARBON AB The three-dimensional solution structure has been determined by NMR spectroscopy of the 75 residue C-terminal domain of ribosomal protein L11 (L11-C76) in its RNA-bound state. L11-C76 recognizes and binds tightly to a highly conserved 58 nucleotide domain of 23 S ribosomal RNA, whose secondary structure consists of three helical stems and a central junction loop. The NMR data reveal that the conserved structural core of the protein, which consists of a bundle of three alpha-helices and a two-stranded parallel beta-sheet four residues in length, is nearly the same as the solution structure determined for the non-liganded form of the protein. There are however, substantial chemical shift perturbations which accompany RNA binding, the largest of which map onto an extended loop which bridges the C-terminal end of alpha-helix 1 and the first strand of parallel beta-sheet. Substantial shift perturbations are also observed in the N-terminal end of alpha-helix 1, the intervening loop that bridges helices 2 and 3, and alpha-helix 3. The four contact regions identified by the shift perturbation data also displayed protein-RNA NOEs, as identified by isotope-filtered three-dimensional NOE spectroscopy. The shift perturbation and NOE data not only implicate helix 3 as playing an important role in RNA binding, but also indicate that regions flanking helix 3 are involved as well. Loop 1 is of particular interest as it was found to be flexible and disordered for L11-C76 free in solution, but not in the RNA-bound form of the protein, where it appears rigid and adopts a specific conformation as a result of its direct contact to RNA. (C) 1997 Academic Press Limited. C1 NIDR,NIH,BETHESDA,MD 20892. FORSCHUNGSZENTRUM,JULICH,GERMANY. HEBREW UNIV JERUSALEM,JERUSALEM,ISRAEL. JOHNS HOPKINS UNIV,DEPT CHEM,BALTIMORE,MD 21218. NR 47 TC 49 Z9 50 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 21 PY 1997 VL 274 IS 1 BP 101 EP 113 DI 10.1006/jmbi.1997.1379 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YK495 UT WOS:A1997YK49500011 PM 9398519 ER PT J AU Bonner, RF EmmertBuck, M Cole, K Pohida, T Chuaqui, R Goldstein, S Liotta, LA AF Bonner, RF EmmertBuck, M Cole, K Pohida, T Chuaqui, R Goldstein, S Liotta, LA TI Cell sampling - Laser capture microdissection: Molecular analysis of tissue SO SCIENCE LA English DT Article ID POLYMERASE CHAIN-REACTION; TUMORS; CANCER C1 NCI,PATHOL LAB,FREDERICK,MD 21701. NIH,BIOMED ENGN PROGRAM,BETHESDA,MD 20892. NIH,COMPUTAT BIOSCI & ENGN LAB,BETHESDA,MD 20892. RP Bonner, RF (reprint author), NICHHD,LAB INTEGRAT & MED BIOPHYS,BETHESDA,MD 20892, USA. RI Bonner, Robert/C-6783-2015; Cole, Kristina/M-3922-2015 NR 11 TC 632 Z9 681 U1 7 U2 34 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 21 PY 1997 VL 278 IS 5342 BP 1481 EP & DI 10.1126/science.278.5342.1481 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YG858 UT WOS:A1997YG85800052 PM 9411767 ER PT J AU Peters, R Sikorski, R AF Peters, R Sikorski, R TI Aromatic probes SO SCIENCE LA English DT Article C1 NCI,BETHESDA,MD 20892. RP Peters, R (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA 02115, USA. NR 2 TC 1 Z9 1 U1 1 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 21 PY 1997 VL 278 IS 5342 BP 1484 EP 1485 DI 10.1126/science.278.5342.1484 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YG858 UT WOS:A1997YG85800053 ER PT J AU Sikorski, R Peters, R AF Sikorski, R Peters, R TI ''Lighting'' rods SO SCIENCE LA English DT Article C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Sikorski, R (reprint author), NCI,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 21 PY 1997 VL 278 IS 5342 BP 1485 EP 1486 DI 10.1126/science.278.5342.1485 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YG858 UT WOS:A1997YG85800054 ER PT J AU Peters, R Sikorski, R AF Peters, R Sikorski, R TI Cookie monster? SO SCIENCE LA English DT Article C1 NCI,BETHESDA,MD 20892. RP Peters, R (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA 02115, USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 21 PY 1997 VL 278 IS 5342 BP 1486 EP 1487 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YG858 UT WOS:A1997YG85800056 ER PT J AU Sikorski, R Peters, R AF Sikorski, R Peters, R TI Internet photoshopping SO SCIENCE LA English DT Article C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Sikorski, R (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 21 PY 1997 VL 278 IS 5342 BP 1486 EP 1486 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YG858 UT WOS:A1997YG85800055 ER PT J AU Katz, E Moss, B AF Katz, E Moss, B TI Immunogenicity of recombinant vaccinia viruses that display the HIV type 1 envelope glycoprotein on the surface of infectious virions SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID EXPRESSION; PROTEIN AB A chimeric protein, consisting of the extracellular domain of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein attached to the transmembrane and cytoplasmic domains of the vaccinia virus B5R glycoprotein, is displayed on the surface of extracellular recombinant vaccinia virus particles, whereas the unmodified full-length HIV-1 glycoprotein is not (Katz E, et al., J Virol 1997;71:3178-3187). Here, we report that rabbits and mice inoculated with recombinant vaccinia viruses that express the chimeric protein developed higher HIV-specific antibody responses than animals inoculated with vaccinia virus that expressed the unmodified HIV glycoprotein. These data suggest that the immunogenicity of recombinant proteins may be enhanced by their presentation on the surface of vaccinia virus particles. C1 NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. RP Katz, E (reprint author), HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT VIROL,POB 12272,IL-91120 JERUSALEM,ISRAEL. NR 14 TC 17 Z9 17 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV 20 PY 1997 VL 13 IS 17 BP 1497 EP 1500 DI 10.1089/aid.1997.13.1497 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA YH236 UT WOS:A1997YH23600006 PM 9390748 ER PT J AU Baim, DS Leon, MB Popma, JJ Kuntz, RE Safian, RD Nickens, PD Detre, KM AF Baim, DS Leon, MB Popma, JJ Kuntz, RE Safian, RD Nickens, PD Detre, KM TI Problems in the evaluation of new devices for coronary intervention: What have we learned since 1989? SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID BALLOON ANGIOPLASTY; ARTERY DISEASE; REGISTRY; ATHERECTOMY AB The objectives of this study are to review the problems associated with the evaluation process since 1989, and the role played by the New Approaches to Coronary Intervention (NACI) registry. In 1988-1989, the first wave of new coronary devices (stents, atherectomy, laser catheters) were entering clinical investigation. It seemed unlikely that the small manufacturer-run registries used to gain approval for earlier ballon catheters would be adequate to evaluate the host of complex new devices, each of which might be used for a restricted set of anatomic indications. Moreover, the wide range of arbitrary definitions then in use for fundamental outcomes (such as success, complication, and restenosis), effectively precluded meaningful device-to-device comparisons. Against this backdrop, the NACI registry was formed with National Heart, Lung, and Blood Institute funding to provide an independent and standardized evaluation of the first 8 new devices under evaluation in the United States, across the broad range of their application. The registry employed a unique modular form set to track the sequence of events during complex cases in which serial new devices and ballon angioplasty might be used, either in a planned way, or an unplanned way (to treat complications or suboptimal results). Outcomes were subjected to standardized criteria for (1) the reason for device use (planned, unplanned); success (2) (device, lesion, and procedural success); (3) complications (a) major (death, Q-wave myocardial infarction, and emergency coronary artery bypass grafting); or (b) other (groin complications, non-Q-wave myocardial infarction, etc); and (4) clinical restenosis (any subsequent revascularization, target lesion revascularization). Separate funding for an angiographic core laboratory was obtained in 1992, which analyzed 3,936 (88.9%) of the 4,429 films obtained on patients enrolled between November 1990 and March 1994. The NACI registry has addressed a broad range of problems inherent in the evaluation of new devices for coronary intervention. Whereas the approval process has moved progressively toward randomized clinical trials (and away from registries), the NACI registry offers a unique view of current practice, outside the narrow scope of the limited number of randomized trials that have been performed to date. This article shows, however, that we have learned about more than the devices themselves since 1989-we have also learned about the importance of knowing the reason for device use, using precise definitions of endpoint variables, understanding the financial and reimbursement ramifications of new device trials, and upholding strict investigator ethics during the conduct of such evaluations. C1 Beth Israel Hosp, Intervent Cardiol Sect, Boston, MA 02215 USA. Washington Hosp Ctr, Dept Internal Med Cardiol, Washington, DC 20010 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. NHLBI, Washington, DC USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. RP Baim, DS (reprint author), Beth Israel Hosp, Intervent Cardiol Sect, 330 Brookline Ave, Boston, MA 02215 USA. NR 11 TC 9 Z9 9 U1 2 U2 3 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 20 PY 1997 VL 80 IS 10A SI SI BP 3K EP 9K DI 10.1016/S0002-9149(97)00759-5 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YM156 UT WOS:000071035400002 PM 9409687 ER PT J AU Robertson, T Kennard, ED Mehta, S Popma, JJ Carrozza, JP King, SB Holmes, DR Cowley, MJ Hornung, CA Kent, KM Roubin, GS Litvack, F Moses, JW Safian, RD Desvigne-Nickens, P Detre, KM AF Robertson, T Kennard, ED Mehta, S Popma, JJ Carrozza, JP King, SB Holmes, DR Cowley, MJ Hornung, CA Kent, KM Roubin, GS Litvack, F Moses, JW Safian, RD Desvigne-Nickens, P Detre, KM CA NACI Investigators TI Influence of gender on in-hospital clinical and angiographic outcomes and on one-year follow-up in the New Approaches to Coronary Intervention (NACI) registry SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; PERIPHERAL VASCULAR COMPLICATIONS; HEART-DISEASE; SEX-DIFFERENCES; BYPASS-SURGERY; ARTERY DISEASE; UNITED-STATES; ANGIOPLASTY; ATHERECTOMY; WOMEN AB Higher complication rates and lower success rates for treatment of women compared with men have been reported in prior studies of coronary angioplasty and in most early reports of outcome with new coronary interventional devices. In multivariate analysis this has been attributed largely to older age and other unfavorable clinical characteristics. These results are reflected in the current guidelines for coronary angioplasty. Women in prior studies have also had different distributions of vessel and lesion characteristics, but the influence of these differences on the outcome of new-device interventions have not been adequately evaluated. This article evaluates the influence of gender on clinical and angiographic characteristics, interventional procedure and complications, angiographic success, and clinical outcomes at hospital discharge and 1-year follow-vp, as observed in the New Approaches to Coronary Intervention (NACI) registry. The NACI registry methodology has been reported in detail elsewhere in this supplement. This study focuses on the 90% of patients-975 women and 1,880 men-who had planned procedures with a single new device and also had angiographic core laboratory readings. Women compared with men were older, had more recent onset of coronary ischemic pain that was more severe and unstable, and had more frequent histories of other adverse clinical conditions. The distributions of several but not all angiographic characteristics before intervention were considered more favorable to angioplasty outcome in women. Differences were observed in device use and procedure staging. Angiographically determined average gain in lumen diameter after new-device intervention, with or without balloon angioplasty, was significantly less in women (1.38 mm) than in men (1.53 mm; p < 0.001); this 0.15 mm difference is consistent with the 0.16-mm smaller reference vessel lumen diameter of women. However, final percent diameter stenoses and TIMI flow and lesion compliance characteristics were similar. Among procedural complications, only treatment for hypotension, blood transfusion, and vascular repair occurred more often in women. More women than men were clinically unstable (2.1% vs 1.1%) or went directly to emergent coronary artery bypass graft surgery (CABG; 1.2% vs 0.6%) on leaving the interventional laboratory. However, in-hospital death (1.4% vs 1.1%), Q-wave myocardial infarction (MI) (0.9% vs 1.1%), and emergent CABG (1.5% vs 1.0%, for women and men, respectively) were not significantly different. Nonemergent CABG was more frequent in women (1.8% vs 0.9%; p <0.05) and length of hospital stay after device intervention was longer (4.4 days vs 3.8 days in men; p <0.01). In both univariate and multivariate analyses gender did not emerge as a significant variable in relation to the combined endpoint, death, Q-wave MI, or emergent CABG at hospital discharge. At 1-year follow-vp more women than men reported improvement In angina (70% vs 62%) and fewer women than men had had repeat revascularization (32% vs 36%). Similar proportions were alive and free of angina, Q-wave MI and repeat revascularization (46% of women vs 45% of men). Although several procedure-related complications were more frequent in women than men after coronary interventions with new devices, no important disadvantages were observed for women in the rates of major clinical events at hospital discharge and at 1-year clinical follow-up. Additional studies are needed to evaluate the complex interplay of clinical, vessel, and lesion characteristics on success and complications of specific interventional techniques and to determine whether gender, per se, is a risk factor and whether gender specific interventional strategies may be beneficial. (C) 1997 by Excerpta Medico, Inc. C1 Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Cedars Sinai Med Ctr, Miami, FL USA. Washington Hosp Ctr, Dept Internal Med Cardiol, Washington, DC 20010 USA. Beth Israel Hosp, Intervent Cardiol Sect, Boston, MA 02215 USA. Emory Univ Hosp, Atlanta, GA 30322 USA. Mayo Clin, Rochester, MN USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23284 USA. Univ S Carolina, Columbia, MD USA. Univ Alabama, Birmingham, AL USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Lenox Hill Hosp, New York, NY 10021 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. NHLBI, Washington, DC USA. RP Detre, KM (reprint author), Univ Pittsburgh, Dept Epidemiol, 130 De Soto St, Pittsburgh, PA 15261 USA. NR 36 TC 71 Z9 74 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 20 PY 1997 VL 80 IS 10A SI SI BP 26K EP 39K DI 10.1016/S0002-9149(97)00762-5 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YM156 UT WOS:000071035400005 PM 9409690 ER PT J AU Wahlfors, JJ Xanthopoulos, KG Morgan, RA AF Wahlfors, JJ Xanthopoulos, KG Morgan, RA TI Semliki Forest virus-mediated production of retroviral vector RNA in retroviral packaging cells SO HUMAN GENE THERAPY LA English DT Article ID CLOTTING FACTOR-VIII; VIRAL MESSENGER-RNA; EXPRESSION VECTORS; TYPE-1 AFFECTS; REV PROTEIN; GENE; SEQUENCES; TRANSDUCTION; REPLICATION; PARTICLES AB Retroviral vectors are efficient tools for gene transfer studies. Their major advantage is that they can permanently integrate the transgene into the target cell's genome. However, because of the compulsory nuclear expression phase of their life cycle, it can be difficult for retroviruses to carry complex expression cassettes. In a attempt to mimic the structural features of most eukaryotic genes and obtain a potentially self-amplifying system for retrovirus production, we tested the feasibility of Semliki Forest virus (SFV) expression to mediate cytoplasmic synthesis of retrovirus vector RNA. An equivalent of a retrovirus virion RNA (retrovirus vector cassette, RVC) was cloned under the SFV 26S promoter, and full-length chimeric SFV-RVC RNA was produced in vitro. This RNA was introduced into retrovirus packaging cells, either via electroporation or transduction in SFV virions, and supernatants were analyzed for the presence of biologically active retroviruses. We demonstrate that this strategy can be used for cytoplasmic retrovirus production. The resulting viral particles are fully functional; they can transduce target cells, undergo reverse transcription, and integrate into genomic DNA. We also demonstrate that the SFV virion-based RVC delivery into packaging cells can yield high transient titers, in this case more than 10(5) G418(R) cfu/ml. This study shows that a simple, one-plasmid, heterologous viral RNA production system can be used to create functional retroviral RNA outside the cell nucleus. C1 NATL HUMAN GENOME RES INST,CLIN GENE THERAPY BRANCH,NIH,BETHESDA,MD 20892. NR 26 TC 22 Z9 24 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV 20 PY 1997 VL 8 IS 17 BP 2031 EP 2041 DI 10.1089/hum.1997.8.17-2031 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA YJ340 UT WOS:A1997YJ34000005 PM 9414252 ER PT J AU Jensen, TG Sullivan, DM Morgan, RA Taichman, LB Nussenblatt, RB Blaese, RM Csaky, KG AF Jensen, TG Sullivan, DM Morgan, RA Taichman, LB Nussenblatt, RB Blaese, RM Csaky, KG TI Retrovirus-mediated gene transfer of ornithine-delta-aminotransferase into keratinocytes from gyrate atrophy patients SO HUMAN GENE THERAPY LA English DT Article ID EPIDERMAL-KERATINOCYTES; EXPRESSION; CELLS; LINE; FIBROBLASTS; SKIN AB Gyrate atrophy is a progressive blindness associated with deficiency of ornithine aminotransferase (OAT), The strategy of using an autologous keratinocyte graft, modified to express high levels of OAT as an ornithine-catabolizing skin-based enzyme sink, is investigated, Two OAT-containing retroviral vectors were constructed with or without a resistance gene. When packaged in a retroviral vector particle generated with the gibbon ape leukemia (GALV) virus envelope (PG13), these vectors could readily transduce >50% of target keratinocytes. The transduced keratinocytes in culture expressed up to 75-fold more OAT than normal control keratinocytes and these gene-modified cells extracted [C-14]ornithine more efficiently than controls, The vector prepared without neo transduced cells more efficiently and led to higher levels of OAT expression than the neo-containing vector, Ornithine catabolism was maintained at high levels when the transduced patient keratinocytes were differentiated in vitro as a multilayered cutaneous organoid. C1 NEI,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NIH,CLIN GENE THERAPY BRANCH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. SUNY STONY BROOK,DEPT ORAL BIOL & PATHOL,STONY BROOK,NY 11794. FU NIDCR NIH HHS [R37 DE04511]; NIDDK NIH HHS [R01 DK49093] NR 26 TC 22 Z9 22 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV 20 PY 1997 VL 8 IS 17 BP 2125 EP 2132 DI 10.1089/hum.1997.8.17-2125 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA YJ340 UT WOS:A1997YJ34000013 PM 9414260 ER PT J AU Itoh, K Ozaki, M Stevens, B Fields, RD AF Itoh, K Ozaki, M Stevens, B Fields, RD TI Activity-dependent regulation of N-cadherin in DRG neurons: Differential regulation of N-cadherin, NCAM, and L1 by distinct patterns of action potentials SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE cell adhesion molecules; synaptogenesis; fasciculation; neurite outgrowth; activity-dependent plasticity; DRG; N-cadherin; L1; NCAM ID CELL-ADHESION MOLECULE; VERTEBRATE NERVOUS-SYSTEM; SYNAPTIC PLASTICITY; NEURITE OUTGROWTH; FUNCTIONAL COMPONENTS; ELECTRICAL-ACTIVITY; GENETIC DISSECTION; PERIPHERAL-NERVE; SENSORY NEURONS; POLYSIALIC ACID AB Cell adhesion molecule (CAM) expression is highly regulated during nervous system development to control cell migration, neurite outgrowth, fasciculation, and synaptogenesis, Using electrical stimulation of mouse dorsal root ganglion (DRG) neurons in cell culture, this work shows that N-cadherin expression is regulated by neuronal firing, and that expression of different CAMs is regulated by distinct patterns of neural impulses. N-cadherin was down-regulated by 0.1 or 1 Hz stimulation, but NCAM mRNA and protein levels were not altered by stimulation, L1 was down-regulated by 0.1 Hz stimulation, but not by 0.3 Hz, 1 Hz, or pulsed stimulation, N-cadherin expression,vas lowered with faster kinetics than L1 (1 vs. 5 days), and LI mRNA returned to higher levels after terminating the stimulus. The RSLE splice variant of L1 was not regulated by action potential stimulation, and activity-dependent influences on L1 expression were blocked by target-derived influences, The results are consistent with changes in firing pattern accompanying DRG development and suggest that functional activity can influence distinct developmental processes by regulating the relative abundance of different CAMs, (C) 1997 John Wiley & Sons, Inc. C1 NICHHD,UNIT NEUROCYTOL & PHYSIOL,DEV NEUROBIOL LAB,UNP,NIH,BETHESDA,MD 20892. NR 77 TC 85 Z9 86 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD NOV 20 PY 1997 VL 33 IS 6 BP 735 EP 748 DI 10.1002/(SICI)1097-4695(19971120)33:6<735::AID-NEU3>3.0.CO;2-A PG 14 WC Neurosciences SC Neurosciences & Neurology GA YD471 UT WOS:A1997YD47100003 PM 9369148 ER PT J AU Liu, QY Schaffner, AE Chang, YH Vaszil, K Barker, JL AF Liu, QY Schaffner, AE Chang, YH Vaszil, K Barker, JL TI Astrocytes regulate amino acid receptor current densities in embryonic rat hippocampal neurons SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE receptor; ion channels; neuronal development; astrocyte; hippocampus ID ACETYLCHOLINE-RECEPTORS; CULTURED ASTROCYTES; IN-VITRO; PARASYMPATHETIC NEURONS; INTRACELLULAR CALCIUM; SYMPATHETIC NEURONS; NEUROTROPHIC FACTOR; CONDITIONED MEDIA; NEURITE OUTGROWTH; CELL-INTERACTIONS AB Embryonic rat hippocampal neurons were cultured in a serum-fre e defined medium (MEM/N3) either directly on poly-D-lysine (PDL) or on a confluent monolayer of postnatal cortical astrocytes, C6 glioma cells, or Rat2 fibroblasts. Neurons on PDL were grown in MEM/N3 or in MEM/N3 conditioned for 24 h by astrocytes or C6 cells. Membrane capacitance (C-m) and gamma-aminobutyric acid (GABA)-, glycine-, kainate-, and N-methyl-D-aspartate (NMDA)-induced currents were quantified using whole-cell patch-clamp recordings. C-m as well as the amplitude and the density of these currents in neurons cultured on astrocytes were significantly greater than those in neurons grown on PDL after 24 and 48 h. C6 cells mimicked astrocytes in promoting C-m and GABA-, glycine-, and NMDA-evoked, but not kainate-evoked, currents. C-m and currents in neurons grown on Rat2 cells were comparable to those in neurons on PDL. Astrocytes maintained in culture for 3 months were noticeably less effective than freshly prepared ones just grown to confluence. Suppression of spontaneous cytoplasmic Ca2+ (Ca-c(2+)) elevations in astrocytes by 1,2-bis(2-aminophenoxy) ehane-N, N, N, N-tetraacetic acid acetoxymethyl ester (BAPTA-AM) loaded intracellularly blocked the observed modulatory effects. Medium conditioned by either astrocytes or C6 cells mimicked the effects of direct coculture of neurons on these cells in promoting C-m and amino acid-evoked currents. Inclusion of antagonists at GABA and glutamate receptors in coculture experiments blocked the observed effects. Thus, diffusible substances synthesized and/or secreted by astrocytes in a Ca-c(2+)-dependent manner can regulate neuronal growth and aminoacid receptor function, and these effects may involve neuronal GABA and glutamate receptors. (C) 1997 John Wiley & Sons, Inc. RP Liu, QY (reprint author), NINCDS,NEUROPHYSIOL LAB,NIH,BLDG 36,ROOM 2C02,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 66 TC 23 Z9 24 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD NOV 20 PY 1997 VL 33 IS 6 BP 848 EP 864 DI 10.1002/(SICI)1097-4695(19971120)33:6<848::AID-NEU11>3.0.CO;2-0 PG 17 WC Neurosciences SC Neurosciences & Neurology GA YD471 UT WOS:A1997YD47100011 PM 9369156 ER PT J AU Henderson, DK AF Henderson, DK TI Postexposure: Treatment of HIV - Taking some risks for safety's sake SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; OCCUPATIONAL EXPOSURE; ZIDOVUDINE; INFECTION; WORKERS RP Henderson, DK (reprint author), NATL INST HLTH CLIN CTR,BETHESDA,MD 20892, USA. NR 11 TC 16 Z9 16 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 20 PY 1997 VL 337 IS 21 BP 1542 EP 1543 DI 10.1056/NEJM199711203372109 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA YG249 UT WOS:A1997YG24900009 PM 9366587 ER PT J AU Bustelo, XR Crespo, P LopezBarahona, M Gutkind, JS Barbacid, M AF Bustelo, XR Crespo, P LopezBarahona, M Gutkind, JS Barbacid, M TI Cbl-b, a member of the Sli-1/c-Cbl protein family, inhibits Vav-mediated c-Jun N-terminal kinase activation SO ONCOGENE LA English DT Article DE Cbl family; Vav; tyrosine phosphorylation; JNK activation ID PROTOONCOGENE PRODUCT; TYROSINE PHOSPHORYLATION; HEMATOPOIETIC-CELLS; SIGNALING PATHWAY; STEEL FACTOR; SH2 DOMAIN; T-CELLS; BINDING; RECEPTORS; P95(VAV) AB We have used the yeast two-hybrid system to identify proteins that interact with Vav, a GDP/GTP exchange factor for the Rac-1 GTPase that plays an important role in cell signaling and oncogenic transformation, This experimental approach resulted in the isolation of Cbl-b, a signal transduction molecule highly related to the mammalian c-cbl proto-oncogene product and to the C. elegans Sli-1 protein, a negative regulator of the EGF-receptor-like Let23 protein, The interaction between Vav and Cbl-b requires the entire SH3-SH2-SH3 carboxy-terminal domain of Vav and a long stretch of proline-rich sequences present in the central region of Cbl-b. Stimulation of quiescent rodent fibroblasts with either epidermal or platelet-derived growth factors induces an increased affinity of Vav for Cbl-b and results in the subsequent formation of a Vav-dependent trimeric complex with the ligand-stimulated tyrosine kinase receptors. During this process, Vav, but not Cbl-b, becomes highly phosphorylated on tyrosine residues, Overexpression of Cbl-b inhibits the signal transduction pathway of Vav that leads to the stimulation of c-Jun N-terminal kinase. By contrast, expression of truncated Cbl-b proteins and of missense mutants analogous to those found in inactive Sli-1 proteins have no detectable effect on Vav activity, These results indicate that Vav and Cbl-b act coordinately in the first steps of tyrosine protein kinase receptor-mediated signaling and suggest that members of the Sli-l/Cbl family are also negative regulators of signal transduction in mammalian cells. C1 SUNY STONY BROOK,SCH MED,DEPT PATHOL,STONY BROOK,NY 11794. SUNY STONY BROOK,UNIV HOSP,STONY BROOK,NY 11794. NIDR,CELLULAR DEV & ONCOL LAB,NIH,BETHESDA,MD 20892. RP Bustelo, XR (reprint author), BRISTOL MYERS SQUIBB PHARMACEUT RES INST,DEPT MOL ONCOL,POB 4000,PRINCETON,NJ 08543, USA. RI Gutkind, J. Silvio/A-1053-2009; Crespo, Piero/M-3273-2014 OI Crespo, Piero/0000-0003-2825-7783 NR 37 TC 70 Z9 73 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 20 PY 1997 VL 15 IS 21 BP 2511 EP 2520 DI 10.1038/sj.onc.1201430 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA YG732 UT WOS:A1997YG73200001 PM 9399639 ER PT J AU deMora, JF Uren, A Heidaran, M Santos, E AF deMora, JF Uren, A Heidaran, M Santos, E TI Biological activity of p27(kip1) and its amino- and carboxy-terminal domains in G2/M transition of Xenopus oocytes SO ONCOGENE LA English DT Article DE p27(kip1); Xenopus oocytes; cell cycle; cdc2 kinase; MPF; GVBD ID DEPENDENT-KINASE INHIBITOR; P34CDC2 PROTEIN-KINASE; FIBROBLAST CELL-CYCLE; PHOSPHORYLATION SITES; TYROSINE PHOSPHATASE; ACTIVATING KINASE; CDK6 INHIBITOR; CDC2; P27; CLONING AB p27(kip1) is a general inhibitor of Cdks that preferentially accumulates and functions during G1 phase, before the restriction point of the mammalian cell cycle. We observed that injection of purified p27(kip1) into Xenopus oocytes potently inhibits the G2/M transition and activation/dephosphorylation of the maturation promoting factor (MPF, p34(cdc2)/cyclin B complex) kinase associated with germinal vesicle breakdown (GVBD) induced by progesterone or insulin. Addition of exogenous p27(kip1) in vitro to lysates of hormonally matured oocytes blocked the enzymatic activity of the activated MPF kinase present in those extracts. Interestingly, the isolated amino-terminal region of p27(kip1) (p27N), encompassing only the Cdk binding site, exhibited a similar inhibitory behavior in vitro and a weaker inhibitory effect in vivo than the complete p27(kip1) protein. Surprisingly, the remaining carboxy-terminal region of p27(kip1) (p27C) actually induced GVBD when injected alone into the oocytes, and also accelerated the kinetics of insulin-or progesterone-induced GVBD. Consistent with the in vivo observations, p27C formed a complex with, and activated, the MPF kinase in lysates of immature oocytes, although this activation was blocked by simultaneous addition of p27N or complete p27(kip1). Active MPF was able to phosphorylate p27C only in the absence of p27N or whole p27(kip1), suggesting that the inhibitory activity associated with the amino terminus is dominant over the activation produced by p27C. These results demonstrate the functional interaction of p27(kip1) with cyclin B/p34(cdc2) complexes during G2/M progression in oocytes, and suggest that the amino and carboxy terminal portions of this protein may play opposite regulatory roles, reminiscent of the corresponding N- and C-terminal portions of p21(waf). We speculate that accumulation of a truncated, C-terminal p27 fragment may play a physiological regulatory role in progression through G2 and later stages of the cell cycle. RP deMora, JF (reprint author), NCI, MOL & CELLULAR BIOL LAB, DBS, BETHESDA, MD 20892 USA. NR 55 TC 15 Z9 16 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 20 PY 1997 VL 15 IS 21 BP 2541 EP 2551 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA YG732 UT WOS:A1997YG73200004 ER PT J AU Chen, SL Zhang, XK Halverson, DO Byeon, MK Schweinfest, CW Ferris, DK Bhat, NK AF Chen, SL Zhang, XK Halverson, DO Byeon, MK Schweinfest, CW Ferris, DK Bhat, NK TI Characterization of human N8 protein SO ONCOGENE LA English DT Article DE leucine zipper protein; homodimerization; phosphorylation; cytoplasmic protein; epithelial cells ID DNA-BINDING DOMAIN; LEUCINE ZIPPER; DIMERIZATION; EXPRESSION; SEQUENCE; COMPLEX; FAMILY; GENES; MYC; MAX AB We have shown before that the N8 mRNA is expressed at higher levels in lung tumor and lung tumor-derived cell lines than normal lung cells. In this paper, we have characterized the N8 protein, and studied its properties. The N8 gene encodes a major 24 kDa protein and its expression correlates well with the N8 mRNA expression pattern observed in different cell lines. N8 protein is capable of forming a homodimer or multimeter in vitro. It is a phosphorylated cytoplasmic protein and phosphorylation occurs mainly at serine residues, N8 protein is expressed at higher levels in epithelial cells than in mesenchymal cells, Ns protein expression is induced in a fibroblast cell line expressing adenoviral Ela protein, which acquired epithelial-like characteristics. Furthermore, ectopic expression of N8 protein in NIH3T3 cells converts them into a spheroid form. These spheroids also have some of the characteristic features of epithelial cells. Taken together, these results suggest that the N8 protein may be associated with the development or maintenance of epithelial cell phenotype. C1 NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,FREDERICK,MD 21702. NCI,MOL ONCOL LAB,FREDERICK,MD 21702. MED UNIV S CAROLINA,HOLLINGS CANC CTR,CTR MOL & STRUCT BIOL,CHARLESTON,SC 29425. NR 15 TC 20 Z9 24 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 20 PY 1997 VL 15 IS 21 BP 2577 EP 2588 DI 10.1038/sj.onc.1201437 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA YG732 UT WOS:A1997YG73200007 PM 9399645 ER PT J AU Fisher, B Dignam, J Wolmark, N DeCillis, A Emir, B Wickerham, DL Bryant, J Dimitrov, NV Abramson, N Atkins, JN Shibata, H Deschenes, L Margolese, RG AF Fisher, B Dignam, J Wolmark, N DeCillis, A Emir, B Wickerham, DL Bryant, J Dimitrov, NV Abramson, N Atkins, JN Shibata, H Deschenes, L Margolese, RG TI Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor-positive breast cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SURGICAL ADJUVANT BREAST; SEQUENTIAL METHOTREXATE; TUMORS; THERAPY; FLUOROURACIL AB Background: The B-20 study of the National Surgical Adjuvant Breast and Bowel Project (NSABP) was conducted to determine whether chemotherapy plus tamoxifen would be of greater benefit than tamoxifen alone in the treatment of patients with axillary lymph node-negative, estrogen receptor-positive breast cancer. Methods: Eligible patients (n = 2306) were randomly assigned to one of three treatment groups following surgery. A total of 771 patients with followup data received tamoxifen alone; 767 received methotrexate, fluorouracil, and tamoxifen (MFT); and 768 received cyclophosphamide, methotrexate, fluorouracil, and tamoxifen (CMFT). The Kaplan-Meier method was used to estimate disease-free survival, distant disease-free survival, and survival. Reported P values are two-sided. Results: Through 5 years of follow-up, chemotherapy plus tamoxifen resulted in significantly better disease-free survival than tamoxifen alone (90% for MFT versus 85% for tamoxifen [P = .01]; 89% for CMFT versus 85% for tamoxifen [P = .001]). A similar benefit was observed in both distant disease-free survival (92% for MFT versus 87% for tamoxifen [P = .008]; 91% for CMFT versus 87% for tamoxifen [P = .006]) and survival (97% for MFT versus 94% for tamoxifen [P = .05]; 96% for CMFT versus 94% for tamoxifen [P = .03]). Compared with tamoxifen alone, MFT and CMFT reduced the risk of ipsilateral breast tumor recurrence after lumpectomy and the risk of recurrence at other local, regional, and distant sites. Risk of treatment failure was reduced after both types of chemotherapy, regardless of tumor size, tumor estrogen or progesterone receptor level, or patient age; however, the reduction was greatest in patients aged 49 years or less. No subgroup of patients evaluated in this study failed to benefit from chemotherapy. Conclusions: Findings from this and other NSABP studies indicate that patients with breast cancer who meet NSABP protocol criteria, regardless of age, lymph node status, tumor size, or estrogen receptor status, are candidates for chemotherapy. C1 UNIV PITTSBURGH,NATL SURG ADJUVANT BREAST & BOWEL PROJECT,DEPT BIOSTAT,PITTSBURGH,PA 15260. ALLEGHENY GEN HOSP,NSABP,PITTSBURGH,PA 15212. MICHIGAN STATE UNIV,NSABP,E LANSING,MI 48824. BAPTIST REG CANC INST,NSABP,JACKSONVILLE,FL. SE CANC CONTROL CONSORTIUM,COMMUNITY CLIN ONCOL PROGRAM,NSABP,WINSTON SALEM,NC. ROYAL VICTORIA HOSP,NSABP,MONTREAL,PQ H3A 1A1,CANADA. ST SACREMENT HOSP,NSABP,QUEBEC CITY,PQ,CANADA. MCGILL UNIV,JEWISH GEN HOSP,NSABP,MONTREAL,PQ H3T 1E2,CANADA. FU NCI NIH HHS [U10CA12027, U10CA37377, U10CA39086] NR 17 TC 289 Z9 296 U1 1 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 19 PY 1997 VL 89 IS 22 BP 1673 EP 1682 DI 10.1093/jnci/89.22.1673 PG 10 WC Oncology SC Oncology GA YG503 UT WOS:A1997YG50300011 PM 9390536 ER PT J AU Potosky, AL Merrill, RM Riley, GF Taplin, SH Barlow, W Fireman, BH BallardBarbash, R AF Potosky, AL Merrill, RM Riley, GF Taplin, SH Barlow, W Fireman, BH BallardBarbash, R TI Breast cancer survival and treatment in health maintenance organization and fee-for-service settings SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; MEDICAL OUTCOMES; MANAGED CARE; SOCIOECONOMIC-STATUS; HMO; MORTALITY; SYSTEMS; MAMMOGRAPHY; IRRADIATION; VALIDATION AB Background: Enrollment in health maintenance organizations (HMOs) has increased rapidly during the past 10 years, reflecting a growing emphasis on health care cost containment. To determine whether there is a difference in the treatment and outcome for female patients with breast cancer enrolled in HMOs versus a fee-for-service setting, we compared the 10-year survival and initial treatment of patients with breast cancer enrolled in both types of plans. Methods: With the use of tumor registries covering the greater San Francisco-Oakland and Seattle-Puget Sound areas, respectively, we obtained information on the treatment and outcome for 13 358 female patients with breast cancer, aged 65 gears and older, diagnosed between 1985 and 1992. We linked registry information with Medicare data and data from the two large HMOs included in the study. We compared the survival and treatment differences between HMO and fee-for-service care after adjusting for tumor stage, comorbidity, and sociodemographic characteristics. Results: In San Francisco-Oakland, the 10-year adjusted risk ratio for breast cancer deaths among HMO patients compared with fee-for-service patients was 0.71 (95% confidence interval [CI] = 0.59-0.87) and was comparable for all deaths. In Seattle-Puget Sound, the risk ratio for breast cancer deaths was 1.01 (95% CI = 0.77-1.33) but somewhat lower for all deaths. Women enrolled in HMOs were more likely to receive breast-conserving surgery than women in fee-for-service (odds ratio = 1.55 in San Francisco-Oakland; 3.39 in Seattle). HMO enrollees undergoing breast-conserving surgery were also more likely to receive adjuvant radiotherapy (San Francisco-Oakland odds ratio = 2.49; Seattle odds ratio = 4.62). Conclusions: Long-term survival outcomes in the two prepaid group practice HMOs in this study were at least equal to, and possibly better than, outcomes in the fee-for-service system. In addition, the use of recommended therapy for early stage breast cancer was more frequent in the two HMOs. C1 US HLTH CARE FINANCING ADM,DIV HLTH SYST RES,BALTIMORE,MD 21207. GRP HLTH COOPERAT PUGET SOUND,CTR HLTH STUDIES,SEATTLE,WA 98101. KAISER PERMANENTE,DIV RES,OAKLAND,CA. RP Potosky, AL (reprint author), NCI,APPL RES BRANCH,DIV CANC CONTROL & POPULAT SCI,NIH,EXECUT PLAZA N,RM 313,BETHESDA,MD 20892, USA. NR 47 TC 67 Z9 67 U1 3 U2 3 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 19 PY 1997 VL 89 IS 22 BP 1683 EP 1691 DI 10.1093/jnci/89.22.1683 PG 9 WC Oncology SC Oncology GA YG503 UT WOS:A1997YG50300012 PM 9390537 ER PT J AU Harty, LC Caporaso, NE Hayes, RB Winn, DM BravoOtero, E Blot, WJ Kleinman, DV Brown, LM Armenian, HK Fraumeni, JF Shields, PG AF Harty, LC Caporaso, NE Hayes, RB Winn, DM BravoOtero, E Blot, WJ Kleinman, DV Brown, LM Armenian, HK Fraumeni, JF Shields, PG TI Alcohol dehydrogenase 3 genotype and risk of oral cavity and pharyngeal cancers SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HUMAN-LIVER ALCOHOL; ALDEHYDE DEHYDROGENASE; GENETIC-POLYMORPHISM; ENZYMATIC AMPLIFICATION; HUMAN-LYMPHOCYTES; LUNG-CANCER; HUMAN COLON; ACETALDEHYDE; CONSUMPTION; SMOKING AB Background: The consumption of alcoholic beverages is a strong risk factor for cancers of the oral cavity and pharynx (oral cancers). Alcohol dehydrogenase type 3 (ADH(3)) metabolizes ethanol to acetaldehyde, a carcinogen. We evaluated whether individuals homozygous for the fast-metabolizing ADH(3)(1) allele (ADH(3)(1-1)) have a greater risk of developing oral cancer in the presence of alcoholic beverage consumption than those with the slow-metabolizing ADH(3)(2) allele (ADH(3)(1-2) and ADH(3)(2-2)). Methods: As part of a population-based study of oral cancer conducted in Puerto Rico, the ADH(3) genotypes of 137 patients with histologically confirmed oral cancer and of 146 control subjects (i.e., individuals with no history of oral cancer) were determined by molecular genetic analysis of oral epithelial cell samples. Risks were estimated by use of multiple logistic regression analyses. Results: Compared with nondrinkers with the ADH(3)(1-1) genotype, consumers of at least 57 alcoholic drinks per week with the ADH(3)(1-1), ADH(3)(1-2), and ADH(3)(2-2) genotypes had 40.1-fold (95% confidence interval [CI] = 5.4-296.0), 7.0-fold (95% CI = 1.4-35.0), and 4.4-fold (95% CI = 0.6-33.0) increased risks of oral cancer, respectively; the risk associated with the ADH(3)(1-1) genotype, compared with the ADH(3)(1-2) and ADH(3)(2-2) genotypes combined, was 5.3 (95% CI = 1.0-28.8) among such drinkers. Considering all levels of alcohol consumption. the risk of oral cancer per additional alcoholic drink per week increased 3.6% (95% CI = 1.9%-5.4%) for subjects with the ADH(3)(1-1) genotype and 2.0% (95% CI = 0.9%-3.0%) for subjects with the ADH(3)(1-2) or ADH(3)(2-2) genotype (two-sided P = .04). Conclusions: The ADH(3)(1-1) genotype appears to substantially increase the risk of ethanol-related oral cancer, thus providing further evidence for the carcinogenicity of acetaldehyde. C1 NCI,DIV BASIC SCI,BETHESDA,MD 20892. NIDR,DIV INTRAMURAL RES,BETHESDA,MD 20892. NIDR,OFF DIRECTOR,BETHESDA,MD 20892. UNIV PUERTO RICO,SCH DENT,SAN JUAN,PR 00936. INT EPIDEMIOL INST LTD,ROCKVILLE,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD. RP Harty, LC (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,NIH,EXECUT PLAZA N,SUITE 439,MSC 7372,BETHESDA,MD 20892, USA. NR 58 TC 146 Z9 153 U1 0 U2 4 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 19 PY 1997 VL 89 IS 22 BP 1698 EP 1705 DI 10.1093/jnci/89.22.1698 PG 8 WC Oncology SC Oncology GA YG503 UT WOS:A1997YG50300014 PM 9390539 ER PT J AU Swanson, CA Brown, CC Brownson, RC Alavanja, MCR AF Swanson, CA Brown, CC Brownson, RC Alavanja, MCR TI Saturated fat intake and lung cancer risk among nonsmoking women in Missouri SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID DIETARY-CHOLESTEROL; NUTRITIONAL EPIDEMIOLOGY; CIGARETTE-SMOKING; ENERGY; HAWAII; MEN C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. NCI,BIOMETRY BRANCH,DIV CANC CONTROL & PREVENT,BETHESDA,MD 20892. ST LOUIS UNIV,SCH PUBL HLTH,ST LOUIS,MO 63103. NR 23 TC 9 Z9 9 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 19 PY 1997 VL 89 IS 22 BP 1724 EP 1725 DI 10.1093/jnci/89.22.1724 PG 2 WC Oncology SC Oncology GA YG503 UT WOS:A1997YG50300020 PM 9390544 ER PT J AU DeMarini, DM Hastings, SB Brooks, LR Eischen, BT Bell, DA Watson, MA Felton, JS Sandler, R Kohlmeier, L AF DeMarini, DM Hastings, SB Brooks, LR Eischen, BT Bell, DA Watson, MA Felton, JS Sandler, R Kohlmeier, L TI Pilot study of free and conjugated urinary mutagenicity during consumption of pan-fried meats: possible modulation by cruciferous vegetables, glutathione S-transferase-M1, and N-acetyltransferase-2 SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE urinary mutagenicity; diet; phenotype ID S-TRANSFERASE M1; COLON-CANCER; COLORECTAL-CANCER; BRUSSELS-SPROUTS; HETEROCYCLIC AMINES; CARCINOGEN-METABOLISM; GENETIC-POLYMORPHISM; CYTOCHROME P4501A2; AROMATIC-AMINES; RISK AB Epidemiological and experimental evidence indicates that consumption of fried meats in conjunction with certain genotypes of phase I and II metabolism genes poses an elevated risk for colorectal cancer. Parallel to this, the consumption of cruciferous vegetables is associated with a reduced risk of colon cancer. Therefore, we designed a 6-week pilot feeding study to evaluate the effect of these variables on urinary mutagenicity, which is a biomarker associated with fried-meat consumption. Eight subjects were fed fried meats daily for six weeks; four ate cruciferous vegetables, and four ate non-cruciferous vegetables, Urinary mutagenicity was evaluated in the presence of S9 in strain YG1024 of Salmonella, which is a frameshift strain that overproduces acetyltransferase. C18/methanol extracts of 24-h urines collected once each week were tested unhydrolyzed (free mutagenicity) and hydrolyzed (total mutagenicity); the difference between the two was the conjugated mutagenicity. Although not significant, the levels of conjugated urinary mutagenicity doubled among crucifera consumers and decreased to 30% of the initial levels among non-crucifera consumers, suggesting the possibility that crucifera may enhance the level of conjugated urinary mutagenicity resulting from consumption of fried meats. Such an effect would be consistent with the documented ability of cruciferous vegetables to induce phase II enzymes. The NAT2 rapid phenotype was significantly associated with similar to 2-fold increases in conjugated(p = 0.05) and total (p = 0.004) urinary mutagenicity relative to NAT2 slow subjects, consistent with the elevated risk confirmed by the NAT2 rapid phenotype for colorectal cancer among meat consumers, An similar to 2-fold increase in urinary mutagenicity among the GSTMI(-) subjects relative to the GSTM1(+) subjects approached significance for free (p = 0.18) and total (p = 0.13) urinary mutagenicity. This is the first report on (a) the mutagenicity of hydrolyzed urine, which was consistently more mutagenic than unhydrolyzed urine; (b) the potential enhancement of conjugated urinary mutagenicity by crucifera; and (c) the association of the rapid NAT2 and possibly the GSTM1(-) phenotype with elevated levels of fried meat-associated urinary mutagenicity. (C) 1997 Elsevier Science B.V. C1 UNIV N CAROLINA,DEPT NUTR,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT EPIDEMIOL,CHAPEL HILL,NC 27599. NIEHS,RES TRIANGLE PK,NC 27709. LAWRENCE LIVERMORE NATL LAB,LIVERMORE,CA 94551. UNIV N CAROLINA,SCH MED,CHAPEL HILL,NC 27599. RP DeMarini, DM (reprint author), US EPA,DIV ENVIRONM CARCINOGENESIS,RES TRIANGLE PK,NC 27711, USA. NR 78 TC 25 Z9 25 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD NOV 19 PY 1997 VL 381 IS 1 BP 83 EP 96 DI 10.1016/S0027-5107(97)00152-8 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA YH086 UT WOS:A1997YH08600010 PM 9403034 ER PT J AU Lin, BC Morris, DW Chou, JY AF Lin, BC Morris, DW Chou, JY TI The role of HNF1 alpha, HNF3 gamma, and cyclic AMP in glucose-6-phosphatase gene activation SO BIOCHEMISTRY LA English DT Article ID RAT-LIVER GLUCOSE-6-PHOSPHATASE; STORAGE-DISEASE TYPE-1A; NUCLEAR FACTOR; PHOSPHOENOLPYRUVATE CARBOXYKINASE; TRANSCRIPTION FACTORS; REGULATED EXPRESSION; RESPONSE ELEMENT; ENZYME-DEFICIENT; HEPATOMA-CELLS; PROTEINS AB The gene for glucose-6-phosphatase (G6Pase), the key enzyme in glucose homeostasis, is expressed in a tissue-specific manner in the liver and kidney. To understand the molecular mechanisms regulating liver-specific expression of the G6Pase gene, we characterized G6Pase promoter activity by transient expression assays. The G6Pase promoter is active in HepG2 hepatoma cells? but inactive in JEG3 choriocarcinoma or 3T3 cells. DNA elements essential for optimal and liver-specific expression of the G6Pase gene were contained within nucleotides -234 to +3. Deletion analysis revealed that the G6Pase promoter contained three activation elements (AEs) at nucleotides -234 to -212 (AE-I), -146 to -125 (AE-II), and -124 to -71 (AE-III). AE-I contains binding sites for hepatocyte nuclear factors (HNF) 1 and it. Electromobility shift and cotransfection assays demonstrated that HNF1 alpha, but not HNF4, bound to its cognate site and transactivated G6Pase gene expression. The G6Pase promoter contained five HNF3 motifs, 1 (-180/-174), 2 (-139/-133), 3 (-91/-85), 3 (-81/-75), and 5 (-72/-66), and all five sites bound HNF3 gamma with high affinity. Transient expression and cotransfection assays showed that HNF3 site I is not required for basal promoter activity but is essential for HNF3 gamma-activated transcription from the G6Pase promoter. We further showed that HNF3 sites 3! 3, and 5 were essential for basal G6Pase promoter activity and transactivation by HNF3 gamma. AE-H contains, in addition to a HNF3 motif, a cAMP-response element (CRE) and a C/EBP half-site. The G6Pase(-146/-116) DNA containing AE-II formed multiple protein-DNA complexes with HepG2 nuclear extracts, including HNF3 gamma. CRE-binding protein (CREB), C/EBP alpha, and C/EBP beta. We showed that AE-LI mediated transcription activation of the G6Pase gene by cAMP. C1 NICHHD,HERITABLE DISORDERS BRANCH,NIH,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,DEPT BIOL SCI,WASHINGTON,DC 20052. RI Lin, Baochuan/A-8390-2009 OI Lin, Baochuan/0000-0002-9484-0785 NR 53 TC 66 Z9 69 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 18 PY 1997 VL 36 IS 46 BP 14096 EP 14106 DI 10.1021/bi9703249 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YG697 UT WOS:A1997YG69700015 PM 9369482 ER PT J AU Cannon, RO AF Cannon, RO TI Does coronary endothelial dysfunction cause myocardial ischemia in the absence of obstructive coronary artery disease? SO CIRCULATION LA English DT Editorial Material DE editorials; endothelium; endothelium-derived factors; ischemia; microcirculation ID CHOLESTEROL-LOWERING THERAPY; SYNDROME-X; ANGINA-PECTORIS; NITRIC-OXIDE; RISK-FACTORS; VASOMOTOR RESPONSE; RESISTANCE VESSELS; BLOOD-FLOW; EXERCISE; VASODILATION RP Cannon, RO (reprint author), NHLBI,CARDIOL BRANCH,NIH,BLDG 10,ROOM 7B15,10 CTR DR MSC 1650,BETHESDA,MD 20892, USA. NR 37 TC 22 Z9 23 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 18 PY 1997 VL 96 IS 10 BP 3251 EP 3254 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YH188 UT WOS:A1997YH18800001 PM 9396408 ER PT J AU Kenagy, RD Hart, CE StetlerStevenson, WG Clowes, AW AF Kenagy, RD Hart, CE StetlerStevenson, WG Clowes, AW TI Primate smooth muscle cell migration from aortic explants is mediated by endogenous platelet-derived growth factor and basic fibroblast growth factor acting through matrix metalloproteinases 2 and 9 SO CIRCULATION LA English DT Article; Proceedings Paper CT ASBMB / ASIP / AAI Meeting CY JUN 02-06, 1996 CL NEW ORLEANS, LA SP ASBMB, ASIP, AAI DE atherosclerosis; metalloproteinases; muscle, smooth; platelet-derived factors; tissue ID RAT CAROTID-ARTERY; FACTOR-B-CHAIN; IV COLLAGENASE; PLASMINOGEN ACTIVATORS; MESSENGER-RNA; INTERSTITIAL COLLAGENASE; INTIMAL HYPERPLASIA; BASEMENT-MEMBRANE; 92-KD GELATINASE; VASCULAR INJURY AB Background Migration of arterial smooth muscle cells (SMCs) is regulated by basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), and matrix metalloproteinases (MMPs) in the injured rat carotid artery. We have recently shown that migration of SMCs from baboon aortic explants depends on the activity of MMPs, but the identity of the stimulatory MMPs and the role of bFGF and PDGF in this primate system are not known. Methods and Results These experiments were designed to determine whether MMP2, MMP9, bFGF, or PDGF plays a role in SMC migration from medial explants of baboon aorta. Explants were cultured in serum-free medium with insulin, transferrin, and ovalbumin. Neutralizing antibodies to MMP2 and antibodies that inhibit activation of proMMP9 decreased SMC migration from the aortic explants. Antibodies to bFGF and to the alpha- and beta-subunits of the PDGF receptor also inhibited migration from the explants. Addition of bFGF and PDGF-BB but not PDGF-AA increased migration. The antibodies to bFGF but not the antibodies to the PDGF receptor subunits decreased the levels of MMP9, whereas all the antibodies decreased activated MMP2. Conclusions These data demonstrate that SMC migration from primate aortic explants is dependent on endogenous MMP2, MMP9, PDGF, and bFGF. The data also suggest that PDGF-induced (PDGF-BB or possibly PDGF-AB) migration is dependent on MMP2, whereas bFGF-induced migration depends on both MMP2 and MMP9. C1 ZYMOGENET INC,SEATTLE,WA 98105. NCI,PATHOL LAB,DIV CLIN SCI,BETHESDA,MD 20892. RP Kenagy, RD (reprint author), UNIV WASHINGTON,SCH MED,DEPT SURG,BOX 356410,1959 NE PACIFIC ST,SEATTLE,WA 98195, USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU NCRR NIH HHS [RR-00166]; NHLBI NIH HHS [HL-30946, HL-18645] NR 73 TC 115 Z9 120 U1 1 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 18 PY 1997 VL 96 IS 10 BP 3555 EP 3560 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YH188 UT WOS:A1997YH18800048 PM 9396455 ER PT J AU Shiota, T Jones, M Delabays, A Li, XK Yamada, I Ishii, M Acar, P Holcomb, S Pandian, NG Sahn, DJ AF Shiota, T Jones, M Delabays, A Li, XK Yamada, I Ishii, M Acar, P Holcomb, S Pandian, NG Sahn, DJ TI Direct measurement of three-dimensionally reconstructed flow convergence surface area and regurgitant flow in aortic regurgitation - In vitro and chronic animal model studies SO CIRCULATION LA English DT Article DE regurgitation; echocardiography; blood flow; Doppler analysis ID ORIFICE AREA; MITRAL REGURGITATION; IN-VITRO; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; QUANTITATIVE ASSESSMENT; VALVULAR REGURGITATION; DIFFERENT SHAPES; CONTINUOUS-WAVE; DOPPLER; REGION AB Background Evaluation of flow convergence (FC) with two-dimensional (2D) imaging systems may not be sufficiently accurate to characterize these often asymmetric, complex phenomena. The aim of this study was to validate a three-dimensional (3D) method for determining the severity of aortic regurgitation (AR) in an experimental animal model. Methods and Results In six sheep with surgically induced chronic AR, 20 hemodynamically different states were studied. Instantaneous regurgitant flow rates were obtained by aortic and pulmonary electromagnetic flow meters. Video composite data of color Doppler flow mapping images were transferred into a TomTec computer after computer-controlled 180 degrees rotational acquisition. Direct measurement of the 3D reconstructed FC surface areas as well as measurements of FC areas estimated with 2D methods with hemispherical and hemielliptical assumptions were performed, and values were multiplied by the aliasing velocity to obtain peak regurgitant flow rates. There was better agreement between 3D and electromagnetically derived flow rates than there was between the 2D and the reference values (r=.94, y=1.0x-0.16, difference=0.02 L/min for the 3D method; r=.80, y=1.6x-0.3, difference=1.2 L/min for the 2D hemispherical method; r=.75, y=0.90x+0.2, difference=-0.20 L/min for the 2D hemielliptical method). Conclusions Without any geometrical assumption, the 3D method provided better delineation of the FC zones and direct measurements of FC surface areas, permitting more accurate quantification of the severity of AR than the 2D methods. C1 NHLBI,LAB ANIM MED & SURG,NIH,BETHESDA,MD 20892. OREGON HLTH SCI UNIV,CLIN CARE CTR CONGENITAL HEART DIS,PORTLAND,OR 97201. TUFTS UNIV,NEW ENGLAND MED CTR,NONINVAS CARDIAC LAB,BOSTON,MA 02111. FU NHLBI NIH HHS [HL-43287] NR 35 TC 35 Z9 37 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 18 PY 1997 VL 96 IS 10 BP 3687 EP 3695 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YH188 UT WOS:A1997YH18800065 PM 9396472 ER PT J AU Sudhir, K Chou, TM Chatterjee, K Smith, EP Williams, TC Kane, JP Malloy, MJ Korach, KS Rubanyi, GM AF Sudhir, K Chou, TM Chatterjee, K Smith, EP Williams, TC Kane, JP Malloy, MJ Korach, KS Rubanyi, GM TI Premature coronary artery disease associated with a disruptive mutation in the estrogen receptor gene in a man SO CIRCULATION LA English DT Article DE estrogen; men; coronary disease ID APOLIPOPROTEIN-A-I; POSTMENOPAUSAL WOMEN; DENSITY-LIPOPROTEINS; COMPUTED-TOMOGRAPHY; CHOLESTEROL LEVELS; HEART-DISEASE; MEN; QUANTIFICATION; ACETYLCHOLINE; VASODILATION AB Background While estrogens protect against coronary ar tery disease in women, it is unclear whether they influence cardiovascular function in men. The present report describes coronary vascular abnormalities and the lipoprotein profile of a male patient with estrogen insensitivity caused by a disruptive mutation in the estrogen-receptor gene. Methods and Results Stress thallium scintigraphy, echocardiography, and electron-beam computed tomography (CT) scanning of the coronary arteries and detailed lipoprotein analysis were performed. Electron-beam CT scanning of the coronary arteries showed calcium in the left anterior descending artery. Lipoprotein analysis showed relatively low levels of total (130 mg/dL), LDL (97 mg/dL), and HDL (34 mg/dL) cholesterol; apolipoprotein A-I (91.7 mg/dL;); and lipoprotein(a) (4.1 nmol/L), but normal levels of triglycerides (97 mg/dL) and pre-beta-l-HDL cholesterol (61 mu g/mL). Conclusions The absence of functional estrogen receptors may be a novel risk factor for coronary artery disease in men. C1 UNIV CALIF SAN FRANCISCO,INST CARDIOVASC RES,SAN FRANCISCO,CA 94143. UNIV CINCINNATI,CHILDRENS HOSP,MED CTR,DIV ENDOCRINOL,CINCINNATI,OH 45221. UNIV CINCINNATI,COLL MED,DIV ENDOCRINOL,CINCINNATI,OH 45221. NIEHS,RES TRIANGLE PK,NC 27709. BERLIX BIOSCI,RICHMOND,CA. RP Sudhir, K (reprint author), UNIV CALIF SAN FRANCISCO,DEPT MED,DIV CARDIOL,BOX 0124,SAN FRANCISCO,CA 94143, USA. OI Korach, Kenneth/0000-0002-7765-418X NR 33 TC 143 Z9 148 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 18 PY 1997 VL 96 IS 10 BP 3774 EP 3777 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YH188 UT WOS:A1997YH18800075 PM 9396482 ER PT J AU Lee, IJ Soh, YJ Song, BJ AF Lee, IJ Soh, YJ Song, BJ TI Molecular characterization of fetal alcohol syndrome using mRNA differential display SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MESSENGER-RNA; GENE-EXPRESSION; TROPOMYOSIN GENE; STRESS PROTEIN; ETHANOL; CELLS; INDUCTION; BRAIN; TRANSCRIPTION; MECHANISMS AB The molecular pathogenesis of fetal alcohol syndrome (FAS) has not been well elucidated. The technique of mRNA differential display was used to characterize the etiology and to identify potential markers for FAS. Out of approximately 1,080 mRNA transcripts in mouse embryos that were analyzed, the levels of three mRNAs were altered by ethanol. Two of these mRNAs (one novel and one encoding heat shock protein 47) were also modulated by another teratogen, 3-methylcholanthrene. The third mRNA, encoding alpha-tropomyosin, was specifically up-regulated by ethanol. Consistent with the Northern blot data, immunoblot analysis demonstrated that the level of alpha-tropomyosin protein (31 kDa, most likely a brain specific isoform) was elevated in the embryos exposed to ethanol. (C) 1997 Academic Press. C1 NIAAA,NEUROGENET LAB,ROCKVILLE,MD 20852. NR 33 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 17 PY 1997 VL 240 IS 2 BP 309 EP 313 DI 10.1006/bbrc.1997.7655 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YG935 UT WOS:A1997YG93500011 PM 9388474 ER PT J AU Vitek, MP Snell, J Dawson, H Colton, CA AF Vitek, MP Snell, J Dawson, H Colton, CA TI Modulation of nitric oxide production in human macrophages by apolipoprotein-E and amyloid-beta peptide SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; OXIDATIVE DAMAGE; MICROGLIAL CELLS; PROTEIN; RECEPTOR; ISOFORM; BRAIN AB Induction of oxidative stress has been implicated as a causative factor in chronic neurodegenerative diseases such as Alzheimer's disease, Apolipoprotein-E (apoE) and amyloid-beta eta peptide (A beta) have been reported to alter the redox state of the brain. Using human monocyte-derived macrophages as a model of brain microglia, physiological levels of apolipoprotein-E were found to stimulate nitric oxide (NO) production in polyinosinic:polycytidylic acid (poly I:C) primed cells. ApoE treatment released 68% more NO than cells treated with poly I:C alone and almost threefold more NO than unprimed cells, In contrast to mouse microglia, human cells failed to generate NO in response to A beta peptides, with or without poly I:C treatments. Furthermore, the combination of A beta plus apoE inhibited the increase in NO production induced by apoE. Since Alzheimer's is strongly associated with the presence of an APOE4 allele, our study predicts a mechanism where apoE and A beta regulate nitric oxide production in human brain. (C) 1997 Academic Press. C1 NINCDS,UNIT REACT OXYGEN SPECIES,NIH,BETHESDA,MD 20892. GEORGETOWN UNIV,SCH MED,DEPT PHYSIOL & BIOPHYS,WASHINGTON,DC 20007. RP Vitek, MP (reprint author), DUKE UNIV,MED CTR,DIV NEUROL,POB 2900,DURHAM,NC 27710, USA. FU NIA NIH HHS [AG 13839] NR 25 TC 54 Z9 55 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 17 PY 1997 VL 240 IS 2 BP 391 EP 394 DI 10.1006/bbrc.1997.7408 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YG935 UT WOS:A1997YG93500025 PM 9388488 ER PT J AU Hiraiwa, M Campana, WM Martin, BM OBrien, JS AF Hiraiwa, M Campana, WM Martin, BM OBrien, JS TI Prosaposin receptor: Evidence for a G-protein-associated receptor SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SPHINGOLIPID ACTIVATOR PROTEINS; GAMMA-S BINDING; SAPOSIN PROTEINS; IN-VIVO; PRECURSOR; MEMBRANES; STORAGE; CELLS AB Prosaposin, the precursor of sphingolipid activator protein (saposins A-D), has been identified as a neurotrophic factor capable of inducing neural differentiation and preventing cell death. The putative prosaposin receptor was partially purified from baboon brain membranes by affinity chromatography using a saposin C-column. The purified preparation gave a single major protein band with an apparent molecular weight of 54 kDa on SDS-PAGE. Affinity cross-linking of 11 kDa I-125-saposin C demonstrated the presence of a 66 kDa product, indicative of an apparent molecular weight of 55 kDa for the receptor. A GTP gamma S-binding assay using cell membranes from SHSY5Y neural cells demonstrated agonist stimulated binding of [S-35]GTP gamma S upon treatment with prosaptide TX14(A) a peptide from the neurotrophic region; maximal binding was obtained at 2 nM. TX14(A) stimulated binding was abolished by prior treatment of SHSY5Y cells with pertussis toxin and by a scrambled and an all D-amino acid-derivative of the 14-mer. A 14-mer mutant prosaptide (N-6-->D-6) competed with TX14(A) with a Ki of 0.7 nM. Immunoblot analysis using an antibody against the G(o alpha) subunit demonstrated that the purified receptor preparation contained a 40 kDa reactive band consistent with association of G(o alpha) and the receptor. These findings indicate that the signaling induced by prosaposin and TX14(A) is generated by binding to a G(o)-protein associated receptor. (C) 1997 Academic Press. C1 UNIV CALIF SAN DIEGO,SCH MED,CTR MOL GENET,DEPT NEUROSCI,LA JOLLA,CA 92093. NIMH,CLIN NEUROSCI BRANCH,SECT MOL NEUROGENET,BETHESDA,MD 20892. FU NIDDK NIH HHS [DK07318-18] NR 23 TC 51 Z9 55 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 17 PY 1997 VL 240 IS 2 BP 415 EP 418 DI 10.1006/bbrc.1997.7673 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YG935 UT WOS:A1997YG93500030 PM 9388493 ER PT J AU Jenkins, TM Esposito, D Engelman, A Craigie, R AF Jenkins, TM Esposito, D Engelman, A Craigie, R TI Critical contacts between HIV-1 integrase and viral DNA identified by structure-based analysis and photo-crosslinking SO EMBO JOURNAL LA English DT Article DE HIV-1; integrase; photo-crosslinking; protein-DNA interaction ID HUMAN-IMMUNODEFICIENCY-VIRUS; AMINO-ACID-RESIDUES; CARBOXYL-TERMINAL DOMAINS; TYPE-1 INTEGRASE; CATALYTIC DOMAIN; BINDING DOMAIN; IN-VITRO; SUBSTRATE-SPECIFICITY; RETROVIRAL INTEGRASES; ESCHERICHIA-COLI AB Analysis of the crystal structure of HIV-I integrase reveals a cluster of lysine residues near the active site. Using site-directed mutagenesis and photo-crosslinking we find that Lys156 and Lys159 are critical for the functional interaction of integrase with viral DNA. Mutation of Lys156 or Lys159 to glutamate led to a loss of both 3' processing and strand transfer activities irt vitro while maintaining the ability to interact with nonspecific DNA and support disintegration, However, mutation of both residues to glutamate produced a synergistic effect eliminating nearly all nonspecific DNA interaction and disintegration activity, In addition, virus containing either of these changes was replication-defective at the step of integration, Photo-crosslinking, using 5-iododeoxyuracil-substituted oligonucleotides, suggests that Lys159 interacts at the N7 position of the conserved deoxyadenosine adjacent to the scissile phosphodiester bond of viral DNA. Sequence conservation throughout retroviral integrases and certain bacterial transposases (e.g. Tn10/IS10) supports the premise that within those families of polynucleotidyl transferases, these residues are strategic for DNA interaction. C1 NCI,MOL BIOL LAB,NIH,BETHESDA,MD 20892. DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. FU NCRR NIH HHS [RR-01081]; NIAID NIH HHS [AI39394] NR 70 TC 199 Z9 203 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 17 PY 1997 VL 16 IS 22 BP 6849 EP 6859 DI 10.1093/emboj/16.22.6849 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YJ207 UT WOS:A1997YJ20700023 PM 9362498 ER PT J AU SloanLancaster, J Zhang, WG Presley, J Williams, BL Abraham, RT LippincottSchwartz, J Samelson, LE AF SloanLancaster, J Zhang, WG Presley, J Williams, BL Abraham, RT LippincottSchwartz, J Samelson, LE TI Regulation of ZAP-70 intracellular localization: Visualization with the green fluorescent protein SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CELL ANTIGEN RECEPTOR; SEVERE COMBINED IMMUNODEFICIENCY; TANDEM SH2 DOMAINS; TYROSINE KINASES; PHOSPHOLIPASE C-GAMMA-1; MONOCLONAL-ANTIBODIES; SIGNAL-TRANSDUCTION; ACTIVATION MOTIFS; T-CELLS; PHOSPHORYLATION AB To investigate the cellular dynamics of ZAP-70, we have studied the distribution and regulation of its intracellular location using a ZAP-70 green fluorescent protein chimera. Initial experiments in epithelial cells indicated that ZAP-70 is diffusely located throughout the quiescent cell, and accumulates at the: plasma membrane upon cellular activation, a phenotype enhanced hy the coexpression of Lck and the initiation of: ZAP-70 kinase activity. Subsequent studies in T cells confirmed this phenotype. Intriguingly, a large amount of ZAP-70, both chimeric and endogenous, resides in the nucleus of quiescent and activated cells. Nuclear ZAP-70 becomes tyrosine phosphorylated upon stimulation via the T cell receptor, indicating that it may have an important biologic function. C1 NICHHD,CELL BIOL & METAB BRANCH,SECT LYMPHOCYTE SIGNALING,NIH,BETHESDA,MD 20892. NICHHD,CELL BIOL & METAB BRANCH,UNIT ORGANELLE BIOL,NIH,BETHESDA,MD 20892. MAYO CLIN & MAYO FDN,DEPT IMMUNOL,ROCHESTER,MN 55905. FU NIGMS NIH HHS [GM47286, R01 GM047286] NR 49 TC 35 Z9 35 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 17 PY 1997 VL 186 IS 10 BP 1713 EP 1724 DI 10.1084/jem.186.10.1713 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA YH435 UT WOS:A1997YH43500010 PM 9362531 ER PT J AU Davis, CB Dikic, I Unutmaz, D Hill, CM Arthos, J Siani, MA Thompson, DA Schlessinger, J Littman, DR AF Davis, CB Dikic, I Unutmaz, D Hill, CM Arthos, J Siani, MA Thompson, DA Schlessinger, J Littman, DR TI Signal transduction due to HIV-1 envelope interactions with chemokine receptors CXCR4 or CCR5 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; MONONUCLEAR PHAGOCYTES; CELL-LINES; INFECTION; GP120; REPLICATION; PYK2; CD4; IDENTIFICATION; GLYCOPROTEINS AB Infection with HIV-1 requires expression of CD4 and the chemokine receptors CXCR4 or CCR5 at the target cell surface. Engagement of these receptors by the HIV-1 envelope glycoprotein is essential for membrane fusion, but may additionally activate intracellular signaling pathways. In this study, we demonstrate that chemokines and HIV-1 envelope glycoproteins from both T-tropic and macrophage-tropic strains rapidly induce tyrosine phosphorylation of the protein tyrosine kinase Pyk2. The response requires CXCR3 and CCR5 to be accessible on the cell surface. The results presented here provide the first evidence for activation of an intracellular signaling event that can initiate multiple signaling pathways as a consequence of contact between HIV-1 and chemokine receptors. C1 NYU,MED CTR,HOWARD HUGHES MED INST,NEW YORK,NY 10016. NYU,MED CTR,DEPT PHARMACOL,NEW YORK,NY 10016. NIAID,NIH,BETHESDA,MD 20892. GRYPHON SCI,S SAN FRANCISCO,CA 94080. RP Davis, CB (reprint author), NYU,MED CTR,SKIRALL INST BIOMOL MED,DIV MOL PATHOGENESIS,540 1ST AVE,NEW YORK,NY 10016, USA. RI Dikic, Ivan/O-4650-2015 OI Dikic, Ivan/0000-0001-8156-9511 NR 35 TC 317 Z9 321 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 17 PY 1997 VL 186 IS 10 BP 1793 EP 1798 DI 10.1084/jem.186.10.1793 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA YH435 UT WOS:A1997YH43500020 PM 9362541 ER PT J AU DiFronzo, NL PiseMasison, CA FernandezLarsson, R Holland, CA AF DiFronzo, NL PiseMasison, CA FernandezLarsson, R Holland, CA TI Viral determinants of HIV-1 sufficient to extend tropism to macrophages are distinct from the determinants that control the cytopathic phenotype in HL-60 cells SO AIDS LA English DT Article DE HIV; tropism; HL-60 cells; cytopathicity ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTIOUS MOLECULAR CLONE; T-CELL; HOST-RANGE; ENVELOPE GLYCOPROTEIN; MONONUCLEAR PHAGOCYTES; PRODUCTIVE INFECTION; FUSION COFACTORS; TYPE-1 TROPISM; V3 LOOP AB Design: Infection of the human promyelocytic cell line HL-60 with NL4-3, a molecularly cloned HIV-1 strain that productively infects T cells, results in adaptation of the virus and production of a variant, NL4-3(M). Unlike NL4-3, NL4-3(M) has a rapid cytopathic effect in HL-60 and other myeloid cell lines. Objective: To demonstrate that the tropism of NL4-3(M) is extended to primary monocyte-derived macrophages (MDM), and to determine whether the envelope gene, env, of NL4-3(M) is responsible for cytopathicity in HL-60 cells and replication in MDM. Methods: A chimeric virus (NL4-3envA) containing the majority of env of NL4-3(M) was generated, and tested for virus replication and cytopathic effect in H9 and HL-60 cells, as well as for virus replication in primary MDM. To assess virus replication, the cultures were analyzed for expression of viral envelope glycoproteins on the infected cells and production of extracellular HIV-1 p24 antigen. Cytopathic effect on HL-60 cells was evaluated by monitoring the viabilities of the cultures. In addition, the majority of env of NL4-3envA was sequenced. Results: The biological phenotypes of NL4-3, NL4-3(M), and NL4-3envA are distinctly different. Although both NL4-3(M) and NL4-3envA replicate in MDM, only NL4-3(M) is rapidly cytopathic in HL-60 cells. Nine amino-acid changes were identified within the envelope glycoproteins of NL4-3envA compared with NL4-3. Conclusions: The viral determinants of NL4-3(M) sufficient to extend the tropism of this virus to MDM reside, in part, in env. These genetic determinants are distinct from the viral determinants that control the cytopathic phenotype of this virus in HL-60 cells. C1 CHILDRENS NATL MED CTR,CTR VIROL IMMUNOL & INFECT DIS RES,R5700,WASHINGTON,DC 20010. NCI,MOL VIROL LAB,DIV CANC ETIOL,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [CA-41510] NR 46 TC 6 Z9 6 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD NOV 15 PY 1997 VL 11 IS 14 BP 1681 EP 1688 DI 10.1097/00002030-199714000-00004 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA YE604 UT WOS:A1997YE60400004 PM 9386802 ER PT J AU Kipnis, V Freedman, LS Brown, CC Hartman, AM Schatzkin, A Wacholder, S AF Kipnis, V Freedman, LS Brown, CC Hartman, AM Schatzkin, A Wacholder, S TI Effect of measurement error on energy-adjustment models in nutritional epidemiology SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE energy intake; epidemiologic methods; measurement error; models, statistical; nutrient intake; regression analysis ID EXPOSURE MEASUREMENT ERROR; DIET; CANCER; MISCLASSIFICATION; IMPACT; DESIGN AB The use and interpretation of energy-adjustment regression models in nutritional epidemiology has been vigorously debated recently. There has been little discussion, however, regarding the effect of dietary measurement error on the performance of such models. Contrary to conventional assumptions invoked in the standard treatment of the effect of measurement error in regression analysis, reporting errors in dietary studies are usually biased, correlated with true nutrient intakes and with each other, heteroscedastic, and nonnormally distributed. Methods developed in this paper allow for this more complex error structure and are therefore more appropriate for dietary data, For practical illustration, these methods are applied to data from the Women's Health Trial Vanguard Study. The results demonstrate considerable shrinkage in the magnitude of the estimated main exposure effect in energy-adjustment models due to attenuation of the true effect and contamination from the effect of an adjusting covariate. In most cases, this shrinkage causes a sharply reduced statistical power of the corresponding significance test in comparison with measurement without error. These results emphasize the need to understand the measurement error properties of dietary instruments through validation/calibration studies and, where possible, to correct for the impact of measurement error when applying energy-adjustment models. C1 NCI,DIV CANC PREVENT & CONTROL,APPL RES BRANCH,BETHESDA,MD 20892. NCI,DIV CANC PREVENT & CONTROL,APPL RES BRANCH,BETHESDA,MD. NCI,DIV CANC PREVENT & CONTROL,CANC PREVENT STUDIES BRANCH,BETHESDA,MD 20892. NCI,DIV CANC EPIDEMIOL & GENET,BIOSTAT BRANCH,BETHESDA,MD 20892. RP Kipnis, V (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,EXECUT PLAZA N,SUITE 344,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 30 TC 58 Z9 58 U1 2 U2 3 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 15 PY 1997 VL 146 IS 10 BP 842 EP 855 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YF882 UT WOS:A1997YF88200007 PM 9384205 ER PT J AU Kakuda, TN AF Kakuda, TN TI Somatropin for treating AIDS-related wasting syndrome SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article ID HUMAN GROWTH-HORMONE; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; PLACEBO-CONTROLLED TRIAL; VIRUS INFECTION; DOUBLE-BLIND C1 NIH,DEPT PHARM,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD. RP Kakuda, TN (reprint author), UNIV MINNESOTA,MINNEAPOLIS,MN 55455, USA. NR 23 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD NOV 15 PY 1997 VL 54 IS 22 BP 2618 EP 2620 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YH015 UT WOS:A1997YH01500020 PM 9397228 ER PT J AU Craxton, A Caffrey, JJ Burkhart, W Safrany, ST Shears, SB AF Craxton, A Caffrey, JJ Burkhart, W Safrany, ST Shears, SB TI Molecular cloning and expression of a rat hepatic multiple inositol polyphosphate phosphatase SO BIOCHEMICAL JOURNAL LA English DT Article ID ENDOPLASMIC-RETICULUM; ACTIVE-SITE; METABOLISM; BINDING; PENTAKISPHOSPHATE; HEXAKISPHOSPHATE; SPECIFICITY; PROTEIN; 1,4,5,6-TETRAKISPHOSPHATE; TETRAKISPHOSPHATE AB The characterization of the multiple inositol polyphosphate phosphatase (MIPP) is fundamental to our understanding of how cells control the signalling activities of 'higher' inositol polyphosphates. We now describe our isolation of a 2.3 kb cDNA clone of a rat hepatic form of MIPP. The predicted amino acid sequence of MIPP includes an 18 amino acid region that aligned with approximately 60% identity with the catalytic domain of a fungal inositol hexakisphosphate phosphatase (phytase A); the similarity encompassed conservation of the RHGXRXP signature of the histidine acid phosphatase family. A histidine-tagged, truncated form of MIPP was expressed in Escherichia coli and the enzymic specificity of the recombinant protein was characterized: Ins(1,3,4,5,6)P-5 was hydrolysed, first to Ins(1,4,5,6)P-4 and then to Ins(1,4,5)P-3, by consecutive 3- and 6-phosphatase activities. Inositol hexakisphosphate was catabolized without specificity towards a particular phosphate group, but in contrast, MIPP only removed the beta-phosphate from the 5-diphosphate group of diphosphoinositol pentakisphosphate. These data, which are consistent with the substrate specificities of native (but not homogeneous) MIPP isolated from rat liver, provide the first demonstration that a single enzyme is responsible for this diverse range of specific catalytic activities. A 2.5 kb transcript of MIPP mRNA was present in all rat tissues that were examined, but was most highly expressed in kidney and liver. The predicted C-terminus of MIPP is comprised of the tetrapeptide SDEL, which is considered a signal for retaining soluble proteins in the lumen of the endoplasmic reticulum; the presence of this sequence provides a molecular explanation for our earlier biochemical demonstration that the endoplasmic reticulum contains substantial MIPP activity [Ali, Craxton and Shears (1993) J. Biol. Chem. 268, 6161-6167]. C1 NIEHS,LAB SIGNAL TRANSDUCT,INOSITIDE SIGNALING SECT,RES TRIANGLE PK,NC 27709. GLAXO WELLCOME INC,RES & DEV,DEPT ANALYT CHEM,RES TRIANGLE PK,NC 27709. NR 30 TC 49 Z9 54 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 NOV 15 PY 1997 VL 328 BP 75 EP 81 PN 1 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YJ098 UT WOS:A1997YJ09800010 PM 9359836 ER PT J AU Gallagher, PG Romana, M Cline, AP Sabatino, DE Garrett, LL Bodine, DM Forget, BG AF Gallagher, PG Romana, M Cline, AP Sabatino, DE Garrett, LL Bodine, DM Forget, BG TI The beta-spectrin gene promoter directs erythroid expression in vitro and in vivo. SO BLOOD LA English DT Meeting Abstract C1 YALE UNIV,NEW HAVEN,CT. NHGRI,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2 EP 2 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400002 ER PT J AU Gubin, AN Njoroge, JM Miller, JL AF Gubin, AN Njoroge, JM Miller, JL TI Transcriptional phenotyping of immature human erythroblasts. SO BLOOD LA English DT Meeting Abstract C1 NIDDKD,BIOL CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 17 EP 17 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400017 ER PT J AU Stabler, SP Allen, RH Fried, LP Pahor, M Kittner, SJ Guralnik, JM AF Stabler, SP Allen, RH Fried, LP Pahor, M Kittner, SJ Guralnik, JM TI Racial differences in prevalence of cobalamin and folate deficiency in disabled elderly women. SO BLOOD LA English DT Meeting Abstract C1 UNIV COLORADO,HLTH SCI CTR,DENVER,CO. UNIV MARYLAND,BALTIMORE,MD 21201. JOHNS HOPKINS UNIV,BALTIMORE,MD. UNIV TENNESSEE,MEMPHIS,TN. NIH,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 39 EP 39 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400039 ER PT J AU Yu, JM Emmons, RVB Hanazono, Y Sellers, S Young, NS Dunbar, CE AF Yu, JM Emmons, RVB Hanazono, Y Sellers, S Young, NS Dunbar, CE TI Expression of interferon-gamma-by stromal cells inhibits murine long-term repopulating stem cell activity and gene transfer. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 41 EP 41 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400041 ER PT J AU Zhan, SX Zhan, SL Chanock, SJ AF Zhan, SX Zhan, SL Chanock, SJ TI Structural and functional characterization of the human p40-phox gene promoter: PU.1 is required for promoter activity. SO BLOOD LA English DT Meeting Abstract C1 NCI,PEDIAT ONCOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 58 EP 58 PN 1 PG 2 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400058 ER PT J AU Hiraoka, W Vazquez, N Chanock, SJ Pommier, Y AF Hiraoka, W Vazquez, N Chanock, SJ Pommier, Y TI Role of oxygen radicals generated by NADPH oxidase in apoptosis induced in human leukemia cells. SO BLOOD LA English DT Meeting Abstract C1 NCI,MOL PHARMACOL LAB,BETHESDA,MD 20892. NCI,PEDIAT ONCOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 63 EP 63 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400063 ER PT J AU Hornung, RL Zea, AH Ochoa, AC Taub, DD Kwak, LW AF Hornung, RL Zea, AH Ochoa, AC Taub, DD Kwak, LW TI Altered expression and function of TCR signal transduction proteins in T cells from follicular lymphoma (FL) patients before treatment: Not an obstacle to tumor-specific T-cell activation by active immunotherapy. SO BLOOD LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,IRSP,MED BRANCH,DCS,SAIC FREDERICK,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,CSP,MED BRANCH,DCS,SAIC FREDERICK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 79 EP 79 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400079 ER PT J AU Du, J Xin, F Rhoads, E Xanthopoulos, KG Tenen, DG Yamaguchi, Y Ackerman, SJ AF Du, J Xin, F Rhoads, E Xanthopoulos, KG Tenen, DG Yamaguchi, Y Ackerman, SJ TI Differential transactivation of eosinophil-specific promoters by members of the C/EBP family of transcription factors. SO BLOOD LA English DT Meeting Abstract C1 UNIV ILLINOIS,COLL MED,CHICAGO,IL. NATL HUMAN GENOME & RES INST,NIH,BETHESDA,MD. BETH ISRAEL DEACONESS MED CTR,BOSTON,MA. KUMAMOTO UNIV,SCH MED,KUMAMOTO 860,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 177 EP 177 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400177 ER PT J AU Himmelmann, A Wilson, GL Kane, V Fehr, J Kehrl, JH AF Himmelmann, A Wilson, GL Kane, V Fehr, J Kehrl, JH TI NF-kB/Rel proteins p50 and p65 are involved in the regulation of the B cell specific RGS1 ((R)under-bar-egulator of (G)under-bar protein (S)under-bar-ignaling) gene. SO BLOOD LA English DT Meeting Abstract C1 UNIV ZURICH HOSP,DEPT INTERNAL MED,HEMATOL SECT,ZURICH,SWITZERLAND. NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 197 EP 197 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400197 ER PT J AU Kitada, S Krajewska, M Zhang, X Scudiero, D Zapata, JM Wang, HG Shabaik, A Tudor, G Krajewski, S Myers, TG Johnson, GS Sausville, EA Reed, JC AF Kitada, S Krajewska, M Zhang, X Scudiero, D Zapata, JM Wang, HG Shabaik, A Tudor, G Krajewski, S Myers, TG Johnson, GS Sausville, EA Reed, JC TI Expression of pro-apoptotic Bcl-2 family protein bad in normal hematolymphoid tissues and human tumor lines. SO BLOOD LA English DT Meeting Abstract C1 BURNHAM INST,CANC RES CTR,LA JOLLA,CA 92037. NCI,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,AIC FREDERICK,BETHESDA,MD 20892. UNIV CALIF SAN DIEGO,DEPT PATHOL,SAN DIEGO,CA 92103. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 224 EP 224 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400224 ER PT J AU Castilla, L Liu, P AF Castilla, L Liu, P TI Analysis of a conditional Cbfb-MYH11 knock-in for inv (16) acute myeloid leukemia. SO BLOOD LA English DT Meeting Abstract C1 NIH,NATL HUMAN GENOME RES INST,BETHESDA,MD 20892. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 253 EP 253 PN 1 PG 2 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400253 ER PT J AU Cao, W Liu, PP Friedman, AD AF Cao, W Liu, PP Friedman, AD TI Two domains of CBF beta-SMMHC are required for inhibition of CBF DNA-binding and cell cycle progression in hematopoietic cells. SO BLOOD LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21205. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 256 EP 256 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400256 ER PT J AU Kontny, HY Mackall, CL AF Kontny, HY Mackall, CL TI Simultaneous expression of FAS-ligand and susceptibility to FAS-mediated cell death in Ewings' sarcoma. SO BLOOD LA English DT Meeting Abstract C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 266 EP 266 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400266 ER PT J AU Feldstein, JT Jaffe, ES Berkowitz, JR Burd, PR Kingma, DW Ferry, JA Harris, NL Wilson, WH Tosato, G AF Feldstein, JT Jaffe, ES Berkowitz, JR Burd, PR Kingma, DW Ferry, JA Harris, NL Wilson, WH Tosato, G TI Expression of interferon gamma inducing factor (IGIF or IL18) in EBV-associated lymphoproliferative diseases with vascular damage and necrosis. SO BLOOD LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. US FDA,BETHESDA,MD 20014. MGH,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 333 EP 333 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400333 ER PT J AU Gutierrez, MI Cherney, B Hussain, A Magrath, I Bhatia, K AF Gutierrez, MI Cherney, B Hussain, A Magrath, I Bhatia, K TI Expression of death inducing genes and the activation of death inducing pathway in Burkitt's lymphoma. SO BLOOD LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 335 EP 335 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400335 ER PT J AU Gutierrez, MI Capello, D Cherney, B Gaidano, G Magrath, I Bhatia, K AF Gutierrez, MI Capello, D Cherney, B Gaidano, G Magrath, I Bhatia, K TI Intraclonal molecular heterogeneity suggests a hierarchy of pathogenetic events in Burkitt's lymphoma. SO BLOOD LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. US FDA,BETHESDA,MD 20014. UNIV TURIN,NOVARA,ITALY. RI Capello, Daniela/J-4110-2012 OI Capello, Daniela/0000-0001-9157-8753 NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 336 EP 336 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400336 ER PT J AU Molldrem, J Caples, M Mavroudis, D Young, NS Barrett, AJ AF Molldrem, J Caples, M Mavroudis, D Young, NS Barrett, AJ TI Treatment with antithymocyte globulin (ATG) induces sustained transfusion independence in patients with refractory anemia and myelodysplastic syndrome. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 368 EP 368 PN 1 PG 2 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400368 ER PT J AU Molldrem, JJ Jiang, YZ Mavroudis, D Raptis, A Hensel, N Barrett, AJ AF Molldrem, JJ Jiang, YZ Mavroudis, D Raptis, A Hensel, N Barrett, AJ TI Hematological response of patients with myelodysplastic syndrome (MDS) to antithymocyte globulin (ATG) treatment is associated with a loss of CD8+ T-cell mediated CFU-GM inhibition. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BONE MARROW TRANSPLANT UNIT,NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 369 EP 369 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400369 ER PT J AU Barrett, AJ Read, EJ Vigue, F Mavroudis, D Carter, C Dunbar, C Phang, S Benyunes, M Jacobs, C Young, NS AF Barrett, AJ Read, EJ Vigue, F Mavroudis, D Carter, C Dunbar, C Phang, S Benyunes, M Jacobs, C Young, NS TI Rapid hematological recovery without graft-vs-host disease (GVHD) following G-CSF-mobilized T cell depleted allogeneic peripheral blood precursor cell (PBPC) transplants for hematological malignancy. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BONE MARROW TRANSPLANT UNIT,BETHESDA,MD 20892. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. CELLPRO INC,BOTHELL,WA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 452 EP 452 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400452 ER PT J AU Munshi, NC Tricot, G Jagannath, S Mehta, J Desikan, K Siegle, S Singhal, S Fassas, A Fink, L Schichman, S Chiang, Y Reynolds, C Barlogie, B AF Munshi, NC Tricot, G Jagannath, S Mehta, J Desikan, K Siegle, S Singhal, S Fassas, A Fink, L Schichman, S Chiang, Y Reynolds, C Barlogie, B TI Clinical results of thymidine kinase (TK) gene transduced donor lymphocyte infusion following allogeneic transplantation in myeloma. SO BLOOD LA English DT Meeting Abstract C1 UNIV ARKANSAS MED SCI,LITTLE ROCK,AR 72205. JOHN L MCCLELLAN MEM VET ADM MED CTR,LITTLE ROCK,AR 72205. GENET THERAPY INC,GAITHERSBURG,MD. NCI,FREDERICK,MD 21701. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 485 EP 485 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400485 ER PT J AU Orlic, D Broxmeyer, HE Girard, LJ Anderson, SM Bodine, DM AF Orlic, D Broxmeyer, HE Girard, LJ Anderson, SM Bodine, DM TI Hematopoietic stem cells (HSC) from cryopreserved cord blood have the higher levels of amphotropic retrovirus receptor mRNA than any other population of HSC: Implications for gene therapy. SO BLOOD LA English DT Meeting Abstract C1 NHGRI,HEMATOPOIESIS SECT,LGT,NIH,BETHESDA,MD. INDIANA UNIV,DEPT MICROBIOL,INDIANAPOLIS,IN 46204. INDIANA UNIV,DEPT IMMUNOL,INDIANAPOLIS,IN 46204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 505 EP 505 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400505 ER PT J AU Wu, T Bloom, ML Yu, JM Tisdale, JF Dunbar, CE AF Wu, T Bloom, ML Yu, JM Tisdale, JF Dunbar, CE TI Murine bone marrow stem tells expressing the neomycin resistance gene have no competitive disadvantage assessed in vivo. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 512 EP 512 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400512 ER PT J AU Chen, L Nelson, D Zheng, ZL Morgan, R AF Chen, L Nelson, D Zheng, ZL Morgan, R TI Re-evaluation of the ex vivo autologous fibroblast transduction model in rabbits: Achievement of long term (>600 days) factor IX expression in a small percentage of animals. SO BLOOD LA English DT Meeting Abstract C1 NCI,CLIN GENE THERAPY BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 520 EP 520 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400520 ER PT J AU Nelson, DM Morgan, RA AF Nelson, DM Morgan, RA TI Sindbis-mediated gene transfer of human Factor IX towards gene therapy for hemophilia B. SO BLOOD LA English DT Meeting Abstract C1 NIH,NATL HUMAN GENOME RES INST,CLIN GENE THERAPY BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 524 EP 524 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400524 ER PT J AU Ikonomi, P Noguchi, CT Schechter, AN AF Ikonomi, P Noguchi, CT Schechter, AN TI Thalassemia and globin gene regulation I 23-II GATA-1/GATA-2 levels modulate expression of embryonic and fetal hemoglobins. SO BLOOD LA English DT Meeting Abstract C1 NIDDK,NIH,BIOL CHEM LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 561 EP 561 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400561 ER PT J AU Lim, MS Guedez, L Sausville, J StetlerStevenson, WG StetlerStevenson, M AF Lim, MS Guedez, L Sausville, J StetlerStevenson, WG StetlerStevenson, M TI Tissue inhibitor of metalloproteinase-2 (TIMP-2) induces apoptosis in human T lymphocytes. SO BLOOD LA English DT Meeting Abstract C1 NCI,PATHOL LAB,EXTRACELLULAR MATRIX SECT,HEMATOPATHOL SECT,NIH,BETHESDA,MD 20892. RI Guedez, Liliana/H-4951-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 612 EP 612 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400612 ER PT J AU Brown, KE Dickstein, B Luban, NLC Jubran, RF Young, NS AF Brown, KE Dickstein, B Luban, NLC Jubran, RF Young, NS TI GBV-C hepatitis G viremia is frequent in normal children SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. CHILDRENS HOSP,NATL MED CTR,DEPT TRANSFUS MED,WASHINGTON,DC 20010. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 683 EP 683 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400683 ER PT J AU Granovsky, MO Tess, BH Goedert, JJ AF Granovsky, MO Tess, BH Goedert, JJ TI Hepatitis C virus infection in the mothers and infants cohort study. SO BLOOD LA English DT Meeting Abstract C1 NCI,VIRAL EPIDEMIOL BRANCH,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 691 EP 691 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400691 ER PT J AU Linnekin, D Mou, S DeBerry, C AF Linnekin, D Mou, S DeBerry, C TI Mapping studies define the regions of c-Kit which mediate interaction with components of the JAK/STAT and Src family pathways. SO BLOOD LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,LAB LEUKOCYTE BIOL,DBS,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,IRSP,SAIC,FREDERICK,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 724 EP 724 PN 1 PG 2 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400724 ER PT J AU Mufson, RA Gubina, E Rinaudo, M Szallasi, Z Blumberg, PM AF Mufson, RA Gubina, E Rinaudo, M Szallasi, Z Blumberg, PM TI Overexpression of protein kinase C isoform epsilon but not delta suppresses apoptosis and induces bcl-2 expression in human IL-3 dependent myeloid cells. SO BLOOD LA English DT Meeting Abstract C1 ARC,DEPT IMMUNOL,HOLLAND LAB,ROCKVILLE,MD. NCI,DIV CANC ETIOL,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 736 EP 736 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400736 ER PT J AU Kurzrock, R Paquette, R Gratwohl, A Doney, K Gabrilove, J Patterson, M Rivera, C Wyres, M Davis, MW Young, N AF Kurzrock, R Paquette, R Gratwohl, A Doney, K Gabrilove, J Patterson, M Rivera, C Wyres, M Davis, MW Young, N TI Use of stem cell factor (Stegmen(R), SCF) and filgrastim (G-CSF) in aplastic anemia (AA) patients (Pts) who have failed ATG/ALG therapy SO BLOOD LA English DT Meeting Abstract C1 UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. AMGEN INC,THOUSAND OAKS,CA 91320. NHLBI,BETHESDA,MD 20892. UNIV HOSP,BASEL,SWITZERLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 762 EP 762 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400762 ER PT J AU Takayama, S Krajewski, S Krajewska, M Kitada, S Zapata, JM Kochel, K Knee, D Scudiero, D Tudor, G Reed, JC AF Takayama, S Krajewski, S Krajewska, M Kitada, S Zapata, JM Kochel, K Knee, D Scudiero, D Tudor, G Reed, JC TI Novel isoforms of Hsp70/Hsc-binding anti-apoptotic protein BAG-1 (HAP-1) are expressed in leukemia cell lines SO BLOOD LA English DT Meeting Abstract C1 BURNHAM INST,LA JOLLA,CA 92037. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,FREDERICK,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 777 EP 777 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400777 ER PT J AU Fest, T Clark, H Sorbara, L Dang, CV Raffeld, M AF Fest, T Clark, H Sorbara, L Dang, CV Raffeld, M TI Functional consequences of Burkitt's lymphoma associated mutations occurring within myc box II. SO BLOOD LA English DT Meeting Abstract C1 NCI,HEMATOPATHOL SECT,PATHOL LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 778 EP 778 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400778 ER PT J AU Frankel, AE Hall, PD Safa, AR Bhalla, K Tagge, EP Kreitman, RJ AF Frankel, AE Hall, PD Safa, AR Bhalla, K Tagge, EP Kreitman, RJ TI Targeted toxins are cell-specific modulators of drug resistance in AML. SO BLOOD LA English DT Meeting Abstract C1 MED UNIV S CAROLINA,CHARLESTON,SC 29425. EMORY UNIV,ATLANTA,GA 30322. NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 807 EP 807 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400807 ER PT J AU Sazawal, S Bhatia, K Gurbuxani, S Arya, LS Raina, V Vats, T Magrath, I Bhargava, M AF Sazawal, S Bhatia, K Gurbuxani, S Arya, LS Raina, V Vats, T Magrath, I Bhargava, M TI Significance of immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements in childhood acute lymphoblastic leukemia (ALL) in India. SO BLOOD LA English DT Meeting Abstract C1 ALL INDIA INST MED SCI,NEW DELHI,INDIA. NCI,NIH,BETHESDA,MD 20892. TEXAS TECH UNIV,HLTH SCI CTR,AMARILLO,TX. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 823 EP 823 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400823 ER PT J AU Magrath, I Adde, M Shad, A Venzon, D Seibel, N Neeley, J Gootenberg, J Arndt, C Nieder, M Owen, W Wilson, W Horak, I AF Magrath, I Adde, M Shad, A Venzon, D Seibel, N Neeley, J Gootenberg, J Arndt, C Nieder, M Owen, W Wilson, W Horak, I TI Relative efficacy of G and GM-CSFs in ameliorating toxicity in an intensive treatment protocol for advanced, diffuse B-cell NHLs, predominantly small noncleaved cell lymphomas. SO BLOOD LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 847 EP 847 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400847 ER PT J AU Tanawattanacharoen, P Molldrem, J Boccuni, P Kirby, MR Young, NS Dunn, DE AF Tanawattanacharoen, P Molldrem, J Boccuni, P Kirby, MR Young, NS Dunn, DE TI Glycosylphosphatidyl-inositol-anchored protein-deficient cells in myelodysplasia. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 890 EP 890 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400890 ER PT J AU Childs, R Sanchez, C Dunbar, C vanRhee, F Raptis, A Phang, S Barrett, AJ AF Childs, R Sanchez, C Dunbar, C vanRhee, F Raptis, A Phang, S Barrett, AJ TI High incidence of severe adeno- and polyomavirus-induced hemorrhagic cystitis following T-cell-depleted bone marrow allotransplantation for hematological malignancy SO BLOOD LA English DT Meeting Abstract C1 NHLBI,BONE MARROW TRANSPLANT UNIT,HEMATOL UNIT,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 988 EP 988 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400988 ER PT J AU Horwitz, EM Prockop, DJ Marini, JC Fitzpatrick, LA Gordon, P Koo, W Neel, M Orchard, P Brenner, MK AF Horwitz, EM Prockop, DJ Marini, JC Fitzpatrick, LA Gordon, P Koo, W Neel, M Orchard, P Brenner, MK TI Bone marrow transplantation (BMT) to correct the mesenchymal defect of children with osteogenesis imperfecta. SO BLOOD LA English DT Meeting Abstract C1 ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38105 USA. NICHHD, BETHESDA, MD USA. MAYO CLIN, ROCHESTER, MN USA. WAYNE STATE UNIV, DETROIT, MI USA. UNIV MINNESOTA, MINNEAPOLIS, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1014 EP 1014 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401014 ER PT J AU Tisdale, JF Sellers, S Hanazono, Y Agricola, BA Donahue, RE Dunbar, CE AF Tisdale, JF Sellers, S Hanazono, Y Agricola, BA Donahue, RE Dunbar, CE TI Clinically-relevant levels of retroviral gene transfer in primates using Flt-3 ligand and autologous stroma. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1040 EP 1040 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401040 ER PT J AU Tisdale, JF Moscow, J Huang, H Sellers, SE Agricola, BA Donahue, RE McDonagh, K Cowan, K Dunbar, CE AF Tisdale, JF Moscow, J Huang, H Sellers, SE Agricola, BA Donahue, RE McDonagh, K Cowan, K Dunbar, CE TI Long term culture retroviral transduction does not improve gene transfer efficiency into rhesus CD34+ PB cells. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1041 EP 1041 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401041 ER PT J AU Sellers, S Tisdale, JF Bodine, DM Williams, DA Karlsson, S Meztger, M Donahue, RE Dunbar, CE AF Sellers, S Tisdale, JF Bodine, DM Williams, DA Karlsson, S Meztger, M Donahue, RE Dunbar, CE TI Comparison of in vivo gene marking efficiency assessed in peripheral blood populations compared to bone marrow progenitors or CD34+ cells. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NIHGR,BETHESDA,MD. INDIANA UNIV,SCH MED,INDIANAPOLIS,IN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1042 EP 1042 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401042 ER PT J AU Dunbar, CE Kohn, DB Schiffman, R Barton, NW Nolta, J Wells, S Esplin, J Pensiero, M Emmons, RVB Leitman, S Kreps, CB Carter, C Kimball, J Young, NS Brady, RO Karlsson, S AF Dunbar, CE Kohn, DB Schiffman, R Barton, NW Nolta, J Wells, S Esplin, J Pensiero, M Emmons, RVB Leitman, S Kreps, CB Carter, C Kimball, J Young, NS Brady, RO Karlsson, S TI Retroviral gene transfer of the glucocerebrosidase gene into PB or BM CD34+ cells from patients with Gaucher disease: Results from a clinical trial. SO BLOOD LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. GENET THERAPY INC,GAITHERSBURG,MD. CHILDRENS HOSP LOS ANGELES,LOS ANGELES,CA 90027. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1044 EP 1044 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401044 ER PT J AU Liu, JM Kim, S Read, EJ Dokal, I Carter, CS Leitman, SF Pensiero, M Young, NS Walsh, CE AF Liu, JM Kim, S Read, EJ Dokal, I Carter, CS Leitman, SF Pensiero, M Young, NS Walsh, CE TI Experimental trial of gene therapy for group C Fanconi anemia patients: 2 year follow-up. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NIH,DTM,BETHESDA,MD 20892. HAMMERSMITH HOSP,LONDON,ENGLAND. GTI NOVARTIS,GAITHERSBURG,MD. UNIV N CAROLINA,GENE THERAPY CTR,CHAPEL HILL,NC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1050 EP 1050 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401050 ER PT J AU Evans, GL Morgan, RA AF Evans, GL Morgan, RA TI Genetic induction of immune tolerance to factor VIII in a murine model for hemophilia A. SO BLOOD LA English DT Meeting Abstract C1 NIH,CLIN GENE THERAPY BRANCH,NATL HUMAN GENOME RES INST,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1053 EP 1053 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401053 ER PT J AU Wang, J Hoshino, T Redner, R Kajigaya, S Liu, JM AF Wang, J Hoshino, T Redner, R Kajigaya, S Liu, JM TI Novel human nuclear receptor co-repressor: Cloning and identification as a binding partner for the ETO proto-oncoprotein. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. UNIV PITTSBURGH,DEPT MED,PITTSBURGH,PA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1078 EP 1078 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401078 ER PT J AU Gutierrez, MI Spangler, G Magrath, IT Bhatia, K AF Gutierrez, MI Spangler, G Magrath, IT Bhatia, K TI The wild type sequence of EBNA-1 is incompatible with EBV associated lymphomas: Evidence that tumor associated EBNA-1 mutations arise in vivo. SO BLOOD LA English DT Meeting Abstract C1 NCI,PEDIAT BRANCH,LYMPHOMA BIOL SECT,NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1081 EP 1081 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401081 ER PT J AU Rao, CR Gutierrez, MI Hussain, A Magrath, I Bhatia, K AF Rao, CR Gutierrez, MI Hussain, A Magrath, I Bhatia, K TI Constitutive expression of Fas-ligand in B cell lymphomas. SO BLOOD LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1084 EP 1084 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401084 ER PT J AU Bendandi, M Sternas, L Reynolds, CW Kwak, LW AF Bendandi, M Sternas, L Reynolds, CW Kwak, LW TI Induction of autologous lymphoma-specific CD8(+) T cells by patient-specific vaccination against follicular lymphoma (FL) in first remission. SO BLOOD LA English DT Meeting Abstract C1 NCI,DEPT EXPT TRANSPLANTAT & IMMUNOL,MED BRANCH,DIV CLIN SCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1096 EP 1096 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401096 ER PT J AU Mukouyama, Y Hara, T Xu, M Tamura, K Donovan, PJ Kim, H Kogo, H Tsuji, K Nakahata, T Miyajima, A AF Mukouyama, Y Hara, T Xu, M Tamura, K Donovan, PJ Kim, H Kogo, H Tsuji, K Nakahata, T Miyajima, A TI Oncostatin M (OSM) supports expansion of hematopoietic progenitors derived from the aorta gonad mesonephros (AGM) region of mouse embryo. SO BLOOD LA English DT Meeting Abstract C1 UNIV TOKYO,INST MOL & CELLULAR BIOSCI,TOKYO,JAPAN. UNIV TOKYO,INST MED SCI,TOKYO,JAPAN. TOKYO UNIV PHARM & LIFE SCI,TOKYO,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1135 EP 1135 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401134 ER PT J AU Hanazono, Y Brown, KE Metzger, M Young, NS Kurtzman, G Donahue, RE Dunbar, CE AF Hanazono, Y Brown, KE Metzger, M Young, NS Kurtzman, G Donahue, RE Dunbar, CE TI Successful in vivo marking of nonhuman primate lymphocytes by recombinant adeno-associated viral vectors: Direct comparison with retroviral vectors. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. AVIGEN INC,ALAMEDA,CA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1156 EP 1156 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401155 ER PT J AU Sabatino, DE Cline, AP Gallagher, P Seidel, NE Garrett, LL Stamatoyannopoulos, G Forget, BG Bodine, DM AF Sabatino, DE Cline, AP Gallagher, P Seidel, NE Garrett, LL Stamatoyannopoulos, G Forget, BG Bodine, DM TI Hemoglobin switching requires both locus control region and globin gene promoter sequences. SO BLOOD LA English DT Meeting Abstract C1 NHGRI,LGT,HEMATOPOEISIS SECT,BETHESDA,MD. YALE UNIV,NEW HAVEN,CT. UNIV WASHINGTON,SEATTLE,WA 98195. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1209 EP 1209 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401208 ER PT J AU Drew, LR Tang, DC Beg, PE Rodgers, GP AF Drew, LR Tang, DC Beg, PE Rodgers, GP TI The role of erythroid-specific trans-activators and DNA-bending in the regulation of human beta-globin gene expression. SO BLOOD LA English DT Meeting Abstract C1 NIDDK,BIOL CHEM LAB,NIH,BETHESDA,MD. UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1211 EP 1211 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401210 ER PT J AU Tang, DC Bodine, D Rodgers, GP AF Tang, DC Bodine, D Rodgers, GP TI Activation of adult delta-globin gene in primary adult erythroid cells. SO BLOOD LA English DT Meeting Abstract C1 NIDDK,MOL HEMATOL SECT,NIH,BETHESDA,MD. NHGRI,HEMATOPOIESIS SECT,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1213 EP 1213 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401212 ER PT J AU Wojda, U Njoroge, JM Miller, JL AF Wojda, U Njoroge, JM Miller, JL TI Endocytosis of crosslinked ligands targeted to glycosylphosphatidylinositol anchored proteins (GPI-proteins) on malignant hematopoietic cells. SO BLOOD LA English DT Meeting Abstract C1 NIDDKD,BIOL CHEM LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1464 EP 1464 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401462 ER PT J AU Belch, AR Bergsagel, D Wilson, D Klimo, P White, D Zee, B Johnston, D AF Belch, AR Bergsagel, D Wilson, D Klimo, P White, D Zee, B Johnston, D TI Is melphalan therapy of multiple myeloma linked to the development of acute leukemia? SO BLOOD LA English DT Meeting Abstract C1 NCI,CLIN TRIALS GRP,EDMONTON,AB,CANADA. CROSS CANC INST,EDMONTON,AB T6G 1Z2,CANADA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1584 EP 1584 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401580 ER PT J AU Fowler, D Whitfield, B Chrobak, P Gress, R AF Fowler, D Whitfield, B Chrobak, P Gress, R TI Donor CD8(+) T cells of Tc2 phenotype potently abrogate marrow rejection by a veto-type mechanism. SO BLOOD LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1611 EP 1611 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401607 ER PT J AU vanRhee, F Jiang, YZ Vigue, F Kirby, M Raptis, A Hensel, N Agarwala, V Read, EJ Barrett, AJ AF vanRhee, F Jiang, YZ Vigue, F Kirby, M Raptis, A Hensel, N Agarwala, V Read, EJ Barrett, AJ TI Granulocyte-colony-stimulating-factor (G-CSF) mobilized CD34+ cells process and present exogenous antigen to T-cells. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BONE MARROW TRANSPLANT UNIT,BETHESDA,MD 20892. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1614 EP 1614 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401610 ER PT J AU KeeverTaylor, CA Collins, NH Carter, S Kelley, L Gee, A Fuller, S AF KeeverTaylor, CA Collins, NH Carter, S Kelley, L Gee, A Fuller, S TI Report on the standardization of clonogeneic hematopoietic precursor assays for the unrelated donor bone marrow transplantation trial. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,UNRELATED DONOR BONE MARROW TRANSPLANTAT TRIAL LA,BETHESDA,MD. MED COLL WISCONSIN,MILWAUKEE,WI 53226. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1639 EP 1639 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401635 ER PT J AU Verfaillie, CM Bhatia, R Steinbuch, M Hirsch, E Arthur, D Delforge, M Miller, JS Weisdorf, D McGlave, PB AF Verfaillie, CM Bhatia, R Steinbuch, M Hirsch, E Arthur, D Delforge, M Miller, JS Weisdorf, D McGlave, PB TI Mobilized autologous BMPC or PBPC transplants for CML: effect of mobilization regimen and BM or PB origin of cells on cytogenetic response in graft and after transplant. SO BLOOD LA English DT Meeting Abstract C1 UNIV MINNESOTA,MINNEAPOLIS,MN. CITY HOPE NATL MED CTR,DUARTE,CA 91010. NIH,BETHESDA,MD 20892. KATHOLIEKE UNIV LEUVEN,B-3001 LOUVAIN,BELGIUM. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1658 EP 1658 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401654 ER PT J AU Barrett, AJ Mavroudis, D Read, EJ Molldrem, J Dunbar, C Carter, C Phang, S AF Barrett, AJ Mavroudis, D Read, EJ Molldrem, J Dunbar, C Carter, C Phang, S TI Granulocyte-colony-stimulating factor (G-CSF) modified, T cell depleted allogeneic bone marrow transplantation for hematological malignancy improves CD34+ cell yield but causes delayed pancytopenia. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,BONE MARROW TRANSPLANT UNIT,HEMATOL BRANCH,BETHESDA,MD 20892. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1668 EP 1668 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401664 ER PT J AU Rowlings, PA Curtis, RE Kingma, D Jaffe, ES Socie, G Deeg, HJ Travis, L Horowitz, MM AF Rowlings, PA Curtis, RE Kingma, D Jaffe, ES Socie, G Deeg, HJ Travis, L Horowitz, MM TI Hodgkin Disease following allogeneic bone marrow transplantation: Long latency and association with Epstein-Barr virus. SO BLOOD LA English DT Meeting Abstract C1 MED COLL WISCONSIN,HLTH POLICY INST,INT BONE MARROW TRANSPLANT REGISTRY,MILWAUKEE,WI 53226. NCI,BETHESDA,MD 20892. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1686 EP 1686 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401682 ER PT J AU Izraeli, S Lowe, L Bertness, V Good, D Kuehn, M Kirsch, IR AF Izraeli, S Lowe, L Bertness, V Good, D Kuehn, M Kirsch, IR TI SIL, a gene commonly disrupted in T-cell acute lymphoblastic leukemia, encodes a cell cycle regulated cytosolic protein which is critical for embryonic development. SO BLOOD LA English DT Meeting Abstract C1 NCI,MED BRANCH,BETHESDA,MD 20892. NCI,EXPT IMMUNOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1723 EP 1723 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401719 ER PT J AU Feldstein, JT Jaffe, ES Berkowitz, JR Burd, PR Tosato, G AF Feldstein, JT Jaffe, ES Berkowitz, JR Burd, PR Tosato, G TI Eotaxin-1, a specific chemoattractant for eosinophils in Hodgkin's disease tissues. SO BLOOD LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. US FDA,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1726 EP 1726 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401722 ER PT J AU Kohn, DB Weinberg, KI Shigeoka, A Carbonaro, D Brooks, J Smogorzewska, EM Barsky, LW Annett, G Nolta, JA Kapoor, N Crooks, GM Elder, M Wara, D Bowen, T Muul, L Hershfield, M Blaese, RM Parkman, R AF Kohn, DB Weinberg, KI Shigeoka, A Carbonaro, D Brooks, J Smogorzewska, EM Barsky, LW Annett, G Nolta, JA Kapoor, N Crooks, GM Elder, M Wara, D Bowen, T Muul, L Hershfield, M Blaese, RM Parkman, R TI PEG-ADA reduction in recipients of ADA gene-transduced autologous umbilical cord blood CD34+ cells. SO BLOOD LA English DT Meeting Abstract C1 CHILDRENS HOSP LOS ANGELES,LOS ANGELES,CA 90027. UNIV UTAH,SALT LAKE CITY,UT 84112. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. DUKE UNIV,DURHAM,NC 27706. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1798 EP 1798 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401794 ER PT J AU Morgan, RA Bunnell, B Walker, R Lane, C Blaese, RM AF Morgan, RA Bunnell, B Walker, R Lane, C Blaese, RM TI An AIDS gene therapy trial in HIV-1 discordant identical twins. SO BLOOD LA English DT Meeting Abstract C1 NATL HUMAN GENOME RES INST,CLIN GENE THERAPY BRANCH,BETHESDA,MD 20892. NIAID,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1803 EP 1803 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401799 ER PT J AU Dunn, DE Nagakura, S Tanawattanacharoen, P Knez, J Medof, ME Young, NS AF Dunn, DE Nagakura, S Tanawattanacharoen, P Knez, J Medof, ME Young, NS TI The PNH phenotype (GPI-anchored protein-deficiency) protects hematopoietic targets against-lymphocytotoxic attack. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1811 EP 1811 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401807 ER PT J AU Fu, KL Lo, JR TenFoe, JRL Joenje, H Rao, KW Liu, JM Walsh, CE AF Fu, KL Lo, JR TenFoe, JRL Joenje, H Rao, KW Liu, JM Walsh, CE TI Functional correction of Fanconi anemia group A hematopoietic cells - clinical and diagnostic implications. SO BLOOD LA English DT Meeting Abstract C1 UNIV N CAROLINA,GENE THERAPY CTR,CHAPEL HILL,NC. FREE UNIV AMSTERDAM,DEPT GENET,NL-1081 HV AMSTERDAM,NETHERLANDS. NHLBI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1926 EP 1926 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401922 ER PT J AU Rosenfeld, SJ Young, NS AF Rosenfeld, SJ Young, NS TI Aplastic anemia treated by immunosuppression is a chronic relapsing illness, but prognosis is unaffected by relapse. SO BLOOD LA English DT Meeting Abstract C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CLIN PATHOL,HEMATOL SERV,BETHESDA,MD 20892. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1929 EP 1929 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401925 ER PT J AU Youssoufian, H Hoshino, T Liu, JM Joseph, P Jaiswal, AK AF Youssoufian, H Hoshino, T Liu, JM Joseph, P Jaiswal, AK TI Binding of the Fanconi anemia group C protein to NADPH cytochrome P-450 reductase: Implications for mitomycin C activation. SO BLOOD LA English DT Meeting Abstract C1 BAYLOR COLL MED,DEPT MOL & HUMAN GENET,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1945 EP 1945 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401941 ER PT J AU Brown, KE Young, NS AF Brown, KE Young, NS TI HLA antigens in patients with severe aplastic anemia (SAA) and hepatitis-associated aplastic anemia. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1950 EP 1950 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401946 ER PT J AU Jiang, YZ Clave, E Molldrem, J Raptis, A vanRhee, F Mavroudis, D Hensel, N Barrett, AJ AF Jiang, YZ Clave, E Molldrem, J Raptis, A vanRhee, F Mavroudis, D Hensel, N Barrett, AJ TI Bone marrow and blood show consistent differences in the T-cell receptor (TCR) V beta repertoire. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,BONE MARROW TRANSPLANTAT UNIT,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2014 EP 2014 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402010 ER PT J AU McKeown, L Hansmann, K Wilson, O Gralnick, H Rosenfeld, K Rosenfeld, S Horne, M Rick, M AF McKeown, L Hansmann, K Wilson, O Gralnick, H Rosenfeld, K Rosenfeld, S Horne, M Rick, M TI The role of von Willebrand factor in the hemostatic defect in Hermansky-Pudlak syndrome. SO BLOOD LA English DT Meeting Abstract C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,SERV HEMATOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2080 EP 2080 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402076 ER PT J AU Miller, JL Njoroge, JM Gubin, AN Rodgers, GP AF Miller, JL Njoroge, JM Gubin, AN Rodgers, GP TI Prospective identification and isolation of colony forming erythroblasts generated in liquid cultured blood. SO BLOOD LA English DT Meeting Abstract C1 NIDDKD,BIOL CHEM LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2124 EP 2124 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402120 ER PT J AU Molldrem, JJ Mavroudis, D Jiang, YZ Dermime, S StetlerStevenson, MA Amen, MJ Barrett, AJ AF Molldrem, JJ Mavroudis, D Jiang, YZ Dermime, S StetlerStevenson, MA Amen, MJ Barrett, AJ TI Hematological response in cyclosporine-treated T-cell large granular lymphocytic leukemia (T-LGL) correlates with an increase killer inhibitory receptor (KIR) expression and loss of CFU-GM inhibition. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. RI Dermime, Said/C-6235-2009 OI Dermime, Said/0000-0002-5526-7496 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2241 EP 2241 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402237 ER PT J AU Molldrem, JJ Clave, E Raptis, A Hensel, N Barrett, AJ AF Molldrem, JJ Clave, E Raptis, A Hensel, N Barrett, AJ TI Cytotoxic T cell lines (CTL) specific for a proteinase 3 (P3) - derived peptide lyse a P3-transfected B-cell line and inhibit growth of clonogenic chronic myeloid leukemia (CML) cells. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BONE MARROW TRANSPLANT UNIT,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2242 EP 2242 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402238 ER PT J AU Fanslow, WC Lofton, TE Brasel, K Rousseau, AC Murphy, WJ Armitage, RJ Ghalie, R AF Fanslow, WC Lofton, TE Brasel, K Rousseau, AC Murphy, WJ Armitage, RJ Ghalie, R TI Recombinant human CD40 ligand (RhuCD40L) mediates tumor growth inhibition and apoptosis of Burkitt's B-cell lymphoma in vitro and in SCID mice. SO BLOOD LA English DT Meeting Abstract C1 NCI,FCRD,FREDERICK,MD 21701. IMMUNEX CORP,SEATTLE,WA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2274 EP 2274 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402270 ER PT J AU Kreitman, RJ White, JD Pearson, D Top, LE Waldmann, TA Pastan, I AF Kreitman, RJ White, JD Pearson, D Top, LE Waldmann, TA Pastan, I TI Phase I clinical trial of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) in patients with hematologic malignancies. SO BLOOD LA English DT Meeting Abstract C1 NCI,MED BRANCH,NIH,BETHESDA,MD 20892. NCI,METAB BRANCH,NIH,BETHESDA,MD 20892. NCI,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2282 EP 2282 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402278 ER PT J AU Byrd, JC Shinn, CA Bedi, A Waselenko, JK Fuchs, E Flinn, IW Diehl, LF Sausville, E Grever, MR AF Byrd, JC Shinn, CA Bedi, A Waselenko, JK Fuchs, E Flinn, IW Diehl, LF Sausville, E Grever, MR TI Flavopiridol has marked in vitro activity against human B-chronic lymphocytic leukemia (B-CLL) and induces apoptosis independent of p53 status. SO BLOOD LA English DT Meeting Abstract C1 WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. NATL CANC INST,BETHESDA,MD. JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2366 EP 2366 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402362 ER PT J AU Byrd, JC Waselenko, JK Shinn, CA Bedi, A Flinn, IW Diehl, LF Sausville, E Grever, MR AF Byrd, JC Waselenko, JK Shinn, CA Bedi, A Flinn, IW Diehl, LF Sausville, E Grever, MR TI FR901228, a novel antitumor bicyclic depsipeptide, has significant in vitro activity against human B-chronic lymphocytic leukemia (B-CLL). SO BLOOD LA English DT Meeting Abstract C1 WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. NCI,BETHESDA,MD 20892. JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2367 EP 2367 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402363 ER PT J AU Waselenko, JK Przygodzki, R Grever, MR Shinn, CA Sausville, E Byrd, JC AF Waselenko, JK Przygodzki, R Grever, MR Shinn, CA Sausville, E Byrd, JC TI Flavopiridol, UCN-01, FR901228 and gemcitabine have significant in vitro activity in de novo B-cell prolymphocytic leukemia with aberrant p53 Function. SO BLOOD LA English DT Meeting Abstract C1 WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. NCI,BETHESDA,MD 20892. JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2369 EP 2369 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402365 ER PT J AU Mackall, CL Punt, J Morgan, P Farr, AG Gress, RE AF Mackall, CL Punt, J Morgan, P Farr, AG Gress, RE TI Thymic T cell regenerative capacity in aged hosts given young bone marrow is quantitatively reduced but qualitatively intact. SO BLOOD LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. UNIV WASHINGTON,SEATTLE,WA 98195. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2374 EP 2374 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402370 ER PT J AU Clave, E Molldrem, J Hensel, N Raptis, A Barrett, AJ AF Clave, E Molldrem, J Hensel, N Raptis, A Barrett, AJ TI Donor-recipient polymorphism of the proteinase 3 gene in bone marrow transplantation. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,BONE MARROW TRANSPLANTAT UNIT,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2379 EP 2379 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402375 ER PT J AU Raptis, A Clave, E Mavroudis, D vanRhee, F Hensel, N Ledakis, P Molldrem, J Barrett, AJ AF Raptis, A Clave, E Mavroudis, D vanRhee, F Hensel, N Ledakis, P Molldrem, J Barrett, AJ TI Polymorphism of the leukocyte differentiation antigen CD33 - A myeloid-restricted minor antigen? SO BLOOD LA English DT Meeting Abstract C1 NHLBI,BONE MARROW TRANSPLANT UNIT,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2386 EP 2386 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402382 ER PT J AU Hakim, F Cepeda, R Cusack, G Halverson, D Weng, D Gress, R AF Hakim, F Cepeda, R Cusack, G Halverson, D Weng, D Gress, R TI Increased susceptibility to apoptosis in CD4 cells post autologous transplantation. SO BLOOD LA English DT Meeting Abstract C1 NATL CANC INST,MED BRANCH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2408 EP 2408 PN 1 PG 2 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402404 ER PT J AU Adya, N Liu, PP AF Adya, N Liu, PP TI Biochemical analyses of inv(16) fusion gene CBFB-MYH11. SO BLOOD LA English DT Meeting Abstract C1 NATL HUMAN GENOME RES INST,LGT,NIH,BETHESDA,MD. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2477 EP 2477 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402473 ER PT J AU vanRhee, F Jiang, YZ Vigue, F Carter, C Raptis, A Read, EJ Barrett, AJ AF vanRhee, F Jiang, YZ Vigue, F Carter, C Raptis, A Read, EJ Barrett, AJ TI Highly purified CD34+ cells induce primary and secondary immune responses despite lack of expression of co-stimulatory molecules on resting cells. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,BONE MARROW TRANSPLANT UNIT,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2508 EP 2508 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402504 ER PT J AU Broxmeyer, HE Cooper, S Hangoc, G Gao, JL Murphy, PM AF Broxmeyer, HE Cooper, S Hangoc, G Gao, JL Murphy, PM TI Chemokine receptor CCR1 acts as a dominant receptor for MIP-1 alpha enhancement of proliferation of mature progenitors in vitro, MIP-1 alpha mobilization of progenitors in vivo and MIP-1 alpha enhancement of G-CSF induced mobilization, but not for MIP-1 alpha suppression of immature progenitors in vitro: Effects elucidated using CCR1 knock-out mice. SO BLOOD LA English DT Meeting Abstract C1 INDIANA UNIV,SCH MED,DEPT MICROIMMUNOL,INDIANAPOLIS,IN. INDIANA UNIV,SCH MED,DEPT MED,INDIANAPOLIS,IN. INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,INDIANAPOLIS,IN 46202. NIAID,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2541 EP 2541 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402537 ER PT J AU Sloand, EM Kumar, PN Zella, D Young, NS Gallo, RC Weichold, FF AF Sloand, EM Kumar, PN Zella, D Young, NS Gallo, RC Weichold, FF TI HIV-1 protease inhibitor modulates activation of peripheral blood derived CD4+ T-cells and decreases their susceptibility to apoptosis in vitro and in vivo. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. GEORGETOWN UNIV HOSP,WASHINGTON,DC 20007. UNIV MARYLAND,INST HUMAN VIROL,BALTIMORE,MD 21201. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2568 EP 2568 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402564 ER PT J AU Flinn, IW Kopecky, KJ Foucar, MK Head, D Bennett, JM Hutchison, RE Corbett, WEN Cassileth, PA Habermann, T Golomb, H Rai, K Eisenhauer, E Appelbaum, FR Cheson, BD Grever, M AF Flinn, IW Kopecky, KJ Foucar, MK Head, D Bennett, JM Hutchison, RE Corbett, WEN Cassileth, PA Habermann, T Golomb, H Rai, K Eisenhauer, E Appelbaum, FR Cheson, BD Grever, M TI Long-term results in hairy cell leukemia (HCL) treated with pentostatin. SO BLOOD LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV, BALTIMORE, MD 21218 USA. SW ONCOL GRP, CTR STAT, SEATTLE, WA USA. UNIV NEW MEXICO HOSP, ALBUQUERQUE, NM USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38105 USA. UNIV ROCHESTER, ROCHESTER, NY 14627 USA. SUNY HLTH SCI CTR, SYRACUSE, NY 13210 USA. KINGSTON GEN HOSP, KINGSTON, ON K7L 2V7, CANADA. UNIV MIAMI, MIAMI, FL 33152 USA. MAYO CLIN, ROCHESTER, MN USA. UNIV CHICAGO, CHICAGO, IL 60637 USA. LONG ISL JEWISH MED CTR, NEW HYDE PK, NY USA. CANADIAN CLIN TRIALS GRP, NATL CANC INST, KINGSTON, ON, CANADA. NCI, BETHESDA, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2575 EP 2575 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402571 ER PT J AU Kwak, LW Sternas, LA Jagannath, S Siegel, D Munshi, NC Barlogie, B AF Kwak, LW Sternas, LA Jagannath, S Siegel, D Munshi, NC Barlogie, B TI T-cell responses elicited by immunization of multiple myeloma patients with idiotypic M-protein plus GM-CSF in remission after autologous transplantation (PSCT). SO BLOOD LA English DT Meeting Abstract C1 NCI,DEPT EXP TRANSPLANT & IMMUNOL,MED BRANCH,DCS,BETHESDA,MD 20892. UNIV ARKANSAS MED SCI,DIV HEMATOL,LITTLE ROCK,AR 72205. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2576 EP 2576 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402572 ER PT J AU Tisdale, JF Stewart, AK Dickstein, B Dube, ID Cappe, D Dunbar, CE Brown, KE AF Tisdale, JF Stewart, AK Dickstein, B Dube, ID Cappe, D Dunbar, CE Brown, KE TI Human herpesvirus 8 in patients with multiple myeloma. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. TORONTO GEN HOSP,TORONTO,ON,CANADA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2614 EP 2614 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402610 ER PT J AU Sloand, EM Maciejewski, JP Sato, T Kim, S Young, NS AF Sloand, EM Maciejewski, JP Sato, T Kim, S Young, NS TI Inhibition of interleukin-converting enzyme in human hematopoietic progenitor cells results in blockade of cytokine-mediated apoptosis and expansion of their proliferative potential. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2650 EP 2650 PN 1 PG 2 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402646 ER PT J AU Horwitz, M Malech, HL Anderson, SM Girard, LJ Bodine, D Orlic, D AF Horwitz, M Malech, HL Anderson, SM Girard, LJ Bodine, D Orlic, D TI G-CSF mobilized peripheral blood CD34+ CD38- hematopoietic stem cells (HSC) are candidate target cells for high efficiency retrovirus gene transfer. SO BLOOD LA English DT Meeting Abstract C1 NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. NIH,NATL HUMAN GENOME RES INST,HEMATOPOIESIS SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2669 EP 2669 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402665 ER PT J AU Wahlfors, JJ Xanthopoulos, KG Morgan, RA AF Wahlfors, JJ Xanthopoulos, KG Morgan, RA TI Cytoplasmic production of retroviral vectors with Semliki Forest virus: A new tool for gene therapy of hemophilia. SO BLOOD LA English DT Meeting Abstract C1 NHGRI,CLIN GENE THERAPY BRANCH,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2673 EP 2673 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402669 ER PT J AU Allerson, CA Rouault, TA Cazzola, M AF Allerson, CA Rouault, TA Cazzola, M TI Specific mutations in the iron-responsive element (IRE) of ferritin L-chain mRNA variably affect IRE's affinity for both iron regulatory proteins (IRPs) 1 and 2. SO BLOOD LA English DT Meeting Abstract C1 NIH,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. UNIV PAVIA,SCH MED,IRCCS,POLICLIN SAN MATTEO,I-27100 PAVIA,ITALY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2679 EP 2679 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402675 ER PT J AU Joenje, H Liu, JM Panayiotidis, P Pronk, JC Arwert, F Dokal, I Gluckman, E AF Joenje, H Liu, JM Panayiotidis, P Pronk, JC Arwert, F Dokal, I Gluckman, E TI Spontaneous lymphocyte mosaicism in Fanconi anemia: Implications for diagnosis and treatment. SO BLOOD LA English DT Meeting Abstract C1 FREE UNIV AMSTERDAM,DEPT HUMAN GENET,AMSTERDAM,NETHERLANDS. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. UNIV ATHENS,SCH MED,GR-10679 ATHENS,GREECE. HAMMERSMITH HOSP,LONDON,ENGLAND. HOP ST LOUIS,PARIS,FRANCE. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2752 EP 2752 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500062 ER PT J AU Sloand, EM Maciejewski, JP Kirby, M Kim, S Young, NS AF Sloand, EM Maciejewski, JP Kirby, M Kim, S Young, NS TI Bone marrow and peripheral blood lymphocytes of patients with severe aplastic anemia contain IFN-gamma detectable by flow cytometric analysis. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2774 EP 2774 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500084 ER PT J AU TranSonTay, R Damay, E Lottenberg, R Noguchi, C Schechter, A AF TranSonTay, R Damay, E Lottenberg, R Noguchi, C Schechter, A TI Viscosity of blood cells in sickle cell disease. SO BLOOD LA English DT Meeting Abstract C1 NIDDK,BIOL CHEM LAB,NIH,BETHESDA,MD. UNIV FLORIDA,GAINESVILLE,FL 32611. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2829 EP 2829 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500139 ER PT J AU Matsuo, K Procter, J Eiber, G Stroncek, D AF Matsuo, K Procter, J Eiber, G Stroncek, D TI Expression of NA1 and NA2 alleles of Fc-gamma-receptor IIIB in Japanese, African American and white people. SO BLOOD LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. AMER RED CROSS,N CENT BLOOD SERV,ST PAUL,MN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2899 EP 2899 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500209 ER PT J AU Raptis, A Mavroudis, D Jiang, YZ vanRhee, F Molldrem, J Barrett, AJ AF Raptis, A Mavroudis, D Jiang, YZ vanRhee, F Molldrem, J Barrett, AJ TI P21 is specifically inhibited in the initial phase of the mixed lymphocyte reaction. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,BONE MARROW TRANSPLANT UNIT,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2973 EP 2973 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500283 ER PT J AU Alpan, O Horne, MK Parker, RI AF Alpan, O Horne, MK Parker, RI TI Heparin induced platelet activation is associated with Na+ loading of platelets. SO BLOOD LA English DT Meeting Abstract C1 NIH,CTR CLIN,SERV HEMATOL,BETHESDA,MD 20892. SUNY STONY BROOK,DEPT PEDIAT,STONY BROOK,NY 11794. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2980 EP 2980 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500290 ER PT J AU Williams, S Sano, M Smith, N Gralnick, H AF Williams, S Sano, M Smith, N Gralnick, H TI Glycocalicin levels in the plasma of HIV+ patients: An indicator of platelet turnover. SO BLOOD LA English DT Meeting Abstract C1 NIH,DEPT CLIN PATHOL,WARREN G MAGNUSON CTR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3115 EP 3115 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500425 ER PT J AU Horne, M Merryman, P Cullinane, A Hutchison, K AF Horne, M Merryman, P Cullinane, A Hutchison, K TI Fibrinolysis in clots of blood obtained by fingerstick. SO BLOOD LA English DT Meeting Abstract C1 NIH,DEPT CLIN PATHOL,CC,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3141 EP 3141 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500451 ER PT J AU Lozier, JN Morgan, RA AF Lozier, JN Morgan, RA TI Sequence of cDNA for coagulation factor IX from the rhesus macaque and the derived amino acid sequence. SO BLOOD LA English DT Meeting Abstract C1 NATL HUMAN GENOME RES INST,CLIN GENE THERAPY BRANCH,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3150 EP 3150 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500460 ER PT J AU Horne, M Mayo, DJ Chang, R AF Horne, M Mayo, DJ Chang, R TI Treatment of VAD-related axillary-subclavian vein thrombosis with pulse-spray rTPA and anticoagulation. SO BLOOD LA English DT Meeting Abstract C1 NIH,DEPT CLIN PATHOL,CC,BETHESDA,MD 20892. NIH,DEPT RADIOL,CC,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3230 EP 3230 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500540 ER PT J AU Heim, KF Klein, HG AF Heim, KF Klein, HG TI Acute post-operative hemolysis in a patient with previously undetected sickle trait. SO BLOOD LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3305 EP 3305 PN 2 PG 2 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500615 ER PT J AU Stroncek, DF Procter, J Steitz, M AF Stroncek, DF Procter, J Steitz, M TI Cefotetan-dependent hemolysis: Comparison of cefotetan and penicillin-dependent red cell antibodies. SO BLOOD LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3338 EP 3338 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500648 ER PT J AU Bloom, ML SimonStoos, KL Young, NS AF Bloom, ML SimonStoos, KL Young, NS TI Assessment of quiescent stem cell engraftment in the transplant model. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3349 EP 3349 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500659 ER PT J AU Wang, M Fibach, E Rodgers, GP AF Wang, M Fibach, E Rodgers, GP TI Stimulation of erythroid progenitors by low concentration of hydroxyurea. SO BLOOD LA English DT Meeting Abstract C1 NIDDK,MOL HEMATOL SECT,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3397 EP 3397 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500707 ER PT J AU Harris, JE Plate, JMD Gebel, H Shadidi, H Stratakis, CA Anderson, KM AF Harris, JE Plate, JMD Gebel, H Shadidi, H Stratakis, CA Anderson, KM TI What factors participate in the induction of type I programmed cell death induced in U937 cells by inhibitors of 5-lipoxygenase? SO BLOOD LA English DT Meeting Abstract C1 RUSH MED COLL,DEPT MED,CHICAGO,IL 60612. RUSH MED COLL,DEPT MICROBIOL IMMUNOL,CHICAGO,IL 60612. RUSH MED COLL,DEPT BIOCHEM,CHICAGO,IL 60612. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3478 EP 3478 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500788 ER PT J AU Schwartz, GN Rothwell, SW Zujewski, J Halverson, DC OShaughnessy, J Cowan, KH Gress, RE AF Schwartz, GN Rothwell, SW Zujewski, J Halverson, DC OShaughnessy, J Cowan, KH Gress, RE TI Inhibitory effects of postchemotherapy and GM-CSF pretreated marrow stromal cell layers on hematopoiesis from normal donor CD34+ cells. SO BLOOD LA English DT Meeting Abstract C1 WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,WASHINGTON,DC 20307. NCI,MED BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3509 EP 3509 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500819 ER PT J AU Donahue, RE Wersto, RP Metzger, ME Wang, M Leitman, SF Noguchi, CT Schechter, AN Rodgers, GP AF Donahue, RE Wersto, RP Metzger, ME Wang, M Leitman, SF Noguchi, CT Schechter, AN Rodgers, GP TI Enhanced F-cell production in non-human primates following granulocyte-colony stimulating factor (G-CSF) and stem cell factor (SCF) mobilization and reinfusion of peripheral blood mononuclear (PBMN) cells. SO BLOOD LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NIH,CC,BETHESDA,MD 20892. NIDDK,BIOL CHEM LAB,BETHESDA,MD. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3550 EP 3550 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500860 ER PT J AU Janik, J Kopp, W Eliot, H Alvord, WG Curti, B Gause, B Elwood, P Alexander, HR AF Janik, J Kopp, W Eliot, H Alvord, WG Curti, B Gause, B Elwood, P Alexander, HR TI Dissimilar regulation of leptin expression by IL-1 and TNF in humans. SO BLOOD LA English DT Meeting Abstract C1 NCI,MED BRANCH,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. SAIC FREDERICK,FREDERICK,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3555 EP 3555 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500865 ER PT J AU Raptis, A Jiang, YZ Ledakis, P Barrett, AJ AF Raptis, A Jiang, YZ Ledakis, P Barrett, AJ TI Fludarabine specifically inhibits the expression of cyclin dependent kinase inhibitor P21 in molt-4 cell line. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,BONE MARROW TRANSPLANT UNIT,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3654 EP 3654 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500964 ER PT J AU Berg, PE Huguenin, S Ruscetti, FW Karp, JE Ross, DD Haga, S AF Berg, PE Huguenin, S Ruscetti, FW Karp, JE Ross, DD Haga, S TI BP1, a new homeobox gene, is aberrantly expressed in acute leukemias. SO BLOOD LA English DT Meeting Abstract C1 NCI,FRDC,LAB LEUKOCYTE BIOL,FREDERICK,MD 21701. UNIV MARYLAND,SCH MED,DEPT PEDIAT,DIV HUMAN GENET,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,GREENEBAUM CANC CTR,BALTIMORE,MD 21201. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3670 EP 3670 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500980 ER PT J AU Byrd, JC Waselenko, JK Shinn, CA Miller, C Gore, S Sausville, E Grever, MR AF Byrd, JC Waselenko, JK Shinn, CA Miller, C Gore, S Sausville, E Grever, MR TI FR901228, a novel antitumor bicyclic depsipeptide, has marked in vitro activity against both the K-562 cell line and human acute leukemia cells. SO BLOOD LA English DT Meeting Abstract C1 WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. NCI,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,BALTIMORE,MD 21205. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3810 EP 3810 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42501120 ER PT J AU Hall, PD Kreitman, RJ Willingham, MC Frankel, AE AF Hall, PD Kreitman, RJ Willingham, MC Frankel, AE TI Pharmacology and toxicology of DT388-GM-CSF, a fusion toxin consisting of a truncated diphtheria toxin linked to granulocyte-macrophage colony stimulating factor (GM-CSF). SO BLOOD LA English DT Meeting Abstract C1 MED UNIV S CAROLINA,HOLLINGS CANC CTR,CHARLESTON,SC 29425. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3828 EP 3828 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42501138 ER PT J AU Shinn, CA Byrd, JC Waselenko, JK Sausville, E Miller, C Gore, S Grever, MR AF Shinn, CA Byrd, JC Waselenko, JK Sausville, E Miller, C Gore, S Grever, MR TI UCN-01 has significant in vitro activity in both the resistant K562 cell line and human acute leukemia cells. SO BLOOD LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21205. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3848 EP 3848 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42501158 ER PT J AU Waselenko, JK Byrd, JC Shinn, CA Miller, C Gore, S Sausville, E Grever, MR AF Waselenko, JK Byrd, JC Shinn, CA Miller, C Gore, S Sausville, E Grever, MR TI Flavopiridol has marked in vitro activity against the K-562 cell line and human acute leukemia cells. SO BLOOD LA English DT Meeting Abstract C1 WALTER REED ARMY MED CTR,HEMATOL ONCOL SERV,WASHINGTON,DC 20307. NCI,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,JOHNS HOPKINS ONCOL CTR,DIV HEMATOL MALIGNANCY,BALTIMORE,MD 21205. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3858 EP 3858 PN 2 PG 2 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42501168 ER PT J AU Bishop, PC Wilson, WH Janik, J Little, R Pearson, D Jaffe, ES Elwood, PC AF Bishop, PC Wilson, WH Janik, J Little, R Pearson, D Jaffe, ES Elwood, PC TI CNS involvement in primary mediastinal (thymic) large B-cell lymphoma. SO BLOOD LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3874 EP 3874 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42501184 ER PT J AU Himmelmann, A Riva, A Wilson, GL Lucas, BP Thevenin, C Kehrl, JH AF Himmelmann, A Riva, A Wilson, GL Lucas, BP Thevenin, C Kehrl, JH TI PU.1/Pip and basic helix loop helix zipper transcription factors interact with binding sites in the CD20 promoter to help confer lineage- and stage-specific expression of CD20 in B lymphocytes SO BLOOD LA English DT Article ID CELL DIFFERENTIATION; REGULATES EXPRESSION; GENE-EXPRESSION; IMMUNOGLOBULIN ENHANCER; FAMILY MEMBER; MOTIF PRESENT; ETS ONCOGENE; CHAIN GENE; FACTOR USF; PROTEINS AB CD20 is a B-lineage-specific gene expressed at the pre-B-cell stage of B-cell development that disappears on differentiation to plasma cells. As such, it serves as an excellent paradigm for the study of lineage and developmental stage-specific gene expression. Using in vivo footprinting we identified two sites in the promoter at -45 and -160 that were occupied only in CD20(+) B cells. The -45 site is an E box that binds basic helix-loop-helix-zipper proteins whereas the -160 site is a composite PU.1 and Pip binding site. Transfection studies with reporter constructs and various expression vectors verified the importance of these sites. The composite PU.1 and Pip site likely accounts for both lineage and stage-specific expression of CD20 whereas the CD20 E box binding proteins enhance overall promoter activity and may link the promoter to a distant enhancer. C1 NIAID,IMMUNOREGULAT LAB,CELL MOL IMMUNOL SECT B,NIH,BETHESDA,MD 20892. OI Kehrl, John/0000-0002-6526-159X NR 50 TC 68 Z9 68 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 BP 3984 EP 3995 PG 12 WC Hematology SC Hematology GA YF299 UT WOS:A1997YF29900020 PM 9354667 ER PT J AU Candotti, F Oakes, SA Johnston, JA Giliani, S Schumacher, RF Mella, P Fiorini, M Ugazio, AG Badolato, R Notarangelo, LD Bozzi, F Macchi, P Strina, D Vezzoni, P Blaese, RM OShea, JJ Villa, A AF Candotti, F Oakes, SA Johnston, JA Giliani, S Schumacher, RF Mella, P Fiorini, M Ugazio, AG Badolato, R Notarangelo, LD Bozzi, F Macchi, P Strina, D Vezzoni, P Blaese, RM OShea, JJ Villa, A TI Structural and functional basis for JAK3-deficient severe combined immunodeficiency SO BLOOD LA English DT Article ID COMMON GAMMA-CHAIN; JAK2 TYROSINE KINASE; MICE LACKING JAK3; SIGNAL-TRANSDUCTION; JANUS KINASE; INTERLEUKIN-4 RECEPTOR; LYMPHOID DEVELOPMENT; ENDOTHELIAL-CELLS; B-CELLS; IL-4 AB Mutations of the Janus family kinase JAK3 have been found to be responsible for autosomal recessive severe combined immunodeficiency (SCID) in humans. We report here the analysis of four new unrelated patients affected by JAK3-deficient SCID. The genetic defects were heterogeneous and included a large intragenic deletion as well as different point mutations, leading to missense substitutions, early stop codons, or splicing defects. We performed a series of studies of the biochemical events induced by cytokines on lymphoblastoid B-cell lines obtained from these patients. Abnormalities in tyrosine phosphorylation of JAK3 in response to interleukin-9 (IL-2) and IL-4 were present in all patients. Accordingly, IL-2-mediated phosphorylation of STATE was also absent or barely detectable. On the contrary, in all cases, we could show reduced but clear phosphorylation of STATE upon IL-4 stimulation. In one patient carrying a single amino acid change (Glu481Gly) in the JH3 domain of JAK3, we observed partially conserved IL-2 responses resulting in reduced but detectable levels of JAK3 and STAT5 phosphorylation. Interestingly, the patient bearing this mutation developed a substantial number of circulating CD4(+)/CD45RO(+) activated T lymphocytes that were functionally impaired. In two cases, patients' cells expressed JAK3 proteins with mutations in the JH2 pseudo-kinase domain. A single cysteine to arginine substitution (Cys759Arg) in this region resulted in high basal levels of constitutive JAK3 tyrosine phosphorylation unresponsive to either downregulation by serum starvation or cytokine-mediated upregulation. The characterization of the genetic defects and biochemical abnormalities in these JAK3-deficient patients will help define the role of JAK3 in the ontogeny of a competent immune system and may lead to a better understanding of the JAK3 functional domains. (C) 1997 by The American Society of Hematology. C1 CNR,IST TECNOL BIOMED AVANZATE,I-20131 MILAN,ITALY. NIH,NATL CTR HUMAN GENOME RES,CLIN GENE THERAPY BRANCH,BETHESDA,MD 20892. NIAMSD,LEUKOCYTE CELL BIOL SECT,NIH,BETHESDA,MD 20892. UNIV BRESCIA,DEPT PEDIAT,BRESCIA,ITALY. RI Badolato, Raffaele/A-8081-2010; Notarangelo, Luigi/F-9718-2016; OI Badolato, Raffaele/0000-0001-7375-5410; Notarangelo, Luigi/0000-0002-8335-0262; Villa, Anna/0000-0003-4428-9013 FU Telethon [A.042] NR 31 TC 91 Z9 97 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 BP 3996 EP 4003 PG 8 WC Hematology SC Hematology GA YF299 UT WOS:A1997YF29900021 PM 9354668 ER PT J AU Waller, CF Maran, A Paranjape, JM Li, GY Xiao, W Zhang, K Kalaycioglu, M Torrence, PF Silverman, RH AF Waller, CF Maran, A Paranjape, JM Li, GY Xiao, W Zhang, K Kalaycioglu, M Torrence, PF Silverman, RH TI Specific degradation of BCR/ABL mRNA and growth suppression of CML cells by 2-5A antisense oligonucleotides. SO BLOOD LA English DT Meeting Abstract C1 CLEVELAND CLIN FDN,DEPT CANC BIOL,RES INST,CLEVELAND,OH 44195. CLEVELAND CLIN FDN,DEPT HEMATOL & ONCOL,CLEVELAND,OH 44195. NIDDKD,SECT BIOCHEM CHEM,NIH,BETHESDA,MD 20892. UNIV FREIBURG,DEPT INTERNAL MED HEMATOL ONCOL 1,FREIBURG MED CTR,FREIBURG,GERMANY. NR 0 TC 1 Z9 1 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 4020 EP 4020 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42501329 ER PT J AU Jiang, YZ Molldrem, J Clave, E Mavroudis, D Barrett, AJ AF Jiang, YZ Molldrem, J Clave, E Mavroudis, D Barrett, AJ TI Response to antithymocyte globulin (ATG) treatment in patients with myelodysplastic syndrome (MDS) is associated with reduced clonality of the TCR V beta repertoire. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BONE MARROW TRANSPLANT UNIT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 4042 EP 4042 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42501351 ER PT J AU Mock, BA Hartley, J LeTissier, P Wax, JS Potter, M AF Mock, BA Hartley, J LeTissier, P Wax, JS Potter, M TI The plasmacytoma resistance gene, Pctr2, delays the onset of tumorigenesis and resides in the telomeric region of chromosome 4 SO BLOOD LA English DT Article ID LOCUS AFFECTING RESISTANCE; MURINE LEUKEMIA VIRUSES; MOUSE CHROMOSOME-4; MICE; MAP; NEUROBLASTOMA; INSTABILITY; INFECTION; DELETION; CELLS AB Mouse plasmacytomas share pathogenetic features in common with both multiple myeloma and Burkitt's lymphoma in humans. Susceptibility to plasmacytoma induction by intraperitoneal pristane in mice is controlled by multiple genes. At least two of these genes reside on mouse chromosome 4 in regions of the genome sharing linkage homology with human chromosomes 9p21, 1p32. and 1p36. A series of congenic strains recombinant for regions of mouse chromosome 4 in the vicinity of the Pctr2 predisposition locus were created and typed for their tumor susceptibility/resistance-phenotypes, These strains were derived by introgressively backcrossing alleles from resistant DBA/2 mice onto the susceptible BALB/cAnPt background. Six resistant and two susceptible strains were allelotyped for 10 genes and 49 random DNA markers to identify the smallest region of overlap in the resistant strains. These studies have determined that the Pctr2 locus resides in either a 500-kb interval proximal to Nppa, or in a 1- to 2-centiMorgan (cM) interval distal to Nppa. In these congenic strain analyses, the Nppa and Fv1 loci, in addition to genes within about 1 cM of these loci, have been excluded as candidates for the Pctr2 locus. A relevant locus that may reside in this interval is Rep2; it is associated with the efficiency of repairing X-ray induced DNA damage sustained during the G2 phase of the mitotic cycle. The Pctr2 locus acts in a codominant fashion. F1 hybrids between resistant and susceptible congenic strains exhibit a reduced tumor incidence and a significant delay in the onset of tumorigenesis. Identification and eventual cloning of the Pctr2 locus may assist in the identification of genes involved in many types of cancer showing aberrations in human chromosome 1p36. (C) 1997 by The American Society of Hematology. C1 NIAID,IMMUNOPATHOL LAB,NIH,BETHESDA,MD 20892. NATL INST MED RES,DIV VIROL,LONDON NW7 1AA,ENGLAND. PERIMMUNE INC,ROCKVILLE,MD. RP Mock, BA (reprint author), NCI,GENET LAB,NIH,BLDG 37,37 CONVENT DR,MSC 4255,RM 2B08,BETHESDA,MD 20892, USA. RI Le Tissier, Paul/G-3079-2011; OI Le Tissier, Paul/0000-0002-7220-5705 FU Medical Research Council [MC_U117570590] NR 30 TC 28 Z9 28 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 BP 4092 EP 4098 PG 7 WC Hematology SC Hematology GA YF299 UT WOS:A1997YF29900032 PM 9354679 ER PT J AU TeruyaFeldstein, J Jaffe, ES Burd, PR Kanegane, H Kingma, DW Wilson, WH Longo, DL Tosato, G AF TeruyaFeldstein, J Jaffe, ES Burd, PR Kanegane, H Kingma, DW Wilson, WH Longo, DL Tosato, G TI The role of mig, the monokine induced by interferon-gamma, and IP-10, the interferon-gamma-inducible protein-10, in tissue necrosis and vascular damage associated with Epstein-Barr virus-positive lymphoproliferative disease SO BLOOD LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 1996 CL ORLANDO, FL SP Amer Soc Hematol, US Dept Vet Affairs Merit Res Funds, NIH ID T-LYMPHOCYTES; IN-VIVO; CELL LYMPHOMAS; B-CELLS; EXPRESSION; CHEMOKINE; PROLIFERATION; PROGENITORS; REGRESSION; MIGRATION AB The mechanisms of tissue necrosis and vascular damage characteristics of certain Epstein-Barr virus (EBV)-associated lymphoproliferative disorders are unknown. The CXC chemokines interferon-gamma-inducible protein-10 (IP-10) and the monokine induced by interferon-gamma (Mig) caused tissue necrosis and vascular damage in Burkitt's lymphoma tumors established in nude mice. We report higher levels of IF-10 and Mig gene expression, in tissues with necrosis and vascular damage from EBV-positive lymphomatoid granulomatosis and nasal or nasal-type T/natural killer (NK)-cell lymphomas compared with tissues with lymphoid hyperplasia, which tacked tissue necrosis and vascular damage. By immunohistochemistry, Mig and IP-10 proteins localized with similar patterns in viable tissue surrounding dead tissue, mostly within endothelial cells, monocyte/macrophages, and lymphocytes. Circulating levels of IP-10 were abnormally elevated in patients with EBV-positive lymphomatoid granulomatosis and nasal or nasal-type T/NK-ceIl lymphomas. These experiments provide the first description of the presence of Mig in any human normal or diseased tissue and the first description of IF-10 in certain lymphoproliferative lesions. These data suggest that Mig and IF-10 play an important role in the pathogenesis of tissue necrosis and vascular damage associated with certain EBV-positive lymphoproliferative processes. (C) 1997 by The American Society of Hematology. C1 NCI,HEMATOPATHOL SECT,PATHOL LAB,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. NCI,MED BRANCH,NIH,BETHESDA,MD 20892. NIA,NIH,BALTIMORE,MD 21224. NR 33 TC 110 Z9 111 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 BP 4099 EP 4105 PG 7 WC Hematology SC Hematology GA YF299 UT WOS:A1997YF29900033 PM 9354680 ER PT J AU Byrd, JC Shinn, CA Bedi, A Waselenko, JK Flinn, IW Diehl, LF Sausville, E Grever, MR AF Byrd, JC Shinn, CA Bedi, A Waselenko, JK Flinn, IW Diehl, LF Sausville, E Grever, MR TI UCN-O1: A promising new agent for B-cell chronic lymphocytic leukemia (B-CLL) that induces apoptosis independent of p53 status. SO BLOOD LA English DT Meeting Abstract C1 WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. NATL CANC INST,BETHESDA,MD. JOHNS HOPKINS UNIV,SCH MED,JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21205. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 4125 EP 4125 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42501434 ER PT J AU Waselenko, JK Byrd, JC Shinn, CA Flinn, IW Diehl, LF Sausville, E Grever, MR AF Waselenko, JK Byrd, JC Shinn, CA Flinn, IW Diehl, LF Sausville, E Grever, MR TI Carboxyamido-triazole (CAI), a signal transduction inhibitor, demonstrates marginal activity against human B-cell chronic lymphocytic leukemia in vitro. SO BLOOD LA English DT Meeting Abstract C1 WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. NCI,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 4147 EP 4147 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42501456 ER PT J AU Raptis, A Mavroudis, D Clave, E vanRhee, F Childs, R Barrett, AJ AF Raptis, A Mavroudis, D Clave, E vanRhee, F Childs, R Barrett, AJ TI Polymorphism of the CD34 gene does not result in the production of an allelic protein. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,BONE MARROW TRANSPLANT UNIT,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 4190 EP 4190 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42501499 ER PT J AU Stroncek, D Clay, ME Smith, J Herr, G Jaszcz, W McCullough, J AF Stroncek, D Clay, ME Smith, J Herr, G Jaszcz, W McCullough, J TI Comparison of the quantity of blood stem cells collected after 4 or 5 days of granulocyte-colony-stimulating factor. SO BLOOD LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. UNIV MINNESOTA,SCH MED,BLOOD BANK,MINNEAPOLIS,MN 55455. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 4261 EP 4261 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42501570 ER PT J AU Stroncek, D Clay, ME Smith, J Herr, G Lalezari, P McCullough, J AF Stroncek, D Clay, ME Smith, J Herr, G Lalezari, P McCullough, J TI G-CSF lowers blood cholesterol, low density lipoprotein and high density lipoprotein in healthy donors. SO BLOOD LA English DT Meeting Abstract C1 BERGEN COMMUNITY BLOOD CTR,PARAMUS,NJ. UNIV MINNESOTA,SCH MED,BLOOD BANK,MINNEAPOLIS,MN 55455. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 4262 EP 4262 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42501571 ER PT J AU Raptis, A Mavroudis, D Molldrem, J Childs, R Ledakis, P Bahceci, E vanRhee, F Hensel, N Phang, S Barrett, AJ AF Raptis, A Mavroudis, D Molldrem, J Childs, R Ledakis, P Bahceci, E vanRhee, F Hensel, N Phang, S Barrett, AJ TI High dose methylprednisolone improves outcome of diffuse alveolar hemorrhage (DAH) following bone marrow transplantation (BMT) for hematological malignancies. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,BONE MARROW TRANSPLANT UNIT,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 4382 EP 4382 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42501691 ER PT J AU Clever, LH Colaianni, LA Davidoff, F Hoey, J Horton, R Lundberg, G Glass, R Nylenna, M Smith, R Utiger, R VanDerWeyden, M Woolf, P AF Clever, LH Colaianni, LA Davidoff, F Hoey, J Horton, R Lundberg, G Glass, R Nylenna, M Smith, R Utiger, R VanDerWeyden, M Woolf, P TI Policies for posting biomedical journal information on the Internet SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Editorial Material C1 NATL LIB MED,BETHESDA,MD 20894. ANNALS INT MED,PHILADELPHIA,PA. JOURNAL AMER MED ASSOC,SAN FRANCISCO,CA. BRITISH MED JOURNAL,LONDON,ENGLAND. NEW ENGLAND JOURNAL MED,BOSTON,MA. MED JOURNAL AUSTRALIA,SYDNEY,NSW,AUSTRALIA. PRINCETON UNIV,PRINCETON,NJ 08544. NR 1 TC 0 Z9 0 U1 0 U2 0 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA ON K1G 3Y6, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD NOV 15 PY 1997 VL 157 IS 10 BP 1378 EP 1378 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA YF893 UT WOS:A1997YF89300046 ER PT J AU London, SJ Lehman, TA Taylor, JA AF London, SJ Lehman, TA Taylor, JA TI Myeloperoxidase genetic polymorphism and lung cancer risk SO CANCER RESEARCH LA English DT Article ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; (+/-)-TRANS-7,8-DIHYDROXY-7,8-DIHYDROBENZOPYRENE; ACTIVATION; LAVAGE; CELLS; DNA AB Myeloperoxidase is a lysosomal enzyme found in high concentrations in human lung due to recruitment of neutrophils. Myeloperoxidase activates benzo[a]pyrene as well as aromatic amines in tobacco smoke and generates carcinogen-free radicals. A single base substitution (G to A) in the promoter region of the myeloperoxidase gene has recently been demonstrated to markedly reduce transcription. We developed an RFLP/PCR assay to test the hypothesis that the allele favoring lower transcription (A allele) reduces the risk of lung cancer, Among population controls, 7.8% of 459 Caucasians and 9.4% of 244 African-Americans inherited two copies of the A allele. Caucasians with the A/A genotype were at 70% reduced risk of lung cancer (odds ratio, 0.30; 95% confidence interval, 0.10-0.93; P = 0.04; 182 cases), A lesser reduction in risk was observed for African-Americans with this genotype (odds ratio, 0.61; 95% confidence interval, 026-1.41; 157 cases), Individuals who inherit two copies of an allele that reduces transcription of the myeloperoxidase gene may be at decreased risk of lung cancer. C1 NIEHS,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. BIOSERVE BIOTECHNOL LTD,LAUREL,MD 20707. RP London, SJ (reprint author), NIEHS,EPIDEMIOL BRANCH,POB 12233,MD A3-05,RES TRIANGLE PK,NC 27709, USA. OI taylor, jack/0000-0001-5303-6398; London, Stephanie/0000-0003-4911-5290 FU NCI NIH HHS [N01-CN-25403] NR 19 TC 202 Z9 213 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1997 VL 57 IS 22 BP 5001 EP 5003 PG 3 WC Oncology SC Oncology GA YF745 UT WOS:A1997YF74500005 PM 9371491 ER PT J AU Matsumoto, Y Takano, H Fojo, T AF Matsumoto, Y Takano, H Fojo, T TI Cellular adaptation to drug exposure: Evolution of the drug-resistant phenotype SO CANCER RESEARCH LA English DT Article ID DNA TOPOISOMERASE-II; CASEIN KINASE-II; C-TERMINAL DOMAIN; HUMAN-TUMOR-CELLS; MULTIDRUG-RESISTANCE; POINT MUTATION; PROTEIN MRP; ETOPOSIDE RESISTANCE; ANTICANCER-DRUG; REDUCED LEVELS AB The efficacy of all chemotherapeutic agents is limited by the occurrence of drug resistance, For etoposide (VP-16), increased expression of MDR-1 or MRP and alterations in topoisomerase II alpha have been shown to confer tolerance, To further understand resistance to VP-16, three sublines, designated MCF-7-VP17, ZR-75B-VP13, and MDA-MB-231-VP7, were initially isolated as single clones from parental cells by exposure to VP-16, Subsequently, a population of cells from each subline was exposed to 3-fold higher drug concentrations, allowing stable sublines to be established at higher extracellular drug concentrations, Characterization of the resistant sublines demonstrates the adaptation that occurs with advancing drug concentrations during in vitro selections, Reduced topoisomerase II mRNA and protein levels were observed in the initial isolates, This reduction was accompanied by a decrease in topoisomerase II activity and cellular growth rate and was associated with 6-314-fold resistance to topoisomerase II poisons. With advancing resistance, MRP expression increased and VP-16 accumulation decreased. This adaptation allowed for partial restoration of topoisomerase II activity as a result of increased expression (MCF-7-VP17 and ZR-75B-VP13) or hyperphosphorylation (MDA-MB-231-VP7), with a resultant increase in growth rate, In MDA-MB-231-VP7 cells, hyperphosphorylation coincided with increased casein kinase II mRNA and protein levels, suggesting a role for this kinase in the acquired hyperphosphorylation. In this cell line, hyperphosphorylation mediated the increased activity despite a fall in topoisomerase II alpha protein levels secondary to an acquired 600-bp deletion in one topoisomerase II alpha allele, which resulted in reduced protein levels, In all three sublines, high levels of resistance were attained as a result of synergism between the reduced topoisomerase II alpha levels and MRP overexpression, These studies demonstrate how cellular adaptation to increasing drug pressure occurs and how more than one mechanism can contribute to the resistant phenotype when increasing selecting pressure is applied. Reduced expression of topoisomerase II is sufficient to confer substantial resistance early in the selection process, with synergy from MRP overexpression helping to confer high levels of resistance. C1 NCI,MED BRANCH,DIV CLIN SCI,NIH,BETHESDA,MD 20892. NR 42 TC 36 Z9 37 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1997 VL 57 IS 22 BP 5086 EP 5092 PG 7 WC Oncology SC Oncology GA YF745 UT WOS:A1997YF74500021 PM 9371507 ER PT J AU Mulders, P Figlin, R deKernion, JB Wiltrout, R Linehan, M Parkinson, D deWolf, W Belldegrun, A AF Mulders, P Figlin, R deKernion, JB Wiltrout, R Linehan, M Parkinson, D deWolf, W Belldegrun, A TI Renal cell carcinoma: Recent progress and future directions SO CANCER RESEARCH LA English DT Editorial Material ID TUMOR-SUPPRESSOR GENE; RECOMBINANT INTERLEUKIN-2 THERAPY; HIPPEL-LINDAU DISEASE; PHASE-II TRIAL; INFILTRATING LYMPHOCYTES; ANTITUMOR-ACTIVITY; DENDRITIC CELLS; MESSENGER-RNA; VHL GENE; IN-VITRO C1 UNIV CALIF LOS ANGELES, SCH MED, DEPT UROL, LOS ANGELES, CA 90095 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT MED, DIV MED ONCOL, LOS ANGELES, CA 90095 USA. NCI, BETHESDA, MD 20892 USA. HARVARD UNIV, BETH ISRAEL HOSP, CAMBRIDGE, MA 02215 USA. NR 76 TC 83 Z9 93 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1997 VL 57 IS 22 BP 5189 EP 5195 PG 7 WC Oncology SC Oncology GA YF745 UT WOS:A1997YF74500037 PM 9371523 ER PT J AU Kiernan, AE Nunes, F Wu, DK Fekete, DM AF Kiernan, AE Nunes, F Wu, DK Fekete, DM TI The expression domain of two related homeobox genes defines a compartment in the chicken inner ear that may be involved in semicircular canal formation SO DEVELOPMENTAL BIOLOGY LA English DT Article ID DEVELOPMENTAL DEFECTS; SENSORY ORGANS; SONIC-HEDGEHOG; MOUSE EMBRYO; DISTAL-LESS; ZEBRAFISH; MICE; BRAIN; IDENTIFICATION; ABNORMALITIES AB Homeobox-containing genes encode a class of proteins that control patterning in developing systems, in some cases by acting as selector genes that define compartment identity. In an effort to demonstrate a similar role for such genes during ear development in the chicken, we present a detailed expression study of two related homeobox-containing genes, SOHo-1 and GH6, using in situ hybridization. At otocyst stages the two genes define a broad lateral domain of expression, which may represent a developmental compartment. Three-dimensional computer reconstructions of SOHo-1 expression at these and later stages revealed that the lateral domain becomes progressively restricted to the three semicircular canals. Thus, SOHo-1 and GH6 are among a small group of markers for a specific structural component of the inner ear. The gene expression domain initially includes the sensory regions of the semicircular canals, known as the cristae ampullaris, but none of the other four sensory organs which were recognizable by BMP4 expression during early morphogenesis (stages 19-24). Significantly, two of the sensory organs (the superior and posterior cristae) were found at the limits, or boundaries, of the SOHo-1/GH6 expression domain, suggesting that compartment boundaries may be involved in specifying sensory organ location as well as identity. Maintained expression at the boundaries may aid in specifying the location of canal outgrowth. These concepts are presented as a formal model which emphasizes that patterning information could be provided at the boundaries of gene expression domains in the inner ear. (C) 1997 Academic Press. C1 NATL INST DEAFNESS & COMMUN DISORDERS,ROCKVILLE,MD 20850. RP Kiernan, AE (reprint author), BOSTON COLL,DEPT BIOL,CHESTNUT HILL,MA 02167, USA. RI Nunes, Fabio/B-4543-2011; Fekete, Donna/B-9170-2009 OI Nunes, Fabio/0000-0002-7785-6785; Fekete, Donna/0000-0003-0662-0246 NR 53 TC 37 Z9 38 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD NOV 15 PY 1997 VL 191 IS 2 BP 215 EP 229 DI 10.1006/dbio.1997.8716 PG 15 WC Developmental Biology SC Developmental Biology GA YH801 UT WOS:A1997YH80100005 PM 9398436 ER PT J AU Brown, JC Sasaki, T Gohring, W Yamada, Y Timpl, R AF Brown, JC Sasaki, T Gohring, W Yamada, Y Timpl, R TI The C-terminal domain V of perlecan promotes beta 1 integrin-mediated cell adhesion, binds heparin, nidogen and fibulin-2 and can be modified by glycosaminoglycans SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE basement membranes; cell-matrix interaction; protein binding; proteoglycan ID DENSITY-LIPOPROTEIN-RECEPTOR; EPIDERMAL-GROWTH-FACTOR; COLLAGEN TYPE-IV; EXTRACELLULAR-MATRIX PROTEIN; SULFATE PROTEOGLYCAN; BASEMENT-MEMBRANE; CORE PROTEIN; GLOBULAR DOMAIN; CALCIUM-BINDING; LAMININ AB Domain V of the major basement-membrane proteoglycan perlecan, a domain which consists of three laminin type G (LG) and four epidermal-growth-factor-like (EG) modules, was obtained in recombinant form by transfecting embryonic kidney cells with an episomal expression vector. A major 90-kDa fragment V was obtained together with fragments Va (74 kDa) and Vb (26 kDa) which were generated by endogenous proteolysis in front of the most C-terminal LG module. All three fragments bound to a heparin affinity column and could be displaced at a moderate (0.2 M) NaCl concentration. Rotary-shadowing electron microscopy demonstrated a three-globule structure for fragment V. Fragment V also showed a strong immunological cross-reaction with tissue-derived perlecan, indicating that it was folded into a native structure. A further, larger fragment, Vc, was apparently substituted with heparan sulphate and/or chondroitin sulphate chains and failed to bind to heparin. Fragment V but not fragment Vc promoted a distinct adhesion of several cell lines and this could be blocked by antibodies against the integrin beta 1 chain. This domain may, however, represent only one of several cell-adhesive sites of perlecan. The recombinant perlecan fragment V bound in surface plasmon resonance assays to fibulin-2, laminin-nidogen complex, nidogen and two nidogen fragments. This indicated two different nidogen-binding epitopes on perlecan domain V with about a 10-fold difference in their affinities (K-d = 0.05-0.2 mu M and about 2 mu M) Perlecan domain V therefore seems to participate in the supramolecular assembly and cell connections of basement membranes. C1 MAX PLANCK INST BIOCHEM,D-82152 MARTINSRIED,GERMANY. NIDR,NIH,BETHESDA,MD 20892. NR 51 TC 112 Z9 112 U1 1 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD NOV 15 PY 1997 VL 250 IS 1 BP 39 EP 46 DI 10.1111/j.1432-1033.1997.t01-1-00039.x PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YJ274 UT WOS:A1997YJ27400004 PM 9431988 ER PT J AU Medvedev, A Chistokhina, A Hirose, T Jetten, AM AF Medvedev, A Chistokhina, A Hirose, T Jetten, AM TI Genomic structure and chromosomal mapping of the nuclear orphan receptor ROR gamma (RORC) gene SO GENOMICS LA English DT Article ID STEROID-HORMONE RECEPTORS; NGFI-B; SUPERFAMILY; ALPHA; ACID; MEMBER; ORGANIZATION; CLONING; IDENTIFICATION; HOMODIMERS AB The nuclear orphan receptor subfamily ROR/RZR is part of the steroid and thyroid hormone/retinoid receptor superfamily and consists of three different genes, alpha, beta, and gamma. In this study, we determined the genomic structure of mouse ROR gamma and the chromosomal localization of both mouse ROR gamma and human ROR gamma (HGMW-approved symbol RORC). The genomic structure of the mouse ROR gamma gene was derived from the analysis of P1 vector clones containing large genomic fragments encoding ROR gamma. These results revealed that the mROR gamma gene has a complex structure consisting of 11 exons separated by 10 introns spanning more than 21 kb of genomic DNA. The DNA-binding domain is contained in two exons, 3 and 4, each encoding one zinc-finger. The splice site between exon 3 and exon 4 is identical to that found in RAR and TR3 receptors. ROR gamma is expressed as two mRNAs, 2.3 and 3.0 kb in size, that are derived by the use of alternative polyadenylation signals. We show by fluorescence ill situ hybridization that the mouse ROR gamma gene is located on chromosome 3, in a region that corresponds to band 3F2.1-2.2. The human ROR gamma was mapped to chromosome region 1q21. The results demonstrate that the ROR gamma genes are located in chromosomal regions that are syntenic between mouse and human. (C) 1997 Academic Press. C1 NIEHS,CELL BIOL SECT,PULM PATHOBIOL LAB,NIH,RES TRIANGLE PK,NC 27709. OSAKA UNIV,SCH MED,DEPT MED 3,SUITA,OSAKA 565,JAPAN. RI Hirose, Takahisa /E-6117-2011; OI Jetten, Anton/0000-0003-0954-4445 NR 43 TC 38 Z9 40 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 15 PY 1997 VL 46 IS 1 BP 93 EP 102 DI 10.1006/geno.1997.4980 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA YK552 UT WOS:A1997YK55200012 PM 9403063 ER PT J AU Miyazaki, S Imatani, A Ballard, L Marchetti, A Buttitta, F Albertsen, H Nevanlinna, HA Gallahan, D Callahan, R AF Miyazaki, S Imatani, A Ballard, L Marchetti, A Buttitta, F Albertsen, H Nevanlinna, HA Gallahan, D Callahan, R TI The chromosome location of the human homolog of the mouse mammary tumor-associated gene INT6 and its status in human breast carcinomas SO GENOMICS LA English DT Article ID LINKAGE MAP; MUTATIONS; GENOME AB The INT6 gene is a common integration site for the mouse mammary tumor virus in mouse mammary tumors. We have determined that the human homolog of INT6 is located on chromosome region 8q22-q23. ii processed INT6 pseudogene is located on chromosome 6q. INT6 is composed of 13 exons that span 45 kb of genomic DNA. The deduced amino acid sequence of the gene product is identical to the mouse protein and contains three potential translation start signals. We have examined 100 primary breast carcinoma DNAs for evidence of genetic alteration affecting INT6. Loss of heterozyosity (LOH) was detected in 11 of 39 (28%) of the tumor samples informative for a polymorphic sequence in intron 7 of INT6. Since single-strand conformation and hybrid mismatch analysis of the remaining allele in these tumor DNAs failed to detect any mutations, we conclude that the target gene for LOH must be closely linked to INT6. (C) 1997 Academic Press. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. UNIV UTAH,HUNTSMAN CANC INST,SALT LAKE CITY,UT 84112. UNIV PISA,DEPT ONCOL,MOL PATHOL SECT,PISA,ITALY. UNIV HELSINKI,CENT HOSP,FIN-00290 HELSINKI,FINLAND. NR 14 TC 36 Z9 39 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 15 PY 1997 VL 46 IS 1 BP 155 EP 158 DI 10.1006/geno.1997.4996 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA YK552 UT WOS:A1997YK55200022 PM 9403073 ER PT J AU Nakajima, H Leonard, WJ AF Nakajima, H Leonard, WJ TI Impaired peripheral deletion of activated T cells in mice lacking the common cytokine receptor gamma-chain - Defective fas ligand expression in gamma-chain-deficient mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; FAMILY PROTEASE INHIBITORS; MEDIATED CYTOTOXICITY; LYMPHOID DEVELOPMENT; NEGATIVE SELECTION; MOLECULAR-BASIS; APOPTOSIS; DEATH; BCL-2; INTERLEUKIN-2 AB Mice lacking the common cytokine receptor gamma-chain (gamma(c)) exhibit severely compromised lymphoid development. T cells that develop in these mice exhibit decreased Bcl-2 levels and accelerated apoptosis; nevertheless, these mice exhibit an age-dependent accumulation of activated CD4(+) T cells, To investigate the basis for this accumulation, we analyzed both thymic and peripheral deletion in these mice, gamma(c)-deficient mice had increased numbers of V beta 11(+) T cells, consistent with a possible defect in Mtv-9-induced deletion; however, the deletion of V beta 5(+) T cells by Mtv-9 and that of V beta 6(+) T cells by Mls-1(a) were normal, Moreover, antigenic peptide could induce wild-type levels of deletion of CD4(+)CD8(+) thymocytes in TCR-transgenic gamma(c)-deficient mice, In contrast to this relatively normal deletion of thymocytes, bacterial superantigen (staphylococcal enterotoxin B)-induced elimination of peripheral T cells was greatly impaired, suggesting that defective peripheral deletion contributed to the accumulation of activated T cells, Interestingly, despite CD4(+) T cell accumulation, these cells exhibited increased sensitivity to Fas-mediated death in vitro, Correction of the defect in Bcl-2 expression by mating to Bcl-2 transgenic mice augmented the splenic T cell accumulation and substantially enhanced the survival of gamma(c)-deficient T cells; however, these cells still exhibited significant Fas-mediated death, indicating that the increased Fas-mediated death was not simply due to diminished Bcl-2 expression, Moreover, these T cells exhibit decreased expression of Fas ligand, suggesting that Fas-bearing cells cannot be effectively eliminated in vivo in gamma(c)-deficient mice, Thus, gamma(c)-dependent signals play a role in peripheral T cell deletion, presumably by inducing Fas ligand on activated T cells. C1 NHLBI, Lab Mol Immunol, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, Bldg 10,Room 7N244,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wjl@helix.nih.gov NR 51 TC 32 Z9 32 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 1997 VL 159 IS 10 BP 4737 EP 4744 PG 8 WC Immunology SC Immunology GA YW262 UT WOS:000071914700012 PM 9366397 ER PT J AU Garraud, O Perler, FB Bradley, JE Nutman, TB AF Garraud, O Perler, FB Bradley, JE Nutman, TB TI Induction of parasite antigen-specific antibody responses in unsensitized human B cells is dependent on the presence of cytokines after T cell priming SO JOURNAL OF IMMUNOLOGY LA English DT Article ID KEYHOLE LIMPET HEMOCYANIN; IN-VITRO; NAIVE DONORS; IFN-GAMMA; IL-4; INTERLEUKIN-12; LYMPHOCYTES; LEISHMANIA; PHENOTYPE; SUBSETS AB Using two recombinant filarial protein Ags and keyhole limpet hemocyanin, we sensitized T cells from uninfected, nonatopic individuals in such a manner that they were able to provide help for the selective induction of an Ag-specific Ab response, IL-2 and IL-4 were shown to be critical for sensitizing the T cells; once sensitized, these T cells could provide the necessary signals for B cells to produce Ag-specific Abs, provided that IL-4 (or IL-2) was supplied exogenously, Primary exposure of T cells to IFN-gamma, but not to IL-12, prevented the Ag-sensitized T cells from helping B cells to produce specific Abs, apart from the IgG2 isotype, These data suggest that Ab-producing B cells of a defined Ag specificity and isotype can be generated differentially after in vitro priming of human T cells by Ag, providing regulatory cytokines are also present. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. New England Biolabs Inc, Beverly, MA 01915 USA. Univ Salford, Salford M5 4WT, Lancs, England. RP Nutman, TB (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Room 126, Bethesda, MD 20892 USA. EM nutman@nih.gov OI Bradley, Janette/0000-0003-3973-7977 NR 36 TC 9 Z9 10 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 NOV 15 PY 1997 VL 159 IS 10 BP 4793 EP 4798 PG 6 WC Immunology SC Immunology GA YW262 UT WOS:000071914700018 PM 9366403 ER PT J AU Kushida, MM Dey, A Zhang, XL Campbell, J Heeney, M Carlyle, J Ganguly, S Ozato, K Vasavada, H Chamberlain, JW AF Kushida, MM Dey, A Zhang, XL Campbell, J Heeney, M Carlyle, J Ganguly, S Ozato, K Vasavada, H Chamberlain, JW TI A 150-base pair 5 ' region of the MHC class I HLA-B7 gene is sufficient to direct tissue-specific expression and locus control region activity - The alpha site determines efficient expression and in vivo occupancy at multiple cis-active sites throughout this region SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; EMBRYONAL CARCINOMA-CELLS; ENHANCER-LIKE SEQUENCES; TRANSGENIC MICE; REGULATORY ELEMENT; DIFFERENTIAL REGULATION; TRANSCRIPTION FACTORS; TARGETED DISRUPTION; NEGATIVE REGULATION; SURFACE EXPRESSION AB To characterize cis- and trans-acting mechanisms that regulate MHC class I transcription during development and in adult tissues, we have used transgenic mice to study a series of human MHC (HLA)-B7 class I gene constructs. Previous studies identified the 5' -0.66-kb to -0.075-kb region as sufficient to direct appropriate and efficient tissue-specific levels of HLA-B7 RNA relative to H-2 class I. Results here show that DNA 5' of -0.26 kb is not required for any aspect of expression. As the expression level correlated with the transgene copy number, was comparable to H-2 or a per-gene copy basis and was independent of integration site, the -0.075 to -0.26-kb segment also functions as a locus control region. With this region, sequences 3' of -0.075 kb, possibly at the promoter, appear to direct the appropriate tissue distribution. Of conserved sequences in the -0.075 to -0.26-kb region, enhancer B box is nonessential. In contrast, in vivo "footprinting" implicated region I/enhancer A/NF-kappa B, IFN consensus/response sequence, and alpha in class I regulation as they are "occupied" in a tissue-specific pattern that correlates with expression. Mutation of alpha leads to decreased expression and loss of occupancy not only at alpha but also at region I/enhancer A/NF-kappa B and IFN consensus/response sequence. Thus, site alpha is an essential class I regulatory element, the dominant function of which is to mediate tissue-specific occupancy at multiple adjacent cis-active sites, possibly by facilitating stable synergistic interactions between factors at these distinct elements. C1 Hosp Sick Children, Res Inst, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Immunol, Toronto, ON, Canada. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. SmithKline Beecham Pharmaceut, Dept Gene Express Sci, King Of Prussia, PA 19406 USA. Bayer, Div Pharmaceut, Inst Bone & Joint Disorder & Canc, W Haven, CT 06516 USA. RP Chamberlain, JW (reprint author), Hosp Sick Children, Res Inst, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM jchamber@sickkids.on.ca NR 68 TC 26 Z9 26 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 1997 VL 159 IS 10 BP 4913 EP 4929 PG 17 WC Immunology SC Immunology GA YW262 UT WOS:000071914700032 PM 9366417 ER PT J AU Wynn, TA Morawetz, R Scharton-Kersten, T Hieny, S Morse, HC Kuhn, R Muller, W Cheever, AW Sher, A AF Wynn, TA Morawetz, R Scharton-Kersten, T Hieny, S Morse, HC Kuhn, R Muller, W Cheever, AW Sher, A TI Analysis of granuloma formation in double cytokine-deficient mice reveals a central role for IL-10 in polarizing both T helper cell 1- and T helper cell 2-type cytokine responses in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MURINE SCHISTOSOMIASIS-MANSONI; ENDOGENOUS IFN-GAMMA; IN-VIVO; TOXOPLASMA-GONDII; MEDIATED-IMMUNITY; GENE-EXPRESSION; DOWN-REGULATION; TH2 CYTOKINES; TNF-ALPHA; INTERLEUKIN-10 AB In response to i.v.-injected eggs of Schistosoma mansoni, normal mice develop a dominant type 2 response, whereas IL-10-deficient animals generate a mixed type 1/type 2 cytokine profile and show reduced pulmonary granuloma formation. IL-4-deficient mice, while displaying diminished type 2 responses and granulomatous inflammation, also do not fully default to a type 1 cytokine profile. Strikingly, mice doubly deficient in IL-4 and IL-10 are completely defective in pulmonary granuloma formation and develop a highly polarized type 1 cytokine pattern. In analogous fashion, mice deficient in both IL-12 and IL-10 generate highly exacerbated type 2 cytokine responses, whereas in wild-type animals, IL-12 depletion minimally effects egg-induced cytokine production. Together, these results argue first that IL-10 is an important endogenous down-regulator of type 2 as well as type 1 cytokine synthesis, and second, that its induction is critical for type 2 response polarization in vivo. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunopathol Lab, Immunobiol Sect, NIH, Bethesda, MD 20892 USA. Univ Cologne, Inst Genet, D-5000 Cologne, Germany. RP Wynn, TA (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Room 126,9000 Rockville Pike, Bethesda, MD 20892 USA. EM twynn@pop.niaid.nih.gov RI Wynn, Thomas/C-2797-2011; Muller, Werner/B-9044-2008; OI Muller, Werner/0000-0002-1297-9725; Morse, Herbert/0000-0002-9331-3705 NR 44 TC 100 Z9 104 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 1997 VL 159 IS 10 BP 5014 EP 5023 PG 10 WC Immunology SC Immunology GA YW262 UT WOS:000071914700044 PM 9366429 ER PT J AU Moller, DR Wysocka, M Greenlee, BM Ma, XJ Wahl, L Flockhart, DA Trinchieri, G Karp, CL AF Moller, DR Wysocka, M Greenlee, BM Ma, XJ Wahl, L Flockhart, DA Trinchieri, G Karp, CL TI Inhibition of IL-12 production by thalidomide SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; VERSUS-HOST DISEASE; BLOOD MONONUCLEAR-CELLS; PULMONARY SARCOIDOSIS; RHEUMATOID-ARTHRITIS; IMMUNE-RESPONSES; INTERLEUKIN-12; CYTOKINE; MICE AB The immunomodulatory properties of thalidomide are currently being exploited therapeutically in conditions as diverse as erythema nodosum leprosum, chronic graft-vs-host disease, rheumatoid arthritis, and sarcoidosis. The relevant mechanism of action of thalidomide in these diseases remains unclear, The important role recently ascribed to IL-12, a cytokine critical to the development of cellular immune responses, in the pathogenesis of several of these conditions led us to examine whether thalidomide affects the production of IL-12, Thalidomide potently suppressed the production of IL-12 from human PBMC and primary human monocytes in a concentration-dependent manner. Thalidomide-induced inhibition of IL-12 production was additive to that induced by suboptimal inhibiting doses of dexamethasone, and occurred by a mechanism independent of known endogenous inhibitors of IL-12 production. These results suggest that thalidomide may have therapeutic utility in a wide range of immunologic disorders that are characterized by inappropriate cellular immune responses. C1 Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. NIDR, Immunol Lab, NIH, Bethesda, MD 20892 USA. Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. Georgetown Univ, Med Ctr, Dept Med & Pharmacol, Div Clin Pharmacol, Washington, DC 20007 USA. RP Moller, DR (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, 5501 Hopkins Bayview Circle,Room 4B-63, Baltimore, MD 21224 USA. FU NHLBI NIH HHS [HL-45115, P01-HL49545]; NIAID NIH HHS [AI-01223] NR 30 TC 165 Z9 170 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 1997 VL 159 IS 10 BP 5157 EP 5161 PG 5 WC Immunology SC Immunology GA YW262 UT WOS:000071914700061 PM 9366446 ER PT J AU Yajima, S Lammers, CH Lee, SH Hara, Y Mizuno, K Mouradian, MM AF Yajima, S Lammers, CH Lee, SH Hara, Y Mizuno, K Mouradian, MM TI Cloning and characterization of murine glial cell-derived neurotrophic factor inducible transcription factor (MGIF) SO JOURNAL OF NEUROSCIENCE LA English DT Article DE glial cell-derived neurotrophic factor (GDNF); zinc finger; Sp1; transcription; cloning; transforming growth factor-beta (TGF-beta) ID EPIDERMAL GROWTH-FACTOR; BOX-BINDING-PROTEINS; MICE LACKING GDNF; DOPAMINE-RECEPTOR GENE; MESSENGER-RNA; TYROSINE KINASE; NERVOUS-SYSTEM; PHEOCHROMOCYTOMA CELLS; HIRSCHSPRUNG DISEASE; HIPPOCAMPAL-NEURONS AB The potent neurotrophic factor glial cell-derived neurotrophic factor (GDNF) is a distant member of the transforming growth factor-beta (TGF-beta) superfamily of proteins. We report a transcription factor that is the first nuclear protein known to be induced by GDNF, thus designated murine GDNF inducible factor (mGIF). The cDNA was cloned in the course of investigating transcription factors that bind to Sp1 consensus sequences, using the in situ filter detection method, and it was found to encode a protein having the same C-2-H-2 zinc finger motif as Sp1. Sequence analysis indicated that mGIF is homologous to the human TGF-beta inducible early gene (TIEG) and human early growth response gene-alpha (EGR-alpha). mGIF is widely distributed in the adult mouse with high mRNA levels in kidney, lung, brain, liver, heart, and testis. In the adult brain, mGIF is abundantly expressed in hippocampus, cerebral cortex, cerebellum, and amygdala with lower amounts in striatum, nucleus accumbens, olfactory tubercle, thalamus, and substantia nigra. During development, mGIF mRNA also has a wide distribution, including in cerebral cortex, cerebellar primordium, kidney, intestine, liver, and lung. GDNF induces the expression of mGIF rapidly and transiently both in a neuroblastoma cell line and in primary cultures of rat embryonic cortical neurons. Co-transfection of the Drosophila SL2 cells using mGIF expression plasmid and reporter constructs having Spl binding sites indicated that mGIF represses transcription from a TATA-containing as well as from a TATA-less promoter. These observations suggest that the zinc finger transcription factor mGIF could be important in mediating some of the biological effects of GDNF. C1 NHLBI,LAB BIOCHEM GENET,BETHESDA,MD 20892. NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892. NINCDS,GENET PHARMACOL UNIT,EXPT THERAPEUT BRANCH,BETHESDA,MD 20892. OI Mouradian, M. Maral/0000-0002-9937-412X NR 63 TC 52 Z9 53 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 15 PY 1997 VL 17 IS 22 BP 8657 EP 8666 PG 10 WC Neurosciences SC Neurosciences & Neurology GA YE666 UT WOS:A1997YE66600001 PM 9348334 ER PT J AU PozzoMiller, LD Pivovarova, NB Leapman, RD Buchanan, RA Reese, TS Andrews, SB AF PozzoMiller, LD Pivovarova, NB Leapman, RD Buchanan, RA Reese, TS Andrews, SB TI Activity-dependent calcium sequestration in dendrites of hippocampal neurons in brain slices SO JOURNAL OF NEUROSCIENCE LA English DT Article DE calcium regulation; calcium sequestration; hippocampus; CA3; dendrites; endoplasmic reticulum; synaptic activity; hippocampal slice cultures; X-ray microanalysis ID ELECTRON-PROBE ANALYSIS; GATED CA2+ CHANNELS; ENDOPLASMIC-RETICULUM; PYRAMIDAL NEURONS; INOSITOL 1,4,5-TRISPHOSPHATE; SYNAPTIC ACTIVATION; NMDA RECEPTORS; MITOCHONDRIA; STORES; LOCALIZATION AB Synaptic activity-dependent changes in the spatio-temporal distribution of calcium ions regulate important neuronal functions such as dendritic integration and synaptic plasticity but the processes that terminate the free Ca2+ transients associated with these changes remain unclear. We have characterized at the electron microscopic level the intracellular compartments involved in buffering free Ca2+ transients in dendritic cytoplasm of CA3 neurons by measuring the larger changes in the concentrations of total Ca that persist for several minutes after neuronal activity. Quantitative energy-dispersive x-ray microanalysis of cryosections from hippocampal slice cultures rapidly frozen 3 min after afferent synaptic activity identified a subset of dendritic endoplasmic reticulum (ER) as a high-capacity Ca2+ buffer. Calcium sequestration by cisterns of this subset of ER was graded, reversible, and dependent on a thapsigargin-sensitive Ca2+-ATPase. Sequestration was so robust that after repetitive high-frequency stimulation the Ca content of responsive ER cisterns increased as much as 20-fold. These results demonstrate that a subpopulation of ER is the major dendritic Ca sequestration compartment in the minutes after neuronal activity. C1 NINCDS, NEUROBIOL LAB, NIH, BETHESDA, MD 20892 USA. MARINE BIOL LAB, WOODS HOLE, MA 02543 USA. NIH, BIOMED ENGN & INSTRUMENTAT PROGRAM, NATL CTR RES RESOURCES, BETHESDA, MD 20892 USA. NR 58 TC 63 Z9 64 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 15 PY 1997 VL 17 IS 22 BP 8729 EP 8738 PG 10 WC Neurosciences SC Neurosciences & Neurology GA YE666 UT WOS:A1997YE66600009 PM 9348342 ER PT J AU Gay, D Lavi, E Zhao, HZ Mumin, A Bhandoola, A AF Gay, D Lavi, E Zhao, HZ Mumin, A Bhandoola, A TI OlP-1, a novel protein that distinguishes early oligodendrocyte precursors SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE oligodendrocyte; development; mouse; myelin ID CENTRAL-NERVOUS-SYSTEM; PDGF ALPHA-RECEPTOR; RAT OPTIC-NERVE; MONOCLONAL-ANTIBODIES O1; GLIAL PROGENITOR-CELL; MYELIN BASIC-PROTEIN; GROWTH-FACTOR; CULTURED OLIGODENDROCYTES; SUBVENTRICULAR ZONE; MACROGLIAL CELLS AB Oligodendrocyte development may be divided into three distinct stages: I) commitment of neuroectoderm cells to the oligodendrocyte lineage, IF) migration of precursors into the surrounding parenchyma concomitant with increased proliferation, and III) cessation of migration and proliferation and initiation of myelination, Stage II of development has remained enigmatic because of the paucity of known molecules that distinguish these immature migratory cells, We describe a novel surface protein, termed OIP-1, which is restricted in expression to this developmental stage in the mouse, Cytofluorographic comparisons with known developmental markers showed OIP-1 to be expressed primarily by stage II precursors in vitro. Histologic analyses supported this conclusion by showing co-localization of OIP-1 with stage II molecules in vivo. Two conclusions were drawn from these results, First, OIP-1 was a novel protein expressed by murine oligodendrocyte precursors at a point in development that suggested a role in migration or proliferation, Second, dispersal of OIP-1-positive cells throughout the developing brain did not correlate with the location of myelination which, observed days later, progressed in a caudal to rostral manner, These data supported the concept that the final steps of maturation and myelin gene expression may be dependent upon extrinsic factors located predominantly within white matter tracts. (C) 1997 Wiley-Liss, Inc. C1 NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. RP Gay, D (reprint author), UNIV PENN,SCH MED,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104, USA. FU NCRR NIH HHS [RR10209-02]; NEI NIH HHS [5T32EY07131] NR 69 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD NOV 15 PY 1997 VL 50 IS 4 BP 591 EP 604 PG 14 WC Neurosciences SC Neurosciences & Neurology GA YH628 UT WOS:A1997YH62800010 PM 9404721 ER PT J AU Dalgaard, JZ Klar, AJ Moser, MJ Holley, WR Chatterjee, A Mian, IS AF Dalgaard, JZ Klar, AJ Moser, MJ Holley, WR Chatterjee, A Mian, IS TI Statistical modeling and analysis of the LAGLIDADG family of site-specific endonucleases and identification of an intein that encodes a site-specific endonuclease of the HNH family SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GROUP-I INTRON; HIDDEN MARKOV-MODELS; RIBOSOMAL-RNA GENE; YEAST MITOCHONDRIAL-DNA; PI-SCEI ENDONUCLEASE; SACCHAROMYCES-CEREVISIAE; PYROBACULUM-ORGANOTROPHUM; INTERVENING SEQUENCES; SPEECH RECOGNITION; ESCHERICHIA-COLI AB The LAGLIDADG and HNH families of site-specific DNA endonucleases encoded by viruses, bacteriophages as well as archaeal, eucaryotic nuclear and organellar genomes are characterized by the sequence motifs 'LAGLIDADG' and 'HNH', respectively, These endonucleases have been shown to occur in different environments: LAGILIDADG endonucleases are found in inteins, archaeal and group I introns and as free standing open reading frames (ORFs); HNH endonucleases occur in group I and group II introns and as ORFs, Here, statistical models (hidden Markov models, HMMs) that encompass both the conserved motifs and more variable regions of these families have been created and employed to characterize known and potential new family members, A number of new, putative LAGLIDADG and HNH endonucleases have been identified including an intein-encoded HNH sequence. Analysis of an HMM-generated multiple alignment of 130 LAGLIDADG family members and the th ree-dimensional structure of the I-CreI endonuclease has enabled definition of the core elements of the repeated domain (similar to 90 residues) that is present in this family of proteins, A conserved negatively charged residue is proposed to be involved in catalysis, Phylogenetic analysis of the two families indicates a lack of exchange of endonucleases between different mobile elements (environments) and between hosts from different phylogenetic kingdoms, However, there does appear to have been considerable exchange of endonuclease domains amongst elements of the same type, Such events are suggested to be important for the formation of elements of new specficity. C1 UNIV CALIF BERKELEY, LAWRENCE BERKELEY LAB, DIV LIFE SCI, BERKELEY, CA 94720 USA. RP NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM,POB B,BLDG 549, ROOM 154, FREDERICK, MD 21702 USA. NR 85 TC 153 Z9 156 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 15 PY 1997 VL 25 IS 22 BP 4626 EP 4638 DI 10.1093/nar/25.22.4626 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YJ405 UT WOS:A1997YJ40500027 PM 9358175 ER PT J AU Fay, MP Feuer, EJ AF Fay, MP Feuer, EJ TI A semi-parametric estimate of extra-Poisson variation for vital rates SO STATISTICS IN MEDICINE LA English DT Article ID REGRESSION; MODELS; HETEROSCEDASTICITY AB We introduce a method for estimating overdispersion in Poisson models for vital rates, We assume smoothness conditions on the counts to obtain pointwise variance estimates that we combine to obtain an estimate of the overdispersion parameter. We create confidence intervals about the observed rates using this estimate and an approximation based on the gamma distribution. The advantage of this method is that the estimates of the superpopulation rates do not depend on the smoothness assumption, yet when this assumption is met we obtain approximately unbiased estimates of the overdispersion parameter. Thus, we may calculate confidence intervals for vital rates under an overdispersed Poisson model without making parametric assumptions on the mean rates. (C) 1997 by John Wiley & Sons, Ltd. RP Fay, MP (reprint author), NCI,DIV CANC PREVENT & CONTROL,EXECUT PLAZA N,SUITE 344,6130 EXECUT BLVD,MSC 735,BETHESDA,MD 20892, USA. RI Fay, Michael/A-2974-2008; OI Fay, Michael P./0000-0002-8643-9625 NR 16 TC 6 Z9 6 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 15 PY 1997 VL 16 IS 21 BP 2389 EP 2401 DI 10.1002/(SICI)1097-0258(19971115)16:21<2389::AID-SIM683>3.0.CO;2-J PG 13 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA YC779 UT WOS:A1997YC77900001 PM 9364649 ER PT J AU Morrell, CH Pearson, JD Brant, LJ GordonSalant, S AF Morrell, CH Pearson, JD Brant, LJ GordonSalant, S TI Construction of hearing percentiles in women with non-constant variance from the linear mixed-effects model SO STATISTICS IN MEDICINE LA English DT Article ID REFERENCE RANGES; LIKELIHOOD; THRESHOLDS AB Current age-specific reference standards for adult hearing thresholds are primarily cross-sectional in nature and vary in the degree of screening of the reference sample for noise-induced hearing loss and other hearing problems, We develop methods to construct age-specific percentiles for longitudinal data that have been modelled using the linear mixed-effects model, We apply these methods to construct percentiles of hearing level using data from a carefully screened sample of women from the Baltimore Longitudinal Study of Aging, However, the variation in the residuals and random effects from the linear mixed-effects model does not remain constant with age and frequency of the stimulus tone. In addition, the distribution of the hearing levels is not symmetric about the mean, We develop a number of methods to use the output from the linear mixed-effects model to construct percentiles that do not have constant variance. We use a transformation of the hearing levels to provide for skewness in the final percentile curves. The change in the variation of the residuals and random effects is modelled as a function of beginning age and frequency and we use this variance function to construct the hearing percentiles, We present a number of approaches, First, we use the absolute values of the population residuals to model the total deviation about the mean as a function of beginning age and frequency, Second, we model the standard deviation in the person-specific (cluster) residuals as well as the standard deviation in the estimated random effects. Finally, we use weighted least squares with the regressions on the absolute cluster residuals and absolute estimated random effects where the weights are the reciprocal of the standard deviations of their estimates. (C) 1997 by John Wiley & Sons, Ltd. C1 NIA,GERONTOL RES CTR,LONGITUDINAL STUDIES BRANCH,BALTIMORE,MD 21224. UNIV MARYLAND,COLLEGE PK,MD 20742. RP Morrell, CH (reprint author), LOYOLA COLL,DEPT MATH SCI,4501 N CHARLES ST,BALTIMORE,MD 21210, USA. FU NIDCD NIH HHS [1 R03 DC 02566-01] NR 17 TC 6 Z9 6 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 15 PY 1997 VL 16 IS 21 BP 2475 EP 2488 PG 14 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA YC779 UT WOS:A1997YC77900007 PM 9364655 ER PT J AU Yang, W Mizuuchi, K AF Yang, W Mizuuchi, K TI Site-specific recombination in plane view SO STRUCTURE LA English DT Review ID HOMOLOGY; LAMBDA; CLEAVAGE; STRANDS AB Biochemists have worked long and hard on each reaction component and chemical step to reach the point of asking the question as to how protein and DNA molecules are arranged and rearranged in the process of site-specific recombination. The structures of several lambda integrase family members published recently have answered many of the questions about this process. RP Yang, W (reprint author), NIDDKD,MOL BIOL LAB,NIH,9000 ROCKVILLE PIKE,BLDG 5,RM B1-03,BETHESDA,MD 20892, USA. RI Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 NR 19 TC 38 Z9 38 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0969-2126 J9 STRUCTURE JI Structure PD NOV 15 PY 1997 VL 5 IS 11 BP 1401 EP 1406 DI 10.1016/S0969-2126(97)00290-6 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA YJ947 UT WOS:A1997YJ94700001 PM 9384556 ER PT J AU Everhart, JE Lombardero, M Detre, KM Zetterman, RK Wiesner, RH Lake, JR Hoofnagle, JH AF Everhart, JE Lombardero, M Detre, KM Zetterman, RK Wiesner, RH Lake, JR Hoofnagle, JH TI Increased waiting time for liver transplantation results in higher mortality SO TRANSPLANTATION LA English DT Article AB Background. Waiting time to liver transplantation (LTx) has dramatically lengthened, but the proportion of candidates who die awaiting transplantation has not increased, We evaluated whether longer waiting time for LTx candidates increases mortality, Methods. A cohort of candidates listed for LTx between 1990 and 1993 by three large transplantation programs was followed for 2 years, The exposure measure was ABO blood type, which is not inherently related to outcome, but is a major determinant of waiting time, The main outcome measure was a-year mortality, as evaluated by logistic regression analysis that controlled for differences in clinical status at the time of evaluation for LTx. Results., The 308 candidates with type O blood waited longer for LTx (median 109 days) than the 399 candidates with other blood types (median 58 days) (P=0.001), Candidates listed for LTx with type O blood had better clinical status at evaluation, but then had higher pretransplantation mortality (13.3%) than other candidates (7.0%) (P=0.005). Blood group O candidates had higher a-year mortality (26.6%) than other candidates (22.1%), which on multivariate analysis resulted in a mortality odds ratio at 2 years of 1.52 (95% confidence interval=1.04-2.23). With the difference in median waiting time between blood groups increasing from 44 days in the first year to 108 days in the third year, the a-year mortality odds ratio also rose from 0.94 to 1.97., Conclusions, When compared with LTx candidates with other blood types, blood type O candidates have longer waiting times and higher pretransplantation mortality, which results in higher a-year mortality. C1 NIDDK,NIH,BETHESDA,MD. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,PITTSBURGH,PA 15260. UNIV NEBRASKA,MED CTR,OMAHA,NE. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. FU NIDDK NIH HHS [N01-DK-0-2251, N01-DK-0-2253, N01-DK-0-2252] NR 10 TC 74 Z9 76 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 15 PY 1997 VL 64 IS 9 BP 1300 EP 1306 DI 10.1097/00007890-199711150-00012 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA YG537 UT WOS:A1997YG53700012 PM 9371672 ER PT J AU Gottesman, S Maurizi, MR Wickner, S AF Gottesman, S Maurizi, MR Wickner, S TI Regulatory subunits of energy-dependent proteases SO CELL LA English DT Review ID ESCHERICHIA-COLI; CLPAP PROTEASE; MEMBRANE; COMPLEX; ATP; LON C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. RP Gottesman, S (reprint author), NCI,MOL BIOL LAB,BLDG 37,BETHESDA,MD 20892, USA. NR 18 TC 133 Z9 136 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD NOV 14 PY 1997 VL 91 IS 4 BP 435 EP 438 DI 10.1016/S0092-8674(00)80428-6 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YG492 UT WOS:A1997YG49200003 PM 9390551 ER PT J AU Edelmann, W Yang, K Umar, A Heyer, J Lau, K Fan, KH Liedtke, W Cohen, PE Kane, MF Lipford, JR Yu, NJ Crouse, GF Pollard, JW Kunkel, T Lipkin, M Kolodner, R Kucherlapati, R AF Edelmann, W Yang, K Umar, A Heyer, J Lau, K Fan, KH Liedtke, W Cohen, PE Kane, MF Lipford, JR Yu, NJ Crouse, GF Pollard, JW Kunkel, T Lipkin, M Kolodner, R Kucherlapati, R TI Mutation in the mismatch repair gene Msh6 causes cancer susceptibility SO CELL LA English DT Article ID NONPOLYPOSIS COLON-CANCER; COLORECTAL TUMORIGENESIS; HETERODUPLEX REPAIR; TUMOR-CELLS; DNA; MICE; HETERODIMER; HOMOLOG; MOUSE; DEFICIENCY AB Mice carrying a null mutation in the mismatch repair gene Msh6 were generated by gene targeting. Cells that were homozygous for the mutation did not produce any detectable MSH6 protein, and extracts prepared from these cells were defective for repair of single nucleotide mismatches. Repair of 1, 2, and 4 nucleotide insertion/deletion mismatches was unaffected. Mice that were homozygous for the mutation had a reduced life span. The mice developed a spectrum of tumors, the most predominant of which were gastrointestinal tumors and B-as well as T-cell lymphomas. The tumors did not show any microsatellite instability. We conclude that MSH6 mutations, like those in some other members bf the family of mismatch repair genes, lead to cancer susceptibility, and germline mutations in this gene may be associated with a cancer predisposition syndrome that does not show microsatellite instability. C1 YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT MOL GENET,BRONX,NY 10461. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT PATHOL,BRONX,NY 10461. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT DEV & MOL BIOL,BRONX,NY 10461. YESHIVA UNIV ALBERT EINSTEIN COLL MED,STRANG CANC RES LAB,BRONX,NY 10461. NIEHS,NIH,RES TRIANGLE PK,NC 27709. DANA FARBER CANC INST,BOSTON,MA 02115. LUDWIG INST CANC RES,LA JOLLA,CA 92093. EMORY UNIV,ATLANTA,GA 30322. RP Edelmann, W (reprint author), YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT CELL BIOL,1300 MORRIS PK AVE,BRONX,NY 10461, USA. RI Liedtke, Wolfgang/G-4633-2011 FU NCI NIH HHS [CA 67944, CA 44704, CA 54050] NR 51 TC 274 Z9 280 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD NOV 14 PY 1997 VL 91 IS 4 BP 467 EP 477 DI 10.1016/S0092-8674(00)80433-X PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YG492 UT WOS:A1997YG49200008 PM 9390556 ER PT J AU Haile, RW Witte, JS Longnecker, MP ProbstHensch, N Chen, MJ Harper, J Frankl, HD Lee, ER AF Haile, RW Witte, JS Longnecker, MP ProbstHensch, N Chen, MJ Harper, J Frankl, HD Lee, ER TI A sigmoidoscopy-based case-control study of polyps: Macronutrients, fiber and meat consumption SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID BLOOD SCREENING-PROGRAM; COLORECTAL ADENOMAS; COLON-CANCER; PHYSICAL-ACTIVITY; RISK-FACTORS; DIET; EPIDEMIOLOGY; MEN AB We conducted a large, sigmoidoscopy-based case-control study to examine the relation of intake of macronutrients, meat, and fiber to occurrence of adenomas of the large bowel. Cases were subjects diagnosed for the first time with one or more histologically confirmed adenomas. Controls had no polyps of any type at sigmoidoscopy, had no history of polyps, and were individually matched to cases by gender, age, date of sigmoidoscopy, and Kaiser Center. The response rate was 84% for cases and 82% for controls. Complete dietary data for 488 matched pairs were available. All odds ratios are from matched analyses adjusted for energy. We observed positive associations with risk of adenomas for calories, animal fat, saturated fat, red meat, and the ratio of red meat to poultry and fish. protective effects were observed for vegetable protein, carbohydrates, and dietary fiber. The fiber effects diminished after adjusting for fruits and vegetables. Results after mutually adjusting for the effects of saturated fat, fiber and the ratio of red meat to chicken and fish suggest that each of these variables has an effect on risk of adenomas that is independent of the other 2 exposures. (C) 1997 Wiley-Liss, Inc. C1 CASE WESTERN RESERVE UNIV,SCH MED,DEPT EPIDEMIOL & BIOSTAT,CLEVELAND,OH 44106. NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT EPIDEMIOL,LOS ANGELES,CA 90024. KAISER PERMANENTE,LOS ANGELES,CA. KAISER PERMANENTE,BELLFLOWER,CA. RP Haile, RW (reprint author), UNIV SO CALIF,KENNETH NORRIS JR COMPREHENS CANC CTR,DEPT PREVENT MED,SCH MED,LOS ANGELES,CA 90033, USA. OI Longnecker, Matthew/0000-0001-6073-5322 FU NCI NIH HHS [CA66794, CA51923] NR 21 TC 34 Z9 34 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 14 PY 1997 VL 73 IS 4 BP 497 EP 502 DI 10.1002/(SICI)1097-0215(19971114)73:4<497::AID-IJC7>3.0.CO;2-V PG 6 WC Oncology SC Oncology GA YG992 UT WOS:A1997YG99200007 PM 9389562 ER PT J AU Patel, V Jakus, J Harris, CM Ensley, JF Robbins, KC Yeudall, WA AF Patel, V Jakus, J Harris, CM Ensley, JF Robbins, KC Yeudall, WA TI Altered expression and activity of G(1)/s cyclins and cyclin-dependent kinases characterize squamous cell carcinomas of the head and neck SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID GROWTH ARREST; CANCER; LINES; GENE; OVEREXPRESSION; P53; AMPLIFICATION; MUTATIONS; INHIBITORS; DYSPLASIA AB Progressive deregulation of the cell-division cycle is thought to contribute to the establishment and progression of neoplasia. Previously, we have documented the in vivo inactivation of p16(INK4A), an inhibitor of G(1) cyclin-dependent kinases, in squamous cell carcinomas of the head and neck region. In the present study, we extend these findings by examining the expression and functional activity of cyclin dependent kinases (CDKs) and their regulatory subunits using a model system of cell lines derived from squamous cell carcinomas. Increased activity of CDK4 and 6 was universal in tumor cells compared with normal keratinocytes, reflecting over-expression of either or both kinases. In contrast to other studies, overexpression of cyclin D1, a regulatory subunit of CDK4 and 6, was not observed. Increased activity of CDK2 was less frequent and was related to over expression of cyclin A and/or E, AII tumor cell lines showed increased expression of proliferating cell nuclear antigen compared to normal keratinocytes. Four SCC cell lines, including one tumor-metastasis pair derived from a single patient, failed to express the p15(INK4B) transcript. Western blot analysis of cell lysates revealed normal or reduced levels of p27(KIP1) tumor cells compared to normal keratinocytes. However, failure to express wildtype p53 was not reflected by lower levels of p21(WAF1). Our data suggest that cell-cycle deregulation is likely to occur by multiple mechanisms during the genesis of head and neck squamous cell carcinomas. Furthermore, p16(INK4A) likely to be the primary target for inactivation on chromosome 9p21 in these tumors as p15(INK4B) loss occurs less frequently. (C) 1997 Wiley-Liss, Inc. C1 NIDR,ORAL & PHARYNGEAL CANC BRANCH,BETHESDA,MD. WAYNE STATE UNIV,DIV HEMATOL ONCOL,DETROIT,MI. NR 37 TC 39 Z9 43 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 14 PY 1997 VL 73 IS 4 BP 551 EP 555 DI 10.1002/(SICI)1097-0215(19971114)73:4<551::AID-IJC16>3.0.CO;2-C PG 5 WC Oncology SC Oncology GA YG992 UT WOS:A1997YG99200016 PM 9389571 ER PT J AU Yu, YK Zhang, L Yin, XX Sun, H Uhl, GR Wang, JB AF Yu, YK Zhang, L Yin, XX Sun, H Uhl, GR Wang, JB TI mu opioid receptor phosphorylation, desensitization, and ligand efficacy SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; OPIATE RECEPTOR; FUNCTIONAL DESENSITIZATION; DIFFERENTIAL REGULATION; POTASSIUM CHANNEL; CYCLIC-AMP; AGONIST; CELLS; METHADONE AB mu opioid receptors are subject to phosphorylation and desensitization through actions of at least two distinct biochemical pathways: agonist-dependent mu receptor phosphorylation and desensitization induced by a biochemically distinct second pathway dependent on protein kinase C activation (1), To better understand the nature of the agonist-induced mu receptor phosphorylation events, we have investigated the effects of a variety of opiate ligands of varying potencies and intrinsic activities on mu receptor phosphorylation and desensitization, Exposure to the potent full agonists sufentanil, dihydroetorphine, etorphine, etonitazine, and [D-Ala2, MePhe4, Glyol5]enkephalin (DAMGO) led to strong receptor phosphorylation, while methadone, l-alpha-acetyl-methadone (LAAM), morphine, meperidine, DADL, beta-endorphin((1-31)), enkephalins, and dynorphin A((1-17)) produced intermediate effects, The partial agonist buprenorphine minimally enhanced receptor phosphorylation while antagonists failed to alter phosphorylation, Buprenorphine and full antagonists each antagonized the enhanced mu receptor phosphorylation induced by morphine or DAMGO, The rank order of opiate ligand efficacies in producing mu receptor-mediated functional desensitization generally paralleled their rank order of efficacies in producing receptor phosphorylation, Interestingly, the desensitization and phosphorylation mediated by methadone and LAAM were disproportionate to their efficacies in two distinct test systems, This generally good fit between the efficacies of opiates in mu receptor activation, phosphorylation, and desensitization supports the idea that activated receptor/agonist/G-protein complexes and/or receptor conformational changes induced by agonists are required for agonist-induced mu receptor phosphorylation, Data for methadone and LAAM suggest possible contribution from their enhanced desensitizing abilities to their therapeutic efficacies. C1 UNIV MARYLAND,SCH PHARM,DEPT PHARMACEUT SCI,BALTIMORE,MD 21201. NIAAA,LAB MOL & CELLULAR NEUROBIOL,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. NIDA,MOL NEUROBIOL BRANCH,BALTIMORE,MD 21224. NR 28 TC 174 Z9 175 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 14 PY 1997 VL 272 IS 46 BP 28869 EP 28874 DI 10.1074/jbc.272.46.28869 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF684 UT WOS:A1997YF68400013 PM 9360954 ER PT J AU Bhat, MK Yu, CL Yap, N Zhan, QM Hayashi, Y Seth, P Cheng, SY AF Bhat, MK Yu, CL Yap, N Zhan, QM Hayashi, Y Seth, P Cheng, SY TI Tumor suppressor p53 is a negative regulator in thyroid hormone receptor signaling pathways SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CO-REPRESSOR; NUCLEAR; PROTEIN; CELLS; GENE; EXPRESSION; PROMOTER; BINDING AB Thyroid hormone nuclear receptors (TRs) are ligand-dependent transcription factors which regulate growth, differentiation, and development, The molecular mechanisms by which TRs mediate these diverse effects are unclear, One emerging hypothesis suggests that TRs could mediate these diverse effects via cooperation with different transcription factors/receptors, Indeed, we have recently shown that the human TR subtype beta 1 (h-TR beta 1) interacts with the tumor suppressor p53, p53 is a transcription factor that plays a critical role in cell cycle regulation and tumor development, To assess the physiological relevance of the interaction of h-TR beta 1 with p53, the present study addressed the question as to whether the functions of h-TR beta 1 could be modulated by p53, We first compared the h-TR beta 1-mediated transcriptional activity in two pairs of isogenic cell lines, RKO/RKO E6 and MCF-7/MCF-7 E6, RKO and MCF-7 cells are colon and breast carcinoma cell lines, respectively, that contain p53 but lack TR beta 1, The isogenic RKO E6 and MCF-7 E6 cells are stable clones expressing high levels of papillomavirus type 16 E6 protein, In these cells, the level of p53 protein was lower than the parental cells, The impairment of p53 functions in these EG-containing cells led to an activation of TR beta 1-mediated transcriptional activity, Furthermore, in a growth hormone-producing cell line in which the expression of the growth hormone gene is positively regulated by TRs, overexpression of the wild-type p53 led to repression in the expression of the growth hormone gene, Thus, TRs could cross-talk with p53 in its signaling pathways to regulate gene regulatory functions, The present findings further strengthen the hypothesis that mediation of the pleiotropic effects of T-3 requires the cooperation of TRs with a large network of transcription factors. C1 NCI,MOL BIOL LAB,MED BRANCH,NIH,BETHESDA,MD 20892. NCI,MOL PHARMACOL LAB,NIH,BETHESDA,MD 20892. NAGOYA UNIV,ENVIRONM MED RES INST,DEPT ENDOCRINOL & METAB,NAGOYA,AICHI 464,JAPAN. OI Hayashi, Yoshitaka/0000-0002-7557-4303 NR 34 TC 46 Z9 46 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 14 PY 1997 VL 272 IS 46 BP 28989 EP 28993 DI 10.1074/jbc.272.46.28989 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF684 UT WOS:A1997YF68400030 PM 9360971 ER PT J AU Oligino, L Lung, FDT Sastry, L Bigelow, J Cao, T Curran, M Burke, TR Wang, SM Krag, D Roller, PP King, CR AF Oligino, L Lung, FDT Sastry, L Bigelow, J Cao, T Curran, M Burke, TR Wang, SM Krag, D Roller, PP King, CR TI Nonphosphorylated peptide ligands for the Grb2 Src homology 2 domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR TYROSINE KINASES; MITOGENIC SIGNAL-TRANSDUCTION; GUANINE-NUCLEOTIDE EXCHANGE; PHAGE DISPLAY LIBRARIES; TERMINAL SH2 DOMAIN; ADAPTER PROTEIN; EGF RECEPTOR; CRYSTAL-STRUCTURE; RAS PATHWAY; CELL-LINES AB Critical intracellular signals in normal and malignant cells are transmitted by the adaptor protein Grb2 by means of its Src homology 2 (SH2) domain, which binds to phosphotyrosyl (pTyr) residues generated by the activation of tyrosine kinases, To understand this important control point and to design inhibitors, previous investigations have focused on the molecular mechanisms by which the Grb2 SH2 domain selectively binds pTyr containing peptides, In the current study, we demonstrate that the Grb2 SH2 domain can also bind in a pTyr independent manner, Using phage display, an 11-amino acid cyclic peptide, G1, has been identified that binds to the Grb2 SH2 domain but not the src SH2 domain, Synthetic G1 peptide blocks GrbP SH2 domain association (IC50 10-25 mu M) with a g-amino acid pTyr-containing peptide derived from the SHC protein (pTyr317), These data and amino acid substitution analysis indicate that G1 interacts in the phosphopeptide binding site, G1 peptide requires a YXN sequence similar to that found in natural pTyr-containing ligands, and phosphorylation of the tyrosine increases G1 inhibitory activity. G1 also requires an internal disulfide bond to maintain the active binding conformation, Since the G1 peptide does not contain pTyr, it defines a new type of SH2 domain binding motif that may advance the design of Grb2 antagonists. C1 GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. UNIV VERMONT,VERMONT CANC CTR,BURLINGTON,VT 05405. NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT NEUROL,WASHINGTON,DC 20007. RI Burke, Terrence/N-2601-2014 NR 62 TC 94 Z9 96 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 14 PY 1997 VL 272 IS 46 BP 29046 EP 29052 DI 10.1074/jbc.272.46.29046 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF684 UT WOS:A1997YF68400037 PM 9360978 ER PT J AU Boneca, IG Xu, NX Gage, DA deJonge, BLM Tomasz, A AF Boneca, IG Xu, NX Gage, DA deJonge, BLM Tomasz, A TI Structural characterization of an abnormally cross-linked muropeptide dimer that is accumulated in the peptidoglycan of methicillin- and cefotaxime-resistant mutants of Staphylococcus aureus SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STRAIN AB Laboratory mutants of Staphylococcus aureus strain ATCC 8325 (275) selected for increased minimal inhibitory concentration (MIG) values to methicillin and cefotaxime showed increased rates of cell wall turnover and detergent-induced autolysis in virtual parallel with the increasing MIC for the antibiotic. Also in parallel with the increasing MICs for the particular antibiotic used in the selection was the gradual accumulation of an unusual muropeptide in the peptidoglycan of the mutants, muropeptide 12, which is a minor component of the cell wall of the parental strain. Analysis of muropeptide 12, its peptide derivative, and its lysostaphin degradation products by high pressure liquid chromatography, Edman degradation, and mass spectrometry suggests that muropeptide 12 is a dimer in which the two monomeric components are interlinked by two pentaglycyl crossbridges, thus generating a Ii-member macrocyclic ring structure, This unusual cross-linked structure may be the product of the abnormal activity of penicillin-binding protein 2 which has grossly reduced antibiotic binding capacity in the mutant staphylococci. C1 ROCKEFELLER UNIV,MICROBIOL LAB,NEW YORK,NY 10021. MICHIGAN STATE UNIV,DEPT BIOCHEM,NIH,MASS SPECTROMETRY FACIL,E LANSING,MI 48824. RI Boneca, Ivo/H-1677-2014 OI Boneca, Ivo/0000-0001-8122-509X NR 12 TC 14 Z9 14 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 14 PY 1997 VL 272 IS 46 BP 29053 EP 29059 DI 10.1074/jbc.272.46.29053 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF684 UT WOS:A1997YF68400038 PM 9360979 ER PT J AU Soucek, T Pusch, O Wienecke, R DeClue, JE Hengstschlager, M AF Soucek, T Pusch, O Wienecke, R DeClue, JE Hengstschlager, M TI Role of the tuberous sclerosis gene-2 product in cell cycle control - Loss of the tuberous sclerosis gene-2 induces quiescent cells to enter S phase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DOMINANTLY INHERITED CANCER; TUBEROUS-SCLEROSIS-2 TSC2 GENE; EKER RAT MODEL; DEPENDENT KINASES; THYMIDINE KINASE; RENAL-CARCINOMA; MUTATION; HETEROZYGOSITY; TRANSFORMATION; REGION AB Tuberous sclerosis is an autosomal dominant disorder characterized by the development of benign growths in many tissues and organs. Linkage analysis revealed two disease-determining genes on chromosome 9 and chromosome 16. The TSC2 gene on chromosome 16 encodes a 1784-amino acid tumor suppressor protein, tuberin, that functions as a GTPase activating protein for Rap1, a member of the superfamily of Ras-related proteins, By immunoblot analyses, we found TSC2 expression to be high in G(0) as well as in early small G(1) cells. Analyses after different cell synchronization procedures revealed that TSC2 mRNA and protein expression do not fluctuate throughout the cell cycle, Using inducible expression systems we further demonstrated that TSC2 expression is not affected by overexpression of the mitogenic transcription factor E2F-1 or c-Myc. Nevertheless, antisense inhibition of tuberin expression in logarithmically growing cells markedly decreased the percentage of cells in G(1). Furthermore, we found that cells exposed to TSC2 antisense oligonucleotides did not undergo G(0) arrest after serum withdrawal, Antisense inhibition of TSC2 expression also induced quiescent G(0)-arrested fibroblasts to reenter the cell cycle. Our data show for the first time that the absence of tuberin can both induce cells to pass through the G(1)/S transition of the eukaryotic cell cycle and prevent them from entering a quiescent state. These results have clear implications for the tumor suppressor function of TSC2, We further found that reentry into the cell cycle upon loss of TSC2 is dependent on the activity of the G(1) cyclin-dependent kinases (CDKs), Cdk2 or Cdk4. Taken together with our finding that antisense inhibition of TSC2 causes up regulation of cyclin D1 expression, these results provide the first evidence for a connection between tuberin/Rap1 and the G(1) CDK-dependent regulation of the transition from G(0)/G(1) to S phase. C1 UNIV VIENNA, DEPT PRENATAL DIAGNOSIS & THERAPY, A-1090 VIENNA, AUSTRIA. NCI, CELLULAR ONCOL LAB, NIH, BETHESDA, MD 20892 USA. NR 42 TC 156 Z9 157 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 14 PY 1997 VL 272 IS 46 BP 29301 EP 29308 DI 10.1074/jbc.272.46.29301 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF684 UT WOS:A1997YF68400069 PM 9361010 ER PT J AU Alkema, MJ Jacobs, J Voncken, JW Jenkins, NA Copeland, NG Satijn, DPE Otte, AP Berns, A vanLohuizen, M AF Alkema, MJ Jacobs, J Voncken, JW Jenkins, NA Copeland, NG Satijn, DPE Otte, AP Berns, A vanLohuizen, M TI MPc2, a new murine homolog of the Drosophila polycomb protein is a member of the mouse polycomb transcriptional repressor complex SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE Bmi1; polycomb; nuclear distribution; chromosomal localization; transcriptional repressor ID GENE-EXPRESSION; CHROMOSOMAL LOCALIZATION; BMI-1 PROTOONCOGENE; AXIAL SKELETON; CHROMOBOX GENE; MICE; TRANSFORMATION; MELANOGASTER; REGULATOR; CHROMATIN AB The evolutionarily conserved polycomb and trithorax-group genes are required to maintain stable expression patterns of homeotic genes and other target genes throughout development. Here, we report the cloning and characterization of a novel mouse polycomb homolog, MPc2, in addition to the previously described M33 polycomb gene. Co-immunoprecipitations and subnuclear co-localization studies show that MPc2 interacts with the mouse polycomb-group oncoprotein Bmi1 and is a new member of the mouse polycomb multiprotein complex. Gal4DB- MPc2 or -M33 fusion proteins mediate a five-to tenfold repression of stably integrated-reporter constructs carrying GAL4 binding sites, demonstrating that these proteins are transcriptional repressors. The MPc2 gene is localized on chromosome 11, in close proximity to the classical mouse mutations tail short (Ts) and rabo torcido (Rbt). Ts and Xbt hemizygous mice display anemia and transformations of the axial skeleton reminiscent of phenotypes observed in mice with mutated polycomb or trithorax-group :genes, suggesting that MPc2 is a candidate gene for Ts and Rbt. (C) 1997 Academic Press Limited. C1 UNIV AMSTERDAM,NETHERLANDS CANC INST,DIV MOL CARCINOGENESIS,NL-1066 CX AMSTERDAM,NETHERLANDS. UNIV AMSTERDAM,NETHERLANDS CANC INST,DIV MOL GENET,NL-1066 CX AMSTERDAM,NETHERLANDS. UNIV AMSTERDAM,DEPT BIOCHEM,NL-1066 CX AMSTERDAM,NETHERLANDS. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. UNIV AMSTERDAM,EC SLATER INST BIOCHEM RES,NL-1018 TV AMSTERDAM,NETHERLANDS. NR 39 TC 52 Z9 54 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 14 PY 1997 VL 273 IS 5 BP 993 EP 1003 DI 10.1006/jmbi.1997.1372 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YH779 UT WOS:A1997YH77900004 PM 9367786 ER PT J AU Erickson, KL Beutler, JA Cardellina, JH Boyd, MR AF Erickson, KL Beutler, JA Cardellina, JH Boyd, MR TI Salicylihalamides A and B, novel cytotoxic macrolides from the marine sponge Haliclona sp. SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID ABSOLUTE-CONFIGURATION; NUDIBRANCH EGGMASSES; ANTIFUNGAL MACROLIDE; ALKALOIDS; HALICHONDRAMIDE AB Two novel, highly potent, cytotoxic macrolides, salicylihalamides A (1) and B (2), were isolated from the sponge Haliclona sp. This new macrolide class incorporates salicylic acid, a 12-membered lactone ring, and an enamide side chain. COMPARE pattern-recognition analyses of the NCI 60-cell mean graph screening profiles of 1 did not reveal any significant correlations to the profiles of known antitumor compounds in the NCI's ''standard agent database'', thus supporting the conclusion that the salicylihalamides represent a potentially important new class for antitumor lead optimization and in vivo investigations. C1 NCI,FREDERICK CANC RES & DEV CTR,LAB DRUG DISCOVERY RES & DEV,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 29 TC 194 Z9 199 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD NOV 14 PY 1997 VL 62 IS 23 BP 8188 EP 8192 DI 10.1021/jo971556g PG 5 WC Chemistry, Organic SC Chemistry GA YG452 UT WOS:A1997YG45200048 ER PT J AU Zhang, L Barker, JL Xing, GQ Giorgi, O Ma, W Chang, YH Hu, QA Choi, NN Rubinow, DR AF Zhang, L Barker, JL Xing, GQ Giorgi, O Ma, W Chang, YH Hu, QA Choi, NN Rubinow, DR TI 5-HT1A receptor mRNA expressions differ in the embryonic spinal cord of male and female rats SO NEUROSCIENCE LETTERS LA English DT Article DE serotonin; testosterone; spinal cord; dimorphism; mRNA; embryo ID MOTOR-NEURON GROUPS; SEXUAL DIFFERENCES; HORMONAL-CONTROL; NUCLEUS; BULBOCAVERNOSUS; MANIPULATION; TESTOSTERONE; STEROIDS; NUMBER; FIBERS AB During critical periods of development, the effects of testosterone (T) on promoting androgenization of the central nervous system (CNS) are reflected not only by behavior, morphology, and hormone secretion but also by gene expression. The mechanisms involved in sexual differentiation of the CNS, however, remain incompletely defined. The current set of experiments examined with in situ hybridization the dimorphism in 5-HT1A receptor mRNA expression in the embryonic rat spinal cord and the possible role of T in the dimorphism. We found sex-related differences in expression of 5-HT1A mRNA in the spinal cord, which were altered by a single injection of T. The results suggest that this gonadal steroid is responsible for the sexual dimorphism in 5-HT1A mRNA expression occurring during the critical period. (C) 1997 Elsevier Science Ireland Ltd. C1 NINCDS,NEUROPHYSIOL LAB,NIH,BETHESDA,MD 20892. UNIV CAGLIARI,DEPT TOXICOL,CAGLIARI,ITALY. RP Zhang, L (reprint author), NIMH,BEHAV ENDOCRINOL BRANCH,BLDG 36,2C02,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 22 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV 14 PY 1997 VL 237 IS 1 BP 41 EP 44 DI 10.1016/S0304-3940(97)00801-X PG 4 WC Neurosciences SC Neurosciences & Neurology GA YJ806 UT WOS:A1997YJ80600011 PM 9406875 ER PT J AU Zajicek, KB Higley, JD Suomi, SJ Linnoila, M AF Zajicek, KB Higley, JD Suomi, SJ Linnoila, M TI Rhesus macaques with high CSF 5-HIAA concentrations exhibit early sleep onset SO PSYCHIATRY RESEARCH LA English DT Article DE primate; sleep; serotonin; 5-hydroxyindoleacetic acid; cerebrospinal fluid; activity ID 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS; CEREBROSPINAL-FLUID MONOAMINE; DIMINISHED SOCIAL COMPETENCE; NONHUMAN PRIMATE MODEL; AMINE METABOLITES; VIOLENT OFFENDERS; SEVERE AGGRESSION; DIURNAL RHYTHMS; FIRE SETTERS; RAT-BRAIN AB The relationship between central nervous system serotonergic activity, as reflected by cerebrospinal fluid (CSF) concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), and sleep/wakefulness behavior was investigated in socially housed, juvenile rhesus macaques. Two cohorts of rhesus monkeys (Macaca mulatta), numbering 42 subjects (seventeen 39-month-olds and twenty-five 20-month-olds) were observed in their home cages between 21.30 h and 23.30 h for 10 nights using an infrared night scope. Over each 90-min observation period, the following states were recorded every 5 min using a scan sampling procedure: Sleep, Drowsy, Passive-awake and Active. After more than one quarter of the animals in the group had fallen asleep, states were recorded as they occurred. Six weeks prior to the collection of the behavioral data, a sample of cisternal CSF was obtained to assay for 5-HIAA concentrations. With cohort effects statistically controlled, there was a negative correlation between latency to fall asleep and CSF S-HIAA concentrations (i.e., subjects with high CSF 5-HIAA concentrations were more likely to fall asleep early). Subjects with low CSF 5-HIAA concentrations were also more active during the daytime hours. Subjects who fell asleep first were, on average, also less active during nighttime hours. The positive correlation between CSF 5-HIAA and sleep onset was not a result of social status since there was no correlation between social dominance rank and time of sleep onset. These results support the hypothesis that the serotonergic system may play a role in sleep onset and possibly in the regulation of diurnal activity rhythms in non-human primates. Published by Elsevier Science Ireland Ltd. C1 NICHD, Comparat Ethol Lab, NIH, Anim Ctr, Poolesville, MD 20837 USA. NIAAA, Clin Studies Lab, Primate Unit, DICBR, Poolesville, MD 20837 USA. RP Higley, JD (reprint author), NICHD, Comparat Ethol Lab, NIH, Anim Ctr, Bldg 112,POB 529, Poolesville, MD 20837 USA. NR 59 TC 10 Z9 10 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD NOV 14 PY 1997 VL 73 IS 1-2 BP 15 EP 25 DI 10.1016/S0165-1781(97)00112-1 PG 11 WC Psychiatry SC Psychiatry GA YQ291 UT WOS:000071370600002 PM 9463835 ER PT J AU Polymeropoulos, MH AF Polymeropoulos, MH TI Genetics of Parkinson's disease - Response SO SCIENCE LA English DT Letter RP Polymeropoulos, MH (reprint author), NATL HUMAN GENOME RES INST,NIH,BETHESDA,MD 20892, USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 14 PY 1997 VL 278 IS 5341 BP 1213 EP 1213 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YG043 UT WOS:A1997YG04300009 ER PT J AU Solovev, VN Sergeev, GB Nemukhin, AV Burt, SK Topol, IA AF Solovev, VN Sergeev, GB Nemukhin, AV Burt, SK Topol, IA TI IR matrix isolation and ab initio identification of products of the reactions of CH3Cl and CH3Br with Mg SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID MAGNESIUM CLUSTER GRIGNARD; VIBRATIONAL FORCE-FIELDS; INFRARED-SPECTRA; EXACT EXCHANGE; ABINITIO; APPROXIMATION; MOLECULES; ENERGY; ATOM AB IR spectra of products of the reactions of methyl halogen molecules CH3Cl and CH3Br with Mg have been studied under matrix isolation conditions. Comparison of the spectra with ab initio frequencies and intensities allows us to identify the primary reaction products as monomagnesium Grignard complexes CH3MgX = (X Cl, Br) and therefore reject the possibility of creation of energetically more stable bimagnesium species CH3-MgMgX. Those species according to ab initio calculations should be bound with respect to the decomposition CH3MgX + Mg. Ab initio calculations have been carried out at several levels, including the large basis set MP2 and DFT treatments. The scaling factors, which bring the computed harmonic frequencies into correspondence with the experimental band positions, have been deduced. It is shown that, unlike the majority of organic molecules, organometallic complexes should be considered more carefully, in the sense that the scaling factors of the advanced MP2 and DFT procedures are not as close to unity as is believed. C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK BIOMED COMP CTR,SAIC FREDERICK,FREDERICK,MD 21702. MOSCOW MV LOMONOSOV STATE UNIV,DEPT CHEM,MOSCOW 119899,RUSSIA. RI Sergeev, Gleb/C-2644-2015; Nemukhin, Alexander/P-9662-2015 NR 24 TC 33 Z9 33 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD NOV 13 PY 1997 VL 101 IS 46 BP 8625 EP 8630 DI 10.1021/jp971968t PG 6 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA YG462 UT WOS:A1997YG46200008 ER PT J AU Barnett, SM Edwards, CM Butler, IS Levin, IW AF Barnett, SM Edwards, CM Butler, IS Levin, IW TI Pressure-induced transmembrane alpha(II)- to alpha(I)-helical conversion in bacteriorhodopsin: An infrared spectroscopic study SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Letter ID TRANS-N-METHYLACETAMIDE; PURPLE MEMBRANE; CONFORMATIONAL-CHANGES; HYDROSTATIC-PRESSURE; VIBRATIONAL-SPECTRA; SECONDARY STRUCTURE; RAMAN-SPECTROSCOPY; DARK-ADAPTATION; C-13 NMR; TEMPERATURE AB Decreases in the infrared spectroscopic amide A frequencies from 3308 to 3291 cm(-1) of native purple membrane as a function of pressure are consistent with a gradual alpha(II)- to alpha(I)-helical conversion for the transmembrane helixes of bacteriorhodopsin. This structural transition reaches completion near 3.7 kbar. Only negligible frequency shifts are observed, however, as a function of pressure in the 1660 cm(-1) amide I region, suggesting that additional factors such as hydrogen bonding and helix-helix interactions are important in modulating the; frequency of this mode. The pressure dependence of the feature at 2927 cm(-1), arising from a Fermi resonance couplet originating from both protein and lipid methyl groups, indicates that global environmental changes occur near 4 kbar. C1 NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. MCGILL UNIV,DEPT CHEM,MONTREAL,PQ H3A 2K6,CANADA. NR 42 TC 13 Z9 13 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1089-5647 J9 J PHYS CHEM B JI J. Phys. Chem. B PD NOV 13 PY 1997 VL 101 IS 46 BP 9421 EP 9424 DI 10.1021/jp972086x PG 4 WC Chemistry, Physical SC Chemistry GA YG463 UT WOS:A1997YG46300001 ER PT J AU Munoz, V Thompson, PA Hofrichter, J Eaton, WA AF Munoz, V Thompson, PA Hofrichter, J Eaton, WA TI Folding dynamics and mechanism of beta-hairpin formation SO NATURE LA English DT Article ID SHORT LINEAR PEPTIDE; AQUEOUS-SOLUTION; PROTEIN; STABILITY; DESIGN AB Protein chains coil into alpha-helices and beta-sheet structures. Knowing the timescales and mechanism of formation of these basic structural elements is essential for understanding how proteins fold(1). For the past 40 years, alpha-helix formation has been extensively investigated in synthetic and natural peptides(2-5), including by nanosecond kinetic studies(6,7). In contrast, the mechanism of formation of beta structures has not been studied experimentally. The minimal beta-structure element is the beta-hairpin, which is also the basic component of antiparallel beta-sheets. Here we use a nanosecond laser temperature-jump apparatus to study the kinetics of folding a beta-hairpin consisting of 16 amino-acid residues. Folding of the hairpin occurs in 6 mu s at room temperature, which is about 30 times slower than the rate of alpha-helix formation(6,7). We have developed a simple statistical mechanical model that provides a structural explanation for this result, Our analysis also shows that folding of a beta-hairpin captures much of the basic physics of protein folding; including stabilization by hydrogen bonding and hydrophobic interactions, two-state behaviour, and a funnel-like, partially rugged energy landscape. RP Munoz, V (reprint author), NIDDK,PHYS CHEM LAB,NIH,BLDG 5,BETHESDA,MD 20892, USA. NR 24 TC 758 Z9 763 U1 10 U2 81 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD NOV 13 PY 1997 VL 390 IS 6656 BP 196 EP 199 DI 10.1038/36626 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YF494 UT WOS:A1997YF49400060 PM 9367160 ER PT J AU Linet, MS Tarone, RE Robison, LL AF Linet, MS Tarone, RE Robison, LL TI Leukemia and exposure to magnetic fields - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID CANCER C1 CHILDRENS CANC GRP,ARCADIA,CA 91006. RP Linet, MS (reprint author), NCI,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 13 PY 1997 VL 337 IS 20 BP 1473 EP 1474 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA YF253 UT WOS:A1997YF25300020 ER PT J AU Nelson, KB Grether, JK AF Nelson, KB Grether, JK TI More on prenatal magnesium sulfate and risk of cerebral palsy SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP Nelson, KB (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 12 PY 1997 VL 278 IS 18 BP 1493 EP 1493 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA YE445 UT WOS:A1997YE44500027 PM 9363965 ER EF