FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Sinha, R Caporaso, N AF Sinha, R Caporaso, N TI Diet, genetic susceptibility and human cancer etiology SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Assembly and Physiology of Apolipoprotein B-Containing Lipoproteins - Its Not Just for Heart Disease Anymore, as part of Experimental Biology 98 CY APR 18-22, 1998 CL SAN FRNACISCO, CALIFORNIA SP Amer Soc Nutr Sci, Energy & Macronutrient Res Interest Sect, Egg Nutr Ctr, Amer Heart Assoc, W States Affiliate, Merck Res Labs, Bristol Meyers Squibb Pharmaceut Res Inst, Parke Davis Pharmaceut Res DE heterocyclic amines; cytochrome P4501A2; N-acetyltransferase; MelQx; genotype; phenotype; inducible ID HETEROCYCLIC AROMATIC-AMINES; CAFFEINE URINARY METABOLITES; VITAMIN-D-RECEPTOR; COLORECTAL-CANCER; CYTOCHROME P4501A2; ALDEHYDE DEHYDROGENASES; ALCOHOL-DEHYDROGENASE; N-ACETYLTRANSFERASE; PROSTATE-CANCER; COLON CANCER AB There is evidence that high penetrance hereditary genes cause a number of relatively uncommon tumors in the familial setting, whereas common cancers are influenced by multiple loci that alter susceptibility to cancer and other conditions. The latter category of genes are involved in the metabolism of carcinogens (activation, detoxification) as well as those that interact with dietary exposure. This paper will consider some of the basic principles in studying susceptibility genes and provide a few examples in which they interact with dietary components. C1 NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA. RP Sinha, R (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 40 TC 22 Z9 24 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD FEB PY 1999 VL 129 IS 2 SU S BP 556S EP 559S PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 167YP UT WOS:000078662900026 PM 10064331 ER PT J AU Ambrosone, CB Coles, BF Freudenheim, JL Shields, PG AF Ambrosone, CB Coles, BF Freudenheim, JL Shields, PG TI Glutathione-S-transferase (GSTM1) genetic polymorphisms do not affect human breast cancer risk, regardless of dietary antioxidants SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Assembly and Physiology of Apolipoprotein B-Containing Lipoproteins - Its Not Just for Heart Disease Anymore, as part of Experimental Biology 98 CY APR 18-22, 1998 CL SAN FRNACISCO, CALIFORNIA SP Amer Soc Nutr Sci, Energy & Macronutrient Res Interest Sect, Egg Nutr Ctr, Amer Heart Assoc, W States Affiliate, Merck Res Labs, Bristol Meyers Squibb Pharmaceut Res Inst, Parke Davis Pharmaceut Res DE breast neoplasms; epidemiology/molecular; glutathione-S-transferase; oxidative stress; antioxidants ID NEW-YORK; SUSCEPTIBILITY; EPIDEMIOLOGY; FAMILY AB Glutathione-S-transferases catalyze the detoxication of carcinogen metabolites and reactive oxygen species (ROS) produced through a number of mechanisms. Glutathione-S-transferase (GST) M1 is polymorphic, and the null allele results in a lack of enzyme activity. Because there are indications that ROS may be involved in breast carcinogenesis, we sought to determine whether the GSTM1 null allele was associated with increased breast cancer, particularly among women with tower consumption of dietary sources of alpha-tocopherol, carotenoids and ascorbic acid. in a study of diet and cancer in western New York, women with primary, incident, histologically confirmed breast cancer (n = 740) and community controls (n = 810) were interviewed and an extensive food-frequency questionnaire administered. A subset of these women provided a blood specimen. DNA was extracted and genotyping performed for GSTM1. Data were available for 279 cases and 340 controls. The null allele did not increase breast cancer risk, regardless of menopausal status. There were also no differences in associations between the polymorphism and risk among lower and higher consumers of dietary sources of antioxidants or smokers and nonsmokers. These results indicate that GSTM1 genetic polymorphisms are not associated with breast cancer risk, even in an environment low in antioxidant defenses. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14214 USA. NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Ambrosone, CB (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. FU NCI NIH HHS [CA/ES62995, CA11535, CA01633] NR 23 TC 29 Z9 31 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD FEB PY 1999 VL 129 IS 2 SU S BP 565S EP 568S PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 167YP UT WOS:000078662900028 PM 10064333 ER PT J AU Ciotti, M Werlin, SL Owens, IS AF Ciotti, M Werlin, SL Owens, IS TI Delayed response to phenobarbital treatment of a Crigler-Najjar type II patient with partially inactivating missense mutations in the bilirubin UDP-glucuronosyltransferase gene SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article ID DIFFERENTIAL-DIAGNOSIS; COMPLEX LOCUS; IDENTIFICATION; EXPRESSION; DISEASE C1 NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. RP Owens, IS (reprint author), NICHHD, Heritable Disorders Branch, NIH, Bldg 10,Room 9S-242, Bethesda, MD 20892 USA. NR 23 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD FEB PY 1999 VL 28 IS 2 BP 210 EP 213 DI 10.1097/00005176-199902000-00024 PG 4 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 177TH UT WOS:000079226800023 PM 9932859 ER PT J AU Yamazaki, Y Savva, M Kleinman, HK Oka, S Mokotoff, M AF Yamazaki, Y Savva, M Kleinman, HK Oka, S Mokotoff, M TI Enhanced cleavage of diaminopimelate-containing isopeptides by leucine aminopeptidase and matrix metalloproteinases in tumors: application to bioadhesive peptides SO JOURNAL OF PEPTIDE RESEARCH LA English DT Article DE diaminopimelate-containing peptides; isopeptides; leucine aminopeptidase; matrix metalloproteinases; C3 sarcoma homogenates; HT1080 attachment assay; peptide-prodrugs ID PRODRUGS; INVASION; SEQUENCE; ANALOGS; FK-156; CELLS; CHAIN; IKVAV AB We prepared (2S,GS)-Z-Dpm(Z)(OMe) (4) by protease-mediated hydrolysis of (R,R/S,S)-Z-Dpm(Z)(OMe)-OMe (3), converted it to (2S,GS)-Dpm(Z)(OMe) (6) via PCl5 to an NCA intermediate and hydrolysis, protected the amino group with Boc to give (2S,GS)-Boc-Dpm(Z)(OMe) (7), which upon ammonolysis of the Me ester afforded (2S,6S)-Boc-Dpm(Z)(NH2) (8). Hydrogenolysis of 8 and protection with Fmoc gave (2S,6S)-Boc-Dpm(Fmoc)(NH2) (10). Using 10 and SPPS, we prepared three Dpm-containing peptides and their corresponding Lys peptides. Enzymatic studies with mLAP and cLAP showed that the Leu moiety in Ac-Gly-(2S,GS)-Dpm(Leu)(NH2)-Ala (14) was hydrolyzed 68-fold and >1000-fold more rapidly, respectively, than that in Ac-Gly-Lys(Leu)-Ala (12). The enhanced rate of Leu formation from 14 compared to 12 was also observed with homogenates of mouse C3 sarcomas. This homogenate also hydrolyzed Ac-Gly- (2S,GS)-Dpm(Ac-Gly-Pro-Gln-Gly-Leu)(NH2) (16) to Ac-Gly- (2S,GS)-Dpm(NH2)-Ala (13), Leu and Ac-Gly-Pro-Gln-Gly (17). This implies the side chain is cleaved first by endopeptidases, such as matrix metalloproteinases (MMPs), and then the remaining Leu is cleaved by LAP-like exopeptidases. The rate of liberation of 17 from 16 and the corresponding Lys isopeptide, Ac-Gly-Lys(Ac-Gly-Pro-Gln-Gly-Leu)-Ala (15), was not significantly different. The rate of formation of 13 was faster from 16 than Ac-Gly-Lys-Ala (11) was from 15. Thus, the entire isopeptide side chain can be removed by the cooperative action of LAP-like and MMP-like peptidases present in tumor tissue, which occurs faster in the Dpm peptide 16 than in the Lys peptide 15. The rate of formation of 13 from 16 by lung, liver, and intestine homogenates (from the same C3 tumor-bearing mice) was comparable to or higher than from the tumor homogenates, but the rate by blood was only 4% the value of the tumor homogenates. Analogs of a bioadhesive fragment from the laminin alpha 1 chain were prepared by replacing the essential Lys with Dpm(NH2) (20) and Dpm(Leu)(NH2) (21). Both Dpm-containing peptides were active, although considerably weaker than the corresponding Lys peptides 18 and 19, in a cell attachment assay with human fibrosarcoma MT-1080 cells. C1 Univ Pittsburgh, Dept Pharmaceut Sci, Sch Pharm, Pittsburgh, PA 15261 USA. Agcy Ind Sci & Technol, Natl Inst Biosci & Human Technol, Tsukuba, Ibaraki 305, Japan. NIDR, NIH, Bethesda, MD 20892 USA. RP Mokotoff, M (reprint author), Univ Pittsburgh, Dept Pharmaceut Sci, Sch Pharm, 736 Salk Hall, Pittsburgh, PA 15261 USA. EM mokotoffm@msx.upmc.edu NR 29 TC 1 Z9 1 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1397-002X J9 J PEPT RES JI J. Pept. Res. PD FEB PY 1999 VL 53 IS 2 BP 177 EP 187 DI 10.1034/j.1399-3011.1999.00021.x PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 177HL UT WOS:000079204500009 PM 10195455 ER PT J AU Rady, JJ Elmer, GI Fujimoto, JM AF Rady, JJ Elmer, GI Fujimoto, JM TI Opioid receptor selectivity of heroin given intracerebroventricularly differs in six strains of inbred mice SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SWISS-WEBSTER MICE; NOR-BINALTORPHIMINE; BETA-FUNALTREXAMINE; INDUCED ANALGESIA; MORPHINE; MOUSE; MU; ANTINOCICEPTION; OPIATE; ANTAGONIST AB Heroin administered i.c.v. acts on supraspinal mu opioid receptors in ICR mice but on delta receptors in Swiss Webster mice. The purpose of this study was to determine the degree to which genotype plays a role in the opioid receptor selectivity of heroin across a range of fully inbred strains of mice. Six inbred strains were given heroin i.c.v. 10 min before the tail-flick test. Differences in the descending neurotransmitter systems involved in supraspinal opioid-induced analgesia were evaluated as the first step. Antagonism by bicuculline given intrathecally indicated the involvement of supraspinal delta receptors in activating spinal gamma-aminobutyric acid (GABA) receptors; antagonism by intrathecal methysergide indicated either mu or kappa receptor involvement. Antagonism by intrathecal yohimbine implicated mu and eliminated kappa receptor involvement. Intracerbroventricular opioid antagonists (beta-funaltrexamine, 7-benzylidenenaltrexone, naltriben, or nor-binaltorphimine) provided further differentiation. Based on these initial results, receptor selectivity was determined by more extensive ED50 experiments with i.c.v. administration of heroin with opioid antagonists, beta-funaltrexamine (for mu), naltrindole (for delta), and nor-binaltorphimine (for kappa). The combined results indicated that heroin analgesia was predominantly mediated in C57BL/6J by delta, in DBA/2J and CBA/J by mu, and in BALB/cByJ and AKR/J by kappa receptors. The response in C3H/HeJ appeared to involve mu receptors. The results indicate that the opioid receptor selectivity of heroin is genotype-dependent. Because these genotypes are fully inbred, the genetically determined molecular and neurochemical substrate mediating the different opioid receptor selectivities of heroin can be studied further. C1 Vet Affairs Med Ctr, Res Serv 151, Milwaukee, WI 53295 USA. Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53226 USA. NIDA, Behav Pharmacol & Genet Sect, Div Intramural Res, NIH, Baltimore, MD USA. RP Fujimoto, JM (reprint author), Vet Affairs Med Ctr, Res Serv 151, Milwaukee, WI 53295 USA. FU NIDA NIH HHS [DA00451] NR 40 TC 21 Z9 21 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 FEB PY 1999 VL 288 IS 2 BP 438 EP 445 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 161KA UT WOS:000078286700007 PM 9918543 ER PT J AU Wojnicki, FHE Rothman, RB Rice, KC Glowa, JR AF Wojnicki, FHE Rothman, RB Rice, KC Glowa, JR TI Effects of phentermine on responding maintained under multiple fixed-ratio schedules of food and cocaine presentation in the rhesus monkey SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CHOICE PROCEDURE; DOPAMINE; DRUGS; REINFORCEMENT; FENFLURAMINE; DECREASES; STRENGTH AB Drugs that decrease drug-maintained responding at doses that do not decrease other behaviors in animals may be suitable candidates for development as medications to treat drug abuse in humans. The present study examined whether this effect could be obtained with phentermine, a drug that has been reported to decrease cocaine intake in humans. Rhesus monkeys were trained under multiple fixed-ratio 30-response schedules of food and i.v. cocaine delivery. Phentermine was always given as a slow, i.v. infusion. Acute treatment with phentermine (0.3-10 mg/kg) decreased cocaine-maintained responding at doses that did not decrease, or decreased less, food-maintained responding for each of three unit doses of cocaine (10-100 mu g/kg/injection). Subacute treatment with phentermine (3 or 5.6 mg/kg, daily) also decreased cocaine-maintained responding more than food-maintained responding. After subacute treatment was terminated, rates of cocaine-maintained responding generally recovered to levels comparable to those seen during untreated control sessions. Phentermine (0.3-3 mg/kg) did not generally increase responding associated with a very low (1 mu g/kg/injection) unit dose of cocaine, suggesting that the decrease in cocaine-maintained responding at higher unit doses was not the result of a leftward shift in the cocaine unit dose-effect function. Phentermine (0.1-3 mg/kg) decreased responding maintained by 1-[2-[bis(4-fluorophenyl) methoxy]ethyl]-4-[3-phenylpropyl] piperazine (GBR 12909) (30 mu g/kg/injection) at doses similar to those that decreased food-maintained responding. These results show that phentermine is effective in decreasing cocaine self-administration and suggest that it may be an effective medication for cocaine abuse. C1 Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Glowa, JR (reprint author), Louisiana State Univ, Sch Med, Dept Pharmacol & Therapeut, POB 33932, Shreveport, LA 71103 USA. EM jglowa@lsumc.edu FU NIDA NIH HHS [R01 DA09820] NR 37 TC 34 Z9 34 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 FEB PY 1999 VL 288 IS 2 BP 550 EP 560 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 161KA UT WOS:000078286700022 PM 9918558 ER PT J AU Kokate, TG Banks, MK Magee, T Yamaguchi, SI Rogawski, MA AF Kokate, TG Banks, MK Magee, T Yamaguchi, SI Rogawski, MA TI Finasteride, a 5 alpha-reductase inhibitor, blocks the anticonvulsant activity of progesterone in mice SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GABA-A RECEPTOR; RAT-BRAIN; METABOLITE 5-ALPHA-PREGNAN-3-ALPHA-OL-20-ONE; DEOXYCORTICOSTERONE; NEUROSTEROIDS; MECHANISM; COMPLEX; ALLOPREGNANOLONE; EXPRESSION; MODULATION AB Progesterone is an effective anticonvulsant against pentylenetetrazol (PTZ) seizures. This action is hypothesized to require the metabolic conversion of progesterone to the gamma-aminobutyric acid(A) receptor potentiating neuroactive steroid allopregnanolone by 5 alpha-reductase isoenzymes followed by 3 alpha-hydroxy oxidoreduction. We evaluated this possibility using the competitive 5 alpha-reductase inhibitor finasteride. Progesterone (50-200 mg/kg, i.p.) protected mice against PTZ-induced seizures in a dose-dependent manner (ED50, 94 mg/kg). Pretreatment with finasteride (50-300 mg/kg, i.p.) produced a dose-dependent (ED50, 146 mg/kg) reversal of the protective effects of progesterone (2 x ED50 dose = 188 mg/kg). In contrast, finasteride (up to 300 mg/kg) failed to affect the anticonvulsant activity of allopregnanolone (10-30 mg/kg, i.p.; ED50, 12 mg/kg). Finasteride (up to 300 mg/kg) did not block the protective effect of high doses of progesterone (250-350 mg/kg) on tonic hindlimb extension in the maximal electroshock seizure test (progesterone ED50, 235 mg/kg). The anticonvulsant activity of progesterone against PTZ-induced seizures can be blocked by 5 alpha-reductase inhibition, providing strong evidence that the anticonvulsant effect of the steroid in this model is mediated by its active metabolite allopregnanolone. C1 NINDS, Neuronal Excitabil Sect, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. RP Rogawski, MA (reprint author), NINDS, Neuronal Excitabil Sect, Epilepsy Res Branch, NIH, Bldg 10,Room 5N-250,10 Ctr Dr MSC 1408, Bethesda, MD 20892 USA. EM rogawski@nih.gov RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 38 TC 132 Z9 132 U1 0 U2 2 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 FEB PY 1999 VL 288 IS 2 BP 679 EP 684 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 161KA UT WOS:000078286700039 PM 9918575 ER PT J AU Gatev, P Thomas, S Kepple, T Hallett, M AF Gatev, P Thomas, S Kepple, T Hallett, M TI Feedforward ankle strategy of balance during quiet stance in adults SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID POSTURAL CONTROL; OPEN-LOOP; DISTURBANCES; ORGANIZATION; CONSTRAINTS; MECHANISMS; MOVEMENTS; REFLEXES; INPUT AB 1. We studied quiet stance investigating strategies for maintaining balance. Normal subjects stood with natural stance and with feet together, with eyes open or closed. Kinematic, kinetic and EMG data were evaluated and cross-correlated. 2. Cross-correlation analysis revealed a high, positive, zero-phased correlation between anteroposterior motions of the centre of gravity (COG) and centre of pressure (COP), head and COG, and between linear motions of the shoulder and knee in both sagittal and frontal planes. There was a moderate, negative, zero-phased correlation between the anteroposterior motion of COP and ankle angular motion. 3. Narrow stance width increased ankle angular motion, hip angular motion, mediolateral sway of the COG, and the correlation between linear motions of the shoulder and knee in the frontal plane. Correlations between COG and COP and linear motions of the shoulder and knee in the sagittal plane were decreased. The correlation between the hip angular sway in the sagittal and frontal planes was dependent on interaction between support and vision. 4. Low, significant positive correlations with time lags of the maximum of cross-correlation of 250-300 ms were found between the EMG activity of the lateral gastrocnemius muscle and anteroposterior motions of the COG and COP during normal stance. Narrow stance width decreased both correlations whereas absence of vision increased the correlation with COP. 5. Ankle mechanisms dominate during normal stance especially in the sagittal plane. Narrow stance width decreased the role of the ankle and increased the role of hip mechanisms in the sagittal plane, while in the frontal plane both increased. 6. The modulation pattern of the lateral gastrocnemius muscle suggests a central program of control of the ankle joint stiffness working to predict the loading pattern. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. Bulgarian Acad Sci, Inst Physiol, Sofia 1113, Bulgaria. NIH, Warren Grant Magnuson Clin Ctr, Dept Rehabil Med, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N-226,10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA. EM hallett@codon.nih.gov NR 39 TC 275 Z9 277 U1 6 U2 24 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3751 EI 1469-7793 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD FEB 1 PY 1999 VL 514 IS 3 BP 915 EP 928 DI 10.1111/j.1469-7793.1999.915ad.x PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 174DJ UT WOS:000079018600027 PM 9882761 ER PT J AU Masi, AT Chrousos, GP Bornstein, SR AF Masi, AT Chrousos, GP Bornstein, SR TI Enigmas of adrenal androgen and glucocorticoid dissociation in premenopausal onset rheumatoid arthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Editorial Material ID AXIS; CORTEX C1 Univ Illinois, Coll Med, Dept Med, Peoria, IL 61605 USA. NICHHD, Dev Endocrinol Branch, Ctr Clin, NIH, Bethesda, MD USA. RP Masi, AT (reprint author), Univ Illinois, Coll Med, Dept Med, 1 Illini Dr, Peoria, IL 61605 USA. OI Masi, Alfonse/0000-0002-9695-6634 NR 26 TC 42 Z9 42 U1 1 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD FEB PY 1999 VL 26 IS 2 BP 247 EP 250 PG 4 WC Rheumatology SC Rheumatology GA 162CJ UT WOS:000078327600003 PM 9972953 ER PT J AU Adams, EM Pucino, F Yarboro, C Hicks, JE Thornton, B McGarvey, C Sonies, BC Bartlett, ML Villalba, ML Fleisher, T Plotz, PH AF Adams, EM Pucino, F Yarboro, C Hicks, JE Thornton, B McGarvey, C Sonies, BC Bartlett, ML Villalba, ML Fleisher, T Plotz, PH TI A pilot study: Use of fludarabine for refractory dermatomyositis and polymyositis, and examination of endpoint measures SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE myositis; fludarabine; lymphocyte; MRI; outcome measures ID IDIOPATHIC INFLAMMATORY MYOPATHIES; DISEASE-ACTIVITY; LYMPHOID MALIGNANCIES; PURINE ANTIMETABOLITE; RHEUMATOID-ARTHRITIS; MULTIPLE-SCLEROSIS; MUSCLE; 2-CHLORODEOXYADENOSINE; CLADRIBINE; MYOSITIS AB Objective. To study the effects of the adenine analog, fludarabine, on patients with refractory dermatomyositis and polymyositis, and to assess variables used in following myositis patients during medical intervention. Methods. Patients whose myositis was not controlled by prednisone and at least one other immunosuppressive medication were entered into a pilot study during which they received 6 monthly cycles of intravenous fludarabine. Patients were assessed at baseline, every other month. and at month 7 for primary outcome measures of strength and function. Other measurements including peripheral blood cell subsets, muscle enzymes, and various assessments of disease activity were followed monthly during the fludarabine infusion period and for up to 6 months post therapy. Results. Of 16 patients who entered the study, 4 patients were classified as improved, and 7 patients were classified as unchanged. Five patients who withdrew before month 7 were classified as treatment failures. Fludarabine caused a significant and prolonged lymphopenia without an increase in infectious complications over that seen with other immunosuppressive agents used for myositis. A sudden death of one patient at the end of the study was not thought to be drug related. Variables followed during the study emphasized the distinction between patient functional improvement nt and disease remission. Conclusion. A subset of patients with refractory myositis may benefit from fludarabine therapy and controlled trials an indicated. Refinement and validation of variables useful for following myositis patients await larger studies. C1 NIAMSD, Arthrit Branch, NIH, Bethesda, MD 20892 USA. RP Plotz, PH (reprint author), NIAMS, NIH, B10-9N244,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 38 TC 28 Z9 28 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD FEB PY 1999 VL 26 IS 2 BP 352 EP 360 PG 9 WC Rheumatology SC Rheumatology GA 162CJ UT WOS:000078327600019 PM 9972969 ER PT J AU Smolen, JS Strand, V Cardiel, M Edworthy, S Furst, D Gladman, D Gordon, C Isenberg, DA Klippel, JH Petri, M Simon, L Tugwell, P Wolfe, F AF Smolen, JS Strand, V Cardiel, M Edworthy, S Furst, D Gladman, D Gordon, C Isenberg, DA Klippel, JH Petri, M Simon, L Tugwell, P Wolfe, F TI Randomized clinical trials and longitudinal observational studies in systemic lupus erythematosus: Consensus on a preliminary core set of outcome domains SO JOURNAL OF RHEUMATOLOGY LA English DT Article; Proceedings Paper CT OMERACT IV Conference CY APR 16-20, 1998 CL CANCUN, MEXICO DE systemic lupus erythematosus; clinical trials; outcome ID DISEASE-ACTIVITY; DAMAGE AB The OMERACT module on systemic lupus erythematosus (SLE) dealt with the definition of preliminary core sets of outcome domains for randomized clinical trials (RCT) and longitudinal observational studies (LOS), After lectures introducing the problems and addressing the key issues, 6 discussion groups, 3 each for LOS and RCT, discussed and weighted more than a dozen possible items for use as outcome domains, The means of the respective 3 groups were calculated, For both RCT and LOS the same outcome domains received more than IO of a total maximum of 100 points: disease activity, health related quality of life (HRQOL), damage, and toxicity/adverse events. However, the weights for HRQOL and damage were different for LOS and RCT. A final vote led to the acceptance of these 4 variables as a preliminary core set fur outcome in SLE by more than 80% of the participants. This core set will allow for improved design, performance, and evaluation of future studies in SLE, However, a number of domains not included in the core set were regarded as important for further analysis and research. C1 Univ Vienna, Dept Internal Med 3, Div Rheumatol, A-1090 Vienna, Austria. Stanford Univ, Stanford, CA 94305 USA. Ist Nacl Nutr, Mexico City, DF, Mexico. Univ Calgary, Calgary, AB, Canada. Virginia Mason Res Ctr, Seattle, WA 98101 USA. Univ Toronto, Ctr Prognosis Studies Rheumat Dis, Toronto, ON, Canada. Univ Birmingham, Sch Med, Birmingham B15 2TT, W Midlands, England. UCL, London, England. NIAMS, NIH, Bethesda, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Ottawa, Ottawa, ON, Canada. Arthris Res Ctr, Wichita, KS USA. Ctr Clin, Wichita, KS USA. RP Smolen, JS (reprint author), Univ Vienna, Dept Internal Med 3, Div Rheumatol, Waehringer Guertel 18-20, A-1090 Vienna, Austria. OI Isenberg, David/0000-0001-9514-2455; Tugwell, Peter/0000-0001-5062-0556 NR 6 TC 64 Z9 65 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD FEB PY 1999 VL 26 IS 2 BP 504 EP 507 PG 4 WC Rheumatology SC Rheumatology GA 162CJ UT WOS:000078327600046 PM 9972996 ER PT J AU Sarlis, NJ Bayly, SF Szapary, D Simons, SS AF Sarlis, NJ Bayly, SF Szapary, D Simons, SS TI Quantity of partial agonist activity for antiglucocorticoids complexed with mutant glucocorticoid receptors is constant in two different transactivation assays but not predictable from steroid structure SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE glucocorticoid receptors; point mutations; antiglucocorticoids; activation assays ID LIGAND-BINDING DOMAIN; AMINOTRANSFERASE GENE-EXPRESSION; RETINOIC ACID RECEPTOR; BREAST-CANCER CELLS; PROGESTERONE-RECEPTOR; ESTROGEN-RECEPTOR; DNA-BINDING; HORMONE RECEPTORS; NUCLEAR RECEPTORS; PROMOTER-CONTEXT AB An unsolved question in steroid hormone action is why the amount of agonist activity displayed by antisteroids is not constant but varies with the assay conditions. Receptor mutations have provided insight into hormone action, presumably due to changes in the tertiary structure of the receptor that alter its interaction surfaces with the transcriptional machinery or/and co-factors. We have now employed two mechanistically different induction assays to determine whether disparate transactivation processes are similarly altered by receptor mutations. The two activation assays studied were (i) the standard induction of GREtkLUC in transiently transfected CV-1 cells and (ii) a never modulation of endogenous receptor activity by transiently transfected receptors in HeLa cells. Five different mutations in the ligand binding and DNA binding domains of the rat glucocorticoid receptor (CS1, CS1/CD, 451/9, C656G, and R732Q) and seven steroids of varied structures (five antagonists and two agonists) were selected for use. The results in both induction assays were the same. However, no generalizations regarding steroid structure and activity emerged. Neither of two potent glucocorticoids were active with GR-CS1, or GR-CS1/CD, while RU 486 was the only antisteroid with appreciable agonist activity. With the GR-451/9 mutant, three antagonists afforded partial agonist activity. We confirmed that the C656G mutant is both "super-sensitive" and "super-selective" for transactivation. In contrast, the R732Q mutation caused significant decreases in activity with both antagonists and subsaturating concentrations of agonists. This inability to generalize about the behavior of any class of steroids with mutant receptors may reflect an induced fit for each receptor-steroid complex. Nevertheless, the activity of a given steroid appeared to be constant in two different transactivation assays for a given mutant receptor. Thus, disparate transactivation processes may utilize identical receptor surfaces, even in the expression of partial agonist activity for specific antiglucocorticoids. Published by Elsevier Science Ltd. C1 NIDDKD, Mol & Cellular Biol Lab, Steroid Hormones Sect, NIH, Bethesda, MD 20892 USA. RP Simons, SS (reprint author), NIDDKD, Mol & Cellular Biol Lab, Steroid Hormones Sect, NIH, Bethesda, MD 20892 USA. NR 69 TC 26 Z9 26 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD FEB PY 1999 VL 68 IS 3-4 BP 89 EP 102 DI 10.1016/S0960-0760(99)00021-7 PG 14 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 198XH UT WOS:000080449200001 PM 10369406 ER PT J AU Jensen, PS Brooks-Gunn, J Graber, JA AF Jensen, PS Brooks-Gunn, J Graber, JA TI Dimensional scales and diagnostic categories: Constructing crosswalks for child psychopathology assessments - Introduction SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material C1 NIMH, Dev Psychopathol Res Branch, Rockville, MD 20857 USA. Columbia Univ, Teachers Coll, Adolescent Study Program, Dept Psychol, New York, NY 10027 USA. RP Jensen, PS (reprint author), NIMH, Dev Psychopathol Res Branch, Parklawn Bldg,Room 18C-17,5600 Fishers Lane, Rockville, MD 20857 USA. OI Jensen, Peter/0000-0003-2387-0650 NR 6 TC 13 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD FEB PY 1999 VL 38 IS 2 BP 118 EP 120 DI 10.1097/00004583-199902000-00009 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 161KF UT WOS:000078287300009 PM 9951209 ER PT J AU Jensen, PS Watanabe, H AF Jensen, PS Watanabe, H TI Sherlock Holmes and child psychopathology assessment approaches: The case of the false-positive SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE assessment; diagnosis; screening; behavioral scales; psychopathology; Diagnostic Interview Schedule for Children; Child Behavior Checklist ID DIAGNOSTIC INTERVIEW SCHEDULE; BEHAVIOR PROBLEM SYNDROMES; PSYCHIATRIC-DIAGNOSIS; CRITERION VALIDITY; SCALES; CONVERGENCE; ALGORITHMS; CONTEXT; ANXIETY; CBCL AB Objective: To explore the relative value of various methods of assessing childhood psychopathology, the authors compared 4 groups of children: those who met criteria for one or more DSM diagnoses and scored high on parent symptom checklists, those who met psychopathology criteria on either one of these two assessment approaches alone, and those who met no psychopathology assessment criterion. Method: Parents of 201 children completed the Child Behavior Checklist (CBCL), after which children and parents were administered the Diagnostic Interview Schedule for Children (version 2.1). Children and parents also completed other survey measures and symptom report inventories. The 4 groups of children were compared against "external validators" to examine the merits of "false-positive" and "false-negative" cases. Results: True-positive cases (those that met DSM criteria and scored high on the CBCL) differed significantly from the true-negative cases on most external validators. "False-positive" and "false-negative" cases had intermediate levels of most risk factors and external validators. "False-positive" cases were not normal per se because they scored significantly above the true-negative group on a number of risk factors and external validators. A similar but less marked pattern was noted for "false-negatives," Conclusions: Findings call into question whether cases with high symptom checklist scores despite no formal diagnoses should be considered "false-positive." Pending the availability of robust markets for mental illness, researchers and clinicians must resist the tendency to reify diagnostic categories or to engage in arcane debates about the superiority of one assessment approach over another. C1 NIMH, Dev Psychopathol Res Branch, Rockville, MD 20857 USA. Univ Nevada, Reno, NV 89557 USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Dept Mil Psychiat, Div Neuropsychiat, Washington, DC 20307 USA. RP Jensen, PS (reprint author), NIMH, Dev Psychopathol Res Branch, Parklawn Bldg,Room 18C-17,5600 Fishers Lane, Rockville, MD 20857 USA. OI Jensen, Peter/0000-0003-2387-0650 NR 38 TC 33 Z9 33 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD FEB PY 1999 VL 38 IS 2 BP 138 EP 146 DI 10.1097/00004583-199902000-00012 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 161KF UT WOS:000078287300012 PM 9951212 ER PT J AU Kant, AK Schatzkin, A AF Kant, AK Schatzkin, A TI Relation of age and self-reported chronic medical condition status with dietary nutrient intake in the US population SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article; Proceedings Paper CT Experimental Biology 98 Meeting CY APR 18-22, 1998 CL SAN FRANCISCO, CALIFORNIA DE chronic diseases; age; aging; elderly; nutrient intake; CSFII; NFCS; nutrition survey; morbidity; nutritional status; diet quality ID NUTRITIONAL-STATUS; LIVING ARRANGEMENTS; UNITED-STATES; OLDER ADULTS; QUALITY; HEALTH AB Objective: To examine the association of nutrient intake with age and self-reported chronic medical condition status in a large, nationally representative sample. Methods: We used data from the Continuing Survey of Food Intakes by Individuals, 1989-1991. The analytic sample included subjects aged greater than or equal to 25 years with 3 days of dietary data, and medical condition information (n=7,207). A positive response to having been informed by a doctor of having diabetes, heart disease, high blood pressure, cancer, osteoporosis, and stroke indicated the presence of chronic medical condition(s) (n=2,368). Sex-specific linear and logistic regression analyses adjusted for multiple covariates were used to examine the relation of age and morbidity status with nutrient intake. Results: In men, age was associated with an increased risk of consuming <100% of the Recommended Dietary Allowance (RDA) of Vitamin E, vitamin B-12, calcium, zinc, and iron (p<0.05), and self-reported morbidity was associated with an increased risk of consuming <100% of the RDA of protein. Relative to men, women were more likely to report less than the RDA of most nutrients examined; however, neither age nor chronic disease status were associated with increased Likelihood of reporting <100% of the RDA of any of the nutrients examined. In women, the probability of reporting < 100% of the RDA of vitamin A, vitamin B-6, folate, vitamin C, and iron, and in men, the probability of reporting <100% of the RDA of vitamin C, declined with age (p<0.05). No adverse effect of age and chronic disease interaction on intake of most nutrients was noted in men or women. Conclusions: Chronologic age and morbidity were associated with an increased risk of inadequate intake of several nutrients in free-living, independent men but not in women. C1 CUNY Queens Coll, Dept Family Nutr & Exercise Sci, Flushing, NY 11367 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Kant, AK (reprint author), CUNY Queens Coll, Dept Family Nutr & Exercise Sci, Remsen Hall,Room 306E,65-30 Kissena Blvd, Flushing, NY 11367 USA. NR 34 TC 9 Z9 9 U1 1 U2 1 PU AMER COLL NUTRITION PI NEW YORK PA C/O HOSP. JOINT DIS. 301 E. 17TH ST., NEW YORK, NY 10003 USA SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD FEB PY 1999 VL 18 IS 1 BP 69 EP 76 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 167JT UT WOS:000078629700011 PM 10067661 ER PT J AU Slavkin, HC AF Slavkin, HC TI The significance of a human smile: Observations on Bell's palsy SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article C1 Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. RP Slavkin, HC (reprint author), Natl Inst Dent & Craniofacial Res, 31 Ctr Dr,MSC 2290,Bldg 31,Room 2C39, Bethesda, MD 20892 USA. NR 5 TC 6 Z9 7 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD FEB PY 1999 VL 130 IS 2 BP 269 EP 272 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 165XW UT WOS:000078548000033 PM 10036851 ER PT J AU Acar, P Jones, M Shiota, T Masani, N Delabays, A Yamada, I Sahn, DJ Pandian, NG AF Acar, P Jones, M Shiota, T Masani, N Delabays, A Yamada, I Sahn, DJ Pandian, NG TI Quantitative assessment of chronic aortic regurgitation with 3-dimensional echocardiographic reconstruction: Comparison with electromagnetic flowmeter measurements SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID LEFT-VENTRICULAR VOLUME; MITRAL REGURGITATION; DOPPLER ASSESSMENT; SURFACE-AREA; ANIMAL-MODEL; BLOOD-FLOW; JET AREAS; VARIABILITY; QUANTIFICATION; INSUFFICIENCY AB Two-dimensional echocardiography and color Doppler are useful in the qualitative assessment of aortic regurgitation. However, color Doppler planar methods are not accurate in quantifying regurgitant flow, in part because of the complex geometry of aortic regurgitant flow events. Three-dimensional echocardiographic reconstruction is a new technique that provides dynamic 3-dimensional images of intracardiac color flow lets. We sought to determine whether the measurement of aortic regurgitant jet volume by 3-dimensional echocardiography correlated with the true regurgitant volume, measured by electromagnetic flowmeter in vivo, to accurately reflect the severity of aortic regurgitation. We performed volume-rendered 3-dimensional echocardiography in 6 sheep with surgically induced chronic eccentric aortic regurgitation. We obtained a total of 22 aortic regurgitation states by altering loading conditions. Instantaneous regurgitant flow rates were obtained by aortic and pulmonary electromagnetic flowmeters. The maximum aortic regurgitant jet volume by 3-dimensional echocardiography and the maximum jet area by 2-dimensional echocardiography were measured and compared with electromagnetic flowmeter data. By electromagnetic flowmeter, aortic regurgitant flow rate varied from 0.14 to 3.1 L/min (mean 1.25 +/- 0.78); aortic regurgitant stroke volume varied from 1 to 34 mL/beat (mean 12 +/- 8), and regurgitant fraction varied from 3% to 42% (mean 25% +/- 12%). The maximum jet volume by S-dimensional echocardiography correlated very well with the aortic regurgitant stroke volume (r = 0.92; P <.0001), with the mean regurgitant flow rate (r = 0.87; P <.0001), and with the regurgitant fraction (r = 0.87; P <.0001) derived from electromagnetic flowmeter. Both intraobserver and interobserver variability on the measurement of the jet volume by 3-dimensional echocardiography were excellent (r = 0.98; P<.0001 and r = 0.90; P<.001, respectively). The maximum jet area by 2-dimensional echocardiography did not correlate with the aortic regurgitant stroke volume (r = 0.41; P = not significant) and related poorly with the regurgitant fraction (r = 0.52; P <.05) by electromagnetic flowmeter. Dynamic 3-dimensional echocardiography can allow better determination of the geometry of the aortic regurgitant jet and may assist of quantifying the severity of aortic regurgitation. C1 Tufts Univ, Sch Med, New England Med Ctr, Cardiovasc Imaging & Hemodynam Lab, Boston, MA 02111 USA. NIH, LAMS, Bethesda, MD USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. RP Acar, P (reprint author), Necker Enfants Malad, 149 Rue Sevres, F-75743 Paris 15, France. NR 42 TC 20 Z9 21 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD FEB PY 1999 VL 12 IS 2 BP 138 EP 148 DI 10.1016/S0894-7317(99)70126-4 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 168EM UT WOS:000078678600010 PM 9950973 ER PT J AU Mozes, MM Bottinger, EP Jacot, TA Kopp, JB AF Mozes, MM Bottinger, EP Jacot, TA Kopp, JB TI Renal expression of fibrotic matrix proteins and of transforming growth factor-beta (TGF-beta) isoforms in TGF-beta transgenic mice SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID MESSENGER-RNA; RAT-KIDNEY; COMPLEX REGULATION; COLLAGEN-SYNTHESIS; EPITHELIAL-CELLS; MESANGIAL CELLS; FACTOR GENE; GROWTH-FACTOR-BETA-1; FACTOR-BETA-1; FIBROSIS AB Renal pathology in mice that are transgenic for the murine albumin enhancer/promoter linked to a full-length porcine transforming growth factor-beta 1 (TGF-beta 1) gene has been described previously. In these mice, transgene expression is limited to the liver and the plasma level of TGF-beta is increased. The earliest renal pathologic change is glomerulosclerosis, at 3 wk of age, and this is followed by tubulointerstitial fibrosis. In this study, it was hypothesized that circulating TGF-beta 1 increases renal extracellular matrix accumulation and activates local TGF-beta gene expression. Immunostaining at 5 wk revealed increased amounts of collagen I and II within the mesangium, glomerular capillary loops, and interstitium, while the amount of collagen IV was normal. Similarly, Northern analysis showed increased expression of mRNA encoding collagen I and III, as well as biglycan and decorin, while the expression of collagen IV was unchanged. These changes began as early as 1 wk of age, a time before the appearance of glomerulosclerosis. To evaluate matrix degradation, collagenase IV activity was evaluated by gelatin zymography and an increase in matrix metalloproteinase-2 was found. Finally, the production of tissue inhibitors of metalloproteinase was evaluated. Tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA was increased 18-fold, while TIMP-2 and TIMP-3 were unchanged. In 2-wk-old transgenic kidney, local expression of TGF-beta 1, beta 2, and beta 3 protein was similar to wild-type mice. In 5-wk-old transgenic mice, TGF-beta 1 and beta 2 protein was present in increased amounts within glomeruli, and renal TGF-beta 1 mRNA was increased threefold. It is concluded that elevated levels of circulating TGF-beta 1 may act on the kidney to increase matrix protein production and decrease matrix remodeling. Only after glomerulosclerosis is established does local glomerular overproduction of TGF-beta become manifest. C1 NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. NIDDKD, Renal Cell Biol Sect, NIH, Bethesda, MD 20892 USA. NCI, Chemoprevent Lab, NIH, Bethesda, MD 20892 USA. Semmelweis Univ Med, Sch Med, Inst Pathophysiol, Budapest, Hungary. RP Kopp, JB (reprint author), NIDDKD, Kidney Dis Sect, NIH, Bldg 10,Room 3N116, Bethesda, MD 20892 USA. RI Mozes, Miklos/E-9003-2011 NR 29 TC 90 Z9 96 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD FEB PY 1999 VL 10 IS 2 BP 271 EP 280 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 161ZP UT WOS:000078320700009 PM 10215326 ER PT J AU Ito, Y Oka, H AF Ito, Y Oka, H TI Countercurrent chromatography: Principle and application to food analysis SO JOURNAL OF THE FOOD HYGIENIC SOCIETY OF JAPAN LA Japanese DT Article ID PREPARATIVE SEPARATION; SYNTHETIC MIXTURE; PHLOXINE-B; PURIFICATION; COMPONENTS C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 27 TC 0 Z9 0 U1 0 U2 0 PU FOOD HYG SOC JPN PI TOKYO PA 6-1 JINGU-MAE 2-CHOME SHIBUYA-KU, TOKYO, JAPAN SN 0015-6426 J9 J FOOD HYG SOC JPN JI J. Food Hyg. Soc. Jpn. PD FEB PY 1999 VL 40 IS 1 BP J15 EP J27 PG 13 WC Food Science & Technology SC Food Science & Technology GA 173JE UT WOS:000078976700018 ER PT J AU Gilman, S Low, PA Quinn, N Albanese, A Ben-Shlomo, Y Fowler, CJ Kaufman, H Klockgether, T Lang, AE Lantos, PL Litvan, I Mathias, CJ Oliver, E Robertson, D Schatz, I Wenning, GK AF Gilman, S Low, PA Quinn, N Albanese, A Ben-Shlomo, Y Fowler, CJ Kaufman, H Klockgether, T Lang, AE Lantos, PL Litvan, I Mathias, CJ Oliver, E Robertson, D Schatz, I Wenning, GK TI Consensus statement on the diagnosis of multiple system atrophy SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE multiple system atrophy; parkinsonism; cerebellar ataxia; autonomic insufficiency; urinary dysfunction; glial cytoplasmic inclusion ID CLINICAL-FEATURES; NATURAL-HISTORY; DYSFUNCTION; CRITERIA AB We report the results of a consensus conference on the diagnosis of multiple system atrophy (MSA). We describe the clinical features of the disease, which include four domains: autonomic failure/urinary dysfunction, parkinsonism and cerebellar ataxia, and corticospinal dysfunction. We set criteria to define the relative importance of these features. The diagnosis of possible MSA requires one criterion plus two features from separate other domains. The diagnosis of probable MSA requires the criterion for autonomic failure/urinary dysfunction plus poorly levodopa responsive parkinsonism or cerebellar ataxia. The diagnosis of definite MSA requires pathological confirmation. (C) 1999 Published by Elsevier Science B.V. All rights reserved. C1 Univ Michigan, Med Ctr, Dept Neurol, Ann Arbor, MI 48109 USA. Mayo Clin, Dept Neurol, Rochester, MN 55905 USA. Natl Hosp Neurol & Neurosurg, Dept Neurol, London WC1N 3BG, England. Univ Cattolica, Ist Neurol, Dept Neurol, I-00168 Rome, Italy. Dept Social Med, Bristol BS8 2P, Avon, England. Mt Sinai Med Ctr, Dept Neurol, New York, NY 10029 USA. Univ Bonn, Dept Neurol, D-53105 Bonn, Germany. Toronto Western Hosp, Dept Neurol, Toronto, ON MP11 304, Canada. Inst Psychiat, Dept Neuropathol, London SE5 8AF, England. NINDS, NIH, Bethesda, MD 20892 USA. St Marys Hosp, Pickering Unit, Imperial Coll Sch Med St Marys, Dept Neurovasc Med, London W2 1NY, England. Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37232 USA. Vanderbilt Univ, Dept Neurol, Nashville, TN 37232 USA. Univ Hawaii Manoa, Dept Med, Honolulu, HI 96813 USA. Univ Innsbruck, Neurol Klin, A-6020 Innsbruck, Austria. RP Gilman, S (reprint author), Univ Michigan, Med Ctr, Dept Neurol, 1500 E Med Ctr Dr 1914 TC, Ann Arbor, MI 48109 USA. EM sgilman@umich.edu RI Fowler, Clare /B-2812-2009; OI Litvan, Irene/0000-0002-3485-3445 NR 26 TC 747 Z9 786 U1 2 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD FEB 1 PY 1999 VL 163 IS 1 BP 94 EP 98 DI 10.1016/S0022-510X(98)00304-9 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 182RV UT WOS:000079512700020 PM 10223419 ER PT J AU Walther, MM Keiser, HR Choyke, PL Rayford, W Lyne, JC Linehan, WM AF Walther, MM Keiser, HR Choyke, PL Rayford, W Lyne, JC Linehan, WM TI Management of hereditary pheochromocytoma in von Hippel-Landau kindreds with partial adrenalectomy SO JOURNAL OF UROLOGY LA English DT Article DE pheochromocytoma; Hippel-Lindau disease; treatment outcome; adrenalectomy ID ALDOSTERONE-PRODUCING ADENOMA; ENDOCRINE NEOPLASIA TYPE-2; BILATERAL ADRENALECTOMY; DISEASE AB Purpose: In patients with von Hippel-Lindau disease multiple bilateral adrenal pheochromocytoma can develop, which has traditionally been treated with adrenalectomy. Partial adrenalectomy can preserve normal adrenal function and avoid the morbidity associated with medical adrenal replacement. We demonstrate whether adrenal function could be preserved by partial adrenalectomy in patients with von Hippel-Lindau disease. Materials and Methods: From 1995 to 1998, 13 consecutive von Hippel-Lindau disease patients with pheochromocytoma underwent 14 partial and 6 complete unilateral adrenalectomies. Function of residual normal adrenal and recurrence of adrenal pheochromocytoma were determined at followup. Results: Of the patients 2 had undergone unilateral adrenalectomy and 1. had undergone complete and partial adrenalectomy previously. Following surgery residual normal adrenal tissue consisted of 1 partial adrenal in 3 patients, bilateral partial adrenal in 5, partial and complete adrenal gland in 1, 1 complete adrenal gland in 3 and no adrenal tissue in 1. Three patients with residual adrenal tissue were placed on medical adrenal replacement until adrenocorticotropic hormone stimulation testing demonstrated adrenocortical function. In 2 patients 1 adrenal and 2 extra-adrenal new pheochromocytomas developed 11 and 152 months, respectively, after partial adrenalectomy. No morbidity related to pheochromocytoma was observed during followup. Conclusions: Partial adrenalectomy can preserve adrenal function in patients with a hereditary form of pheochromocytoma. C1 NHLBI, Urol Oncol Branch, NCI, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Walther, MM (reprint author), NHLBI, Urol Oncol Branch, NCI, Bethesda, MD 20892 USA. NR 16 TC 59 Z9 59 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD FEB PY 1999 VL 161 IS 2 BP 395 EP 398 DI 10.1016/S0022-5347(01)61900-1 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 158UZ UT WOS:000078136900004 PM 9915410 ER PT J AU Hanno, PM Landis, JR Matthews-Cook, Y Kusek, J Nyberg, L AF Hanno, PM Landis, JR Matthews-Cook, Y Kusek, J Nyberg, L CA Interstitial Cystitis Database Study Grp TI The diagnosis of interstitial cystitis revisited: Lessons learned from the National Institutes of Health Interstitial Cystitis Database study SO JOURNAL OF UROLOGY LA English DT Article DE cystitis, interstitial; diagnosis; bladder ID CELLS AB Purpose: The lack of a precise working definition of interstitial cystitis may have resulted in the de facto use of the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) "research" definition by clinicians. We evaluated these strict criteria in light of the broader inclusion criteria for patients evaluated in the Interstitial Cystitis Database study to determine their utility in clinical practice as a useful basis for the diagnosis of interstitial cystitis. Materials and Methods: A total of 379 women who completed screening for the Interstitial Cystitis Database before January 1, 1996 met the basic criteria of urinary frequency, urgency or pain for at least 6 months in duration without a diagnosable etiology. Of these patients 148 underwent cystoscopy and hydrodistention of the bladder as a part of the evaluation. All patients were followed for a minimum of 1 year. Comparisons were made between patients judged to have a clinical diagnosis of interstitial cystitis and those who met the NIDDK research definition of the syndrome. Results: Almost 90% of patients potentially meeting NIDDK criteria are believed by experienced clinicians to have interstitial cystitis, confirming the research value of these criteria in defining a homogeneous population for study. However, strict application of NIDDK criteria would have misdiagnosed more than 60% of patients regarded by researchers as definitely or likely to have interstitial cystitis. Conclusions: The NIDDK criteria are too restrictive to he used by clinicians as the diagnostic definition of interstitial cystitis. C1 Univ Penn, Grad Hosp, Philadelphia, PA 19104 USA. Temple Univ, Philadelphia, PA 19122 USA. Penn State Univ, Hershey, PA USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Oklahoma, Oklahoma City, OK USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Wisconsin, Madison, WI USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Henry Ford Hosp, Detroit, MI 48202 USA. NIDDKD, Bethesda, MD 20892 USA. RP Hanno, PM (reprint author), Temple Univ Hosp, Dept Urol, 3 Parkinson Pavil,Broad & Tioga St, Philadelphia, PA 19140 USA. RI Landis, J. Richard/A-9330-2010 FU NIDDK NIH HHS [UO1 DK45859] NR 15 TC 257 Z9 267 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD FEB PY 1999 VL 161 IS 2 BP 553 EP 557 DI 10.1016/S0022-5347(01)61948-7 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 158UZ UT WOS:000078136900052 PM 9915447 ER PT J AU McGovern, FJ Wood, BJ Goldberg, SN Mueller, PR AF McGovern, FJ Wood, BJ Goldberg, SN Mueller, PR TI Radio frequency ablation of renal cell carcinoma via image guided needle electrodes SO JOURNAL OF UROLOGY LA English DT Article DE kidney; carcinoma; renal cell; neoplasms; ultrasonography ID RADIOFREQUENCY C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NIH, Dept Radiol, Bethesda, MD 20892 USA. RP McGovern, FJ (reprint author), Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 3 TC 126 Z9 134 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD FEB PY 1999 VL 161 IS 2 BP 599 EP 600 DI 10.1016/S0022-5347(01)61961-X PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 158UZ UT WOS:000078136900065 PM 9915457 ER PT J AU Scheinman, M Ascher, E Levi, GS Hingorani, A Shirazian, D Seth, P AF Scheinman, M Ascher, E Levi, GS Hingorani, A Shirazian, D Seth, P TI p53 gene transfer to the injured rat carotid artery decreases neointimal formation SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 1998 Lifeline-Foundation-Research-Initiatives-in-Vascular-Disease Conference CY FEB 19-20, 1998 CL BETHESDA, MD SP Lifeline Fdn Res Initiat Vasc Surg ID SMOOTH-MUSCLE CELLS; WILD-TYPE P53; DEPENDENT KINASE INHIBITOR; CYCLE ARREST; APOPTOSIS; PROLIFERATION; EXPRESSION; THERAPY; ANGIOPLASTY; CARCINOMA AB Purpose: We studied the effect of adenovirus-mediated p53 gene transfer on the injured rat carotid artery to determine its ability to decrease the formation of neointima. Methods: In vivo gene transfer was used in isolated segments of balloon-injured rat carotid arteries. Genetically modified adenovirus containing the gene encoding for wild-type p53 (AdWTp53) was applied in three concentrations: 8 x 10(10), 1.6 x 10(10), and 8 x 10(9) pfu/mL. Control rats received either adenovirus null (AdNull), 8 x 1010 pfu/mL, or Medium-199 solution (vehicle). Expression of p53 was determined 4 days after gene transfer by Western blotting. Neointimal formation was assessed after 14 days by harvesting carotid arteries and determining the intima/media (I/M) ratio based on cross sectional area measurement. Simultaneously, immunohistochemistry was done to detect the presence of p53 on smooth muscle cell nuclei. Results: P53 expression was confirmed by Western blotting. There was a significant reduction in neointimal formation on all treated animals compared with controls. The highest dose of AdWTp53 (8 x 10(10) pfu/ml) resulted in a near-total arrest of neointimal formation (I/M = 0.09 +/- 0.03, mean +/- SEM) with P < .0001 versus vehicle (I/M = 2.23 +/- 0.15) or AdNull (I/M = 2.12 +/- .12). The intermediate dose of AdWTp53 (1.6 x 1010 pfu/ml) resulted in an I/M value of 1.04 +/- 0.18, with P < .001 versus vehicle and P=.001 versus AdNull. The lowest dose (8 x 109 pfu/mL) resulted in an I/M value of 1.12 +/- 0.18, with P<.001 versus vehicle and P<.002 versus AdNull. The immunohistochemistry was positive for the presence of p53 in rats infected with AdWTp53. Conclusions: Adenovirus-mediated gene transfer of p53 protein significantly decreases the formation of neointima in the rat carotid injury model. This map represent a potential therapy for restenosis in humans. C1 Maimonides Hosp, Div Vasc Surg, Brooklyn, NY 11219 USA. Maimonides Hosp, Dept Surg, Brooklyn, NY 11219 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Ascher, E (reprint author), Maimonides Hosp, Div Vasc Surg, 4802 10th Ave, Brooklyn, NY 11219 USA. NR 30 TC 32 Z9 34 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD FEB PY 1999 VL 29 IS 2 BP 360 EP 369 DI 10.1016/S0741-5214(99)70389-7 PG 10 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 165QB UT WOS:000078528900028 PM 9950994 ER PT J AU Hugin, AW Tang, Y AF Hugin, AW Tang, Y TI An immunochemical focus assay to quantify replication competent and defective viruses involved in murine acquired immunodeficiency syndrome SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE MAIDS; murine AIDS; murine leukemia virus; MuLV; defective virus; immunofocus assay; titration ID RETROVIRUS-INDUCED IMMUNODEFICIENCY; LEUKEMIA VIRUSES; INDUCTION; DISEASE; MOUSE; MAIDS; MODEL; MICE; AIDS AB Murine acquired immunodeficiency syndrome is a lymphoproliferative disease with a concurrently developing immunodeficiency. The disease is induced after injection of supernatant of a chronically infected cell line that releases a mixture of two replication competent virus classes and a replication incompetent virus species responsible for pathogenicity. An immunochemical detection assay for virus infected foci on cell monolayers has been developed. This assay allows quantification of all three types of virus. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Hosp Geneva, Dept Dermatol, CH-1211 Geneva 14, Switzerland. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. RP Hugin, AW (reprint author), Univ Hosp Geneva, Dept Dermatol, CH-1211 Geneva 14, Switzerland. EM ambros.hugin@hcuge.ch NR 13 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD FEB PY 1999 VL 77 IS 2 BP 217 EP 224 DI 10.1016/S0166-0934(98)00156-6 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 168PP UT WOS:000078701700011 PM 10092145 ER PT J AU Whitehead, SS Firestone, CY Karron, RA Crowe, JE Elkins, WR Collins, PL Murphy, BR AF Whitehead, SS Firestone, CY Karron, RA Crowe, JE Elkins, WR Collins, PL Murphy, BR TI Addition of a missense mutation present in the L gene of respiratory syncytial virus (RSV) cpts530/1030 to RSV vaccine candidate cpts248/404 increases its attenuation and temperature sensitivity SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSCRIPTION ELONGATION-FACTOR; SERONEGATIVE CHIMPANZEES; MESSENGER-RNA; TS PHENOTYPE; LIVE; CHILDREN; MUTANT; IMMUNIZATION; EXPRESSION; INFANTS AB Respiratory syncytial virus (RSV) cpts530/1030 is an attenuated, temperature-sensitive subgroup A vaccine candidate derived previously from cold-passaged RSV (cpRSV) by two sequential rounds of chemical mutagenesis and biological selection. Here, cpts530/1030 was shown to be highly attenuated in the upper and lower respiratory tracts of seronegative chimpanzees. However, evaluation in seropositive children showed that it retains sufficient replicative capacity and virulence to preclude its direct use as a live attenuated vaccine. Nucleotide sequence analysis of the genome of cpts530/1030 showed that it had acquired two nucleotide substitutions (compared to its cpts530 parent), both of which were in the L gene: a silent mutation at nucleotide position 8821 (amino acid 108) and a missense mutation at nucleotide position 12458 resulting in a tyrosine-to-asparagine change at amino acid 1321, herein referred to as the 1030 mutation. It also contained the previously identified 530 missense mutation at nucleotide 10060 in the L gene. The genetic basis of attenuation of cpts530/1030 was defined by the introduction of the 530 and 1030 mutations into a cDNA clone of cpRSV, from which recombinant RSV was derived and analyzed to determine the contribution of each mutation to the temperature sensitivity (ts) and attenuation (att) phenotypes of cpts530/1030. The 530 mutation, derived from cpts530, was previously shown to be responsible for the ts and aft phenotypes of that virus. In the present study, the 1030 mutation was shown to be responsible for the increased temperature sensitivity of cpts530/1030. In addition, the 1030 mutation was shown to be responsible for the increased level of attenuation of cpts530/1030 in the upper and lower respiratory tracts of mice. The 530 and 1030 mutations were additive in their effects on the ts and aft phenotypes. It was possible to introduce the 1030 mutation, but not the 530 mutation, into an attenuated vaccine candidate with residual reactogenicity in very young infants, namely, cpts248/404, by use of reverse genetics. The inability to introduce the 530 mutation into the cpts248/404 virus was shown to be due to its incompatibility with the 248 missense mutation at the level of L protein function. The resulting rA2cp248/404/1030 mutant virus was more temperature sensitive and more attenuated than the cpts248/404 parent virus, making it a promising new RSV vaccine candidate created by use of reverse genetics to improve upon an existing vaccine virus. C1 NIAID, Resp Viruses Sect, Infect Dis Lab, Bethesda, MD 20892 USA. NIAID, Expt Primate Virol Sect, Infect Dis Lab, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Int Hlth, Ctr Immunizat Res, Baltimore, MD 21205 USA. RP Whitehead, SS (reprint author), NIAID, Resp Viruses Sect, Infect Dis Lab, 7 Ctr Dr,MSC 0720, Bethesda, MD 20892 USA. RI Crowe, James/B-5549-2009 OI Crowe, James/0000-0002-0049-1079 NR 28 TC 65 Z9 69 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1999 VL 73 IS 2 BP 871 EP 877 PG 7 WC Virology SC Virology GA 156TE UT WOS:000078017500002 PM 9882287 ER PT J AU Schubert, U Bour, S Willey, RL Strebel, K AF Schubert, U Bour, S Willey, RL Strebel, K TI Regulation of virus release by the macrophage-tropic human immunodeficiency virus type 1 AD8 isolate is redundant and can be controlled by either Vpu or Env SO JOURNAL OF VIROLOGY LA English DT Article ID HIV ACCESSORY PROTEINS; ENVELOPE GLYCOPROTEIN; CYTOPLASMIC DOMAIN; PARTICLE RELEASE; MOLECULAR CLONE; CD4; CELLS; INFECTION; PHOSPHORYLATION; REPLICATION AB The human immunodeficiency virus type 1 (HIV-1) Vpu and Env proteins are expressed from a bicistronic mRNA. To address the biological significance of the coordinated expression of vpu and env, we compared the relative effects on particle release of HIV-1 isolates containing an intact vpu gene or carrying point mutations in its initiation codon or internal deletions, respectively. We found that the primary AD8 isolate, which is unable to express vpu due to a mutation in its translation initiation codon, was able to replicate in primary macrophages and peripheral blood mononuclear cells with efficiency similar to that of an isogenic variant expressing Vpu. Interestingly, AD8 lacking a vpu initiation codon produced higher levels of Env protein than its Vpu-expressing isogenic variant. In contrast, disabling Vpu without removing the vpu initiation codon did not alter Env expression but significantly reduced virus production. AD8 Env when provided in trans was capable of enhancing release not only of AD8 particles but also of viruses of the T-cell-tropic NL4-3 isolate. We conclude that AD8 Env encodes a Vpu-like activity similar to that previously reported for HIV-2 Env proteins and is thus able to augment virus secretion. When expressed at elevated levels, i.e., following mutation of the vpu initiation codon, AD8 Env was able to compensate for the lack of Vpu and thereby ensure efficient virus release. Thus, the ability to regulate virus release is redundant in AD8 and can be controlled by either Vpu or Env. Since Vpu controls several independent functions, including CD4 degradation, our results suggest that some HIV-1 isolates may have evolved a mechanism to regulate Vpu activity without compromising their ability to efficiently replicate in the host cells. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Strebel, K (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Room 312,9000 Rockville Pike, Bethesda, MD 20892 USA. EM ks10z@nih.gov NR 59 TC 49 Z9 50 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1999 VL 73 IS 2 BP 887 EP 896 PG 10 WC Virology SC Virology GA 156TE UT WOS:000078017500004 PM 9882289 ER PT J AU Hirsch, VM Campbell, BJ Bailes, E Goeken, R Brown, C Elkins, WR Axthelm, M Murphey-Corb, M Sharp, PM AF Hirsch, VM Campbell, BJ Bailes, E Goeken, R Brown, C Elkins, WR Axthelm, M Murphey-Corb, M Sharp, PM TI Characterization of a novel simian immunodeficiency virus (SIV) from L'Hoest monkeys (Cercopithecus l'hoesti): Implications for the origins of SIVmnd and other primate lentiviruses SO JOURNAL OF VIROLOGY LA English DT Article ID AFRICAN-GREEN MONKEYS; CROSS-SPECIES TRANSMISSION; WILD-CAPTURED CHIMPANZEE; HIGHLY DIVERGENT; GENETIC DIVERSITY; TANTALUS MONKEYS; SOOTY MANGABEYS; SYKES MONKEYS; PROVIRAL DNA; SEQUENCE AB The human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) appear to have originated by cross-species transmission of simian immunodeficiency virus (SN) from asymptomatically infected African primates. Few of the SIVs characterized to date efficiently infect human primary lymphocytes. Interesting, two of the three identified to infect such cultures (SIVsm and SIVcpz) have appeared in human populations as genetically related HIVs. In the present study, we characterized a novel SIV isolate from an East African monkey of the Cercopithecus genus, the l'hoest monkey (C. l'hoesti), which we designated SIVlhoest. This SN isolate efficiently infected both human and macaque lymphocytes and resulted in a persistent infection of macaques, characterized by high primary virus load and a progressive decline in circulating CD4 lymphocytes, consistent with progression to AIDS. Phylogenetic analyses showed that SIVIhoest is genetically distinct from other previously characterized primate lentiviruses but clusters in the same major lineage as SIV from mandrills (SIVmnd), a West African primate species. Given the geographic distance between the ranges of l'hoest monkeys and mandrills, this may indicate that SIVmnd arose through cross-species transmission from close relatives of l'hoest monkeys that are sympatric with mandrills. These observations lend support to the hypothesis that the primate lentiviruses originated and coevolved within monkeys of the Cercopithecus genus. Regarded in this light, lentivirus infections of primates not belonging to the Cercopithecus genus may have resulted from cross-species transmission in the not-too-distant past. C1 NIAID, Mol Microbiol Lab, NIH, Rockville, MD 20852 USA. NIAID, Infect Dis Lab, NIH, Rockville, MD 20852 USA. Univ Nottingham, Queens Med Ctr, Div Genet, Nottingham NG7 2UH, England. Oregon Reg Primate Res Ctr, Div Pathobiol, Beaverton, OR 97006 USA. Univ Pittsburgh, Dept Microbiol, Pittsburgh, PA USA. RP Hirsch, VM (reprint author), NIAID, Mol Microbiol Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. RI Sharp, Paul/F-5783-2010 OI Sharp, Paul/0000-0001-9771-543X NR 51 TC 77 Z9 77 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1999 VL 73 IS 2 BP 1036 EP 1045 PG 10 WC Virology SC Virology GA 156TE UT WOS:000078017500019 PM 9882304 ER PT J AU Roper, RL Moss, B AF Roper, RL Moss, B TI Envelope formation is blocked by mutation of a sequence related to the HKD phospholipid metabolism motif in the vaccinia virus F13L protein SO JOURNAL OF VIROLOGY LA English DT Article ID EXTRACELLULAR VIRUS; CELL-MEMBRANE; GENE; GLYCOPROTEIN; ANTIGEN; RELEASE; IDENTIFICATION; DISSEMINATION; SUPERFAMILY; DELETION AB The outer envelope of the extracellular form of vaccinia virus is derived from Golgi membranes that have been modified by the insertion of specific viral proteins, of which the major component is the 37-kDa, palmitylated, nonglycosylated product of the F13L gene. The F13L protein contains a variant of the HKD (His-Lys-Asp) motif, which is conserved in numerous enzymes of phospholipid metabolism. Vaccinia virus mutants with a conservative substitution of either the K (K314R) or the D (D319E) residue of the F13L protein formed only tiny plaques similar to those produced by an F13L deletion mutant, were unable to produce extracellular enveloped virions, and failed to mediate low-pH-induced fusion of infected cells. Membrane-wrapped forms of intracellular virus were rarely detected in electron microscopic images of cells infected with either of the mutants. Western blotting and pulse-chase experiments demonstrated that the D319E protein was less stable than either the K314R or wild-type F13L protein. Most striking, however, was the failure of either of the two mutated proteins to concentrate in the Golgi compartment. Palmitylation, oleation, and partitioning of the F13L protein in Triton X-114 detergent were unaffected by the K314R substitution. These results indicated that the F13L protein must retain the K314 and D319 for it to localize in the Golgi compartment and function in membrane envelopment of vaccinia virus. C1 NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, Bldg 4,Room 229,4 Ctr Dr,MSC 0445, Bethesda, MD 20892 USA. NR 51 TC 30 Z9 32 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1999 VL 73 IS 2 BP 1108 EP 1117 PG 10 WC Virology SC Virology GA 156TE UT WOS:000078017500027 PM 9882312 ER PT J AU Davis, DA Yusa, K Gillim, LA Newcomb, FM Mitsuya, H Yarchoan, R AF Davis, DA Yusa, K Gillim, LA Newcomb, FM Mitsuya, H Yarchoan, R TI Conserved cysteines of the human immunodeficiency virus type 1 protease are involved in regulation of polyprotein processing and viral maturation of immature virions SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 PROTEASE; OXIDATIVE STRESS; IN-VITRO; ASPARTIC PROTEASE; INFECTED-CELLS; INHIBITOR; INFECTIVITY; PROTEINASE; ACTIVATION; PARTICLES AB We investigated the role of the two highly conserved cysteine residues, cysteines 67 and 95, of the human immunodeficiency virus type 1 (HIV-1) protease in regulating the activity of that protease during viral maturation. To this end, we generated four HIV-1 molecular clones: the wild type, containing both cysteine residues; a protease mutant in which the cysteine at position 67 was replaced by an alanine (C67A); a C95A protease mutant; and a double mutant (C67A C95A). When immature virions were produced in the presence of an HIV-1 protease inhibitor, KNI-272, and the inhibitor was later removed, limited polyprotein processing was observed for wild-type virion preparations over a 20-h period, Treatment of immature wild-type virions with the reducing agent dithiothreitol considerably improved the rate and extent of Gag processing, suggesting that the protease is, in part, reversibly inactivated by oxidation of the cysteine residues. In support of this, C67A C95A virions processed Gag up to fivefold faster than wild-type virions in the absence of a reducing agent. Furthermore, oxidizing agents, such as H2O2 and diamide, inhibited Gag processing of wild-type virions, and this effect was dependent on the presence of cysteine 95. Electron microscopy revealed that a greater percentage of double-mutant virions than wild-type virions developed a mature-like morphology on removal of the inhibitor. These studies provide evidence that under normal culture conditions the cysteines of the HIV-1 protease are susceptible to oxidation during viral maturation, thus preventing immature virions from undergoing complete processing following their release. This is consistent with the cysteines being involved in the regulation of viral maturation in cells under oxidative stress. C1 NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. NCI, Expt Retrovirol Sect, Med Branch, Bethesda, MD 20892 USA. RP Davis, DA (reprint author), NCI, HIV & AIDS Malignancy Branch, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. FU NCI NIH HHS [ZO1 CM06737] NR 46 TC 33 Z9 34 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1999 VL 73 IS 2 BP 1156 EP 1164 PG 9 WC Virology SC Virology GA 156TE UT WOS:000078017500032 PM 9882317 ER PT J AU Chiorini, JA Kim, F Yang, L Kotin, RM AF Chiorini, JA Kim, F Yang, L Kotin, RM TI Cloning and characterization of adeno-associated virus type 5 SO JOURNAL OF VIROLOGY LA English DT Article ID RECOMBINANT ADENOASSOCIATED VIRUS; INHIBITS CELLULAR-TRANSFORMATION; SITE-SPECIFIC ENDONUCLEASE; REP PROTEINS; HUMAN PARVOVIRUS; DNA-REPLICATION; GENE-EXPRESSION; SEQUENCE REQUIREMENTS; BOVINE PAPILLOMAVIRUS; MUTATIONAL ANALYSIS AB Adeno-associated virus type 5 (AAV5) is distinct from other dependovirus serotypes based on DNA hybridization and serological data. To better understand the biology of AAV5, we have cloned and sequenced its genome and generated recombinant AAV5 particles. The single-stranded DNA genome is similar in length and genetic organization to that of AAV2. The rep gene of AAV5 is 67% homologous to AAV2, with the majority of the changes occurring in the carboxyl and amino termini. This homology is much less than that observed with other reported AAV serotypes. The inverted terminal repeats (ITRs) are also unique compared to those of the other AAV serotypes. While the characteristic AAV hairpin structure and the Rep DNA binding site are retained, the consensus terminal resolution site is absent. These differences in the Rep proteins and the ITRs result in a lack of cross-complementation between AAV2 and AAV5 as measured by the production of recombinant AAV particles. Alignment of the cap open reading frame with that of the other AAV serotypes identifies both conserved and variable regions which could affect tissue tropism and particle stability. Comparison of transduction efficiencies in a variety of cells lines and a lack of inhibition by soluble heparin indicate that AAV5 may utilize a distinct mechanism of uptake compared to AAV2. C1 NHLBI, Mol Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Kotin, RM (reprint author), NHLBI, Mol Hematol Branch, NIH, Bldg 10,7D18,10 Ctr Dr,MSC 1654, Bethesda, MD 20892 USA. RI kotin, robert/B-8954-2008 NR 56 TC 240 Z9 245 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1999 VL 73 IS 2 BP 1309 EP 1319 PG 11 WC Virology SC Virology GA 156TE UT WOS:000078017500051 PM 9882336 ER PT J AU Skiadopoulos, MH Surman, S Tatem, JM Paschalis, M Wu, SL Udem, SA Durbin, AP Collins, PL Murphy, BR AF Skiadopoulos, MH Surman, S Tatem, JM Paschalis, M Wu, SL Udem, SA Durbin, AP Collins, PL Murphy, BR TI Identification of mutations contributing to the temperature-sensitive, cold-adapted, and attenuation phenotypes of the live-attenuated cold-passage 45 (cp45) human parainfluenza virus 3 candidate vaccine SO JOURNAL OF VIROLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; INFLUENZA-A/UDORN/72 H3N2 VIRUS; CLONED CDNA; WEANLING HAMSTERS; GENETIC-ANALYSIS; TYPE-3 VIRUS; RNA; RECOVERY; MUTANTS; EXPRESSION AB The live-attenuated human parainfluenza virus 3 (PIV3) cold-passage 45 (cp45) candidate vaccine was shown previously to be safe, immunogenic, and phenotypically stable in seronegative human infants. Previous findings indicated that each of the three amino acid substitutions in the L polymerase protein of cp45 independently confers the temperature-sensitive (ts) and attenuation (aft) phenotypes but not the cold-adaptation (ca) phenotype (29). cp45 contains 12 additional potentially important point mutations in other proteins (N, C, M, F, and hemagglutinin-neuraminidase [HN]) or in cis-acting sequences (the leader region and the transcription gene start [GSI signal of the N gene), and their contribution to these phenotypes was undefined. To further characterize the genetic basis for the ts, ca, and an phenotypes of this promising vaccine candidate, we constructed, using a reverse genetics system, a recombinant cp45 virus that contained all 15 cp45-specific mutations mentioned above, and found that it was essentially indistinguishable from the biologically derived cp45 on the basis of plaque size, level of temperature sensitivity, cold adaptation, level of replication in the upper and lower respiratory tract of hamsters, and ability to protect hamsters from subsequent wild-type PIV3 challenge. We then constructed recombinant viruses containing the cp45 mutations in individual proteins as well as several combinations of mutations. Analysis of these recombinant viruses revealed that multiple cp45 mutations distributed throughout the genome contribute to the ts, ca, and an phenotypes, In addition to the mutations in the L gene, at least one other mutation in the 3' N region (i.e., including the leader, N GS, and N coding changes) contributes to the fs phenotype. A recombinant virus containing all the cp45 mutations except those in L was more ts than cp45, illustrating the complex nature of this phenotype. The ea phenotype of cp45 also is a complex composite phenotype, reflecting contributions of at least three separate genetic elements, namely, mutations within the 3' N region, the L protein, and the C-M-F-HN region. The an phenotype is a composite of both ts and non-ts mutations. Attenuating ts mutations are located in the L protein, and non-ts attenuating mutations are located in the C and F proteins. The presence of multiple ts and non-ts attenuating mutations in cp45 likely contributes to the high level of attenuation and phenotypic stability of this promising vaccine candidate. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Wyeth Lederle Vaccines & Pediat, Pearl River, NY 10965 USA. RP Skiadopoulos, MH (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 7,Rm 100,7 Ctr Dr,MSC 0720, Bethesda, MD 20892 USA. NR 38 TC 64 Z9 65 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1999 VL 73 IS 2 BP 1374 EP 1381 PG 8 WC Virology SC Virology GA 156TE UT WOS:000078017500057 PM 9882342 ER PT J AU Patton, JT Chen, DY AF Patton, JT Chen, DY TI RNA-binding and capping activities of proteins in rotavirus open cores SO JOURNAL OF VIROLOGY LA English DT Article ID MESSENGER-RNA; GUANYLYLTRANSFERASE ACTIVITY; NUCLEOTIDYL TRANSFER; COVALENT CATALYSIS; REPLICASE ACTIVITY; ENZYME; PARTICLES; GENOME; VP2; SEGMENT-1 AB Guanylyltransferases are members of the nucleotidyltransferase family and function in mRNA capping by transferring GMP to the phosphate end of nascent RNAs. Although numerous guanylyltransferases have been identified, studies which define the nature of the interaction between the capping enzymes of any origin and their RNA substrates have been limited. Here, we have characterized the RNA-binding activity of VP3, a minor protein component of the core of rotavirions that has been proposed to function as the viral guanylyltransferase and to direct the capping of the 11 transcripts synthesized from the segmented double-stranded RNA (dsRNA) genome of these viruses. Gel shift analysis performed with disrupted (open) virion-derived cores and virus-specific RNA probes showed that VP3 has affinity for single-stranded RNA (ssRNA) but nut for dsRNA. While the ssRNA-binding activity of VP3 was found to be sequence independent, the protein does exhibit preferential affinity for uncapped over capped RNA. Like the RNA-binding activity, RNA capping assays performed with open cores indicates that the guanylyltransferase activity of VP3 is nonspecific and is able to cap RNAs initiating with a G or an A residue. These data establish that all three rotavirus core proteins, VP1, the RNA polymerase; VP2, the core capsid protein; and VP3, the guanylyltransferase, have affinity for RNA but that only in the case of the RNA polymerase is the affinity sequence specific. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Patton, JT (reprint author), NIAID, Infect Dis Lab, NIH, 7 Ctr Dr,MSC 0720,Rm 117, Bethesda, MD 20892 USA. EM JPATTON@atlas.niaid.nih.gov RI Patton, John/P-1390-2014 NR 34 TC 39 Z9 41 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1999 VL 73 IS 2 BP 1382 EP 1391 PG 10 WC Virology SC Virology GA 156TE UT WOS:000078017500058 PM 9882343 ER PT J AU Mahalingam, S Farber, JM Karupiah, G AF Mahalingam, S Farber, JM Karupiah, G TI The interferon-inducible chemokines MuMig and Crg-2 exhibit antiviral activity in vivo SO JOURNAL OF VIROLOGY LA English DT Article ID RECOMBINANT VACCINIA VIRUSES; BROAD SPECIES-SPECIFICITY; GAMMA-INTERFERON; IMMUNODEFICIENT MICE; VIRAL-INFECTIONS; FUSION COFACTOR; T-LYMPHOCYTES; TROPIC HIV-1; CELL-LINE; RECEPTOR AB MuMig (murine monokine induced by gamma interferon) and Crg-2 (cytokine responsive gene 2) are two murine chemokines of the CXC family that are induced by the interferons (IFNs): MuMig specifically by IFN-gamma and Crg-2 by IFN-alpha, IFN-beta, and IFN-gamma. To investigate the biological roles of these chemokines, recombinant vaccinia viruses (rVVs) encoding either MuMig or Crg-2 were constructed. In vitro, the chemokine-encoding rVVs replicated to similar levels to the control virus. Athymic nude mice inoculated with 10(5) PFU or less of VV-HA-Mig or VV-HA-Crg-2 resolved the infection successfully whereas mice given a similar dose of the control virus VV-HA-TK died from generalized infection. nt higher doses, there was mortality in all groups but death was significantly delayed in mice infected with either chemokine-encoding rVV compared with those infected with the control virus. Virus-encoded MuMig and Crg-2 enhanced the cytolytic activity of Ng cells and splenic cellularity by two- to threefold and resulted in significant increases in mononuclear cell infiltration in the livers of mice. Using specific neutralizing or depleting antibodies, we have established that the control of rVV replication in athymic nude mice, as a consequence of virus-expressed MuMig and Crg-2, requires NK cells and IFN-alpha, IFN-beta, and IFN-gamma. C1 Australian Natl Univ, John Curtin Sch Med Res, Div Immunol & Cell Biol, Host Def Lab,Viral Engn & Cytokines Grp, Canberra, ACT 2601, Australia. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Karupiah, G (reprint author), Univ Sydney, Dept Pathol, Blackburn Bldg,D06, Sydney, NSW 2006, Australia. RI Karupiah, Gunasegaran/J-4707-2013 NR 54 TC 91 Z9 91 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1999 VL 73 IS 2 BP 1479 EP 1491 PG 13 WC Virology SC Virology GA 156TE UT WOS:000078017500069 PM 9882354 ER PT J AU Racusen, LC Solez, K Colvin, RB Bonsib, SM Castro, MC Cavallo, T Croker, BP Demetris, AJ Drachenberg, CB Fogo, AB Furness, P Gaber, LW Gibson, IW Glotz, D Goldberg, JC Grande, J Halloran, PF Hansen, HE Hartley, B Hayry, PJ Hill, CM Hoffman, EO Hunsicker, LG Lindblad, AS Marcussen, N Mihatsch, MJ Nadasdy, T Nickerson, P Olsen, TS Papadimitriou, JC Randhawa, PS Rayner, DC Roberts, I Rose, S Rush, D Salinas-Madrigal, L Salomon, DR Sund, S Taskinen, E Trpkov, K Yamaguchi, Y AF Racusen, LC Solez, K Colvin, RB Bonsib, SM Castro, MC Cavallo, T Croker, BP Demetris, AJ Drachenberg, CB Fogo, AB Furness, P Gaber, LW Gibson, IW Glotz, D Goldberg, JC Grande, J Halloran, PF Hansen, HE Hartley, B Hayry, PJ Hill, CM Hoffman, EO Hunsicker, LG Lindblad, AS Marcussen, N Mihatsch, MJ Nadasdy, T Nickerson, P Olsen, TS Papadimitriou, JC Randhawa, PS Rayner, DC Roberts, I Rose, S Rush, D Salinas-Madrigal, L Salomon, DR Sund, S Taskinen, E Trpkov, K Yamaguchi, Y TI The Banff 97 working classification of renal allograft pathology SO KIDNEY INTERNATIONAL LA English DT Article DE biopsy interpretation; allograft pathology; lesion scoring; kidney; transplantation ID ACUTE REJECTION; KIDNEY-TRANSPLANTATION; CLINICAL-SIGNIFICANCE; CYCLOSPORINE TOXICITY; VIRUS INFECTION; BIOPSIES; CRITERIA; DIAGNOSIS; EPISODES; SCHEMA AB Background. Standardization of renal allograft biopsy interpretation is necessary to guide therapy and to establish an objective end point for clinical trials. This manuscript describes a classification, Banff 97, developed by investigators using the Banff Schema and the Collaborative Clinical Trials in Transplantation (CCTT) modification for diagnosis of renal allograft pathology. Methods. Banff 97 grew from an international consensus discussion begun at Banff and continued via the Internet. This schema developed from (a) analysis of data using the Banff classification, (b) publication of and experience with the CCTT modification, (c) international conferences, and (d) data from recent studies on impact of vasculitis on transplant outcome. Results. Semiquantitative lesion scoring continues to focus on tubulitis and arteritis but includes a minimum threshold for interstitial inflammation. Banff 97 defines "types" of acute/active rejection. Type I is tubulointerstitial rejection without arteritis. Type II is vascular rejection with intimal arteritis, and type III is severe rejection with transmural arterial changes. Biopsies with only mild inflammation are graded as "borderline/suspicious for rejection." Chronic/sclerosing allograft changes are graded based on severity of tubular atrophy and interstitial fibrosis. Antibody-mediated rejection, hyperacute or accelerated acute in presentation, is also categorized, as are other significant allograft findings. Conclusions. The Banff 97 working classification refines earlier schemas and represents input from two classifications most widely used in clinical rejection trials and in clinical practice worldwide. Major changes include the following: rejection with vasculitis is separated from tubulointerstitial rejection; severe rejection requires transmural changes in arteries; "borderline" rejection can only be interpreted in a clinical context; antibody-mediated rejection is further defined, and lesion scoring focuses on most severely involved structures. Criteria for specimen adequacy have also been modified. Banff 97 represents a significant refinement of allograft assessment, developed via international consensus discussions. C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Univ Alberta, Edmonton, AB, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Arkansas, Little Rock, AR 72204 USA. Univ Sao Paulo, Sao Paulo, Brazil. Univ Cincinnati, Cincinnati, OH USA. Univ Florida, Gainesville, FL USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Maryland, Baltimore, MD 21201 USA. Vanderbilt Univ, Nashville, TN USA. Univ Leicester, Leicester, Leics, England. Univ Tennessee, Memphis, TN USA. Univ Glasgow, Glasgow, Lanark, Scotland. Hop Broussais, F-75674 Paris, France. Inst Pathol, Buenos Aires, DF, Argentina. Mayo Clin, Rochester, MN USA. Univ Aarhus, Aarhus, Denmark. Guys & St Thomas Hosp, London SE1 9RT, England. Univ Helsinki, Helsinki, Finland. Queens Univ Belfast, Belfast, Antrim, North Ireland. Louisiana State Univ, New Orleans, LA USA. Univ Iowa, Iowa City, IA USA. EMMES Corp, Potomac, MD USA. Univ Basel, Basel, Switzerland. Univ Manitoba, Winnipeg, MB, Canada. Univ Manchester, Manchester, Lancs, England. NIAID, NIH, Bethesda, MD 20892 USA. St Louis Univ, St Louis, MO 63103 USA. Scripps Inst, La Jolla, CA USA. Univ Oslo, Natl Hosp, Oslo, Norway. RP Racusen, LC (reprint author), Johns Hopkins Med Inst, 519 Ross Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. EM lracusen@welchlink.welch.jhu.edu RI Glotz, Denis/F-7881-2011; Salomon, Daniel/E-9380-2012; Halloran, Philip/J-1390-2012; OI Halloran, Philip/0000-0003-1371-1947; Nickerson, Peter/0000-0002-7393-7799 NR 51 TC 2165 Z9 2332 U1 2 U2 53 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 1999 VL 55 IS 2 BP 713 EP 723 DI 10.1046/j.1523-1755.1999.00299.x PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 160AJ UT WOS:000078207900033 PM 9987096 ER PT J AU Willy, ME Woodward, RA Thornton, VB Wolff, AV Flynn, BM Heath, JL Villamarzo, YS Smith, S Bellini, WJ Rota, PA AF Willy, ME Woodward, RA Thornton, VB Wolff, AV Flynn, BM Heath, JL Villamarzo, YS Smith, S Bellini, WJ Rota, PA TI Management of a measles outbreak among old world nonhuman primates SO LABORATORY ANIMAL SCIENCE LA English DT Article ID VIRUS-INDUCED IMMUNOSUPPRESSION; ENZYME IMMUNOASSAYS; RHESUS MACAQUE; INFECTION; CELLS; HOST; RNA AB Background and Purpose: A measles outbreak in a facility housing Old World nonhuman primates developed over a 8-month period in 1996, providing an opportunity to study the epidemiology of this highly infectious disease in an animal-handling setting. Methods: Serum and urine specimens were collected from monkeys housed in the room where the initial measles cases were identified, other monkeys with suspicious measles-like signs, and employees working in the affected areas, Serum specimens were tested for measles virus-specific IgG and IgM antibodies, and urine specimens were tested for measles virus by virus isolation or reverse transcriptase-polymerase chain reaction (RT-PCR). Results: A total of 94 monkeys in two separate facilities had evidence of an acute measles infection. The outbreak was caused by a wild-type virus that had been associated with recent human cases of acute measles in the United States; however, an investigation was unable to identify the original source of the outbreak. Quarantine and massive vaccination helped to control further spread of infection. Conclusions: Results emphasize the value of having a measles control plan in place that includes a preventive measles vaccination program involving human and nonhuman primates to decrease the likelihood of a facility outbreak. C1 Ctr Dis Control & Prevent, Measles Virus Sect, Resp & Enter Viruses Branch, Div Viral & Rickettsial Dis,Natl Ctr Infect Dis, Atlanta, GA 30333 USA. NIH, Warren Grant Magnuson Clin Ctr, Hosp Epidemiol Serv, Bethesda, MD 20892 USA. NIH, Vet Resources Program, Bethesda, MD 20892 USA. RP Rota, PA (reprint author), Ctr Dis Control & Prevent, Measles Virus Sect, Resp & Enter Viruses Branch, Div Viral & Rickettsial Dis,Natl Ctr Infect Dis, MS-C-22,Bldg 1,1600 Clifton Rd, Atlanta, GA 30333 USA. NR 34 TC 19 Z9 19 U1 0 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD FEB PY 1999 VL 49 IS 1 BP 42 EP 48 PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 175HH UT WOS:000079087000007 PM 10090093 ER PT J AU Preisegger, KH Factor, VM Fuchsbichler, A Stumptner, C Denk, H Thorgeirsson, SS AF Preisegger, KH Factor, VM Fuchsbichler, A Stumptner, C Denk, H Thorgeirsson, SS TI Atypical ductular proliferation and its inhibition by transforming growth factor beta 1 in the 3,5-diethoxycarbonyl-1,4-dihydrocollidine mouse model for chronic alcoholic liver disease SO LABORATORY INVESTIGATION LA English DT Article ID BILIARY EPITHELIAL-CELLS; OVAL CELLS; RAT-LIVER; BILE DUCTULES; HEPATOCYTES; ORIGIN; EXPRESSION; CARCINOGENESIS; REGENERATION; MICE AB Many acute and chronic liver diseases are often associated with atypical ductular proliferation (ADP). These ADPs have gained increasing interest since a number of recent observations suggest that ADPs may represent progenies of the putative liver stem cell compartment. In this study, we show that feeding mice with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) results in persistent proliferation of primitive ductules with poorly defined lumens. Similar to oval cell proliferation in other rodent models as well as in various human liver diseases, DDC-induced ADP originated from the portal tract, spread into the hepatic lobule, and was associated closely with appearance of hepatocytes harboring an antigen (A6), which normally is expressed in biliary epithelium. Furthermore, DDC treatment severely inhibited the regenerative capacity of mice after partial hepatectomy. The development of ADP was selectively blocked in DDC-fed TGF-beta 1 transgenic mice producing active TGF-beta 1 in the liver and no accumulation of new hepatocytes expressing the A6 antigen was observed. Moreover, the transforming growth factor pi (TGF-beta 1) transgenic mice did not survive beyond 3 weeks from starting the DDC-containing diet. The results suggest that persistent activation of the hepatic stem cell compartment is essential for liver regeneration in the DDC model and that active TGF-beta 1 may negatively control activation of stem cells in the liver. These data further emphasize the relevance of the DDC model as an experimental tool for studying chronic liver diseases. C1 Graz Univ, Dept Pathol, A-8036 Graz, Austria. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Preisegger, KH (reprint author), Graz Univ, Dept Pathol, A-8036 Graz, Austria. NR 45 TC 124 Z9 129 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 1999 VL 79 IS 2 BP 103 EP 109 PG 7 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 171DU UT WOS:000078847900007 PM 10068199 ER PT J AU Bartlett, ML Ginn, L Beitz, L Villalba, ML Plotz, P Bacharach, SL AF Bartlett, ML Ginn, L Beitz, L Villalba, ML Plotz, P Bacharach, SL TI Quantitative assessment of myositis in thigh muscles using magnetic resonance imaging SO MAGNETIC RESONANCE IMAGING LA English DT Article DE myositis; quantitative evaluation; muscle disease ID IDIOPATHIC INFLAMMATORY MYOPATHIES; DERMATOMYOSITIS; POLYMYOSITIS; THERAPY; TRIAL AB Magnetic resonance (MR) imaging has been suggested as a technique for diagnosing and monitoring myositis, an inflammatory muscle disease. To date, the assessment of disease from MR images has been by subjective visual analysis. We describe here an objective, semi-automatic, computer-based method for quantifying the degree of disease from MR images, without the need for a radiologist or physician trained in the visual assessment of the MR images. The method is based on analysis of the histogram of intensity values produced from the MR images. The analysis yielded measures of the intensity and extent of disease. These two measures were combined to produce a calculated myositis index (CMI) which described the degree of disease evident from the MR images, This index was compared with a clinical assessment of the patient's condition, based on currently accepted, invasive and non-invasive, non-imaging criteria. Receiver operating characteristic (ROC) curve analysis showed that calculated myositis index agreed at least as well with clinical assessment as did visual analysis (receiver operating characteristic area = 0.93 and 0.94, p = not significant (NS), respectively, for separating remission from disease). Even using only two central MR slices for each patient, the receiver operating characteristic area for calculated myositis index was 0.92, implying that very short acquisition times are possible. We conclude that quantitative histogram analysis of MR images can be successfully performed with minimal operator input and using few MR slices. Agreement with more invasive clinical assessment is good and the method has the advantages of repeatability, objectivity, and decreased scan and analysis time. (C) 1999 Elsevier Science Inc. C1 NIAMSD, Dept Nucl Med, CC, NIH, Bethesda, MD 20892 USA. RP Bacharach, SL (reprint author), NIAMSD, Dept Nucl Med, CC, NIH, Bldg 10,Room 1C-401,10 Ctr Dr, Bethesda, MD 20892 USA. NR 13 TC 15 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD FEB PY 1999 VL 17 IS 2 BP 183 EP 191 DI 10.1016/S0730-725X(98)00092-7 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 159HH UT WOS:000078166100003 PM 10215472 ER PT J AU Shepard, JS Remmers, EF Chen, S Chang, L Kawahito, Y Gulko, PS Joe, B Longman, RE Dracheva, S Ge, L Wang, JP Reese, VR Cannon, GW Griffiths, MM Wilder, RL AF Shepard, JS Remmers, EF Chen, S Chang, L Kawahito, Y Gulko, PS Joe, B Longman, RE Dracheva, S Ge, L Wang, JP Reese, VR Cannon, GW Griffiths, MM Wilder, RL TI A genetic linkage map of rat chromosome 15 derived from five F-2 crosses SO MAMMALIAN GENOME LA English DT Article ID LOCI C1 NIAMSD, Inflammatory Joint Dis Sect, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. Univ Utah, Dept Med Rheumatol, Vet Affairs Med Ctr, Res Serv, Salt Lake City, UT 84132 USA. RP Wilder, RL (reprint author), NIAMSD, Inflammatory Joint Dis Sect, Arthrit & Rheumatism Branch, NIH, Bldg 10,Room 9N240,10 Ctr Dr,MSC 1820, Bethesda, MD 20892 USA. NR 15 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD FEB PY 1999 VL 10 IS 2 BP 186 EP 188 DI 10.1007/s003359900966 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 163BQ UT WOS:000078382700018 PM 9922401 ER PT J AU Danielson, KG Siracusa, LD Donovan, PJ Iozzo, RV AF Danielson, KG Siracusa, LD Donovan, PJ Iozzo, RV TI Decorin, epiphycan, and lumican genes are closely linked on murine chromosome 10 and are deleted in lethal steel mutants SO MAMMALIAN GENOME LA English DT Article ID KERATAN SULFATE PROTEOGLYCAN; MOUSE LUMICAN; SI-LOCUS; ORGANIZATION; EXPRESSION; LOCALIZATION; ASSIGNMENT; CARTILAGE; SEQUENCE; RECEPTOR C1 Thomas Jefferson Univ, Jefferson Med Coll, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Jefferson Med Coll, Kimmel Canc Ctr, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA. NCI, Frederick Canc Res & Dev Ctr, Mammalian Genet Lab, Cell Biol Dev & Differentiat Grp, Frederick, MD 21702 USA. RP Iozzo, RV (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Pathol Anat & Cell Biol, Room 249,Jefferson Alumni Hall,1020 Locust St, Philadelphia, PA 19107 USA. OI Iozzo, Renato/0000-0002-5908-5112 FU NCI NIH HHS [CA21124, R01 CA39481, R01 CA47282] NR 24 TC 13 Z9 14 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD FEB PY 1999 VL 10 IS 2 BP 201 EP 203 DI 10.1007/s003359900971 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 163BQ UT WOS:000078382700023 PM 9922406 ER PT J AU Buckner, JC Malkin, MG Reed, E Cascino, TL Reid, JM Ames, MM Tong, WPY Lim, S Figg, WD AF Buckner, JC Malkin, MG Reed, E Cascino, TL Reid, JM Ames, MM Tong, WPY Lim, S Figg, WD TI Phase II study of antineoplastons A10 (NSC 648539) and AS2-1 (NSC 620261) in patients with recurrent glioma SO MAYO CLINIC PROCEEDINGS LA English DT Article ID PHENYLACETATE; CANCER; CELLS; DIFFERENTIATION; INHIBITION; PHENYLKETONURIA; DERIVATIVES; GROWTH; ALPHA AB Objective: To assess the pharmacokinetics, toxicity, and efficacy of antineoplastons A10 (NSC 648539) and AS2-1 (NSC 620261), Design: We initiated a phase II trial in order to determine whether evidence of antitumor activity of A10 and AS2-1 could be documented, Material and Methods: Patients with anaplastic astrocytoma or glioblastoma multiforme recurring after radiation therapy were eligible for enrollment in the trial, Patients received escalating doses of A10 and AS2-1 by multiple intermittent intravenous injections with use of a portable programmable pump to the target daily dose of 1.0 g/kg for A10 and of 0.4 g/kg for AS2-1, Results: Nine patients were treated, in six of whom the treatment response was assessable in accordance with protocol stipulations, No patient demonstrated tumor regression. Reversible grade 2 or 3 neurocortical toxicity, consisting of transient somnolence, confusion, and exacerbation of an underlying seizure disorder, was noted in five patients, Mean steady-state plasma concentrations of phenylacetate and phenylacetylglutamine after escalation to the target doses of A10 and AS2-1 were 177 +/- 101 mu g/mL and 302 +/- 102 mu g/mL, respectively, Patients who exhibited confusion tended to have higher phenylacetate levels, Conclusion: Although we could not confirm any tumor regression in patients in this study, the small sample size precludes definitive conclusions about treatment efficacy. Antineoplaston-related toxicity was acceptable in most patients with appropriate dose modification, although severe neurocortical toxicity may occur. Steady-state plasma concentrations of phenylacetate with use of A10 and AS2-1 were similar to those reported with use of similar doses of phenylacetate alone. C1 Mayo Clin & Mayo Fdn, Dept Oncol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Neurol, Rochester, MN 55905 USA. Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Pharmaceut Analyt Lab, New York, NY 10021 USA. NCI, Clin Pharmacol Branch, Div Clin Sci, Bethesda, MD 20892 USA. RP Buckner, JC (reprint author), Mayo Clin & Mayo Fdn, Dept Oncol, 200 1st St SW, Rochester, MN 55905 USA. RI Figg Sr, William/M-2411-2016 FU NCI NIH HHS [P30 CA 15083, U01 CA 69912]; NCRR NIH HHS [MO1 RR 00585] NR 23 TC 11 Z9 13 U1 0 U2 0 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD FEB PY 1999 VL 74 IS 2 BP 137 EP 145 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 166YT UT WOS:000078606200005 PM 10069350 ER PT J AU Sinden, RR Bat, O Kramer, PR AF Sinden, RR Bat, O Kramer, PR TI Psoralen cross-linking as probe of torsional tension and topological domain size in vivo SO METHODS-A COMPANION TO METHODS IN ENZYMOLOGY LA English DT Article ID SITE-SPECIFIC RECOMBINATION; ESCHERICHIA-COLI-CELLS; FIBROIN GENE PROMOTER; CHROMATIN STRUCTURE; DROSOPHILA-MELANOGASTER; DNA-STRUCTURE; IN-VIVO; TRANSCRIPTION; INVIVO; TOPOISOMERASES AB DNA within a cell is organized with unrestrained torsional tension, and each molecule is divided Into multiple individual topological domains. Psoralen photobinding can be used as an assay for supercoiling and topological domain size in living cells. Psoralen photobinds to DNA at a rate nearly linearly proportional to superhelical density. Comparison of the rate of photobinding to supercoiled and relaxed DNA in cells provides a measure of superhelical density. For this, in vivo superhelical tension is relaxed by the introduction of nicks by either ionizing radiation or photolysis of bromodeoxyuridine in the DNA. Since nicks are introduced in a random fashion, the distribution of nicks is described by a Poisson distribution. Thus, after nicking, the fraction of topological domains containing no nicks is described by the zero term of the Poisson distribution. From measurement of the number of nicks introduced in the DNA and the fraction of torsional tension remaining, an average topological domain size can be estimated. Using this logic, procedures were designed and described for measuring supercoiling and domain size at specific sites in eukaryotic genomes. (C) 1999 Academic Press. C1 NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Sinden, RR (reprint author), Texas A&M Univ, Inst Biosci & Technol, Ctr Genome Res, 2121 W Holcombe Blvd, Houston, TX 77030 USA. OI Kramer, Phillip/0000-0003-0117-542X NR 58 TC 3 Z9 3 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD FEB PY 1999 VL 17 IS 2 BP 112 EP 124 DI 10.1006/meth.1998.0723 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 178WA UT WOS:000079291100004 PM 10075890 ER PT J AU Chaussee, MS Wilson, J Hill, SA AF Chaussee, MS Wilson, J Hill, SA TI Characterization of the recD gene of Neisseria gonorrhoeae MS11 and the effect of recD inactivation on pilin variation and DNA transformation SO MICROBIOLOGY-UK LA English DT Article DE Neisseria; recD; pilin variation; DNA transformation ID COMPLETE NUCLEOTIDE-SEQUENCE; PILUS ANTIGENIC VARIATION; ESCHERICHIA-COLI; RECBCD ENZYME; GONOCOCCUS INFECTION; DEFICIENT MUTANTS; STRUCTURAL GENE; EXONUCLEASE-V; RECOMBINATION; CHI AB Pilin antigenic variation in Neisseria gonorrhoeae may result following intrachromosomal recombination between homologous pil genes. Despite extensive study, recA is the only previously characterized gene known to be involved in this process. In this study, the gonococcal recD gene, encoding one subunit of the putative RecBCD holoenzyme, was characterized and its role in pilin variation assessed. The complete recD gene of IV. gonorrhoeae MS11 was cloned and its nucleotide sequence determined. The gonococcal recD gene complemented a defined Escherichia coli recD mutant, based on plaque formation of bacteriophage lambda and the restoration of ATP-dependent nuclease activity. Inactivation of the gonococcal recD gene had no measurable effect on cell viability or survival following UV exposure, but did decrease the frequency of DNA transformation approximately threefold. The frequency at which nonparental pilin phenotypes were spawned was 12-fold greater in MS11 recD mutants compared with the parental MS11 rec(+) strain. Similar results were obtained using recD mutants that were not competent for DNA transformation. Complementation of the MS11 recD mutant with a wild-type recD gene copy restored the frequency of pilin phenotypic variation to approximately wild-type levels. The nucleotide changes at pilE in the recD mutants were confined to the variable regions of the gene and were similar to changes previously attributed to gene conversion. C1 NIAID, Rocky Mt Labs, NIH, Microbial Struct & Funct Lab, Hamilton, MT 59840 USA. No Illinois Univ, Dept Biol Sci, De Kalb, IL 60115 USA. RP Chaussee, MS (reprint author), NIAID, Rocky Mt Labs, NIH, Microbial Struct & Funct Lab, Hamilton, MT 59840 USA. EM mchaussee@nih.gov FU NIAID NIH HHS [AI38399] NR 53 TC 27 Z9 27 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 1350-0872 J9 MICROBIOL-UK JI Microbiology-(UK) PD FEB PY 1999 VL 145 BP 389 EP 400 PN 2 PG 12 WC Microbiology SC Microbiology GA 168AV UT WOS:000078668700014 PM 10075421 ER PT J AU Jaffe, ES AF Jaffe, ES TI Hematopathology: Integration of morphologic features and biologic markers for diagnosis SO MODERN PATHOLOGY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 28-MAR 06, 1998 CL BOSTON, MASSACHUSETTS SP US & Canadian Acad Pathol DE classification; Hodgkin's disease; immunohistochemistry; lymphoma; leukemia; molecular diagnostics ID HAIRY-CELL LEUKEMIA; LYMPHOMA; PROPOSAL AB The Revised European-American Classification of Lymphoid Neoplasms (REAL) represented a new paradigm for the classification of lymphomas, Although earlier classification schemes relied strictly on morphologic features or immunophenotype for the definition of diagnostic categories, the REAL classification emphasized that each disease was a distinct entity, defined by a constellation of clinical and laboratory features, i.e., morphologic and genetic features, immunophenotype, clinical presentation, and course. It also noted that the site(s) of presentation were often a signpost for important underlying biologic distinctions. The inclusion of clinical criteria for the definition of disease entities was one of the more novel aspects of the REAL classification, These principles of classification of lymphomas and leukemias also have an impact on diagnostic hematopathology, The REAL classification stresses that diagnoses are based on a multiparameter approach. Although morphologic features alone might suffice for some diagnoses, diagnostic accuracy and reproducibility are enhanced when immunophenotypic and genetic studies are also used. In addition, adequate clinical information is essential for some diagnoses, in particular the mature T-cell lymphomas and leukemias, The proposed World Health Organization classification of lymphoid and hematopoietic neoplasms incorporates these principles of classification and diagnosis. C1 NCI, Pathol Lab, Hematopathol Sect, NIH, Bethesda, MD 20892 USA. RP Jaffe, ES (reprint author), NCI, Pathol Lab, Hematopathol Sect, NIH, Bldg 10-2N202,10 Ctr Dr,MSC-1500, Bethesda, MD 20892 USA. NR 36 TC 36 Z9 38 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 1999 VL 12 IS 2 BP 109 EP 115 PG 7 WC Pathology SC Pathology GA 169HK UT WOS:000078741500001 PM 10071336 ER PT J AU Gorospe, M Egan, JM Zbar, B Lerman, M Geil, L Kuzmin, I Holbrook, NJ AF Gorospe, M Egan, JM Zbar, B Lerman, M Geil, L Kuzmin, I Holbrook, NJ TI Protective function of von Hippel-Lindau protein against impaired protein processing in renal carcinoma cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; TUMOR-SUPPRESSOR GENE; FACTOR MESSENGER-RNA; BREFELDIN-A; PRODUCT; EXPRESSION; GLUCOSE; HYPOXIA; TRANSCRIPTION; ANGIOGENESIS AB The absence of functional von Hippel-Lindau (VHL) tumor suppressor gene leads to the development of neoplasias characteristic of VHL disease, including renal cell carcinoma (RCC). Here, we compared the sensitivity of RCC cells lacking VHL gene function with that of RCC cells expressing the wild-type VHL gene (wtVHL) after exposure to various stresses. While the response to most treatments was not affected by the VHL gene status, glucose deprivation was found to be much more cytotoxic for RCC cells lacking VHL gene function than for wtVHL-expressing cells. The heightened sensitivity of VHL-deficient cells was not attributed to dissimilar energy requirements or to differences in glucose uptake, but more likely reflects a lesser ability of VHL-deficient cells to handle abnormally processed proteins arising from impaired glycosylation. In support of this hypothesis, other treatments which act through different mechanisms to interfere with protein processing (i.e., tunicamycin, brefeldin A, and azetidine) were also found to be much more toxic for VHL-deficient cells. Furthermore, ubiquitination of cellular proteins was elevated in VHL-deficient cells, particularly after glucose deprivation, supporting a role for the VHL gene in ubiquitin-mediated proteolysis. Accordingly, the rate of elimination of abnormal proteins was lower in cells lacking a functional VHL gene than in wtVHL-expressing cells. Thus, pVHL appears to participate in the elimination of misprocessed proteins, such as those arising in the cell due to the unavailability of glucose or to other stresses. C1 NIA, Biol Chem Lab, GRC, NIH, Baltimore, MD 21224 USA. NIA, Lab Clin Physiol, NIH, Baltimore, MD 21224 USA. NCI, Immunobiol Lab, SAIC Frederick, NIH, Frederick, MD 21702 USA. NCI, Intramural Res Support Program, SAIC Frederick, NIH, Frederick, MD 21702 USA. RP Gorospe, M (reprint author), NIA, Biol Chem Lab, GRC, NIH, Box 12,5600 Nathan Schock Dr, Baltimore, MD 21224 USA. NR 59 TC 49 Z9 51 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1999 VL 19 IS 2 BP 1289 EP 1300 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 158WR UT WOS:000078140900032 PM 9891063 ER PT J AU Zhou, Y Gottesman, MM Pastan, I AF Zhou, Y Gottesman, MM Pastan, I TI Studies of human MDR1-MDR2 chimeras demonstrate the functional exchangeability of a major transmembrane segment of the multidrug transporter and phosphatidylcholine flippase SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN P-GLYCOPROTEIN; TRANSIENT-EXPRESSION SYSTEM; RESISTANT TUMOR-CELLS; VACCINIA VIRUS; EPITOPE INSERTION; LABELING SITES; DRUG-BINDING; MDR2 GENE; ORGANIZATION; SPECIFICITY AB P-glycoprotein (P-gp), encoded by the MDR1 gene, is a plasma membrane transporter which effluxes a large number of structurally nonrelated hydrophobic compounds. The molecular basis of the broad substrate recognition of P-gp is not well understood. Despite the 78% amino acid sequence identity of the MDR1 and MDR2 transporter, MDR2, which has been identified as a phosphatidylcholine transporter, does not transport most MDR1 substrates. The structural and functional differences between MDR1 and MDR2 provide an opportunity to identify the residues essential for the broad substrate spectrum of MDR1. Using an approach involving exchanging homologous segments of MDR1 and MDR2 and site-directed mutagenesis, we have demonstrated that MDR1 residues Q330, V331, and L332 in transmembrane domain 6 are sufficient to allow an MDR2 backbone in the N-terminal half of P-gp to transport several MDR1 substrates, including bisantrene, colchicine, vinblastine, and rhodamine-123. These studies help define some residues important for multidrug transport and indicate the close functional relationship between the multidrug transporter (MDR1) and phosphatidylcholine flippase (MDR2). C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37,Room 4E16, Bethesda, MD 20892 USA. EM pasta@helix.nih.gov NR 36 TC 27 Z9 29 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1999 VL 19 IS 2 BP 1450 EP 1459 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 158WR UT WOS:000078140900047 PM 9891078 ER PT J AU Bertram, MJ Berube, NG Hang-Swanson, X Ran, Q Leung, JK Bryce, S Spurgers, K Bick, RJ Baldini, A Ning, Y Clark, LJ Parkinson, EK Barrett, JC Smith, JR Pereira-Smith, OM AF Bertram, MJ Berube, NG Hang-Swanson, X Ran, Q Leung, JK Bryce, S Spurgers, K Bick, RJ Baldini, A Ning, Y Clark, LJ Parkinson, EK Barrett, JC Smith, JR Pereira-Smith, OM TI Identification of a gene that reverses the immortal phenotype of a subset of cells and is a member of a novel family of transcription factor-like genes SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HYDROPHOBIC CLUSTER-ANALYSIS; FINITE LIFE-SPAN; INDEFINITE DIVISION; COMPLEMENTATION GROUP; CELLULAR SENESCENCE; TRANSFORMED-CELLS; EXPRESSION; HYBRIDS; LINES; CHROMOSOME-4 AB Based on the dominance of cellular senescence over immortality, immortal human cell lines have been assigned to four complementation groups for indefinite division. Human chromosomes carrying senescence genes have been identified, including chromosome 4. We report the cloning and identification of a gene, mortality factor 4 (MORF 4), which induces a senescent-like phenotype in immortal cell lines assigned to complementation group B with concomitant changes in two markers for senescence. MORF 4 is a member of a novel family of genes with transcription factor-like motifs, We present here the sequences of the seven family members, their chromosomal locations, and a partial characterization of the three members that are expressed. Elucidation of the mechanism of action of these genes should enhance our understanding of growth regulation and cellular aging. C1 Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA. Baylor Coll Med, Div Mol Virol, Houston, TX 77030 USA. Baylor Coll Med, Div Mol & Human Genet, Houston, TX 77030 USA. Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Univ Texas, Sch Med, Dept Pathol, Houston, TX 77030 USA. Beatson Inst Canc Res, Glasgow G61 1BD, Lanark, Scotland. George Washington Univ, Med Ctr, Wilson Genet Ctr, Washington, DC 20037 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Bertram, MJ (reprint author), Baylor Coll Med, Huffington Ctr Aging, 1 Baylor Plaza, Houston, TX 77030 USA. RI Bertram, Michael/F-7501-2010; genes, anthony/F-2541-2012 FU NCI NIH HHS [T32 CA009197]; NIA NIH HHS [T32AG00183, F32 AG005732, P01AG13663, R37AG05333, T32 AG000183] NR 44 TC 119 Z9 124 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1999 VL 19 IS 2 BP 1479 EP 1485 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 158WR UT WOS:000078140900050 PM 9891081 ER PT J AU Lee, S Neumann, M Stearman, R Stauber, R Pause, A Pavlakis, GN Klausner, RD AF Lee, S Neumann, M Stearman, R Stauber, R Pause, A Pavlakis, GN Klausner, RD TI Transcription-dependent nuclear-cytoplasmic trafficking is required for the function of the von Hippel-Lindau tumor suppressor protein SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; FACTOR MESSENGER-RNA; GENE-PRODUCT; EXPORT SIGNAL; RENAL-CARCINOMA; POSTTRANSCRIPTIONAL REGULATION; NUCLEOCYTOPLASMIC TRANSPORT; SOMATIC MUTATIONS; HUMAN TISSUES; LEPTOMYCIN-B AB Mutation of the von Hippel-Lindau tumor suppressor gene (vhl) causes the von Hippel-Lindau cancer syndrome as well as sporadic renal clear cell carcinoma, To pursue our study of the intracellular localization of VHL protein in relation to its function, we fused VHL to the green fluorescent protein (GFP) to produce the VHL-GFP fusion protein. Like VHL, VHL-GFP binds to elongins B and C and Cullin-2 and regulates target gene product levels, including levels of vascular endothelial growth factor and glucose transporter 1, VHL-GFP localizes predominantly to the cytoplasm, with some detectable nuclear signal. Inhibition of transcription by actinomycin D or 5,6 dichlorobenzimidazole riboside (DRB) causes VHL to be redistributed to the nucleus. A cellular fusion assay was used to demonstrate that inhibition of transcription induces a decrease in the nuclear export rate of VHL. The dependence of transcription for trafficking is lost with a deletion of exon 2, a region with a mutation causing a splice defect in the VHL gene in sporadic renal clear cell carcinoma. Addition of a strong nuclear export signal (NES) derived from the Rev protein results in complete nuclear exclusion and abrogates the redistribution of VHL-GFP-NES into the nucleus upon inhibition of transcription. Leptomycin B, which inhibits NES-mediated nuclear export, reverts the distribution of VHL-GFP-NES to that of VHL GFP and restores sensitivity to actinomycin D and DRB. Uncoupling of VHL-GFP trafficking to transcription either by an exon 2 deletion or fusion to NES abolishes VHL function. We suggest that VHL function requires not only nuclear or cytoplasmic localization, but also exon 2-mediated transcription-dependent trafficking between these two cellular compartments. C1 NCI, Off Director, NIH, Bethesda, MD 20892 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Lee, S (reprint author), Univ Ottawa, Fac Med, Dept Cellular & Mol Med, 451 Smyth Rd, Ottawa, ON K1H 8M5, Canada. OI Stauber, Roland/0000-0002-1341-4523 NR 69 TC 101 Z9 103 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1999 VL 19 IS 2 BP 1486 EP 1497 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 158WR UT WOS:000078140900051 PM 9891082 ER PT J AU Debnath, J Chamorro, M Czar, MJ Schaeffer, EM Lenardo, MJ Varmus, HE Schwartzberg, PL AF Debnath, J Chamorro, M Czar, MJ Schaeffer, EM Lenardo, MJ Varmus, HE Schwartzberg, PL TI rlk/TXK encodes two forms of a novel cysteine string tyrosine kinase activated by Src family kinases SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RI CROSS-LINKING; BRUTON TYROSINE; PROTEIN; PHOSPHORYLATION; PALMITOYLATION; ASSOCIATION; MEMBRANES; ITK; LCK; TRANSLATION AB Rlk/Txk is a member of the BTK/Tec family of tyrosine kinases and is primarily expressed in T lymphocytes. Unlike other members of this kinase family, Rlk lacks a pleckstrin homology (PH) domain near the amino terminus and instead contains a distinctive cysteine string motif We demonstrate here that Rlk protein consists of two isoforms that arise by alternative initiation of translation from the same cDNA. The shorter, internally initiated protein species lacks the cysteine string motif and is located in the nucleus when expressed in the absence of the larger form. In contrast, the larger form is cytoplasmic We show that the larger form is palmitoylated and that mutation of its cysteine string motif both abolishes palmitoylation and allows the protein to migrate to the nucleus, The cysteine string, therefore, is a critical determinant of both fatty acid modification and protein localization for the larger isoform of Rlk, suggesting that Rlk regulation is distinct from the other Btk family kinases, We further show that Rlk is phosphorylated and changes localization in response to T-cell-receptor (TCP) activation and, like the other Btk family kinases, can be phosphorylated and activated by Src family kinases, However, unlike the other Btk family members, Rlk is activated independently of the activity of phosphatidylinositol 3-kinase, consistent with its lack of a PA domain. Thus, Rlk has tao distinct isoforms, each of which may have unique properties in signaling downstream from the TCR. C1 NCI, NIH, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Res Scholars Program, NIH, Bethesda, MD 20892 USA. Natl Inst Human Genome Res, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. George Washington Inst Biomed Sci, Washington, DC USA. RP Schwartzberg, PL (reprint author), NIH, Natl Human Genome Res Inst, 49-4A38, Bethesda, MD 20892 USA. NR 38 TC 64 Z9 66 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1999 VL 19 IS 2 BP 1498 EP 1507 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 158WR UT WOS:000078140900052 PM 9891083 ER PT J AU Qyang, YB Luo, X Lu, T Ismail, PM Krylov, D Vinson, C Sawadogo, M AF Qyang, YB Luo, X Lu, T Ismail, PM Krylov, D Vinson, C Sawadogo, M TI Cell-type-dependent activity of the ubiquitous transcription factor USF in cellular proliferation and transcriptional activation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HELIX-LOOP-HELIX; UPSTREAM STIMULATORY FACTOR; DNA-BINDING; GENE-EXPRESSION; MAMMALIAN-CELLS; MYC PROTEINS; FAMILY; PROMOTER; MOTIF; FORMS AB USF1 and USF2 are basic helix-loop-helix transcription factors implicated in the control of cellular proliferation, In HeLa cells, the USF proteins are transcriptionally active and their overexpression causes marked growth inhibition. In contrast, USF overexpression had essentially no effect on the proliferation of the Saos-2 osteosarcoma cell line. USF1 and USF2 also lacked transcriptional activity in Saos-2 cells when assayed by transient cotransfection with USF-dependent reporter genes. Yet, there was no difference in the expression, subcellular localization, or DNA-binding activity of the USF proteins in HeLa and Saos-2 cells. Furthermore, Gal4-USF1 and Gal4-USF2 fusion proteins activated transcription similarly in both cell lines. Mutational analysis and domain swapping experiments revealed that the small, highly conserved USF-specific region (USR) was responsible for the inactivity of USF in Saos-2 cells. In HeLa, the USR serves a dual function. It acts as an autonomous transcriptional activation domain at promoters containing an initiator element and also induces a conformational change that is required for USF activity at promoters lacking an initiator. Taken together, these results suggest a model in which the transcriptional activity of the USF proteins, and consequently their antiproliferative activity, is tightly controlled by interaction with a specialized coactivator that recognizes the conserved USR domain and, in contrast to USF, is not ubiquitous. The activity of USF is therefore context dependent, and evidence for USF DNA-binding activity in particular cells is insufficient to indicate USF function in transcriptional activation and growth control. C1 Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. NCI, Biochem Lab, Bethesda, MD 20892 USA. RP Sawadogo, M (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, 1515 Holcombe Blvd, Houston, TX 77030 USA. FU NCI NIH HHS [P30 CA016672, CA09299, CA16672, CA79578, T32 CA009299] NR 41 TC 135 Z9 140 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1999 VL 19 IS 2 BP 1508 EP 1517 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 158WR UT WOS:000078140900053 PM 9891084 ER PT J AU Chu, E Copur, SM Ju, JF Chen, TM Khleif, S Voeller, DM Mizunuma, N Patel, M Maley, GF Maley, F Allegra, CJ AF Chu, E Copur, SM Ju, JF Chen, TM Khleif, S Voeller, DM Mizunuma, N Patel, M Maley, GF Maley, F Allegra, CJ TI Thymidylate synthase protein and p53 mRNA form an in vivo ribonucleoprotein complex SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID 3' UNTRANSLATED REGION; TUMOR-SUPPRESSOR GENE; COLON-CANCER-CELLS; MESSENGER-RNA TRANSLATION; IRON-RESPONSIVE ELEMENTS; TRANSCRIPTIONAL ACTIVATION; P53-DEPENDENT APOPTOSIS; CONSERVED SEQUENCE; OWN TRANSCRIPTION; POLY(A) TAIL AB A thymidylate synthase (TS)-ribonucleoprotein (RNP) complex composed of TS protein and the mRNA of the tumor suppressor gene p53 was isolated from cultured human colon cancer cells. RNA gel shift assays confirmed a specific interaction between TS protein and the protein-coding region of p53 mRNA, and in vitro translation studies demonstrated that this interaction resulted in the specific repression of p53 mRNA translation To demonstrate the potential biological role of the TS protein-p53 mRNA interaction, Western immunoblot analysis revealed nearly undetectable levels of p53 protein in TS-overexpressing human colon cancer H630-R10 and rat hepatoma H35(F/F) cell lines compared to the levels in their respective parent H630 and H35 cell lines. Polysome analysis revealed that the p53 mRNA was associated with higher-molecular-weight polysomes in H35 cells compared to H35(F/F) cells. While the level of p53 mRNA expression was identical in parent and TS-overexpressing cell lines, the level of p53 RNA bound to TS in the form of RNP complexes was significantly higher in TS-overexpressing cells. The effect of TS on p53 expression was also investigated with human colon cancer RKO cells by use of a tetracycline-inducible system. Treatment of RKO cells with a tetracycline derivative, doxycycline! resulted in 15-fold-induced expression of TS protein and nearly complete suppression of p53 protein expression. However, p53 mRNA levels were identical in transfected RKO cells in the absence and presence of doxycycline. Taken together, these findings suggest that TS regulates the expression of p53 at the translational level. This study identifies a novel pathway for regulating p53 gene expression and expands current understanding of the potential role of TS as a regulator of cellular gene expression. C1 Yale Univ, Sch Med, Dept Med & Pharmacol, Yale Canc Ctr, New Haven, CT 06520 USA. Yale Univ, Sch Med, VA CT Canc Ctr, New Haven, CT 06520 USA. NCI, Div Clin Sci, Med Branch, Bethesda, MD 20889 USA. New York State Dept Hlth, Wadsworth Ctr Labs & Res, Albany, NY 12201 USA. RP Chu, E (reprint author), VA Ct Healthcare Syst, Canc Ctr 111D, 950 Campbell Ave, W Haven, CT 06516 USA. OI Ju, Jingfang/0000-0002-4821-7458 FU NCI NIH HHS [CA44355, P30 CA016359, R01 CA075712, CA16359, CA75712] NR 72 TC 66 Z9 73 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1999 VL 19 IS 2 BP 1582 EP 1594 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 158WR UT WOS:000078140900060 PM 9891091 ER PT J AU Modi, WS Yoshimura, T AF Modi, WS Yoshimura, T TI Isolation of novel GRO genes and a phylogenetic analysis of the CXC chemokine subfamily in mammals SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE CXC chemokines; mammals; phylogeny ID NUCLEOTIDE SUBSTITUTION; BETA-THROMBOGLOBULIN; STIMULATORY ACTIVITY; CDNA CLONING; GUINEA-PIG; SEQUENCE; EXPRESSION; INTERLEUKIN-8; PURIFICATION; IDENTIFICATION AB Approximately 15 different alpha, or CXC, chemokines have thus far been isolated from 11 species of mammals. Among the best studied chemokines are the 12 human proteins that are encoded by 11 paralogous genes. In order to better understand the evolution and function of this group of genes, we isolated and characterized six novel GRO and GRO-related cDNA sequences from the cow (Bos taurus), the sheep (Ovis aries), the rabbit (Oryctolagus cuniculus), and the guinea pig (Cavia porcellus). The amino acid sequence of the diverged guinea pig GRO or KC gene is only 50%-60% similar to presumed orthologs from other species, while the sheep and cow GRO proteins are 90%-99% similar to each other. The presence of multiple GRO genes in the cow, the rabbit, and the sheep is consistent with what has been observed for humans. Phylogenetic analyses of amino acid sequences from 44 proteins indicate that genes orthologous to many of the 11 known from humans exist in other species. One such gene, interleukin 8, or IL8, has been isolated from nine species, including the rodent guinea pie; however, this gene is absent in the rat and the mouser indicating a unique gene loss event in the rat/mouse (muroid rodent) lineage. The KC (or MIP2) gene of rodents appears to be orthologous to the GRO gene found in other taxonomic orders. Combined evidence from different sources suggests that IP10 and MIG share sister taxon relationships on the evolutionary tree, while the remaining paralogous genes represent independent lineages, with limited evidence for kinship between them. This observation indicates that these genes originated nearly contemporaneously via a series of gene duplication events. Relative-rate tests for synonymous and nonsynonymous nucleotide substitutions in the KC and IL8 genes did not detect rate heterogeneity; however, there are several notable features regarding the ILS genes. For example, the IL8 proteins from two Old World monkeys are as similar to one another as they are to the IL8 protein from humans, and all observed nucleotide differences between the IL8 genes of the two monkeys cause amino acid changes, in other words, there are no synonymous differences between them. C1 NCI, Intramural Res Support Program, SAIC Frederick, Fred Hutchinson Canc Res Ctr, Frederick, MD 21702 USA. NCI, Immunopathol Sect, Immunobiol Lab, Fred Hutchinson Canc Res Ctr, Frederick, MD 21702 USA. RP Modi, WS (reprint author), NCI, Intramural Res Support Program, SAIC Frederick, Fred Hutchinson Canc Res Ctr, Frederick, MD 21702 USA. EM modi@ncifcrf.gov NR 44 TC 61 Z9 68 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD FEB PY 1999 VL 16 IS 2 BP 180 EP 193 PG 14 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 165JX UT WOS:000078518600005 PM 10028286 ER PT J AU Htun, H Holth, LT Walker, D Davie, JR Hager, GL AF Htun, H Holth, LT Walker, D Davie, JR Hager, GL TI Direct visualization of the human estrogen receptor alpha reveals a role for ligand in the nuclear distribution of the receptor SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID GREEN FLUORESCENT PROTEIN; IMMUNOELECTRON MICROSCOPIC LOCALIZATION; HUMAN-BREAST-CANCER; STEROID-RECEPTORS; TRANSCRIPTIONAL ACTIVATION; PROGESTERONE-RECEPTOR; CHROMATIN STRUCTURE; CELL-LINE; IN-VIVO; HORMONE AB The human estrogen receptor ct (ER ct) has been tagged at its amino terminus with the S65T variant of the green fluorescent protein (GFP), allowing subcellular trafficking and localization to be observed in living cells by fluorescence microscopy. The tagged receptor, GFP-ER, is functional as a ligand-dependent transcription factor, responds to both agonist and antagonist ligands, and can associate with the nuclear matrix. Its cellular localization was analyzed in four human breast cancer epithelial cell lines, two ER+ (MCF7 and T47D) and two ER- (MDA-MB-231 and MDA-MB-435A), under a variety of ligand conditions. In all cell lines, GFP-ER is observed only in the nucleus in the absence of ligand. Upon the addition of agonist or antagonist ligand, a dramatic redistribution of GFP-ER from a reticular to punctate pattern occurs within the nucleus. In addition, the full antagonist ICI 182780 alters the nucleocytoplasmic compartmentalization of the receptor and causes partial accumulation in the cytoplasm in a process requiring continued protein synthesis. GFP-ER localization varies between cells, despite being cultured and treated in a similar manner. Analysis of the nuclear fluorescence intensity for variation in its frequency distribution helped establish localization patterns characteristic of cell line and ligand. During the course of this study, localization of GFP-ER to the nucleolar region is observed for ER- but not ER+ human breast cancer epithelial cell lines. Finally, our work provides a visual description of the "unoccupied" and ligand-bound receptor and is discussed in the context of the role of ligand in modulating receptor activity. C1 NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. Univ Manitoba, Dept Biochem & Mol Biol, Winnipeg, MB R3E 0W3, Canada. RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. EM hagerg@exchange.nih.gov NR 67 TC 201 Z9 205 U1 0 U2 10 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD FEB PY 1999 VL 10 IS 2 BP 471 EP 486 PG 16 WC Cell Biology SC Cell Biology GA 182AE UT WOS:000079475700016 PM 9950689 ER PT J AU Wu, ZD Rosen, ED Brun, R Hauser, S Adelmant, G Troy, AE McKeon, C Darlington, GJ Spiegelman, BM AF Wu, ZD Rosen, ED Brun, R Hauser, S Adelmant, G Troy, AE McKeon, C Darlington, GJ Spiegelman, BM TI Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity SO MOLECULAR CELL LA English DT Article ID ENHANCER-BINDING-PROTEIN; ACTIVATED RECEPTOR-GAMMA; NECROSIS-FACTOR-ALPHA; GENE-EXPRESSION; ADIPOCYTE DIFFERENTIATION; 3T3-L1 PREADIPOCYTES; ECTOPIC EXPRESSION; CELLS; PROMOTES; FAMILY AB Mice deficient in C/EBP alpha have defective development of adipose tissue, but the precise role of C/EBP alpha has not been defined. Fibroblasts from C/EBP alpha(-/-) mice undergo adipose differentiation through expression and activation of PPAR gamma, though several clear defects are apparent. C/EBP alpha-deficient adipocytes accumulate less lipid, and they do not induce endogenous PPAR gamma, indicating that cross-regulation between C/EBP alpha and PPAR gamma is important in maintaining the differentiated state. The cells also show a complete absence of insulin-stimulated glucose transport, secondary to reduced gene expression and tyrosine phosphorylation for the insulin receptor and IRS-1, These results define multiple roles for C/EBP alpha in adipogenesis and show that cross-regulation between PPAR gamma and C/EBP alpha is a key component of the transcriptional control of this cell lineage. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. NIDKDD, Diabet Branch, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu FU NIDDK NIH HHS [DK31405, DK45285] NR 44 TC 550 Z9 574 U1 4 U2 34 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 FEB PY 1999 VL 3 IS 2 BP 151 EP 158 DI 10.1016/S1097-2765(00)80306-8 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 172ZK UT WOS:000078956100003 PM 10078198 ER PT J AU Anikster, Y Lucero, C Touchman, JW Huizing, M McDowell, G Shotelersuk, V Green, ED Gahl, WA AF Anikster, Y Lucero, C Touchman, JW Huizing, M McDowell, G Shotelersuk, V Green, ED Gahl, WA TI Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS) SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE cystinosis; deletion; multiplex PCR; sample sequencing; founder effect ID CYSTEAMINE THERAPY; INSUFFICIENCY; TRANSPORT; LYSOSOMES; FRACTIONS; DEPLETION; CHILDREN; REMOVAL; REGION; 17P13 AB The most common mutation in the cystinosis gene, CTNS, is a 65-kb deletion thought to have originated in Germany. Although homozygotes for this deletion are detectable by the absence of the D17S829 polymorphic marker, no method exists to identify heterozygotes. We identified the 65-kb deletion breakpoints and used flanking PCR primers to amplify a 423-bp fragment present only in the deletion alleles. Using this method, we determined that 121 of 216 (56%) cystinosis alleles examined bore the 65-kb deletion. We found no non-Europeans with the deletion, and the deletion size and breakpoints appeared identical in all patients studied, supporting the concept of a founder effect. The addition of D17S829 primers (266 bp apart) to the PCR created a multiplex PCR system useful for diagnosing cystinosis patients homozygous and heterozygous for the 65-kb deletion. C1 NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NIH, Intramural Sequencing Ctr, Gaithersburg, MD 20877 USA. RP Anikster, Y (reprint author), NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. NR 32 TC 50 Z9 52 U1 1 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 1999 VL 66 IS 2 BP 111 EP 116 DI 10.1006/mgme.1998.2790 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 172ZG UT WOS:000078955800005 PM 10068513 ER PT J AU van Steeg, H Kraemer, KH AF van Steeg, H Kraemer, KH TI Xeroderma pigmentosum and the role of UV-induced DNA damage in skin cancer SO MOLECULAR MEDICINE TODAY LA English DT Review ID NUCLEOTIDE EXCISION-REPAIR; RNA-POLYMERASE-II; COCKAYNE-SYNDROME; MICE LACKING; ULTRAVIOLET-RADIATION; GENE; TRANSCRIPTION; COMPLEX; PROTEIN; TRICHOTHIODYSTROPHY AB Xeroderma pigmentosum (XP) is a rare, autosomal recessive disease that is characterized by the extreme sensitivity of the skin to sunlight. Compared to normal individuals, XP patients have a move than 1000-fold increased risk of developing cancer on sun-exposed areas of the skin. Genetic and molecular analyses have revealed that the repair of ultraviolet (UV)-induced DNA damage is impaired in XP patients owing to mutations in genes that form part of a DNA-repair pathway known as nucleotide excision repair (NER), Two other diseases, Cockayne syndrome (CS) and the photosensitive form of trichothiodystrophy (TTD), are linked to a defect in the NER pathway. Strikingly, although CS and TTD patients are UV-sensitive, they do not develop skin cancer. The recently developed animal models that mimic the human phenotypes of XP, CS and TTD will contribute to a better understanding of the etiology of these diseases and the role of UV-induced DNA damage in the development of skin cancer. C1 Natl Inst Publ Hlth & Environm, Hlth Effects Res Lab, Dept Carcinogenesis Mutagenesis & Genet, NL-3720 BA Bilthoven, Netherlands. NCI, Mol Carcinogenesis Lab, Bethesda, MD 20892 USA. RP van Steeg, H (reprint author), Natl Inst Publ Hlth & Environm, Hlth Effects Res Lab, Dept Carcinogenesis Mutagenesis & Genet, NL-3720 BA Bilthoven, Netherlands. FU Intramural NIH HHS [Z01 BC004517-31] NR 53 TC 121 Z9 124 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1357-4310 J9 MOL MED TODAY JI Mol. Med. Today PD FEB PY 1999 VL 5 IS 2 BP 86 EP 94 DI 10.1016/S1357-4310(98)01394-X PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 180YC UT WOS:000079412600009 PM 10200950 ER PT J AU Hoffmann, B Mosch, HU Sattlegger, E Barthelmess, IB Hinnebusch, A Braus, GH AF Hoffmann, B Mosch, HU Sattlegger, E Barthelmess, IB Hinnebusch, A Braus, GH TI The WD protein Cpc2p is required for repression of Gcn4 protein activity in yeast in the absence of amino-acid starvation SO MOLECULAR MICROBIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; TRANSFER-RNA; GENERAL CONTROL; TRANSLATIONAL CONTROL; BETA-SUBUNIT; TRANSCRIPTIONAL ACTIVATOR; REGULATORY SEQUENCES; BIOSYNTHETIC GENES; GLUCOSE REPRESSION; NEUROSPORA-CRASSA AB The CPC2 gene of the budding yeast Saccharomyces cerevisiae encodes a G beta-like WD protein which is involved in regulating the activity of the general control activator Gcn4p. The CPC2 gene encodes a premRNA which is spliced and constitutively expressed in the presence or absence of amino acids. Loss of CPC2 gene function suppresses a deletion of the GCN2 gene encoding the general control sensor kinase, but not a deletion in the GCN4 gene. The resulting phenotype has resistance against amino-acid analogues. The Neurospora crassa cpc-2 and the rat RACK1 genes are homologues of CPC2 that complement the yeast cpc2 deletion. The cpc2 Delta mutation leads to increased transcription of Gcn4p-dependent genes under non-starvation conditions without increasing GCN4 expression or the DNA binding activity of Gcn4p. Cpc2p-mediated transcriptional repression requires the Gcn4p transcriptional activator and a Gcn4p recognition element in the target promoter. Frameshift mutations resulting in a shortened G beta-like protein cause a different phenotype that has sensitivity against amino-acid analogues similar to a gcn2 deletion. Cpc2p seems to be part of an additional control of Gcn4p activity, independent of its translational regulation. C1 Univ Gottingen, Inst Microbiol & Genet, D-037077 Gottingen, Germany. NICHHD, Lab Eukaryot Gene Regulat, Bethesda, MD 20892 USA. Univ Hannover, Inst Appl Genet, D-30419 Hannover, Germany. RP Braus, GH (reprint author), Univ Gottingen, Inst Microbiol & Genet, Grisebachstr 8, D-037077 Gottingen, Germany. EM gbraus@gwdg.de RI Braus, Gerhard/G-3999-2012; Hoffmann, Bernd/I-7237-2013 OI Braus, Gerhard/0000-0002-3117-5626; NR 70 TC 39 Z9 41 U1 0 U2 5 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD FEB PY 1999 VL 31 IS 3 BP 807 EP 822 DI 10.1046/j.1365-2958.1999.01219.x PG 16 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 168TG UT WOS:000078708300007 PM 10048025 ER PT J AU Chen, JY Capdevila, JH Zeldin, DC Rosenberg, RL AF Chen, JY Capdevila, JH Zeldin, DC Rosenberg, RL TI Inhibition of cardiac L-type calcium channels by epoxyeicosatrienoic acids SO MOLECULAR PHARMACOLOGY LA English DT Article ID PLANAR LIPID BILAYERS; ARACHIDONIC-ACID; MOLECULAR-CLONING; CA2+ ENTRY; CELLS; EPOXYGENASE; INACTIVATION; METABOLITE; ACTIVATION; EXPRESSION AB Epoxyeicosatrienoic acids (EETs), products of the cytochrome P-450 monooxygenase metabolism of arachidonic acid, can regulate the activity of ion channels. We examined the effects of EETs on cardiac L-type Ca2+ channels that play important roles in regulating cardiac contractility, controlling heart rate, and mediating slow conduction in normal nodal cells and ischemic myocardium. Our experimental approach was to reconstitute porcine L-type Ca2+ channels into planar lipid bilayers where we could control the aqueous and lipid environments of the channels and the regulatory pathways that change channel properties. We found that 20 to 125 nM EETs inhibited the open probability of reconstituted L-type Ca2+ channels, accelerated the inactivation of the channels, and reduced the unitary current amplitude of open channels. There was no selectivity among different EET regioisomers or stereoisomers, When 11,12-EET was esterified to the sn-2 position of phosphatidylcholine, restricting it to the hydrophobic phase of the planar lipid bilayer, the reconstituted channels were similarly inhibited, suggesting that the EET interacts directly with Ca2+ channels through the lipid phase. The inhibitory effects of EET persisted in the presence of microcystin, an inhibitor of protein phosphatases 1 and 2A, suggesting that dephosphorylation was not the mechanism through which these eicosanoids down-regulate channel activity, This inhibition may be an important protective mechanism in the setting of cardiac ischemia where arachidonic acid levels are dramatically increased and EETs have been shown to manifest preconditioning-like effects. C1 Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. NIEHS, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. RP Rosenberg, RL (reprint author), Univ N Carolina, Dept Pharmacol, CB 7365, Chapel Hill, NC 27599 USA. EM bobr@med.unc.edu FU NHLBI NIH HHS [HL27430, HL49449]; NIGMS NIH HHS [GM37922] NR 37 TC 73 Z9 83 U1 0 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 FEB PY 1999 VL 55 IS 2 BP 288 EP 295 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 165JQ UT WOS:000078518000013 PM 9927620 ER PT J AU Redfern, CH Coward, P Degtyarev, MY Lee, EK Kwa, AT Hennighausen, L Bujard, H Fishman, GI Conklin, BR AF Redfern, CH Coward, P Degtyarev, MY Lee, EK Kwa, AT Hennighausen, L Bujard, H Fishman, GI Conklin, BR TI Conditional expression and signaling of a specifically designed G(i)-coupled receptor in transgenic mice SO NATURE BIOTECHNOLOGY LA English DT Article DE G protein signaling; engineered opioid receptor; synthetic ligand ID PROTEIN-COUPLED RECEPTORS; GENE-EXPRESSION; DILATED CARDIOMYOPATHY; MAMMALIAN-CELLS; GI-ALPHA; HEART; TRANSDUCTION; ACTIVATION; LIGANDS AB To control G protein signaling in vivo, we have modified G protein-coupled receptors to respond exclusively to synthetic small molecule agonists and not to their natural agonist(s), These engineered receptors are designated RASSLs (receptor activated solely by a synthetic ligand), A prototype RASSL (Ro1) based on the G(j)-coupled kappa opioid receptor was expressed in transgenic mice under the control of the tetracycline transactivator (tet) system, Activation of Ro1 expressed in the heart decreased heart rate by up to 80%, an expected effect of increased G(j) signaling. Maximal heart rate changes occurred in less than 1 min, demonstrating the speed of this inducible signaling system. This Ro1-mediated slowing of heart rate was also subject to desensitization, which lasted more than 24 h. Both the initial effect on heart rate and the desensitization occurred, even though Ro1 is derived from a human opioid receptor not normally involved in heart rate control. In addition, the tet system was used to induce Ro1 expression in hepatocytes and salivary gland, where G(j) signaling is known to control physiologic events such as proliferation and secretion, These studies demonstrate that a RASSL can be inducibly expressed in several mouse tissues and used in vivo to activate G protein signaling in a controllable fashion. C1 Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, Gladstone Inst Neurol Dis, San Francisco, CA 94141 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94141 USA. NIDDKD, NIH, Bethesda, MD 20982 USA. Univ Heidelberg, Zentrum Mol Biol, D-6900 Heidelberg, Germany. Mt Sinai Sch Med, New York, NY 10029 USA. RP Conklin, BR (reprint author), Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, Gladstone Inst Neurol Dis, POB 419100, San Francisco, CA 94141 USA. FU NCI NIH HHS [CA71779]; NHLBI NIH HHS [HL60664-01] NR 24 TC 125 Z9 126 U1 0 U2 6 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD FEB PY 1999 VL 17 IS 2 BP 165 EP 169 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 165EX UT WOS:000078508300025 PM 10052353 ER PT J AU Watanabe, H Yamada, Y AF Watanabe, H Yamada, Y TI Mice lacking link protein develop dwarfism and craniofacial abnormalities SO NATURE GENETICS LA English DT Article ID HORMONE-RELATED PEPTIDE; PARATHYROID-HORMONE; CHONDROCYTE DIFFERENTIATION; SKELETAL DEVELOPMENT; ENDOCHONDRAL BONE; INDIAN HEDGEHOG; CORE PROTEIN; GENE; CARTILAGE; AGGRECAN AB Link protein (LP), an extracellular matrix protein in cartilage, stabilizes aggregates of aggrecan and hyaluronan, giving cartilage its tensile strength and elasticity(1-3). Cartilage provides the template for endochondral ossification and is crucial for determining the length and width of the skeleton. During endochondral bone formation, hypertrophic chondrocytes die and the cartilage is replaced with bone matrix. Here, we have generated targeted mutations in mice in the gene encoding LP (Crtl1). Homozygotes showed defects in cartilage development and delayed bone formation with short limbs and craniofacial anomalies. Most Crtl1(tm1Nid/tm1Nid) mice died shortly after birth due to respiratory failure, but some survived and developed progressive dwarfism and lordosis of the cervical spine. They showed small epiphysis, slightly flared metaphysis of long bones and flattened vertebrae, characteristic of spondyloepiphyseal dysplasias. The cartilage contained significantly reduced aggrecan depositions in the hypertrophic zone, and decreased numbers of prehypertrophic and hypertrophic chondrocytes. Reduced Indian hedgehog (Ihh) expression was observed in prehypertrophic chondrocytes, and apoptosis was inhibited in hypertrophic chondrocytes. These results indicate that LP is important for the formation of proteoglycan aggregates and normal organization of hypertrophic chondrocytes, and suggest that cartilage matrix has a role in chondrocyte differentiation and maturation. C1 Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Yamada, Y (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. EM yamada@yoda.nidr.nih.gov NR 29 TC 119 Z9 120 U1 0 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 1999 VL 21 IS 2 BP 225 EP 229 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 163MH UT WOS:000078399500029 PM 9988279 ER PT J AU Terauchi, Y Tsuji, Y Satoh, S Minoura, H Murakami, K Okuno, A Inukai, K Asano, T Kaburagi, Y Ueki, K Nakajima, H Hanafusa, T Matsuzawa, Y Sekihara, H Yin, YX Barrett, JC Oda, H Ishikawa, T Akanuma, Y Komuro, I Suzuki, M Yamamura, K Kodama, T Suzuki, H Koyasu, S Aizawa, S Tobe, K Fukui, Y Yazaki, Y Kadowaki, T AF Terauchi, Y Tsuji, Y Satoh, S Minoura, H Murakami, K Okuno, A Inukai, K Asano, T Kaburagi, Y Ueki, K Nakajima, H Hanafusa, T Matsuzawa, Y Sekihara, H Yin, YX Barrett, JC Oda, H Ishikawa, T Akanuma, Y Komuro, I Suzuki, M Yamamura, K Kodama, T Suzuki, H Koyasu, S Aizawa, S Tobe, K Fukui, Y Yazaki, Y Kadowaki, T TI Increased insulin sensitivity and hypoglycaemia in mice lacking the P85 alpha subunit of phosphoinositide 3-kinase SO NATURE GENETICS LA English DT Article ID RECEPTOR TYROSINE KINASES; RAT ADIPOSE-CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; REGULATORY SUBUNIT; GLUCOSE-TRANSPORT; 3T3-L1 ADIPOCYTES; GROWTH-FACTOR; PROTEIN; SUBSTRATE-1; TRANSLOCATION AB The hallmark of type 2 diabetes, the most common metabolic disorder, is a defect in insulin-stimulated glucose transport in peripheral tissues. Although a role for phosphoinositide-3-kinase (PI3K) activity in insulin-stimulated glucose transport and glucose transporter isoform 4 (Glut4) translocation has been suggested in vitro(1,2), its role in vive and the molecular link between activation of PI3K and translocation has not yet been elucidated. To determine the role of PI3K in glucose homeostasis, we generated mice with a targeted disruption of the gene encoding the p85 alpha regulatory subunit of PI3K (Pik3r1; refs 3-5). Pik3r1(-/-) mice showed increased insulin sensitivity and hypoglycaemia due to increased glucose transport in skeletal muscle and adipocytes. Insulin-stimulated PI3K activity associated with insulin receptor substrates (IRSs) was mediated via full-length p85 alpha in wild-type mice, but via the p50 alpha alternative splicing isoform of the same gene(6,7) in Pik3r1(-/-) mice. This isoform switch was associated with an increase in insulin-induced generation of phosphatidylinositol(3, 4, 5)triphosphate (PtdIns(3, 4, 5)P-3) in Pik3r1(-/-) adipocytes and facilitation of Glut4 translocation from the law-density microsome (LDM) fraction to the plasma membrane (PM). This mechanism seems to be responsible for the phenotype of Pik3r1(-/-) mice, namely increased glucose transport and hypoglycaemia. Our work provides the first direct evidence that PI3K and its regulatory subunit have a role in glucose homeostasis in vive. C1 Univ Tokyo, Dept Internal Med, Tokyo 1138655, Japan. Univ Tokyo, Dept Pathol, Tokyo 1138655, Japan. Univ Tokyo, Adv Sci & Technol Res Ctr, Dept Mol Biol & Med, Tokyo 1138655, Japan. Univ Tokyo, Dept Appl Biol Chem, Biol Chem Lab, Tokyo 1138655, Japan. Osaka Univ, Dept Internal Med 2, Suita, Osaka 565, Japan. Yokohama City Univ, Dept Internal Med, Yokohama, Kanagawa 236, Japan. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. Asahi Life Fdn, Inst Diabet Care & Res, Tokyo 100, Japan. Kumamoto Univ, Sch Med, Lab Transgen Technol, Kumamoto 860, Japan. Kumamoto Univ, Sch Med, Dept Dev Genet, Kumamoto 860, Japan. Kumamoto Univ, Sch Med, Inst Mol Embryol & Genet, Dept Morphogenesis, Kumamoto 860, Japan. Keio Univ, Sch Med, Dept Immunol, Tokyo 160, Japan. RP Kadowaki, T (reprint author), Univ Tokyo, Dept Internal Med, Tokyo 1138655, Japan. RI Fukui, Yasuhisa/E-8806-2010; Suzuki, Harumi/L-1271-2013; Koyasu, Shigeo/J-5583-2015 OI Suzuki, Harumi/0000-0003-3616-9361; Koyasu, Shigeo/0000-0001-9585-3038 NR 28 TC 286 Z9 291 U1 1 U2 12 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 1999 VL 21 IS 2 BP 230 EP 235 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 163MH UT WOS:000078399500030 PM 9988280 ER PT J AU Dittmer, U Brooks, DM Hasenkrug, KJ AF Dittmer, U Brooks, DM Hasenkrug, KJ TI Requirement for multiple lymphocyte subsets in protection by a live attenuated vaccine against retroviral infection SO NATURE MEDICINE LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; MURINE LEUKEMIA VIRUSES; STREET RABIES VIRUS; FRIEND-LEUKEMIA; T-CELLS; IMMUNE-RESPONSE; NEF DELETION; SIV VACCINE; HIV; ERYTHROLEUKEMIA AB Infection by live attenuated retroviruses provides excellent protection from challenge with pathogenic viruses in several animal models, but little is known about which immune effecters are necessary for protection. We examined this using adoptive transfer experiments in the Friend virus mouse model. Transfers of immune spleen cells into naive mice conferred complete protection, and transfers of purified lymphocyte subsets demonstrated that this effect required complex immune responses involving CD4(+) and CD8(+) T cells and also B cells. In addition, passive immunization experiments demonstrated that antibodies alone reduced virus loads but did not prevent infection. These findings may have implications for retroviral vaccine design in general. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. RP Hasenkrug, KJ (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 50 TC 77 Z9 77 U1 0 U2 1 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 FEB PY 1999 VL 5 IS 2 BP 189 EP 193 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 161DX UT WOS:000078274400028 PM 9930867 ER PT J AU Shibata, R Igarashi, T Haigwood, N Buckler-White, A Ogert, R Ross, W Willey, R Cho, MW Martin, MA AF Shibata, R Igarashi, T Haigwood, N Buckler-White, A Ogert, R Ross, W Willey, R Cho, MW Martin, MA TI Neutralizing antibody directed against the HIV-1 envelope glycoprotein can completely block HIV-1/SIV chimeric virus infections of macaque monkeys SO NATURE MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE GLOBULIN; MONOCLONAL-ANTIBODY; VACCINE DEVELOPMENT; CHIMPANZEES; TYPE-1; CHALLENGE; PROTECTION; GP120; PREVENTION AB Virus-specific antibodies protect individuals against a wide variety of viral infections(1-7). To assess whether human immunodeficiency virus type 1 (HIV-1) envelope-specific antibodies confer resistance against primate lentivirus infections, we purified immunoglobulin (IgG) from chimpanzees infected with several different HIV-1 isolates, and used this for passive immunization of pig-tailed macaques. These monkeys were subsequently challenged intravenously with a chimeric simian-human immunodeficiency virus (SHIV) bearing an envelope glycoprotein derived form HIV-1(DH12), a dual-tropic primary virus isolate. Here we show that anti-SHIV neutralizing activity, determined in vitro using an assay measuring loss of infectivity, is the absolute requirement for antibody-mediated protection in vivo. Using an assay that measures 100% neutralization, the titer in plasma for complete protection of the SHIV-challenged macaques was in the range of 1:5-1:8. The HIV-1-specific neutralizing antibodies studied are able to bind to native gp120 present on infectious virus particles. Administration of non-neutralizing anti-HIV IgG neither inhibited nor enhanced a subsequent SHIV infection. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. Seattle Biomed Res Inst, Seattle, WA 98109 USA. Georgetown Med Ctr, Div Mol Virol & Immunol, Rockville, MD 20852 USA. RP Shibata, R (reprint author), VaxGen, 1000 Marina Blvd, Brisbane, CA 94005 USA. NR 31 TC 435 Z9 443 U1 1 U2 9 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 FEB PY 1999 VL 5 IS 2 BP 204 EP 210 DI 10.1038/5568 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 161DX UT WOS:000078274400030 PM 9930869 ER PT J AU Igarashi, T Brown, C Azadegan, A Haigwood, N Dimitrov, D Martin, MA Shibata, R AF Igarashi, T Brown, C Azadegan, A Haigwood, N Dimitrov, D Martin, MA Shibata, R TI Human immunodeficiency virus type 1 neutralizing antibodies accelerate clearance of cell-free virions from blood plasma SO NATURE MEDICINE LA English DT Article ID INFECTED CHIMPANZEES; HIV-1 INFECTION; IN-VIVO; MONKEYS; REPLICATION; GENERATION; RESISTANCE; STRAIN; LIVE; MAC AB The concentration of human immunodeficiency virus type 1 (HIV-1) particles in blood plasma is very predictive of the subsequent disease course in an infected individual; its measurement has become one of the most important parameters for monitoring clinical status'. Steady-state virus levels in plasma reflect a balance between the rates of virions entering and leaving the peripheral blood(2). We analyzed the rate of virus clearance in the general circulation in rhesus macaques receiving a continuous infusion of cell-free particles in the presence and absence of virus-specific antibodies. Here we show, by measuring virion RNA, particle-associated p24 Gag protein and virus infectivity, that the clearance of physical and infectious particles from a primary, dual-tropic virus isolate, HIV-1(DH12), is very rapid in naive animals, with half-lives ranging from 13 to 26 minutes. In the presence of high-titer HIV-1(DH12)-specific neutralizing antibodies, the half-life of virion RNA was considerably reduced (to 3.9-7.2 minutes), and infectious virus in the blood became undetectable. Although physical virus particles were eliminated extravascularly, the loss of virus infectivity in the blood reflected the combined effects of extravascular clearance and intravascular inactivation of HIV-1 infectivity due to antibody binding. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NIH, Vet Resources Program, Bethesda, MD 20892 USA. Seattle Biomed Res Inst, Seattle, WA 98109 USA. NCI, Lab Expt & Computat Biol, NIH, Ft Detrick, MD 21702 USA. RP Igarashi, T (reprint author), NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NR 28 TC 117 Z9 118 U1 0 U2 1 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 FEB PY 1999 VL 5 IS 2 BP 211 EP 216 DI 10.1038/5576 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 161DX UT WOS:000078274400031 PM 9930870 ER PT J AU Ilardi, JM Mochida, S Sheng, ZH AF Ilardi, JM Mochida, S Sheng, ZH TI Snapin: a SNARE-associated protein implicated in synaptic transmission SO NATURE NEUROSCIENCE LA English DT Article ID RAT SYMPATHETIC NEURONS; NEUROTRANSMITTER RELEASE; MEMBRANE-PROTEIN; SYNTAXIN; IDENTIFICATION; INHIBITION; PEPTIDES; FUSION; SYNAPTOTAGMIN; EXOCYTOSIS AB Synaptic vesicle docking and fusion are mediated by the assembly of a stable SNARE core complex of proteins, which include the synaptic vesicle membrane protein VAMP/synaptobrevin and the plasmalemmal proteins syntaxin and SNAP-25. We have now identified another SNAP-25-binding protein, called Snapin. Snapin was enriched in neurons and exclusively located on synaptic vesicle membranes. It associated with the SNARE complex through direct interaction with SNAP-25. Binding of recombinant Snapin-CT to SNAP-25 blocked the association of the SNARE complex with synaptotagmin. Introduction of Snapin-CT and peptides containing the SNAP-25 binding sequence into presynaptic superior cervical ganglion neurons in culture reversibly inhibited synaptic transmission. These results suggest that Snapin is an important component of the neurotransmitter release process through its modulation of the sequential interactions between the SNAREs and synaptotagmin. C1 NINDS, Synapt Funct Unit, NIH, Bethesda, MD 20892 USA. Tokyo Med Univ, Dept Physiol, Tokyo 1608402, Japan. RP Sheng, ZH (reprint author), NINDS, Synapt Funct Unit, NIH, Bldg 36,Room 5A23,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 31 TC 144 Z9 155 U1 1 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD FEB PY 1999 VL 2 IS 2 BP 119 EP 124 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 160LF UT WOS:000078231600009 PM 10195194 ER PT J AU Iadecola, C Zhang, FY Niwa, K Eckman, C Turner, SK Fischer, E Younkin, S Borchelt, DR Hsiao, KK Carlson, GA AF Iadecola, C Zhang, FY Niwa, K Eckman, C Turner, SK Fischer, E Younkin, S Borchelt, DR Hsiao, KK Carlson, GA TI SOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein SO NATURE NEUROSCIENCE LA English DT Article ID ALZHEIMERS-DISEASE; TRANSGENIC MICE; CHRONIC HYPERTENSION; BLOOD-FLOW; SUPEROXIDE-DISMUTASE; CALCIUM IONOPHORE; BASILAR ARTERY; MOUSE-BRAIN; ARTERIOLES; RESPONSES AB Peptides derived from proteolytic processing of the beta-amyloid precursor protein (APP), including the amyloid-beta peptide, are important for the pathogenesis of Alzheimer's dementia. We found that transgenic mice overexpressing APP have a profound and selective impairment in endothelium-dependent regulation of the neocortical microcirculation. Such endothelial dysfunction was not found in transgenic mice expressing both APP and superoxide dismutase-1 (SOD1) or in APP transgenics in which SOD was topically applied to the cerebral cortex. These cerebrovascular effects of peptides derived from APP processing may contribute to the alterations in cerebral blood flow and to neuronal dysfunction in Alzheimer's dementia. C1 Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA. Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. McLaughlin Res Inst, Great Falls, MT 59405 USA. NIAID, Rocky Mt Lab, Hamilton, MT 59840 USA. Johns Hopkins Univ, Sch Med, Div Neuropathol, Baltimore, MD 21205 USA. RP Iadecola, C (reprint author), Univ Minnesota, Dept Neurol, 420 Delaware St SE, Minneapolis, MN 55455 USA. EM iadec001@tc.umn.edu FU NINDS NIH HHS [NS34179, NS35806, NS37853] NR 46 TC 267 Z9 275 U1 1 U2 6 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD FEB PY 1999 VL 2 IS 2 BP 157 EP 161 DI 10.1038/5715 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 160LF UT WOS:000078231600015 PM 10195200 ER PT J AU Weliky, DP Bennett, AE Zvi, A Anglister, J Steinbach, PJ Tycko, R AF Weliky, DP Bennett, AE Zvi, A Anglister, J Steinbach, PJ Tycko, R TI Solid-state NMR evidence for an antibody-dependent conformation of the V3 loop of HIV-1 gp120 SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID PRINCIPAL NEUTRALIZING DETERMINANT; IMMUNODEFICIENCY-VIRUS TYPE-1; ENVELOPE GLYCOPROTEIN; EXCHANGE SPECTROSCOPY; MOLECULAR-STRUCTURE; CRYSTAL-STRUCTURE; PEPTIDE; PROTEIN; DOMAIN; FUSION AB Solid-state NMR measurements have been carried out on frozen solutions of the complex of a 24-residue peptide derived from the third variable (V3)\ loop of the HIV-1 envelope glycoprotein gp120 bound to the lab fragment of an anti-gp120 antibody. The measurements place strong constraints on the conformation of the conserved central GPGR motif of the V3 loop in the antibody-bound state. In combination with earlier crystal structures of V3 peptide-antibody complexes and existing data on the cross-reactivity of the antibodies, the solid-state NMR measurements suggest that the Gly-Pro-Gly-Arg (GPGR) motif adopts an antibody-dependent conformation in the bound state and may be conformationally heterogeneous in unbound, full-length gp120, These measurements are the first application of solid-state NMR methods in a structural study of a peptide-protein complex. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Michigan State Univ, Dept Chem, E Lansing, MI 48824 USA. Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel. NIH, Ctr Mol Modeling, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. NR 44 TC 88 Z9 89 U1 1 U2 7 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD FEB PY 1999 VL 6 IS 2 BP 141 EP 145 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 161JH UT WOS:000078285100012 PM 10048925 ER PT J AU Garrett, DS Seok, YJ Peterkofsky, A Gronenborn, AM Clore, GM AF Garrett, DS Seok, YJ Peterkofsky, A Gronenborn, AM Clore, GM TI Solution structure of the 40,000 M-r phosphoryl transfer complex between the N-terminal domain of enzyme I and HPr SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID SUGAR PHOSPHOTRANSFERASE SYSTEM; PHOSPHOCARRIER PROTEIN HPR; ESCHERICHIA-COLI PHOSPHOENOLPYRUVATE; HISTIDINE-CONTAINING PROTEIN; RESTRAINED MOLECULAR-DYNAMICS; HIGH-RESOLUTION STRUCTURE; GRAM-POSITIVE BACTERIA; BACILLUS-SUBTILIS; SALMONELLA-TYPHIMURIUM; GLUCOSE PERMEASE AB The solution structure of the first protein-protein complex of the bacterial phosphoenolpyruvate: sugar phosphotransferase system between the N-terminal domain of enzyme I (EIN) and the histidine-containing phosphocarrier protein HPr has been determined by NMR spectroscopy, including the use of residual dipolar couplings that provide long-range structural information, The complex between EIN and HPr is a classical example of surface complementarity, involving an essentially all helical interface, comprising helices 2, 2', 3 and 4 of the cr-subdomain of EIN and helices 1 and 2 of HPr, that requires virtually no changes in conformation of the components relative to that in their respective free states, The specificity of the complex is dependent on the correct placement of both van der Waals and electrostatic contacts, The transition state can be formed with minimal changes in overall conformation, and is stabilized in favor of phosphorylated HPr, thereby accounting for the directionality of phosphoryl transfer. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. Seoul Natl Univ, Coll Nat Sci, Dept Microbiol, Seoul 151742, South Korea. RP Clore, GM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. EM gronenborn@vger.niddk.nih.gov; clore@speck.niddk.nih.gov RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 47 TC 189 Z9 193 U1 0 U2 9 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD FEB PY 1999 VL 6 IS 2 BP 166 EP 173 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 161JH UT WOS:000078285100016 PM 10048929 ER PT J AU Rohrenbeck, AM Bette, M Hooper, DC Nyberg, F Eiden, LE Dietzschold, B Weihe, E AF Rohrenbeck, AM Bette, M Hooper, DC Nyberg, F Eiden, LE Dietzschold, B Weihe, E TI Upregulation of COX-2 and CGRP expression in resident cells of the Borna disease virus-infected brain is dependent upon inflammation SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Borna disease virus; cyclooxygenase; prostaglandin; calcitonin gene-related peptide; neuropeptide; neocortex; hippocampus; macrophage/microglia; endothelium; encephalitis; dexamethasone; neuroimmunology; neurotoxicity; neuroprotection ID GENE-RELATED PEPTIDE; CYCLOOXYGENASE-2 MESSENGER-RNA; CENTRAL-NERVOUS-SYSTEM; RAT MICROGLIAL CULTURES; GROWTH-FACTOR; SUBSTANCE-P; SPINAL-CORD; INDUCIBLE CYCLOOXYGENASE; IMMUNODEFICIENCY-VIRUS; SIGNAL-TRANSDUCTION AB Infection of immunocompetent adult rats with Borna disease virus (BDV) causes severe encephalitis and neural dysfunction. The expression of COX-2 and CORP, genes previously shown to be implicated in CNS disease and peripheral inflammation, was dramatically upregulated in the cortical neurons of acutely BDV-infected rats. Neuronal COX-2 and CGRP upregulation was predominantly seen in brain areas where ED1-positive macrophages/microglia accumulated. In addition, COX-2 expression was strongly induced in brain endothelial cells and the number of COX-2 immunoreactive microglial cells was increased. In contrast, despite increased expression of viral antigens, neither COX-2 nor CGRP expression was altered in the CNS of BDV-infected rats treated with dexamethasone, or tolerant to BDV. Thus, increased CGRP and COX-2 expression in the BDV-infected brain is the result of the inflammatory response and likely to be involved in the pathogenesis of virus-induced encephalitis. (C) Press Academic Press. C1 Univ Marburg, Inst Anat & Cell Biol, D-35032 Marburg, Germany. Thomas Jefferson Univ, Dept Microbiol & Immunol, Ctr Neurovirol, Philadelphia, PA 19107 USA. Univ Uppsala, Dept Pharmaceut Sci, Ctr Biomed, S-75105 Uppsala, Sweden. NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Rohrenbeck, AM (reprint author), Univ Marburg, Inst Anat & Cell Biol, D-35032 Marburg, Germany. OI Eiden, Lee/0000-0001-7524-944X; Hooper, Douglas/0000-0002-8578-5104 NR 98 TC 30 Z9 30 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD FEB PY 1999 VL 6 IS 1 BP 15 EP 34 DI 10.1006/nbdi.1998.0225 PG 20 WC Neurosciences SC Neurosciences & Neurology GA 168XH UT WOS:000078718100002 PM 10078970 ER PT J AU Parent, A Linden, DJ Sisodia, SS Borchelt, DR AF Parent, A Linden, DJ Sisodia, SS Borchelt, DR TI Synaptic transmission and hippocampal long-term potentiation in transgenic mice expressing FAD-linked presenilin 1 SO NEUROBIOLOGY OF DISEASE LA English DT Article ID FAMILIAL ALZHEIMERS-DISEASE; AMYLOID BETA-PROTEIN; IN-VIVO; MUTANT PRESENILIN-1; LOCALIZATION; PLASTICITY; CELLS; MUTATIONS; CURRENTS; PLAQUES AB Mutations in two related genes, presenilin 1 acid presenilin 2 (PS1 and PSZ), cause a subset of early-onset familial Alzheimer's disease (FAD). PS1 is expressed in a variety of neuronal and peripheral tissues, including neuronal populations known to be at risk in Alzheimer's disease such as CA1 hippocampal neurons. To examine whether FAD-linked mutations in PS1 directly influence the physiology of learning and memory, we measured the field excitatory postsynaptic potential (fEPSP) at the Schaffer collateral-CA1 synapse in hippocampal slices. Basal synaptic transmission and long-term potentiation (LTP) were examined in neurons of transgenic mice expressing wild-type human PS1 (WtTg) and FAD-linked A246E PS1 variant (MTg) and in neurons of nontransgenic littermates (NTg). Several measures of basal synaptic transmission were unaltered in WtTg and MTg compared to NTg mice, including maximum fEPSP slope, maximum fEPSP amplitude, maximum fiber volley amplitude, and the function relating fiber volley amplitude to fEPSP slope, an index of basal synaptic strength. In addition, paired-pulse facilitation was not changed. However, upon theta burst stimulation or high-frequency stimulation, input-specific LTP in MTg animals had a larger initial amplitude and was more persistent than that in WtTg or NTg animals. These data suggest that the FAD-linked A246E variant of PS1 leads to higher degree of LTP induction in mice. (C) 1999 Academic Press. C1 Univ Chicago, Dept Pharmacol & Physiol Sci, Chicago, IL 60637 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. NINDS, Epilepsy Res Branch, Bethesda, MD 20892 USA. RP Parent, A (reprint author), Univ Chicago, Dept Pharmacol & Physiol Sci, 947 E 58th St, Chicago, IL 60637 USA. EM aparent@helix.nih.gov FU NIA NIH HHS [AG14248] NR 26 TC 92 Z9 93 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD FEB PY 1999 VL 6 IS 1 BP 56 EP 62 DI 10.1006/nbdi.1998.0207 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 168XH UT WOS:000078718100005 PM 10078973 ER PT J AU Tzeng, SF Deibler, GE DeVries, GH AF Tzeng, SF Deibler, GE DeVries, GH TI Myelin basic protein and myelin basic protein peptides induce the proliferation of Schwann cells via ganglioside GM1 and the FGF receptor SO NEUROCHEMICAL RESEARCH LA English DT Article DE myelin basic protein; mitogens; Schwann cell; ganglioside ID FIBROBLAST GROWTH-FACTORS; NERVE AB Myelin basic protein (MBP) and two peptides derived from MBP (MBP1-44 and MBP152-167) stimulated Schwann cell (SC) proliferation in a cAMP-mediated process. The two mitogenic regions of MBP did not compete with one another for binding to SC suggesting a distinctive SC receptor for each mitogenic peptide. Neutralizing antibodies to the fibroblast growth factor receptor blocked the mitogenic effect of the myelin-related SC mitogen found in the supernatant of myelin-fed macrophages. The binding of I-125-MBP to Schwann cells was specifically inhibited by basic fibroblast growth factor (bFGF) and conversely the binding of I-125-bFGF was competitively inhibited by MBP. These data suggested that the mitogenic effect of one MBP peptide was mediated by a bFGF receptor. The binding of MBP to ganglioside GM1 and the ability of MBP peptides containing homology to the B subunit of cholera toxin (which binds ganglioside GM1 ) to compete for the binding of a mitogenic peptide (MBP1-44) to SC, identified ganglioside GM1 as a second SC receptor. Based on these results, we conclude that MBP1-44 and MBP152-167 associate with ganglioside GM1 and the bFGF receptor respectively to stimulate SC mitosis. C1 Edward Hines Vet Adm Hosp, Res Serv, Res 151, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Dept Cell Biol Neurobiol & Anat, Maywood, IL 60153 USA. NIMH, Cerebral Metab Lab, NIH, Bethesda, MD 20892 USA. RP DeVries, GH (reprint author), Edward Hines Vet Adm Hosp, Res Serv, Res 151, 5th Ave & Roosevelt Rd, Hines, IL 60141 USA. FU NINDS NIH HHS [NS15408] NR 18 TC 23 Z9 23 U1 0 U2 3 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD FEB PY 1999 VL 24 IS 2 BP 255 EP 260 DI 10.1023/A:1022514105129 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 160LN UT WOS:000078232300010 PM 9972872 ER PT J AU Zirzow, GC Sanchez, OA Murray, GJ Brady, RO Oldfield, EH AF Zirzow, GC Sanchez, OA Murray, GJ Brady, RO Oldfield, EH TI Delivery, distribution, and neuronal uptake of exogenous mannose-terminal glucocerebrosidase in the intact rat brain SO NEUROCHEMICAL RESEARCH LA English DT Article DE Gaucher disease; glucocerebrosidase delivery to brain ID MACROPHAGE-TARGETED GLUCOCEREBROSIDASE; GAUCHERS-DISEASE; INFUSION; THERAPY AB Gaucher disease is caused by insufficient activity of the enzyme glucocerebrosidase. Great benefit has been obtained through enzyme replacement therapy for patients with type 1 (non-neuronopathic) Gaucher disease. In contrast, inconsistent effects of enzyme therapy have been observed in patients with type 3 (chronic neuronopathic) Gaucher disease, and no benefit on the lethal course of the disease occurs in patients with Type 2 (acute neuronopathic) Gaucher disease. We examined the use of convection-enhanced delivery to augment the delivery and distribution of exogenous glucocerebrosidase (m.w. 63,000) to the brain by infusing it under slight hydrostatic pressure into the striatal region of rats. The enzyme was comparatively stable under these conditions. It was distributed from the site of injection toward the cerebral cortex where it became primarily localized in neurons. These findings provide considerable incentive far the exploration of intracerebral microinfusion of enzyme to the brain of patients with metabolic storage disorders involving the CNS. C1 NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Brady, RO (reprint author), NINDS, Dev & Metab Neurol Branch, NIH, Bldg 10,Room 3D04,10 Ctr Dr MSC 1260, Bethesda, MD 20892 USA. EM robrady@codon.nih.gov NR 20 TC 36 Z9 37 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD FEB PY 1999 VL 24 IS 2 BP 301 EP 305 DI 10.1023/A:1022578424693 PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 160LN UT WOS:000078232300017 PM 9972879 ER PT J AU Sokoloff, L AF Sokoloff, L TI Energetics of functional activation in neural tissues SO NEUROCHEMICAL RESEARCH LA English DT Article DE [B-14]deoxyglucose; Na+,K+-ATPase; glutamate; astrocyte; sodium; potassium; glucose utilization ID CEREBRAL GLUCOSE-UTILIZATION; ELECTRICAL-STIMULATION; CULTURED ASTROCYTES; EXTRACELLULAR K+; GLUTAMATE UPTAKE; SODIUM-PUMP; RAT; METABOLISM; SYSTEM; DEOXYGLUCOSE AB Glucose utilization (1CMR(glc)) increases linearly with spike frequency in neuropil but not perikarya of functionally activated neural tissues. Electrical stimulation, increased extracellular [K+] ([K+](alpha)), or opening of Na+ channels with veratridine stimulates 1CMR(glc) in neural tissues; these increases are blocked by ouabain, an inhibitor of Na+,K-divided by-ATPase. Stimulating Na+,K-divided by-ATPase activity to restore ionic gradients degraded by enhanced spike activity appears to trigger these increases in 1CMR(glc). Cultured neurons behave similarly. Astrocytic processes that envelop synapses in neuropil probably contribute to the increased 1CMR(glc). 1CMR(glc) in cultured astroglia is unaffected by elevated [K+](alpha) but is stimulated by increased intracellular [Na+] ([Na+](i)), and this stimulation is blocked by ouabain or tetrodotoxin. L-Glutamate also stimulates 1CMR(glc), in astroglia. This effect is unaffected by inhibitors of NMDA or non-NMDA receptors, blocked by ouabain, and absent in Na+ -free medium; it appears to be mediated by increased [Na+](i), due to combined uptake of Na+ with glutamate via Na+/glutamate co-transporters. C1 NIMH, Cerebral Metab Lab, NIH, Bethesda, MD 20892 USA. RP Sokoloff, L (reprint author), NIMH, Cerebral Metab Lab, NIH, Bldg 36,1A-05,36 Convent Dr MSC 4030, Bethesda, MD 20892 USA. NR 29 TC 160 Z9 162 U1 0 U2 11 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD FEB PY 1999 VL 24 IS 2 BP 321 EP 329 DI 10.1023/A:1022534709672 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 160LN UT WOS:000078232300020 PM 9972882 ER PT J AU Gross, RA Theodore, WH AF Gross, RA Theodore, WH TI "The seat of the discharge" and the molecules that govern seizures SO NEUROLOGY LA English DT Editorial Material ID TEMPORAL-LOBE EPILEPSY; POSITRON EMISSION TOMOGRAPHY; GAMMA-AMINOBUTYRIC-ACID; RECEPTOR-BINDING; NEURONS C1 Univ Rochester, Med Ctr, Strong Epilepsy Ctr, Rochester, NY 14642 USA. Univ Rochester, Dept Neurol, Rochester, NY 14642 USA. Univ Rochester, Dept Pharmacol & Physiol, Rochester, NY 14642 USA. NIH, Bethesda, MD 20892 USA. RP Gross, RA (reprint author), Univ Rochester, Med Ctr, Strong Epilepsy Ctr, Box 673,601 Elmwood Ave, Rochester, NY 14642 USA. NR 19 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 1999 VL 52 IS 3 BP 441 EP 443 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 165GQ UT WOS:000078512900003 PM 10025769 ER PT J AU Siegel, H McCutchen, C Dalakas, MC Freeman, A Graham, B Alling, D Sato, S AF Siegel, H McCutchen, C Dalakas, MC Freeman, A Graham, B Alling, D Sato, S TI Physiologic events initiating REM sleep in patients with the postpolio syndrome SO NEUROLOGY LA English DT Article ID EYE-MOVEMENTS; PGO WAVES; BEHAVIOR AB Background: We previously studied the occurrence of muscle tone reduction (MTR), sawtooth waves (STW), and REM in sleep, and found a stereotypical sequence of these events in normal subjects. Patients with the postpolio syndrome may have involvement of the reticular formation in the brainstem, an area known to mediate initiation of REM sleep. We hypothesized that such brainstem pathology might affect the stereotyped sequence of events initiating REM sleep. Methods: We measured the latencies to the onsets of the first MTR, the first STW, and the first REM in 13 patients with postpolio syndrome, 7 of whom had bulbar involvement. All latencies were calculated from the last body movement before the onset of REM sleep. Results: Using analysis of variance, we found highly significant differences among the overall mean latencies of the three types of onset (MTR, STW, REM) and also between the mean latencies of the two subgroups of patients (bulbar, nonbulbar). Although the latencies for the entire group were longer than those of the normal volunteers, the differences were not significant. However, when the bulbar and nonbulbar groups were compared, analysis of variance showed significantly longer latencies for the bulbar group than for the nonbulbar group (p < 0.0001). The values for the nonbulbar patients closely resembled those for the normal controls. Although the latencies differed, the slopes of the regressions of REM on STW, STW on MTR, and REM on MTR resembled each other closely (p = 0.924). Conclusion: Prolongation of these latencies may be due to prolonged recruitment time for neurons in the pontine tegmentum, following damage from polio. This may be a sensitive marker of a brainstem lesion, and may also represent a type of sleep pathology not previously explored. C1 NINCDS, EEG Sect, Off Clin Director, NIH, Bethesda, MD 20892 USA. NINCDS, Neuromuscular Dis Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. NIH, Off Director, Bethesda, MD 20892 USA. RP Sato, S (reprint author), NINCDS, EEG Sect, Off Clin Director, NIH, Bldg 10,Room 5C-101,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 18 TC 8 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 1999 VL 52 IS 3 BP 516 EP 522 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 165GQ UT WOS:000078512900014 PM 10025780 ER PT J AU Corthout, E Uttl, B Ziemann, U Cowey, A Hallett, M AF Corthout, E Uttl, B Ziemann, U Cowey, A Hallett, M TI Two periods of processing in the (circum)striate visual cortex as revealed by transcranial magnetic stimulation SO NEUROPSYCHOLOGIA LA English DT Article DE transcranial magnetic stimulation (TMS); human; visual cortex; occipital lobe; vision; perception; suppression ID MACAQUE MONKEY; AREAS V1; RESPONSE LATENCIES; OCCIPITAL CORTEX; PERCEPTION; SUPPRESSION; V5; ORIENTATION; NEURONS; V2 AB To determine the timing of visual processing in the (circum)striate visual cortex, we examined the effect of single pulse transcranial magnetic stimulation over the occipital pole of healthy subjects who were engaged in a forced-choice visual letter identification task. Single letters, subtending a visual angle of 0.35 degrees, were foveally presented for 10 ms and were immediately followed by a mask. We investigated 30 different delays (d), defined as the time between the onset of the visual stimulus and the onset of the magnetic stimulus, from d = - 100 ms to d = + 190 ms, and 4 different midsagittal coil positions (x), defined as the distance between the lower edge of the coil and the upper edge of the inion, from x = 1 cm to x = 7 cm. Three out of four subjects showed three distinct delay intervals (dips) at which application of TMS resulted in an impairment of the task. The first dip was centred around d = - 50 ms and occurred independently of the coil position; the second dip was centred around d = 0 ms and was elicitable only with the two lowest coil positions; the third dip was centred around d = 100 ms and was also elicitable only with the lower coil positions. In the fourth subject, only the first and the third dip were found. We conclude that there are two distinct periods when the activity in the (circum)striate visual cortex is necessary for the identification of visually presented letters. (C) 1999 Published by Elsevier Science Ltd. All rights reserved. C1 Univ Oxford, Dept Expt Psychol, Oxford OX1 2JD, England. NINDS, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Corthout, E (reprint author), Univ Oxford, Dept Expt Psychol, Oxford OX1 2JD, England. NR 21 TC 75 Z9 76 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD FEB PY 1999 VL 37 IS 2 BP 137 EP 145 PG 9 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 166JE UT WOS:000078571800002 PM 10080371 ER PT J AU Grafman, J Wassermann, E AF Grafman, J Wassermann, E TI Transcranial magnetic stimulation can measure and modulate learning and memory SO NEUROPSYCHOLOGIA LA English DT Article DE Transcranial Magnetic Stimulation; learning; memory ID POSITRON EMISSION TOMOGRAPHY; SUPPLEMENTARY MOTOR AREA; SHORT-TERM-MEMORY; DORSOLATERAL PREFRONTAL CORTEX; BRAIN-STIMULATION; WORKING-MEMORY; SEQUENCES; IMPLICIT; CONNECTIVITY; FREQUENCY AB The potential uses for Transcranial Magnetic Stimulation (TUS) in the study of learning and memory range from a method to map the topography and intensity of motor output maps during visuomotor learning to inducing reversible lesions that allow for the precise temporal and spatial dissection of the brain processes underlying learning and remembering. Single-pulse TMS appears to be adequate to examine motor output maps but repetitive TMS (rTMS) appears necessary to affect most cognitive processes in measurable ways. The results we have reviewed in this article indicate that rTMS may have a potential clinical application in patients with epilepsy in whom it is important to identify the lateralization of verbal memory. Single-pulse TMS can help identify changes in motor output maps during training, that may indicate improved or diminished learning and memory processes following a stroke or other neurological insult. Other evidence indicates that rTMS may even have the capability of facilitating various aspects of memory performance. From a research perspective, rTMS has demonstrated site- and time-specific effects primarily in interfering with explicit retrieval of episodic information from long-term memory. rTMS may also be able to modulate retrieval from semantic memory as evidenced by response-time and accuracy changes after rTMS. All these findings suggest that the use of transcranial magnetic stimulation in the study of learning and memory will increase in the future and that it is already a valuable tool in the cognitive neuroscientists' belt. (C) 1999 Published by Elsevier Science Ltd. C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. NINDS, Off Clin Director, NIH, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 10,Room 5C205,10 Ctr Dr,MSC 14, Bethesda, MD 20892 USA. NR 51 TC 58 Z9 60 U1 2 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD FEB PY 1999 VL 37 IS 2 BP 159 EP 167 PG 9 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 166JE UT WOS:000078571800004 PM 10080373 ER PT J AU Steiner, H Gerfen, CR AF Steiner, H Gerfen, CR TI Enkephalin regulates acute D-2 dopamine receptor antagonist-induced immediate-early gene expression in striatal neurons SO NEUROSCIENCE LA English DT Article DE enkephalin; delta and mu opioids; immediate-early genes; D-2 dopamine receptor; striatum ID MESSENGER-RNA EXPRESSION; IN-SITU HYBRIDIZATION; MU-OPIOID RECEPTOR; ULTRASTRUCTURAL IMMUNOCYTOCHEMICAL LOCALIZATION; SENSITIVE ADENYLATE-CYCLASE; C-FOS INDUCTION; RAT STRIATUM; SUBSTANCE-P; NUCLEUS-ACCUMBENS; GLOBUS-PALLIDUS AB Projection neurons of the striatum release opioid peptides in addition to GABA. Our previous studies showed that the opioid peptide dynorphin regulates that subtype of projection neurons which sends axons to the substantia nigra/entopeduncular nucleus, as indicated by an inhibitory action of dynorphin/agonists on D-1 dopamine receptor-mediated immediate-early gene induction in these neurons. The other subtype of striatal projection neurons projects to the globus pallidus and contains the opioid peptide enkephalin. Here, we investigated whether enkephalin regulates the function of striatopallidal neurons, by analysing opioid effects on immediate-early gene induction by D-1 dopamine receptor blockade that occurs in these neurons. Thus, the effects of systemic and intrastriatal administration of various opioid receptor agonists and antagonists on immediate-early gene expression (c-fos, zif 268) induced by the D-2 receptor antagonist eticlopride were examined with in situ hybridization histochemistry. Intrastriatal infusion of enkephalin (delta and mu), but not dynorphin (kappa), receptor agonists suppressed immediate-early gene induction by eticlopride in a dose-dependent manner. This suppression was blocked by the opioid receptor antagonist naloxone, confirming the involvement of opioid receptors. Repeated treatment with D-2 receptor antagonists produces increased enkephalin expression and diminished immediate-early gene inducibility in striatopallidal neurons, as well as behavioral effects that are attenuated compared to those of acute treatment (e.g., reduced akinesia). Naloxone reversed such behavioral recovery (i.e. reinstated akinesia), but did not significantly affect suppressed immediate-early gene induction. Our results indicate that enkephalin acts, via mu and delta receptors in the striatum, to inhibit acute effects of D-2 receptor blockade in striatopallidal neurons. Moreover, the present findings suggest that increased enkephalin expression after repealed D-2 receptor antagonist treatment is an adaptive response that counteracts functional consequences of D-2 receptor blockade, but is not involved in suppressed immediate-early gene induction. Together with our earlier findings of the role of dynorphin, these results indicate that opioid peptides in the striatum serve as negative feedback systems to regulate the striatal output pathways in which they are expressed. (C) 1998 IBRO. Published by Elsevier Science Ltd. C1 Univ Tennessee, Coll Med, Dept Anat & Neurobiol, Memphis, TN 38163 USA. NIMH, Neurophysiol Lab, Bethesda, MD 20892 USA. RP Steiner, H (reprint author), Univ Tennessee, Coll Med, Dept Anat & Neurobiol, Memphis, TN 38163 USA. FU NINDS NIH HHS [NS20702, NS26473] NR 69 TC 46 Z9 48 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD FEB PY 1999 VL 88 IS 3 BP 795 EP 810 DI 10.1016/S0306-4522(98)00241-3 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 138UW UT WOS:000076992500012 PM 10363818 ER PT J AU Chalecka-Franaszek, E Chen, H Chuang, DM AF Chalecka-Franaszek, E Chen, H Chuang, DM TI 5-hydroxytryptamine(2A) receptor stimulation induces activator protein-1 and cyclic AMP-responsive element binding with cyclic AMP-responsive element-binding protein and Jun D as common components in cerebellar neurons SO NEUROSCIENCE LA English DT Article DE DOI; AP-1; CRE; CREB; jun D; cerebellar granule cells ID TRANSCRIPTION FACTORS; SEROTONIN RECEPTORS; AP-1 ACTIVATION; GRANULE CELLS; RAT-BRAIN; HA-RAS; C-JUN; CREB; GENE; KINASE AB Previous studies from our laboratory have demonstrated that stimulation of 5-hydroxytryptamine(2A) receptors in rat cerebellar granule cells produces an increase in the levels of 5-hydroxytryptamine(2A) receptor messenger RNA and binding sites, and that this up-regulation requires de novo RNA and protein synthesis. Here we showed that up-regulation of 5-hydroxytryptamine(2A) receptor binding sites induced by stimulation with the 5-hydroxytryptamine(2A/2C) receptor agonist, (+/-)-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), is associated with an increase in the 5-hydroxytryptamine(2A) receptor transcription rate. To examine the possible role of transcriptional activation in DOI-induced 5-hydroxytryptamine(2A) receptor up-regulation, we studied the effects of DOI on transcription Factor binding to activator protein-1 and cyclic AMP-responsive element (CRE) DNA consensus sequences. We found that DOI induces a time-dependent increase in activator protein-1 and CRE transcription factor binding activity, which is blocked by 5-hydroxytryptamine(2A) receptor antagonists. Similar to 5-hydroxytryptamine(2A) receptor up-regulation. DOI-induced activator protein-1 binding is suppressed by inhibitors of calmodulin and Ca2+/calmodulin-dependent kinases. The increased activator protein-1 binding is effectively competed by excessive activator protein-1 and CRE sequences as well as endogenous activator protein-1-like sequences present in the rat 5-hydroxytryptamine(2A) receptor gene. Supershift assays revealed that cAMP-responsive element-binding protein (CREB) and Jun D are common components of both activator protein-1 and CRE binding complexes. DOI also increased the level of phospho-CREB in a time-dependent manner. The binding of phospho-CREB transcription Factor to the activator protein-1 site suggests that CREB may modulate the transcription of genes that contain activator protein-1 but lack CRE site in their promoters, through interaction with the activator protein-1 site. The rat 5-hydroxytryptamine(2A) receptor up-regulation may involve such a mechanism. (C) 1998 IBRO. Published by Elsevier Science Ltd. C1 NIMH, Mol Neurobiol Sect, Biol Psychiat Branch, Bethesda, MD 20892 USA. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, Biol Psychiat Branch, Bethesda, MD 20892 USA. NR 42 TC 17 Z9 18 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD FEB PY 1999 VL 88 IS 3 BP 885 EP 898 DI 10.1016/S0306-4522(98)00269-3 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 138UW UT WOS:000076992500019 PM 10363825 ER PT J AU Brodkin, ES Kosten, TA Haile, CN Heninger, GR Carlezon, WA Jatlow, P Remmers, EF Wilder, RL Nestler, EJ AF Brodkin, ES Kosten, TA Haile, CN Heninger, GR Carlezon, WA Jatlow, P Remmers, EF Wilder, RL Nestler, EJ TI Dark Agouti and Fischer 344 rats: Differential behavioral responses to morphine and biochemical differences in the ventral tegmental area SO NEUROSCIENCE LA English DT Article DE inbred rat strains; morphine; behavioral sensitization; mesolimbic dopamine system; tyrosine hydroxylase; corticosterone ID MESOLIMBIC DOPAMINE SYSTEM; INDUCED CORTICOSTERONE SECRETION; CONDITIONED PLACE PREFERENCE; STRESS-INDUCED SENSITIZATION; TYROSINE-HYDROXYLASE; LEWIS RAT; NEUROFILAMENT PROTEINS; LOCOMOTOR-ACTIVITY; STRAIN DIFFERENCES; INDUCED ARTHRITIS AB We sought to identify behavioral and biochemical differences between Dark Agouti and Fischer 344 inbred rat strains to assess whether they could serve as a model of genetically determined differences in sensitivity to drugs of abuse. We compared the strains for the following traits: morphine-induced locomotor activity and sensitization; circadian variation in plasma levels of corticosterone, a hormone reported to affect sensitivity to drugs of abuse; and several biochemical parameters in the ventral tegmental area and nucleus accumbens, brain regions implicated in the locomotor activating and reinforcing actions of drugs of abuse. Fischer 344 rats exhibited greater initial locomotor responses to morphine but, unlike Dark Agouti rats, did not develop sensitization to a second morphine exposure. Fischer 344 rats displayed a marked rise in basal plasma corticosterone levels in the late light phase and early dark phase, whereas Dark Agouti rats showed no significant circadian variation in corticosterone levels. Relative to drug-naive Fischer 344 rats, drug-naive Dark Agouti rats showed higher levels of tyrosine hydroxylase and glial fibrillary acidic protein, and lower levels of neurofilament proteins, in the ventral tegmental area. In contrast, no strain differences were found in levels of tyrosine hydroxylase, specific G protein subunits or protein kinase A in the nucleus accumbens. Together, these results demonstrate that Dark Agouti rats and Fischer 344 rats exhibit differences in specific behavioral, endocrine and biochemical parameters related to sensitivity to drugs of abuse. (C) 1998 IBRO. Published by Elsevier Science Ltd. C1 Yale Univ, Sch Med, Dept Psychiat, Lab Mol Psychiat, New Haven, CT 06508 USA. Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06508 USA. Connecticut Mental Hlth Ctr, New Haven, CT 06508 USA. Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06510 USA. NIAMSD, Inflammatory Joint Dis Sect, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. RP Nestler, EJ (reprint author), Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. OI Haile, Colin/0000-0001-8293-7291 FU NIDA NIH HHS [DA04060, DA08227] NR 48 TC 15 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD FEB PY 1999 VL 88 IS 4 BP 1307 EP 1315 DI 10.1016/S0306-4522(98)00291-7 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 146PJ UT WOS:000077439300027 PM 10336139 ER PT J AU Horti, AG Koren, AO Lee, KS Mukhin, AG Vaupel, DB Kimes, AS Stratton, M London, ED AF Horti, AG Koren, AO Lee, KS Mukhin, AG Vaupel, DB Kimes, AS Stratton, M London, ED TI Radiosynthesis and preliminary evaluation of 5-[I-123/125]iodo3-(2(S)-azetidinylmethoxy)pyridine: A radioligand for nicotinic acetylcholine receptors SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE radiotracer; A-85380; I-123; I-125; radioiodination; nicotinic receptors; acetylcholine; receptor binding; SPECT ID CHOLINERGIC RECEPTORS; IN-VIVO; RADIOIODINATED ANALOG; EPIBATIDINE ANALOG; CEREBRAL-CORTEX; BINDING-SITES; H-3 CYTISINE; RAT-BRAIN; AFFINITY; FLUORINE-18-FPH AB The radiochemical syntheses of 5-[I-125]iodo-3-(2 (S)-azetidinylmethoxy)pyridine (5-[I-125]iodo-A-85380, [I-125]1) and 5-[I-123]-iodo-A-85380, [I-123]1, were accomplished by radioiodination of 5-trimethylstannyl-3-( (1-tert-butoxycarbonyl-2 (S)-azetidinyl)methoxy)pyridine, 2, followed by acidic deprotection. Average radiochemical yields of [I-125]1 and [I-123]1 were 40-55%; and the average specific radioactivities were 1,700 and 7,000 mCi/mu mol, respectively. Binding affinities of [I-125]1 and [I-123]1 in vitro (rat brain membranes) were each characterized by a K-d value of 11 pM. Preliminary in vivo assay and ex vivo autoradiography of mouse brain indicated that [I-125]1 selectively labels nicotinic acetylcholine receptors (nAChRs) with very high affinity and specificity. These studies suggest that [I-123]1 may be useful as a radioligand for single photon emission computed tomography (SPECT) imaging of nAChRs. NUCL MED BIOL 26;2:175-182, 1999. Published by Elsevier Science Inc. C1 NIDA, Brain Imaging Ctr, Intramural Res Program, Baltimore, MD 21224 USA. NIMH, Clin Brain Disorders Branch, Washington, DC 20032 USA. RP London, ED (reprint author), NIDA, Brain Imaging Ctr, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 40 TC 43 Z9 47 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD FEB PY 1999 VL 26 IS 2 BP 175 EP 182 DI 10.1016/S0969-8051(98)00086-9 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 167MB UT WOS:000078636100003 PM 10100216 ER PT J AU Wolffe, AP Hayes, JJ AF Wolffe, AP Hayes, JJ TI Chromatin disruption and modification SO NUCLEIC ACIDS RESEARCH LA English DT Review ID YEAST SWI/SNF COMPLEX; RIBOSOMAL-RNA GENE; TRANSCRIPTION FACTOR ACCESS; NUCLEOSOME CORE STRUCTURE; DNASE-I SENSITIVITY; HISTONE ACETYLATION; LINKER HISTONE; N-TERMINI; GLOBULAR DOMAIN; FACILITATED BINDING AB Chromatin disruption and modification are associated with transcriptional regulation by diverse coactivators and corepressors. Here we discuss the possible structural basis and functional consequences of the observed alterations in chromatin associated with transcriptional activation and repression. Recent advances in defining the roles of individual histones and their domains in the assembly and maintenance of regulatory architectures provide a framework for understanding how chromatin remodelling machines, histone acetyltransferases and deacetylases function. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. Univ Rochester, Med Ctr, Dept Biochem & Biophys, Rochester, NY 14642 USA. RP Wolffe, AP (reprint author), NICHHD, Mol Embryol Lab, NIH, Bldg 18T,Room 106, Bethesda, MD 20892 USA. EM awlme@helix.nih.gov NR 173 TC 355 Z9 375 U1 2 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 1 PY 1999 VL 27 IS 3 BP 711 EP 720 DI 10.1093/nar/27.3.711 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 164EH UT WOS:000078449400001 PM 9889264 ER PT J AU Clark, AB Cook, ME Tran, HT Gordenin, DA Resnick, MA Kunkel, TA AF Clark, AB Cook, ME Tran, HT Gordenin, DA Resnick, MA Kunkel, TA TI Functional analysis of human MutS alpha and MutS beta complexes in yeast SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CANCER CELL-LINES; DNA MISMATCH REPAIR; HUMAN MSH2 PROTEIN; SACCHAROMYCES-CEREVISIAE; MICROSATELLITE INSTABILITY; ENDOMETRIAL CANCER; BINDS; HETERODIMER; REPLICATION; SEQUENCES AB Mismatch repair (MMR) is initiated when a heterodimer of hMSH2.hMSH6 or hMSH2.hMSH3 binds to mismatches. Here we perform functional analyses of these human protein complexes in yeast. We use a sensitive genetic system wherein the rate of single-base deletions in a homopolymeric run in the LYS2 gene is 10 000-fold higher in an msh2 mutant than in a wild-type strain. Expression of the human proteins alone or in combination does not reduce the mutation rate of the msh2 strain, and expression of the individual human proteins does not increase the row mutation rate of a wild-type strain. However, co-expression of hMSH2 and hMSH6 in wild-type yeast increases the mutation rate 4000-fold, while co-expression of hMSH2 and hMSH3 elevates the rate 5-fold. Analysis of cell extracts indicates that the proteins are expressed and bind to mismatched DNA. The results suggest that hMutS alpha and hMutS beta complexes form, bind to and prevent correction of replication slippage errors in yeast. Expression of hMSH6 with hMSH2 containing a proline substituted for a conserved Arg(524) eliminates the mutator effect and reduces mismatch binding. The analogous mutation in humans is associated with microsatellite instability, defective MMR and cancer, illustrating the utility of the yeast system for studying human disease alleles. C1 NIEHS, Genet Mol Lab, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Genet Mol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 35 TC 44 Z9 45 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 1 PY 1999 VL 27 IS 3 BP 736 EP 742 DI 10.1093/nar/27.3.736 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 164EH UT WOS:000078449400004 PM 9889267 ER PT J AU Feledy, JA Morasso, MI Jang, SI Sargent, TD AF Feledy, JA Morasso, MI Jang, SI Sargent, TD TI Transcriptional activation by the homeodomain protein Distal-less 3 SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DLX GENE FAMILY; HOMEOBOX GENES; PROXIMAL PROMOTER; TRANSGENIC MICE; EXPRESSION; BINDING; CELLS; EVOLUTION; DNA; EPIDERMIS AB PCR-based methods and mobility shift competition assays were used to determine the basic biochemical features of the homeodomain transcription factor Distal-less 3 (Dlx3), including an optimal DNA binding site, the binding constant and dissociation rates of this protein. Expression of Dlx3 protein in either HeLa cells or Xenopus embryos resulted in strong activation of a model target gene construct containing three tandem copies of the Dlx3 binding site upstream from the TATA element. In addition, deletion analysis revealed that transcriptional activation by Dlx3 depends on two subdomains located on either side of the homeobox: removal of either subdomain resulted in complete loss of Dlx3 function. These observations provide new insight regarding the function of Dlx3 in vertebrate development and tissue differentiation and also suggest a mechanism for the dominant inheritance pattern of a hereditary disease resulting from mutation of the DLX3 gene in human. C1 NICHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. NIAMS, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. RP Sargent, TD (reprint author), NICHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. EM tsargent@nih.gov FU NIAMS NIH HHS [Z01 AR041124-06] NR 33 TC 65 Z9 66 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 1 PY 1999 VL 27 IS 3 BP 764 EP 770 DI 10.1093/nar/27.3.764 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 164EH UT WOS:000078449400008 PM 9889271 ER PT J AU Shultzaberger, RK Schneider, TD AF Shultzaberger, RK Schneider, TD TI Using sequence logos and information analysis of Lrp DNA binding sites to investigate discrepancies between natural selection and SELEX SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RESPONSIVE REGULATORY PROTEIN; ESCHERICHIA-COLI K-12; PHASE VARIATION; CRYSTAL-STRUCTURE; PILI OPERONS; LEUCINE; EXPRESSION; TRANSCRIPTION; PAP; METHYLATION AB In vitro experiments that characterize DNA-protein interactions by artificial selection, such as SELEX, are often performed with the assumption that the experimental conditions are equivalent to natural ones. To test whether SELEX gives natural results, we compared sequence logos composed from naturally occurring leucine-responsive regulatory protein (Lrp) binding sites with those composed from SELEX-generated binding sites. The sequence logos were significantly different, indicating that the binding conditions are disparate. A likely explanation is that the SELEX experiment selected for a dimeric or trimeric Lrp complex bound to DNA. In contrast, natural sites appear to be bound by a monomer. This discrepancy suggests that in vitro selections do not necessarily give binding site sets comparable with the natural binding sites. C1 NCI, Math Biol Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Catoctin High Sch, Thurmont, MD 21788 USA. RP Schneider, TD (reprint author), NCI, Math Biol Lab, Frederick Canc Res & Dev Ctr, POB B,Bldg 469,Room 144, Frederick, MD 21702 USA. OI Schneider, Thomas/0000-0002-9841-1531 NR 44 TC 30 Z9 35 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 1 PY 1999 VL 27 IS 3 BP 882 EP 887 DI 10.1093/nar/27.3.882 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 164EH UT WOS:000078449400024 PM 9889287 ER PT J AU Adesanya-Famuyiwa, OO Zhou, JA Wu, G Bondy, C AF Adesanya-Famuyiwa, OO Zhou, JA Wu, G Bondy, C TI Localization and sex steroid regulation of androgen receptor gene expression in rhesus monkey uterus SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID EMBEDDED HUMAN TISSUES; HUMAN-ENDOMETRIUM; IMMUNOCYTOCHEMICAL LOCALIZATION; POLYCLONAL ANTIBODY; TESTOSTERONE; ESTROGEN; FEMALE; RATS AB Objective: To characterize the cellular sites and hormonal regulation of uterine androgen receptor gene expression in the monkey. Methods: Ovariectomized rhesus monkeys (five in each group) were treated with placebo (the control group), estradiol (E2), E2 plus progesterone, or E2 plus testosterone by sustained-release pellets administered subcutaneously. After 3 days of treatment, uteri were removed and uterine sections were analyzed by in situ hybridization for androgen receptor messenger RNA (mRNA). Results: Androgen receptor mRNA was detected in endometrial stromal cells and myometrial smooth muscle cells, with lesser expression in endometrial epithelial cells. Both E2 and E2 plus progesterone treatment doubled androgen receptor mRNA levels in stromal cells (P <.01), whereas E2 plus testosterone treatment increased stromal androgen receptor mRNA levels by about five-fold (P <.001) compared with placebo treatment. In the endometrial epithelium, E2 alone did not increase androgen receptor mRNA levels significantly. However, the E2 plus progesterone and E2 plus testosterone treatments increased epithelial androgen receptor mRNA levels by 4.3 and 5 times, respectively (P =.008 and P <.002, respectively). Androgen receptor mRNA was distributed homogeneously in smooth muscle cells across the myometrium. Estradiol treatment alone did not increase myometrial androgen receptor mRNA levels significantly, but the E2 plus progesterone and E2 plus testosterone treatments increased myometrial androgen receptor mRNA levels by 1.8 and 2 times, respectively (P =.001 and P <.001, respectively). Conclusion: Androgen receptor gene expression was detected in all uterine cell compartments where it was subject to significant sex steroid regulation. The fact that androgen receptor mRNA levels were consistently up-regulated by a combined E2 plus testosterone treatment while E2 treatment alone had little or no effect shows that a collaborative action of E2 and testosterone enhances androgen receptor expression in the monkey uterus. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Adesanya-Famuyiwa, OO (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N 262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. NR 22 TC 29 Z9 29 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 1999 VL 93 IS 2 BP 265 EP 270 DI 10.1016/S0029-7844(98)00384-6 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 161JE UT WOS:000078284800020 PM 9932567 ER PT J AU Murgo, A Cannon, DJ Blatner, G Cheson, BD AF Murgo, A Cannon, DJ Blatner, G Cheson, BD CA Natl Canc Inst TI Clinical trials of MGI-114 SO ONCOLOGY-NEW YORK LA English DT Article ID 6-HYDROXYMETHYLACYLFULVENE C1 NCI, Bethesda, MD 20892 USA. RP Murgo, A (reprint author), NCI, Bethesda, MD 20892 USA. NR 12 TC 12 Z9 12 U1 0 U2 0 PU P R R INC PI HUNTINGTON PA 17 PROSPECT ST, HUNTINGTON, NY 11743 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD FEB PY 1999 VL 13 IS 2 BP 233 EP + PG 2 WC Oncology SC Oncology GA 170FC UT WOS:000078794800014 PM 10079472 ER PT J AU Larkin, G Lightman, S AF Larkin, G Lightman, S TI Mycophenolate mofetil - A useful immunosuppressive in inflammatory eye disease SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT 1st Meeting of the American-Uveitis-Society CY JAN, 1997 CL BRECKENRIDGE, COLORADO SP Amer Uveitis Soc ID ACID; UVEITIS; PURINE AB Objective: To assess the usefulness of mycophenolate mofetil (MMF) (Cellcept, Roche), a potent selective uncompetitive and reversible inhibitor of ionisine monophosphate dehydrogenase involved in purine synthesis, as an immunosuppressive and steroid-sparing agent in the management of ocular inflammatory disease. Design: Open-label, prospective, uncontrolled pilot study. Participants: Eleven patients with uncontrolled ocular inflammation. Intervention: Mycophenolate mofetil, at a dosage of 1 g twice daily, was given in conjunction with steroids, as a steroid-sparing agent, or as an additional agent with cyclosporine (CsA), or instead of CsA or azathioprine, Main Outcome Measures: The inflammatory response, side effects, and toxicity were monitored, Results: The addition of MMF to immunosuppressive regimens led to the improvement in symptoms and the ability to reduce the dose of prednisone in most patients. Ten of 11 patients showed a favorable response to MMF, with few side effects noted, Conclusion: These findings suggest that MMF is a useful immunosuppressive drug for controlling ocular inflammation with minimal side effects. C1 Moorfields Eye Hosp, London, England. RP Larkin, G (reprint author), NIH, 10 Ctr Dr,Bldg 10,Rm 10N112, Bethesda, MD 20892 USA. NR 21 TC 91 Z9 94 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 1999 VL 106 IS 2 BP 370 EP 374 DI 10.1016/S0161-6420(99)90078-7 PG 5 WC Ophthalmology SC Ophthalmology GA 162QD UT WOS:000078357500039 PM 9951492 ER PT J AU O'Connell, AC Marini, JC AF O'Connell, AC Marini, JC TI Evaluation of oral problems in an osteogenesis imperfecta population SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID DENTIN DEFECTS; DENTINOGENESIS IMPERFECTA; REHABILITATION; CLASSIFICATION; EXPRESSION AB Objective. The incidence of craniofacial and dental anomalies in children with the more severe nonlethal forms of osteogenesis imperfecta was evaluated. Study design. The study evaluated 49 children (age range, 1-17.5 years) with types III and IV osteogenesis imperfecta. In each case, the dentition was evaluated for the presence of dentinogenesis imperfecta, attrition, and caries, as well as for radiographic appearance, dental development, and malocclusion. Results. The incidence of dentinogenesis imperfecta was greater than 80% in the primary dentition. Clinically, the color of the dentition was of predictive value in appropriate management of the primary dentition. Tooth discoloration and attrition did not occur to the same extent in the permanent dentition as in the primary dentition in either group. Class III dental malocclusion occurred in 70% to 80% of this osteogenesis imperfecta population, with a high incidence of anterior and posterior cross bites and open bites. A delay in dental development was observed in 21% of patients type III osteogenesis imperfecta, whereas accelerated development was noted in 23% of the patients with type IV. In addition, ectopic eruption occurred in 13 patients. Conclusions. In addition to dentinogenesis imperfecta, significant oral problems occur in types III and IV osteogenesis imperfecta. Other features that impact the dental management of this population are highlighted. C1 NIDR, NIH, Bethesda, MD 20892 USA. NICHHD, Heritable Disorders Branch, Bethesda, MD 20892 USA. RP O'Connell, AC (reprint author), NIDR, NIH, Bethesda, MD 20892 USA. OI O'Connell, Anne C/0000-0002-1495-3983 NR 31 TC 64 Z9 65 U1 1 U2 11 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD FEB PY 1999 VL 87 IS 2 BP 189 EP 196 DI 10.1016/S1079-2104(99)70272-6 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 167MD UT WOS:000078636300014 PM 10052375 ER PT J AU Treede, RD Kenshalo, DR Gracely, RH Jones, AKP AF Treede, RD Kenshalo, DR Gracely, RH Jones, AKP TI The cortical representation of pain SO PAIN LA English DT Review DE nociceptive pathways; somatosensory cortex; limbic system; multidimensional pain experience; imaging ID POSITRON EMISSION TOMOGRAPHY; ELECTRICAL SOURCE ANALYSIS; NOXIOUS HEAT STIMULI; CINGULATE CORTEX; SPINAL-CORD; SOMATOTOPIC ORGANIZATION; NOCICEPTIVE NEURONS; ANTERIOR CINGULATE; EVOKED-POTENTIALS; CEREBRAL-CORTEX AB Anatomical and physiological studies in animals, as well as functional imaging studies in humans have shown that multiple cortical areas are activated by painful stimuli. The view that pain is perceived only as a result of thalamic processing has, therefore, been abandoned, and has been replaced by the question of what functions can be assigned to individual cortical areas. The following cortical areas have been shown to be involved in the processing of painful stimuli: primary somatosensory cortex, secondary somato sensory cortex and its vicinity in the parietal operculum, insula, anterior cingulate cortex and prefrontal cortex. These areas probably process different aspects of pain in parallel. Previous psychophysical research has emphasized the importance of separating pain experience into sensory-discriminative and affective-motivational components. The sensory-discriminative component of pain can be considered a sensory modality similar to vision or olfaction; it becomes more and more evident that it is subserved by its own apparatus up to the cortical level. The affective-motivational component is close to what may be considered 'suffering from pain'; it is clearly related to aspects of emotion, arousal and the programming of behaviour. This dichotomy, however, has turned out to be too simple to explain the functional significance of nociceptive cortical networks. Recent progress in imaging technology has, therefore, provided a new impetus to study the multiple dimensions of pain. (C) 1999 International Association for the Study of Pain. Published by Elsevier Science B.V. C1 Univ Mainz, D-55099 Mainz, Germany. NIDR, Bethesda, MD 20892 USA. Hope Hosp, Ctr Rheumat Dis, Manchester, Lancs, England. RP Treede, RD (reprint author), Univ Mainz, Saarstr 21, D-55099 Mainz, Germany. OI Jones, Anthony/0000-0001-6944-9365 NR 56 TC 609 Z9 630 U1 5 U2 37 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD FEB PY 1999 VL 79 IS 2-3 BP 105 EP 111 DI 10.1016/S0304-3959(98)00184-5 PG 7 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 167GN UT WOS:000078624300001 PM 10068155 ER PT J AU Benoliel, R Eliav, E Mannes, AJ Caudle, RM Leeman, S Iadarola, MJ AF Benoliel, R Eliav, E Mannes, AJ Caudle, RM Leeman, S Iadarola, MJ TI Actions of intrathecal diphtheria toxin substance P fusion protein on models of persistent pain SO PAIN LA English DT Article DE cytotoxins; immunotoxins; substance P ID RECEPTOR MESSENGER-RNA; RAT SPINAL-CORD; NK1 RECEPTOR; DORSAL HORN; IN-VIVO; PERIPHERAL MONONEUROPATHY; C-FOS; NEURONS; EXPRESSION; CELLS AB Substance P (SP) plays a central role in the transduction of second messenger signals from primary afferent nociceptive terminals to second-order neurons in the spinal cord. We have tested a recombinant engineered diphtheria toxin/SP fusion protein (DAB389SP) in acute and chronic pain models in the rat. DAB389SP binds to the SP receptor (SPR) and is internalized and kills SPR-expressing cells by blocking cellular protein synthesis. DAB389SP delivery was by intrathecal infusion, of varying duration, at the lumbar level. In the chronic constriction injury model of neuropathic pain a significant reduction in mechanically induced hyperalgesia was obtained. This effect was less marked in an acute carageenan inflammation model. Although other pain characteristics (mechano-allodynia, cold-allodynia, and heat-hyperalgesia) showed some improvement, these were less pronounced. Immunocytochemistry revealed a toxin-induced reduction in lamina I, of SPR and of NMDA NR1 subunit receptor expressing neurons, and of c-Fos, an inducible molecular marker of persistent nociceptive activity. The use of cytotoxic fusion proteins to target specific cell types may be of considerable benefit in the study of nociception and the treatment of chronic pain. (C) 1999 International Association for the Study of Pain. Published by Elsevier Science B.V. C1 Natl Inst Dent & Craniofacial Res, Neuronal Gene Express Unit, Pain & Neurosensory Mechanisms Branch, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Hadassah Sch Dent Med, Dept Oral Diag, Jerusalem, Israel. Hosp Univ Penn, Dept Anesthesiol, Philadelphia, PA 19104 USA. Boston Univ, Sch Med, Dept Pharmacol, Boston, MA 02118 USA. RP Iadarola, MJ (reprint author), Natl Inst Dent & Craniofacial Res, Neuronal Gene Express Unit, Pain & Neurosensory Mechanisms Branch, NIH, 49 Convent Dr,Room 1A11,MSC 4410, Bethesda, MD 20892 USA. EM iadarola@yoda.nidr.nih.gov OI Mannes, Andrew/0000-0001-5834-5667 NR 48 TC 31 Z9 31 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD FEB PY 1999 VL 79 IS 2-3 BP 243 EP 253 DI 10.1016/S0304-3959(98)00170-5 PG 11 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 167GN UT WOS:000078624300016 PM 10068170 ER PT J AU Eliav, E Herzberg, JU Caudle, RM AF Eliav, E Herzberg, JU Caudle, RM TI The kappa opioid agonist GR89696 blocks hyperalgesia and allodynia in rat models of peripheral neuritis and neuropathy SO PAIN LA English DT Article DE hyperalgesia; allodynia; opioids; analgesia ID NMDA RECEPTOR ANTAGONISTS; BEHAVIORAL HYPERALGESIA; UNILATERAL INFLAMMATION; MECHANICAL ALLODYNIA; DOUBLE-BLIND; SPINAL-CORD; PAIN; NERVE; MONONEUROPATHY; KETAMINE AB Previous work demonstrated that, in rats, intrathecal GR89 696, a putative kappa-2 opioid receptor agonist, inhibited hyperalgesia to noxious heat in an inflamed hind paw (anti-hyperalgesic effect). Non-inflamed paws were not influenced by kappa-2 receptor activation. The question addressed in this study was whether GR89 696 was as effective in blocking hyperalgesia and allodynia in nerve injury models as it was in the inflammation model. GR89 696 (6 nmoles, i.t.) completely reversed the hyperalgesia and allodynia observed in both the neuropathy and neuritis models in all sensory tests. However, it did not alter sensory function in non-injured limbs nor in sham operated animals. Naloxone (1 mg/kg, i.p.) reversed the anti-hyperalgesic and anti-allodynic effects of GR89 696. The mu agonist DAMGO (6 nmoles, i.t.) and the kappa-1 agonist U69 593 (100 nmoles, i.t.) only partially reversed hyperalgesia and allodynia. These findings suggest that kappa-2 opioid receptors may be a useful target for the pharmacological control of hyperalgesia and allodynia. (C) 1999 Published by Elsevier Science B.V. C1 NIDR, Pain & Neurosensory Mechanisms Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Neurol Dis & Stroke, NIH, Clin Neurosci Branch, Bethesda, MD 20892 USA. RP Caudle, RM (reprint author), NIDR, Pain & Neurosensory Mechanisms Branch, NIH, Bldg 49,IW26,49 Convent Dr,MSC 4410, Bethesda, MD 20892 USA. NR 32 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD FEB PY 1999 VL 79 IS 2-3 BP 255 EP 264 DI 10.1016/S0304-3959(98)00177-8 PG 10 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 167GN UT WOS:000078624300017 PM 10068171 ER PT J AU Bonville, CA Rosenberg, HF Domachowske, JB AF Bonville, CA Rosenberg, HF Domachowske, JB TI Macrophage inflammatory protein-1 alpha and RANTES are present in nasal secretions during ongoing upper respiratory tract infection SO PEDIATRIC ALLERGY AND IMMUNOLOGY LA English DT Article DE CC chemokines; upper respiratory tract infection ID AIRWAY EPITHELIAL-CELLS; A VIRUS-INFECTION; SYNCYTIAL VIRUS; MIP-1-ALPHA; CHEMOKINES; PROTEIN; EXPRESSION; MIP-1-BETA; MIGRATION; MONOCYTE AB Marcophage inflammatory protein-1 alpha (MIP-1 alpha) and RANTES (regulated upon activation, normal T-cell expressed and secreted) were measured by enzyme-linked immunosorbent assay (ELISA) from virus-infected respiratory cell culture supernatants and from 100 nasal wash samples obtained from patients aged 8 d to 10 yr. The results of the nasal wash samples were analyzed in relation to the etiology of the viral infection. In vitro, respiratory syncytial virus (RSV) induced the production of MIP-1 alpha, while both RSV and adenovirus were associated with the production of RANTES. Both MIP-1 alpha and RANTES were detected in nasopharyngeal secretions from pediatric patients with acute upper respiratory tract RSV, adenovirus, influenza, and parainfluenza virus infection (p<0.001 by Fisher's exact test). As both of these chemokines have potent effects on the recruitment and degranulation of eosinophils and basophils, further understanding of their role in upper respiratory tract infections may provide valuble insights into the immunopathogenesis of respiratory viral infections. C1 SUNY Hlth Sci Ctr, Dept Pediat, Div Infect Dis, Syracuse, NY 13210 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Domachowske, JB (reprint author), SUNY Hlth Sci Ctr, Dept Pediat, Div Infect Dis, 750 E Adams St, Syracuse, NY 13210 USA. NR 19 TC 68 Z9 70 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0905-6157 J9 PEDIATR ALLERGY IMMU JI Pediatr. Allergy Immunol. PD FEB PY 1999 VL 10 IS 1 BP 39 EP 44 DI 10.1034/j.1399-3038.1999.101005.x PG 6 WC Allergy; Immunology; Pediatrics SC Allergy; Immunology; Pediatrics GA 211EM UT WOS:000081147000008 PM 10410916 ER PT J AU Read, JS Bethel, J Harris, DR Meyer, WA Korelitz, J Mofenson, LM Moye, J Pahwa, S Rich, K Nugent, RP AF Read, JS Bethel, J Harris, DR Meyer, WA Korelitz, J Mofenson, LM Moye, J Pahwa, S Rich, K Nugent, RP CA Natl Inst Child Hlth Human Dev Intravonous Immu TI Serum vitamin A concentrations in a North American cohort of human immunodeficiency virus type 1-infected children SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article; Proceedings Paper CT XIth International Conference on AIDS CY JUL 07-13, 1996 CL VANCOUVER, CANADA DE vitamin A; human immunodeficiency virus; disease progression; mortality ID HIV-1 DISEASE PROGRESSION; A-DEFICIENCY; INTRAVENOUS IMMUNOGLOBULIN; INFECTED CHILDREN; UNITED-STATES; HIV-1-INFECTED CHILDREN; BACTERIAL-INFECTIONS; MICRONUTRIENT INTAKE; HOMOSEXUAL MEN; MORTALITY AB Background. Vitamin A deficiency is associated with increased risks of vertical transmission of HIV-1 (HIV) and of disease progression and mortality among HIV-infected adults. The objectives of the study were to describe serum vitamin A concentrations among HIV-infected children in the National Institute of Child Health and Human Development IVIG; Clinical Trial, to examine changes in vitamin A concentrations and to investigate the relationships between vitamin A concentrations and morbidity and mortality. methods. Blood was collected from children at baseline and at 3-month intervals throughout the study. Serum samples were stored at -70 degrees C at a central repository until retrieved for vitamin A assay. Samples were hexane-extracted and assayed by high performance liquid chromatography, The rate of change in vitamin A concentrations, calculated by fitting a linear regression model, was expressed as micrograms/dl/year. Results, The median vitamin A concentration at baseline (n = 207 children) was 31.0 mu g/dl [range, undetectable (<10 mu g/dl) to 98 mu g/dl]. The rate of change in vitamin A concentrations (n 180 children) did not vary significantly by any factor other than baseline vitamin A concentration. Baseline vitamin A concentration was not associated with morbidity (incidence of infections, growth failure, CD4(+) percent decline below 15%, increases in serum HIV RNA concentrations above either 10(5) or 10(6) copies/ml or acute care hospitalization). Neither baseline vitamin A concentration nor the rate of change of vitamin A concentrations was associated with mortality. Conclusions, Among these North American children with relatively normal vitamin A concentrations, vitamin A was not observed to be associated with morbidity or mortality. C1 NICHHD, Pediat Adolescent & Maternal Branch, NIH, Bethesda, MD 20892 USA. WESTAT Corp, Rockville, MD 20850 USA. Quest Diagnost Inc, Baltimore, MD USA. N Shore Univ Hosp, Manhasset, NY USA. Univ Illinois, Chicago, IL USA. RP Read, JS (reprint author), NICHHD, Pediat Adolescent & Maternal Branch, NIH, Execut Bldg,Room 4B11F,6100 Execut Blvd,MSC 7510, Bethesda, MD 20892 USA. EM jr92o@nih.gov OI Mofenson, Lynne/0000-0002-2818-9808 NR 44 TC 5 Z9 5 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD FEB PY 1999 VL 18 IS 2 BP 134 EP 142 DI 10.1097/00006454-199902000-00010 PG 9 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 166FX UT WOS:000078566500009 PM 10048685 ER PT J AU Warren, KE Gidvani-Diaz, V Duval-Arnould, B AF Warren, KE Gidvani-Diaz, V Duval-Arnould, B TI Renal medullary carcinoma in an adolescent with sickle cell trait SO PEDIATRICS LA English DT Article DE sickle cell trait; hematuria; renal medullary carcinoma; renal tumors AB We describe the complex presentation of a patient with renal medullary carcinoma, a newly described entity primarily affecting young patients with sickle cell trait. Renal medullary carcinoma is an aggressive, rapidly destructive tumor associated with a delayed diagnosis and a poor outcome. The most common presenting signs and symptoms include hematuria, abdominal or flank pain, and weight loss. Sickle cell trait as the sole cause of hematuria in young black patients is a diagnosis of exclusion. Hemoglobin electrophoresis, intravenous pyelography, and computed tomography scans should be the minimal studies performed in young black patients with hematuria. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Natl Naval Med Res Inst, Dept Pediat, Bethesda, MD USA. RP Warren, KE (reprint author), NCI, Pediat Oncol Branch, Bldg 10,Room 13N240, Bethesda, MD 20892 USA. NR 8 TC 16 Z9 16 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD FEB PY 1999 VL 103 IS 2 AR e22 DI 10.1542/peds.103.2.e22 PG 3 WC Pediatrics SC Pediatrics GA 163ZU UT WOS:000078437800051 PM 9925868 ER PT J AU Cravchik, A Sibley, DR Gejman, PV AF Cravchik, A Sibley, DR Gejman, PV TI Analysis of neuroleptic binding affinities and potencies for the different human D-2 dopamine receptor missense variants SO PHARMACOGENETICS LA English DT Article DE dopamine; neuroleptics; schizophrenia; potency ID TARDIVE-DYSKINESIA; MALIGNANT SYNDROME; INHIBITION CURVES; GENE; SCHIZOPHRENIA; IDENTIFICATION; POLYMORPHISM; ASSOCIATION; ALCOHOLISM AB Neuroleptics, or antipsychotics, are widely used for the treatment of psychotic symptoms such as hallucinations and delusions in schizophrenia and other psychiatric disorders. Pharmacotherapy of these diseases is frequently complicated by a great variability in the clinical response to neuroleptics and by the development of serious and potentially life-threatening side-effects. Brain D-2 dopamine receptors are one of the major targets of neuroleptic treatment. The human D-2 dopamine receptor (DRD2) gene has three variants predicting the amino acid substitutions Ser311Cys, Pro310Ser and Val96Ala in the receptor protein. We show that several typical and atypical neuroleptics commonly used in the treatment of psychotic disorders have differences in binding affinities and potencies for the D-2 dopamine receptor variants. Functional differences between dopamine receptor variants might be related to genetically determined differences in response to neuroleptic treatment. Pharmacogenetics 9:17-23 (C) 1999 Lippincott Williams & Wilkins. C1 NIMH, Clin Neurogenet Branch, Unit Mol Clin Invest, Bethesda, MD 20892 USA. NINDS, Mol Neuropharmacol Sect, Bethesda, MD 20892 USA. RP Cravchik, A (reprint author), NIAAA, Neurogenet Lab, Pk 5 Bldg,12420 Parklawn Dr,Room 451,MSC 8110, Bethesda, MD 20892 USA. NR 26 TC 33 Z9 35 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD FEB PY 1999 VL 9 IS 1 BP 17 EP 23 DI 10.1097/00008571-199902000-00003 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 181KU UT WOS:000079441200003 PM 10208638 ER PT J AU Kidd, RS Straughn, AB Meyer, MC Blaisdell, J Goldstein, JA Dalton, JT AF Kidd, RS Straughn, AB Meyer, MC Blaisdell, J Goldstein, JA Dalton, JT TI Pharmacokinetics of chlorpheniramine, phenytoin, glipizide and nifedipine in an individual homozygous for the CYP2C9*3 allele SO PHARMACOGENETICS LA English DT Article DE cytochrome P450; polymorphism; pharmacokinetics; phenytoin ID GENETIC-POLYMORPHISM; CYP2C SUBFAMILY; LIVER-MICROSOMES; CYTOCHROME-P450; TOLBUTAMIDE; METABOLISM; EXPRESSION; WARFARIN; CAUCASIANS; JAPANESE AB Genetic polymorphisms in the cytochrome P450 (CYP) family are widely known to contribute to interindividual differences in the pharmacokinetics of many drugs, Several alleles for the CYP2C9 gene have been reported. Individuals homozygous for the Leu(359) variant (CYP2C9*3) have been shown to have significantly lower drug clearances compared with Ile(359) (CYP2C9*1) homozygous individuals. A male Caucasian who participated in six bioavailability studies in our laboratory over a period of several years showed extremely low clearance of two drugs: phenytoin and glipizide (both substrates of CYP2C9), but not for nifedipine (a CYP3A4 substrate) and chlorpheniramine (a CYP2D6 substrate). His oral clearance of phenytoin was 21% of the mean of the other 11 individuals participating in the study, and his oral clearance of glipizide, a second generation sulfonylurea structurally similar to tolbutamide, was only 18% of the mean of the other 10 individuals. However, his oral clearance of nifedipine and chlorpheniramine did not differ from individuals in other studies performed at our laboratories. An additional blood sample was obtained from this individual to determine if he possessed any of the known CYP2C9 or CYP2C19 allelic variants that would account for his poor clearance of the CYP2C9 substrates (phenytoin and glipizide) compared with the CYP3A4 (nifedipine) and CYP2D6 (chlorpheniramine) substrates, The results of the genotype testing showed that this individual was homozygous for the CYP2C9*S allele and did not possess any of the known defective CYP2C19 alleles. This study establishes that the Leu(359) mutation is responsible for the phenytoin and glipizide/tolbutamide poor metabolizer phenotype, Pharmacogenetics 9:71-80 (C) 1999 Lippincott Williams & Wilkins. C1 Univ Tennessee, Coll Pharm, Dept Pharmaceut Sci, Memphis, TN 38163 USA. Shenandoah Univ, Sch Pharm, Dept Biopharmaceut Sci, Winchester, VA USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Dalton, JT (reprint author), Univ Tennessee, Coll Pharm, Dept Pharmaceut Sci, 874 Union Ave,Crowe Res Bldg,Room 5, Memphis, TN 38163 USA. OI dalton, James T/0000-0002-3915-7326 NR 32 TC 118 Z9 121 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD FEB PY 1999 VL 9 IS 1 BP 71 EP 80 DI 10.1097/00008571-199902000-00010 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 181KU UT WOS:000079441200010 PM 10208645 ER PT J AU Dillon, J Ortwerth, BJ Chignell, CF Reszka, KJ AF Dillon, J Ortwerth, BJ Chignell, CF Reszka, KJ TI Electron paramagnetic resonance and spin trapping investigations of the photoreactivity of human lens proteins SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID FREE-RADICALS; HYDROGEN-PEROXIDE; PULSE-RADIOLYSIS; UVA IRRADIATION; OXIDATION; ASCORBATE; CYSTEINE; SUPEROXIDE; GENERATION; CATARACT AB Oxidation of cysteine, glutathione and ascorbate by photoexcited proteins from normal and cataractous lenses was investigated using electron paramagnetic resonance in combination with spin trapping. We report that illumination of these proteins in pH 7 buffer with light >300 nm in the presence of thiols (RSH) and a spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO), afforded DMPO/.S-cysteine and DMPO/.SG adducts, suggesting the formation of the corresponding thiyl radicals. In a nonbuffered aqueous solution, illumination of the proteins and glutathione also produced superoxide detected as a DMPO/.O2H adduct. Irradiation of these proteins in the presence of ascorbate generated ascorbate radical, We conclude that chromophores present in the natural normal and cataractous lenses are capable of initiating photooxidative processes involving endogenous thiols and ascorbic acid. This observation may be pertinent to UV-induced development of cataract. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA. Univ Missouri, Mason Inst Visual Sci, Columbia, MO 65211 USA. RP Reszka, KJ (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM reszka@niehs.nih.gov FU NEI NIH HHS [EY02283, EY02035] NR 30 TC 9 Z9 10 U1 0 U2 0 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD FEB PY 1999 VL 69 IS 2 BP 259 EP 264 DI 10.1111/j.1751-1097.1999.tb03284.x PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 168VQ UT WOS:000078714200026 PM 10048318 ER PT J AU Croarkin, E AF Croarkin, E TI Osteopenia in the patient with cancer SO PHYSICAL THERAPY LA English DT Article DE cancer; osteopenia; physical therapy ID EWINGS-SARCOMA; METHOTREXATE; RADIOTHERAPY; WOMEN AB Osteopenia commonly occurs in elderly women and women who are postmenopausal. This condition, however, can occur in either sex at any age. It can go undiagnosed until injury or an osteoporotic fracture is sustained.(1) Therapists who prescribe progressive mobility and strengthening programs, therefore, should understand the risk factors for osteopenia. The purpose of this article is to examine the etiology of osteopenia and the predisposition that patients with cancer have toward osteopenia. Bone growth, remodeling, and osteopenia development are described. Given the scope of this article, only the most common interventions for cancer are discussed. During adolescence, people accumulate bone mass. Maintenance of bone mass becomes very important between the ages of 20 and 50 years, and bone loss is associated with decreases in estrogen between the ages of 50 and 65 years.(2) After the age of 65 years, bone loss occurs due to age-related factors, which vary with genetics, hormones, or environmental issues.(2) Consequently, adult bone mass is mainly dependent on 2 factors: (1) the acquisition of peak bone mass between the ages of 15 and 25 years and (2) age-related bone loss.(2) This lifelong pattern of alteration in bone mass overlies smaller cyclic changes in bone mass or density, which are mediated by intrinsic osteoclastic and osteoblastic cell activity or extrinsic forces on bone structure. The osteoblastic and osteoclastic cycle remodels bone and takes approximately 100 days to complete.(1) Osteoclastic cells reabsorb bony material and leave abandoned cells. Osteoblastic cells then reform bone by depositing bony material into osteoclast cell cavities. The material becomes mineralized, and bone structure is formed. Nearly 25% of trabecular or cancellous bone, which composes vertebrae, the distal radius, and parts of the femur, is resorbed each year.(2) This resorption rate is more frequent for trabecular or cancellous bone than for cortical or compact bone, which predominately makes up long bones. This process occurs because trabecular bone has a greater surface area-to-volume ratio. Cortical bone remodeling is thought to be 8-fold lower than that of trabecular bone.(2) For this process to continue, metabolic and hormonal homeostasis needs to be maintained, and bone must be challenged by mechanical stress. C1 NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Croarkin, E (reprint author), NIH, Warren G Magnuson Clin Ctr, Bldg 10,Room 6S-235, Bethesda, MD 20892 USA. EM earllaine_simpler@nih.gov NR 31 TC 4 Z9 4 U1 2 U2 4 PU AMER PHYSICAL THERAPY ASSOC PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA SN 0031-9023 EI 1538-6724 J9 PHYS THER JI Phys. Ther. PD FEB PY 1999 VL 79 IS 2 BP 196 EP 201 PG 6 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA 166TA UT WOS:000078592200007 PM 10029059 ER PT J AU Perry, NB Burgess, EJ Baek, SH Weavers, RT Geis, W Mauer, AB AF Perry, NB Burgess, EJ Baek, SH Weavers, RT Geis, W Mauer, AB TI 11-oxygenated cytotoxic 8,9-secokauranes from a New Zealand liverwort, Lepidolaena taylorii SO PHYTOCHEMISTRY LA English DT Article DE Lepidolaena taylorii; L-palpebrifolia; liverworts; bioactive plant products; cytotoxicity; diterpenes; 8,9-secokauranes; kauren-15-ones ID TUMOR INHIBITORS; DITERPENOIDS; TERPENOIDS; ANTITUMOR; ENTRY AB Four new cytotoxic 8,9-secokauranes have been identified from the liverwort Lepidolaena taylorii. The 11-oxygenation found in three of these has not been encountered in the 8,9-secokauranes known from higher plants. NMR studies were combined with molecular modelling to determine the preferred conformations. Six structurally related kauren-15-ones were also found, including three new compounds. Some of these compounds showed differential cytotoxic activity against human tumor cell lines. The probable mode of cytotoxic action was supported by Michael addition of a thiol. Two 8,9-secokauranes were the main cytotoxins in another New Zealand liverwort, L. palpebrifolia. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Univ Otago, Dept Chem, New Zealand Inst Crop & Food Res Ltd, Plant Extracts Res Unit, Dunedin, New Zealand. Wonkwang Univ, Dept Chem, Iksan 570749, South Korea. Univ Saarland, D-66041 Saarbrucken, Germany. NCI, Drug Synth & Chem Branch, Bethesda, MD 20892 USA. RP Perry, NB (reprint author), Univ Otago, Dept Chem, New Zealand Inst Crop & Food Res Ltd, Plant Extracts Res Unit, POB 56, Dunedin, New Zealand. RI Perry, Nigel/G-5574-2010 OI Perry, Nigel/0000-0003-3196-3945 NR 26 TC 25 Z9 25 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9422 J9 PHYTOCHEMISTRY JI Phytochemistry PD FEB PY 1999 VL 50 IS 3 BP 423 EP 433 DI 10.1016/S0031-9422(98)00602-5 PG 11 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA 160EM UT WOS:000078217500011 PM 9933954 ER PT J AU Potterf, SB Virador, V Wakamatsu, K Furumura, M Santis, C Ito, S Hearing, VJ AF Potterf, SB Virador, V Wakamatsu, K Furumura, M Santis, C Ito, S Hearing, VJ TI Cysteine transport in melanosomes from murine melanocytes SO PIGMENT CELL RESEARCH LA English DT Article DE pigmentation; cysteine; transport; melanin; melanosomes ID HUMAN FIBROBLAST LYSOSOMES; CARRIER-MEDIATED TRANSPORT; ALTERED COPPER-METABOLISM; AMINO-ACID TRANSPORT; HUMAN-MELANOMA CELLS; RAT-THYROID CELLS; 5-S-CYSTEINYLDOPA FORMATION; TYROSINE TRANSPORT; SYSTEM; PROTEIN AB The synthesis of pheomelanin requires the incorporation of thiol-containing compound(s) during the process of mammalian melanogenesis. Since melanins are produced only in specialized, membrane-bound organelles, known as melanosomes, such thiol donor(s) must cross the membrane barrier from the cytosol to the melanosome interior, Cysteine and/or glutathione (GSH) were proposed as suitable thiol donors, although uptake of these compounds into melanosomes was not previously characterized, In this study, we show that cysteine is transported, in a temperature- and concentration-dependent manner, across membranes of melanosomes derived from murine melanocytes, Additional proof that cysteine uptake results from a carrier-mediated process and is not due to simple diffusion or to a membrane channel, was obtained in countertransport experiments, in which melanosomes preloaded with cysteine methyl eater took up significantly more [S-35]cysteine than did unloaded controls, In contrast, we were unable to detect any significant uptake of [S-35]GSH over a wide concentration range, in the presence or in the absence of reducing agent, This study is the first demonstration of melanosomal membrane transport of cysteine, and it strongly suggests that free cysteine is the thiol source utilized for pheomelanin synthesis in mammalian melanocytes. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Fujita Hlth Univ, Sch Hlth Sci, Dept Chem, Toyoake, Aichi, Japan. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 1B25, Bethesda, MD 20892 USA. NR 55 TC 35 Z9 36 U1 1 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD FEB PY 1999 VL 12 IS 1 BP 4 EP 12 DI 10.1111/j.1600-0749.1999.tb00502.x PG 9 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA 178FX UT WOS:000079256500002 PM 10193677 ER PT J AU Kos, L Aronzon, A Takayama, H Maina, F Ponzetto, C Merlino, G Pavan, W AF Kos, L Aronzon, A Takayama, H Maina, F Ponzetto, C Merlino, G Pavan, W TI Hepatocyte growth factor scatter factor MET signaling in neural crest-derived melanocyte development SO PIGMENT CELL RESEARCH LA English DT Article DE HGF/SF-MET; neural crest; melanocyte; hypopigmentation; tyrosinase ID TYROSINE KINASE RECEPTOR; C-MET; W-LOCUS; STEEL FACTOR; PROTO-ONCOGENE; MOUSE EMBRYOS; SI-LOCUS; IN-VITRO; CELLS; MUTATIONS AB The mechanisms governing development of neural crest-derived melanocytes, and how alterations in these pathways lead to hypopigmentation disorders, are not completely understood. Hepatocyte growth factor/scatter factor (HGF/SF) signaling through the tyrosine-kinase receptor, MET, is capable of promoting the proliferation, increasing the motility, and maintaining high tyrosinase activity and melanin synthesis of melanocytes in vitro. In addition, transgenic mice that ubiquitously overexpress HGF/SF demonstrate hyperpigmentation in the skin and leptomenigenes and develop melanomas. To investigate whether HGF/SE-MET signaling is involved in the development of neural crest-derived melanocytes, transgenic embryos, ubiquitously overexpressing HGF/SF, were analyzed. In HGF/SF transgenic embryos, the distribution of melanoblasts along the characteristic migratory pathway was not affected. However, additional ectopically localized melanoblasts were also observed in the dorsal root ganglia and neural tube, as early as 11.5 days post coitus (p.c.). We utilized an in vitro neural crest culture assay to further explore the role of HGF/SF-MET signaling in neural crest development. HGF/SF added to neural crest cultures increased melanoblast number, permitted differentiation into pigmented melanocytes, promoted melanoblast survival, and could replace mast-cell growth factor/Steel factor (MGF) in explant cultures. To examine whether HGF/SF-MET signaling is required for the proper development of melanocytes, embryos with a targeted Met null mutation (Met -/-) were analysed. In Met -/- embryos, melanoblast number and location were not overtly affected up to 14 days p.c. These results demonstrate that HGF/SF-MET signaling influences, but is not required for, the initial development of neural crest-derived melanocytes in vivo and in vitro. C1 NHGRI, Lab Genet Dis Res, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Turin, Sch Med, Dept Biomed Sci & Oncol, Turin, Italy. RP Pavan, W (reprint author), NHGRI, Lab Genet Dis Res, NIH, Bldg 49,Room 4A82,49 Convent Dr MSC 4472, Bethesda, MD 20892 USA. NR 47 TC 56 Z9 59 U1 0 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD FEB PY 1999 VL 12 IS 1 BP 13 EP 21 DI 10.1111/j.1600-0749.1999.tb00503.x PG 9 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA 178FX UT WOS:000079256500003 PM 10193678 ER PT J AU Simons-Morton, B Crump, AD Haynie, DL Saylor, KE Eitel, P Yu, K AF Simons-Morton, B Crump, AD Haynie, DL Saylor, KE Eitel, P Yu, K TI Psychosocial, school, and parent factors associated with recent smoking among early-adolescent boys and girls SO PREVENTIVE MEDICINE LA English DT Article DE adolescent behavior; smoking; cigarettes; psychosocial aspects ID CIGARETTE-SMOKING; UNITED-STATES; SELF-REPORTS; TOBACCO USE; INITIATION; PEER; PREVENTION; ONSET; COMPETENCES; BEHAVIOR AB Background. Experimentation with smoking often begins during adolescence, but an adequate understanding of the factors associated with early initiation remains elusive. Methods. Sixth- to eighth-grade students (n = 4,263, 67.1% white, 23.5% black, 7.2% other) from seven middle schools were surveyed. Results. The overall prevalence of recent smoking (past 30 days) of 10.4% was similar for boys and girls and by race, but increased from 3.7% in sixth to 17.8% in eighth grade. fn multiple logistic regression analyses positive outcome expectations, high perceived prevalence, deviance acceptance, and trouble at school were independently associated with smoking for both boys and girls. Among boys, problem-behaving friends, peer pressure, authoritative parenting, and mother's education and among girls, self-control problems, knowledgeable parents, and grade were independently associated with smoking. Conclusions. This is one of the Few studies to report an independent association between smoking and outcome expectations, the first study to report an independent effect for peer influences among boys only, and one of several to find a negative association between smoking and positive parenting behavior. These findings suggest that the effectiveness of preventive interventions might be improved by targeting parent, school, and student outcomes, including outcome expectations, deviance acceptance, and social norms for both boys and girls, peer influences among boys, and self-control among girls. (C) 1999 American Health Foundation and Academic Press. C1 NICHD, DESPR, Prevent Res Branch, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Hlth Educ, College Pk, MD 20742 USA. Behav & Hlth Res Inc, Rockville, MD USA. RP Simons-Morton, B (reprint author), NICHD, DESPR, Prevent Res Branch, NIH, Bldg 6100,Room 7B05,9000 Rockville Pike, Bethesda, MD 20892 USA. EM MORTONB@exchange.nih.gov OI Simons-Morton, Bruce/0000-0003-1099-6617; Haynie, Denise/0000-0002-8270-6079 FU NICHD NIH HHS [N01-HD-4-3207] NR 50 TC 103 Z9 106 U1 0 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD FEB PY 1999 VL 28 IS 2 BP 138 EP 148 DI 10.1006/pmed.1998.0404 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 165EC UT WOS:000078506100005 PM 10048105 ER PT J AU Merrill, RM Kessler, LG Udler, JM Rasband, GC Feuer, EJ AF Merrill, RM Kessler, LG Udler, JM Rasband, GC Feuer, EJ TI Comparison of risk estimates for selected diseases and causes of death SO PREVENTIVE MEDICINE LA English DT Article DE disease incidence; disease mortality; lifetime risk; age-conditional risk; life table ID ACUTE MYOCARDIAL-INFARCTION; PROSTATE-CANCER INCIDENCE; DEVELOPING BREAST-CANCER; CORONARY HEART-DISEASE; DIABETES-MELLITUS; UNITED-STATES; ALZHEIMERS-DISEASE; PHYSICAL-ACTIVITY; STROKE INCIDENCE; MORTALITY-RATES AB Background. Lifetime risk estimates of disease are limited by long-term data extrapolations and are less relevant to individuals who have already lived a period of time without the disease, but are approaching the age at which the disease risk becomes common. In contrast, short-term age-conditional risk estimates, such as the risk of developing a disease in the next 10 years among those alive and free of the disease at a given age, are less restricted by long-term extrapolation of current rates and can present patients with risk information tailored to their age. This study focuses on short-term age-conditional risk estimates for a broad set of important chronic diseases and nondisease causes of death among white and black men and women. Methods. The Feuer et al. (1993, Journal of the National Cancer Institute) [15] method was applied to data from a variety of sources to obtain risk estimates for select cancers, myocardial infarction, diabetes mellitus, multiple sclerosis, Alzheimer's, and death from motor vehicle accidents, homicide or legal intervention, and suicide. Results. Acute deaths from suicide, homicide or legal intervention, and fatal motor vehicle accidents dominate the risk picture for persons in their 20s, with only diabetes mellitus and end-stage renal disease therapy (for blacks only) having similar levels of risk in this age range. Late in life, cancer, acute myocardial infarction, Alzheimer's, and stroke become most common. The chronic diseases affecting the population later in life present the most likely diseases someone will face. Several interesting differences in disease and death risks were derived and reported among age specific race and gender subgroups of the population. Conclusion, Presentation of risk estimates for a broad set of chronic diseases and nondisease causes of death within short-term age ranges among population subgroups provides tailored information that may lead to better educated prevention, screening, and control behaviors and more efficient allocation of health resources. (C) 1999 American Health Foundation and Academic Press. C1 NCI, Div Canc Control & Populat Sci, Can Control Res Program, Bethesda, MD 20892 USA. US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Rockville, MD 20850 USA. RP Merrill, RM (reprint author), Brigham Young Univ, Dept Hlth Sci, 229-L RB, Provo, UT 84602 USA. NR 93 TC 25 Z9 27 U1 3 U2 9 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD FEB PY 1999 VL 28 IS 2 BP 179 EP 193 DI 10.1006/pmed.1998.0399 PG 15 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 165EC UT WOS:000078506100010 PM 10048110 ER PT J AU Kleinman, HK AF Kleinman, HK TI The laminins SO PROCEEDINGS OF THE INDIAN ACADEMY OF SCIENCES-CHEMICAL SCIENCES LA English DT Article; Proceedings Paper CT Satellite Symposium on Trends in Collagen, at the XXV Congress of the International-Union-of-Leather-Technologists-and-Chemists-Societies CY JAN 27-30, 1999 CL CHENNAI, INDIA SP Int Union Leather Technologists & Chemists Soc DE basement membrane; extracellular matrix; cell adhesion; laminin; cell differentiation; malignancy ID CELL AB The laminins are a family of trimeric basement membrane glycoproteins containing an alpha, beta and gamma chain. At least eleven family members have been described and others are likely to exist, many in tissue-specific locations. Five alpha, four beta and three gamma chains have been described further suggesting additional isoforms. Laminins are very biologically active with laminin-l (composed of alpha 1 beta 1 gamma 1 chains) being the most studied. Laminin-l increases cell adhesion, migration, growth, differentiation, neurite outgrowth, protease production, and malignancy. The response of the cell is dependent on the cell type. A number of active sites on laminin including cryptic domains have been defined using protease-derived fragments, recombinant material and synthetic peptides. Various diseases involving mutations, deletions and autoantibodies to laminins have been identified demonstrating the important functions of this family of molecules in both development and disease. These studies demonstrate that the structural diversity of the laminins allows for many highly specialized functions. C1 Natl Inst Dent Craniofacial Res, Cell Biol Sect, NIH, Bethesda, MD 20892 USA. RP Kleinman, HK (reprint author), Natl Inst Dent Craniofacial Res, Cell Biol Sect, NIH, Bethesda, MD 20892 USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU INDIAN ACADEMY SCIENCES PI BANGALORE PA P B 8005 C V RAMAN AVENUE, BANGALORE 560 080, INDIA SN 0253-4134 J9 P INDIAN AS-CHEM SCI JI Proc. Indian Acad. Sci.-Chem. Sci. PD FEB PY 1999 VL 111 IS 1 BP 179 EP 184 PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA 209JZ UT WOS:000081045600019 ER PT J AU McClure, RK AF McClure, RK TI Backward masking in bipolar affective disorder SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE backward masking; bipolar affective disorder; bipolar disorder; cognitive deficits; psychotic disorders; visual perception; visual channels ID CEREBRAL LATERALITY; SCHIZOPHRENIA; DEPRESSION; CHANNELS; MANIA AB 1. When an informational stimulus, the target, is followed closely in time by a noninformational stimulus, the mask, the visual system's processing of the informational stimulus is disturbed. This disturbance is known as backward visual masking. 2. Transient and sustained visual pathways detect different characteristics of a visual stimulus, at different times in early visual information processing, and have unique anatomic distribution with regard to retinal origin, thalamic and cortical projections. 3. Backward masking occurs by two mechanisms. Interruption occurs when activity in the transient channels of the mask disrupt activity in the sustained channels of the target. integration occurs when activity in the sustained channels of the mask disrupt activity of the sustained channels of the target. 4. Characteristics of the mask-energy, location, or the time presented after the target-can be altered to enhance interruption or integration. Interruption is a bell-shaped function of, and integration is an exponential function of, visual performance and interstimulus interval. 5. An impairment in backward masking is present in bipolar subjects during manic episodes, is not related to the presence of psychotic symptoms, and persists when mania resolves. Lithium appears to have a detrimental effect on backward masking. C1 Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC USA. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP McClure, RK (reprint author), 20405 Shadow Oak Court, Gaithersburg, MD 20886 USA. NR 13 TC 14 Z9 14 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD FEB PY 1999 VL 23 IS 2 BP 195 EP 206 DI 10.1016/S0278-5846(98)00105-5 PG 12 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 179JM UT WOS:000079323500002 PM 10368864 ER PT J AU Lazarus, LH Bryant, SD Cooper, PS Salvadori, S AF Lazarus, LH Bryant, SD Cooper, PS Salvadori, S TI What peptides these deltorphins be SO PROGRESS IN NEUROBIOLOGY LA English DT Review ID DELTA-OPIOID RECEPTOR; BLOOD-BRAIN-BARRIER; MOUSE VAS-DEFERENS; AGONIST-INDUCED DESENSITIZATION; PROTEIN-COUPLED RECEPTORS; I-LIKE IMMUNOREACTIVITY; 3RD EXTRACELLULAR LOOP; CATION-PI INTERACTIONS; NITRIC-OXIDE SYNTHASE; RAT CAUDATE-PUTAMEN AB The deltorphins are a class of highly selective delta-opioid heptapeptides from the skin of the Amazonian frogs Phyllomedusa sauvagei and P, bicolor. The first of these fascinating peptides came to light in 1987 by cloning of the cDNA of from frog skins, while the other members of this family were identified either by cDNA or isolation of the peptides. The distinctive feature of deltorphins is the presence of a naturally occurring D-enantiomer at the second position in their common N-terminal sequence, Tyr-D-Xaa-Phe, comparable to dermorphin, which is the prototype of a group of mu-selective opioids from the same source. The D-amino acid and the anionic residues, either Glu or Asp, as well as their unique amino acid compositions are responsible for the remarkable biostability, high delta-receptor affinity, bioactivity and peptide conformation. This review summarizes a decade of research from many laboratories that defined which residues and substituents in the deltorphins interact with the delta-receptor and characterized pharmacological and physiological activities in vitro and in vivo. It begins with a historical description of the topic and presents general schema for the synthesis of peptide analogues of deltorphins A, B and C as a means to document the methods employed in producing a myriad of analogues. Structure-activity studies of the peptides and their pharmacological activities in vitro are detailed in abundantly tabulated data. A brief compendium of the current level of knowledge of the delta-receptor assists the reader to appreciate the rationale for the design of these analogues. Discussion of the conformation of these peptides addresses how structure leads to further hypotheses regarding ligand-receptor interaction. The review ends with a broad discussion of the potential applications of these peptides in clinical and therapeutic settings. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy. RP NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. OI SALVADORI, Severo/0000-0002-8224-2358 NR 406 TC 59 Z9 63 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD FEB PY 1999 VL 57 IS 4 BP 377 EP 420 DI 10.1016/S0301-0082(98)00050-1 PG 44 WC Neurosciences SC Neurosciences & Neurology GA 163PE UT WOS:000078413300001 PM 10080383 ER PT J AU Iyer, LK Qasba, PK AF Iyer, LK Qasba, PK TI Molecular dynamics simulation of alpha-lactalbumin and calcium binding c-type lysozyme SO PROTEIN ENGINEERING LA English DT Article DE calcium-binding proteins; lactose synthase; c-type lysozyme; atomic fluctuations; functionally important motion ID EQUINE LYSOZYME; HYDROPHOBIC-INTERACTION; 1.7-A RESOLUTION; LACTOSE SYNTHASE; MILK; SITE; MOTIONS; FLUCTUATIONS; TRANSITION; MECHANISM AB alpha-Lactalbumins (LAs) and c-type lysozymes (LYZs) are two classes of proteins which have a 35-10% sequence homology and share a common three dimensional fold but perform different functions. Lysozymes bind and cleave the glycosidic bond linkage in sugars,where as, a-lactalbumin does not bind sugar but participates in the synthesis of lactose, a-Lactalbumin is a metallo-protein and binds calcium, where as, only a few of the LYZs bind calcium. These proteins consist of two domains, an a-helical and a beta-strand domain, separated by a cleft. Calcium is bound at a loop situated at the bottom of the cleft and is important for the structural integrity of the protein. Calcium is an ubiquitous intracellular signal in higher eukaryotes and structural changes induced on calcium binding have been observed in a number of proteins. In the present study, molecular dynamics simulations of equine LYZ and human LA, with and without calcium, were carried out. We detail the differences in the dynamics of equine LYZ and human LA, and discuss it in the light of experimental data already available and relate it to the behavior of the functionally important regions of both the proteins. These simulations bring out the role of calcium in the conformation and dynamics of these metallo-proteins. In the calcium bound LA, the region of the protein around the calcium binding site is not only frozen but the atomic fluctuations are found to increase away from the binding site and peak at the exposed sites of the protein. This channeling of fluctuations away from the metal binding site could serve as a general mechanism by which the effect of metal binding at a site is transduced to other parts of the protein and could play a key role in protein-ligand and/or protein-protein interaction. C1 NCI, Struct Glycobiol Sect, Lab Expt & Computat Biol, Div Biol Sci,NIH, Frederick, MD 21702 USA. RP Qasba, PK (reprint author), NCI, Struct Glycobiol Sect, Lab Expt & Computat Biol, Div Biol Sci,NIH, Frederick, MD 21702 USA. OI Iyer, Lakshmanan/0000-0001-9167-6396 NR 51 TC 22 Z9 22 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD FEB PY 1999 VL 12 IS 2 BP 129 EP 139 DI 10.1093/protein/12.2.129 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 174ZH UT WOS:000079066100006 PM 10195284 ER PT J AU Lin, L Gillies, SD Schlom, J Pestka, S AF Lin, L Gillies, SD Schlom, J Pestka, S TI Construction of phosphorylatable chimeric monoclonal antibody CC49 with a casein kinase I recognition site SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID TUMOR-ASSOCIATED ANTIGENS; COLORECTAL-CANCER; PROTEIN-KINASE; COLON CANCER; PHASE-I; B72.3; EXPRESSION; CELLS; CARCINOMA; ALPHA AB Phosphorylation sites for casein kinase I were introduced into chimeric monoclonal antibody CC49 (MAb-chCC49) by inserting a synthetic fragment (CK1) encoding two casein kinase I phosphorylation sites into an expression vector. The phosphorylation sites were created by incorporating the predicted consensus sequences for phosphorylation by the casein kinase I at the carboxyl terminus of the heavy-chain constant region of the MAb-chCC49. The resultant modified MAb-chCC49 (MAb-chCC49CK1) was expressed and purified. The MAb-chCC49CK1 protein can be phosphorylated by the casein kinase I with [gamma-P-32]ATP to high radiospecific activity. The P-32-labeled MAb-chCC49CK1 protein binds to cells expressing TAG-72 antigens. The introduction of phosphorylation sites into MAb provides new reagents for the diagnosis and treatment of cancer. This demonstrates that, as was described for the cAMP-dependent protein kinase site, the casein kinase I recognition site can also be used to introduce phosphorylation sites into proteins. (C) 1999 Academic Press. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Mol Genet & Microbiol, Piscataway, NJ 08854 USA. Lexigen Pharmaceut Corp, Lexington, MA 02173 USA. NCI, Bethesda, MD 20892 USA. RP Pestka, S (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Mol Genet & Microbiol, 675 Hoes Lane, Piscataway, NJ 08854 USA. FU NCI NIH HHS [R01 CA46465, R01 CA52363] NR 37 TC 8 Z9 8 U1 0 U2 3 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 FEB PY 1999 VL 15 IS 1 BP 83 EP 91 DI 10.1006/prep.1998.1000 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 165PV UT WOS:000078531000012 PM 10024474 ER PT J AU Bertelsen, EB Zhou, HJ Lowry, DF Flynn, GC Dahlquist, FW AF Bertelsen, EB Zhou, HJ Lowry, DF Flynn, GC Dahlquist, FW TI Topology and dynamics of the 10 kDa C-terminal domain of DnaK in solution SO PROTEIN SCIENCE LA English DT Article DE DnaK; molecular chaperone; NMR; N-15 relaxation ID ESCHERICHIA-COLI DNAJ; ROTATIONAL DIFFUSION ANISOTROPY; NMR STRUCTURE DETERMINATION; NUCLEAR-MAGNETIC-RESONANCE; MOLECULAR CHAPERONE DNAK; PEPTIDE-BINDING DOMAIN; SHOCK COGNATE PROTEIN; SIDE-CHAIN RESONANCES; BACKBONE DYNAMICS; SUBSTRATE-BINDING AB Hsp70 molecular chaperones contain three distinct structural domains, a 44 kDa N-terminal ATPase domain, a 17 kDa peptide-binding domain, and a 10 kDa C-terminal domain. The ATPase and peptide binding domains are conserved in sequence and are functionally well characterized. The function of the 10 kDa variable C-terminal domain is less well understood. We have characterized the secondary structure and dynamics of the C-terminal domain from the Escherichia coli Hsp70, DnaK, in solution by high-resolution NMR. The domain was shown to be comprised of a rigid structure consisting of four helices and a flexible C-terminal subdomain of approximately 33 amino acids. The mobility of the flexible region is maintained in the context of the full-length protein and does not appear to be modulated by the nucleotide state. The flexibility of this region appears to be a conserved feature of Hsp70 architecture and may have important functional implications. We also developed a method to analyze N-15 nuclear spin relaxation data, which allows us to extract amide bond vector directions relative to a unique diffusion axis. The extracted angles and rotational correlation times indicate that the helices form an elongated, bundle-like structure in solution. C1 Univ Oregon, Inst Mol Biol, Eugene, OR 97403 USA. NCI, Macromol NMR Sect, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. Pacific NW Lab, Environm Mol Sci Lab, Richland, WA 99352 USA. RP Dahlquist, FW (reprint author), Univ Oregon, Inst Mol Biol, Eugene, OR 97403 USA. NR 70 TC 30 Z9 31 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD FEB PY 1999 VL 8 IS 2 BP 343 EP 354 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 164VG UT WOS:000078483800009 PM 10048327 ER PT J AU Gronenborn, AM Clore, GM Louis, JM Wingfield, PT AF Gronenborn, AM Clore, GM Louis, JM Wingfield, PT TI Is human thioredoxin monomeric or dimeric? SO PROTEIN SCIENCE LA English DT Article DE analytical ultracentrifugation; correlation times; heteronuclear relaxation rates; human thioredoxin ID RELAXATION MEASUREMENTS; BACKBONE DYNAMICS; MUTANT AB We have examined the molecular weight and rotational correlation time of human thioredoxin by analytical ultracentrifugation and NMR spectroscopy, respectively. Two variants of human thioredoxin were studied, namely human thioredoxin identical in amino acid sequence to the one whose NMR structure we previously determined (C62A, C69A, C73A, M74T) and human thioredoxin (C62A, C69A, C73A, M74) containing the wild-type amino acid methionine at position 74. In both cases, the experimental data indicate that the predominant species is monomeric and we find no evidence for the existence of a well-defined dimeric form as was observed in the recently reported crystal structure (Weichsel et al., 1996) of human thioredoxin and the C73S mutant. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. RP Gronenborn, AM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. EM gronenborn@vger.niddk.nih.gov; clore@speck.niddk.nih.gov RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 9 TC 17 Z9 17 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD FEB PY 1999 VL 8 IS 2 BP 426 EP 429 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 164VG UT WOS:000078483800018 PM 10048336 ER PT J AU Verbitsky, G Nussinov, R Wolfson, H AF Verbitsky, G Nussinov, R Wolfson, H TI Flexible structural comparison allowing hinge-bending, swiveling motions SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE domain motions; hinge-bending motions; flexible protein structure comparison; computer vision; detection of conformational changes ID PROTEIN STRUCTURES; COMPUTER VISION; SECONDARY STRUCTURE; DOMAIN MOVEMENTS; HOUGH TRANSFORM; MOTIFS; IDENTIFICATION; ALIGNMENT; MUTANT AB We present an efficient method for flexible comparison of protein structures, allowing swiveling motions. In all currently available methodologies developed and applied to the comparisons of protein structures, the molecules are considered to be rigid objects. The method described here extends and generalizes current approaches to searches for structural similarity between molecules by vie viewing proteins as objects consisting of rigid parts connected by rotary joints. During the matching, the rigid subparts are allowed to be rotated with respect to each other around swiveling points in one of the molecules, This technique straightforwardly detects structural motifs having hinge(s) between their domains. Whereas other existing methods detect hinge-bent motifs by initially finding the matching rigid parts and subsequently merging these together, our method automatically detects recurring substructures, allowing full 3 dimensional rotations about their swiveling points. Yet the method is extremely fast, avoiding the time-consuming full conformational space search. Comparison of two protein structures, without a predefinition of the motif, takes only seconds to one minute on a workstation per hinge. Hence, the molecule can be scanned for many potential hinge sites, allowing practically all C-alpha atoms to be tried as swiveling points. This algorithm provides a highly efficient, fully automated tool. Its complexity is only O(n(2)), where n is the number of C-alpha atoms in the compared molecules. As in our previous methodologies, the matching is independent of the order of the amino acids in the polypeptide chain. Here Fee illustrate the performance of this highly powerful tool on a large number of proteins exhibiting hinge-bending domain movements. Despite the motions, known hinge-bent domains/motifs which have been assembled and classified, are correctly identified. Additional matches are detected as well. This approach has been motivated by a technique for model based recognition of articulated objects originating in computer vision and robotics. Published 1999 Wiley-Liss, Inc.(dagger) C1 NCI, Frederick Canc Res & Dev Ctr, Frederick Canc Res Facil,Lab Expt & Computat Biol, Intramural Res Support Program,SAIC, Frederick, MD 21702 USA. Tel Aviv Univ, Sch Math Sci, Dept Comp Sci, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Frederick Canc Res & Dev Ctr, Frederick Canc Res Facil,Lab Expt & Computat Biol, Intramural Res Support Program,SAIC, Bldg 469,Room 151, Frederick, MD 21702 USA. RI Wolfson, Haim/A-1837-2011 FU NCI NIH HHS [N01 CO56000] NR 31 TC 30 Z9 31 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-3585 J9 PROTEINS JI Proteins PD FEB 1 PY 1999 VL 34 IS 2 BP 232 EP 254 DI 10.1002/(SICI)1097-0134(19990201)34:2<232::AID-PROT9>3.0.CO;2-9 PG 23 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 153KN UT WOS:000077832400009 PM 10022359 ER PT J AU Lansdell, H AF Lansdell, H TI Intelligence test scores from infancy to adulthood for a craniopagus twin pair neurosurgically separated at 4 months of age SO PSYCHOLOGICAL REPORTS LA English DT Article ID WAIS-R SCORES; CONJOINED TWINS; WISC-R; PERFORMANCE; MECHANISMS; PLASTICITY; ANOMALIES; STUDENTS; CORTEX AB Long-term effects in a neurosurgically separated twin pair were illuminated by standard psychological test scores obtained over a period from 2 to 38 years of age. Interdigitation of the gyri of their right frontal lobes had necessitated separation in two stages at 4 months of age. One twin clearly suffered some brain injury and showed some impairment during the testing at 5 years of age. The scores of both twins rose at the adult testing. The brighter twin has an IQ comparable to that of the mother. The unique data set is a kind of model for long-term assessment of early brain surgery, particularly with craniopagus twins. C1 Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. RP Lansdell, H (reprint author), McGill Univ, Dept Psychol, 1205 Dr Penfield Ave,Stewart Biol Sci Bldg, Montreal, PQ H3A 1B1, Canada. EM hcl@ego.psych.mcgill.ca NR 43 TC 1 Z9 1 U1 0 U2 1 PU AMMONS SCIENTIFIC, LTD PI MISSOULA PA PO BOX 9229, MISSOULA, MT 59807-9229 USA SN 0033-2941 J9 PSYCHOL REP JI Psychol. Rep. PD FEB PY 1999 VL 84 IS 1 BP 209 EP 217 DI 10.2466/PR0.84.1.209-217 PG 9 WC Psychology, Multidisciplinary SC Psychology GA 181JX UT WOS:000079439200037 PM 10203953 ER PT J AU Tseng, M Everhart, JE Sandler, RS AF Tseng, Marilyn Everhart, James E. Sandler, Robert S. TI Dietary intake and gallbladder disease: a review SO PUBLIC HEALTH NUTRITION LA English DT Review DE Cholelithiasis; Diet; Energy intake; Dietary fats; Cholesterol; Fibre; Sucrose; Alcohol AB Objective: Dietary intake has long been looked upon as a potentially modifiable risk factor for gallbladder disease (GBD), here defined as either having gallstones or having had surgery for gallstones. This paper reviews the epidemiological evidence for an association between dietary intake and GBD, focusing on six dietary factors that have received the most attention in studies in this area: energy intake, fatty acids, cholesterol, carbohydrates and fibre, calcium and alcohol. The objectives of this review are to evaluate the potential usefulness of altering the diet to prevent GBD and to consider future research in this area. Design: We reviewed all English-language epidemiological studies on diet and cholelithiasis that were cross-sectional, cohort or case-control in design and that were indexed in the Medline database from 1966 to October 1997. Results: A positive association was suggested with simple sugars and inverse associations with dietary fibre and alcohol. No convincing evidence was found for a role for energy intake or intake of fat or cholesterol. Variable means of ascertaining cases and inaccurate measurement of dietary intake may contribute to variation in results across studies. Conclusions: Some specific components of the diet that may affect GBD include simple sugars, fibre and alcohol, but whether risk for GBD can be reduced by altering intake of a specific dietary factor has not been established. Although no specific dietary recommendations can be made to reduce risk of GBD per se, a 'healthy' diet aimed at reducing risk of other diseases might be expected to reduce risk for GBD as well. C1 [Tseng, Marilyn] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA. [Everhart, James E.] NIDDK, Bethesda, MD USA. [Sandler, Robert S.] Univ N Carolina, Dept Med, Div Digest Dis & Nutr, Chapel Hill, NC 27515 USA. RP Tseng, M (reprint author), Fox Chase Canc Ctr, Div Populat Sci, 7701 Burholme Ave, Philadelphia, PA 19111 USA. EM m_tseng@fccc.edu RI Tseng, Marilyn/B-9334-2016 OI Tseng, Marilyn/0000-0002-9969-9055 FU National Institutes of Health [T32 DK07634, P30 DK34987] FX The authors thank Dr Matthew Longnecker for his valuable comments on this manuscript. This research was supported in part by grants T32 DK07634 and P30 DK34987 from the National Institutes of Health. NR 100 TC 18 Z9 18 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 1368-9800 EI 1475-2727 J9 PUBLIC HEALTH NUTR JI Public Health Nutr. PD FEB PY 1999 VL 2 IS 2 BP 161 EP 172 DI 10.1017/S136898009900021X PG 12 WC Public, Environmental & Occupational Health; Nutrition & Dietetics SC Public, Environmental & Occupational Health; Nutrition & Dietetics GA V32XS UT WOS:000208984500001 PM 10447244 ER PT J AU O'Connell, AC Redman, RS Evans, RL Ambudkar, IS AF O'Connell, AC Redman, RS Evans, RL Ambudkar, IS TI Radiation-induced progressive decrease in fluid secretion in rat submandibular glands is related to decreased acinar volume and not impaired calcium signaling SO RADIATION RESEARCH LA English DT Article ID PAROTID-GLAND; SALIVARY-GLANDS; IONIZING-RADIATION; INOSITOL PHOSPHATE; X-IRRADIATION; CELLS; INJURY; ACTIVATION; MEMBRANE; RADIOSENSITIVITY AB The mechanism(s) of radiation-induced salivary gland dysfunction is poorly understood. In the present study, we have assessed the secretory function (muscarinic agonist-stimulated saliva flow, intracellular calcium mobilization, Na+/K+/2Cl(-) cotransport activity) in rat submandibular glands 12 months postirradiation (single dose, 10 Gy), The morphological status of glands from control and irradiated rats was also determined, Pilocarpine-stimulated salivary flow was decreased by 67% at 12 months (but not at 3 months) after irradiation, This was associated with a 47% decrease in the wet weight of the irradiated glands. Histological and morphometric analysis demonstrated that acinar cells were smaller and occupied relatively less volume and convoluted granular tubules were smaller but occupied the same relative volume, while intercalated and striated ducts maintained their size but occupied a greater relative volume in submandibular glands from irradiated compared to control animals. In addition, no inflammation or fibrosis was observed in the irradiated tissues. Carbachol- or thapsigargin-stimulated mobilization of Ca2+ was similar in dispersed submandibular gland cells from control and irradiated animals. Further, [Ca2+](i) imaging of individual ducts and acini from control and irradiated groups showed, for the first time, that mobilization of Ca2+ in either cell type was not altered by the radiation treatment. The carbachol-stimulated, bumetanide-sensitive component of the Na+/K+/2Cl(-) cotransport activity was also similar in submandibular gland cells from control and irradiated animals. These data demonstrate that a single dose of gamma radiation induces a progressive loss of submandibular gland tissue and function. This loss of salivary flow is not due to chronic inflammation or fibrosis of the gland or an alteration in the neurotransmitter signaling mechanism in the acinar or ductal cells. The radiation-induced decrease in fluid secretion appears to be related to a change in either the water-handling capacity of the acini or the number of acinar cells in the gland. (C) 1999 by Radiation Research Society. C1 NIDCR, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. Dept Vet Affairs Med Ctr, Oral Pathol Res Lab, Washington, DC USA. RP O'Connell, AC (reprint author), NIDCR, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. OI O'Connell, Anne C/0000-0002-1495-3983 NR 36 TC 37 Z9 38 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD FEB PY 1999 VL 151 IS 2 BP 150 EP 158 DI 10.2307/3579765 PG 9 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 168YH UT WOS:000078720400005 PM 9952299 ER PT J AU Leidy, NK Haase, JE AF Leidy, NK Haase, JE TI Functional status from the patient's perspective: The challenge of preserving personal integrity SO RESEARCH IN NURSING & HEALTH LA English DT Article DE functional status; integrity; chronic obstructive pulmonary disease; qualitative methods ID OBSTRUCTIVE PULMONARY-DISEASE; CHRONIC RESPIRATORY ILLNESS; AIR-FLOW LIMITATION; SOCIAL SUPPORT; QUALITY; SELF; PREDICTORS; DISABILITY; OUTCOMES; LIFE AB The purpose of this naturalistic, qualitative study was to describe the meaning of functional performance from the perspective of patients themselves. Twelve men and women with moderate to severe chronic obstructive pulmonary disease (COPD) participated in unstructured, tape-recorded interviews. The essential structure of the experience of finding purpose and meaning through activity was derived through an adaptation of Colaizzi's phenomenological method and the consensus dialogue approach to concept clarification. Results suggest people who are ill face an ongoing challenge of preserving their personal integrity, defined as a satisfying sense of wholeness, as they encounter a variety of physical changes that can interfere with day-to-day activity. Qualities most salient to integrity are a sense of effectiveness, or "being able," and of connectedness, or "being with." Identifying personal integrity as a motivating and explanatory factor in day-to-day activity performance may be an important consideration in designing effective intervention programs to improve capacity, strengthen performance, and enhance quality of life. (C) 1999 John Wiley & Sons, Inc. C1 MEDTAP Int Inc, Ctr Hlth Outcomes Res, Bethesda, MD 20814 USA. Natl Inst Nursing Res, Div Intramural Res, NIH, Bethesda, MD USA. Univ Arizona, Coll Nursing, Tucson, AZ USA. RP Leidy, NK (reprint author), MEDTAP Int Inc, Ctr Hlth Outcomes Res, 7101 Wisconsin Ave,Suite 600, Bethesda, MD 20814 USA. NR 44 TC 42 Z9 42 U1 0 U2 4 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0160-6891 J9 RES NURS HEALTH JI Res. Nurs. Health PD FEB PY 1999 VL 22 IS 1 BP 67 EP 77 DI 10.1002/(SICI)1098-240X(199902)22:1<67::AID-NUR8>3.0.CO;2-D PG 11 WC Nursing SC Nursing GA 160MN UT WOS:000078234600009 PM 9928965 ER PT J AU Stewart, PA Fears, T Kross, B Ogilvie, L Blair, A AF Stewart, PA Fears, T Kross, B Ogilvie, L Blair, A TI Exposure of farmers to phosmet, a swine insecticide SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Article DE exposure assessment; exposure determinants; farmers; pesticides ID PESTICIDE EXPOSURE; DERMAL EXPOSURE; APPLICATORS AB Objectives The goal of this study was to measure dermal and inhalation exposures to phosmet during application to animals and to identify what determinants of exposure influence the exposure levels. Methods Ten farmers were monitored using dermal patches, gloves, and air sampling media during normal activities of applying phosmet to pigs for insect control. Exposures were measured on the clothing (outer), under the clothing (inner), on the hands, and in the air. Possible exposure determinants were identified, and a questionnaire on work practices was administered. Results The geometric mean of the outer exposure measurements was 79 mu g/h, whereas the geometric mean of the inner exposure measurements was 6 mu g/h. The geometric mean for hand exposure was 534 mu g/h, and the mean air concentration was 0.2 mu g/m(3). Glove use was associated with the hand and total dermal exposure levels, but no other determinant was associated with any of the exposure measures. The average penetration through the clothing was 54%, which dropped to 8% when the farmers wearing short sleeves were excluded. The farmers reported an average of 40 hours a year performing insecticide-related tasks. Conclusions Farmers who applied phosmet to animals had measurable exposures, but the levels were lower than what has been seen in other pesticide applications. Inhalation exposures were insignificant when compared with dermal exposures, which came primarily from the hands. Clothing, particularly gloves, provided substantial protection from exposures. No other exposure determinant was identified. C1 NCI, Bethesda, MD 20892 USA. Univ Iowa, Ctr Int Rural & Environm Hlth, Iowa City, IA USA. RP Stewart, PA (reprint author), NCI, 6120 Execut Blvd,Room 8102,MSC 7240, Bethesda, MD 20892 USA. NR 17 TC 8 Z9 8 U1 0 U2 0 PU SCAND J WORK ENV HEALTH PI HELSINKI PA TOPELIUKSENKATU 41A, SF-00250 HELSINKI, FINLAND SN 0355-3140 J9 SCAND J WORK ENV HEA JI Scand. J. Work Environ. Health PD FEB PY 1999 VL 25 IS 1 BP 33 EP 38 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 176MC UT WOS:000079154300005 PM 10204668 ER PT J AU Koch, CA Robyn, JA AF Koch, CA Robyn, JA TI Can the long-term prognosis of patients with seizures and structural brain lesions be improved by surgical treatment? SO SEIZURE-EUROPEAN JOURNAL OF EPILEPSY LA English DT Letter C1 NICHD, NIH, DEB, Bethesda, MD 20892 USA. RP Koch, CA (reprint author), NICHD, NIH, DEB, Bldg 10,Rm 10 N 262, Bethesda, MD 20892 USA. RI Koch, Christian/A-4699-2008; OI Koch, Christian/0000-0003-3127-5739; Koch, Christian/0000-0003-0678-1242 NR 5 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1059-1311 J9 SEIZURE-EUR J EPILEP JI Seizure PD FEB PY 1999 VL 8 IS 1 BP 70 EP 70 DI 10.1053/seiz.1998.0249 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 171GT UT WOS:000078855400014 PM 10091853 ER PT J AU Londos, C Brasaemle, DL Schultz, CJ Segrest, JP Kimmel, AR AF Londos, C Brasaemle, DL Schultz, CJ Segrest, JP Kimmel, AR TI Perilipins, ADRP, and other proteins that associate with intracellular neutral lipid droplets in animal cells SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE adipocyte; ADRP; lipid storage droplets; perilipin ID DIFFERENTIATION-RELATED PROTEIN; HORMONE-SENSITIVE LIPASE; TUMOR-NECROSIS-FACTOR; ADIPOSE CONVERSION; EICOSANOID FORMATION; STEROIDOGENIC CELLS; STORAGE DROPLET; LEYDIG-CELLS; 3T3-L1 CELLS; OIL BODIES AB Although all animal cells package and store neutral lipids in discrete intracellular storage droplets, there is little information on the molecular processes that govern either the deposition or catabolism of the stored lipid components. Studies on anipocytes have uncovered the perilipins and ADRP, related proteins that appear to be intrinsic to the surfaces of intracellular lipid storage droplets. We discuss the properties, distribution, localization, and potential functions of these proteins, as well as those of vimentin and the recently-described 'capsular' proteins, in lipid storage and metabolism. C1 NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Alabama, Med Ctr, Birmingham, AL 35294 USA. RP Londos, C (reprint author), NIDDKD, Cellular & Dev Biol Lab, NIH, Bldg 6,RM B1-32A,6 Ctr Dr MSC-2715, Bethesda, MD 20892 USA. OI Brasaemle, Dawn/0000-0002-8553-8285 NR 41 TC 306 Z9 311 U1 2 U2 21 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD FEB PY 1999 VL 10 IS 1 BP 51 EP 58 DI 10.1006/scdb.1998.0275 PG 8 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 189VH UT WOS:000079926500007 PM 10355028 ER PT J AU Bhadelia, RA Anderson, M Polak, JF Manolio, TA Beauchamp, N Knepper, L O'Leary, DH AF Bhadelia, RA Anderson, M Polak, JF Manolio, TA Beauchamp, N Knepper, L O'Leary, DH CA CHS Collaborative Res Grp TI Prevalence and associations of MRI-demonstrated brain infarcts in elderly subjects with a history of transient ischemic attack - The Cardiovascular Health Study SO STROKE LA English DT Article DE cerebral infarction; cerebral ischemia, transient; magnetic resonance imaging ID SILENT CEREBRAL INFARCTION; CAROTID ATHEROSCLEROSIS; CEREBROVASCULAR-DISEASE; COMPUTED-TOMOGRAPHY; ATRIAL-FIBRILLATION; OLDER ADULTS; STROKE; PROGNOSIS; LESIONS; EVALUATE AB Background and Purpose - MRI is more sensitive than CT, but the significance of brain abnormalities seen on MR images obtained in older subjects with transient ischemic attack (TIA) is not clear. We studied the prevalence and risk factors associated with MRI-demonstrated infarcts in elderly subjects with a history of TIA. Methods - Participants of the Cardiovascular Health Study, aged 65 years or more and without prior stroke, were studied with brain MRI (n = 3456). The prevalence of brain infarcts (greater than or equal to 3 mm) on MRI was determined in subjects with and without TIA, The cardiovascular risk factors and clinical and subclinical cardiovascular disease associated with MRI infarcts were studied in subjects with TIA. Results - Subjects with TLA (n = 100) had a higher prevalence of MRI infarcts than subjects without TIA (46% versus 28%; P < 0.001), The unadjusted odds ratio for having MRI infarcts in subjects with TIA was 2.20 (95% CI, 1.47 to 3.30) and remained significantly elevated after adjustments for risk factors and cerebrovascular disease (odds ratio, 1.86; 95% CI, 1.23 to 2.83), In subjects with TIA, diastolic blood pressure (P = 0.01) and internal carotid artery intima-media thickness (P = 0.01) were the only factors predictive of the presence of MRI infarcts by stepwise logistic regression analysis. Conclusion - MRI infarcts are imaging manifestations of clinically important cerebrovascular disease in subjects with a history of TIA, given their increased prevalence and positive association with increased diastolic blood pressure and internal carotid artery intima-media thickness. C1 Tufts Univ, New England Med Ctr, Dept Radiol, Boston, MA 02111 USA. Cardiovasc Hlth Study Coordinating Ctr, Seattle, WA USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Johns Hopkins Radiol, Baltimore, MD USA. Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. RP Bhadelia, RA (reprint author), Tufts Univ, New England Med Ctr, Dept Radiol, 750 Washington St, Boston, MA 02111 USA. EM rafeeque.bhadelia@es.nemc.org FU NHLBI NIH HHS [N0 1-HC85079, N0 1-HC85086] NR 50 TC 17 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 1999 VL 30 IS 2 BP 383 EP 388 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 163BD UT WOS:000078381600017 PM 9933275 ER PT J AU Liu, LX Burgess, LH Gonzalez, AM Sibley, DR Chiodo, LA AF Liu, LX Burgess, LH Gonzalez, AM Sibley, DR Chiodo, LA TI D-2S, D-2L, D-3, and D-4 dopamine receptors couple to a voltage-dependent potassium current in N18TG2 x mesencephalon hybrid cell (MES-23.5) via distinct G proteins SO SYNAPSE LA English DT Article DE K+ current; D-2 receptors; D-2L; D-2S; D-3; MES-23.5; signal transduction ID GTP-BINDING PROTEIN; HAMSTER OVARY CELLS; ALPHA-SUBUNIT; SIGNAL-TRANSDUCTION; ANTERIOR-PITUITARY; MOLECULAR-CLONING; NG108-15 CELLS; D2; EXPRESSION; AUTORECEPTORS AB We utilized the approach of stably expressing different dopamine (DA) receptors into identified cell lines in an attempt to better understand the coupling of these receptors to membrane ion channels via second messenger systems. Recently, we examined the N18TG2 X mesencephalon (MES-23.5) cell line that is phenotypically similar to mesencephalic dopamine-containing neurons. Whole-cell voltage-clamp methods were used to investigate a voltage-dependent K+ current present in these cells. Untransfected MES-23.5 cells displayed a voltage-dependent slow-onset, slowly inactivating outward current which was not altered by bath application of either the D-2 DA receptor agonist quinpirole (QUIN; 10-100 mu M) or the D-1 DA receptor agonist SKF38393, indicating that these cells were devoid of DA receptors. The K+ current studied was activated upon depolarization from a holding potential of -60 mV to a level more positive than -20 mV and was observed to be sensitive to bath application of tetraethylammonium. When MES-23.5 cells were transfected, to stably express the D-2S, D-2L, D-3, and D-4 receptors, the same current was observed. In cells expressing D2L, D-2S, and D-3 receptors, application of the DA receptor agonists QUIN (1-80 mu M), 7-hydroxy-dipropylaminoteralin (7-OH-DPAT, 1-80 mu M), and dopamine (DA, 1-80 mu M), increased the peak outward current by 35-40%. In marked contrast, cells stably expressing the D-4 receptor demonstrated a significant DA agonist-induced reduction of the peak K+ current by 40%. For all four receptor subtypes, the D-2-like receptor antagonist sulpiride (SUL 5 mu M), when coapplied with QUIN (10 mu M), totally abolished the change in K+ current normally observed, while coapplication of the D-1-like receptor antagonist SCH23390 was without effect. The modulation of K+ current by D-2L, D-3, and D-4 receptor stimulation was prevented by pretreatment of the cells with pertussis toxin (PTX, 500 ng/ml for 4 h). In addition, the intracellular application of a polyclonal antibody which specifically recognizes G(o alpha) completely blocked the ability of D-2L, D-3, and D-4 receptors to modulate outward K+ currents. In contrast, the intracellular application of an antibody directed against G(o alpha) was without effect, whereas intracellular application of an antibody recognizing G(s alpha) abolished tile ability of the D-2S receptor to enhance K+ current. These findings demonstrate that different members of the D-2 DA receptor family may couple in a given cell to a common effector in dramatically different ways. Synapse 31:108-118, 1999. (C) 1999 Wiley-Liss, Inc. C1 Texas Tech Univ, Hlth Sci Ctr, Dept Pharmacol, Lubbock, TX 79430 USA. NINDS, Mol Neuropharmacol Sect, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Chiodo, LA (reprint author), Texas Tech Univ, Hlth Sci Ctr, Dept Pharmacol, Lubbock, TX 79430 USA. EM phrlac@ttuhsc.edu NR 46 TC 23 Z9 23 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD FEB PY 1999 VL 31 IS 2 BP 108 EP 118 DI 10.1002/(SICI)1098-2396(199902)31:2<108::AID-SYN3>3.0.CO;2-V PG 11 WC Neurosciences SC Neurosciences & Neurology GA 149ZJ UT WOS:000077636900003 PM 10024007 ER PT J AU Kirschner, LS Mariash, CN AF Kirschner, LS Mariash, CN TI Adipose S14 mRNA is abnormally regulated in obese subjects SO THYROID LA English DT Article ID THYROID-HORMONE; CARBOXYPEPTIDASE-E; SPOT-14 PROTEIN; MESSENGER-RNA; GENE; EXPRESSION; MICE; FAT; HYBRIDIZATION; LIPOGENESIS AB In rat hepatocyte culture, the S14 gene is necessary for induction of lipogenesis by carbohydrate metabolism and thyroid hormone. To determine if this gene plays a role in regulation of lipid storage in humans we compared the response to fasting of the human S14 gene between obese and nonobese subjects. We measured the relative content of human S14 mRNA in abdominal subcutaneous fat before and after a 48-hour fast. We found that mRNA-S14 is strongly downregulated in nonobese subjects in response to the fast, but only minimally downregulated in obese subjects. There is an excellent correlation between the body mass index, and the fasting induced fall in S14 mRNA. There was no difference in the postfasting glucose, insulin, and ketone levels between the 2 groups of subjects. Therefore, the S14 gene is abnormally downregulated during fasting in adipose tissue of obese individuals. Further study of this gene could provide important information on the mechanism of the acquisition or maintenance of obesity in humans. C1 Natl Inst Child Hlth & Dev, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Dept Med, Div Endocrinol & Diabetes, Minneapolis, MN 55455 USA. RP Mariash, CN (reprint author), Box 101 F-UMC,420 Delaware St SE, Minneapolis, MN 55455 USA. FU NCRR NIH HHS [NCRR-M01-RR00400]; NIDDK NIH HHS [R01 DK32885, P30 DK50456] NR 27 TC 10 Z9 12 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD FEB PY 1999 VL 9 IS 2 BP 143 EP 148 DI 10.1089/thy.1999.9.143 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 171XH UT WOS:000078889200007 PM 10090313 ER PT J AU Hulla, JE Miller, MS Taylor, JA Hein, DW Furlong, CE Omiecinski, CJ Kunkel, TA AF Hulla, JE Miller, MS Taylor, JA Hein, DW Furlong, CE Omiecinski, CJ Kunkel, TA TI Symposium overview: The role of genetic polymorphism and repair deficiencies in environmental disease SO TOXICOLOGICAL SCIENCES LA English DT Article DE N-acetyltransferase; paraoxonase; epoxide hydrolase; DNA polymerase; environment; polymorphism; cancer; susceptibility; predisposition; mismatch repair ID MICROSOMAL EPOXIDE HYDROLASE; SERUM PARAOXONASE POLYMORPHISM; CONGENIC SYRIAN-HAMSTERS; ACETYLATOR INBRED RATS; RECOMBINANT HUMAN NAT1; ABERRANT CRYPT FOCI; COLORECTAL-CANCER; N-ACETYLATION; METABOLIC-ACTIVATION; MISMATCH REPAIR AB A symposium of this title was presented at the 37(th) Annual Meeting of the Society of Toxicology held in Seattle, Washington during March of 1998, The symposium focused on heritable variations in metabolism, DNA replication, and DNA repair that may predispose humans to environmental diseases. Human metabolic, replication, and repair enzymes function in protective roles, Metabolic enzymes are protective because they detoxify a stream of chemicals to which the body is exposed. Replication and repair enzymes are also protective; they function to maintain the integrity of the human genome. Polymorphisms in the genes that code for some of these enzymes are known to give rise to variations in their protective functions. For example, functional polymorphisms of the N-acetyltransferases, paraoxonases, and microsomal epoxide hydrolases vary in their capacity to metabolize environmental chemicals. Specific isoforms of the N-acetyltransferases and microsomal epoxide hydrolases are increasingly associated with incidences of cancer attributable to exposure to these chemicals. Thus, maintenance of cellular-growth homeostasis, normally and in the face of environmental challenge, is dependent on an inherited assortment of metabolic isoforms. Since replication and repair are also protective cellular functions, and since mutations in genes that code for these functions are associated with tumorigenesis, one can reasonably speculate that common functional polymorphisms of replication and repair enzymes may also impart susceptibility to environmental disease. C1 Univ N Dakota, Sch Med, Dept Pharmacol & Toxicol, Grand Forks, ND 58202 USA. Wake Forest Univ, Sch Med, Ctr Comprehens Canc, Dept Canc Biol, Winston Salem, NC 27157 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Univ Louisville, Hlth Sci Ctr, Sch Med, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Genet, Seattle, WA 98195 USA. Univ Washington, Dept Environm Hlth, Seattle, WA 98195 USA. NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Hulla, JE (reprint author), Univ N Dakota, Sch Med, Dept Pharmacol & Toxicol, Grand Forks, ND 58202 USA. RI Hein, David/A-9707-2008; OI taylor, jack/0000-0001-5303-6398 FU NIEHS NIH HHS [P42 ES004696]; NIGMS NIH HHS [R01 GM032281] NR 90 TC 16 Z9 17 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD FEB PY 1999 VL 47 IS 2 BP 135 EP 143 DI 10.1093/toxsci/47.2.135 PG 9 WC Toxicology SC Toxicology GA 251PU UT WOS:000083454700001 PM 10220849 ER PT J AU Pan, BF Sweet, DH Pritchard, JB Chen, R Nelson, JA AF Pan, BF Sweet, DH Pritchard, JB Chen, R Nelson, JA TI A transfected cell model for the renal toxin transporter, rOCT2 SO TOXICOLOGICAL SCIENCES LA English DT Article DE organic cation transport; cisplatin; daunomycin; vinblastine; 2-chlorodeoxyadenosine; 2 '-deoxytubercidin; tetraethylammonium; rat kidney ID ORGANIC CATION TRANSPORTER; FUNCTIONAL-CHARACTERIZATION; ANION TRANSPORTER; RAT-KIDNEY; MOLECULAR-CLONING; P-GLYCOPROTEIN; SECRETION; EXPRESSION; MICE; MECHANISMS AB A cDNA for the organic cation transporter (rOCT2) of the rat kidney was inserted into the retroviral plasmid pLXSN. This plasmid was used to stably transfect NIH3T3 cells. The transfected cell line exhibited an enhanced rate of tetraethylammonium (TEA) uptake and efflux compared to wild-type NIH3T3 cells. Uptake of TEA by the transfected cells was markedly reduced upon incubation at 4 degrees C. When the extracellular pH was lowered from 8.1 to 5.9, uptake was also reduced, suggesting inhibition of rOCT2 by extracellular protons. The apparent K-m for TEA in the transfected cells was 141 mu M. The classical organic cation transport inhibitors, cyanine 863 and cimetidine, produced noncompetitive inhibition with apparent K-i values of 0.81 and 198 mu M, respectively. Daunomycin, vinblastine, and the deoxyadenosine analogs, 2'-deoxytubercidin and 2-chlorodeoxyadenosine, did not appear to be substrates for rOCT2. However, the anticancer drug, cisplatin, competitively inhibited TEA uptake by rOCT2 with an apparent K-i value of 925 mu M, suggesting that rOCT2 may play a role in its renal secretion. In summary, transfected NIH3T3 cells provide a facile system by which this and other organic ion transporters can be studied. C1 Univ Texas, MD Anderson Canc Ctr, Dept Expt Pediat, Houston, TX 77030 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Nelson, JA (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Expt Pediat, 1515 Holcombe Blvd, Houston, TX 77030 USA. RI Sweet, Douglas/H-7914-2013 OI Sweet, Douglas/0000-0002-8911-9184 FU NCI NIH HHS [2-P30-CA16672]; NIDDK NIH HHS [DK-41606] NR 34 TC 31 Z9 31 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD FEB PY 1999 VL 47 IS 2 BP 181 EP 186 DI 10.1093/toxsci/47.2.181 PG 6 WC Toxicology SC Toxicology GA 251PU UT WOS:000083454700007 PM 10220855 ER PT J AU Morgan, DL Mahler, JF Kirkpatrick, DT Price, HC O'Connor, RW Wilson, RE Moorman, MP AF Morgan, DL Mahler, JF Kirkpatrick, DT Price, HC O'Connor, RW Wilson, RE Moorman, MP TI Characterization of inhaled alpha-methylstyrene vapor toxicity for B6C3F1 mice and F344 rats SO TOXICOLOGICAL SCIENCES LA English DT Article DE alpha-methylstyrene; styrene; epoxides; hyaline droplet nephropathy ID STYRENE INHALATION TOXICITY; ALPHA-2U-GLOBULIN NEPHROPATHY; HEPATOTOXICITY; PATHOBIOLOGY; OXIDE AB alpha-Methylstyrene (AMS) is a chemical intermediate used in the synthesis of specialty polymers and copolymers. Inhalation studies of AMS were conducted because of the lack of toxicity data and the structural similarity of AMS to styrene, a toxic and potentially carcinogenic chemical. Male and female B6C3F1 mice were exposed to 0, 600, 800, or 1000 ppm AMS 6 h/day, 5 days/week, for 12 days. After 1 exposure, 21% (5/24) of female mice were found dead in the 1000-ppm group, 56% (10/18) in the 800-ppm group, and 6% (1/18) in the 600-ppm concentration group. After 12 exposures, relative liver weights were significantly increased and relative spleen weights were significantly decreased in both male and female mice at all concentrations. No microscopic treatment-related lesions were observed. A decrease in hepatic glutathione (GSH) was associated with AMS exposure for 1 and 5 days. Male and female F344 rats were exposed to 0, 600 or 1000 ppm AMS for 12 days. No mortality or sedation occurred in AMS-exposed rats. Relative liver weights were significantly increased in both males and females after 12 exposures to 600 or 1000 ppm. An increased hyaline droplet accumulation was detected in male rats in both concentration groups; no significant microscopic lesions were observed in other tissues examined. Exposure of male and female F344 rats and male NBR rats to 0, 125, 250 or 500 ppm AMS, 6 h/day for 9 days resulted in increased accumulation of hyaline droplets in the renal tubules of male F344 rats in the 250 and 500 ppm concentration groups. Although AMS and styrene are structurally very similar, AMS was considerably less toxic for mice and more toxic for male rats than styrene. C1 NIEHS, Res Triangle Pk, NC 27709 USA. ManTech Environm Technol Inc, Res Triangle Pk, NC 27709 USA. RP Morgan, DL (reprint author), NIEHS, Mail Stop IF-00,POB 12233, Res Triangle Pk, NC 27709 USA. NR 26 TC 4 Z9 4 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD FEB PY 1999 VL 47 IS 2 BP 187 EP 194 DI 10.1093/toxsci/47.2.187 PG 8 WC Toxicology SC Toxicology GA 251PU UT WOS:000083454700008 PM 10220856 ER PT J AU Walker, NJ Portier, CJ Lax, SF Crofts, FG Li, Y Lucier, GW Sutter, TR AF Walker, NJ Portier, CJ Lax, SF Crofts, FG Li, Y Lucier, GW Sutter, TR TI Characterization of the dose-response of CYP1B1, CYP1A1, and CYP1A2 in the liver of female Sprague-Dawley rats following chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE CYP1B1; CYP1A1; CYP1A2; TCDD; dioxin; liver; dose-response; cytochrome P-450 ID ARYL-HYDROCARBON RECEPTOR; NUCLEOTIDE-SEQUENCE; CANCER MORTALITY; ADRENAL CYTOCHROME-P450; CELL-PROLIFERATION; DIOXIN; MODEL; HEPATOCARCINOGENESIS; EXPRESSION; WORKERS AB One of the current knowledge gaps in the evaluation of risk for human exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the relationship between gene expression induced by TCDD and more complex biological responses such as altered growth, differentiation, and neoplasia This study investigates the dose-dependent expression of CYP1A1, CYP1A2, and CYP1B1 in the livers of female Sprague-Dawley rats chronically exposed to TCDD. Animals were treated biweekly for 30 weeks with daily averaged doses of 0 to 125 ng TCDD/kg/day. Immunoblot analysis showed that protein levels for CYP1B1, CYP1A1, and CYP1A2 exhibited a dose-dependent induction by TCDD. However, CYP1A1 and CYP1A2 protein levels were approximately 100-fold higher than CYP1B1, which could not be detected by either immunoblot analysis or immunohistochemistry in the livers of rats treated with TCDD for 30 weeks at a dose-equivalent less than 35.7 ng/kg/day. In control animals, CYP1A1 and CYP1A2 RNA levels, measured by quantitative RT-PCR, were 1100- and 15,000-fold higher than that of CYP1B1, respectively. TCDD induced CYP1B1 RNA levels at all doses, although absolute TCDD-induced levels of CYP1A1 and CYP1A2 at the highest dose (125 ng/kg/day) were more than 40-fold higher than that of CYP1B1. While the liver concentration of TCDD required for half-maximal induction of CYP1A1, CYP1A2, and CYP1B1 RNA levels was similar, the shaping parameter (Hill coefficient) of the dose-response curve for CYP1B1 was significantly higher than that for CYP1A1 or CYP1A2. The low level of TCDD-induced CYP1B1 expression in the liver relative to that of the CYP1A1 and CYP1A2 suggest that, if CYP1B1 is involved in TCDD-induced hepatocarcinogenesis, its endogenous function is likely to be unique and not overlapping with that of CYP1A1 or CYP1A2. (C) 1999 Academic Press. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Johns Hopkins Med Inst, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. RP Walker, NJ (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. RI Portier, Christopher/A-3160-2010; Walker, Nigel/D-6583-2012 OI Portier, Christopher/0000-0002-0954-0279; Walker, Nigel/0000-0002-9111-6855 FU NIEHS NIH HHS [ES07141, ES03819, ES08148] NR 35 TC 72 Z9 75 U1 1 U2 1 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 FEB 1 PY 1999 VL 154 IS 3 BP 279 EP 286 DI 10.1006/taap.1998.8595 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 167GD UT WOS:000078623400009 PM 9931287 ER PT J AU Cowley, H Wojda, U Cipolone, KM Procter, JL Stroncek, DF Miller, JL AF Cowley, H Wojda, U Cipolone, KM Procter, JL Stroncek, DF Miller, JL TI Biotinylation modifies red cell antigens SO TRANSFUSION LA English DT Article ID BLOOD-GROUP ANTIGENS; BIOTIN; SURVIVAL; ERYTHROCYTES; EXPRESSION; VOLUME; BAND-3 AB BACKGROUND: Chemical biotinylation of red cell membranes may be useful for several clinical applications, including red cell survival studies. STUDY DESIGN AND METHODS: To examine the possible effects of biotinylation on red cell antigens, standard hemagglutination assays were performed on matched sets of control and biotinylated red cells. The red cells were biotinylated at a final concentration of 2.0 pg of sulfo-N-hydroxysuccinimide-biotin per cell, and antigen-negative cells were directly compared to antigen-positive cells when possible. The hemagglutination assays were graded in a blinded fashion. Forty-one red cell antigens from 21 of the 23 established blood group systems were tested. RESULTS: Hemagglutination based upon antibody binding to A, A(1), M, N, S, s, P-1, D, C, E, c, e, C-w, Lu-b, K, k, Kp(b), Le(a), Le(b), Fy(a), Fy(b), Jk(a), Jk(b), Di(a), Wr(a), Wr(b), Yt(a), Xg(a), Sc1, Do(b), Co-a, Ch, H, Ge2, Cr-a, Kn(a), I, and P was not affected by biotinylation. Unexpectedly, the hemagglutination of Di(b+) and LW(a+) red cells was blocked after biotinylation. Conversely, MH04 monoclonal anti-A agglutinated red cells expressing B only after biotinylation. BIRMA-1 monoclonal anti-A and polyclonal anti-A from sera did not agglutinate the biotinylated B red cells. CONCLUSION: Biotinylation of human red cells specifically modified their antigenicity, as measured by standard hemagglutination assays. C1 NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Dept Transfus Med, Bethesda, MD 20892 USA. RP Miller, JL (reprint author), NIDDKD, Biol Chem Lab, NIH, Bldg 10,Room 9N308, Bethesda, MD 20892 USA. RI Wojda, Urszula/M-6079-2015 OI Wojda, Urszula/0000-0002-4525-2004 NR 27 TC 10 Z9 10 U1 0 U2 4 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD FEB PY 1999 VL 39 IS 2 BP 163 EP 168 DI 10.1046/j.1537-2995.1999.39299154730.x PG 6 WC Hematology SC Hematology GA 166PC UT WOS:000078584800008 PM 10037126 ER PT J AU Thomas, F Contreras, J Ricordi, C Ranuneolia, A Cartner, S Eckhoff, D Huang, Z Neville, D Thomas, J AF Thomas, F Contreras, J Ricordi, C Ranuneolia, A Cartner, S Eckhoff, D Huang, Z Neville, D Thomas, J TI Reversal of naturally occurring insulinopenic diabetes and induction of isolated islet xenograft tolerance in a preclinical study SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVIIth World Congress of the Transplantation-Society CY JUL 12-17, 1998 CL MONTREAL, CANADA SP Transplantat Soc ID TRANSPLANTATION; ALLOGRAFTS C1 Univ Alabama, Div Transplantat, Dept Surg, Birmingham, AL 35294 USA. Univ Miami, Diabet Res Inst, Miami, FL USA. NIH, Mol Biol Lab, Bethesda, MD USA. RP Thomas, F (reprint author), Univ Alabama, Div Transplantat, Dept Surg, Suite 719,701 South 19th St, Birmingham, AL 35294 USA. OI Ricordi, Camillo/0000-0001-8092-7153; Cartner, Samuel/0000-0002-2200-2627 FU NIAID NIH HHS [AI 39793, R01 AI 122293] NR 7 TC 1 Z9 1 U1 0 U2 2 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 FEB-MAR PY 1999 VL 31 IS 1-2 BP 637 EP 638 DI 10.1016/S0041-1345(98)01592-9 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 173BG UT WOS:000078960600281 PM 10083272 ER PT J AU Goebel, J Franks, A Robey, F Mikovits, J Lowry, RP AF Goebel, J Franks, A Robey, F Mikovits, J Lowry, RP TI Attenuation of IL-2 receptor signaling by CD4-ligation requires polymerized cytoskeletal actin but not P56LCK SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVIIth World Congress of the Transplantation-Society CY JUL 12-17, 1998 CL MONTREAL, CANADA SP Transplantat Soc ID T-CELLS; TYROSINE PHOSPHORYLATION; TCR DESENSITIZATION; HTLV-I; ACTIVATION; GP120; PROLIFERATION; INHIBITION; ANTIBODY; PATHWAY C1 Tulane Univ, Med Ctr, Div Pediat Nephrol, New Orleans, LA USA. Univ S Alabama, Div Nephrol, Mobile, AL 36688 USA. NIDR, Cellular Dev & Oncol Lab, Rockville, MD USA. NCI, Lab Leukocyte Biol, Frederick, MD 21701 USA. RP Goebel, J (reprint author), Univ Kentucky, Kentucky Clin, Sect Pediat Nephrol, Div Pediat Nephrol, Room J460, Lexington, KY 40536 USA. FU NIAID NIH HHS [AI 30732] NR 16 TC 7 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1999 VL 31 IS 1-2 BP 822 EP 824 DI 10.1016/S0041-1345(98)01788-6 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 173BG UT WOS:000078960600366 PM 10083357 ER PT J AU Wu, A Esnaola, NF Yamada, K Awwad, M Shimizu, A Huang, C Wain, J Zhao, Y Neville, DM Cooper, DKC Sykes, M Sachs, DH AF Wu, A Esnaola, NF Yamada, K Awwad, M Shimizu, A Huang, C Wain, J Zhao, Y Neville, DM Cooper, DKC Sykes, M Sachs, DH TI Xenogeneic thymic transplantation in a pig-to-nonhuman primate model SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVIIth World Congress of the Transplantation-Society CY JUL 12-17, 1998 CL MONTREAL, CANADA SP Transplantat Soc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Biotransplant Inc, Boston, MA USA. NIH, Bethesda, MD 20892 USA. RP Sachs, DH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [P0I AI39755] NR 1 TC 8 Z9 8 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 FEB-MAR PY 1999 VL 31 IS 1-2 BP 957 EP 957 DI 10.1016/S0041-1345(98)01854-5 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 173BG UT WOS:000078960600433 PM 10083424 ER PT J AU Aravind, L Dixit, VM Koonin, EV AF Aravind, L Dixit, VM Koonin, EV TI The domains of death: evolution of the apoptosis machinery SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID PROGRAMMED CELL-DEATH; SIGNALING COMPLEX; KAPPA-B; RETINOBLASTOMA PROTEIN; ELEGANS CED-4; KINASE; RECEPTOR; FAMILY; ACTIVATION; MEDIATORS AB Recent progress in research into programmed cell death has resulted in the identification of the principal protein domains involved in this process. The evolution of many of these domains can be traced back in evolution to unicellular eukaryotes or even bacteria, where the domains appear to be involved in other regulatory functions, Cell-death systems in animals and plants share several conserved domains, in particular the family of apoptotic ATPases; this allows us to suggest a plausible, even if still incomplete, scenario for the evolution of apoptosis, C1 NIH, NCBI, Natl Lib Med, Bethesda, MD 20894 USA. Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. Genentech Inc, Dept Mol Oncol, S San Francisco, CA 94080 USA. RP Aravind, L (reprint author), NIH, NCBI, Natl Lib Med, Bethesda, MD 20894 USA. RI dixit, vishva/A-4496-2012 OI dixit, vishva/0000-0001-6983-0326 NR 53 TC 295 Z9 305 U1 3 U2 22 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD FEB PY 1999 VL 24 IS 2 BP 47 EP 53 DI 10.1016/S0968-0004(98)01341-3 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 180VU UT WOS:000079406500003 PM 10098397 ER PT J AU Ellenberg, J Lippincott-Schwartz, J Presley, JF AF Ellenberg, J Lippincott-Schwartz, J Presley, JF TI Dual-colour imaging with GFP variants SO TRENDS IN CELL BIOLOGY LA English DT Article ID GREEN-FLUORESCENT PROTEIN; TO-GOLGI TRANSPORT; LIVING CELLS; DYNAMICS AB Green fluorescent protein(GFP) has become an important tool in cell biology and is widely used as a reporter far imaging intracellular proteins and structures in live cells. Recently, spectral variants of GFP with red- and blue-shifted fluorescence emissions have been characterized, opening the possibility of double labelling with two different-coloured GFP fusion proteins. This article reviews recent advances in this technique, with special emphasis on time-lapse imaging applications in living cells. C1 Inst Child Hlth & Human Dev, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Ellenberg, J (reprint author), Inst Child Hlth & Human Dev, Cell Biol & Metab Branch, Bldg 18T,Rm 101, Bethesda, MD 20892 USA. EM jpresley@helix.nih.gov RI Ellenberg, Jan/I-4688-2014 OI Ellenberg, Jan/0000-0001-5909-701X NR 31 TC 102 Z9 108 U1 2 U2 15 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD FEB PY 1999 VL 9 IS 2 BP 52 EP 56 DI 10.1016/S0962-8924(98)01420-2 PG 5 WC Cell Biology SC Cell Biology GA 180ZT UT WOS:000079416700004 PM 10087618 ER PT J AU Curcio, MJ Garfinkel, DJ AF Curcio, MJ Garfinkel, DJ TI New lines of host defense: inhibition of Ty1 retrotransposition by Fus3p and NER/TFIIH SO TRENDS IN GENETICS LA English DT Editorial Material ID SACCHAROMYCES-CEREVISIAE; GENE; RECOMBINATION; RETROVIRUS; YEAST; DROSOPHILA; GYPSY AB The genomes of all organisms examined contain transposons whose uncontrolled movement threatens genome function. Fortunately, host cells have evolved defense mechanisms to minimize the level of transposition. In this review we discuss recent work showing that proteins involved in signal transduction and RNA transcription/DNA repair inhibit Ty1 retrotransposition in the yeast Saccharomyces cerevisiae. On the basis of these examples, we hypothesize that the level of Ty1 retrotransposition may be modulated in response to environmental stress signals that affect cellular differentiation and DNA repair. C1 SUNY Albany, Sch Publ Hlth, Wadsworth Ctr, Mol Genet Program, Albany, NY 12201 USA. NCI, Frederick Canc Res & Dev Ctr, Movable Genet Elements Sect, Gene Regulat & Chromosome Biol Lab,ABL Basic Res, Frederick, MD 21702 USA. RP Curcio, MJ (reprint author), SUNY Albany, Sch Publ Hlth, Wadsworth Ctr, Mol Genet Program, POB 22002, Albany, NY 12201 USA. EM joan.curcio@wadsworth.org; garfinke@mail.mcifcrf.gov OI Curcio, M. Joan/0000-0001-5361-3909 FU NIGMS NIH HHS [GM52072, R01 GM052072] NR 19 TC 39 Z9 40 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD FEB PY 1999 VL 15 IS 2 BP 43 EP 45 DI 10.1016/S0168-9525(98)01643-6 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 181AX UT WOS:000079419400001 PM 10098404 ER PT J AU Simonds, WF AF Simonds, WF TI G protein regulation of adenylate cyclase SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID BETA-GAMMA-SUBUNITS; HETEROTRIMERIC G-PROTEINS; PHORBOL ESTER TREATMENT; CRYSTAL-STRUCTURE; KINASE-C; SIGNAL-TRANSDUCTION; MOLECULAR-CLONING; RAT-BRAIN; SF9 CELLS; IN-VIVO AB Adenylate cyclase integrates positive and negative signals that act th rough G protein-coupled cell-surface receptors with other extracellular stimuli to finely regulate levels of cAMP within the cell. Recently,the structures of the cyclase catalytic core complexed with the plant diterpene forskolin, and a cyclase-forskolin complex bound to an activated form of the stimulatory G protein subunit G(s)alpha have been solved by X-ray crystallography. These structures provide a wealth of detail about how different signals could converge at the core cyclase domains to regulate catalysis. In this article, William Simonds reviews recent advances in the molecular and structural biology of this key regulatory enzyme, which provide new insight into its ability to integrate multiple signals in diverse cellular contexts. C1 NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Simonds, WF (reprint author), NIDDK, Metab Dis Branch, NIH, Bldg 10,Room 8C-101,10 Ctr Dr,MSC 1752, Bethesda, MD 20892 USA. NR 79 TC 153 Z9 155 U1 2 U2 11 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD FEB PY 1999 VL 20 IS 2 BP 66 EP 73 DI 10.1016/S0165-6147(99)01307-3 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 180ZM UT WOS:000079416200008 PM 10101967 ER PT J AU Nagai, Y Fleg, JL Kemper, MK Rywik, TM Earley, CJ Metter, EJ AF Nagai, Y Fleg, JL Kemper, MK Rywik, TM Earley, CJ Metter, EJ TI Carotid arterial stiffness as a surrogate for aortic stiffness: Relationship between carotid artery pressure-strain elastic modulus and aortic pulse wave velocity SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE common carotid artery; aorta; stiffness; ultrasonics ID TREATED HYPERTENSIVE PATIENTS; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; SYSTEMIC ARTERIES; ABDOMINAL-AORTA; BLOOD-PRESSURE; RISK FACTOR; B-MODE; DISTENSIBILITY; AGE AB Common carotid arterial (CCA) stiffness can be assessed during carotid ultrasonography, but its association with aortic stiffness, a well-defined cardiovascular risk factor, has not been clarified. This study examines the relationship between CCA and aortic stiffness. CCA pressure-strain elastic modulus (Ep) and aortic pulse wave velocity (APWV) were evaluated in 110 healthy volunteers (age 56.2 +/- 14.6 y) by B-mode and Doppler ultrasonography. CCA Ep increased linearly with age and was higher in men than in women (model r(2) 0.50, p < 0.001). APWV increased quadratically with age (model r(2) = 0.54, p < 0.001), similarly for women and men. Both CCA Ep and APWV were linearly associated with systolic blood pressure (BP) (r = 0.53 and 0.46, respectively) but not with diastolic BP, A linear relationship was found between CCA Ep and APWV (APWV = 194.7 + 5.67 x Ep [model r(2) = 0.42, p < 0.001]). CCA Ep was associated with APWV (p < 0.001) independent of age, gender, and BP (model r(2) = 0.62, p < 0.001), and the most parsimonious model to explain APWV included CCA Ep and age (APWV = 601.73 - 15.64 x age + 0.223 x age(2) + 2.69 x Ep [model r(2) = 0.60, p < 0.001]), Thus, CCA Up is moderately associated with APWV, CCA stiffness as assessed by B-mode may be useful as a surrogate for aortic stiffness. (C) 1999 World Federation for Ultrasound in Medicine & Biology. C1 NIA, NIH, Gerontol Res Ctr, Longitudinal Studies Sect,Lab Clin Invest, Baltimore, MD 21224 USA. NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Dept Neurol, Bayview Med Ctr, Baltimore, MD 21218 USA. RP Metter, EJ (reprint author), NIA, NIH, Gerontol Res Ctr, Longitudinal Studies Sect,Lab Clin Invest, Box 06,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 40 TC 47 Z9 48 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD FEB PY 1999 VL 25 IS 2 BP 181 EP 188 DI 10.1016/S0301-5629(98)00146-X PG 8 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 175XR UT WOS:000079121800003 PM 10320307 ER PT J AU Sanda, MG Smith, DC Charles, LG Hwang, C Pienta, KJ Schlom, J Milenic, D Panicali, D Montie, JE AF Sanda, MG Smith, DC Charles, LG Hwang, C Pienta, KJ Schlom, J Milenic, D Panicali, D Montie, JE TI Recombinant vaccinia-PSA [PROSTVAC] can induce a prostate-specific immune response in androgen-modulated human prostate cancer SO UROLOGY LA English DT Article ID ANTIGEN; VIRUS; SUPPRESSION AB Objectives. Prostate cancer recurrence, evidenced by rising prostate-specific antigen (PSA) levels after radical prostatectomy, is an increasingly prevalent clinical problem in need of new treatment options. Preclinical studies have suggested that for tumors in general, settings of minimal cancer volume may be uniquely suitable for recombinant vaccine therapy targeting tumor-associated antigens. A clinical study was undertaken to evaluate the safety and biologic effects of vaccinia-PSA (PROSTVAC) administered to subjects with postprostatectomy recurrence of prostate cancer and to assess the feasibility of interrupted androgen deprivation as a tool for modulating expression of the vaccine target antigen, as well as detecting vaccine bioactivity in vivo. Methods. A limited Phase I clinical trial was conducted to evaluate the safety and biologic effects of vaccinia-PSA administered in 6 patients with androgen-modulated recurrence of prostate cancer after radical prostatectomy. End points included toxicity, serum PSA rise related to serum testosterone restoration, and immunologic effects measured by Western blot analysis for anti-PSA antibody induction. Results. Toxicity was minimal, and dose-limiting toxicity was not observed. Noteworthy variability in time required for testosterone restoration (after interruption of androgen deprivation therapy) was observed. One subject showed continued undetectable serum PSA (less than 0.2 ng/mL) for over 8 months after testosterone restoration, an interval longer than those reported in previous androgen deprivation interruption studies. Primary anti-PSA Ige antibody activity was induced after vaccinia-PSA immunization in subject, although such antibodies were detectable in several subjects at baseline. Conclusions. Interrupted androgen deprivation may be a useful tool for modulating prostate cancer bioactivity in clinical trials developing novel biologic therapies. Immune responses against PSA may be present among some patients with prostate cancer at baseline and may be induced in others through vaccinia-PSA immunization. (C) 1999, Elsevier Science Inc. All rights reserved. C1 Univ Michigan, Sch Med, Dept Urol Surg, Ann Arbor, MI USA. Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI USA. Vet Adm Med Ctr, Surg Serv, Ann Arbor, MI 48105 USA. Univ Michigan, Sch Med, Dept Med Oncol, Ann Arbor, MI 48109 USA. NCI, Div Basic Sci, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. Therion Biol Corp, Cambridge, MA USA. RP Sanda, MG (reprint author), Univ Michigan, Taubman Ctr 2916, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. RI Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015; Pienta, Kenneth/E-7679-2015 OI Pienta, Kenneth/0000-0002-4138-2186 FU NCI NIH HHS [1P50 CA69568, R29 CA71532-01]; NCRR NIH HHS [M01-RR00042] NR 17 TC 132 Z9 134 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD FEB PY 1999 VL 53 IS 2 BP 260 EP 266 DI 10.1016/S0090-4295(98)00539-1 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 160FL UT WOS:000078219700003 PM 9933036 ER PT J AU Walther, MM Keiser, HR Linehan, WM AF Walther, MM Keiser, HR Linehan, WM TI Pheochromocytoma: evaluation, diagnosis, and treatment SO WORLD JOURNAL OF UROLOGY LA English DT Article ID HIPPEL-LINDAU DISEASE; BILATERAL PHEOCHROMOCYTOMAS; LAPAROSCOPIC ADRENALECTOMY; LOCALIZATION; MANAGEMENT; TUMORS; PARAGANGLIOMAS; SCINTIGRAPHY; PREVALENCE; MIBG AB Pheochromocytoma is a catecholamine-producing tumor of the sympathetic nervous system. Signs and symptoms are generally related to catecholamine excess; these include hypertension, sweating, palpitatione, headaches, and anxiety attacks. Abdominal imaging and 24-h urine collection for catecholamines are usually be sufficient for diagnosis. Catecholamine blockade with phenoxybenzamine and metyrosine generally ameliorates symptoms and is necessary to prevent hypertensive crisis during surgery. Standard treatment is laparoscopic adrenalectomy, although partial adrenalectomy is gaining enthusiastic support in familial forms of pheochromocytoma. C1 NCI, Urol Oncol Branch, DCS, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Walther, MM (reprint author), NCI, Urol Oncol Branch, DCS, NIH, Bldg 10,Room 2B-43,10 Ctr Dr MSC 1501, Bethesda, MD 20892 USA. NR 47 TC 71 Z9 79 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0724-4983 J9 WORLD J UROL JI World J. Urol. PD FEB PY 1999 VL 17 IS 1 BP 35 EP 39 DI 10.1007/s003450050102 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 174AD UT WOS:000079011200008 PM 10096149 ER PT J AU Marth, T Kelsall, BL Strober, W Zeitz, M AF Marth, T Kelsall, BL Strober, W Zeitz, M TI Mechanisms and applications of oral tolerance SO ZEITSCHRIFT FUR GASTROENTEROLOGIE LA German DT Review DE oral tolerance; T helper cell; IL-12; IFN-gamma; transgenic mice; apoptosis; active suppression; autoimmunity; therapy ID MYELIN BASIC-PROTEIN; GROWTH-FACTOR-BETA; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; COLLAGEN-INDUCED ARTHRITIS; INFLAMMATORY BOWEL-DISEASE; SUPPRESSOR T-CELLS; DELAYED-TYPE HYPERSENSITIVITY; RESIDENT INTESTINAL FLORA; MEDIATED IMMUNE-RESPONSES; NONOBESE DIABETIC MICE AB The term oral tolerance (OT) describes the antigen-specific suppression of immune responses following the feeding of the antigen. While some common features with other forms of induction of systemic tolerance have been disclosed, OT can be distinguished by certain immunologic characteristics. Thus, work in experimental animal models revealed the importance of intestinal antigen processing, especially antigen processing in the Peyer's patches, in inducing OT. It has become clear that suppressive T cell cytokines derived from mucosal sites play a major role in mediating OT. The variation of the dose of fed antigen and the modulation of the cytokine milieu both have influences on the underlying immunologic mechanisms active suppression, clonal anergy and clonal deletion folio-wing oral antigen uptake. In several animal models of autoimmunity the disease activity can be suppressed by feeding oral autoantigen. Based on these results, recent clinical studies have begun to explore OT as a means to treat autoimmune disorders such as multiple sclerosis, rheumatoid arthritis and diabetes. C1 Univ Saarlandes Kliniken, D-66421 Homburg, Germany. Natl Inst Hlth, Clin Invest Lab, Mucosal Immun Sect, Bethesda, MD USA. RP Marth, T (reprint author), Univ Saarlandes Kliniken, D-66421 Homburg, Germany. NR 179 TC 5 Z9 6 U1 1 U2 1 PU DEMETER VERLAG GEORG THIEME VERLAG PI STUTTGART PA Z HD PETRA SCHAECHE, RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0044-2771 J9 Z GASTROENTEROL JI Z. Gastroent. PD FEB PY 1999 VL 37 IS 2 BP 165 EP 185 PG 21 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 172VT UT WOS:000078946500006 PM 10190250 ER PT J AU Strasser, A Yasuma, Y Stanimirovic, DB McCarron, RM Spatz, M AF Strasser, A Yasuma, Y Stanimirovic, DB McCarron, RM Spatz, M TI Pathophysiologic effects of nitric oxide (NO) and endothelin-1 in the gerbil model of gobal ischemia - a survey SO ZEITSCHRIFT FUR GERONTOLOGIE UND GERIATRIE LA German DT Article DE nitric oxide; endothelin-1; ischemia; brain; edema ID FOCAL CEREBRAL-ISCHEMIA; L-ARGININE; DOPAMINE RELEASE; STRIATAL DOPAMINE; BRAIN-DAMAGE; BLOOD-FLOW; SYSTEM AB These studies were performed in an attempt to clarify some of the pathophysiologic mechanisms which occur during and after global ischemia. Both nitric oxide and endothelin were demonstrated in gerbils to participate in responses to ischemia. It was shown that endogenous nitric oxide influences early postischemic reperfusion, systemic blood pressure and postischemic dopamine metabolism. Furthermore, the results indicated that nitric oxide played a role in dopamine release and that preischemic intracerebral nitric oxide formation significantly decreased ischemic dopamine release. In addition, ischemic release of endothelin-l was detected; participation of nitric oxide in this release was observed. Further indication of functional interactions between nitric oxide and endothelin-l in postischemic reperfusion were indicated by observations that endothelin-l antagonists inhibited early hypoperfusion caused by Nitro-L-arginin and late hypoperfusion caused by endogenous endothelin-l. Nitric oxide was shown to decrease edema formation during the early postischemic period but contribute to edema formation during the late postischemic period. The findings indicate the importance of nitric oxide in stroke and ischemia. C1 VMU Wien, Inst Physiol, Abt Expt Gerontol, A-1210 Vienna, Austria. NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Strasser, A (reprint author), VMU Wien, Inst Physiol, Abt Expt Gerontol, J Baumann Gasse 1, A-1210 Vienna, Austria. NR 30 TC 2 Z9 2 U1 0 U2 1 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PLATZ DER DEUTSCHEN EINHEIT 25, D-64293 DARMSTADT, GERMANY SN 0044-281X J9 Z GERONTOL GERIATR JI Z. Gerontol. Geriatr. PD FEB PY 1999 VL 32 IS 1 BP 33 EP 40 DI 10.1007/s003910050079 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 200BP UT WOS:000080519400006 PM 10408023 ER PT J AU Hutz, RJ Wimpee, BAB Dasmahapatra, A Weber, DN Heimler, I Chaffin, CL AF Hutz, RJ Wimpee, BAB Dasmahapatra, A Weber, DN Heimler, I Chaffin, CL TI Differential modulation by aromatic hydrocarbon receptor agonist of circulating estradiol-17 beta and estrogen-receptor DNA-binding capability in female rainbow trout (Oncorhynchus mykiss) SO ZOOLOGICAL SCIENCE LA English DT Article ID STEROID-SECRETION; EXPOSURE; INVITRO; CELLS AB We report alterations in serum estradiol-17 beta (E-2) and hepatic estrogen receptor (ER) DNA-binding activity in female rainbow trout given a single ip injection of 0, 6.25, 12.5, 25, or 50 mg beta-naphthoflavone (BNF)/kg body weight, followed by sacrifice at 24 or 48 hr. BNF affected E-2 in a dichotomous fashion at 24 hr, and reduced E-2 at 48 hr with increasing BNF. DNA binding by ER was decreased in an apparently dose-dependent manner after 24 hr and increased after 48 hr. These data suggest that the regulation of ER by AHR agonists may occur both at the ER promoter, and also secondarily via E-2, and that the differential effects observed are both time and dose dependent. C1 NIEHS, Marine & Freshwater Biomed Sci Ctr, Milwaukee, WI 53204 USA. Univ Wisconsin, Dept Biol Sci, Milwaukee, WI 53211 USA. RP Hutz, RJ (reprint author), NIEHS, Marine & Freshwater Biomed Sci Ctr, Milwaukee, WI 53204 USA. NR 18 TC 10 Z9 10 U1 0 U2 1 PU ZOOLOGICAL SOC JAPAN PI TOKYO PA TOSHIN-BUILDING, HONGO 2-27-2, BUNKYO-KU, TOKYO, 113, JAPAN SN 0289-0003 J9 ZOOL SCI JI Zool. Sci. PD FEB PY 1999 VL 16 IS 1 BP 161 EP 166 PG 6 WC Zoology SC Zoology GA 214NG UT WOS:000081333600023 ER PT J AU Hauser, W Johren, O de Oliveira, AM Shibata, S Saavedra, JM AF Hauser, W Johren, O de Oliveira, AM Shibata, S Saavedra, JM TI Ischemia-induced neuronal cell loss is associated with loss of atypical angiotensin type-1 receptor expression in the gerbil hippocampal formation SO BRAIN RESEARCH LA English DT Article DE angiotensin II receptor expression; in situ hybridization; [I-125]Sar(1)-Ang II; receptor autoradiography; hypoxia; cerebral blood flow; gyrus dentatus; hippocampus ID LONG-TERM POTENTIATION; IN-SITU HYBRIDIZATION; II RECEPTOR; MESSENGER-RNA; RAT-BRAIN; GENE-EXPRESSION; AT(1A); FOREBRAIN; SUBTYPES; DEATH AB The hippocampal formation of MongoIian gerbils expresses high amounts of atypical angiotensin II: type-1 receptors. We studied the expression of these receptors by in situ hybridization using specific 135S]-labeled riboprobes and by receptor autoradiography using [I]Sarcosine(1)-angiotensin II. Angiotensin II receptor mRNA was found in the pyramidaI cell layer of the CA1, CA2 and CA3 subfields, with the highest expression in the CA2 subfield, and in the granular cell layer of the dentate gyrus. Angiotensin II binding was detected in the stratum oriens and stratum radiatum of the CA1 and CA2 subfieIds, in the stratum oriens of the CA3 subfield, and in the molecular layer of the dentate gyrus. We then studied the effect of ischemia on hippocampal angiotensin II receptor expression, 1, 4 and 15 days after bilateral occlusion of the common carotid arteries for 5 min. No changes in angiotensin II receptor mRNA or binding were detected 1 day after ischemia. Delayed, progressive loss of angiotensin II mRNA and binding occurred 4 and 15 days after ischemia, in the CA1, CA2 and CA3 subfields. The decline was faster in the CA1 subfield, and paralleled the loss of neurons after ischemia. In the dentate gyrus, angiotensin II receptor mRNA and angiotensin II binding were not changed when compared to sham operated controls. The decrease of angiotensin II receptor expression may reflect the loss of angiotensin II receptor-producing neurons rather than a down-regulation of receptor expression. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NIMH, Pharmacol Sect, Bethesda, MD 20892 USA. RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, 10 Ctr Dr MSC 1514,Bldg 10,Room 2D-57, Bethesda, MD 20892 USA. EM saavedrj@irp.nimh.nih.gov RI Johren, Olaf/G-6967-2011; maria, ana /G-8106-2014 NR 28 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 30 PY 1999 VL 817 IS 1-2 BP 34 EP 44 DI 10.1016/S0006-8993(98)01193-7 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 159XZ UT WOS:000078201800005 PM 9889309 ER PT J AU Janak, PH Chang, JY Woodward, DJ AF Janak, PH Chang, JY Woodward, DJ TI Neuronal spike activity in the nucleus accumbens of behaving rats during ethanol self-administration SO BRAIN RESEARCH LA English DT Article DE nucleus accumbens; addiction; alcohol; self-administration; striatum; basal ganglia; rat; in vivo electrophysiology; ensemble ID FREELY MOVING RATS; INCREASES DOPAMINE TRANSMISSION; MONKEY CAUDATE NEURONS; VENTRAL STRIATUM; EXTRACELLULAR DOPAMINE; FUNCTIONAL-PROPERTIES; INTRAVENOUS COCAINE; FIRING PATTERNS; DEPENDENT RATS; BASAL GANGLIA AB Many lines of evidence support the importance of the nucleus accumbens (NAC) for ethanol-reinforced behavior. The nature of the neuronal activity that occurs in this region during ethanol self-administration is not known. We recorded from ensembles of single-units primarily located within the shell of the NAC during operant responding for oral ethanol solutions by well-trained rats. Of 90 units recorded from seven sessions from seven rats, 41 (46%) did not exhibit si,significant changes in relation to the experimental events. Of the 49 units (54%) that did exhibit significant phasic changes, alterations in firing rate occurred in relation to the following experimental events: operant response (63%), tone stimulus (20%), and ethanol delivery (63%). In addition, changes in spike activity during the intervals between the three experimental events were noted in 33% of the units. Most units (55% of responsive units) responded to multiple experimental events. Thus different but overlapping populations of neurons in the NAC represent each event that occurs along the temporal dimension of a single trial performed to obtain ethanol reward. The data suggest that the NAC plays a crucial role in Linking together conditioned and unconditioned internal and external stimuli with motor plans to allow for ethanol-seeking behavior to occur. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Wake Forest Univ, Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27157 USA. RP Janak, PH (reprint author), NIDA, Intramural Res Program, Cellular Neurobiol Branch, 550 Nathan Shock Dr, Baltimore, MD 21224 USA. EM panak@intra.nida.nih.gov FU NIAAA NIH HHS [AA-10980, AA-07565] NR 70 TC 36 Z9 37 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 30 PY 1999 VL 817 IS 1-2 BP 172 EP 184 DI 10.1016/S0006-8993(98)01245-1 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 159XZ UT WOS:000078201800020 PM 9889360 ER PT J AU Xu, JL Fagerstrom, RM Prorok, PC AF Xu, JL Fagerstrom, RM Prorok, PC TI Estimation of post-lead-time survival under dependence between lead-time and post-lead-time survival SO STATISTICS IN MEDICINE LA English DT Article ID NONPARAMETRIC-ESTIMATION; NATURAL-HISTORY; SCREENING DATA; CANCER; DISEASE; MORTALITY AB Early detection of cancer by screening advances the date of diagnosis, but may or may not alter time to death. Screening programme need to assess the true benefit of screening, that is, the length of time by which survival has been extended, beyond merely the time by which the diagnosis is advanced (lead-time). One method is to estimate the distribution of the time survived post-lead-time using total survival time data for screen-detected cancer cases, under the assumption of independence of the lead-time and the post-lead-time survival. However, it seems biologically reasonable that the lead-time and the post-lead-time survival are positively correlated. This paper investigates the consequences of departures from independence of lead-time and post-lead-time survival on estimation of post-lead-time survival. We introduce a new model that involves dependence between the lead-time and the post-lead-time survival. We show that the new model can be converted to the model discussed by Xu and Prorok. We consider the non-parametric maximum likelihood estimator of the post-lead-time survival under the new model. We apply the method to data from the HIP (Health Insurance Plan of Greater New York) breast cancer screening trial. We make comparisons with the survival of cancer cases not detected by screening, such as interval cases, cases among individuals who refused screening, and randomized control cases. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 Univ Houston, Dept Math, Houston, TX 77204 USA. NCI, Biometry Branch, Div Canc Prevent, Bethesda, MD 20892 USA. RP Xu, JL (reprint author), Univ Houston, Dept Math, Houston, TX 77204 USA. NR 15 TC 6 Z9 6 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 30 PY 1999 VL 18 IS 2 BP 155 EP 162 DI 10.1002/(SICI)1097-0258(19990130)18:2<155::AID-SIM12>3.0.CO;2-D PG 8 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 158DZ UT WOS:000078101900003 PM 10028136 ER PT J AU Juo, SHH Wyszynski, DF Beaty, TH Huang, HY Bailey-Wilson, JE AF Juo, SHH Wyszynski, DF Beaty, TH Huang, HY Bailey-Wilson, JE TI Mild association between the A/G polymorphism in the promoter of the apolipoprotein A-I gene and apolipoprotein A-I levels: A meta-analysis SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE apo A-I; APOAI gene; polymorphism; meta-analysis; association study; linkage disequilibrium ID CORONARY-ARTERY DISEASE; PLASMA APO-AI; COMBINED HYPERLIPIDEMIA; C-III; REGION; CLUSTER; CIII; ATHEROSCLEROSIS; CHOLESTEROL; SUBSTITUTION AB A polymorphism caused by a G-to-A substitution in the promoter area (-75 bp) of the apolipoprotein AI (apo A-I) bene is common in the general population, Several studies have investigated its association with apo A-I levels, but the results were conflicting. Here, we undertook meta-analyses to increase the statistical power to further detect this association. Meta-analyses were first performed for each gender and then on the combined data. The overall sample in this meta-analysis included over 3,000 healthy individuals. Results from healthy individuals suggest that the rare allele A is associated with mildly increased apo A-I levels by about 5 mg/dl (95% CI 2.84 similar to 6.94). This association is weaker among healthy females than males. The present study cannot determine whether this small but significant association was due to a small genetic effect of the A/G polymorphism, or whether the A/G polymorphism is in linkage disequilibrium with a true mutant allele at a quantitative trait locus controlling apo A-I levels. Although smoking status may interact with genotypes, only three studies investigated this interaction and thus no conclusion could be drawn in this regard. Published 1999 Wiley-Liss, Inc.dagger C1 Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA. Natl Human Genome Res Inst, NIH, Baltimore, MD USA. Univ Buenos Aires, Sch Med, Dept Publ Hlth, Buenos Aires, DF, Argentina. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Juo, SHH (reprint author), Rockefeller Univ, Lab Stat Genet, POB 192,1230 York Ave, New York, NY 10021 USA. EM hjuo@linkage.rockefeller.edu RI Juo, Suh-Hang/A-1765-2010; Juo, Suh-Hang/C-9545-2009; OI Bailey-Wilson, Joan/0000-0002-9153-2920 NR 23 TC 42 Z9 44 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JAN 29 PY 1999 VL 82 IS 3 BP 235 EP 241 DI 10.1002/(SICI)1096-8628(19990129)82:3<235::AID-AJMG8>3.0.CO;2-H PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 163DY UT WOS:000078388800008 PM 10215547 ER PT J AU Feigal, EG AF Feigal, EG TI AIDS-associated malignancies: research perspectives SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Article DE AIDS-associated malignancy; Kaposi's sarcoma; AIDS-associated non-Hodgkin's lymphoma; human herpes virus 8; Epstein-Barr virus; papilloma virus; cancer epidemiology; cancer treatment; National Cancer Institute ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; NON-HODGKINS-LYMPHOMA; HUMAN CHORIONIC-GONADOTROPIN; IMMUNE-DEFICIENCY-SYNDROME; EPIDEMIC KAPOSIS-SARCOMA; NERVOUS-SYSTEM LYMPHOMA; DNA-SEQUENCES; HUMAN PAPILLOMAVIRUS; HUMAN HERPESVIRUS-8; RANDOMIZED TRIAL AB The appearance in 1981 of a usually rare malignancy, Kaposi's sarcoma, in homosexual men [1] was one of the first harbingers of an epidemic caused by a retrovirus, human immunodeficiency virus (HIV), which causes the acquired immunodeficiency syndrome (AIDS). Lymphoid and other malignancies were also increased, most strikingly non-Hodgkin's lymphoma and primary central nervous system (CNS) lymphoma. Advances in molecular biology, immunology, virology, and anti-viral therapy have combined to create unique research opportunities. One developing theme is the role of viral coinfection and malignancy. Human herpes virus 8 (HHV8), Epstein-Barr virus (EBV) and papilloma virus each may have a causal role in the development of HIV-associated malignancy. New antiretroviral therapies are able to substantially reverse or delay the profound immunosuppression of HIV infection. The changes in the epidemiology of malignancies, and understanding the mechanism of action of these new therapeutics provide research opportunities to understand the pathogenesis of these malignancies. The opportunities to discover the consequences of T-cell based immunodeficiency and the interactions with specific viral pathogens will likely lead to progress in HIV treatment and new strategies for other malignancies. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Feigal, EG (reprint author), NCI, Div Canc Treatment & Diag, Bldg 31,Room 3A44,NIH Campus, Bethesda, MD 20892 USA. EM feigale@dctod.nci.nih.gov NR 76 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD JAN 29 PY 1999 VL 1423 IS 1 BP C1 EP C9 DI 10.1016/S0304-419X(98)00033-X PG 9 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA 161EV UT WOS:000078276700004 PM 9989205 ER PT J AU Lowy, DR Schiller, JT AF Lowy, DR Schiller, JT TI Papillomaviruses: prophylactic vaccine prospects SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review ID VIRUS-LIKE PARTICLES; COTTONTAIL RABBIT PAPILLOMAVIRUS; L2 CAPSID PROTEINS; BOVINE PAPILLOMAVIRUS; CERVICAL-CANCER; L1 PROTEIN; NEUTRALIZING ANTIBODIES; INSECT CELLS; E6 PROTEINS; TYPE-16 C1 NCI, Div Basic Sci, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Lowy, DR (reprint author), NCI, Div Basic Sci, Cellular Oncol Lab, Bldg 36,Room ID32, Bethesda, MD 20892 USA. NR 60 TC 37 Z9 39 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD JAN 29 PY 1999 VL 1423 IS 1 BP M1 EP M8 DI 10.1016/S0304-419X(98)00037-7 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA 161EV UT WOS:000078276700001 PM 9989208 ER PT J AU Strickler, HD Kirk, GD Figueroa, JP Ward, E Braithwaite, AR Escoffery, C Drummond, J Goebel, B Waters, D McClimens, R Manns, A AF Strickler, HD Kirk, GD Figueroa, JP Ward, E Braithwaite, AR Escoffery, C Drummond, J Goebel, B Waters, D McClimens, R Manns, A TI HPV 16 antibody prevalence in Jamaica and the United States reflects differences in cervical cancer rates SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HUMAN-PAPILLOMAVIRUS TYPE-16; VIRUS-LIKE PARTICLES; INTRAEPITHELIAL NEOPLASIA; RISK WOMEN; INFECTION; DETERMINANTS; COLOMBIA; COHORT; SPAIN; AGE AB Human papillomavirus (HPV) is widely accepted as the primary etiologic agent in the development of cervical cancer. DNA of a particular HPV type, HPV 16, is found in about half of tumors tested. Inconsistent with this causal relationship, however, population-based studies of HPV DNA prevalence have often failed to find high rates of anogenital HPV infection in countries with high cervical cancer rates. To examine this issue, we used serology to compare HPV 16 exposure in healthy volunteer blood donors in the United States (n = 278) and similar subjects from a country with 3-fold higher cervical cancer rates, Jamaica (n = 257). Jamaican sexually transmitted disease (STD) patients (n = 831) were also studied to examine in detail the relation of HPV 16 antibodies with sexual history. Serology was conducted using an ELISA employing HPV 16 virus-like particles (VLPs). Age-adjusted seroprevalence rates were greatest among male (29%) and female (42%) STD patients, intermediate in male (19%) and female (24%) Jamaican blood donors and lowest among male (3%) and female (12%) U.S. blood donors. The higher seroprevalence in women was significant, and prevalence tended to increase with age. In multivariate logistic regression, controlling for age and gender, Jamaican blood donors were 4.2-fold (95% CI 2.4-7.2) and STD patients 8.1-fold (95% CI 5.0-13.2) more likely to have HPV 16 VLP antibodies than U.S. blood donors. Among STD patients, HPV 16 antibodies were associated with lifetime number of sex partners and years of sexual activity, as well as other factors. Our data suggest that HPV 16 VLP antibodies are strongly associated with sexual behavior. Moreover, exposure to HPV 16 appears to be much greater in Jamaica than in the United States, consistent with the high rate of cervical cancer in Jamaica. Published 1999 Wiley-Liss, Inc.dagger. C1 NCI, Viral Epidemiol Branch, NIH, EPN, Bethesda, MD 20892 USA. Jamaican Minist Hlth, Epidemiol Unit, Kingston, Jamaica. Univ W Indies, Dept Pathol, Kingston 7, Jamaica. SAIC, Frederick, MD USA. Informat Management Serv, Rockville, MD USA. RP Strickler, HD (reprint author), NCI, Viral Epidemiol Branch, NIH, EPN, Room 434, Bethesda, MD 20892 USA. RI Kirk, Gregory/A-8484-2009 NR 23 TC 31 Z9 35 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 29 PY 1999 VL 80 IS 3 BP 339 EP 344 DI 10.1002/(SICI)1097-0215(19990129)80:3<339::AID-IJC1>3.0.CO;2-F PG 6 WC Oncology SC Oncology GA 152NB UT WOS:000077782700001 PM 9935171 ER PT J AU Venkatachalam, KV Fuda, H Koonin, EV Strott, CA AF Venkatachalam, KV Fuda, H Koonin, EV Strott, CA TI Site-selected mutagenesis of a conserved nucleotide binding HXGH motif located in the ATP sulfurylase domain of human bifunctional 3 '-phosphoadenosine 5 '-phosphosulfate synthase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; ARABIDOPSIS-THALIANA; SULFATE ACTIVATION; SEQUENCE; IDENTIFICATION; ALIGNMENT; PROTEIN; CLONING; REGION; KINASE AB 3'-Phosphoadenosine-5'-phosphosulfate (PAPS) synthase is a bifunctional protein consisting of an NH,terminal APS kinase and a COOH-terminal ATP sulfurylase. Both catalytic activities require ATP; the APS kinase domain involves cleavage of the beta-gamma phosphodiester bond of ATP, whereas the ATP sulfurylase domain involves cleavage of the alpha-beta phosphodiester bond of ATP. Previous mutational studies have suggested that beta-gamma phosphodiesterase activity involves a highly conserved NTP-binding P-loop motif located in the adenosine-5'-phosphosulfate kinase domain of PAPS syntheses. Sequence alignment analysis of PAPS synthases and the superfamily of TagD-related nucleotidylyltransferases revealed the presence of a highly conserved HXGH motif in the ATP sulfurylase domain of PAPS synthases, a motif implicated in the alpha-beta phosphodiesterase activity of cytidylyltransferases. Thus, site-selected mutagenesis of the HXGH motif in the ATP sulfurylase domain of human PAPS synthase (amino acids 425-428) was performed to examine this possibility. Either H425A or H428A mutation produced an inactive enzyme. In contrast, a N426K mutation resulted in increased enzymatic activity. A G427A single mutant resulted in only a modest 30% reduction in catalytic activity, whereas a G427A/H428A double mutant produced an inactive enzyme. These results suggest an important role for the HXGH histidines in the ATP sulfurylase activity of bifunctional PAPS synthase and support the hypothesis that the highly conserved HXGH motif found in the ATP sulfurylase domain of PAPS synthases is involved in ATP binding and alpha-beta phosphodiesterase activity. C1 NICHD, Sect Steroid Regulat, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Strott, CA (reprint author), NICHD, Sect Steroid Regulat, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Rm 6A36, Bethesda, MD 20892 USA. EM chastro@box-c.nih.gov NR 24 TC 29 Z9 31 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 29 PY 1999 VL 274 IS 5 BP 2601 EP 2604 DI 10.1074/jbc.274.5.2601 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 161ZB UT WOS:000078319500003 PM 9915785 ER PT J AU Bascom, RA Srinivasan, S Nussbaum, RL AF Bascom, RA Srinivasan, S Nussbaum, RL TI Identification and characterization of Golgin-84, a novel Golgi integral membrane protein with a cytoplasmic coiled-coil domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RET-II ONCOGENE; ENDOPLASMIC-RETICULUM; TRANSMEMBRANE DOMAINS; VESICLE DOCKING; SEQUENCES; COMPLEX; RECOGNITION; APPARATUS; RECEPTORS; RETENTION AB The cytoplasmic face of the Golgi contains a variety of proteins with coiled-coil domains. We identified one such protein in a yeast two hybrid screen, using as bait the peripheral Golgi phosphatidylinositol(4,5)P-2 8-phosphatase OCRL1 that is implicated in a human disease, the oculocerebrorenal syndrome. The similar to 2.8-kilobase mRNA is ubiquitously expressed and abundant in testis; it encodes a 731-amino acid protein with a predicted mass of 83 kDa. Antibodies against the sequence detect a novel similar to 84-kDa Golgi protein we termed golgin-84. Golgin-84 is an integral membrane protein with a single transmembrane domain close to its C terminus. In vitro, the protein inserts post-translationally into microsomal membranes with an N-cytoplasmic and C-lumen orientation. Cross-linking indicates that golgin-84 forms dimers, consistent with the prediction of an similar to 400-residue dimerizing coiled coil domain in its N terminus. The dimerization potential is supported by a data base search that showed that the N-terminal 497 residues of golgin-84 contain a coiled-coil domain that when fused to the RET tyrosine kinase domain had the ability to activate it, forming the RET-II oncogene. Data base searching also indicates golgin-84 is similar in structure and sequence to giantin, a membrane protein that tethers coatamer complex I vesicles to the Golgi. C1 NHGRI, GDRB, NIH, Bethesda, MD 20892 USA. RP Nussbaum, RL (reprint author), NHGRI, GDRB, NIH, 49 Convent Dr, Bethesda, MD 20892 USA. NR 46 TC 72 Z9 74 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 29 PY 1999 VL 274 IS 5 BP 2953 EP 2962 DI 10.1074/jbc.274.5.2953 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 161ZB UT WOS:000078319500051 PM 9915833 ER PT J AU Minnick, DT Bebenek, K Osheroff, WP Turner, RM Astatke, M Liu, LX Kunkel, TA Joyce, CM AF Minnick, DT Bebenek, K Osheroff, WP Turner, RM Astatke, M Liu, LX Kunkel, TA Joyce, CM TI Side chains that influence fidelity at the polymerase active site of Escherichia coli DNA polymerase I (Klenow fragment) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID REVERSE-TRANSCRIPTASE; FRAMESHIFT FIDELITY; THUMB SUBDOMAIN; PROCESSIVITY; REPLICATION; PROTEINS; MUTANT AB To investigate the interactions that determine DNA polymerase accuracy, we have measured the fidelity of 26 mutants with amino acid substitutions in the polymerase domain of a 3'-5'-exonuclease-deficient Klenow fragment. Most of these mutant polymerases synthesized DNA with an apparent fidelity similar to that of the wild-type control, suggesting that fidelity at the polymerase active site depends on highly specific enzyme-substrate interactions and is not easily perturbed. In addition to the previously studied Y766A mutator, four novel base substitution mutators were identified; they are R668A R682A, E710A, and N845A, Each of these five mutator alleles results from substitution of a highly conserved amino acid side chain located on the exposed surface of the polymerase cleft near the polymerase active site. Analysis of base substitution errors at four template positions indicated that each of the five mutator polymerases has its own characteristic error specificity, suggesting that the Arg-668, Arg-682, Glu-710, Tyr-766, and Asn-845 side chains may contribute to polymerase fidelity in a variety of different ways. We separated the contributions of the nucleotide insertion and mismatch extension steps by using a novel fidelity assay that scores base substitution errors during synthesis to fill a single nucleotide gap land hence does not require mismatch extension) and by measuring the rates of polymerase-catalyzed mismatch extension reactions. The R682A, E710A, Y766A and N845A mutations cause decreased fidelity at the nucleotide insertion step, whereas R668A results in lower fidelity in both nucleotide insertion and mismatch extension. Relative to wild type, several Klenow fragment mutants showed substantially more discrimination against extension of a TG mismatch under the conditions of the fidelity assay, providing one explanation for the anti-mutator phenotypes of mutants such as R754A and Q849A. C1 Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Joyce, CM (reprint author), Yale Univ, Dept Mol Biophys & Biochem, 266 Whitney Ave,POB 208114, New Haven, CT 06520 USA. EM catherine.joyce@yale.edu FU NIGMS NIH HHS [GM-28550, 5-F31 GM-18508] NR 34 TC 97 Z9 97 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 29 PY 1999 VL 274 IS 5 BP 3067 EP 3075 DI 10.1074/jbc.274.5.3067 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 161ZB UT WOS:000078319500064 PM 9915846 ER PT J AU Slavik, JM Hutchcroft, JE Bierer, BE AF Slavik, JM Hutchcroft, JE Bierer, BE TI CD80 and CD86 are not equivalent in their ability to induce the tyrosine phosphorylation of CD28 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL ANTIGEN RECEPTOR; VAV PROTOONCOGENE PRODUCT; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL-TRANSDUCTION; T-LYMPHOCYTES; COSTIMULATORY RECEPTOR; KINASE SUBSTRATE; B7-2 REGULATION; CLONAL ANERGY; ACTIVATION C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Purdue Univ, Dept Biochem, W Lafayette, IN 47907 USA. RP Bierer, BE (reprint author), NHLBI, Bldg 10,Rm 5D49,10 Ctr Dr, Bethesda, MD 20892 USA. EM BiererB@nih.gov NR 54 TC 40 Z9 45 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 29 PY 1999 VL 274 IS 5 BP 3116 EP 3124 DI 10.1074/jbc.274.5.3116 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 161ZB UT WOS:000078319500068 PM 9915850 ER PT J AU Zhong, M Kim, SJ Wu, C AF Zhong, M Kim, SJ Wu, C TI Sensitivity of Drosophila heat shock transcription factor to low pH SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING ACTIVITY; HEMAGGLUTININ MEMBRANE GLYCOPROTEIN; GENE-TRANSCRIPTION; ACTIVATION DOMAIN; INTRACELLULAR PH; INFLUENZA-VIRUS; COILED-COIL; TRANSACTIVATION DOMAIN; NUCLEAR-LOCALIZATION; PROTEIN-SYNTHESIS AB The heat shock transcription factor (HSF) mediates the induction of heat shock gene expression. The activation of HSF involves heat shock-induced trimerization, binding to its cognate DNA sites, and the acquisition of transcriptional competence. In this study, the oligomeric properties of Drosophila HSF were analyzed by equilibrium analytical ultracentrifugation and gel filtration chromatography. Previous findings showed that trimerization of purified Drosophila HSF was directly sensitive to heat and oxidation (1). Here we report that low pH, in the physiological range, also directly induces HSF trimerization and DNA binding in vitro. Furthermore, the induction of HSF trimerization by low pH is synergistic with the actions of heat and oxidation, Since heat or chemical stress leads to a moderate decrease of intracellular pH, we suggest that intracellular acidification may contribute to activating the heat shock response in vivo. C1 NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wu, C (reprint author), NCI, Mol Cell Biol Lab, NIH, Bldg 37,Rm 5E26, Bethesda, MD 20892 USA. RI yu, yan/C-2322-2012 NR 69 TC 25 Z9 25 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 29 PY 1999 VL 274 IS 5 BP 3135 EP 3140 DI 10.1074/jbc.274.5.3135 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 161ZB UT WOS:000078319500070 PM 9915852 ER PT J AU Mittelstadt, PR Ashwell, JD AF Mittelstadt, PR Ashwell, JD TI Role of Egr-2 in up-regulation of Fas ligand in normal T cells and aberrant double-negative lpr and gld T cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RETINOIC ACID; TRANSCRIPTION FACTORS; CYCLOSPORINE-A; LYMPHOPROLIFERATIVE DISORDERS; TYROSINE PHOSPHORYLATION; DIFFERENTIAL REGULATION; GENE-MUTATIONS; LPR/LPR MICE; FAMILY GENE; NGFI-A AB We previously identified a Fas ligand regulatory element (FLRE) in the Fas ligand (fasL) promoter that binds Egr family proteins and demonstrated that Egr-3 (PILOT) but not Egr-1 (NGFI-A, Krox-24, Tis-8, and Zif-268) induces transcription of fast. The aberrant CD4(-)CD8(-) T cells from lpr/lpr and gld/gld mice, which have mutations in the genes encoding Fas and Fast, respectively, have an activated phenotype and constitutively express high levels of fasL mRNA, prompting us to ask what role if any the FLRE and Egr family proteins have in this aberrant expression of fast. Unstimulated MRL-lpr/lpr and C3H-gld/gld CD4(-)CD8(-) T cells constitutively contained high levels of two proteins that bound to the FLRE, Supershift analysis revealed these proteins to be Egr-1 and Egr-2 (Krox-20); Egr-3 was not detected. Activation of normal lymph node cells resulted in increased expression of Egr-1, -2, and -3, As with egr-3, expression of egr-2 was blocked by cyclosporin A. Although overexpressed Egr-1 was ineffective, overexpressed Egr-2 was as potent as Egr-3 in inducing fast promoter-dependent reporter constructs in T cell hybridomas and HeLa cells, and both up-regulated endogenous fast mRNA in HeLa cells. FasL- dependent reporter constructs in MRL-lpr/lpr and C3H-gld/gld CD4(-)CD8(-) T cells were constitutively active, and this activity was largely prevented by mutation of the critical Egr family binding element. Thus, Egr-2, in addition to Egr-3, regulates Fast expression in activated normal T cells, and Egr-2 is likely to play a direct role in aberrant fast up-regulation in lpr/lpr and gld/gld CD4(-)CD8(-) T cells. C1 NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. RP Ashwell, JD (reprint author), NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. NR 59 TC 68 Z9 73 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 29 PY 1999 VL 274 IS 5 BP 3222 EP 3227 DI 10.1074/jbc.274.5.3222 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 161ZB UT WOS:000078319500081 PM 9915863 ER PT J AU Aravind, L Koonin, EV AF Aravind, L Koonin, EV TI Fold prediction and evolutionary analysis of the POZ domain: Structural and evolutionary relationship with the potassium channel tetramerization domain SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE POZ domains; fold prediction; evolutionary analysis; potassium channels ID PROTEIN INTERACTION MOTIF; BTB/POZ DOMAIN; REGULATORY-PROTEIN; DROSOPHILA KELCH; GENE ENCODES; FAMILY; FINGER; SEQUENCE; SEGMENTATION; ONCOPROTEIN AB Using iterative database searches, a statistically significant sequence similarity was detected between the POZ (<(po)under bar>xvirus and (z) under bar inc finger) domains found in a variety of proteins involved in animal transcription regulation, cytoskeleton organization, and development, and the tetramerization domain of animal potassium channels. Using the crystal structure of the Aplysia Shaker channel tetramerization domain as a template, the common structure of the POZ domain class was predicted. Examination of the structure resulted in the identification of several structural features and specific amino acid residues that may be involved in conserved protein-protein interactions mediated by the POZ domains as well as those that may contribute to the specificity of these interactions. Phylogenetic analysis of the POZ domains suggests that the common ancestor of the crown group eukaryotes already possessed this domain; POZ domains have undergone independent expansion in plants and in different animal lineages. (C) 1999 Academic Press. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NR 52 TC 104 Z9 113 U1 0 U2 5 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JAN 29 PY 1999 VL 285 IS 4 BP 1353 EP 1361 DI 10.1006/jmbi.1998.2394 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 164DN UT WOS:000078447300003 PM 9917379 ER PT J AU Qin, XF Schwers, S Yu, W Papavasiliou, F Suh, HY Nussenzweig, A Rajewsky, K Nussenzweig, MC AF Qin, XF Schwers, S Yu, W Papavasiliou, F Suh, HY Nussenzweig, A Rajewsky, K Nussenzweig, MC TI Secondary V(D)J recombination in B-1 cells SO NATURE LA English DT Article ID LY-1 B-CELLS; TRANSGENIC MOUSE; MICE; GENE; LYMPHOCYTES; ANTIGEN; EXPRESSION; TOLERANCE; RESPONSES; APOPTOSIS AB B-1 B cells are a self-renewing population of B cells that differ from conventional B cells (B-2 cells) in that they are particularly predisposed to auto-antibody production(1-3). Although much is known about the signalling pathways that control B-1-cell growth and development (reviewed in ref. 4), less is known about why these cells are prone to produce autoreactive antibodies. Here we show that B-1 cells, like germinal-centre B cells(5-8), can express recombinase-activating genes 1 and 2 (RAG1 and RAG2) and undergo secondary V(D)J recombination of immunoglobulin genes. In addition, B cells from autoimmune-prone NZB mice show high levels of RAG messenger RNA and recombination. We propose that secondary immunoglobulin-gene rearrangements outside organized lymphoid organs may contribute to the development of autoreactive antibodies. C1 Rockefeller Univ, Lab Mol Immunol, New York, NY 10021 USA. Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Cologne, Inst Genet, D-50931 Cologne, Germany. RP Nussenzweig, MC (reprint author), Rockefeller Univ, Lab Mol Immunol, 1230 York Ave, New York, NY 10021 USA. EM nussen@rockvax.rockefeller.edu NR 30 TC 57 Z9 58 U1 0 U2 1 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 28 PY 1999 VL 397 IS 6717 BP 355 EP 359 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 162BE UT WOS:000078324600051 PM 9950428 ER PT J AU Del Mastro, L Venturini, M AF Del Mastro, L Venturini, M TI Treatment of breast cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 St Chiara Hosp, I-56100 Pisa, Italy. Natl Canc Inst, I-16132 Genoa, Italy. RP Del Mastro, L (reprint author), St Chiara Hosp, I-56100 Pisa, Italy. OI Del Mastro, Lucia/0000-0002-9546-5841 NR 3 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 28 PY 1999 VL 340 IS 4 BP 319 EP 320 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 161YU UT WOS:000078318700020 PM 9935351 ER PT J AU Pearson, SD Sabin, JE Emanuel, EJ AF Pearson, SD Sabin, JE Emanuel, EJ TI Ethical guidelines for physician payment based on capitation - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Pilgrim Hlth Care, Boston, MA 02215 USA. NIH, Bethesda, MD 20892 USA. RP Pearson, SD (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 28 PY 1999 VL 340 IS 4 BP 322 EP 323 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 161YU UT WOS:000078318700030 ER PT J AU Gu, ML Leppla, SH Klinman, DM AF Gu, ML Leppla, SH Klinman, DM TI Protection against anthrax toxin by vaccination with a DNA plasmid encoding anthrax protective antigen SO VACCINE LA English DT Article DE DNA vaccine; anthrax; toxin ID BACILLUS-ANTHRACIS; EUKARYOTIC CELLS; SPORE CHALLENGE; LETHAL FACTOR; MICE; ACTIVATION; ADJUVANTS; INJECTION; VACCINES; SEQUENCE AB A DNA vaccine encoding the immunogenic and biologically active portion of anthrax protective antigen (PA) was constructed. Spleen cells from BALB/c mice immunized intramuscularly with this vaccine were stimulated to secrete IFN gamma and IL-4 when exposed to PA in vitro. Immunized mice also mounted a humoral immune response dominated by IgG1 anti-PA antibody production, the subclass previously shown to confer protection against anthrax toxin. A 1:100 dilution of serum from these animals protected cells in vitro against cytotoxic concentrations of PA. Moreover, 7/8 mice immunized three times with the PA DNA vaccine were protected against lethal challenge with a combination of anthrax protective antigen plus lethal factor. Published by Elsevier Science Ltd. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Sect Retroviral Immunol, Bethesda, MD 20014 USA. NIDR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Sect Retroviral Immunol, Bldg 29A,Room 3 D 10, Bethesda, MD 20014 USA. EM klinman@a1.cber.fda.gov NR 27 TC 66 Z9 67 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JAN 28 PY 1999 VL 17 IS 4 BP 340 EP 344 DI 10.1016/S0264-410X(98)00210-2 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 146EB UT WOS:000077414100006 PM 9987172 ER PT J AU Shahidi, H Vottero, A Stratakis, CA Taymans, SE Karl, M Longui, CA Chrousos, GP Daughaday, WH Gregory, SA Plate, JMD AF Shahidi, H Vottero, A Stratakis, CA Taymans, SE Karl, M Longui, CA Chrousos, GP Daughaday, WH Gregory, SA Plate, JMD TI Imbalanced expression of the glucocorticoid receptor isoforms in cultured lymphocytes from a patient with systemic glucocorticoid resistance and chronic lymphocytic leukemia SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID EPSTEIN-BARR-VIRUS; BETA-ISOFORM; INDUCED APOPTOSIS; MESSENGER-RNA; CELL-LINES; GENE; MUTATION; HUMANS; ASSOCIATION; DNA AB The human glucocorticoid receptor (GR) is expressed as two alternatively spliced isoforms, GR alpha and GR beta. Whereas GR alpha is a hormone-activated transcription factor, GR beta does not bind glucocorticoids (GCs), is transcriptionally inactive, and is a potential inhibitor of activated GR alpha, Differential expression of GR isoforms may play a role in generalized or tissue-specific GC resistance. GCs induce apoptosis in neoplastic lymphoid cells; and, defective apoptosis is implicated in the genesis of chronic lymphocytic leukemia (CLL). We studied a patient with generalized GC resistance and CLL. GR number in the patient's transformed lymphocytes was approximately one half that of control cells with a similar to 10-fold reduction in binding affinity for dexamethasone. In vitro apoptosis induction in CLL cells was delayed in response to GCs, but not to other apoptosis inducers. Sequencing of the GR cDNA and gene including the 2.3-kb coding region, the intron/exon junctions, the known 5'-regulatory region, and similar to 300 bp of the 3'-region revealed no alterations, Western blot with an N-terminal antibody showed normal levels of immunoreactive GR, but quantitative analysis with isoform-specific C-terminal antibodies revealed a markedly reduced GR alpha expression, and high GR beta expression, These findings indicate that imbalanced expression of the GR isoforms may be a mechanism of GC resistance, and may have implications for tumorigenesis by enhancing cell survival, (C) 1999 Academic Press. C1 Rush Presbyterian St Lukes Med Ctr, Dept Med, Div Hematol & Oncol, Chicago, IL 60612 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, St Louis, MO 63130 USA. RP Shahidi, H (reprint author), Rush Presbyterian St Lukes Med Ctr, Dept Med, Div Hematol & Oncol, 1725 W Harrison St,Suite 821, Chicago, IL 60612 USA. NR 30 TC 85 Z9 89 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 27 PY 1999 VL 254 IS 3 BP 559 EP 565 DI 10.1006/bbrc.1998.9980 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 162WV UT WOS:000078370800008 PM 9920778 ER PT J AU Chiantore, MV Giandomenico, V De Luca, LM AF Chiantore, MV Giandomenico, V De Luca, LM TI Carcinoma cell lines resistant for growth inhibition and apoptosis to retinoic acid are responsive to 4-hydroxy-phenyl-retinamide: Correlation with tissue transglutaminase SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID N-(4-HYDROXYPHENYL) RETINAMIDE; GENE PROMOTER; DIFFERENTIATION; FENRETINIDE; EXPRESSION; INDUCTION; CANCER; PROLIFERATION; HEPATOCYTES; RECEPTORS AB Retinoic acid (RA)-resistant cell lines are highly malignant. To inhibit the growth of the RA-resistant cells we used 4-HPR, a synthetic retinoid, which may act through alternative signal transduction pathways. 4-HPR induced cell growth inhibition and apoptosis in all HA-sensitive as well as -resistant cells, demonstrating a wider spectrum of potency over RA. 4-HPR induced tissue TGase activity. A tight correlation between the induction of tissue TGase, the inhibition of cell growth, and apoptosis was evident in all eight RA-sensitive cell lines, However, basal TGase differed in the different cells, suggesting inducibility rather than basal levels as the relevant parameter. In sharp contrast to the RA-sensitive cells, RA-resistant cells showed sporadic response to 4-HPR for tissue TGase, The wider spectrum of activity of 4-HPR in inhibiting cell growth and inducing apoptosis makes it a good candidate for the treatment of RA-resistant cancer cells. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. RP De Luca, LM (reprint author), Bldg 37,Room 3A-17,37 Convent Dr, Bethesda, MD 20892 USA. NR 24 TC 18 Z9 19 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 27 PY 1999 VL 254 IS 3 BP 636 EP 641 DI 10.1006/bbrc.1998.9987 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 162WV UT WOS:000078370800022 PM 9920792 ER PT J AU Notzon, FC Komarov, YM Ermakov, SP Sempos, CT Marks, JS Sempos, EV AF Notzon, FC Komarov, YM Ermakov, SP Sempos, CT Marks, JS Sempos, EV TI The role of alcohol and social stress in Russia's mortality rate - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. Medsoceconominform, Moscow, Russia. NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Kaiser Permanente, Gaithersburg, MD USA. RP Notzon, FC (reprint author), Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. NR 1 TC 0 Z9 0 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 27 PY 1999 VL 281 IS 4 BP 321 EP 322 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 158JB UT WOS:000078111300019 ER PT J AU Tanner, CM Ottman, R Goldman, SM Ellenberg, J Chan, P Mayeux, R Langston, JW AF Tanner, CM Ottman, R Goldman, SM Ellenberg, J Chan, P Mayeux, R Langston, JW TI Parkinson disease in twins - An etiologic study SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID TO-DOOR SURVEY; ALZHEIMERS-DISEASE; MONOZYGOTIC TWINS; QUESTIONNAIRE; CONCORDANCE; PREVALENCE; REGISTRY; VETERANS; MONKEY AB Context The cause of Parkinson disease (PD) is unknown. Genetic linkages have been identified in families with PD, but whether most PD is inherited has not been determined, Objective To assess genetic inheritance of PD by studying monozygotic (MZ) and dizygotic (DZ) twin pairs. Design Twin study comparing concordance rates of PD in MZ and DZ twin pairs. Setting and Participants A total of 19 842 white male twins enrolled in the National Academy of Sciences/National Research Council World War II Veteran Twins Registry were screened for PD and standard diagnostic criteria for PD were applied. Zygosity was determined by polymerase chain reaction or questionnaire. Main Outcome Measure Parkinson disease concordance in twin pairs, stratified by zygosity and age at diagnosis. Results Of 268 twins with suspected parkinsonism and 250 presumed unaffected twin brothers, 193 twins with PD were identified (concordance-adjusted prevalence, 8.67/1000). In 71 MZ and 90 DZ pairs with complete diagnoses, pairwise concordance was similar (0.129 overall, 0.155 MZ, 0.111 DZ; relative risk, 1.39; 95% confidence interval, 0.63-3.1). In 16 pairs with diagnosis at or before age 50 years in at least 1 twin, MZ concordance was 1.0 (4 pairs), and DZ was 0.167 (relative risk, 6.0; 95% confidence interval, 1.69-21.26). Conclusions The similarity in concordance overall indicates that genetic factors do not play a major role in causing typical PD, No genetic component is evident when the disease begins after age 50 years. However, genetic factors appear to be important when disease begins at or before age 50 years. C1 Parkinsons Inst, Sunnyvale, CA 94089 USA. Columbia Univ, Coll Phys & Surg, Gertrude H Sergievsky Ctr, New York, NY USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Tanner, CM (reprint author), Parkinsons Inst, 1170 Morse Ave, Sunnyvale, CA 94089 USA. RI Ottman, Ruth/O-2371-2013 FU ONR [UIONS31321] NR 44 TC 586 Z9 599 U1 2 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 27 PY 1999 VL 281 IS 4 BP 341 EP 346 DI 10.1001/jama.281.4.341 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 158JB UT WOS:000078111300033 PM 9929087 ER PT J AU Ojo, AO Govaerts, TC Schmouder, RL Leichtman, AB Leavey, SF Wolfe, RA Held, PJ Port, FK Agodoa, LY AF Ojo, AO Govaerts, TC Schmouder, RL Leichtman, AB Leavey, SF Wolfe, RA Held, PJ Port, FK Agodoa, LY TI Renal transplantation in end-stage sickle cell nephropathy SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the American-Society-of-Nephrology CY NOV 03-06, 1996 CL NEW ORLEANS, LOUISIANA SP Amer Soc Nephrol ID NATURAL-HISTORY; DISEASE; ANEMIA; ALLOGRAFTS; FAILURE; KIDNEY; TRAIT AB Background. The role of renal transplantation as treatment for end-stage sickle cell nephropathy (SCN) has not been well established. Methods. We performed a comparative investigation of patient and allograft outcomes among age-matched African-American kidney transplant recipients with ESRD as a result of SCN (n=82) and all other causes (Other-ESRD, n=22,565). Results. The incidence of delayed graft function and predischarge acute rejection in SCN group (24% and 26%) was similar to that observed in the Other-ESRD group (29% and 27%). The mean discharge serum creatinine (SCr) was 2.7 (+/- 2.5) mg/dl in the SCN recipients compared to 3.0 (+/- 2.5) mg/dl in the Other-ESRD recipients (P=0.42). There was no difference in the 1-year cadaveric graft survival (SCN: 78% vs. Other-ESRD: 77%), and the multivariable adjusted 1-year risk of graft loss indicated no significant effect of SCN (relative risk [RR]=1.39, P=0.149). However, the 3-year cadaveric graft survival tended to be lower in the SCN group (48% vs. 60%, P=0.055) and their adjusted 3-year risk of graft loss was significantly greater (RR=1.60, P=0.003). There was a trend toward improved survival in the SCN transplant recipients compared to their dialysis-treated, wait-listed counterparts (RR=0.14, P=0.056). In comparison to the Other-ESRD (RR=1.00), the adjusted mortality risk in the SCN group was higher both at 1 year (RR=2.95, P=0.001) and at 3 years (RR=2.82, P=0.0001) after renal transplantation. Conclusions. The short-term renal allograft result in recipients with end-stage SCN was similar to that obtained in other causes of ESRD, but the long-term outcome was comparatively diminished. There was a trend toward better patient survival with renal transplantation relative to dialysis in end-stage SCN. C1 Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. NIDDKD, US Renal Data Syst, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. RP Ojo, AO (reprint author), Univ Michigan, Med Ctr, Dept Internal Med, Taubman Ctr 3914, Box 0364, Ann Arbor, MI 48109 USA. NR 17 TC 38 Z9 39 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 27 PY 1999 VL 67 IS 2 BP 291 EP 295 DI 10.1097/00007890-199901270-00018 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 162NA UT WOS:000078352000018 PM 10075596 ER PT J AU Galazka, G Windsor, LJ Birkedal-Hansen, H Engler, JA AF Galazka, G Windsor, LJ Birkedal-Hansen, H Engler, JA TI Spontaneous propeptide processing of mini-stromelysin-1 mutants blocked by APMA ((4-aminophenyl)mercuric acetate) SO BIOCHEMISTRY LA English DT Article ID MATRIX METALLOPROTEINASE-3 STROMELYSIN-1; HUMAN FIBROBLAST COLLAGENASE; CATALYTIC DOMAIN; CYSTEINE SWITCH; LATENT COLLAGENASE; ACTIVATION; PROTEIN; FAMILY; SPECIFICITY; EXPRESSION AB Human stromelysin-1 (SL-1) is a member of the stromelysin subfamily of matrix metalloproteinases (MMPs). The MMPs play a major role in the degradation of the extracellular matrix (ECM) during normal and pathological conditions. SL-1 like the other MMPs can be activated in vitro by the stepwise removal of the propeptide that contains a single unpaired cysteine which coordinates the active site zinc. Other residues in the propeptide also play a role in maintaining the latency of the enzymes. Deletion mutants and single-site amino acid replacements within the propeptide of a carboxyl-terminally truncated stromelysin-1 (mini-SL-1) were constructed and expressed in Escherichia coli to further examine what amino acids within the propeptide of SL-1 are important for maintaining latency. While the natural enzyme displayed some limited tendency to spontaneously (autolytically) convert to lower M-r in a stepwise manner and finally to the fully processed form, all of the truncation mutants of more than 19 amino acids generated in E. coli showed greatly accelerated self-cleavage indicative of diminished stability and/or resistance to proteolysis of the residual propeptide. Mutant Delta 63 as well as other mutants in which most of the propeptide had been deleted no longer responded to exposure to the organomercurial APMA by accelerated autolytic processing. Rather, APMA inhibited the autolytic processing in these mutants, further confirming the complexity of the action of this organomercurial in the activation of pro-MMPs. C1 Univ Alabama, Oral Biol Res Ctr, Oral Canc Res Ctr, Birmingham, AL 35294 USA. Univ Alabama, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA. NIDR, NIH, Bethesda, MD 20892 USA. RP Engler, JA (reprint author), Univ Alabama, Oral Biol Res Ctr, Oral Canc Res Ctr, Birmingham, AL 35294 USA. EM jengler@bmg.bhs.uab.edu FU NIDCR NIH HHS [DE/CA11910, DE10631, DE08228] NR 37 TC 5 Z9 5 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 26 PY 1999 VL 38 IS 4 BP 1316 EP 1322 DI 10.1021/bi982135b PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 170ZD UT WOS:000078836500020 PM 9930993 ER PT J AU Koh, KK Cardillo, C Bui, MN Hathaway, L Csako, G Waclawiw, MA Panza, JA Cannon, RO AF Koh, KK Cardillo, C Bui, MN Hathaway, L Csako, G Waclawiw, MA Panza, JA Cannon, RO TI Vascular effects of estrogen and cholesterol-lowering therapies in hypercholesterolemic postmenopausal women SO CIRCULATION LA English DT Article DE lipoproteins; endothelium; hormones; cell adhesion molecules; fibrinolysis ID ENDOTHELIUM-DEPENDENT RELAXATION; CELL-ADHESION MOLECULES; NITRIC-OXIDE SYNTHASE; E-SELECTIN; DENSITY-LIPOPROTEINS; CORONARY ENDOTHELIUM; HEART-DISEASE; EXPRESSION; REPLACEMENT; ICAM-1 AB Background-Lipoproteins affect endothelium-dependent vasomotor responsiveness. Because lipoprotein effects of estrogen and cholesterol-lowering therapies differ, we studied the vascular responses to these therapies in hypercholesterolemic postmenopausal women. Methods and Results-We randomly assigned 28 women to conjugated equine estrogen (CE) 0.625 mg, simvastatin 10 mg, and their combination daily for 6 weeks. Compared with respective baseline values, simvastatin alone and combined with CE reduced LDL cholesterol to a greater extent than CE alone (both P<0.05). CE alone and combined with simvastatin raised HDL cholesterol and lowered lipoprotein(a) to a greater extent than simvastatin alone tall P<0.05). Flow-mediated dilation of the brachial artery (by ultrasonography) improved tall P<0.001 versus baseline values) on CE (4.0+/-2.6% to 10.2+/-3.9%), simvastatin (4.3+/-2.4% to 10.0+/-3.9%), and CE combined with simvastatin (4.6+/-2.0% to 9.8+/-2.6%), but similarly among therapies (P=0.507 by ANOVA). None of the therapies improved the dilator response to nitroglycerin tall (P greater than or equal to 0.184). Only therapies including CE lowered levels of plasminogen activator inhibitor type 1 and the cell adhesion molecule E-selectin tall (P<0.05 versus simvastatin). Conclusions-Although estrogen and statin therapies have differing effects on lipoprotein levels, specific improvement in endothelium-dependent vasodilator responsiveness is similar. However, only therapies including estrogen improved markers of fibrinolysis and vascular inflammation. Thus, estrogen therapy appears to have unique properties that may benefit the vasculature of hypercholesterolemic postmenopausal women, even if they are already on cholesterol-lowering therapy. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Clin Pathol, Bethesda, MD 20892 USA. RP Cannon, RO (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10,Room 7B15,10 Ctr Dr MSC-1650, Bethesda, MD 20892 USA. NR 46 TC 183 Z9 184 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 26 PY 1999 VL 99 IS 3 BP 354 EP 360 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 160BW UT WOS:000078211300007 PM 9918521 ER PT J AU Witkop, B AF Witkop, B TI Ehrlich in the cinema SO CHEMICAL & ENGINEERING NEWS LA English DT Letter C1 NIH Inst, Bethesda, MD 20892 USA. RP Witkop, B (reprint author), NIH Inst, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0009-2347 J9 CHEM ENG NEWS JI Chem. Eng. News PD JAN 25 PY 1999 VL 77 IS 4 BP 6 EP 6 PG 1 WC Chemistry, Multidisciplinary; Engineering, Chemical SC Chemistry; Engineering GA 175TV UT WOS:000079112200004 ER PT J AU Persic, L Horn, IR Rybak, S Cattaneo, A Hoogenboom, HR Bradbury, A AF Persic, L Horn, IR Rybak, S Cattaneo, A Hoogenboom, HR Bradbury, A TI Single-chain variable fragments selected on the 57-76 p21Ras neutralising epitope from phage antibody libraries recognise the parental protein SO FEBS LETTERS LA English DT Article DE phage display; p21Ras; Ras neutralizing epitope; single-chain variable fragment ID MONOCLONAL-ANTIBODIES; INTRACELLULAR EXPRESSION; ANTIGENIC DETERMINANTS; ESCHERICHIA-COLI; DISPLAY LIBRARY; FILAMENTOUS PHAGE; NEURAL NETWORKS; ENCODED P21; RAS; SURFACE AB Phage antibodies have been widely prospected as an alternative to the use of monoclonal antibodies prepared by traditional means. Many monoclonal antibodies prepared against peptides are able to recognise the native proteins from which they were derived. Here ne show that the same is also true for phage antibodies. We have selected a number of single-chain variable fragments (scFv) from a large phage scFv library against a peptide from the switch region II of p21Ras. This peptide is known to reside in a mobile area of the native protein and is the epitope of a well characterised monoclonal antibody. Selected scFvs were able to recognise native p21Ras in both ELISA and Western blots, indicating that peptides are also likely to be very useful in selecting from phage antibody libraries. (C) 1999 Federation of European Biochemical Societies. C1 SISSA, Mol Neurobiol Lab, Area Ric, I-34014 Trieste, Italy. Univ Hosp Maastricht, Dept Pathol, CESAME, Maastricht, Netherlands. NCI, Dev Therapeut Program, Frederick Canc Res & Dev Ctr, NIH, Ft Detrick, MD 21702 USA. RP Bradbury, A (reprint author), SISSA, Mol Neurobiol Lab, Area Ric, Padriciano 99, I-34014 Trieste, Italy. EM bradbury@icgeb.trieste.it OI CATTANEO, ANTONINO/0000-0002-6975-8923 NR 52 TC 18 Z9 18 U1 0 U2 0 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 JAN 25 PY 1999 VL 443 IS 2 BP 112 EP 116 DI 10.1016/S0014-5793(98)01684-6 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 162ZL UT WOS:000078377700007 PM 9989586 ER PT J AU Svard, SG Rafferty, C McCaffery, JM Smith, MW Reiner, DS Gillin, FD AF Svard, SG Rafferty, C McCaffery, JM Smith, MW Reiner, DS Gillin, FD TI A signal recognition particle receptor gene from the early-diverging eukaryote, Giardia lamblia SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Giardia lamblia; secretory pathway; signal recognition particle cycle ID PRIMITIVE EUKARYOTE; ENDOPLASMIC-RETICULUM; SECRETORY PATHWAY; PROTEIN; DIFFERENTIATION; EXPRESSION; DOMAIN; ENCYSTATION; EVOLUTION; PROTISTS AB The molecular mechanisms for targeting and translocation of secreted proteins are highly conserved from bacteria to mammalian cells, although the machinery is more complex in higher eukaryotes. To investigate protein transport in the early-diverging eukaryote, Giardia lamblia, we cloned the gene encoding the alpha subunit (SR alpha) of the signal recognition particle (SRP) receptor. SR alpha is a small GTPase that functions in SRP-ribosome targeting to the ER. Sequence and phylogenetic analyses showed that SR alpha from G. lamblia is most homologous to SR alpha proteins from higher eukaryotes, although it lacks some conserved motifs. Specifically, giardial SR alpha has an N-terminal extension that enables SR alpha of higher eukaryotes to interact with a beta subunit that anchors it in the ER membrane. While the C-terminal regions are similar, giardial SR alpha lacks a prominent 13 amino acid regulatory loop that is characteristic of higher eukaryotic versions. Thus, giardial SR alpha resembles that of higher eukaryotes, but likely diverged before the advent of the regulatory loop. The 1.8 kb SR alpha transcript has extremely short untranslated regions (UTRs): a 1-2 nt 5'- and a 9 nt 3' UTR with the polyadenylation signal overlapping with the stop codon. RT-PCR, Northern and Western analyses showed that SR alpha is present at relatively constant levels during vegetative growth and encystation. C1 Univ Calif San Diego, Dept Pathol, Div Infect Dis, San Diego, CA 92103 USA. Univ Calif San Diego, Div Cellular & Mol Med, La Jolla, CA 92093 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD 21710 USA. Univ Calif San Diego, Ctr Mol Genet, La Jolla, CA 92093 USA. RP Gillin, FD (reprint author), Univ Calif San Diego, Dept Pathol, Div Infect Dis, 214 Dickinson St, San Diego, CA 92103 USA. EM fgillin@ucsd.edu RI Smith, Michael/B-5341-2012; Reiner, David/F-6106-2012 OI Reiner, David/0000-0002-8289-7311 FU NHLBI NIH HHS [HLO7491-17]; NIAID NIH HHS [AI24285]; NIGMS NIH HHS [GM53835] NR 37 TC 21 Z9 21 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 JAN 25 PY 1999 VL 98 IS 2 BP 253 EP 264 DI 10.1016/S0166-6851(98)00174-1 PG 12 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 167LJ UT WOS:000078633900008 PM 10080393 ER PT J AU Matsuura, H Adachi, H Smart, RC Xu, XC Arata, J Jetten, AM AF Matsuura, H Adachi, H Smart, RC Xu, XC Arata, J Jetten, AM TI Correlation between expression of peroxisome proliferator-activated receptor beta and squamous differentiation in epidermal and tracheobronchial epithelial cells SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE peroxisome proliferator-activated receptor; epidermis; keratinocyte; trachea; phorbol ester; retinoic acid; transglutaminase ID NUCLEAR HORMONE RECEPTORS; RETINOID-X-RECEPTOR; FATTY-ACIDS; PPAR-GAMMA; GLUCOCORTICOID RECEPTOR; LIPID-METABOLISM; PHORBOL ESTERS; MESSENGER-RNA; KERATINOCYTES; ALPHA AB Previously, several members of the nuclear receptor superfamily have been implicated in the regulation of epidermal differentiation. In this study, we analyze the expression of members of the PPAR nuclear receptor subfamily in relation to the process of squamous differentiation in normal human epidermal keratinocytes (NHEK), human tracheobronchial epithelial (HBE) cells and the epidermis in vivo. Our results demonstrate that induction of differentiation in NHEK by either treatment with the phorbol ester phorbol 12-myristate-13-acetate (PMA), suspension culture or confluence greatly enhances the expression of PPAR beta mRNA. Likewise, topical treatment of mouse skin with PMA results in increased PPAR beta mRNA expression in the epidermis. In addition, the induction of squamous differentiation in HBE cells was also associated with an upregulation of PPAR beta mRNA expression. Finally, in situ hybridization analysis localized PPAR beta mRNA to the suprabasal layers of normal human skin. Our results demonstrate that the expression of PPAR beta is associated with squamous differentiation suggesting a regulatory role for this receptor in the control of specific genes during this differentiation process, (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 NIEHS, Cell Biol Sect, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Toxicol, Raleigh, NC 27695 USA. Univ Texas, MD Anderson Cancer Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA. Okayama Univ, Sch Med, Dept Dermatol, Okayama 700, Japan. RP Jetten, AM (reprint author), NIEHS, Cell Biol Sect, Pulm Pathobiol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM jetten@niehs.nih.gov OI Jetten, Anton/0000-0003-0954-4445 NR 52 TC 73 Z9 74 U1 0 U2 6 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 JAN 25 PY 1999 VL 147 IS 1-2 BP 85 EP 92 DI 10.1016/S0303-7207(98)00214-7 PG 8 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 169TV UT WOS:000078765400010 PM 10195695 ER PT J AU Emanuel, EJ AF Emanuel, EJ TI Eight is too many - The case against octuplets. SO NEW REPUBLIC LA English DT Article C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Emanuel, EJ (reprint author), NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NEW REPUBLIC INC PI WASHINGTON PA 1220 19TH ST NW SUITE 600, WASHINGTON, DC 20036 USA SN 0028-6583 J9 NEW REPUBLIC JI New Repub. PD JAN 25 PY 1999 VL 220 IS 4 BP 8 EP + PG 3 WC Political Science SC Government & Law GA 157EM UT WOS:000078047200011 PM 11657452 ER PT J AU Aceto, MD Harris, LS Abood, ME Rice, KC AF Aceto, MD Harris, LS Abood, ME Rice, KC TI Stereoselective mu- and delta-opioid receptor-related antinociception and binding with (+)-thebaine SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE (-)-thebaine; (+)-thebaine; stereoselectivity; antinociception; mu-opioid receptor; delta-opioid receptor; (mouse) ID MORPHINE; CODEINE; ANTAGONISTS; CONVULSANT; THEBAINE; BRAIN; RAT AB In vivo and in vitro binding studies with natural thebaine and its enantiomer, (+)-thebaine were conducted to elucidate further their interactions with the opioid system. (-)-Thebaine a key intermediate in the biosynthesis of morphine in the poppy plant (Papaver somnniferum) and in mammalian tissue, was poorly effective antinociceptively in mice at doses to 30 mg/kg. Its principal behavioral manifestation was lethal convulsions. Naltrindole, at doses of 1 and 10 mg/kg did not block either the convulsions or lethal effects, suggesting that the delta-opioid receptor system was not involved in this action. Surprisingly, the dextrorotatory isomer exhibited significant antinociceptive activity in the tail-flick [ED50 = 8.9 (3.4-22.1) mg/kg], hot-plate [ED50 = 22.9 (10.9-48.1) mg/kg] and phenylquinone [ED50 = 1.9 (1.6-9.5) mg/kg] assays. Studies with opioid receptor-subtype antagonists, beta-funaltrexamine, nor-binaltorphimine and naltrindole, indicated that antinociception was associated with mu- and delta-opioid receptors. Results of displacement experiments supported the in vivo data. Significant competition for [H-3]diprenorphine binding with both isomers for cloned mu- and delta-opioid receptors was observed. However, (-)-thebaine was more effective at the delta-opioid receptor (K-i = 1.02+/-0.01 mu M) whereas (+)-thebaine was more effective at the mu-opioid receptor (K-i = 2.75+/-0.01 mu M). Opioid-induced antinociception associated with unnatural thebaine raises the possibility of additional mu- and delta-opioid receptor sites. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Virginia Commonwealth Univ, Sch Med, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Aceto, MD (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. FU NIDA NIH HHS [DA 5-8059, DA-09978] NR 23 TC 9 Z9 9 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JAN 22 PY 1999 VL 365 IS 2-3 BP 143 EP 147 DI 10.1016/S0014-2999(98)00862-0 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 160WD UT WOS:000078253900003 PM 9988096 ER PT J AU Chandran, UR Warren, BS Baumann, CT Hager, GL DeFranco, DB AF Chandran, UR Warren, BS Baumann, CT Hager, GL DeFranco, DB TI The glucocorticoid receptor is tethered to DNA-bound Oct-1 at the mouse gonadotropin-releasing hormone distal negative glucocorticoid response element SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FUNCTIONAL HYPOTHALAMIC-AMENORRHEA; PROTEIN-PROTEIN-INTERACTION; NEURONAL CELL-LINES; POU-SPECIFIC DOMAIN; TRANSCRIPTION FACTORS; GENE-EXPRESSION; MEDIATED REPRESSION; PROMOTER ACTIVITY; KINASE-C; LUTEINIZING-HORMONE AB An element required for glucocorticoid repression of mouse gonadotropin-releasing hormone (GnRH) gene transcription, the distal negative glucocorticoid response element (nGRE), is not bound directly by glucocorticoid receptors (GRs) but is recognized by Oct-1 present in GT1-7 cell nuclear extracts or by Oct-1 purified from HeLa cells. Furthermore, purified full-length GRs interact directly with purified Oct-1 bound to the distal nGRE. Increasing the extent of distal nGRE: match to an Oct-1 consensus site not only increases the affinity of Oct-1 binding, but also alters the conformation of DNA-bound Oct-1 and the pattern of protein DNA complexes formed in vitro with GT1-7 cell nuclear extracts. In addition, the interaction of purified GR with DNA-bound Oct-1 is altered when Oct-1 is bound to the consensus Oct-1 site. Mutation of the distal nGRE to a consensus Oct-1 site is also associated with reduced glucocorticoid repression in transfected GT1-7 cells. Furthermore, repression of GnRN gene transcription by 12-O-tetradecanoylphorbol-13-acetate, which utilizes sequences that overlap with the nGRE, is reversed by this distal nGRE mutation leading to activation of GnRH: gene transcription. Thus, changes in the assembly of multi-protein complexes at the distal nGRE can influence the regulation of GnRN gene transcription. C1 Univ Pittsburgh, Dept Sci Biol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15260 USA. NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP DeFranco, DB (reprint author), Univ Pittsburgh, Dept Sci Biol, Pittsburgh, PA 15260 USA. FU NIDDK NIH HHS [R01 DK47938] NR 58 TC 70 Z9 70 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 22 PY 1999 VL 274 IS 4 BP 2372 EP 2378 DI 10.1074/jbc.274.4.2372 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 159QL UT WOS:000078185200072 PM 9891005 ER PT J AU Wolff, EA Greenfield, B Taub, DD Murphy, WJ Bennett, KL Aruffo, A AF Wolff, EA Greenfield, B Taub, DD Murphy, WJ Bennett, KL Aruffo, A TI Generation of artificial proteoglycans containing glycosaminoglycan-modified CD44 - Demonstration of the interaction between RANTES and chondroitin sulfate SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LYMPHOCYTE HOMING RECEPTOR; T-CELL ACTIVATION; FIBROBLAST GROWTH-FACTOR; EXTRACELLULAR-MATRIX; ENDOTHELIAL-CELLS; HEPARAN-SULFATE; SPLICED EXONS; BINDING; ADHESION; HYALURONATE AB All CD44 isoforms are modified with chondroitin sulfate (CS), while only those containing variably spliced exon V3 are modified with both CS and heparan sulfate (HS). The CS is added to a serine-glycine (SG) site in CD44 exon E5, while NS and CS are added to the SGSG site in exon V3, Site-directed mutagenesis and other molecular biology techniques were used to determine the minimal motifs responsible for the addition of CS and HS to CD44 (see accompanying paper (Greenfield, B,, Wang, W,-C,, Marquardt, W., Piepkorn, RI., Wolff, E. A., Aruffo, A., and Bennett, K. L, (1999) J, Biol. Chem. 274, 2511-2517)). We have used this information to generate artificial proteoglycans containing the extracellular domain of the cell adhesion protein lymphocyte function-associated antigen-3 (LFA-3)(CD58) and CD44 motifs modified with CS or a combination of CS and HS. Analysis of the CD44-modified LFA-3 protein showed that it retains the ability to engage and trigger the function of its natural ligand CD2, resulting in T cell activation. In addition, the glycosaminoglycan-modified artificial proteoglycan is capable of binding the chemokine RANTES (regulated upon activation, normally T cell expressed and Secreted) and delivering it to human T cells, resulting in enhanced T cell activation. These data demonstrate that artificial proteoglycans can be;engineered with functional domains that have enhanced activity by codelivering glyaosaminoglycan-binding molecules. The artificial proteoglycans were also used as a model system to explore the glycosaminoglycan binding properties of basic-fibroblast growth factor and the chemokine RANTES. While basic-fibroblast growth factor was shown to bind BS alone, this model revealed that RANTES binds not only HS, as has been demonstrated in the past, but also CS. Thus, artificial proteoglycans can be used for studying the glycosaminoglycan binding patterns of growth factors and chemokines and provide a means to manipulate the levels, types, and activity of glycosaminoglycan-binding proteins in vitro and in vivo. C1 Bristol Myers Squibb Pharmaceut Res Inst, Princeton, NJ 08543 USA. NIA, Clin Immunol Sect, NIH, Baltimore, MD 21224 USA. NCI, Frederick Canc Res & Dev Ctr, NIH, Frederick, MD 21702 USA. RP Wolff, EA (reprint author), Bristol Myers Squibb Pharmaceut Res Inst, POB 4000, Princeton, NJ 08543 USA. NR 46 TC 30 Z9 30 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 22 PY 1999 VL 274 IS 4 BP 2518 EP 2524 DI 10.1074/jbc.274.4.2518 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 159QL UT WOS:000078185200090 PM 9891023 ER PT J AU Marshall, P Sharma, M Hinton, DM AF Marshall, P Sharma, M Hinton, DM TI The bacteriophage T4 transcriptional activator MotA accepts various base-pair changes within its binding sequence SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE activation; AsiA; bacteriophage; MotA; transcription ID COLI RNA-POLYMERASE; ESCHERICHIA-COLI; MIDDLE PROMOTER; ASIA PROTEIN; DNA; GENE; RECOGNITION; MUTANTS; REGION; TERMINATION AB During infection, bacteriophage T4 regulates three sets of genes: early, middle, and late. The host RNA-polymerase is capable of transcribing early genes, but middle transcription requires the T4-encoded transcriptional activator, MotA protein, and the T4 co-activator, AsiA protein, both of which bind to the sigma 70 (sigma(70)) subunit of RNA polymerase. MotA also binds a DNA sequence (a MotA box), centered at position -30. The identification of more than 20 middle promoters suggested that a strong match to the MotA box consensus sequence (t/a)(t/a)TGCTT(t/c)A was critical for MotA activation. We have investigated how specific base changes within the MotA box sequence affect MotA binding and activation in vitro, and we have identified seven new middle promoters in vivo. We find that an excellent match to the sigma(70) -10 consensus sequence, rather than an excellent match to the MotA box consensus sequence, is an invariant feature of MotA-dependent promoters. Many single base changes in the MotA box are tolerated in binding and activation assays, indicating that there is more flexibility in the sequence requirements for MotA than was previously appreciated. We also find that using the natural T4 DNA, which contains glucosylated, 5-hydoxymethylated cytosine residues, affects the ability of particular MotA box sequences to activate transcription. We suggest that MotA and AsiA may function Like certain eukaryotic TAFs (TATA binding protein (TBP) associated factors) whose binding to TBP results in transcription from new core promoter sequences.(C) 1999 Academic Press. C1 NIDDKD, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hinton, DM (reprint author), Ottawa Gen Hosp, Res Inst, 501 Smythe Rd, Ottawa, ON K1H 8L6, Canada. NR 43 TC 22 Z9 22 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JAN 22 PY 1999 VL 285 IS 3 BP 931 EP 944 DI 10.1006/jmbi.1998.2373 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 161ZC UT WOS:000078319600005 PM 9918715 ER PT J AU Bahar, I Erman, B Jernigan, RL Atilgan, AR Covell, DG AF Bahar, I Erman, B Jernigan, RL Atilgan, AR Covell, DG TI Collective motions in HIV-1 reverse transcriptase: Examination of flexibility and enzyme function SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE reverse transcriptase; flexibility; enzyme function; mutations ID IMMUNODEFICIENCY-VIRUS TYPE-1; ANGSTROM RESOLUTION; MUTATIONAL ANALYSIS; RESIDUE POTENTIALS; CRYSTAL-STRUCTURES; SINGLE-PARAMETER; PROTEINS; INHIBITION; FLUCTUATIONS; INFECTIONS AB In order to study the inferences of structure for mechanism, the collective motions of the retroviral reverse transcriptase HIV-1 RT (RT) are examined using the Gaussian network model (GNM) of proteins. This model is particularly suitable for elucidating the global dynamic characteristics of large proteins such as the presently investigated heterodimeric RT comprising a total of 982 residues. Local packing density and coordination order of amino acid residues is inspected by the GNM to determine the type and range of motions, both at the residue level and on a global scale, such as the correlated movements of entire subdomains. Of the two subunits, p66 and p51, forming the RT, only p66 has a DNA-binding cleft and a functional polymerase active site. This difference in the structure of the two subunits is shown here to be reflected in their dynamic characteristics: only p66 has the potential to undergo large-scale cooperative motions in the heterodimer, while p51 is essentially rigid. Taken together, the global motion of the RT heterodimer is comprised of movements of the p66 thumb subdomain perpendicular to those of the p66 fingers, accompanied by anticorrelated fluctuations of the RNase H domain and p51 thumb, thus providing information about the details of one processivity mechanism. A few clusters of residues, generally distant in sequence but close in space, are identified in the p66 palm and connection subdomains, which form the hinge-bending regions that control the highly concerted motion of the subdomains. These regions include the catalytically active site and the non-nucleoside inhibitor binding pocket of p66 polymerase, as well as sites whose mutations have been shown to impair enzyme activity. It is easily conceivable that this hinge region, indicated by GNM analysis to play a critical role in modulating the global motion, is locked into an inactive conformation upon binding of an inhibitor. Comparative analysis of the dynamic characteristics of the unliganded and liganded dimers indicates severe repression of the mobility of the p66 thumb in RT's global mode, upon binding of non-nucleoside inhibitors. (C) 1999 Academic Press. C1 Sci Applicat Int Corp, NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Mol Struct Sect, Lab Expt & Computat Biol, Div Basic Sci,NIH, Bethesda, MD 20892 USA. Bogazici Univ, Polymer Res Ctr, TR-80815 Bebek, Turkey. Bogazici Univ, Sch Engn, TR-80815 Bebek, Turkey. Adv Polymer Mat Res Ctr, TUBITAK, TR-80815 Bebek, Turkey. Sabanci Univ, Sabanci Ctr, TR-80745 Istanbul, Turkey. RP Covell, DG (reprint author), Sci Applicat Int Corp, NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RI Atilgan, Ali Rana/A-7805-2011; Jernigan, Robert/A-5421-2012; OI ERMAN, BURAK/0000-0002-2496-6059 NR 41 TC 165 Z9 172 U1 3 U2 13 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JAN 22 PY 1999 VL 285 IS 3 BP 1023 EP 1037 DI 10.1006/jmbi.1998.2371 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 161ZC UT WOS:000078319600012 PM 9887265 ER PT J AU Nakai, M Qin, ZH Wang, YM Chase, TN AF Nakai, M Qin, ZH Wang, YM Chase, TN TI Free radical scavenger OPC-14117 attenuates quinolinic acid-induced NF-kappa B activation and apoptosis in rat striatum SO MOLECULAR BRAIN RESEARCH LA English DT Article DE neurodegeneration; oxidative stress; excitotoxicity; NMDA receptor; I kappa B alpha; c-Myc; p53 ID METHYL-D-ASPARTATE; CEREBELLAR GRANULE NEURONS; NMDA RECEPTOR ACTIVATION; MESSENGER-RNA EXPRESSION; CORTICAL CELL-CULTURES; TRANSCRIPTION FACTOR; NERVOUS-SYSTEM; NITRIC-OXIDE; FOREBRAIN NEURONS; DNA FRAGMENTATION AB Oxidative stress has long been implicated in the pathogenesis of both the acute and chronic neurotoxic effects of glutamate acting through ionotrophic receptors of the N-methyl-D-aspartate (NMDA) subtype. To evaluate the contribution of oxidative stress to the NMDA receptor-mediated apoptotic death of rat striatal neurons in vivo, the effects of a novel, orally administered free radical scavenger, OPC-14117, was studied following intrastriatal infusion of the NMDA receptor agonist quinolinic acid (QA). Receptor autoradiography and in situ hybridization histochemistry showed that pretreatment with OPC-14117 (600 mg/kg) reduced the QA (120 nmol)-induced loss of striatal D-1 dopamine receptors by about 20% (p < 0.01) and NMDA receptors by 15% (p < 0.01) as well as 67 kDa glutamic acid decarboxylase mRNA (34%; p < 0.01) and proenkephalin mRNA (36%; p < 0.01). OPC-14117 also decreased the apomorphine-induced ipsilateral rotational response in unilaterally QA-lesioned animals by about 70% (p < 0.05). In addition, OPC-14117 pretreatment inhibited QA-induced internucleosomal DNA fragmentation. Western blot analysis and electrophoresis mobility shift assay further revealed that the free radical scavenger (300 and 600 mg/kg) blunted the QA-induced degradation of I kappa B alpha (increased I kappa B alpha levels from about 15% to 33 and 62% of control, respectively; p < 0.01) as well as the ensuing activation of NF-kappa B by 25 to 34%, respectively (p < 0.01) and the augmentation in c-Myc (35 to 70%, respectively) and p53 expression by 50-80%, respectively (both p < 0.01). In contrast, OPC-14117 had no significant effect on the QA-induced increase in AP-1 binding activity. These results suggest that the NMDA receptor-mediated generation of reactive oxygen species contributes to the QA-induced activation of NF-kappa B and further that orally administered OPC-14117 partially protects against excitotoxin-induced apoptosis of striatal neurons through inhibition of the NF-kappa B apoptotic cascade. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Chase, TN (reprint author), NINDS, Expt Therapeut Branch, NIH, Bldg 10,Rm 5C103,10 Ctr Dr, Bethesda, MD 20892 USA. EM chase@helix.nih.gov NR 64 TC 23 Z9 24 U1 1 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 JAN 22 PY 1999 VL 64 IS 1 BP 59 EP 68 DI 10.1016/S0169-328X(98)00310-6 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 159VY UT WOS:000078196900007 ER PT J AU Rodionov, O Lobocka, M Yarmolinsky, M AF Rodionov, O Lobocka, M Yarmolinsky, M TI Silencing of genes flanking the P1 plasmid centromere SO SCIENCE LA English DT Article ID INTEGRATION HOST FACTOR; COLI F-PLASMID; ESCHERICHIA-COLI; PARTITION COMPLEX; NEGATIVE CONTROL; MINI-F; PROTEIN; REPLICATION; CHROMOSOME; REGION AB Partition modules stabilize bacterial plasmids and chromosomes by actively promoting their segregation into daughter cells. The partition module of plasmid P1 is typical and consists of a centromere site, parS, and genes that encode proteins ParA and ParB. We show that ParB can silence genes flanking parS (to which ParB binds), apparently by polymerizing along the DNA from a nucleation site at parS. Wild-type ParB contacts an extensive region of P1 DNA; silencing-defective ParB proteins, which were found to be partition-defective, are Less able to spread. Hence, the silenced structure appears to function in partitioning. C1 NCI, Biochem Lab, Bethesda, MD 20892 USA. RP Yarmolinsky, M (reprint author), NCI, Biochem Lab, 37 Convent Dr, Bethesda, MD 20892 USA. EM myarmo@helix.nih.gov NR 39 TC 150 Z9 150 U1 1 U2 8 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 22 PY 1999 VL 283 IS 5401 BP 546 EP 549 DI 10.1126/science.283.5401.546 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 159YM UT WOS:000078203300040 PM 9915704 ER PT J AU Huang, JD Brady, ST Richards, BW Stenoien, D Resau, JH Copeland, NG Jenkins, NA AF Huang, JD Brady, ST Richards, BW Stenoien, D Resau, JH Copeland, NG Jenkins, NA TI Direct interaction of microtubule- and actin-based transport motors SO NATURE LA English DT Article ID ATAXIC MUTANT RAT; DILUTE COAT COLOR; BRAIN MYOSIN-V; UNCONVENTIONAL MYOSIN; AXONAL-TRANSPORT; PURKINJE-CELLS; KINESIN HEAVY; GENE; CLONING; PROTEIN AB The microtubule network is thought to be used for long-range transport of cellular components in animal cells whereas the actin network is proposed to be used for short-range transport(1), although the mechanism(s) by which this transport is coordinated is poorly understood. For example, in sea urchins long-range Ca2+-regulated transport of exocytotic vesicles requires a microtubule-based motor, whereas an actin-based motor is used for short-range transport(2), In neurons, microtubule-based kinesin motor proteins are used for long-range vesicular transport(3) but microtubules do not extend into the neuronal termini, where actin filaments form the cytoskeletal framework(4), and kinesins are rapidly degraded upon their arrival in neuronal termini(5), indicating that vesicles may have to be transferred from microtubules to actin tracks to reach their final destination. Here we show that an actin-based vesicle-transport motor, MyoVA (ref. 6), can interact directly with a microtubule-based transport motor, KhcU. As would be expected if these complexes were functional, they also contain kinesin light chains and the localization of MyoVA and KhcU overlaps in the cell, These results indicate that cellular transport is, in part, coordinated through the direct interaction of different motor molecules. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Ft Detrick, MD 21702 USA. Univ Texas, SW Med Ctr, Dept Cell Biol & Neurosci, Dallas, TX 75235 USA. RP Jenkins, NA (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Ft Detrick, MD 21702 USA. NR 30 TC 264 Z9 271 U1 1 U2 18 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 21 PY 1999 VL 397 IS 6716 BP 267 EP 270 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 159QH UT WOS:000078184800056 PM 9930703 ER PT J AU Guzick, DS Carson, SA Coutifaris, C Overstreet, JW Factor-Litvak, P Steinkampf, MP Hill, JA Mastroianni, L Buster, JE Nakajima, ST Vogel, DL Canfield, RE AF Guzick, DS Carson, SA Coutifaris, C Overstreet, JW Factor-Litvak, P Steinkampf, MP Hill, JA Mastroianni, L Buster, JE Nakajima, ST Vogel, DL Canfield, RE CA Natl Cooperative Reproductive Med Network TI Efficacy of superovulation and intrauterine insemination in the treatment of infertility SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article AB Background Induction of superovulation with gonadotropins and intrauterine insemination are frequently used to treat infertility. We conducted a large, randomized, controlled clinical trial of these treatments. Methods We studied 932 couples in which the woman had no identifiable infertility factor and the man had motile sperm. The couples were randomly assigned to receive intracervical insemination, intrauterine insemination, superovulation and intracervical insemination, or superovulation and intrauterine insemination. Treatment continued for four cycles unless pregnancy was achieved. Results The 231 couples in the group treated with superovulation and intrauterine insemination had a higher rate of pregnancy (33 percent) than the 234 couples in the intrauterine-insemination group (18 percent), the 234 couples in the group treated with superovulation and intracervical insemination (19 percent), or the 233 couples in the intracervical-insemination group (10 percent). Stratified, discrete-time Cox proportional-hazards analysis showed that the couples in the group treated with superovulation and intrauterine insemination were 3.2 times as likely to become pregnant as those in the intracervical-insemination group (95 percent confidence interval, 2.0 to 5.3) and 1.7 times as likely as those in the intrauterine-insemination group (95 percent confidence interval, 1.2 to 2.6). The couples in the intrauterine-insemination group and in the group treated with superovulation and intracervical insemination were nearly twice as likely to conceive as those in the intracervical-insemination group. Conclusions Among infertile couples, treatment with induction of superovulation and intrauterine insemination is three times as likely to result in pregnancy as is intracervical insemination and twice as likely to result in pregnancy as is treatment with either superovulation and intracervical insemination or intrauterine insemination alone. (N Engl J Med 1999; 340:177-83.) (C) 1999, Massachusetts Medical Society. C1 Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. Univ Rochester, Rochester, NY USA. Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Univ Calif Davis, Sacramento, CA 95817 USA. Columbia Univ, New York, NY USA. Univ Alabama, Birmingham, AL USA. Harvard Univ, Boston, MA 02115 USA. NIH, Bethesda, MD 20892 USA. RP Guzick, DS (reprint author), Baylor Coll Med, Dept Obstet & Gynecol, 6550 Fannin 801, Houston, TX 77030 USA. FU NICHD NIH HHS [U10 HD26975, U10 HD26981, U10 HD27006] NR 12 TC 307 Z9 318 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 21 PY 1999 VL 340 IS 3 BP 177 EP 183 DI 10.1056/NEJM199901213400302 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 159YJ UT WOS:000078202900002 PM 9895397 ER PT J AU Nam, JH Wyatt, LS Chae, SL Cho, HW Park, YK Moss, B AF Nam, JH Wyatt, LS Chae, SL Cho, HW Park, YK Moss, B TI Protection against lethal Japanese encephalitis virus infection of mice by immunization with the highly attenuated MVA strain of vaccinia virus expressing JEV prM and E genes SO VACCINE LA English DT Article DE Japanese encephalitis virus; vaccinia virus; MVA strain ID HOST-RANGE; NUCLEOTIDE-SEQUENCE; RECOMBINANTS; IMMUNITY; PROTEIN; GENOME; GLYCOPROTEIN; INFLUENZA; SECRETION; VIREMIA AB Genes encoding the glycosylated precursor of the membrane (prM) and envelope (E) proteins of a Korean strain of Japanese encephalitis virus (JEV) were inserted into the genome of the host-range restricted, highly attenuated, and safety-tested MVA strain of vaccinia virus. MVA recombinants containing the JEV genes, under strong synthetic or modified H5 vaccinia virus promoters, were isolated. Synthesis of JEV prM and E proteins was detected by immunofluorescence microscopy, flow cytometry, and polyacrylamide gel electrophoresis. Mice inoculated and boosted by various routes with either of the MVA recombinants produced JEV neutralizing antibodies, that had titres comparable with those induced by an inactivated JEV vaccine, as well as haemagglutination-inhibiting antibodies. Mice immunized with 2x10(6) infectious units of MVA/JEV recombinants by intramuscular or intraperitoneal routes were completely protected against a 10(5) LD50 JEV challenge at 9 weeks of age. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Korean NIH, Dept Viral Dis, Div Arborviruses, Seoul, South Korea. Korea Univ, Dept Biol, Seoul 136701, South Korea. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), 4 Ctr Dr MSC 0445, Bethesda, MD 20892 USA. NR 30 TC 35 Z9 37 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JAN 21 PY 1999 VL 17 IS 3 BP 261 EP 268 DI 10.1016/S0264-410X(98)00156-X PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 146EA UT WOS:000077414000008 PM 9987162 ER PT J AU Gorse, GJ Corey, L Patel, GB Mandava, M Hsieh, RH Matthews, TJ Walker, MC McElrath, MJ Berman, PW Eibl, MM Belshe, RB AF Gorse, GJ Corey, L Patel, GB Mandava, M Hsieh, RH Matthews, TJ Walker, MC McElrath, MJ Berman, PW Eibl, MM Belshe, RB CA Natl Inst Allergy Infectious Dis AIDS Vaccine E TI HIV-1(MN) recombinant glycoprotein 160 vaccine-induced cellular and humoral immunity boosted by HIV-1(MN) recombinant glycoprotein 120 vaccine SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 ENVELOPE GLYCOPROTEINS; LYMPHOCYTE PROLIFERATIVE RESPONSES; GP160 SUBUNIT VACCINE; NEUTRALIZING ANTIBODIES; SERONEGATIVE VOLUNTEERS; UNINFECTED RECIPIENTS; BINDING-ANTIBODIES; CANDIDATE VACCINE; PRIMARY ISOLATE AB We evaluated prime-boost immunization with two recombinant envelope glycoprotein subunit vaccines (HIV-1(MN) recombinant gp160 vaccine in alum adjuvant [MN rgp160] and HIV-1(MN) recombinant gp120 vaccine in alum adjuvant [MN rgp120]) for safety and immunogenicity in healthy, HIV-1-uninfected adults. The rationale was to combine the helper T cell memory and binding antibody responses typically induced by rgp160 vaccines with the superior neutralizing antibody responses induced by rgp120 vaccines. In a double-blinded, controlled trial, volunteers were randomly assigned to receive MN rgp160 or adjuvant placebo, and a subset later received MN rgp120, The two vaccines were safe, but reactions to MN rgp160 and its adjuvant placebo exceeded those to MN rgp120, MN rgp160 induced IgG binding antibodies, including all IgG subclasses, to MN rgp160 in all vaccine recipients. HIV-1(MN)-neutralizing and anti-V3 MN peptide-binding antibodies were observed in a majority of volunteers after the fourth MN rgp160 immunization, but at lower levels compared with immunization with MN rgp120 in historical controls. HIV-1-binding, neutralizing, and fusion inhibition antibodies were boosted to the highest levels among MN rgp160 recipients after MN rgp120 booster injections. MN rgp120 boosting appeared to alter the distribution of MN rgp160 vaccine-induced, anti-MN rgp160 IgG subclass antibodies. MN rgp160 induced helper T cell memory, measured by lymphocyte proliferation, Th1 and Th2 cytokine production, and skin testing, Strategies including both subunit vaccines may help maximize antibody and helper T cell memory responses to HIV-1 envelope glycoprotein. C1 Dept Vet Affairs Med Ctr, St Louis, MO 63106 USA. Univ Washington, Seattle, WA 98104 USA. Washington Univ, Sch Med, Div Infect Dis & Immunol, St Louis, MO 63110 USA. EMMES Corp, Potomac, MD 20854 USA. Duke Univ, Sch Med, Dept Surg, Durham, NC 27710 USA. NIAID, Div AIDS, Vaccine Res & Dev Branch, Rockville, MD 20852 USA. Vaxgen Inc, Brisbane, CA 94080 USA. Univ Vienna, A-1090 Vienna, Austria. RP Gorse, GJ (reprint author), St Louis Univ, Hlth Sci Ctr, Dept Internal Med, Div Infect Dis & Immunol, 3635 Vista Ave FDT-8N, St Louis, MO 63110 USA. FU NIAID NIH HHS [N01-AI-05064, N01-AI-15106, N01-AI-45211] NR 65 TC 29 Z9 29 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JAN 20 PY 1999 VL 15 IS 2 BP 115 EP 132 DI 10.1089/088922299311547 PG 18 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 160JB UT WOS:000078225900003 PM 10029244 ER PT J AU Golding, H Ouyang, J Zaitseva, M Broder, CC Dimitrov, DS Lapham, C AF Golding, H Ouyang, J Zaitseva, M Broder, CC Dimitrov, DS Lapham, C TI Increased association of glycoprotein 120-CD4 with HIV type 1 coreceptors in the presence of complex-enhanced anti-CD4 monoclonal antibodies SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ENVELOPE-MEDIATED FUSION; SYNCYTIA FORMATION; CD4-GP120 COMPLEX; DOWN-MODULATION; CD4; BINDING; RECEPTOR; GP120; INFECTION AB CD4-specific monoclonal antibodies (CG1, CG7, and CG8), which bind,vith a 5- to 10-fold higher avidity to preformed CD4-gp120 complexes than to CD4, were previously shown to recognize newly identified conformational epitopes in the D1-CDR3 region of CD4, In the current study, these and other complex-enhanced MAbs were tested in three separate assays of HIV-1 coreceptor (CXCR4/CCR5) recruitment. In these assays, the CD4-specific MAbs CG1, -7, and -8 stabilized the association of coreceptor, gp120, and CD4 in trimolecular complexes. In contrast, the gp120-specific, complex-enhanced MAbs 48d and 17b were inhibitory. These data suggest that conformational changes in the CDR3 region of CD4-D1, induced by gp120 binding, may be involved in coreceptor association and thus play a positive role in the HIV-1 cell fusion process. C1 US FDA, Div Viral Prod, CBER, Bethesda, MD 20892 USA. NCI, Sect Membrane Struct & Funct, FCRDC, NIH, Frederick, MD 21702 USA. Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. RP Golding, H (reprint author), US FDA, Div Viral Prod, CBER, Bldg 29B,Room 4NN04,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 30 TC 6 Z9 6 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JAN 20 PY 1999 VL 15 IS 2 BP 149 EP 159 DI 10.1089/088922299311574 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 160JB UT WOS:000078225900006 PM 10029247 ER PT J AU McGuinness, RP Ge, Y Patel, SD Kashmiri, SVS Lee, HS Hand, PH Schlom, J Finer, MH McArthur, JG AF McGuinness, RP Ge, Y Patel, SD Kashmiri, SVS Lee, HS Hand, PH Schlom, J Finer, MH McArthur, JG TI Anti-tumor activity of human T cells expressing the CC49-zeta chimeric immune receptor SO HUMAN GENE THERAPY LA English DT Article ID FAS LIGAND; IN-VIVO; LYMPHOCYTES; CC49; GLYCOPROTEIN-72; GENERATION; CARCINOMA AB A chimeric immune receptor consisting of an extracellular antigen-binding domain derived from the CC49 humanized single-chain antibody, linked to the CD3 zeta signaling domain of the T cell receptor, was generated (CC49-zeta), This receptor binds to TAG-72, a mucin antigen expressed by most human adenocarcinomas. CC49-zeta was expressed in CD4(+) and CD8(+) T cells and induced cytokine production on stimulation. Human T cells expressing CC49-zeta recognized and killed tumor cell lines and primary tumor cells expressing TAG-72, CC49-zeta T cells did not mediate bystander killing of TAG-72-negative cells. In addition, CC49-zeta T cells not only killed Fast-positive tumor cells in vitro and in vivo, but also survived in their presence, and were immunoprotective in intraperitoneal and subcutaneous murine tumor xenograft models with TAG-72-positive human tumor cells. Finally, receptor-positive T cells were still effective in killing TAG-72-positive targets in the presence of physiological levels of soluble TAG-72, and did not induce killing of TAG-72-negative cells under the same conditions, This approach is being currently being utilized in a phase I clinical trial for the treatment of colon cancer. C1 Cell Genesys Inc, Dept Preclin Biol & Immunol, Foster City, CA 94404 USA. Cell Genesys Inc, Dept Vector Biol, Foster City, CA 94404 USA. NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. RP McArthur, JG (reprint author), Cell Genesys Inc, Dept Preclin Biol & Immunol, 344 Lakeside Dr, Foster City, CA 94404 USA. NR 21 TC 61 Z9 61 U1 0 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JAN 20 PY 1999 VL 10 IS 2 BP 165 EP 173 DI 10.1089/10430349950018968 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 161JW UT WOS:000078286300003 PM 10022542 ER PT J AU Winkler, JD Kim, SH Harrison, S Lewin, NE Blumberg, PM AF Winkler, JD Kim, SH Harrison, S Lewin, NE Blumberg, PM TI Synthesis and biological evaluation of highly functionalized analogues of ingenol SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID PROTEIN-KINASE-C; TUMOR PROMOTERS; PHORBOL ESTERS; STEREOSELECTIVE CONSTRUCTION; RING-SYSTEM; DITERPENES; MODEL; PHARMACOPHORE; TELEOCIDINS; INGENANES AB The synthesis and preliminary biological evaluation of the first analogues of ingenol, a potent activator of protein kinase C, containing all of the oxygen functionality and unsaturation present in the natural product, is described. C1 Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Mol Mech Tumor Promot Sect, Bethesda, MD 20892 USA. RP Winkler, JD (reprint author), Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. NR 29 TC 27 Z9 27 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JAN 20 PY 1999 VL 121 IS 2 BP 296 EP 300 DI 10.1021/ja9741842 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 174NR UT WOS:000079041700005 ER PT J AU Sausville, EA AF Sausville, EA TI A Bcr/Abl kinase antagonist for chronic myelogenous leukemia: A promising path for progress emerges SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID TYROSINE KINASE; PHILADELPHIA-CHROMOSOME; ABL C1 NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Sausville, EA (reprint author), NIH, EPN Bldg,Rm 843, Bethesda, MD 20892 USA. NR 17 TC 20 Z9 20 U1 1 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 20 PY 1999 VL 91 IS 2 BP 102 EP 103 DI 10.1093/jnci/91.2.102 PG 2 WC Oncology SC Oncology GA 158UB UT WOS:000078134400001 PM 9923844 ER PT J AU Neckers, LM AF Neckers, LM TI aHIF: the missing link between HIF-1 and VHL? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID ENDOTHELIAL GROWTH-FACTOR; HIPPEL-LINDAU PROTEIN; MESSENGER-RNA; HYPOXIA; MODULATION C1 NCI, Cell & Canc Biol Dept, Med Branch, Div Clin Sci, Bethesda, MD 20892 USA. RP Neckers, LM (reprint author), NIH, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. NR 17 TC 6 Z9 7 U1 0 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 20 PY 1999 VL 91 IS 2 BP 106 EP 107 DI 10.1093/jnci/91.2.106 PG 2 WC Oncology SC Oncology GA 158UB UT WOS:000078134400003 PM 9923846 ER PT J AU Thrash-Bingham, CA Tartof, KD AF Thrash-Bingham, CA Tartof, KD TI aHIF: A natural antisense transcript overexpressed in human renal cancer and during hypoxia SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID TUMOR-SUPPRESSOR GENE; POLYMERASE CHAIN-REACTION; LACTATE-DEHYDROGENASE-A; MESSENGER-RNA; INDUCIBLE FACTOR-1; POSTTRANSCRIPTIONAL REGULATION; CELL CARCINOMAS; EXPRESSION; PROTEIN; GROWTH AB Background: Nonpapillary renal carcinoma is the predominant form of human kidney cancer and represents a distinct disease entity, morphologically and molecularly, from papillary renal carcinoma. We have discovered a natural antisense transcript that is complementary to the 3' untranslated region of hypoxia inducible factor alpha (HIF1 alpha) messenger RNA (mRNA) and is strikingly overexpressed specifically in nonpapillary kidney cancer. HIF1 alpha. encodes a protein that is known to have two important functions: 1) to act as a transcription factor for hypoxia inducible genes and 2) to stabilize p53 protein during hypoxia, Because of the importance of HIF1 alpha, we have characterized this natural antisense transcript, which we have named "aHIF," Methods: Differential display, reverse transcription-polymerase chain reaction, ribonuclease protection, and DNA-sequencing methods were used in our analysis, Results and Conclusions: We show the following: 1) aHIF is a natural antisense transcript derived from HTF1 alpha gene sequences encoding the 3' untranslated region of HIF1 alpha mRNA; 2) aHIF is specifically overexpressed in all nonpapillary clear-cell renal carcinomas examined, but not in the papillary renal carcinomas examined; 3) aHIF is overexpressed in an established nonpapillary renal carcinoma cell line under both normoxic (i.e., normal aerobic) and hypoxic conditions; and 4) although aHIF is not further induced by hypoxia in nonpapillary disease, it can be induced in lymphocytes where there is a concomitant decrease in HTF1 alpha. mRNA, To our knowledge, this is the first case of overexpression of a natural antisense transcript exclusively associated with a specific human malignant disease. C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NCI, Urol Oncol Branch, Div Clin Sci, Bethesda, MD 20892 USA. RP Thrash-Bingham, CA (reprint author), NIH, Bldg 10,Rm 2B47, Bethesda, MD 20892 USA. EM kdtartof@helix.nih.gov FU NCI NIH HHS [CA06927] NR 54 TC 137 Z9 147 U1 0 U2 7 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 20 PY 1999 VL 91 IS 2 BP 143 EP 151 DI 10.1093/jnci/91.2.143 PG 9 WC Oncology SC Oncology GA 158UB UT WOS:000078134400012 PM 9923855 ER PT J AU Xie, YC Hwang, C Overwijk, W Zeng, Z Eng, MH Mule, JJ Imperiale, MJ Restifo, NP Sanda, MG AF Xie, YC Hwang, C Overwijk, W Zeng, Z Eng, MH Mule, JJ Imperiale, MJ Restifo, NP Sanda, MG TI Induction of tumor antigen-specific immunity in vivo by a novel vaccinia vector encoding safety-modified simian virus 40 T antigen SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HUMAN PAPILLOMAVIRUS TYPE-16; RECOMBINANT VACCINIA; SV40-TRANSFORMED CELLS; HUMAN MESOTHELIOMAS; CHOROID-PLEXUS; DNA-SEQUENCES; LYMPHOCYTES-T; SV40; SIMIAN-VIRUS-40; GENE AB Background: Evidence that simian virus 40 (SV40) is associated with human mesotheliomas, osteosarcomas, and brain tumors suggests that a recombinant vaccine directed against lethal cancers expressing SV40 T antigen (Tag) could have clinical utility, To address this potential need, we designed a novel vaccinia virus construct that encodes an SV40 Tag in which oncogenic domains were excluded and immunogenic domains were preserved. We named this recombinant construct vaccinia-encoding safety-modified SV40 Tag (vac-mTag). Methods: Purified vac-mTag was characterized by DNA sequencing, reverse transcription-coupled polymerase chain reaction, western blot analysis, and immunocytochemical techniques. Induction of Tag-specific immunity was examined by cytolytic T-cell assays, and the efficacy of vac-mTag in protecting animals against Tag-expressing tumors and in treating pre-established microscopic tumors was evaluated in vac-mTag-immunized BALB/c mice. Results: The immune response elicited by vac-mTag in C57BL/6 and BALB/c mice included an SV40 Tag-specific cytolytic T-lymphocyte activity against syngeneic (identical genetic background) SV40 Tag-expressing tumor targets. Immunization of mice with a single dose of vac-mTag resulted in potent protection against subsequent challenge with a lethal mouse cancer expressing SV40 Tag. In addition, single-dose vac-mTag immunization coadministered with interleukin 2 produced a possible therapeutic effect against a preadministered microscopic (but lethal) burden of Tag-expressing tumor cells in vivo. Conclusion: vac-mTag induces an effective immune response in mice that is specific for a tumor-associated antigen. This response protects against a lethal tumor challenge and results in a possible therapeutic effect against Tag-expressing tumors in vivo. Thus, vac-mTag provides a new avenue for the development of therapies for human cancers thought to be associated with SV40. C1 Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. NCI, Surg Branch, Bethesda, MD 20892 USA. Univ Michigan, Dept Urol Surg, Taubman Ctr 2916, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Med Oncol, Ann Arbor, MI 48109 USA. Vet Adm Med Ctr, Surg Serv, Urol Sect, Ann Arbor, MI 48105 USA. RP Sanda, MG (reprint author), Univ Michigan, Dept Urol Surg, Taubman Ctr 2916, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. RI Restifo, Nicholas/A-5713-2008; Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999]; NCI NIH HHS [CA71532] NR 35 TC 29 Z9 30 U1 0 U2 4 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 20 PY 1999 VL 91 IS 2 BP 169 EP 175 DI 10.1093/jnci/91.2.169 PG 7 WC Oncology SC Oncology GA 158UB UT WOS:000078134400016 PM 9923859 ER PT J AU Li, MF Xu, F Muller, J Huang, XJ Hearing, VJ Gorelik, E AF Li, MF Xu, F Muller, J Huang, XJ Hearing, VJ Gorelik, E TI Loss of retrovirus production in JB/RH melanoma cells transfected with H-2K(b) and TAP-1 genes SO VIROLOGY LA English DT Article ID INCREASED SENSITIVITY; EXPRESSION; ANTIGEN; MOUSE; INHIBITION; ANTIBODIES; DNA AB JB/RH1 melanoma cells, as well as other melanomas of C57BL/6 mice (B16 and JB/MS), express a common melanoma-associated antigen (MAA) encoded by an ecotropic melanoma-associated retrovirus (MelARV). JB/RH1 cells do not express the H-2K(b) molecules due to down-regulation of the H-2Kb and TAP-1 genes. When JB/RH1 cells were transfected with the H-2K(b) and cotranfected with the TAP-1 gene, it resulted in the appearance of H-2K(b) molecules and an increase in their immunogenicity, albeit they lost expression of retrovirus-encoded MAA recognized by MM2-9B6 mAb. Loss of MAA was found to result from a complete and stable elimination of ecotropic MelARV production in the H-2K(b)/TAP-1-transfected JB/RH1 cells. Northern blot analysis showed no differences in ecotropic retroviral messages in MelARV-producing and -nonproducing melanoma cells, suggesting that loss of MelARV production was not due to down-regulation of MelARV transcription. Southern blot analysis revealed several rearrangements in the proviral DNA of H-2K(b)-positive JB/RH1 melanoma cells. Sequence analysis of the ecotropic proviral DNA from these cells showed numerous nucleotide substitutions, some of which resulted in the appearance of a novel intraviral PstI restriction site and the loss of a HindIII restriction site in the pol region. PCR amplification of the proviral DNAs indicates that an ecotropic provirus found in the H-2K(b)-positive cells is novel and does not preexist in the parental H-2K(b)-negative melanoma cells. Conversely, the ecotropic provirus of the parental JB/RH1 cells was not amplifable from the H-2K(b)-positive cells. Our data indicate that stable loss of retroviral production in the H-2K(b)/TAP-1-transfected melanoma cells is probably due to the induction of recombination between a productive ecotropic MelARV and a defective nonecotropic provirus leading to the generation of a defective ecotropic provirus and the loss of MelARV production and expression of the retrovirus-encoded MAA. (C) 1999 Academic Press. C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA. US FDA, Div Viral Prod, Bethesda, MD 20014 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gorelik, E (reprint author), Univ Pittsburgh, Inst Canc, Biomed Sci Tower,Room W954, Pittsburgh, PA 15213 USA. FU NCI NIH HHS [CA59903] NR 26 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 20 PY 1999 VL 253 IS 2 BP 230 EP 240 DI 10.1006/viro.1998.9472 PG 11 WC Virology SC Virology GA 162MW UT WOS:000078351600010 PM 9918881 ER PT J AU Gorelick, RJ Benveniste, RE Gagliardi, TD Wiltrout, TA Busch, LK Bosche, WJ Coren, LV Lifson, JD Bradley, PJ Henderson, LE Arthur, LO AF Gorelick, RJ Benveniste, RE Gagliardi, TD Wiltrout, TA Busch, LK Bosche, WJ Coren, LV Lifson, JD Bradley, PJ Henderson, LE Arthur, LO TI Nucleocapsid protein zinc-finger mutants of simian immunodeficiency virus strain Mne produce virions that are replication defective in vitro and in vivo SO VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; GENOMIC RNA; VIRAL-RNA; T-CELL; TYPE-1; MACAQUES; GAG; INFECTIVITY; MUTATIONS; LENTIVIRUS AB All retroviruses (except the spumaretroviruses) contain a nucleocapsid (NC) protein that encodes one or two copies of the Zn2+-finger sequence -Cys-X-2-Cys-X-4-His-X-4-Cys-. This region has been shown to be essential for recognition and packaging of the genomic RNA during virion particle assembly. Additionally, this region has been shown to be involved in early infection events in a wide spectrum of retroviruses, including mammalian type C [e.g., murine leukemia virus (MuLV)], human immunodeficiency Virus type 1 (HIV-1), Rous sarcoma virus, and other retroviruses. Mutations in the two Zn2+-fingers of the NC protein of simian immunodeficiency virus strain Mne [SIV(Mne)] have been generated. The resulting virions contained the normal complement of processed viral proteins with densities indistinguishable from wild-type SIV(Mne). All of the mutants had electron micrograph morphologies similar to those of immature particles observed in wild-type preparations. RNA packaging was less affected by mutations in the NC protein of SIV(Mne) than has been observed for similar mutants in the MuLV and HIV-1 systems. Nevertheless, in vitro replication of SIV(Mne) NC mutants was impaired to levels comparable to those observed far MuLV and HIV-1 NC mutants; replication defective NC mutants are typically 10(5)- to 10(6)-fold less infectious than similar levels of wild-type virus. One mutant, Delta Cys33-Cys36, was also found to be noninfectious in vivo when mutant virus was administered intravenously to a pig-tailed macaque. NC mutations can therefore be used to generate replication defective virions for candidate vaccines in the SIV macaque model for primate lentiviral diseases. C1 SAIC Frederick, AIDS Vaccine Program, Frederick, MD 21702 USA. NCI, Lab Genome Divers, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Gorelick, RJ (reprint author), SAIC Frederick, AIDS Vaccine Program, Frederick, MD 21702 USA. EM gorelick@avpaxp1.ncifcrf.gov FU NCI NIH HHS [N01-CO-56000] NR 41 TC 42 Z9 42 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 20 PY 1999 VL 253 IS 2 BP 259 EP 270 DI 10.1006/viro.1998.9513 PG 12 WC Virology SC Virology GA 162MW UT WOS:000078351600013 PM 9918884 ER PT J AU Hortin, GL AF Hortin, GL TI Screening for thyroid disease SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Hortin, GL (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 19 PY 1999 VL 130 IS 2 BP 161 EP 161 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 158KG UT WOS:000078114200013 PM 10068366 ER PT J AU Banerjee, A Kasmala, LT Hamel, E Sun, L Lee, KH AF Banerjee, A Kasmala, LT Hamel, E Sun, L Lee, KH TI Interaction of novel thiocolchicine analogs with the tubulin isoforms from bovine brain SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID COLCHICINE BINDING; BETA-TUBULIN; B-RING; MONOCLONAL-ANTIBODY; FLUORESCENCE; KINETICS; ISOTYPES; PODOPHYLLOTOXIN; PURIFICATION; COMPLEX AB The antimitotic alkaloid colchicine binds to tubulin and inhibits microtubule assembly. Recently a new series of colchicine derivatives has been synthesized in which the seven-membered B-ring was Shortened to a six-membered ring. In an effort to study the role of the B-ring substituents in this new series, we have studied the interaction of two compounds of this series, THC 5 and THC 18, with tubulin isoforms from bovine brain. We find that THC 18, which has a side chain with a pi-bonded SP2 conformation, binds differently to the tubulin isoforms, while THC 5 with a slightly different side chain does not. The results indicate that the conformation of the B-ring domain plays a major role in the differential interaction of a colchicine derivative with different tubulin isoforms. The results will be very important in designing potent antitumor derivatives of colchicine. (C) 1999 Academic Press. C1 Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA. NCI, NIH, Frederick, MD 21702 USA. Univ N Carolina, Nat Prod Lab, Chapel Hill, NC 27599 USA. RP Banerjee, A (reprint author), Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA. FU NCI NIH HHS [CA 26376, CA 59711] NR 23 TC 8 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 19 PY 1999 VL 254 IS 2 BP 334 EP 337 DI 10.1006/bbrc.1998.9943 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 162VW UT WOS:000078368500011 PM 9918839 ER PT J AU Ponten, I Sayer, JM Pilcher, AS Yagi, H Kumar, S Jerina, DM Dipple, A AF Ponten, I Sayer, JM Pilcher, AS Yagi, H Kumar, S Jerina, DM Dipple, A TI Sequence context effects on mutational properties of cis-opened benzo[c]phenanthrene diol epoxide-deoxyadenosine adducts in site-specific mutation studies SO BIOCHEMISTRY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; INDUCED FRAMESHIFT MUTAGENESIS; SNAKE-VENOM PHOSPHODIESTERASE; SINGLE-STRANDED VECTOR; CARCINOGEN-DNA ADDUCTS; OLIGONUCLEOTIDE TEMPLATES; BASE SEQUENCE; MAJOR ADDUCT; IN-VITRO; BENZOPYRENE AB Diastereomeric N-6-substituted dAdo adducts (cis B[c]PhDE-2/1R and cis B[c]PhDE-2/1S) that correspond to cis-opening at C-1 of the enantiomeric benzo[c]phenanthrene 3,4-diol 1,2-epoxides in which the epoxide oxygen and the benzylic hydroxyl group are trans (DE-2) were synthetically incorporated into oligonucleotide 16-mers. Each adduct was placed at the fourth nucleotide from the 5'-end of each of two different oligonucleotide sequences derived from the E. coli supF gene. Each adduct was also placed in two additional oligonucleotide sequences that were constructed by interchanging the adduct site and the immediately adjacent nucleotides between the two original sequences. These oligonucleotides were designed for use in site-specific mutation studies, with a single-stranded bacteriophage M13mp7L2 vector, to determine if the effects of sequence context on types and frequencies of base substitution mutations are attributable only to nucleotides immediately adjacent to these polycyclic aromatic hydrocarbon diol epoxide-dAdo adducts, or whether more distant nucleotide residues also affect the mutagenic response. In SOS-induced Escherichia coli SMH77, total base substitution mutation frequencies for the cis B[c]PhDE-2/1R-dAdo adduct were relatively low (0.62-5.6%) compared with those for the cis B[c]PhDE-2/1S-dAdo adduct (11.9-56.5%). Depending on sequence context, cis B[c]PhDE-2/1R-dAdo gave predominantly A-->T or a more equal distribution of A-->T and A-G mutations whereas cis B[c]PhDE-2/1S-dAdo gave either predominantly A-->T or predominantly A-->G base substitutions. Our results clearly indicate that nucleotides that are distal as well as those that are proximal to the adduct site are capable of influencing both the mutation frequency and the distribution of base substitution mutations. C1 NCI, Chem Carcinogenesis Lab, Adv Biosci Labs, Basic Res Program,Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. SUNY Coll Buffalo, Great Lakes Ctr, Buffalo, NY 14222 USA. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Ponten, I (reprint author), NCI, Chem Carcinogenesis Lab, Adv Biosci Labs, Basic Res Program,Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 60 TC 20 Z9 20 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 19 PY 1999 VL 38 IS 3 BP 1144 EP 1152 DI 10.1021/bi982436l PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 170ZA UT WOS:000078836200034 PM 9894012 ER PT J AU Brzeska, H Young, R Knaus, U Korn, ED AF Brzeska, H Young, R Knaus, U Korn, ED TI Myosin I heavy chain kinase: Cloning of the full-length gene and acidic lipid-dependent activation by Rac and Cdc42 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ACANTHAMOEBA MYOSIN; P21-ACTIVATED KINASE; MOLECULAR-CLONING; CATALYTIC DOMAIN; SUBSTRATE-SPECIFICITY; COFACTOR PROTEIN; ACTIN ACTIVATION; BINDING DOMAINS; 3RD ISOFORM; PAK AB Acanthamoeba myosin I heavy chain kinase (MIHCK) phosphorylates the heavy chains of amoeba myosins I, increasing their actin-activated ATPase activities. The activity of MIHCK is increased by binding to acidic phospholipids or membranes and by autophosphorylation at multiple sites. Phosphorylation at a single site is necessary and sufficient for full activation of the expressed catalytic domain, The rate of autophosphorylation of native MIHCK is controlled by a region N-terminal to the catalytic domain, By its substrate specificity and the sequence of its C-terminal catalytic domain, MIHCK was identified as a p21-activated kinase (PAK). We have now cloned the full-length genomic DNA and cDNA of MIHCK and have shown it to contain the conserved p21-binding site common to many members of the PAK family, Like some mammalian PAKs, MIHCK is activated by Rac and Cdc42, and this activation is GTP-dependent and accompanied by autophosphorylation, In contrast to mammalian PAKs, activation of MIHCK by Rac and Cdc42 requires the presence of acidic lipids. Also unlike mammalian PAK, MIHCK is not activated by sphingosine or other non-negatively charged lipids, The acidic lipid-binding site is near the N terminus followed by the p21-binding region. The N-terminal regulatory domain of MIHCK contains alternating strongly positive and strongly negative regions. and the extremely Pro-rich middle region of MIHCK has a strongly acidic N-terminal segment and a strongly basic C-terminal segment. We propose that autophosphorylation activates MIHCK by neutralizing the basic segment of the Pro-rich region, thus unfolding the regulatory domain and abolishing its inhibition of the catalytic domain. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Scripps Res Inst, La Jolla, CA 92307 USA. RP Korn, ED (reprint author), NHLBI, Cell Biol Lab, NIH, Bldg 3,Room B1-22, Bethesda, MD 20892 USA. EM edk@nih.gov RI Korn, Edward/F-9929-2012 NR 46 TC 35 Z9 36 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 19 PY 1999 VL 96 IS 2 BP 394 EP 399 DI 10.1073/pnas.96.2.394 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 159RY UT WOS:000078189200018 PM 9892644 ER PT J AU Bai, YW AF Bai, YW TI Kinetic evidence for an on-pathway intermediate in the folding of cytochrome c SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DENATURANT CONCENTRATION; PROTEIN STABILITY; HYDROGEN-EXCHANGE; MOLTEN GLOBULE; MECHANISM; BARNASE; STATE; UREA AB An early folding event of cytochrome c populates a helix-containing intermediate (I-NC) because of a pH-dependent misligation between the heme iron and nonnative ligands in the unfolded state (U), For folding to proceed, the nonnative ligation error must first be corrected. It is not known whether I is on-pathway, with folding to the native state (N) as in U <-> I-NC <-> N, or whether the I must first move back through the U and then fold to the N through some alternative path (I-NC <-> U <-> N). By means of a kinetic test, it is shown here that the cytochrome c I does not first unfold to U, The method used provides an experimental criterion for rejecting the off-pathway I <-> U <-> N option. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Bai, YW (reprint author), NCI, Biochem Lab, NIH, Bldg 37,Room 4A-01, Bethesda, MD 20892 USA. NR 35 TC 67 Z9 67 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 19 PY 1999 VL 96 IS 2 BP 477 EP 480 DI 10.1073/pnas.96.2.477 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 159RY UT WOS:000078189200032 PM 9892658 ER PT J AU Gayko, U Cleghon, V Copeland, T Morrison, DK Perrimon, N AF Gayko, U Cleghon, V Copeland, T Morrison, DK Perrimon, N TI Synergistic activities of multiple phosphotyrosine residues mediate full signaling from the Drosophila Torso receptor tyrosine kinase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GROWTH-FACTOR RECEPTOR; SH2/SH3 ADAPTER PROTEIN; AUTOPHOSPHORYLATION SITES; PHOSPHATIDYLINOSITOL-3 KINASE; TERMINAL SIGNAL; SH2 DOMAIN; TRANSDUCTION; ACTIVATION; SEVENLESS; PATTERN AB Here, we identify four tyrosine residues (Y644, Y698, E767, and Y772) that become phosphorylated after activation of the Torso (Tor) receptor tyrosine kinase. Previously, we characterized phosphotyrosine sites (P-Y630 and P-Y918), Of the six P-Y sites identified, three (Y630, Y644, and Y698) are located in the kinase domain insert region, one (Y918) is located in the C-terminal tail region, and two (Y767 and Y772) are located in the activation loop of the kinase domain. To investigate the function of each P-Y residue in Tor signaling, we have generated transgenic Drosophila embryos expressing mutant Tor receptors containing either single or multiple tyrosine to phenylalanine substitutions. Single P-Y mutations were found to have either positive, negative, or no effect on the signaling activity of the receptor. Elimination of all P-Y sites within the kinase insert region resulted in the complete loss of receptor function, indicating that some combination of these sites is necessary for Tor signaling. Mutation of the C-terminal P-Y918 site revealed that this site is responsible for negative signaling or down-regulation of receptor activity. Mutation of the P-Y sites in the kinase domain activation loop demonstrated that these sites are essential for enzymatic activity. Our analysis provides a detailed in vivo example of the extent of cooperativity between P-Y residues in transducing the signal received by a receptor tyrosine kinase and in vivo data demonstrating the function of P-Y residues in the activation loop of the kinase domain. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. NCI, Frederick Canc Res & Dev Ctr, Cellular Growth Mechanisms Sect, ABL Basic Res Program, Frederick, MD 21702 USA. RP Gayko, U (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RI Perrimon, Norbert/F-9766-2011 NR 48 TC 8 Z9 8 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 19 PY 1999 VL 96 IS 2 BP 523 EP 528 DI 10.1073/pnas.96.2.523 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 159RY UT WOS:000078189200040 PM 9892666 ER PT J AU Henning, KA Novotny, EA Compton, ST Guan, XY Liu, PP Ashlock, MA AF Henning, KA Novotny, EA Compton, ST Guan, XY Liu, PP Ashlock, MA TI Human artificial chromosomes generated by modification of a yeast artificial chromosome containing both human alpha satellite and single-copy DNA sequences SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SOMATIC-CELL HYBRID; HUMAN TELOMERES; MAMMALIAN-CELLS; CENP-C; PROTEIN; CENTROMERES; VECTORS; LOCALIZATION; CONSTRUCTION; SEGREGATION AB A human artificial chromosome (HAC) vector was constructed from a 1-Mb yeast artificial chromosome (YAC) that was selected based on its size from among several YACs identified by screening a randomly chosen subset of the Centre d'Etude du Polymorphisme Humain (CEPH) (Paris) YAC library with a degenerate alpha satellite probe. This YAC, which also included non-alpha satellite DNA, was modified to contain human telomeric DNA and a putative origin of replication from the human beta-globin locus, The resultant HAC vector was introduced into human cells by lipid-mediated DNA transfection, and HACs were identified that bound the active kinetochore protein CENP-E and were mitotically stable in the absence of selection for at least 100 generations. Microdissected HACs used as fluorescence in situ hybridization probes localized to the HAC itself and not to the arms of any endogenous human chromosomes, suggesting that the NAC was not formed by telomere fragmentation. Our ability to manipulate the HAC vector by recombinant genetic methods should allow us to further define the elements necessary for mammalian chromosome function. C1 Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Ashlock, MA (reprint author), Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Room 3A14,49 Convent Dr,MSC 4442, Bethesda, MD 20892 USA. RI Guan, Xin-Yuan/A-3639-2009; Liu, Paul/A-7976-2012 OI Guan, Xin-Yuan/0000-0002-4485-6017; Liu, Paul/0000-0002-6779-025X NR 52 TC 94 Z9 96 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 19 PY 1999 VL 96 IS 2 BP 592 EP 597 DI 10.1073/pnas.96.2.592 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 159RY UT WOS:000078189200052 PM 9892678 ER PT J AU Huber, R Hansen, RS Strazzullo, M Pengue, G Mazzarella, R D'Urso, M Schlessinger, D Pilia, G Gartler, SM D'Esposito, M AF Huber, R Hansen, RS Strazzullo, M Pengue, G Mazzarella, R D'Urso, M Schlessinger, D Pilia, G Gartler, SM D'Esposito, M TI DNA methylation in transcriptional repression of two differentially expressed X-linked genes, GPC3 and SYBL1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CHROMOSOME INACTIVATION; DENOVO METHYLATION; CPG ISLANDS; CELL-LINES; SITES; IDENTIFICATION; PROTEIN; REGION AB Methylation of CpG islands is an established transcriptional repressive mechanism and is a feature of silencing in X chromosome inactivation, Housekeeping genes that are subject to X inactivation exhibit differential methylation of their CpG islands such that the inactive alleles are hypermethylated, In this report, we examine two contrasting X-linked genes with CpG islands for regulation by DNA methylation: SYBL1, a housekeeping gene in the Xq pseudoautosomal region, and GPC3, a tissue-specific gene in Xq26 that is implicated in the etiology of the Simpson-Golabi-Behmel overgrowth syndrome. We observed that in vitro methylation of either the SYBL1 or the GPC3 promoter resulted in repression of reporter constructs. In normal contexts, we found that both the Y and inactive X alleles of SYBL1 are repressed and hypermethylated, whereas the active X allele is expressed and unmethylated. Furthermore, the Y and inactive X alleles of SYBL1 were derepressed by treatment with the demethylating agent azadeoxycytidine, GPC3 is also subject to X inactivation, and the active X allele is unmethylated in nonexpressing leukocytes as well as in an expressing cell line, suggesting that methylation is not involved in the tissue-specific repression of this allele. The inactive X allele, however, is hypermethylated in leukocytes, presumably reflecting early X inactivation events that become important for gene dosage in expressing lineages. These and other data suggest that all CPG islands on Xq, including the pseudoautosomal region, are subject to X inactivation-induced meth ylation, Additionally, methylation of SYBL1 on Yq may derive from a process related to X inactivation that targets large chromatin domains for transcriptional repression. C1 NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Genet, Seattle, WA 98195 USA. Int Inst Genet & Biophys, I-80125 Naples, Italy. Washington Univ, Dept Internal Med, St Louis, MO 63110 USA. Washington Univ, Inst Biomed Comp, St Louis, MO 63110 USA. Inst Ric Talassemie & Anemie Mediterranee, I-09100 Cagliari, Italy. RP Huber, R (reprint author), DuPont Pharmaceut, Wilmington, DE 19880 USA. RI Strazzullo, Maria/B-6050-2015 FU NICHD NIH HHS [HD16659, R01 HD016659]; NIGMS NIH HHS [GM07067, T32 GM007067, GM52463]; Telethon [E.0526] NR 27 TC 38 Z9 40 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 19 PY 1999 VL 96 IS 2 BP 616 EP 621 DI 10.1073/pnas.96.2.616 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 159RY UT WOS:000078189200056 PM 9892682 ER PT J AU Lillard, JW Boyaka, PN Chertov, O Oppenheim, JJ McGhee, JR AF Lillard, JW Boyaka, PN Chertov, O Oppenheim, JJ McGhee, JR TI Mechanisms for induction of acquired host immunity by neutrophil peptide defensins SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE innate immunity; mucosal immunity; T helper; B7-CD28; CD40-CD40L ID VASOACTIVE INTESTINAL PEPTIDE; ANTIMICROBIAL PEPTIDES; ANTIBODY-RESPONSES; RABBIT GRANULOCYTES; EPITHELIAL-CELLS; MUCOSAL IMMUNITY; CHOLERA-TOXIN; SUBSTANCE-P; LYMPHOCYTES; INTERLEUKIN-4 AB Human neutrophil peptide (HNP) defensins were studied to determine their potential effects on adaptive mucosal immunity. Intranasal delivery of HNPs plus ovalbumin (OVA) enhanced OVA-specific serum IgG antibody (Ab) responses. However, OVA-specific IgA Abs were not induced in mucosal secretions or in serum. CD4(+) T cells of intranasally immunized mice displayed higher OVA-specific proliferative responses and elevated production of interferon gamma, interleukin (IL) 5, IL-6, and IL-10 when compared with control groups receiving OVA alone. In vitro, HNPs also enhanced both proliferative responses and T helper (Th) cytokine secretion profiles of CD3 epsilon-stimulated spleen- and Peyer's patch-derived naive CD4(+) T cells. HNPs modulated the expression of costimulatory molecules by lipopolysaccharide- or CD3 epsilon-stimulated splenic and Peyer's patch B or T cell populations, respectively. These studies show that defensins enhance systemic IgG, but not IgA, Ab responses through help provided by CD4(+) Th1- and Th2-type cytokines and foster B and T cell interactions to link innate immunity with the adaptive immune system. C1 Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. NCI, Intramural Res Support Program, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Mol Immunoregulat Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP McGhee, JR (reprint author), Univ Alabama, Dept Microbiol, 273A BBRB,845 19th St S, Birmingham, AL 35294 USA. EM mcghee@uab.edu FU NIAID NIH HHS [AI 18958, AI 43197, R01 AI018958, R01 AI043197]; NIDDK NIH HHS [P01 DK044240, DK 44240] NR 43 TC 212 Z9 226 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 19 PY 1999 VL 96 IS 2 BP 651 EP 656 DI 10.1073/pnas.96.2.651 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 159RY UT WOS:000078189200062 PM 9892688 ER PT J AU Penn, ML Grivel, JC Schramm, B Goldsmith, MA Margolis, L AF Penn, ML Grivel, JC Schramm, B Goldsmith, MA Margolis, L TI CXCR4 utilization is sufficient to trigger CD4+ T cell depletion in HIV-1-infected human lymphoid tissue SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; SYNCYTIUM-INDUCING PHENOTYPE; MACROPHAGE-TROPIC HIV-1; CHEMOKINE RECEPTOR; ENVELOPE GLYCOPROTEINS; BIOLOGICAL PHENOTYPE; CORECEPTOR USAGE; AMINO-ACIDS; SCID MICE; INFECTION AB The human chemokine receptors CCR5 and CXCR4 have emerged as the predominant cofactors, along with CD4, for cellular entry of HIV-1 in vivo whereas the contribution of other chemokine receptors to HIV disease has not been yet determined, CCR5-specific (R5) viruses predominate during primary HIV-1 infection whereas viruses with specificity for CXCR4 (R5/X4 or X4 viruses) often emerge in late stages of HIV disease. The evolution of X4 viruses is associated with a rapid decline in CD4+ T cells, although a causative relationship between viral tropism and CD4+ T cell depletion has not yet been proven. To rigorously test this relationship, we assessed CD4+ T cell depletion in suspensions of human peripheral blood mononuclear cells and in explants of human lymphoid tissue on exposure to paired viruses that are genetically identical (isogenic) except for select envelope determinants specifying reciprocal tropism for CXCR4 or CCR5, In both systems, X4 HIV-1 massively depleted CD4+ lymphocytes whereas matched R5 viruses depleted such cells only mildly despite comparable viral replication kinetics, These findings demonstrate that the coreceptor specificities of HIV-1 are a causal factor in CD4+ cell depletion ex vivo and strongly support the hypothesis that the evolution of viral envelope leading to usage of CXCR4 in vivo accelerates loss of CD4+ T cells, causing immunodeficiency. C1 NICHHD, Lab Mol & Cellular Biophys, Bethesda, MD 20892 USA. Univ Calif San Francisco, Sch Med, Dept Med, Gladstone Inst Virol & Immunol, San Francisco, CA 94141 USA. RP Margolis, L (reprint author), NICHHD, Lab Mol & Cellular Biophys, Bethesda, MD 20892 USA. EM mgoldsmith@gladstone.ucsf.edu; margolis@helix.nih.gov FU NIAID NIH HHS [R21-AI42654] NR 51 TC 111 Z9 113 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 19 PY 1999 VL 96 IS 2 BP 663 EP 668 DI 10.1073/pnas.96.2.663 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 159RY UT WOS:000078189200064 PM 9892690 ER PT J AU Xu, ZQ Hollingshead, MG Borgel, S Elder, C Khilevich, A Flavin, MT AF Xu, ZQ Hollingshead, MG Borgel, S Elder, C Khilevich, A Flavin, MT TI In vivo anti-HIV activity of (+)-calanolide A in the hollow fiber mouse model SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; REVERSE-TRANSCRIPTASE INHIBITOR; ANTIVIRAL ACTIVITY; CALANOLIDE-A; DERIVATIVES; RESISTANCE; RESOLUTION; PRODUCTS; CELLS; AGENT AB In vivo anti-HIV efficacy of(+)-calanolide A has been evaluated in a hollow fiber mouse model. It was demonstrated that the compound was capable of suppressing virus replication in two distinct and separate physiologic compartments (ip and sc) following oral or parenteral administration on a once- or twice-daily treatment schedule. A synergistic effect was observed for the combination of(+)-calanolide A and AZT. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 MediChem Res Inc, Lemont, IL 60439 USA. Sarawak MediChem Pharmaceut Inc, Lemont, IL 60439 USA. NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diagnost, Biol Testing Branch,Dev Therapeut Program,SAIC, Frederick, MD 21701 USA. RP Xu, ZQ (reprint author), MediChem Res Inc, 12305 S New Ave, Lemont, IL 60439 USA. FU NCI NIH HHS [N01-CO-56000] NR 20 TC 30 Z9 34 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JAN 18 PY 1999 VL 9 IS 2 BP 133 EP 138 DI 10.1016/S0960-894X(98)00713-6 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 161YZ UT WOS:000078319300004 PM 10021914 ER PT J AU Tarrant, TK Silver, PB Wahlsten, JL Rizzo, LV Chan, CC Wiggert, B Caspi, RR AF Tarrant, TK Silver, PB Wahlsten, JL Rizzo, LV Chan, CC Wiggert, B Caspi, RR TI Interleukin 12 protects from a T helper type 1-mediated autoimmune disease, experimental autoimmune uveitis, through a mechanism involving interferon gamma, nitric oxide, and apoptosis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article; Proceedings Paper CT AAAAI/AAI/CIS Joint Meeting CY FEB 21-26, 1997 CL SAN FRANCISCO, CALIFORNIA SP AAAAI, AAI, CIS DE interleukin 12; apoptosis; autoimmune disease; uveitis; T helper type 1 ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; NECROSIS-FACTOR-ALPHA; RETINOID-BINDING PROTEIN; CELL STIMULATORY FACTOR; IFN-GAMMA; MEDIATED APOPTOSIS; DENDRITIC CELLS; GENETIC SUSCEPTIBILITY; LEISHMANIA-MAJOR; IMMUNE-RESPONSES AB Pathogenic effector T cells in experimental autoimmune uveitis (EAU) are T helper type 1-like, and interleukin (IL)-12 is required for their generation and function. Therefore, we expected that IL-12 administration would have disease-enhancing effects. Mice were immunized with a uveitogenic regimen of the retinal antigen interphotoreceptor retinoid-binding protein, treated with IL-12 (100 ng/d for 5 d), and EAU was assessed by histopathology. Unexpectedly, IL-12 treatment failed to enhance EAU in resistant strains and downregulated disease in susceptible strains. Only treatment during the first, but not during the second, week after immunization was consistently protective. High levels of interferon gamma (IFN-gamma) were present in the serum during IL-12 treatment, but subsequent antigen-specific IFN-gamma production in protected mice was diminished, as were IL-5 production, lymph node cell proliferation, and serum antibody levels. Treated mice had fewer cells and evidence of enhanced apoptosis in the draining lymph nodes. Unlike wild-type mice, IFN-gamma-deficient, inducible nitric oxide synthase (iNOS)-deficient, and Bcl-2(lck) transgenic mice were poorly protected by IL-12, whereas IL-10-deficient mice were protected. We conclude that administration of IL-12 aborts disease by curtailing development of uveitogenic effector T cells. The data are compatible with the interpretation that IL-12 induces systemic hyperinduction of IFN-gamma, causing activation of iNOS and production of NO, which mediates protection at least in part by triggering Bcl-2 regulated apoptotic deletion of the antigen-specific T cells as they are being primed. C1 NEI, Immunol Lab, Bethesda, MD 20892 USA. NEI, Retinal Cell & Mol Biol Lab, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, NIH Res Scholars Program, Bethesda, MD 20892 USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, 10 Ctr Dr,MSC 1857,Bldg 10,Rm 10N222, Bethesda, MD 20892 USA. EM rsaspi@helix.nih.gov RI Rizzo, Luiz Vicente/B-4458-2009 NR 68 TC 149 Z9 156 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JAN 18 PY 1999 VL 189 IS 2 BP 219 EP 230 DI 10.1084/jem.189.2.219 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 159TY UT WOS:000078191700001 PM 9892605 ER PT J AU Zhao, R Loftus, DJ Appella, E Collins, EJ AF Zhao, R Loftus, DJ Appella, E Collins, EJ TI Structural evidence of T cell xeno-reactivity in the absence of molecular mimicry SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE major histocompatibility complex crystallography; xeno-reactivity; transplantation; T cell receptor ID CLASS-I MOLECULES; 3-DIMENSIONAL STRUCTURE; CRYSTAL-STRUCTURES; PEPTIDE COMPLEXES; VIRAL PEPTIDES; ALPHA-HELICES; MHC MOLECULES; ANTI-IDIOTOPE; RECOGNITION; SELECTION AB The T cell receptor (TCR), from a xeno-reactive murine cytotoxic T lymphocyte clone AHIII12.2, recognizes murine H-2D(b) complexed with peptide p1027 (FAPGVFPYM), as well as human HLA-A2.1 complexed with peptide p1049 (ALWGFFPVL). A commonly proposed model (the molecular mimicry model) used to explain TCR cross-reactivity suggests that the molecular surfaces of the recognized complexes are similar in shape, charge, or both, in spite of the primary sequence differences. To examine the mechanism of xeno-reactivity of AHIII12.2, we have determined the crystal structures of A2/p1049 and D-b/p1027 to 2.5 Angstrom and 2.8 Angstrom resolution, respectively. The crystal structures show that the TCR footprint regions of the two class I complexes are significantly different in shape and charge. We propose that rather than simple molecular mimicry, unpredictable arrays of common and differential contacts on the two class I complexes are used for their recognition by the same TCR. C1 Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Collins, EJ (reprint author), Univ N Carolina, Dept Microbiol & Immunol, CB 7290,804 ME Jones Bldg, Chapel Hill, NC 27599 USA. EM collins1@med.unc.edu FU NIAID NIH HHS [AI29324, AI20288] NR 45 TC 63 Z9 64 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JAN 18 PY 1999 VL 189 IS 2 BP 359 EP 370 DI 10.1084/jem.189.2.359 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 159TY UT WOS:000078191700014 PM 9892618 ER PT J AU Su, SB Gong, WH Gao, JL Shen, WP Murphy, PM Oppenheim, JJ Wang, JM AF Su, SB Gong, WH Gao, JL Shen, WP Murphy, PM Oppenheim, JJ Wang, JM TI A seven-transmembrane, G protein-coupled receptor, FPRL1, mediates the chemotactic activity of serum amyloid A for human phagocytic cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE serum amyloid A; FPRL1; chemotaxis; calcium flux; receptor ID FORMYL PEPTIDE RECEPTOR; LIPOXIN A(4) RECEPTOR; CHEMOATTRACTANT RECEPTORS; HUMAN MONOCYTES; STABLE ANALOGS; A PROTEIN; EXPRESSION; MIGRATION; INHIBITION; INDUCTION AB We have previously reported (Badolato, R., J.M. Wang, W.J. Murphy, A.R. Lloyd, D.F. Michiel, L.L. Bausserman, D.J.. Kelvin, and J.J. Oppenheim. 1994. J. Exp. Med. 180:203; Xu, L., R. Badolato, W.J. Murphy, D.L. Longo, M. Anver, S. Hale, J.J. Oppenheim, and J.M. Wang. 1995. J. Immunol. 155:1184.) that the acute phase protein serum amyloid A (SAA) is a potent chemoattractant for human leukocytes in vitro and mouse phagocytes in vivo. To identify the signaling mechanisms, we evaluated patterns of cross-desensitization between SAA and other leukocyte chemoattrctants. We found that the chemotactic bacterial peptide, N-formylmethionyl-leucyl-phenylalanine (fMLP), was able to specifically attenuate Ca2+ mobilization in human phagocytes induced by SAA, but only at very high concentrations, suggesting that SAA uses a low affinity fMLP receptor. Here we demonstrate that SAA selectively induced Ca2+ mobilization and migration of HEK cells expressing FPRL1, a human seven-transmembrane domain phagocyte receptor with low affinity for fMLP, and high affinity for lipoxin A4. Furthermore, radiolabeled SAA specifically bound to human phagocytes and FPRL1-transfected 293 cells. In contrast, SAA was not a ligand or agonist for FPR, the high affinity fMLP receptor. Thus, SAA is the first chemotactic ligand identified for FPRL1. Our results suggest that FPRL1 mediates phagocyte migration in response to SAA. C1 NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Div Basic Sci, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Wang, JM (reprint author), NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Div Basic Sci, Bldg 560,Rm 31-40, Frederick, MD 21702 USA. EM wangji@mail.ncifcrf.gov FU NCI NIH HHS [N01-CO-56000] NR 43 TC 304 Z9 314 U1 1 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JAN 18 PY 1999 VL 189 IS 2 BP 395 EP 402 DI 10.1084/jem.189.2.395 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 159TY UT WOS:000078191700017 PM 9892621 ER PT J AU Shaw, KTY Greig, NH AF Shaw, KTY Greig, NH TI Chemokine receptor mRNA expression at the in vitro blood-brain barrier during HIV infection SO NEUROREPORT LA English DT Article DE AIDS dementia complex; blood-brain barrier; chemokine receptors; HIV ID ENDOTHELIAL-CELLS; TAT PROTEIN; GP120; INVITRO AB VIRAL entry through the blood-brain barrier (BBB) has not been fully defined and identification of coreceptors that can facilitate this phenomenon is crucial in understanding disease progression. Using a RNAse protection assay to examine chemokine receptor families simultaneously, we analyzed the total RNA of in vitro BBB cultures treated with purified preparations of HIV gp120, gp41, TAT proteins and TNF-alpha. HIV tat protein affected CCR1 and CCR3 mRNA expression whereas -the other viral by-products had no effect. Interestingly, TNF-alpha was able to induce CCR1, CCR3 as well as CXCR1, CXCR2, CXCR4 receptors and Burkitt's lymphoma receptor BLR2. These results suggest that HIV-induced molecules can manipulate the surface receptor expression of the BBB to allow for their preferential entry into brain. (C) 1999 Lippincott Williams & Wilkins. C1 NIA, Cellular & Mol Biol Lab, Gerontol Res Ctr, Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Greig, NH (reprint author), NIA, Cellular & Mol Biol Lab, Gerontol Res Ctr, Intramural Res Program,NIH, 5600 Natham Shock Dr, Baltimore, MD 21224 USA. NR 23 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JAN 18 PY 1999 VL 10 IS 1 BP 53 EP 56 DI 10.1097/00001756-199901180-00010 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 179TW UT WOS:000079346100011 PM 10094132 ER PT J AU Peoples, RW Weight, FF AF Peoples, RW Weight, FF TI Differential alcohol modulation of GABA(A) and NMDA receptors SO NEUROREPORT LA English DT Article DE alcohol; anesthesia; GABA; hippocampus; hydrophobicity; ion channel; neurotransmitter receptor; NMDA ID HIPPOCAMPAL CA1 NEURONS; LONG-CHAIN ALCOHOLS; PROTEIN-KINASE-C; ANESTHETIC POTENCIES; ETHANOL; INHIBITION; CUTOFF; INTOXICATION; POTENTIATION; ALKANOLS AB NMDA and GABA(A) receptors are believed to be important CNS targets of alcohol action. In mouse hippocampal neurons, n-alcohols from ethanol to dodecanol enhanced GABA-activated ion current, whereas higher alcohols had no effect. Alcohols below pentanol affected NMDA receptors more potently than GABA(A) receptors. Increasing alcohol carbon chain length produced a greater average change in apparent binding energy and potency for modulation of GABA(A) than of NMDA receptor-channels, with the result that alcohols above pentanol affected GABA(A) receptors more potently than NMDA receptors. The anesthetic potency of n-alcohols in rats more closely reflected NMDA receptor modulatory potency for lower alcohols and GABA(A) receptor modulatory potency for higher alcohols. The results suggest that there may be fundamental differences in the sites through which alcohols affect NMDA and GABA(A) receptor function. (C) 1999 Lippincott Williams & Wilkins. C1 NIAAA, Mol & Cellular Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Peoples, RW (reprint author), NIAAA, Mol & Cellular Neurobiol Lab, NIH, Pk 5 Bldg,Rm 158,12420 Parklawn Dr,MSC 8115, Bethesda, MD 20892 USA. NR 20 TC 24 Z9 24 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JAN 18 PY 1999 VL 10 IS 1 BP 97 EP 101 DI 10.1097/00001756-199901180-00019 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 179TW UT WOS:000079346100020 PM 10094141 ER PT J AU Kim, HS Lee, JH Suh, YH AF Kim, HS Lee, JH Suh, YH TI C-terminal fragment of Alzheimer's amyloid precursor protein inhibits sodium/calcium exchanger activity in SK-N-SH cell SO NEUROREPORT LA English DT Article DE amyloid precursor protein (APP); Alzheimer's disease; C-terminal fragment; Na+-Ca2+ exchanger activity ID RAT-BRAIN; BETA; DISEASE; NEUROTOXICITY; EXPRESSION; CALCIUM; LTP AB NUMEROUS lines of evidence suggest that some of the neurotoxicity associated with Alzheimer's disease (AD) is due to proteolytic fragments of the amyloid precursor protein (APP). Most research has focused on the amyloid beta peptide (A beta). Ho Never, the possible role of other cleaved products of APP is less clear. We have previously shown that a recombinant carboxy-terminal 105 amino acid fragment (CT 105) of APP induced strong non-selective inward currents and also showed neurotoxicity in PC 12 cells and primary cortical neurons and blocked later phase of long term potentiation (LTP) in rat hippocampus in vivo. In this study, we investigated the effects of CT 105 on Na+-Ca2+ exchanger activity in SK-N-SH human neuroblastoma, in the presence of ouabain and monensin, which are considered to drive Na+-Ca2+ exchanger in the reverse mode. CT 105 inhibited the activity of this exchanger in SK-N-SH cells by similar to 50%. (C) 1999 Lippincott Williams & Wilkins. C1 Seoul Natl Univ, Coll Med, Dept Pharmacol, Seoul 110799, South Korea. Seoul Natl Univ, Neurosci Res Inst, Dept Mol Pharmacol, Seoul 110799, South Korea. Kangwon Natl Univ, Coll Med, Chunchon, South Korea. NIH, Biomed Brain Res Ctr, Bethesda, MD 20892 USA. RP Seoul Natl Univ, Coll Med, Dept Pharmacol, Seoul 110799, South Korea. RI Kim, Hye Sun/J-2752-2012; Suh, Yoo-Hun/J-2761-2012 NR 26 TC 21 Z9 22 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0959-4965 EI 1473-558X J9 NEUROREPORT JI Neuroreport PD JAN 18 PY 1999 VL 10 IS 1 BP 113 EP 116 DI 10.1097/00001756-199901180-00022 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 179TW UT WOS:000079346100023 PM 10094144 ER PT J AU Klausner, RD AF Klausner, RD TI Successfully sharing our stories of science SO SCIENTIST LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. RP Klausner, RD (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD JAN 18 PY 1999 VL 13 IS 2 BP 13 EP 13 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 157PA UT WOS:000078069800013 ER PT J AU Goldberg, ME AF Goldberg, ME TI Phantoms in the brain - Probing the mysteries of the human mind. SO NEW YORK TIMES BOOK REVIEW LA English DT Book Review C1 NIH, Natl Eye Inst, Bethesda, MD 20892 USA. Georgetown Univ, Washington, DC 20057 USA. RP Goldberg, ME (reprint author), NIH, Natl Eye Inst, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU NEW YORK TIMES PI NEW YORK PA 229 W 43RD ST, NEW YORK, NY 10036-3959 USA SN 0028-7806 J9 NY TIMES BK REV JI N. Y. Times Book Rev. PD JAN 17 PY 1999 BP 16 EP 16 PG 1 WC Humanities, Multidisciplinary SC Arts & Humanities - Other Topics GA 156RV UT WOS:000078016600013 ER PT J AU Straus, SE AF Straus, SE TI Bridging the gulf in war syndromes SO LANCET LA English DT Editorial Material C1 NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Straus, SE (reprint author), NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NR 10 TC 14 Z9 14 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JAN 16 PY 1999 VL 353 IS 9148 BP 162 EP 163 DI 10.1016/S0140-6736(98)00399-7 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 159LW UT WOS:000078175600002 PM 9923865 ER PT J AU Rogan, WJ Gladen, BC Guo, YLL Hsu, CC AF Rogan, WJ Gladen, BC Guo, YLL Hsu, CC TI Sex ratio after exposure to dioxin-like chemicals in Taiwan SO LANCET LA English DT Article C1 NIEHS, Res Triangle Pk, NC 27709 USA. Natl Cheng Kung Univ, Tainan 70101, Taiwan. Tainan City Hosp, Tainan, Taiwan. RP Rogan, WJ (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 5 TC 50 Z9 51 U1 0 U2 3 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JAN 16 PY 1999 VL 353 IS 9148 BP 206 EP 207 DI 10.1016/S0140-6736(05)77215-9 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 159LW UT WOS:000078175600017 PM 9923880 ER PT J AU Zhang, YQ Kreger, BE Dorgan, JF Splansky, GL Cupples, LA Ellison, RC AF Zhang, YQ Kreger, BE Dorgan, JF Splansky, GL Cupples, LA Ellison, RC TI Alcohol consumption and risk of breast cancer: The Framingham Study revisited SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE alcohol drinking; breast neoplasms; cohort studies ID POSTMENOPAUSAL WOMEN; BEVERAGE CONSUMPTION; CIGARETTE-SMOKING; YOUNG-WOMEN; COHORT; HEALTH; ASSOCIATION; NUTRITION AB Although many studies report that moderate-to-heavy alcohol intake increases breast cancer risk, the effect of light alcohol consumption remains controversial, and a consistent pattern of association with different types of alcoholic beverages is not evident. The authors examined the relation of average alcohol consumption and of different beverages to the risk of breast cancer in the Framingham Study (Framingham, Massachusetts). Of 2,764 women followed more than 40 years in the Original Cohort from 1948 to 1993 and 2,284 followed up to 24 years in the Offspring Cohort from 1971 to 1993, 221 and 66 incident breast cancer cases occurred, respectively. Breast cancer incidence decreased from 3.60 per 1,000 person-years to 2.47, 2.30, and 2.33 in increasing categories of average alcohol consumption (none, <5.0, 5.0-<15.0, and greater than or equal to 15.0 g/day) among the Original Cohort and from 3.07 to 1.26, 1.24, and 2.22, respectively, among the Offspring Cohort. With the two cohorts combined, multivariate-adjusted rate ratios of breast cancer in each increased category of alcohol consumption were 1.0 (nondrinkers), 0.8 (95% confidence interval (CI) 0.6-1.1), 0.7 (95% CI 0.5-1.1), and 0.7 (95% CI 0.5-1.1), respectively. Breast cancer was not associated with wine, beer, or spirits consumption when assessed separately. The findings suggest that the light consumption of alcohol or any type of alcoholic beverage is not associated with increased breast cancer risk. C1 Boston Univ, Sch Med, Evans Dept Med, Sect Epidemiol, Boston, MA 02118 USA. Boston Univ, Sch Med, Evans Dept Med, Sect Prevent Med, Boston, MA 02118 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Med, Dept Biostat & Epidemiol, Boston, MA 02118 USA. RP Zhang, YQ (reprint author), Boston Univ, Sch Med, Sect Prevent Med & Epidemiol, Evans Dept Med, 80 E Condord St, Boston, MA 02118 USA. FU NHLBI NIH HHS [N01-HC-38038] NR 34 TC 57 Z9 58 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 15 PY 1999 VL 149 IS 2 BP 93 EP 101 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 157HJ UT WOS:000078055300001 PM 9921953 ER PT J AU Longnecker, MP AF Longnecker, MP TI Invited commentary: The Framingham results on alcohol and breast cancer SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material ID PITUITARY-GONADAL-HORMONES; PREMENOPAUSAL WOMEN; CONSUMPTION; RISK; METAANALYSIS; PLASMA; INGESTION; ESTROGENS; MORTALITY; FEMALES C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Longnecker, MP (reprint author), NIEHS, Epidemiol Branch, POB 12233, Res Triangle Pk, NC 27709 USA. NR 32 TC 16 Z9 16 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 15 PY 1999 VL 149 IS 2 BP 102 EP 104 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 157HJ UT WOS:000078055300002 PM 9921954 ER PT J AU Zhang, YQ Kreger, BE Dorgan, JF Splansky, GL Cupples, LA Ellison, RC AF Zhang, YQ Kreger, BE Dorgan, JF Splansky, GL Cupples, LA Ellison, RC TI Authors' response to "the Framingham results on alcohol and breast cancer" SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material ID CONSUMPTION C1 Boston Univ, Sch Med, Evans Dept Med, Sect Prevent Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Evans Dept Med, Epidemiol Sect, Boston, MA 02118 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Dept Biostat & Epidemiol, Boston, MA 02118 USA. RP Zhang, YQ (reprint author), Boston Univ, Sch Med, Sect Prevent Med & Epidemiol, 80 E Concord St, Boston, MA 02118 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 15 PY 1999 VL 149 IS 2 BP 105 EP 105 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 157HJ UT WOS:000078055300003 ER PT J AU Chen, ZG Smithberger, J Sun, B Eggerman, TL AF Chen, ZG Smithberger, J Sun, B Eggerman, TL TI Prevention of heteroduplex formation in mRNA quantitation by reverse transcription polymerase chain reaction SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID MESSENGER-RNA; RT-PCR; GENE-EXPRESSION; COMPETITIVE PCR C1 US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NEI, Sect Immunoregulat, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Eggerman, TL (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 8 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JAN 15 PY 1999 VL 266 IS 2 BP 230 EP 232 DI 10.1006/abio.1998.2938 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 162LY UT WOS:000078349400009 PM 9888980 ER PT J AU Biagini, CP Philpot, RM Celier, CM AF Biagini, CP Philpot, RM Celier, CM TI Nonsubstrate recognition site residues are involved in testosterone hydroxylation by cytochrome P450 CYP 2C11 SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE cytochrome P450; CYP 2C11; mutagenesis; allelic variant; testosterone hydroxylation; rat ID AMINO-ACID; SUBSTRATE-SPECIFICITY; 16-BETA-HYDROXYLASE; MUTAGENESIS; METABOLISM; SEQUENCES; ENZYMES; REGION AB We have previously characterized an allelic variant of cytochrome P450 CYP 2C11 from the Gunn rat that differs at three positions (amino acids 4, 116, and 187) from the predominant allele from Wistar rats and that displays a dramatically reduced testosterone hydroxylation activity. To assess the relative contribution of these mutations to the decrease in the enzymatic activity we constructed single and double mutants and coexpressed them with reductase. Testosterone metabolism was determined with a baculovirus/insect cell expression system. None of the identified positions alone is critical for the activity since the reversion of one of these mutations is unable to restore fully the Wistar-type activity. The activity of CYP 2C11 containing either the Asn116Ser substitution or the Phe187Leu represents congruent to 30% of the activity of the CYP 2C11 Wistar-type protein. In contrast, the activity of the Val4Ala mutated protein is only 10% that of the Wistar-type protein, close to that of the Gunn-type protein. This study reevaluates the contribution of amino acid 4 to the catalysis by cytochrome P450 2C11 and points out the role of extra SRS residues. (C) 1999 Academic Press. C1 Inst Biol Phys Chim, INSERM, U310, F-75005 Paris, France. NIEHS, LST, Res Triangle Pk, NC 27709 USA. RP Celier, CM (reprint author), Inst Biol Phys Chim, INSERM, U310, 13 Rue P & M Curie, F-75005 Paris, France. NR 19 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JAN 15 PY 1999 VL 361 IS 2 BP 309 EP 314 DI 10.1006/abbi.1998.1003 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 158WF UT WOS:000078139900019 PM 9882461 ER PT J AU Jourd'heuil, D Laroux, FS Miles, AM Wink, DA Grisham, MB AF Jourd'heuil, D Laroux, FS Miles, AM Wink, DA Grisham, MB TI Effect of superoxide dismutase on the stability of S-nitrosothiols SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE superoxide dismutase; S-nitrosothiols; S-nitrosoglutathione; S-nitrosocysteine; S-nitrosoalbumin; copper; endothelium-derived relaxing factor; glutathione ID NITRIC-OXIDE; SERUM-ALBUMIN; COPPER; GLUTATHIONE; MECHANISM; NITROSOGLUTATHIONE; NITROSATION; NITROSOHEMOGLOBIN; DECOMPOSITION; RELAXATION AB S-Nitrosothiols formed from the nitric oxide (NO)dependent S-nitrosation of thiol-containing proteins and peptides such as albumin and glutathione (GSH) have been implicated in the transport, storage, and metabolism of NO in vivo. Recent data suggest that certain transition metals enhance the decomposition of S-nitrosothiols in vitro. The objective of this study was to determine what effect Cu, Zn superoxide dismutase (CuZn-SOD) has on the stability of certain S-nitrosothiols such as S-nitrosoglutathione (GSNO) in vitro. We found that CuZn-SOD (20 mu M) but not Mn-SOD in the presence of GSH catalyzed the decomposition of GSNO with a V-max of 6.7 +/- 0.4 mu M/min and a K-m of 5.6 +/- 0.5 mu M at 37 degrees C, Increasing GSH concentrations with respect to CuZn-SOD resulted in complete decomposition of GSNO at concentrations of GSH:SOD of 2:1. Increasing GSH concentrations further from 0.1 to 10 mM resulted in a concentration-dependent attenuation in GSNO decomposition suggesting that SOD-catalyzed decomposition of GSNO would be maximal at concentrations of GSH known to be present in extracellular fluids (e.g., plasma), The decomposition of GSNO by CuZn-SOD resulted in the sustained production of NO, We propose that GSH reduces enzyme-associated Cu2+ to Cu1+ which mediates the reductive decomposition of the S-nitrosothiol to yield free NO, We conclude that CuZn-SOD may represent an important physiological modulator of steady-state concentrations of low-molecular-weight S-nitrosothiols in vivo. (C) 1999 Academic Press. C1 Louisiana State Univ, Med Ctr, Dept Mol & Cellular Physiol, Shreveport, LA 71130 USA. NCI, Bethesda, MD 20892 USA. Grambling State Univ, Dept Chem, Grambling, LA 71245 USA. RP Grisham, MB (reprint author), Louisiana State Univ, Med Ctr, Dept Mol & Cellular Physiol, 1501 Kings Highway,POB 33932, Shreveport, LA 71130 USA. FU NIDDK NIH HHS [DK47663, DK43785] NR 44 TC 94 Z9 96 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JAN 15 PY 1999 VL 361 IS 2 BP 323 EP 330 DI 10.1006/abbi.1998.1010 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 158WF UT WOS:000078139900021 PM 9882463 ER PT J AU Persons, DA Allay, JA Allay, ER Ashmun, RA Orlic, D Jane, SM Cunningham, JM Nienhuis, AW AF Persons, DA Allay, JA Allay, ER Ashmun, RA Orlic, D Jane, SM Cunningham, JM Nienhuis, AW TI Enforced expression of the GATA-2 transcription factor blocks normal hematopoiesis SO BLOOD LA English DT Article ID STEM-CELLS; ERYTHROID-DIFFERENTIATION; MEGAKARYOCYTIC DIFFERENTIATION; FINGER PROTEIN; IN-VITRO; GENE; MICE; PROGENITORS; RETROVIRUS; PRECURSORS AB The zinc finger transcription factor GATA-2 is highly expressed in immature hematopoietic cells and declines with blood cell maturation. To investigate its role in normal adult hematopoiesis a bicistronic retroviral vector encoding GATA-2 and the green fluorescent protein (GFP) was used to maintain the high levels of GATA-2 that are normally present in primitive hematopoietic cells. Coexpression of the GFP marker facilitated identification and quantitation of vector-expressing cells. Bone marrow cells transduced with the GATA-2 vector expressed GFP as judged by flow cytometry and GATA-2 as assessed by immunoblot analysis. A 50% to 80% reduction in hematopoietic progenitor-derived colony formation was observed with GATA-2/GFP-transduced marrow, compared with marrow transduced with a GFP-containing vector lacking the GATA-2 cDNA. Culture of purified populations of GATA-2/GFP-expressing and nonexpressing cells confirmed a specific ablation of the colony-forming ability of GATA-2/GFP-expressing progenitor cells. Similarly, loss of spleen colony-forming ability was observed for GATA-2/GFP-expressing bone marrow cells. Despite enforced GATA-2 expression, marrow cells remained viable and were negative in assays to evaluate apoptosis. Although efficient transduction of primitive Sca-1(+) Lin(-) cells was observed with the GATA-2/GFP vector, GATA-2/GFP-expressing stem cells failed to substantially contribute to the multilineage hematopoietic reconstitution of transplanted mice. Additionally, mice transplanted with purified, GATA-2/ GFP-expressing cells showed post-transplant cytopenias and decreased numbers of total and gene-modified bone marrow Sca-1(+) Lin(-) cells. Although Sca-1(+) Lin(-) bone marrow cells expressing the GATA-2/GFP vector were detected after transplantation, no appreciable expansion in their numbers occurred. In contrast, control GFP-expressing Sca-1(+) Lin(-) cells expanded at least 40-fold after transplantation. Thus, enforced expression of GATA-2 in pluripotent hematopoietic cells blocked both their amplification and differentiation. There appears to be a critical dose-dependent effect of GATA-2 on blood cell differentiation in that downregulation of GATA-2 expression is necessary for stem cells to contribute to hematopoiesis in vivo. (C) 1999 by The American Society of Hematology. C1 St Jude Childrens Res Hosp, Dept Hematol Oncol, Div Expt Hematol, Memphis, TN 38105 USA. St Jude Childrens Res Hosp, Dept Expt Oncol, Memphis, TN 38105 USA. Natl Human Genome Res Inst, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD USA. RP Nienhuis, AW (reprint author), St Jude Childrens Res Hosp, Dept Hematol Oncol, Div Expt Hematol, 332 N Lauderdale St, Memphis, TN 38105 USA. RI Jane, Stephen/D-6659-2011 FU NCI NIH HHS [P30 CA 21765]; NHLBI NIH HHS [P01 HL 53749] NR 39 TC 176 Z9 181 U1 4 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 1999 VL 93 IS 2 BP 488 EP 499 PG 12 WC Hematology SC Hematology GA 155XD UT WOS:000077970900009 PM 9885210 ER PT J AU Weiler, SR Gooya, JM Ortiz, M Tsai, S Collins, SJ Keller, JR AF Weiler, SR Gooya, JM Ortiz, M Tsai, S Collins, SJ Keller, JR TI D3: A gene induced during myeloid cell differentiation of Lin(1o) c-Kit(+) Sca-1(+) progenitor cells SO BLOOD LA English DT Article ID RETINOIC ACID RECEPTOR; TRANSCRIPTION FACTORS; HEMATOPOIETIC STEM; INTERFERON ACTION; INDUCIBLE GENES; PROTEIN; P202; INHIBITION; CLUSTER; LOCALIZATION AB In an effort to characterize molecular events contributing to lineage commitment and terminal differentiation of stem/ progenitor cells, we have used differential display reverse transcription polymerase chain reaction (DDRT-PCR) and cell lines blocked at two distinct stages of differentiation. The cell lines used were EML, which is representative of normal multipotential primitive progenitors (Sca-1(+), CD34(+), c-Kit(+). Thy-1(+)) able to differentiate into erythroid, myeloid, and B-lymphoid cells in vitro, and MPRO, which ir; a more committed progenitor cell line, with characteristics of promyelocytes able to differentiate into granulocytes. One clone isolated by this approach was expressed in MPRO but not in EMIL cells and contained sequence identical to the 3' untranslated region of D3, a gene cloned from activated peritoneal macrophages of unknown function. We have observed a novel pattern of D3 gene expression and found that D3 is induced in EML cells under conditions that promote myeloid cell differentiation (interleukin-3 [IL-3], stem cell factor [SCF], and all-trans-retinoic acid [atRA]) starting at 2 days, corresponding to the appearance of promyelocytes. D3 RNA expression reached a maximum after 5 days, corresponding to the appearance of neutrophilic granulocytes and macrophages, and decreased by day 6 with increased numbers of differentiated neutrophils and macrophages in vitro. Induction of D3 RNA in EML was dependent on IL-3 and was not induced in response to SCF or atRA alone or SCF in combination with 15 other hematopoietic growth factors (HGF) tested. Similarly, D3 was not expressed in the normal bone marrow cell (BMC) counterpart of EML cells, Lin(lo) c-Kit(+) Sca-1(+) progenitor cells. D3 RNA expression was induced in these cells when cultured for 7 days in IL-3 plus SCF. A comparison of the expression of D3 RNA in cell lines and normal BMC populations demonstrated that D3 is induced during macrophage and granulocyte differentiation and suggests a potential physiological role for D3 in normal myeloid differentiation. This is a US government work. There are no restrictions on its use. C1 NCI, Intramural Res & Support Grp, Sci Applicat Int Corp Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Mol Immunoregulat Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Keller, JR (reprint author), NCI, Intramural Res & Support Grp, Sci Applicat Int Corp Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 31 TC 27 Z9 29 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 1999 VL 93 IS 2 BP 527 EP 536 PG 10 WC Hematology SC Hematology GA 155XD UT WOS:000077970900013 PM 9885214 ER PT J AU Yamada, M Ohtsu, M Kobayashi, I Kawamura, N Kobayashi, K Ariga, T Sakiyama, Y Nelson, DL Tsuruta, S Anakura, M Ishikawa, N AF Yamada, M Ohtsu, M Kobayashi, I Kawamura, N Kobayashi, K Ariga, T Sakiyama, Y Nelson, DL Tsuruta, S Anakura, M Ishikawa, N TI Flow cytometric analysis of Wiskott-Aldrich syndrome (WAS) protein in lymphocytes from WAS patients and their familial carriers SO BLOOD LA English DT Letter C1 Hokkaido Univ, Sch Med, Dept Pediat, Hokkaido, Japan. Teijinakai Hosp, Dept Pediat, Hokkaido, Japan. NCI, NIH, Bethesda, MD 20892 USA. Shizuoka Childrens Hosp, Dept Allergy, Shizuoka, Japan. Kohnan Hosp, Dept Pediat, Hokkaido, Japan. Kitami Red Cross Hosp, Dept Pediat, Hokkaido, Japan. RP Yamada, M (reprint author), Hokkaido Univ, Sch Med, Dept Pediat, Hokkaido, Japan. RI Ariga, Tadashi/A-4252-2012; Kobayashi, Ichiro/G-8638-2012 NR 6 TC 36 Z9 38 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 1999 VL 93 IS 2 BP 756 EP 757 PG 2 WC Hematology SC Hematology GA 155XD UT WOS:000077970900038 PM 10215346 ER PT J AU Hudes, GR Lipsitz, S Grem, J Morrisey, M Weiner, L Kugler, JW Benson, A AF Hudes, GR Lipsitz, S Grem, J Morrisey, M Weiner, L Kugler, JW Benson, A TI A phase II study of 5-fluorouracil, leucovorin, and interferon-alpha in the treatment of patients with metastatic or recurrent gastric carcinoma - An Eastern Cooperative Oncology Group Study (E5292) SO CANCER LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 20-23, 1995 CL LOS ANGELES, CALIFORNIA SP Amer Soc Clin Oncol DE gastric carcinoma; 9-fluorouracil; interferon; chemotherapy ID FOLINIC ACID; COLORECTAL-CARCINOMA; FLUOROURACIL; CANCER; TRIAL; COMBINATION; ALFA-2A AB BACKGROUND. Chemotherapy has a limited impact on adenocarcinoma of the stomach. Although biochemical modulation of 5-fluorouracil (5-FU) by leucovorin (LV) and interferon-alpha (IFN-alpha) has improved the outcomes of patients with metastatic colorectal carcinoma compared with 5-FU alone, this approach has not been extensively evaluated in the treatment of advanced gastric carcinoma. METHODS. Twenty-seven patients with bidimensionally measurable, metastatic gastric carcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 received the combination of IFN-alpha (5 million U/m(2) administered subcutaneously daily on Days 1-7), LV (500 mg/m(2) administered intravenously over 30 minutes immediately after IFN-alpha on Days 2-6), and 5-FU (370 mg/m(2) given as an intravenous bolus 60 minutes after LV on Days 2-6), with treatment repeated every 4 weeks. Oral cryotherapy was administered routinely before each dose of 5-FU to reduce the incidence of severe stomatitis. RESULTS. The median age of the patients was 58 years (range, 20-76), and 22 patients had residual, unresectable primary lesions. The median number of cycles received was 3 (range, 1-11). Of 24 patients who received at least 2 cycles of treatment, 15 (62.5%) did not require dose reduction for toxicity during the initial 2 cycles. The predominant toxicities were gastrointestinal: diarrhea and stomatitis of Grade 3-4 occurred in 28.6% and 35.7% of patients, respectively. Other severe (Grade 3-4) toxicities were granulocytopenia (which occurred in 21.4% of patients) and fatigue (in 10.7%). Fever and flu-like symptoms were common but usually mild. Of 24 patients who were evaluable for response, 3 had partial responses (PR) of 16, 23, and 33 weeks' duration, respectively, for a response rate of 12.5% (95% confidence interval = 2.7-32.4%). Two additional patients had reductions in tumor size sufficient for PR, but scans to document the minimum required response duration of 4 weeks were not obtained before progressive disease occurred. The median progression-free and overall survivals were 2.5 and 7.8 months, respectively. CONCLUSIONS, Although this regimen can be administered safely with appropriate supportive care to patients with good performance status, it has limited therapeutic activity in patients with advanced gastric carcinoma. (C) 1999 American Cancer Society. C1 Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. NCI, Med Branch, USN, Med Ctr, Bethesda, MD USA. Illinois Oncol Res Assoc, Peoria, IL USA. Northwestern Univ, Med Ctr, Div Hematol Oncol, Chicago, IL 60611 USA. RP Hudes, GR (reprint author), Fox Chase Canc Ctr, Dept Med Oncol, 7701 Burholme Ave, Philadelphia, PA 19111 USA. FU NCI NIH HHS [CA18281, CA23318, CA21076] NR 14 TC 6 Z9 7 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 15 PY 1999 VL 85 IS 2 BP 290 EP 294 DI 10.1002/(SICI)1097-0142(19990115)85:2<290::AID-CNCR4>3.0.CO;2-P PG 5 WC Oncology SC Oncology GA 160AP UT WOS:000078208400004 PM 10023694 ER PT J AU Moser, AM Adamson, PC Gillespie, AJ Poplack, DG Balis, FM AF Moser, AM Adamson, PC Gillespie, AJ Poplack, DG Balis, FM TI Intraventricular concentration times time (CxT) methotrexate and cytarabine for patients with recurrent meningeal leukemia and lymphoma SO CANCER LA English DT Article; Proceedings Paper CT 16th Annual Meeting of the American-Society-for-Clinical-Oncology CY MAY 16-20, 1997 CL DENVER, COLORADO SP Amer Soc Clin Oncol DE intrathecal; intraventricular; meningeal; methotrexate; cytarabine; leukemia; lymphoma ID CENTRAL-NERVOUS-SYSTEM; CEREBROSPINAL-FLUID; COMPLICATIONS; CHEMOTHERAPY; RESERVOIRS; REMISSION; CHILDREN; CANCER; TRIAL AB BACKGROUND. Intraventricular chemotherapy results in more uniform drug distribution within the subarachnoid space and allows for more flexible drug administration schedules. The authors report their experience with an intraventricular concentration times time (C x T) chemotherapy regimen for recurrent meningeal leukemia and lymphoma. METHODS. Twenty-one patients (median age, 11.6 years) received C x T therapy for meningeal acute lymphoblastic leukemia (n = 18), Burkitt's lymphoma (n = 2), or undifferentiated leukemia (n = 1). Prior therapy included standard intrathecal (IT) methotrexate and cytarabine, cranial or craniospinal radiation (median, 24 Gy), and 0-5 experimental treatment modalities. C x T induction therapy consisted of 2 mg of intraventricular methotrexate administered daily for 3 days every 10 days, for 4 courses. Patients were then consolidated with 4 courses of alternating intraventricular cytarabine (15 mg/day) or methotrexate (2 mg/day) daily for 3 days every 2 weeks (2 courses of methotrexate and 2 courses of cytarabine). Maintenance therapy consisted of alternating monthly courses of C x T methotrexate or cytarabine. RESULTS. Ninety-three percent of patients (14 of 15) who were evaluable for response achieved a complete remission in a median of 10 days (range, 2-40 days). Median remission duration was 15 months. Fourteen patients died of recurrent disease or systemic treatment-related complications; 2 patients are alive, off treatment, and in continuous complete remission for 59+ and 89+ months; 1 patient experienced a meningeal relapse at 24 months on C x T therapy but was reinduced with the C x T regimen, received craniospinal radiation, and is in remission at 142+ months; and 3 are alive with disease at 32+, 72+, and 81+ months. One patient was lost to follow-up. CONCLUSIONS. This regimen appears to be an effective and well-tolerated palliative treatment for patients with recurrent meningeal leukemia and lymphoma. (C) 1999 American Cancer Society. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Balis, FM (reprint author), NCI, Pediat Oncol Branch, Bldg 10,Romm 13N240,10 Ctr Dr, Bethesda, MD 20892 USA. RI MOSER, ASHER/F-1873-2012 NR 20 TC 18 Z9 19 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 15 PY 1999 VL 85 IS 2 BP 511 EP 516 DI 10.1002/(SICI)1097-0142(19990115)85:2<511::AID-CNCR33>3.0.CO;2-H PG 6 WC Oncology SC Oncology GA 160AP UT WOS:000078208400033 PM 10023723 ER PT J AU Nelson, MA Ariza, ME Yang, JM Thompson, FH Taetle, R Trent, JM Wymer, J Massey-Brown, K Broome-Powell, M Easton, J Lahti, JM Kidd, VJ AF Nelson, MA Ariza, ME Yang, JM Thompson, FH Taetle, R Trent, JM Wymer, J Massey-Brown, K Broome-Powell, M Easton, J Lahti, JM Kidd, VJ TI Abnormalities in the p34(cdc2)-related PITSLRE protein kinase gene complex (CDC2L) on chromosome band 1p36 in melanoma SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID EXPRESSION; NEUROBLASTOMA; ASSIGNMENT; CANCERS; REGION; P53 AB The two genes encoding the PITSLRE protein kinase isoforms, CDC2L1 and CDC2L2, are localized to human chromosome band 1p36. The PITSLRE protein kinases are a part of the p34(cdc2) supergene family. Several protein products of the CDC2L locus may be effector(s) in apoptotic signaling. The larger PITSLRE p110 isoforms appear to regulate some aspect of RNA splicing/transcription during the cell cycle. One or more of these genes may function as tumor suppressor genes in melanoma. Using fluorescence in situ hybridization, one allele of the CDC2L gene complex on chromosome 2 was either deleted or translocated in 8 of 14 different melanoma cell lines. We also observed mutations in the 5' promoter region of the CDC2L1 gene in four different cell lines relative to normal melanocytes using PCR-SSCP analysis and direct DNA sequencing. Western blot analysis revealed decreased level of PITSLRE protein expression in several cell lines, as well as in four surgical malignant melanoma specimens relative to normal melanocytes. Thus, the decreased PITSLRE protein expression appears to result from deletion of the CDC2L alleles and possibly by mutations within the 5' promoter region. We propose that aberrations in the CDC2L genes may contribute to the pathogenesis or progression of melanoma. (C) Elsevier Science Inc., 1998. C1 Arizona Canc Ctr, Tucson, AZ 85724 USA. Univ Arizona, Dept Pathol, Tucson, AZ USA. St Jude Childrens Res Hosp, Dept Tumor Cell Biol, Memphis, TN 38105 USA. NIH, Natl Ctr Human Genome Res, Bethesda, MD 20892 USA. RP Nelson, MA (reprint author), Arizona Canc Ctr, Room 4921, Tucson, AZ 85724 USA. FU NCI NIH HHS [CA 70145, CA5197, R29 CA 70145-01] NR 22 TC 41 Z9 43 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD JAN 15 PY 1999 VL 108 IS 2 BP 91 EP 99 DI 10.1016/S0165-4608(98)00122-8 PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 152BC UT WOS:000077754700001 PM 9973934 ER PT J AU Vortmeyer, AO Boni, R Pack, SD Darling, TN Zhuang, ZP AF Vortmeyer, AO Boni, R Pack, SD Darling, TN Zhuang, ZP TI Perivascular cells harboring multiple endocrine neoplasia type 1 alterations are neoplastic cells in angiofibromas SO CANCER RESEARCH LA English DT Article ID PARATHYROID TUMORS; CHROMOSOME 11Q13; GENE AB Although neoplasia is caused by clonal proliferation of cells, the resulting tumors are frequently heterogeneous, being composed of both neoplastic and reactive cells. Therefore, identification of tumors as neoplastic processes is frequently obscured. We studied cutaneous angiofibroma, which is a tumor of unknown etiology. Combined analysis using immunohistochemistry, selective tissue microdissection, fluorescence in situ hybridization, sequencing analysis, and deletion analysis of the multiple endocrine neoplasia type 1 locus succeeded in the identification of a population of genetically altered, neoplastic cells in these tumors. This approach may be valuable in the future in identifying the etiology of other tumors of unknown etiology. C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. NCI, Dermatol Branch, Bethesda, MD 20892 USA. Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. RP Zhuang, ZP (reprint author), NCI, Pathol Lab, Bldg 10,Room 2A33,9000 Rockville Pike, Bethesda, MD 20892 USA. EM aov@helix.nih.gov RI Pack, Svetlana/C-2020-2014; OI Darling, Thomas/0000-0002-5161-1974 NR 16 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1999 VL 59 IS 2 BP 274 EP 278 PG 5 WC Oncology SC Oncology GA 158AB UT WOS:000078092900003 PM 9927030 ER PT J AU Rivoltini, L Squarcina, P Loftus, DJ Castelli, C Tarsini, P Mazzocchi, A Rini, F Viggiano, V Belli, F Parmiani, G AF Rivoltini, L Squarcina, P Loftus, DJ Castelli, C Tarsini, P Mazzocchi, A Rini, F Viggiano, V Belli, F Parmiani, G TI A superagonist variant of peptide MART1/melan A(27-35) elicits anti-melanoma CD8(+) T cells with enhanced functional characteristics: Implication for more effective immunotherapy SO CANCER RESEARCH LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; REACTIVE CTL; IDENTIFICATION; INDUCTION; MART-1; PROLIFERATION; CYTOTOXICITY; STIMULATION; ACTIVATION; VACCINES AB In the present study, me show that a singly substituted peptide derived from the epitope MART1(27-35) and containing a Leu in position 1 (LA-GIGILTV; ii) behaves as a superagonist by in vitro inducing specific T cells with enhanced immunological functions, 1L-specific CTLs can be raised from peripheral blood of HLA-A2(+) melanoma patients more efficiently than T cells specific for the cognate peptide. These T cells show a greater sensitivity to native MARTI,,, when compared with CTL variable raised to parental peptide from the same patients, More importantly, anti-ii but not anti-native T cells display high levels of interferon gamma production at early time points, and readily secreted interleukin-2 in response to native epitope endogenously presented by melanoma cells. Additionally, anti-ii T cells are insensitive to the inhibitory effects of MART1(27-35) natural analogues that antagonize the lytic response of CTLs raised to the cognate peptide. Analysis of T-cell receptor variable beta usage suggests that the native and ii peptides stimulate different components of the MART1(27-35)-reactive T cell population. These data provide rationale to the use of superagonist analogues of tumor antigens for inducing in vivo immunization potentially able to overcome tumor immune escape and mediate a more significant control of tumor growth. C1 Ist Nazl Tumori, Div Expt Oncol D, I-20133 Milan, Italy. Ist Nazl Tumori, Div Med Oncol A, I-20133 Milan, Italy. Ist Nazl Tumori, Div Surg Oncol B, I-20133 Milan, Italy. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Rivoltini, L (reprint author), Ist Nazl Tumori, Div Expt Oncol D, Via Venezian 1, I-20133 Milan, Italy. RI castelli, chiara/K-6899-2012; OI castelli, chiara/0000-0001-6891-8350; Rivoltini, Licia/0000-0002-2409-6225 NR 24 TC 84 Z9 86 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1999 VL 59 IS 2 BP 301 EP 306 PG 6 WC Oncology SC Oncology GA 158AB UT WOS:000078092900009 PM 9927036 ER PT J AU Park, WS Dong, SM Kim, SY Na, EY Shin, MS Pi, JH Kim, BJ Bae, JH Hong, YK Lee, KS Lee, SH Yoo, NJ Jang, JJ Pack, S Zhuang, ZP Schmidt, L Zbar, B Lee, JY AF Park, WS Dong, SM Kim, SY Na, EY Shin, MS Pi, JH Kim, BJ Bae, JH Hong, YK Lee, KS Lee, SH Yoo, NJ Jang, JJ Pack, S Zhuang, ZP Schmidt, L Zbar, B Lee, JY TI Somatic mutations in the kinase domain of the MET/hepatocyte growth factor receptor gene in childhood hepatocellular carcinomas SO CANCER RESEARCH LA English DT Article ID HEPATITIS-B VIRUS; C-MET PROTOONCOGENE AB The MET protooncogene encodes a transmembrane tyrosine kinase identified as the receptor of a polypeptide known as hepatocyte growth factor/scatter factor. We performed PCR-based single-strand conformational polymorphism and sequencing analysis of the tyrosine kinase domain of the MET gene (exon 15-19) in 75 primary liver cancers. Three missense mutations were detected exclusively in 10 childhood hepatocellular carcinomas (HCCs), while no mutations were detected in 16 adult HCCs, 21 cholangiocarcinomas, or 28 hepatoblastomas. The extremely short incubation period from hepatitis B virus infection to the genesis of childhood HCC as compared with the adult HCC suggests that there may be an additional mechanism that accelerates the carcinogenesis of childhood HCC. Our results indicate that mutations of the tyrosine kinase domain of the MET gene may be involved in the acceleration of the carcinogenesis in childhood HCC. C1 Catholic Univ, Coll Med, Dept Pathol, Seoul 137701, South Korea. Catholic Univ, Coll Med, Canc Res Inst, Seoul 137701, South Korea. Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 110799, South Korea. NCI, Pathol Lab, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD USA. RP Lee, JY (reprint author), Catholic Univ, Coll Med, Dept Pathol, Seoul 137701, South Korea. RI Jang, JaJune/F-6647-2011; Seoul National University, Pathology/B-6702-2012; Pack, Svetlana/C-2020-2014 FU NCI NIH HHS [N01-CO-56000] NR 20 TC 193 Z9 201 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1999 VL 59 IS 2 BP 307 EP 310 PG 4 WC Oncology SC Oncology GA 158AB UT WOS:000078092900010 PM 9927037 ER PT J AU Grady, WM Myeroff, LL Swinler, SE Rajput, A Thiagalingam, S Lutterbaugh, JD Neumann, A Brattain, MG Chang, J Kim, SJ Kinzler, KW Vogelstein, B Willson, JKV Markowitz, S AF Grady, WM Myeroff, LL Swinler, SE Rajput, A Thiagalingam, S Lutterbaugh, JD Neumann, A Brattain, MG Chang, J Kim, SJ Kinzler, KW Vogelstein, B Willson, JKV Markowitz, S TI Mutational inactivation of transforming growth factor beta receptor type II in microsatellite stable colon cancers SO CANCER RESEARCH LA English DT Article ID CARCINOMA-CELLS; GENE; INSTABILITY; TUMORIGENICITY; EXPRESSION; SUBSTRATE; PROTEIN; KINASE; MADR2 AB We previously demonstrated that mutational inactivation of transforming growth factor beta type IT receptors (RIIs) is very common among the 13% of human colon cancers with microsatellite instability. These mutations principally duster in the BAT-RII polyadenine sequence repeat. Among microsatellite stable (MSS) colon cancers, we now find that non-BAT-RII point mutations inactivate RII in another 15% of cases, thus doubling the known number of colon cancers in which RII mutations are pathogenetic, Functional analysis confirms that these mutations inactivate RII signaling, Moreover, another 555 of MSS colon cancers demonstrate a transforming growth factor beta signaling blockade distal to RII, The transforming growth factor beta pathway and RII in particular are major targets for inactivation in MSS colon cancers as well as in colon cancers with microsatellite instability. C1 Case Western Reserve Univ, Ireland Canc Ctr, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Surg, Cleveland, OH 44106 USA. Case Western Reserve Univ, BSTP Program, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Univ Texas, Hlth Sci Ctr, Dept Surg, San Antonio, TX 78284 USA. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Johns Hopkins Oncol Ctr, Genet Mol Lab, Baltimore, MD 21231 USA. Howard Hughes Med Inst, Coconut Grove, FL 33133 USA. RP Markowitz, S (reprint author), Case Western Reserve Univ, Ireland Canc Ctr, UCRC 2,Room 2,11001 Cedar Rd, Cleveland, OH 44106 USA. FU NCI NIH HHS [KO8 CA77676-01, R01 CA 72160, R01 CA67409] NR 29 TC 278 Z9 293 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1999 VL 59 IS 2 BP 320 EP 324 PG 5 WC Oncology SC Oncology GA 158AB UT WOS:000078092900013 PM 9927040 ER PT J AU Suh, NJ Wang, YP Honda, T Gribble, GW Dmitrovsky, E Hickey, WF Maue, RA Place, AE Porter, DM Spinella, MJ Williams, CR Wu, GF Dannenberg, AJ Flanders, KC Letterio, JJ Mangelsdorf, DJ Nathan, CF Nguyen, L Porter, WW Ren, RF Roberts, AB Roche, NS Subbaramaiah, K Sporn, MB AF Suh, NJ Wang, YP Honda, T Gribble, GW Dmitrovsky, E Hickey, WF Maue, RA Place, AE Porter, DM Spinella, MJ Williams, CR Wu, GF Dannenberg, AJ Flanders, KC Letterio, JJ Mangelsdorf, DJ Nathan, CF Nguyen, L Porter, WW Ren, RF Roberts, AB Roche, NS Subbaramaiah, K Sporn, MB TI A novel synthetic oleanane triterpenoid, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid, with potent differentiating, antiproliferative, and anti-inflammatory activity SO CANCER RESEARCH LA English DT Article ID NERVE GROWTH-FACTOR; NITRIC-OXIDE; INCREASED EXPRESSION; URSOLIC ACID; CELLS; INHIBITION; MACROPHAGES; PROTEIN; SYSTEM; BRAIN AB The new synthetic oleanane triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) is a potent, multifunctional molecule. It induces monocytic differentiation of human myeloid leukemia cells and adipogenic differentiation of mouse 3T3-L1 fibroblasts and enhances the neuronal differentiation of rat PC12 pheochromocytoma cells caused by nerve growth factor. CDDO inhibits proliferation of many human tumor cell lines, including those derived from estrogen receptor-positive and -negative breast carcinomas, myeloid leukemias, and several carcinomas bearing a Smad4 mutation. Furthermore, it suppresses the abilities of various inflammatory cytokines, such as IFN-gamma, interleukin-l, and tumor necrosis factor-alpha, to induce de novo formation of the enzymes inducible nitric oxide synthase (iNos) and inducible cyclooxygenase (COX-2) in mouse peritoneal macrophages, rat brain microglia, and human colon fibroblasts. CDDO will also protect rat brain hippocampal neurons from cell death induced by beta-amyloid. The above activities have been found at concentrations ranging from 10(-6) to 10(-9) M in cell culture, and these results suggest that CDDO needs further study in vivo, far either chemoprevention or chemotherapy of malignancy as well as for neuroprotection. C1 Dartmouth Med Sch, Dept Pharmacol, Hanover, NH 03755 USA. Dartmouth Med Sch, Dept Pathol, Hanover, NH 03755 USA. Dartmouth Med Sch, Dept Physiol, Hanover, NH 03755 USA. Dartmouth Med Sch, Dept Biochem, Hanover, NH 03755 USA. Dartmouth Med Sch, Norris Cotton Canc Ctr, Hanover, NH 03755 USA. Dartmouth Coll, Dept Chem, Hanover, NH 03755 USA. NCI, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX 75235 USA. Cornell Univ, Weill Med Coll, Dept Med, New York, NY 10021 USA. Strang Canc Prevent Ctr, New York, NY 10021 USA. RP Sporn, MB (reprint author), Dartmouth Med Sch, Dept Pharmacol, 7650 Remsen, Hanover, NH 03755 USA. EM Michael.Sporn@dartmouth.edu RI Spinella, Michael/B-7210-2014 FU NCI NIH HHS [R01 CA 54494, CA-23108, R01 CA 62275, R01 CA062275] NR 33 TC 235 Z9 246 U1 1 U2 17 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1999 VL 59 IS 2 BP 336 EP 341 PG 6 WC Oncology SC Oncology GA 158AB UT WOS:000078092900016 PM 9927043 ER PT J AU Ikawa, H Kamitani, H Calvo, BF Foley, JF Eling, TE AF Ikawa, H Kamitani, H Calvo, BF Foley, JF Eling, TE TI Expression of 15-lipoxygenase-1 in human colorectal cancer SO CANCER RESEARCH LA English DT Article ID HUMAN COLON-CANCER; PROSTAGLANDIN-H SYNTHASE-2; ARACHIDONATE 15-LIPOXYGENASE; MAMMALIAN LIPOXYGENASES; MOLECULAR-CLONING; ASPIRIN USE; ATHEROGENESIS; RETICULOCYTE; INHIBITION; APOPTOSIS AB Recently we reported the induction of reticulocyte type 15-lipoxygenase I (19-Lox-1) in a human colorectal carcinoma cell line that had been stimulated by butyrate to undergo apoptosis and cell differentiation (H. Kamitani et al., J, Biol, Chem., 273: 21569-21577, 1998), To determine if TS-Los-l is expressed in human colorectal cancer tissue, 21 matched pairs of colorectal tumor and adjacent normal tissue were examined by immunoblot analysis using specific antibodies for human 15-Lox-1, prostaglandin H synthase (also railed cyclooxygenase, Cox)-1 and Cox-2. Eighteen of the 21 were found to have 15-Lorr-1 in both tumor tissue and matched adjacent normal tissue, with the 15-Lox-1 expression being significantly higher in most of the tumor tissue. The expression of Cox-2 was also elevated in most tumors, whereas Cox-1 was frequently expressed at lower levels in the tumor tissue than in the paired normal tissue Reverse-phase high-performance liquid chromatography analysis of arachidonate metabolites, formed on incubation of arachidonic acid with a crude enzyme preparation from the colon samples, revealed the formation of 15-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid with a much lower level of 12-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (15-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid:12-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid, 6.5:1) which also indicate the presence of 15-Lox-1. Furthermore, reverse transcription-PCR with primers specific for human 15-Lox-1 or 15-Lox-2 cDNA indicated that 15-Lox-1 mRNA was present in the colorectal tumors. The sequence of the PCR product was identical to the human 15-Lox-1. Immunohistochemical studies showed 15-Lox-1 localization in the glandular epithelium of human colorectal tumor tissue. These results suggest that 15-Lox-1 is highly expressed in human colorectal canter epithelial cells and that its expression may have a role in colorectal carcinogenesis. C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Eling, TE (reprint author), NIEHS, Mol Carcinogenesis Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 42 TC 94 Z9 99 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1999 VL 59 IS 2 BP 360 EP 366 PG 7 WC Oncology SC Oncology GA 158AB UT WOS:000078092900020 PM 9927047 ER PT J AU Samuni, Y Coffin, D DeLuca, AM DeGraff, WG Venson, DJ Ambudkar, I Chevion, M Mitchell, JB AF Samuni, Y Coffin, D DeLuca, AM DeGraff, WG Venson, DJ Ambudkar, I Chevion, M Mitchell, JB TI The use of Zn-desferrioxamine for radioprotection in mice, tissue culture, and isolated DNA SO CANCER RESEARCH LA English DT Article ID LIPID-PEROXIDATION; ZINC-DESFERRIOXAMINE; RADIATION PROTECTION; BIOLOGICAL DAMAGE; METAL CHELATORS; RECOVERY; IRRADIATION; SUPEROXIDE; COPPER; CELLS AB Redox-active metals mediate oxidative injury and might also potentiate radiation damage, The iron chelator desferrioxamine (DFO), which diminishes oxidative damage in many chemical and biological systems as web as in human subjects, has a controversial role in radiobiology and reportedly acts both as a radiosensitizer and a radioprotector. The present research focused on the radioprotective activity of its zinc complex, Zn-DFO was studied using three test systems differing by their complexities: isolated DNA from pUC 19 plasmid, cultured V79 Chinese hamster cells, and C3H mice. Zn-DFO (0.5-2 mM) protected isolated DNA against gamma-radiation better than each of its components alone; however, neither Zn-DFO nor DFO (50-100 mu M) alone affected the radiation sensitivity of cultured cells. With total body irradiation, Zn-DFO, but not DFO alone at 100 mu mol/kg body weight, administered to mice 30 min before irradiation provided significant radioprotection (P < 0.01). Zn-DFO had an LD50/30 of 10.3 Gy, whereas DFO and vehicle alone had LD(50/30)s of 8.03 Gy and 7.91 Gy, respectively, The effect of Zn-DFO on the hemodynamic parameters in mice did not differ from that of the vehicle (saline) alone, This excludes the explanation that the radioprotective activity of Zn-DFO results from its effect on oxygen levels. In addition to the possible direct effect of Zn, other potential modes of action underlying the radioprotective activity of Zn-DFO might involve a displacement of iron and its substitution by zinc, a greater proximity of the drug to DNA, and less Likely an improved penetration of the drug into cells because of its structure. The failure of Zn-DFO to protect cells in tissue cultures indicates that it has some systemic role in the whole animal, possibly due to a prolonged half-life in the animal's circulation. C1 Hebrew Univ Jerusalem, Sch Med, Dept Cellular Biochem, IL-91120 Jerusalem, Israel. Hebrew Univ Jerusalem, Sch Dent, IL-91120 Jerusalem, Israel. NCI, Radiat Biol Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NIDR, Secretory Physiol Sect, Gene Therapy & Therapeut Branch, Div Intramural Res,NIH, Bethesda, MD 20892 USA. RP Samuni, Y (reprint author), Hebrew Univ Jerusalem, Sch Med, Dept Cellular Biochem, IL-91120 Jerusalem, Israel. NR 48 TC 11 Z9 12 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1999 VL 59 IS 2 BP 405 EP 409 PG 5 WC Oncology SC Oncology GA 158AB UT WOS:000078092900027 PM 9927054 ER PT J AU Wildner, O Blaese, RM Morris, JC AF Wildner, O Blaese, RM Morris, JC TI Therapy of colon cancer with oncolytic adenovirus is enhanced by the addition of herpes simplex virus thymidine kinase SO CANCER RESEARCH LA English DT Article ID DNA TOPOISOMERASE-I; GENE-THERAPY; BRAIN-TUMORS; RECOMBINANT ADENOVIRUS; RETROVIRAL VECTORS; CELLS; REPLICATION; TRANSFORMATION; GANCICLOVIR; EXPRESSION AB A major obstacle to the successful application of suicide gene therapy strategics that rely on in situ transduction of tumor tells is the poor distribution of the vector throughout the tumor mass. To address this problem, we evaluated the use of Ad.TKRC, an E1b M-r 55,000 deleted replicating adenoviral sector engineered to express the herpes simplex virus type 1 thymidine kinase gene (HSV-tk) in combination with ganciclovir (GCV) as a treatment for human colon cancer xenografts in nude mice, We compared the efficacy of this system with that of a standard replication-deficient adenovirus expressing HSV-tk (Ad.TK) in mice bearing LS180 tumors. In this system, Ad.TKRC alone was as effective as a traditional Ad.TK vector in combination with GCV. The addition of GCV significantly enhanced the antitumor effect of Ad.TKRC. Furthermore, we demonstrated that the survival of HT-29 human colon cancer xenografted mice treated with Ad.TKRC and GCV was prolonged compared with Ad.TKRC alone or with administration of a single cycle of topotecan. These data demonstrate that the addition of direct viral oncolysis to the HSV-tk/GCV suicide gene system resulted in a striking improvement in treatment efficacy and that it may offer advantages over the use of chemotherapeutic agents for treatment of localized disease. C1 NHGRI, Clin Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. RP Wildner, O (reprint author), NHGRI, Clin Gene Therapy Branch, NIH, 10 Ctr Dr,Bldg 10,Room 10C103, Bethesda, MD 20892 USA. EM owildner@nhgri.nih.gov NR 36 TC 151 Z9 155 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1999 VL 59 IS 2 BP 410 EP 413 PG 4 WC Oncology SC Oncology GA 158AB UT WOS:000078092900028 PM 9927055 ER PT J AU Kobayashi, H Le, N Kim, IS Kim, MG Pie, JE Drumm, D Paik, DS Waldmann, TA Paik, CH Carrasquillo, JA AF Kobayashi, H Le, N Kim, IS Kim, MG Pie, JE Drumm, D Paik, DS Waldmann, TA Paik, CH Carrasquillo, JA TI The pharmacokinetic characteristics of glycolated humanized anti-Tac Fabs are determined by their isoelectric points SO CANCER RESEARCH LA English DT Article ID CHIMERIC MONOCLONAL-ANTIBODY; STABILIZED FV-IMMUNOTOXINS; RECOMBINANT SINGLE-CHAIN; AMINO-ACID INFUSION; RENAL UPTAKE; NUDE-MICE; INTERLEUKIN-2 RECEPTOR; GLOMERULAR-FILTRATION; SOMATOSTATIN ANALOG; RATS AB evaluate a method for preventing the nephrotoxicity caused by the high renal accumulation of radiolabeled or toxin-conjugated small immunoproteins used for cancer therapy, we conjugated humanized anti-Tee Feb fragments with various numbers of glycolate molecules [glycolated Fab fragments (glyco-Fabs)] and separated the conjugates by means of ion-exchange columns into three fractions, depending on their isoelectric points (pIs). We evaluated the biodistribution, pharmacokinetics, and catabolism in normal nude mice of nonglycolated Fab (pl greater than or equal to 9.3) and three different preparations of glyco-Fab, including strongly anionic glyco-Fah (sa-glyco-Fab: pi less than or equal to 4.5), mildly anionic glyco-Fab (pI = 4.5-7), and mildly cationic glyco-Fab (pI = 7-93). In addition, the biodistributions of I-125-labeled sa-glyco-Fab and I-131-labeled nonglycolated Fab were evaluated in normal nude mice coinjected with 50 mg of L-lysine and/or 1 mu g of furosemide and in a control group without coinjection. We then evaluated the serial biodistribution of I-125-labeled sa-glyco-Fab (4 mu Ci/1 mu g) and I-131-labeled nonglycolated Fab (5 mu Ci/1 mu g) in Tac antigen-positive (ATAC4) and -negative (A431) tumor-bearing nude mice dth s.c. tumor xenografts derived from Tac antigen-positive ATAC4 cells and receptor-negative A431 cells. These animals were coinjected with 30 mg of lysine i.v. and 30 mg of lysine i.p. 15 min after the radiolabeled Fab injection. To evaluate the biodistribution data and study scintigraphic imaging, we performed serial scintigraphy on normal and tumor-bearing mice with all four I-131-labeled preparations. I-125-labeled mildly cationic glyco-Fab and I-131-labeled nonglycolated Fab had similar distributions, except in the kidney. However, both I-125-labeled anionic glyco-Fab preparations showed significantly different distributions from both cationic Fabs in the blood, liver, lung, and spleen. Renal accumulation of all four radiolabeled Fab preparations increased significantly as the. pi increased (P < 0.01). In addition, the intact fraction of Fab excreted into urine increased as pi decreased. Therefore, the glomerular filtration depended on whether the charge on the Fab was positive or negative. The proportion of Fab reabsorbed by the proximal tubules increased as pi increased. I-125-labeled sa-glyco-Fab and I-125-labeled mildly anionic glyco-Fab showed a similar distribution in the blood and all organs except the kidney. Lysine led to an additional blocking effect on proximal tubular uptake of both sa-glyco-Fab and nonglycolated Fab. Addition of furosemide yielded only a small effect when used with lysine. With lysine, the sa-glyco-Fab:nonglycolated Fab estimated integral radioactivity ratios were 4.7 and 0.7 in the ATAC4 tumor and in the kidney, respectively. The use of anionic fragments, which may be used in conjunction with lysine, represents a promising approach that may help decrease the renal toxicity of other small fragments, the molecular weights of which range from M-r, 40,000 to 70,000, and, thereby, allow higher doses of radiation to the tumor. C1 NCI, Dept Nucl Med, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Carrasquillo, JA (reprint author), NCI, Dept Nucl Med, Warren G Magnuson Clin Ctr, NIH, Bldg 10,Room 1C496,10 Ctr Dr,MSC 1180, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 38 TC 49 Z9 50 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1999 VL 59 IS 2 BP 422 EP 430 PG 9 WC Oncology SC Oncology GA 158AB UT WOS:000078092900030 PM 9927057 ER PT J AU Tamura, M Gu, JG Takino, T Yamada, KM AF Tamura, M Gu, JG Takino, T Yamada, KM TI Tumor suppressor PTEN inhibition of cell invasion, migration, and growth: Differential involvement of focal adhesion kinase and p130(Cas) SO CANCER RESEARCH LA English DT Article ID SIGNAL-TRANSDUCTION; PROTEIN-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE PHOSPHORYLATION; GERMLINE MUTATIONS; PROSTATE-CANCER; GENE; INTEGRINS; APOPTOSIS; SRC AB PTEN/MMAC1 is a major new tumor suppressor gene that encodes a dual-specificity phosphatase with sequence similarity to the cytoskeletal protein tensin. Recently, we reported that PTEN dephosphorylates focal adhesion kinase (FAK) and inhibits cell migration, spreading, and focal adhesion formation. Here, the effects of PTEN on cell invasion, migration, and growth as wed as the involvement of FAK and p130 Crk-associated substrate (p130(Cas)) were investigated in U87MG glioblastoma cells missing PTEN. Cell invasion, migration, and growth were down-regulated by expression of phosphatase-active forms of PTEN but not by PTEN with an inactive phosphatase domain; these effects were correlated with decreased tyrosine phosphorylation levels of FAK and p130(Cas). Overexpression of FAK concomitant with PTEN resulted in increased total tyrosine phosphorylation levels of FAK and p130(Cas) and effectively antagonized the effects of PTEN on cell invasion and migration and partially on cell growth. Overexpression of p130(Cas) increased total tyrosine phosphorylation levels of p130(Cas) without affecting those of FAK; however, although p130(Cas) could reverse PTEN inhibition of cell invasion and migration, it did not rescue cell growth in U87MG cells. In contrast to FAK, p130(Cas) could not he shown to interact with PTEN in cells, and it was not dephosphorylated directly by PTEN in vitro. These results suggest important roles of PTEN in the phenotype of tumor progression, and that the effects of PTEN on cell invasion, migration, and growth are mediated by distinct downstream pathways that diverge at the level of FAK. C1 NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Yamada, KM (reprint author), NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bldg 30,Room 421,30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. RI TAKINO, Takahisa/D-8460-2015; OI Yamada, Kenneth/0000-0003-1512-6805 NR 71 TC 283 Z9 315 U1 1 U2 9 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1999 VL 59 IS 2 BP 442 EP 449 PG 8 WC Oncology SC Oncology GA 158AB UT WOS:000078092900033 PM 9927060 ER PT J AU McCracken, KA Bowen, WD Matsumoto, RR AF McCracken, KA Bowen, WD Matsumoto, RR TI Novel sigma receptor ligands attenuate the locomotor stimulatory effects of cocaine SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE cocaine; locomotor activity; psychomotor effect ID H-3 (+)-PENTAZOCINE; ANTAGONISM; BINDING; POTENT AB Cocaine interacts with a receptors, suggesting that these sites are important for many of its behavioral effects. Therefore, two novel a receptor Ligands, BD1008 (N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine) and BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine), were evaluated for their ability to attenuate cocaine-induced locomotor activity. Receptor binding studies showed that BD1008 and BD1063 have nanomolar affinities for sigma(1) and sigma(2) sites, but a 250-fold or lower affinity for nine other receptors, making them among the most selective a receptor ligands identified. In behavioral studies, pretreatment of mice with BD1008 or BD1063 produced a two-fold increase in the ED50 for the locomotor stimulatory effects of cocaine. These results suggest that a receptors are involved in the behavioral effects of cocaine. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Oklahoma, Hlth Sci Ctr, Coll Pharm, Dept Pharmacol & Toxicol, Oklahoma City, OK 73190 USA. NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Matsumoto, RR (reprint author), Univ Oklahoma, Hlth Sci Ctr, Coll Pharm, Dept Pharmacol & Toxicol, POB 26901, Oklahoma City, OK 73190 USA. EM rae-matsumoto@uokhsc.edu FU NIMH NIH HHS [MH50564] NR 13 TC 65 Z9 66 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JAN 15 PY 1999 VL 365 IS 1 BP 35 EP 38 DI 10.1016/S0014-2999(98)00876-0 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 160WC UT WOS:000078253800004 PM 9988120 ER PT J AU Schiltz, RL Mizzen, CA Vassilev, A Cook, RG Allis, CD Nakatani, Y AF Schiltz, RL Mizzen, CA Vassilev, A Cook, RG Allis, CD Nakatani, Y TI Overlapping but distinct patterns of histone acetylation by the human coactivators p300 and PCAF within nucleosomal substrates SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACETYLTRANSFERASE ACTIVITY; RNA-POLYMERASE; YEAST GCN5P; IN-VIVO; TRANSCRIPTION; ACTIVATION; CBP; COMPLEX; E1A; REQUIREMENTS AB A number of transcriptional coactivators possess intrinsic histone acetylase activity, providing a direct link between hyperacetylated chromatin and transcriptional activation. We have determined the core histone residues acetylated in vitro by recombinant p300 and PCAF within mononucleosomes. p300 specifically acetylates all sites of histones H2A and H2B known to be acetylated in bulk chromatin in vivo but preferentially acetylates lysines 14 and 18 of histone H3 and lysines 5 and 18 of histone H4. PCAF primarily acetylates lysine 14 of H3 but also less efficiently acetylates lysine 8 of H4. PCAF in its native form, which is present in a stable multimeric protein complex lacking p300/CBP, primarily acetylates H3 to a monoacetylated form, suggesting that PCAF-associated polypeptides do not alter the substrate specificity. These distinct patterns of acetylation by the p300 and PCAF may contribute to their differential roles in transcriptional regulation. C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. Univ Rochester, Dept Biol, Rochester, NY 14627 USA. Baylor Coll Med, Dept Microbiol & Immunol, Houston, TX 77030 USA. RP Nakatani, Y (reprint author), NICHHD, Lab Mol Growth Regulat, NIH, Bldg 6,Rm 416, Bethesda, MD 20892 USA. NR 43 TC 270 Z9 277 U1 3 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 15 PY 1999 VL 274 IS 3 BP 1189 EP 1192 DI 10.1074/jbc.274.3.1189 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 190HL UT WOS:000079956900003 PM 9880483 ER PT J AU Li, JF Pak, JH Huang, FL Huang, KP AF Li, JF Pak, JH Huang, FL Huang, KP TI N-methyl-D-aspartate induces neurogranin/RC3 oxidation in rat brain slices SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; LONG-TERM POTENTIATION; CALMODULIN-BINDING DOMAIN; NITRIC-OXIDE MODIFICATION; SIGNAL-TRANSDUCTION; SUBSTRATE RC3; PHOSPHORYLATION SITE; NMDA RECEPTORS; NEUROMODULIN; SUPEROXIDE AB Neurogranin/RC3 (Ng), a postsynaptic neuronal protein kinase C (PRC) substrate, binds calmodulin (CaM) at low level of Ca2+. In vitro, rat brain Ng can be oxidized by nitric oxide (NO) donors and by oxidants to form an intramolecular disulfide bond with resulting downward mobility shift on nonreducing SDS-polyacrylamide gel electrophoresis. The oxidized Ng, as compared with the reduced form, is a poorer substrate of PKC but like the PKC-phosphorylated Ng has a lower affinity for CaM than the reduced form. To investigate the physiological relevance of Ng oxidation, we tested the effects of neurotransmitter, N-methyl-D-aspartate (NMDA), NO donors, and other oxidants such as hydrogen peroxide and oxidized glutathione on the oxidation of this protein in rat brain slices. Western blot analysis showed that the NMDA-induced oxidation of Ng was rapid and transient, it reached maximum within 3-5 min and declined to base line in 30 min. The response was dose-dependent (EC50 similar to 100 mu M) and could be blocked by NMDA-receptor antagonist 2-amino-5-phosphonovaleric acid and by NO synthase inhibitor N-G-nitro-L-arginine methyl ester and N-G-monomethyl-L-arginine. Ng was oxidized by NO donors, sodium nitroprusside, S-nitroso-N-acetylpenicillamine, and S-nitrosoglutathione, and H2O2 at concentrations less than 0.5 mM. Oxidation of Ng in brain slices induced by sodium nitroprusside could be reversed by dithiothreitol, ascorbic acid, or reduced glutathione. Reversible oxidation and reduction of Ng were also observed in rat brain extracts, in which oxidation was enhanced by Ca2+ and the oxidized Ng could be reduced by NADPH or reduced glutathione. These results suggest that redox of Ng is involved in the NMDA-mediated signaling pathway and that there are enzymes catalyzing the oxidation and reduction of Ng in the brain. We speculate that the redox state of Ng, similar to the state of phosphorylation of this protein, may regulate the level of CaM, which in turn modulates the activities of CaM-dependent enzymes in the neurons. C1 NICHHD, Metab Regulat Sect, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Huang, KP (reprint author), NICHHD, Metab Regulat Sect, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Rm 6A36,49 Convent Dr,MSC 4510, Bethesda, MD 20892 USA. NR 53 TC 50 Z9 56 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 15 PY 1999 VL 274 IS 3 BP 1294 EP 1300 DI 10.1074/jbc.274.3.1294 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 190HL UT WOS:000079956900018 PM 9880498 ER PT J AU Jakubik, J Wess, J AF Jakubik, J Wess, J TI Use of a sandwich enzyme-linked immunosorbent assay strategy to study mechanisms of G protein-coupled receptor assembly SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MUSCARINIC ACETYLCHOLINE-RECEPTORS; BETA(2) ADRENERGIC-RECEPTOR; POSITIVE ALLOSTERIC ACTION; SITE-DIRECTED MUTAGENESIS; V2 VASOPRESSIN RECEPTORS; FUNCTIONAL-ROLE; CONFORMATIONAL-CHANGES; TRANSMEMBRANE HELICES; MUTATIONAL ANALYSIS; ANTAGONIST BINDING AB All G protein-coupled receptors are predicted to consist of a bundle of seven transmembrane helices (I-VII) that are connected by various extracellular and intracellular loops. At present, little is known about the molecular interactions that are critical for the proper assembly of the transmembrane receptor core. To address this issue, we took advantage of the ability of coexpressed N- and C-terminal m3 muscarinic receptor fragments to form functional receptor complexes (Schoneberg, T. Liu, J., and Wess, J. (1995) J. Biol. Chem. 270, 18000-18006). As a model system, we used two polypeptides, referred to, m3-trunk and m3-tail, that were generated by "splitting'' the m3 muscarinic receptor within the third intracellular loop. We initially demonstrated, by employing a sandwich enzyme-linked immunosorbent assay strategy, that the two receptor fragments directly associate with each other when coexpressed in COS-7 cells. Additional studies with N- and C terminal fragments derived from other G protein-coupled receptors showed that fragment association was highly receptor-specific. In subsequent experiments, the sandwich enzyme-linked immunosorbent assay system was used to identify amino acids that are required for proper fragment (receptor) assembly. Point mutations were introduced into m3-trunk or m3-tail, and the ability of these mutations to interfere with efficient fragment assembly was examined. These studies showed that three highly conserved proline residues (located in transmembrane helices V, VI, and VII) are essential for proper fragment association (receptor assembly). Interestingly, incubation with classical muscarinic agonists and antagonists or allosteric ligands led to significant increases in the efficiency of fragment association (particularly upon substitution of the conserved proline residues), indicating that all of these ligands can act as "anchors" between the m3-trunk and m3-tail fragments. The approach described here should be generally applicable to gain deeper insight into the molecular mechanisms governing G protein-coupled receptor structure and assembly. C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Wess, J (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-05, Bethesda, MD 20892 USA. RI Jakubik, Jan/B-7461-2012 OI Jakubik, Jan/0000-0002-1737-1487 NR 40 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 15 PY 1999 VL 274 IS 3 BP 1349 EP 1358 DI 10.1074/jbc.274.3.1349 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 190HL UT WOS:000079956900026 PM 9880506 ER PT J AU Vito, P Pellegrini, L Guiet, C D'Adamio, L AF Vito, P Pellegrini, L Guiet, C D'Adamio, L TI Cloning of AIP1, a novel protein that associates with the apoptosis-linked gene ALG-2 in a Ca2+-dependent reaction SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; PROGRAMMED CELL-DEATH; IL-1-BETA-CONVERTING ENZYME; SIGNAL-TRANSDUCTION; T-CELLS; ACTIVATION; CED-3; STIMULATION; CALCINEURIN; THYMOCYTES AB ALG-2 is a 22-kDa calcium-binding protein necessary for cell death induced by different stimuli in 3DO T-cell hybridoma 3DO cell clones depleted of ALG-2 protein exhibit normal caspases activation, suggesting that ALG-2 function is required downstream or is independent of caspase proteases activity for apoptosis to occur. Using the yeast two-hybrid screening system, we have isolated and characterized the mouse cDNA encoding for ALG-2 interacting protein 1 (AIP1), a novel protein that interacts with ALG-2. ALG-2 and AIP1 colocalize in the cytosol and the presence of calcium is an indispensable requisite for their association. Sequence align ment shows that AIP1 is highly similar to BRO1, a yeast protein related to components of the Pkc1p-MAP kinase cascade. Overexpression of a truncated form of AIP1 protects two different cell types from death induced by trophic factors withdrawal; thus, our data indicate that AIP1 cooperates with ALG-1 in executing the calcium-dependent requirements along the cell death pathway. C1 Basel Inst Immunol, CH-4005 Basel, Switzerland. RP NIAID, Cellular & Mol Immunol Lab, Tcell Mol Biol Unit, NIH, Bethesda, MD 20892 USA. EM vito@mail.bii.ch NR 31 TC 181 Z9 183 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 15 PY 1999 VL 274 IS 3 BP 1533 EP 1540 DI 10.1074/jbc.274.3.1533 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 190HL UT WOS:000079956900050 PM 9880530 ER PT J AU Park, YG Nesterova, M Agrawal, S Cho-Chung, YS AF Park, YG Nesterova, M Agrawal, S Cho-Chung, YS TI Dual blockade of cyclic AMP response element- (CRE) and AP-1-directed transcription by CRE-transcription factor decoy oligonucleotide - Gene-specific inhibition of tumor growth SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; CAMP-MEDIATED INDUCTION; SOMATOSTATIN GENE; DOMINANT REPRESSOR; REGULATORY SUBUNIT; BINDING-PROTEINS; TRANS-ACTIVATOR; EXPRESSION; PROMOTER; CELLS AB Alteration of gene transcription by inhibition of specific transcriptional regulatory proteins has important therapeutic potential. Synthetic double-stranded phosphorothioate oligonucleotides with high affinity for a target transcription factor can be introduced into cells as decoy cis elements to bind the factors and alter gene expression. The CRE (cyclic AMP response element)-transcription factor complex is a pleiotropic activator that participates in the induction of a wide variety of cellular and viral genes. Because the CRE cis-element, TGACGTCA, is palindromic, a synthetic single-stranded oligonucleotide composed of the CRE sequence self;hybridizes to form a duplex/hairpin. Herein we report that the CRE-palindromic oligonucleotide can penetrate into cells, compete with CRE enhancers for binding transcription factors, and specifically interfere with CRE- and AP-1-directed transcription in vivo. These oligonucleotides restrained tumor cell proliferation, without affecting the growth of noncancerous cells. This decoy oligonucleotide approach offers great promise as a tool for defining cellular regulatory processes and treating cancer and other diseases. C1 NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. Hybridon Inc, Milford, MA 01757 USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, NIH, Bldg 10,Rm 5B05, Bethesda, MD 20892 USA. NR 33 TC 112 Z9 120 U1 2 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 15 PY 1999 VL 274 IS 3 BP 1573 EP 1580 DI 10.1074/jbc.274.3.1573 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 190HL UT WOS:000079956900055 PM 9880535 ER PT J AU Steinert, PM Marekov, LN Parry, DAD AF Steinert, PM Marekov, LN Parry, DAD TI Molecular parameters of type IV alpha-internexin and type IV-type III alpha-internexin-vimentin copolymer intermediate filaments SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COILED-COIL MOLECULES; TRANSMISSION ELECTRON-MICROSCOPY; EPIDERMAL KERATIN FILAMENTS; NF-L; NEUROFILAMENT PROTEINS; END DOMAINS; INVITRO; PERIPHERIN; EXPRESSION; CELLS AB During neuronal development, a dynamic replacement mechanism occurs in which the type VI nestin and type III vimentin intermediate filament proteins are replaced by a series of type IV proteins beginning with alpha-internexin. We have explored molecular details of how the type III to type IV replacement process may occur. First, we have demonstrated by cross linking experiments that bacterially expressed forms of alpha-internexin and vimentin form heterodimer molecules in vitro that assemble into copolymer intermediate filaments. We show using a urea disassembly assay that alpha-internexin molecules are likely to be more stable than those of vimentin. Second, by analyses of the induced cross-links, we have determined the axial lengths of alpha-internexin homodimer and alpha-internexin-vimentin heterodimer molecules and their modes of alignments in filaments. We report that these dimensions are the same as those reported earlier for vimentin homopolymer molecules and, by implication are also the same for the other neuronal type IV proteins. These data suggest that during neuronal development, alpha-internexin molecules are readily assimilated onto the pre-existing vimentin cytoskeletal intermediate filament network because the axial lengths and axial alignments of their molecules are the same. Furthermore, the dynamic replacement process may be driven by a positive equilibrium due to the increased stability of the alpha-internexin network. C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. Massey Univ, Inst Fundamental Sci, Palmerston North, New Zealand. RP Steinert, PM (reprint author), NIAMS, Skin Biol Lab, NIH, Bldg 6,Rm 425, Bethesda, MD 20892 USA. NR 59 TC 37 Z9 38 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 15 PY 1999 VL 274 IS 3 BP 1657 EP 1666 DI 10.1074/jbc.274.3.1657 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 190HL UT WOS:000079956900065 PM 9880545 ER PT J AU Tay, CH Yu, LYY Kumar, V Mason, L Ortaldo, JR Welsh, RM AF Tay, CH Yu, LYY Kumar, V Mason, L Ortaldo, JR Welsh, RM TI The role of LY49 NK cell subsets in the regulation of murine cytomegalovirus infections SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; BONE-MARROW ALLOGRAFTS; GENE-COMPLEX; INTERFERON-GAMMA; MICE; RECEPTORS; MOUSE; SPECIFICITY; RESISTANCE; REJECTION AB The distributions and functions of NK cell subsets, as defined by the expression of Ly49 NK cell receptors, were examined in murine CMV (MCMV)-infected mice. MCMV induced a reduction in NK1.1(+) cell number in the spleen and an increase in the peritoneal exudate cells. Within the splenic NK1.1(+) population, proportional increases in Ly49A(+) and Ly49G2(+) cells but decreases in Ly49C(+) and Ly49D(+) cells were observed 3 days post-MCMV infection, but within the peritoneal NK1.1(+) cell populations there were proportional decreases in Ly49A(+) cells and increases in Ly49C+, Ly49D(+), and Ly49G2+ cells. Lymphocytic choriomeningitis virus did not elicit a comparable NK cell subset distribution. Lymphokine-activated killer cells were sorted into different Ly49 NK cell subsets and adoptively transferred into C57BL/6 suckling mice. Regulation of MCMV synthesis in these suckling mice was shown to be an IFN-gamma-dependent, perforin- and Cmv-1-independent process, and each NK cell subset mediated anti-viral activity, In adult C57BL/6 mice, the control of MCMV in the spleen is mediated by a perforin-dependent mechanism, regulated in part by the Cmv-1 gene, which maps closely to the Ly49 family. In vivo depletions of either one or two of the Ly49 subsets in adult mice did not affect the ability of the residual NK cells to regulate MCMV synthesis. These data provide evidence of NK cell subset distribution and function in MCMV infection, but no individual subset was required for the Cmv-1-like regulation of MCMV synthesis. C1 Univ Massachusetts, Med Ctr, Dept Pathol, Worcester, MA 01655 USA. Univ Texas, Dept Pathol, Dallas, TX 75230 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. RP Welsh, RM (reprint author), Univ Massachusetts, Med Ctr, Dept Pathol, 55 Lake Ave N, Worcester, MA 01655 USA. FU NCI NIH HHS [CA34461] NR 34 TC 53 Z9 53 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 JAN 15 PY 1999 VL 162 IS 2 BP 718 EP 726 PG 9 WC Immunology SC Immunology GA 155MR UT WOS:000077951400013 PM 9916691 ER PT J AU Nakajima, H Leonard, WJ AF Nakajima, H Leonard, WJ TI Role of Bcl-2 in alpha beta T cell development in mice deficient in the common cytokine receptor gamma-chain: The requirement for Bcl-2 differs depending on the TCR/MHC affinity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID THYMOCYTE DIFFERENTIATION; LYMPHOID DEVELOPMENT; POSITIVE SELECTION; CYCLE PROGRESSION; INTERLEUKIN-7; EXPRESSION; APOPTOSIS; IL-7; DEATH; THYMUS AB Mice lacking the common cytokine receptor gamma-chain (gamma(c)) exhibit severely compromised T cell development, with diminished Bcl-2 expression in mature (CD4(+) or CD8(+)) thymocytes and peripheral T cells, Enforced expression of Bcl-2 in these mire partially rescued alpha beta T cell development but not gamma delta T cell development. Transgenic expression of the OVA-specific DO11.10 (DO10) TCR also could modestly increase thymocyte numbers, and T cells expressing the transgenic TCR (KJ1-26(+) T cells) were found in the periphery. Interestingly, the presence of KJ1-26(+) T cells was dependent on the MHC background and was seen in the moderate affinity H-2(d/d) background but not in the higher affinity H-2(d/b) background in gamma(c)-deficient mice. In contrast, KJ1-26(+) T cells exist in the periphery in both the H-2(d/d) and H-2(d/b) backgrounds in DO10 transgenic gamma(c) wild-type mice. These results suggest that the importance of gamma(c)-dependent signals for T cell development differs depending on the affinity of TCR for MHC. Moreover, enforced expression of Bcl-2 had a much greater effect on the development of gamma(c)-deficient T cells expressing the DO10 TCR in the high affinity H-2(d/b) background than in the H-2(d/d) background, suggesting that gamma(c)-dependent Bcl-2 expression influences T cell development in a TCR/MHC-dependent manner. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Rm 7N252,10 Ctr Dr, Bethesda, MD 20892 USA. EM wjl@helix.nih.gov NR 51 TC 38 Z9 38 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 1999 VL 162 IS 2 BP 782 EP 790 PG 9 WC Immunology SC Immunology GA 155MR UT WOS:000077951400021 PM 9916699 ER PT J AU Wu, CY Maeda, H Contursi, C Ozato, K Seder, RA AF Wu, CY Maeda, H Contursi, C Ozato, K Seder, RA TI Differential requirement of IFN consensus sequence binding protein for the production of IL-12 and induction of Th1-type cells in response to IFN-gamma SO JOURNAL OF IMMUNOLOGY LA English DT Article ID REGULATORY FACTOR FAMILY; MURINE PERITONEAL-MACROPHAGES; TRANSCRIPTION FACTOR; EXPRESSION; GENES; INFECTION; ELEMENTS; MUTATION; MEMBER; IRF-1 AB IFN-gamma exerts multiple biological activities in the modulation of immune responses by the induction of transcription factors. One transcriptional factor of the IFN regulatory factor family found to be critical in regulating IL-12-dependent IFN-gamma production in vivo following infectious challenge has been designated IFN consensus sequence-binding protein (ICSBP), In this study, the role of ICSBP in regulating type 1 responses to T cell-specific stimulation in vitro was assessed, Total splenocytes from ICSBP-/- mice stimulated with soluble anti-CDS were markedly impaired in the production of IFN-gamma compared with similarly stimulated cells from ICSBP+/+ mice. Consistent with the decrease in IFN-gamma production, splenocytes from ICSBP-/- mice stimulated with anti-CD3 in the presence or absence of IFN-gamma or a soluble CD40 ligand agonist failed to produce IL-12 p40 and IL-12 p70 protein; however, the deficient production of IFN-gamma from ICSBP-/- mice could be restored by the addition of anti-CD28 Ab in an IL-12-independent manner. In contrast to the previous data, production of IFN-gamma from naive CD4(+)/LECAM-1(high) cells of ICSBP-/- mice that had been primed in vitro with anti-CD3 was similar to or greater than that of ICSBP+/+ controls. In addition, the presence of IFN-gamma in priming cultures enhanced both priming for IFN-gamma and IL-12 responsiveness from ICSBP-/- CD4(+) T cells. Overall, these results provide evidence that ICSBP is differentially required for the ability of IFN-gamma to regulate type 1 cytokine responses from APCs and CD4(+) T cells. C1 NIAID, Clin Immunol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Seder, RA (reprint author), NIAID, Clin Immunol Sect, Clin Invest Lab, NIH, Bldg 10,Room 11C215, Bethesda, MD 20892 USA. NR 27 TC 33 Z9 35 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 JAN 15 PY 1999 VL 162 IS 2 BP 807 EP 812 PG 6 WC Immunology SC Immunology GA 155MR UT WOS:000077951400024 PM 9916702 ER PT J AU Burshtyn, DN Lam, AS Weston, M Gupta, N Warmerdam, PAM Long, EO AF Burshtyn, DN Lam, AS Weston, M Gupta, N Warmerdam, PAM Long, EO TI Conserved residues amino-terminal of cytoplasmic tyrosines contribute to the SHP-1-mediated inhibitory function of killer cell Ig-like receptors SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NK CELLS; ACTIVATION; PHOSPHATASES; ASSOCIATION; CLONES; SHP-1; HETEROGENEITY; RECRUITMENT; SPECIFICITY; RECOGNITION AB The sequence I/VxYxxL, often referred to as an immunoreceptor tyrosine-based inhibition motif (ITIM), binds to the C-terminal Src homology 2 domain of the tyrosine phosphatase SHP-1, Conserved residues N-terminal of the tyrosine are not ordinarily found in other Src homology 2 domain binding motifs, The inhibitory forms of killer cell Ig-like receptors (KIR) contain two ITIMs. The role of each ITIM, and of the conserved residues upstream of the tyrosine, in the inhibition of NK cells was tested by vaccinia virus-mediated expression of mutant KIRs, Substitution of the tyrosine in the membrane-proximal ITIM abrogated the ability of KIR to block Ab-dependent cellular cytotoxicity, whereas mutation of the membrane-distal ITIM tyrosine had little effect. Substitution of the conserved hydrophobic amino acid that was located two residues N-terminal to the tyrosine weakened, but did not eliminate, the function of the receptor, In contrast, these substitutions drastically reduced the amount of SHP-1 immunoprecipitated with KIR, suggesting that weak interactions with SHP-1 may be sufficient for inhibition. C1 NIAID, LIG, NIH, Rockville, MD 20852 USA. RP Long, EO (reprint author), NIAID, LIG, NIH, Twinbrook 2,12441 Parklawn Dr, Rockville, MD 20852 USA. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 30 TC 69 Z9 71 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 JAN 15 PY 1999 VL 162 IS 2 BP 897 EP 902 PG 6 WC Immunology SC Immunology GA 155MR UT WOS:000077951400035 PM 9916713 ER PT J AU Chiaramonte, MG Schopf, LR Neben, TY Cheever, AW Donaldson, DD Wynn, TA AF Chiaramonte, MG Schopf, LR Neben, TY Cheever, AW Donaldson, DD Wynn, TA TI IL-13 is a key regulatory cytokine for Th2 cell-mediated pulmonary granuloma formation and IgE responses induced by Schistosoma mansoni eggs SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MESSENGER-RNA EXPRESSION; CD4(+) T-CELLS; HUMAN B-CELLS; IFN-GAMMA; LEISHMANIA-MAJOR; DIFFERENTIAL REGULATION; PHENOTYPE DEVELOPMENT; ADHESION MOLECULE-1; MACROPHAGE FUNCTION; IMMUNE-RESPONSES AB Schistosoma mansoni egg-induced pulmonary granuloma formation is a cell-mediated inflammatory response associated with dominant Th2-type cytokine expression, tissue eosinophilia, and high levels of serum IgE, In the present study, we show that in vivo blockade of the Th2 cytokine IL-13, using soluble IL-13R alpha 2-Fc fusion protein, significantly reduced the size of pulmonary granulomas in unsensitized as well as egg-sensitized mice. Blocking IL-13 also significantly reduced total serum IgE levels. Interestingly, however, IL-13 blockade did not affect the evolving egg-induced Th2-type cytokine response. IL-4, IL-5, as well as IL-13 responses were indistinguishable in control-Fc- and soluble IL-13R alpha 2-Fc fusion protein-treated animals. The smaller granulomas were also phenotypically like the control Fc-treated mice, displaying a similar eosinophil content. Additional studies in IL-4-deficient mice demonstrated that IL-13 was produced, but at much lower levels than in wild-type mice, while IL-4 expression was completely independent of IL-13, Moreover, while granuloma formation was partially reduced in IL-4-deficient mice, blocking IL-13 in these animals almost completely abrogated granuloma development and the pulmonary eosinophilia, while it simultaneously increased IFN-gamma production. Together, these data demonstrate that IL-13 serves as an important mediator of Th2-mediated inflammation and plays a role in eliciting IgE responses triggered by schistosome eggs. C1 NIAID, Immunobiol Sect, Parasit Dis Lab, Schistosomiasis Immunol & Pathol Unit,NIH, Bethesda, MD 20892 USA. Inst Genet, Preclin Res, Andover, MA 01810 USA. Biomed Res Inst, Rockville, MD 20852 USA. RP Wynn, TA (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, Schistosomiasis Immunol & Pathol Unit,NIH, 9000 Rockville Pike,Bldg 4-126, Bethesda, MD 20892 USA. RI Wynn, Thomas/C-2797-2011 NR 64 TC 159 Z9 160 U1 1 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 1999 VL 162 IS 2 BP 920 EP 930 PG 11 WC Immunology SC Immunology GA 155MR UT WOS:000077951400038 PM 9916716 ER PT J AU Zeh, HJ Perry-Lalley, D Dudley, ME Rosenberg, SA Yang, JC AF Zeh, HJ Perry-Lalley, D Dudley, ME Rosenberg, SA Yang, JC TI High avidity CTLs for two self-antigens demonstrate superior in vitro and in vivo antitumor efficacy SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTE; PEPTIDE VACCINATION; TUMOR; IDENTIFICATION; REGRESSION; INDUCTION; MELANOMA; LEAD AB A majority of the human tumor-associated Ags characterized to date are derived from nonmutated "self"-proteins. Little is currently understood about the nature of the self-reactive lymphocytes that recognize these Ags. We recently characterized two nonmutated tumor-associated Ags for the B16 murine melanoma: tyrosinase-related protein-2 (TRP-2) and the endogenous retroviral envelope protein, p15E, We previously reported that both TRP-2 and p15E reactive CTL could be detected in the spleens of naive animals after a single in vitro stimulation using 10(-5)-10(-6) M of the appropriate K-b-binding 9-amino acid epitope. In this report we show that the CTL found in naive animals are low avidity lymphocytes, that respond only to high concentrations of peptide in vitro. We demonstrate that titration of in vitro-stimulating peptide to limiting concentrations distinguishes qualitative differences in the lymphocyte reactivity to these two Ags between vaccinated and unvaccinated animals. We further demonstrate that in vitro expansion of CTL in either high or low concentrations of stimulating peptide generated CTL cultures with different avidities for the relevant epitopes, CTL expanded in low concentrations demonstrated higher avidity for peptide-pulsed targets and better tumor recognition, when compared to CTL generated in the presence of high concentrations of Ag, More importantly, high avidity CTL demonstrated superior in vivo antitumor activity. These results demonstrate that qualitative differences in the CTL that recognize these two self-Ags are critically important to their in vitro and in vivo anti-tumor efficacy. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Yang, JC (reprint author), NCI, Surg Branch, NIH, Bldg 10,Rm 2B-37,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 16 TC 282 Z9 284 U1 1 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 1999 VL 162 IS 2 BP 989 EP 994 PG 6 WC Immunology SC Immunology GA 155MR UT WOS:000077951400046 PM 9916724 ER PT J AU Constantin, G Laudanna, C Brocke, S Butcher, EC AF Constantin, G Laudanna, C Brocke, S Butcher, EC TI Inhibition of experimental autoimmune encephalomyelitis by a tyrosine kinase inhibitor SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; SIGNAL-TRANSDUCTION; HUMAN NEUTROPHILS; DRUG DEVELOPMENT; B-CELLS; ACTIVATION; PHOSPHORYLATION; INTEGRINS; APOPTOSIS; CYTOKINES AB Migration of lymphocytes from the blood into the brain is a critical event in the pathogenesis of experimental autoimmune encephalomyelitis. Lymphocyte adhesion to brain endothelium is the first step in lymphocyte entry into the central nervous system, leading subsequently to myelin damage and paralysis. In this paper we show that the tyrosine kinase inhibitor, tyrphostin AG490, prevents binding of freshly isolated mouse lymph node cells and of in vivo activated lymphocytes to endothelium of inflamed brain in Stamper-Woodruff adhesion assays. Moreover, AG490 inhibits adhesion of encephalitogenic T cell lines to purified ICAM-1 and VCAM-1, molecules implicated in T cell recruitment into the central nervous system. In contrast, 2-h treatment of T cell lines with high doses of tyrphostin AG490 have no effect on the viability, intracellular calcium elevation induced by Con A or TCR crosslinking, proliferation, or TNF production by Ag-stimulated T cell lines. Systemic administration of AG490 prevents the accumulation of leukocytes in the brain and the development of experimental autoimmune encephalomyelitis induced by proteolipid protein, peptide 139-151-specific T cell lines in SJL/J mice. Blood leukocytes isolated from mice treated with tyrphostin AG490 are less adhesive on purified very late Ag-4 ligands compared with adhesion of leukocytes from control animals. Our results suggest that inhibition of signaling pathways involved in lymphocyte adhesion may represent a novel therapeutic approach for demyelinating diseases. C1 Univ Verona, Ist Patol Gen, I-37134 Verona, Italy. Stanford Univ, Sch Med, Dept Pathol, Lab Immunol & Vasc Biol, Stanford, CA 95305 USA. Stanford Univ, Sch Med, Ctr Digest Dis, Stanford, CA 95305 USA. Vet Adm Med Ctr, Foothill Res Ctr, Ctr Mol Biol Med, Palo Alto, CA 94304 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Constantin, G (reprint author), Univ Verona, Ist Patol Gen, Strada le Grazie, I-37134 Verona, Italy. NR 30 TC 36 Z9 37 U1 1 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 JAN 15 PY 1999 VL 162 IS 2 BP 1144 EP 1149 PG 6 WC Immunology SC Immunology GA 155MR UT WOS:000077951400067 PM 9916745 ER PT J AU Kachar, B Liang, FX Lins, U Ding, MX Wu, XR Stoffler, D Aebi, U Sun, TT AF Kachar, B Liang, FX Lins, U Ding, MX Wu, XR Stoffler, D Aebi, U Sun, TT TI Three-dimensional analysis of the 16 nm urothelial plaque particle: Luminal surface exposure, preferential head-to-head interaction, and hinge formation SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE bladder epithelium; asymmetric unit membrane; uroplakin; urothelial plaque; urothelial differentiation ID MAMMALIAN URINARY-BLADDER; ASYMMETRIC UNIT MEMBRANE; TRANSITIONAL EPITHELIUM; 3-DIMENSIONAL STRUCTURE; PLASMA-MEMBRANE; APICAL MEMBRANE; CELL-SURFACE; DIFFERENTIATION; UROPLAKIN; VESICLES AB The luminal surface of mouse urothelium in contact with the urine is almost entirely covered with plaques consisting of uroplakin-containing particles that form p6 hexagonal crystals with a center-to-center distance of 16 nm. A combination of quick-freeze/deep-etch images and our previous negative staining data indicate that the head domain of the uroplakin particle, which is exposed without an extensive glycocalyx shield, interacts closely with the head domains of the neighboring particles, while the membrane-embedded tail domains are farther apart; and that urothelial particles and plaques are not rigid structures as they can change their configuration in response to mechanical perturbations. Based on these data, we have constructed three-dimensional models depicting the structural organization of urothelial particles and plaques. Our models suggest that the head-to-head interaction may play a key role in determining the shape and size of the urothelial plaques. These models can explain many properties of urothelial plaques including their unique shape, detergent-insolubility, and morphological changes during vesicle maturation. (C) 1999 Academic Press. C1 NYU, Sch Med, Kaplan Comprehens Canc Ctr, Epithelial Biol Unit,Ronald O Perelman Dept Derma, New York, NY 10016 USA. Natl Inst Deafness & Commun Disorders, Sect Struct Cell Biol, NIH, Bethesda, MD 20892 USA. Univ Fed Rio de Janeiro, Dept Microbiol, Rio De Janeiro, Brazil. Peking Univ, Coll Life Sci, Beijing 100871, Peoples R China. NYU, Sch Med, Kaplan Comprehens Canc Ctr, Dept Urol, New York, NY 10016 USA. NYU, Sch Med, Kaplan Comprehens Canc Ctr, Dept Microbiol, New York, NY 10016 USA. Vet Adm Med Ctr, New York, NY 10010 USA. Univ Basel, Biozentrum, ME Muller Inst Struct Biol, CH-4056 Basel, Switzerland. NYU, Sch Med, Kaplan Comprehens Canc Ctr, Dept Pharmacol, New York, NY 10016 USA. RP Sun, TT (reprint author), NYU, Sch Med, Kaplan Comprehens Canc Ctr, Epithelial Biol Unit,Ronald O Perelman Dept Derma, 550 1St Ave, New York, NY 10016 USA. RI Lins, Ulysses/N-7282-2015 OI Lins, Ulysses/0000-0002-1786-1144 FU NIDDK NIH HHS [DK49469, DK39753, DK47529] NR 42 TC 84 Z9 86 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JAN 15 PY 1999 VL 285 IS 2 BP 595 EP 608 DI 10.1006/jmbi.1998.2304 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 158VP UT WOS:000078138300015 PM 9878432 ER PT J AU Blanco, FJ Angrand, I Serrano, L AF Blanco, FJ Angrand, I Serrano, L TI Exploring the conformational properties of the sequence space between two proteins with different folds: An experimental study SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE protein folding; secondary structure; protein stability; modeling; evolution ID IMMUNOGLOBULIN-BINDING DOMAIN; SITE-DIRECTED MUTAGENESIS; SH3 DOMAIN; FOLDABILITY LANDSCAPE; SECONDARY STRUCTURE; CRYSTAL-STRUCTURE; KINETIC-ANALYSIS; MODEL PROTEINS; DESIGN; SPECTROSCOPY AB We have examined the conformational properties of 27 polypeptides whose sequences are hybrids of two natural protein domains with 8% sequence identity and different structures. One of the natural sequences (spectrin SH3 domain) was progressively mutated to get closer to the other sequence (protein G B1 domain), with the only constraint of maintaining the residues at the hydrophobic core. Only two of the mutants are folded, each of them having a large sequence identity with one of the two natural proteins. The rest of the mutants display a wide range of structural properties, but they lack a well-defined three-dimensional structure, a result that is not recognized by computational tools commonly used to evaluate the reliability of structural models. Interestingly, some of the mutants exhibit cooperative thermal denaturation curves and a signal in the near-ultraviolet circular dichroism spectra, both typical features of folded proteins. However, they do not have a well-dispersed nuclear magnetic resonance spectrum indicative of a defined tertiary structure. The results obtained here show that both the hydrophobic core residues and the surface residues are important in determining the structure of the proteins, and suggest that the appearance of a completely new fold from an existing one is unlikely to occur by evolution through a route of folded intermediate sequences. (C) 1999 Academic Press. C1 European Mol Biol Lab, D-69117 Heidelberg, Germany. RP Blanco, FJ (reprint author), NIDDK, Chem Phys Lab, NIH, 9000 Rockville Pike ,Bldg 5,Room 406, Bethesda, MD 20892 USA. EM blanco@speck.niddk.nih.gov RI Blanco, Francisco/D-4401-2009; Serrano, Luis/B-3355-2013 OI Blanco, Francisco/0000-0003-2545-4319; Serrano, Luis/0000-0002-5276-1392 NR 52 TC 39 Z9 39 U1 0 U2 7 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JAN 15 PY 1999 VL 285 IS 2 BP 741 EP 753 DI 10.1006/jmbi.1998.2333 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 158VP UT WOS:000078138300025 PM 9878441 ER PT J AU Vaughan, RA Agoston, GE Lever, JR Newman, AH AF Vaughan, RA Agoston, GE Lever, JR Newman, AH TI Differential binding of tropane-based photoaffinity ligands on the dopamine transporter SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cocaine; benztropine; dopamine transporter; photoaffinity label; dopamine uptake; proteolytic peptide mapping; immunoprecipitation ID COCAINE RECEPTOR; NOREPINEPHRINE TRANSPORTERS; MONOAMINE TRANSPORTERS; UPTAKE INHIBITORS; ANALOGS; DOMAINS; POTENT; GBR-12909; SITES; RADIOSYNTHESIS AB Benztropine and its analogs are tropane ring-containing dopamine uptake inhibitors that produce behavioral effects markedly different from cocaine and other dopamine transporter blockers. We investigated the benztropine binding site on dopamine transporters by covalently attaching a benztropine-based photoaffinity ligand, [I-125]N-[n-butyl-4-(4'''-azido-3'''-iodophenyl)]- 4',4 "-difluoro-3 alpha-(diphenylmethoxy)tropane ([I-125]GA II 34), to the protein, followed by proteolytic and immunological peptide mapping. The maps were compared with those obtained for dopamine transporters photoaffinity labeled with a GBR 12935 analog, [I-125]1-[2-(djphenylmethoxy)ethyl]-4-[2-(4-azido 3-iodophenyl)ethyl]piperazine ([I-125]DEEP), and a cocaine analog, [I-125]3 beta-(p-chlorophenyl)tropane-2 beta-carboxylic acid, 4'-azido-3'-iodophenylethyl ester ([I-125]RTI 82), which have been shown previously to interact with different regions of the primary sequence of the protein. [I-125]GA II 34 became incorporated in a membrane-bound, 14 kDa fragment predicted to contain transmembrane domains 1 and 2. This is the same region of the protein that binds [I-125]DEEP, whereas the binding site for [I-125]RTI 82 occurs closer to the C terminal in a domain containing transmembrane helices 4-7. Thus, although benztropine and cocaine both contain tropane rings, their binding sites are distinct, suggesting that dopamine transport inhibition may occur by different mechanisms. These results support previously derived structure-activity relationships suggesting that benztropine and cocaine analogs bind to different domains on the dopamine transporter. These differing molecular interactions may lead to the distinctive behavioral profiles of these compounds in animal models of drug abuse and indicate promise for the development of benztropine-based molecules for cocaine substitution therapies. C1 NIDA, Psychobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NIDA, Mol Neurobiol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Publ Hlth, Yerkes Reg Primate Ctr, Div Neurosci, Baltimore, MD 21205 USA. RP Newman, AH (reprint author), NIDA, Psychobiol Sect, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NIDA NIH HHS [DA 08870] NR 44 TC 59 Z9 59 U1 1 U2 3 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 JAN 15 PY 1999 VL 19 IS 2 BP 630 EP 636 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 155VE UT WOS:000077966400013 PM 9880583 ER PT J AU Chandross, KJ Cohen, RI Paras, P Gravel, M Braun, PE Hudson, LD AF Chandross, KJ Cohen, RI Paras, P Gravel, M Braun, PE Hudson, LD TI Identification and characterization of early glial progenitors using a transgenic selection strategy SO JOURNAL OF NEUROSCIENCE LA English DT Article DE 2 ',3 '-cyclic nucleotide 3 '-phosphodiesterase; beta-galactosidase; CNS; development; glia; neomycin resistance; peripheral nervous system; selection; tissue culture ID 2',3'-CYCLIC NUCLEOTIDE 3'-PHOSPHODIESTERASE; CENTRAL-NERVOUS-SYSTEM; RAT SPINAL-CORD; MYELIN-ASSOCIATED ENZYME; CULTURED SCHWANN-CELLS; BASIC-PROTEIN GENE; OLIGODENDROCYTE PRECURSORS; VENTRICULAR ZONE; MESSENGER-RNA; NEURAL CREST AB To define the spatiotemporal development of and simultaneously select for oligodendrocytes (OLs) and Schwann cells (SCs), transgenic mice were generated that expressed a bacterial beta-galactosidase (beta-gal) and neomycin phosphotransferase fusion protein (beta geo) under the control of murine 2'3'-cyclic nucleotide 3'-phosphodiesterase (muCNP) promoters I and II. Transgenic beta-gal activity was detected at embryonic day 12.5 in the ventral region of the rhombencephalon and spinal cord and in the neural crest. When cells from the rhombencephalon were cultured in the presence of G418, surviving cells differentiated into OLs, indicating that during development this brain region provides one source of OL progenitors. Postnatally, robust P-gal activity was localized to OLs throughout the brain and was absent from astrocytes, neurons, and microglia or monocytes. In the sciatic nerve beta-gal activity was localized exclusively to SCs. Cultures from postnatal day 10 brain or sciatic nerve were grown in the presence of G418, and within 8-9 d exposure to antibiotic, 99% of all surviving cells were beta-gal-positive OLs or SCs. These studies demonstrate that the muCNP-beta geo transgenic mice are useful for identifying OLs and SCs beginning at early stages of the glial cell lineage and throughout their development. This novel approach definitively establishes that the beta-gal-positive cells identified in vivo are glial progenitors, as defined by their ability to survive antibiotic selection and differentiate into OLs or SCs in vitro. Moreover, this experimental paradigm facilitates the rapid and efficient selection of pure populations of mouse OLs and SCs and further underscores the use of cell-specific promoters in the purification of distinct cell types. C1 NINDS, NIH, Lab Dev Neurogenet, Bethesda, MD 20892 USA. McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada. RP Chandross, KJ (reprint author), NINDS, NIH, Lab Dev Neurogenet, Bldg 36,Room 5D21, Bethesda, MD 20892 USA. NR 77 TC 43 Z9 44 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 JAN 15 PY 1999 VL 19 IS 2 BP 759 EP 774 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 155VE UT WOS:000077966400026 PM 9880596 ER PT J AU Palko, ME Coppola, V Tessarollo, L AF Palko, ME Coppola, V Tessarollo, L TI Evidence for a role of truncated trkC receptor isoforms in mouse development SO JOURNAL OF NEUROSCIENCE LA English DT Article DE trkC; truncated receptor; development; neurotrophin; trk receptors; transgenic ID NEUROTROPHIC FACTOR; SENSORY NEURONS; NERVOUS-SYSTEM; TYROSINE KINASE; RAT TRKC; GENE; EXPRESSION; BRAIN; MICE; DISRUPTION AB The trkC locus encodes several receptors for neurotrophin-3, including the well studied full-length tyrosine kinase isoform, in addition to receptor isoforms lacking the kinase active domain. TrkC receptors are widely expressed throughout mouse development in many different organs. To investigate the function of truncated receptors in vivo and to identify cell types that are biologically responsive to this gene product, we have overexpressed a physiological truncated trkC isoform in the mouse. Mice overexpressing this receptor develop to term but die in the first postnatal days. High levels of transgene expression result in severe developmental defects in the peripheral nervous system and in the heart. The severity of neuronal losses observed in these animals suggests that truncated receptors may act by sequestering neurotrophin, thus, closely relating this mouse model to the neurotrophin-3-deficient one. Lower levers of exogenous truncated receptor in transgenic mice result in a more modest phenotype and, in some neuronal populations, do not cause neural deficits. Taken together, these data suggest that truncated trkC receptor isoforms may have modulatory functions in development. C1 NCI, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Neural Dev Grp, Frederick, MD 21702 USA. RP Tessarollo, L (reprint author), NCI, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Neural Dev Grp, POB B, Frederick, MD 21702 USA. RI Coppola, Vincenzo/E-2917-2011 OI Coppola, Vincenzo/0000-0001-6163-1779 NR 38 TC 34 Z9 34 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 15 PY 1999 VL 19 IS 2 BP 775 EP 782 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 155VE UT WOS:000077966400027 PM 9880597 ER PT J AU Higgins, JJ Litvan, I Nee, LE Loveless, JM AF Higgins, JJ Litvan, I Nee, LE Loveless, JM TI A lack of the R406W tau mutation in progressive supranuclear palsy and corticobasal degeneration SO NEUROLOGY LA English DT Article ID DIAGNOSIS; PROTEIN AB Linkage disequilibrium studies suggest that progressive supranuclear palsy (PSP) is an autosomal recessive condition that maps to a polymorphism in the tau gene. These results provide evidence that homozygous mutations in the tau gene may cause PSP. Recently, a missense mutation in exon 13 of one tare allele (R406W) was found in a single family with an atypical clinicopathologic form of dominantly inherited PSP. The authors report that the R406W mutation is lacking in 25 unrelated individuals with PSP and in six unrelated individuals with another tauopathy-corticobasal degeneration. C1 New York State Dept Hlth, Wadsworth Ctr Labs & Res, Lab Clin Neurogenet, Albany, NY 12201 USA. NINDS, Neuroepidemiol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Family Studies Unit, NIH, Bethesda, MD 20892 USA. RP Higgins, JJ (reprint author), New York State Dept Hlth, Wadsworth Ctr, Lab Clin Neurogenet, POB 509, Albany, NY 12201 USA. OI Litvan, Irene/0000-0002-3485-3445 NR 10 TC 10 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN 15 PY 1999 VL 52 IS 2 BP 404 EP 406 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 161DV UT WOS:000078274200035 PM 9932968 ER PT J AU Stubner, S Schon, T Padberg, F Teipel, SJ Schwarz, MJ Haslinger, A Buch, K Dukoff, R Lasser, R Muller, N Sunderland, T Rapoport, SI Moller, HJ Hampel, H AF Stubner, S Schon, T Padberg, F Teipel, SJ Schwarz, MJ Haslinger, A Buch, K Dukoff, R Lasser, R Muller, N Sunderland, T Rapoport, SI Moller, HJ Hampel, H TI Interleukin-6 and the soluble IL-6 receptor are decreased in cerebrospinal fluid of geriatric patients with major depression: no alteration of soluble gp130 SO NEUROSCIENCE LETTERS LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the Society-for-Neuroscience CY NOV 07-12, 1998 CL LOS ANGELES, CALIFORNIA SP Soc Neurosci DE major depression; healthy controls; cerebrospinal fluid; interleukin-6; soluble interleukin-6-receptor; gp130 ID ALZHEIMERS-DISEASE; CYTOKINE PRODUCTION; MULTIPLE-SCLEROSIS; PLASMA-LEVELS; BRAIN; SCHIZOPHRENIA; DEMENTIA; PROTEINS AB Interleukin-6 (IL-6) is hypothesized to play an important role in the interaction between immune mechanisms and the central nervous system. We investigated whether cerebrospinal fluid (CSF) concentrations of interleukin-6 (IL-6), the soluble (IL-6 receptor (sIL-6R) and the soluble form of the signal transducing and affinity converting receptor gp130 (sgp130) are altered in geriatric patients with major depression (MD). In 20 geriatric patients with MD and 20 age-matched healthy control subjects CSF concentrations of the three components of the sIL-6R complex were analyzed by enzyme-linked immunosorbent assays (ELISA). Ail patients except one were treated with psychotropic drugs. We found statistically significant decreased CSF concentrations of IL-6 (P < 0.001) and of the sIL-6R (P < 0.001) of patients with MD. Levels of sgp130 showed no statistically significant difference between patients and controls. (C) 1999 Elsevier Science ireland Ltd. All rights reserved. C1 Univ Munich, Dementia Res Sect, Geriatr Psychiat Branch, Dept Psychiat, D-80337 Munich, Germany. NIMH, NIH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. NIA, NIH, Neurosci Lab, Bethesda, MD 20892 USA. RP Stubner, S (reprint author), Univ Munich, Dementia Res Sect, Geriatr Psychiat Branch, Dept Psychiat, Nussbaumstr 7, D-80337 Munich, Germany. NR 26 TC 33 Z9 33 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 JAN 15 PY 1999 VL 259 IS 3 BP 145 EP 148 DI 10.1016/S0304-3940(98)00916-1 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 162GY UT WOS:000078338600003 PM 10025579 ER PT J AU Metosh-Dickey, CA Mason, RP Winston, GW AF Metosh-Dickey, CA Mason, RP Winston, GW TI Nitroarene reduction and generation of free radicals by cell-free extracts of wild-type, and nitroreductase-deficient and -enriched Salmonella typhimurium strains used in the umu gene induction assay SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID ELECTRON-SPIN-RESONANCE; MUTAGENICITY; SYSTEM; PURIFICATION; MECHANISM; EXISTENCE; LIVER AB Studies of the enzymatic properties of cell-free extracts prepared from overnight cultures of the normal, and nitroreductase-deficient and -enriched strains of Salmonella typhimurium, designed for use in the umu gene induction assay of Oda et al. (1992), were undertaken in an effort to clarify the nature of nitroreductase deficiency in relation to mutagenicity, The ability of these strains to promote oxygen consumption and free radical intermediates of representative nitroarene substrates was measured, respectively, by oxygen polarography and electron spin resonance (ESR) spectroscopy. The substrates 4-nitropyridine N-oxide (4NPO) and 4-nitroquinoline N-oxide (4NQO) stimulated the rate and extent of NADH-dependent oxygen consumption catalyzed by cell-free extracts prepared from wild-type, and nitroreductase-deficient and -enriched strains. The extent of oxygen consumption was greater than stoichiometric with respect to the amount of nitroaromatic substrate, which implied one-electron reduction of 4NQO by these bacterial extracts and subsequent redox cycling with oxygen. ESR spectroscopy confirmed the production of free radical metabolites of the nitroarene substrates, which were inferred by the oxygen consumption studies. At equal protein concentrations the cell-free extracts of each strain catalyzed univalent reduction of 4NPO yielding the 59 line signal characteristic of the 4NPO nitro anion radical. This ESR signal was potently inhibited by the flavoprotein inhibitors CuSO4 and PCMB, albeit a twofold or higher concentration of both inhibitors was required to inhibit the signal produced by extract from the nitroreductase-deficient strain than that produced by the other strains. The results indicate that the nitroreductase-deficient strain of Salmonella typhimurium developed for use in the umu gene induction assay is not deficient in either one-electron nitro group or quinone reductase activity. (C) 1999 Academic Press. C1 N Carolina State Univ, Dept Biochem, Raleigh, NC 27695 USA. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Winston, GW (reprint author), N Carolina State Univ, Dept Biochem, Box 7622, Raleigh, NC 27695 USA. FU NIAAA NIH HHS [AA06758] NR 36 TC 4 Z9 5 U1 0 U2 2 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 JAN 15 PY 1999 VL 154 IS 2 BP 126 EP 134 DI 10.1006/taap.1998.8573 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 167FD UT WOS:000078621100002 PM 9925796 ER PT J AU Garner, CE Jefferson, WN Burka, LT Matthews, HB Newbold, RR AF Garner, CE Jefferson, WN Burka, LT Matthews, HB Newbold, RR TI In vitro estrogenicity of the catechol metabolites of selected polychlorinated biphenyls SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID ENVIRONMENTAL CONTAMINANTS; DIETARY EXPOSURE; PCBS; IDENTIFICATION; RECEPTOR; TROUT; RATS; INDUCTION; MECHANISM; SURVIVAL AB A considerable body of work has demonstrated that phenolic polychlorinated biphenyl (PCB) metabolites, structural analogues to estradiol, bind to the soluble estrogen receptor (ER) and that hydroxy PCB-ER complexes will translocate into the nucleus and bind to ER response elements in cultured cells. Although catechol estrogens exhibit weak estrogenic activity, the catechol PCB metabolites which are structurally similar to these ER agonists have gone untested for potential estrogenicity, In the present work we have assessed the estrogenicity of this second group of PCB metabolites, the catechols. The test compounds used in the present study were chosen to elucidate the effects of chlorine and catechol position on in vitro estrogenicity, Cultured HeLa cells, transfected with the estrogen reporter gene ERET81CAT and mouse ER cDNA, were incubated with PCB catechols. The cells were harvested at 28 h posttransfection and assayed for chloramphenicol acetyl transferase (CAT) activity. The responses elicited by the PCB catechols tested fell within the range of effect measured for the catechol estrogens and phenolic PCBs, and were within the range previously reported for other "environmental estrogens" such as nonylphenol and o,p'-DDT. Maximal measured responses were achieved at concentrations approximately two to three orders of magnitude higher than that of 17-beta-estradiol, indicating that PCB catechols have estrogenic activity in vitro. The extent of chlorination and the position of the catechol (3,4 vs 2,3 substitution) were important in determining estrogenicity in the compounds tested. The 2,3-catechol showed no detectable activity in this system, while activity of the 3,4-catechols increased with the degree of chlorination. The observed estrogenicity of PCB catechols suggests that further oxidative metabolism of estrogenic PCB phenolic metabolites would not necessarily result in lowering the total estrogenic burden of a PCB-exposed organism. The present results imply that if estrogenic activity is assigned to an individual phenol, the potential contribution of its catechol metabolites to the total estrogenic burden should also be taken into consideration. C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NIEHS, Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Garner, CE (reprint author), NIEHS, Lab Pharmacol & Chem, POB 12233, Res Triangle Pk, NC 27709 USA. NR 52 TC 44 Z9 47 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JAN 15 PY 1999 VL 154 IS 2 BP 188 EP 197 DI 10.1006/taap.1998.8560 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 167FD UT WOS:000078621100009 PM 9925803 ER PT J AU Wolff, EC Park, MH AF Wolff, EC Park, MH TI Identification of lysine(350) of yeast deoxyhypusine synthase as the site of enzyme intermediate formation SO YEAST LA English DT Article DE deoxyhypusine synthase; hypusine; eIF5A; yeast; posttranslational modification ID COMPLETE GENOME SEQUENCE; EUKARYOTIC CELL-PROLIFERATION; SACCHAROMYCES-CEREVISIAE; AFFINITY-CHROMATOGRAPHY; HYPUSINE DEPLETION; PURIFICATION; EXPRESSION; SUBSTRATE; CDNA; GENE AB The posttranslational formation of deoxyhypusine in the precursor of eukaryotic initiation factor 5A (eIF5A) is catalysed by deoxyhypusine synthase. This NAD-dependent reaction involves transfer of the 4-aminobutyl moiety of spermidine to a single lysine residue in the eIF5A precursor. The present study shows evidence for the formation of a covalent enzyme-substrate intermediate between a specific lysine residue (Lys(350)) of yeast deoxyhypusine synthase and the 4-aminobutyl moiety from spermidine. Substitution of this lysine residue with Arg or Ala totally prevented the formation of the enzyme intermediate and consequently precluded deoxyhypusine synthesis in the eIF5A precursor, leading to the conclusion that the enzyme intermediate formed at Lys(350) is critical for deoxyhypusine synthesis activity. The results provide a rational basis for the inability of the mutated deoxyhypusine synthase gene encoding arginine in place of Lys(350) to support growth in yeast (Park; er al., 1998). The demonstration of the formation of an enzyme-imine intermediate in yeast deoxyhypusine synthase analogous to that of the human enzyme strongly suggests that the enzyme mechanism is conserved in diverse eukaryotes. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 NIDR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Wolff, EC (reprint author), NIDR, Oral & Pharyngeal Canc Branch, NIH, Bldg 30,Room 211, Bethesda, MD 20892 USA. NR 26 TC 12 Z9 12 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0749-503X J9 YEAST JI Yeast PD JAN 15 PY 1999 VL 15 IS 1 BP 43 EP 50 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA 160PP UT WOS:000078240000005 PM 10028184 ER PT J AU Mofenson, LM Harris, DR Rich, K Meyer, WA Read, JS Moye, J Nugent, RP Korelitz, J Bethel, J Pahwa, S AF Mofenson, LM Harris, DR Rich, K Meyer, WA Read, JS Moye, J Nugent, RP Korelitz, J Bethel, J Pahwa, S CA Natl Inst Child Hlth Human Dev Intravenous Immu TI Serum HIV-1 p24 antibody, HIV-1 RNA copy number and CD4 lymphocyte percentage are independently associated with risk of mortality in HIV-1-infected children SO AIDS LA English DT Article DE pediatric HIV-1 infection; mortality; HIV-1 p24 antibody; HIV-1 RNA; CD4 lymphocyte percentage; immune complex-dissociated p24 antigen ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS-RELATED COMPLEX; T-CELL RESPONSES; INFECTED CHILDREN; INTRAVENOUS IMMUNOGLOBULIN; DISEASE PROGRESSION; SEROLOGIC MARKERS; HOMOSEXUAL MEN; CORE ANTIGENS; TYPE-1 AB Objective: The role of HIV-1 antibody in modulating disease progression must be assessed in the context of other immune and viral load markers. We evaluated the association between HIV-1 p24 antibody, HIV-1 RNA, immune complex-dissociated (ICD) p24 antigen, CD4 cell percentage, and mortality in a cohort of 218 HIV-infected children enrolled in a trial of intravenous immunoglobulin prophylaxis of bacterial infections. Methods: CD4 cell percentage was measured and sera collected and stored at baseline and every 3 months on study (1988-1991). Stored sera were assayed for HIV-1 p24 antibody, HIV-1 RNA, and ICD p24 antigen. Mortality was recorded during the trial and updated through 1996 (mean total follow-up, 6.3 years). Results: Eighty-one (37%) children died; probability of mortality for children with baseline HIV-1 p24 antibody concentrations of undetectable (< 1), 1-4, 5-124, and greater than or equal to 125 reciprocal titer units (RTU) was 61, 50, 24, and 10%, respectively. A 3.5-fold increase in the relative risk (RR) of death [95% confidence interval (CI), 2.2-5.5] was observed among children with baseline HIV-1 p24 antibody concentration < 5 RTU compared with greater than or equal to 5 RTU. In multivariate analyses, p24 antibody, HIV-1 RNA, and CD4 cell percentage but not ICD p24 antigen were independently associated with mortality; the RR of death increased by 1.7 (95% CI, 1.3-2.1) for each log(10) decrement in baseline HIV-1 p24 antibody. Conclusions: HIV-1 p24 antibody, HIV-1 RNA and CD4 cell percentage independently predict mortality amongst infected children. Whereas CD4 cell percentage provides an estimate of the general degree of immune suppression, HIV-1 p24 antibody could provide an easily obtained, inexpensive assessment of CD4 cell function and could augment prognostic information provided by CD4 cell count and viral load for clinical management of infected children. (C) 1999 Lippincott Williams & Wilkins. C1 NICHHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH,Westat, Rockville, MD 20852 USA. Univ Illinois, Chicago, IL USA. Quest Diagnost Inc, Baltimore, MD USA. N Shore Univ Hosp, Manhasset, NY USA. RP Mofenson, LM (reprint author), NICHHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH,Westat, 6100 Execut Blvd,Room 4B11, Rockville, MD 20852 USA. OI Mofenson, Lynne/0000-0002-2818-9808; moye, john/0000-0001-9976-8586 FU NICHD NIH HHS [HD-33162] NR 43 TC 24 Z9 25 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN 14 PY 1999 VL 13 IS 1 BP 31 EP 39 DI 10.1097/00002030-199901140-00005 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 178BT UT WOS:000079246400005 PM 10207542 ER PT J AU Brown, MJ Shaw, S AF Brown, MJ Shaw, S TI T-cell activation: Interplay at the interface SO CURRENT BIOLOGY LA English DT Article AB Recent studies have shown that, when a T cell interacts with a cognate antigen-presenting cell, an organized adhesive contact is formed between the two cells by a process which involves the dynamic, three-dimensional redistribution of entire signaling assemblies. C1 NCI, Human Immunol Sect, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Brown, MJ (reprint author), NCI, Human Immunol Sect, Expt Immunol Branch, NIH, Bldg 10 Room 4B36, Bethesda, MD 20892 USA. NR 10 TC 10 Z9 10 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JAN 14 PY 1999 VL 9 IS 1 BP R26 EP + DI 10.1016/S0960-9822(99)80038-4 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 157XH UT WOS:000078086600013 PM 9889111 ER PT J AU Yao, ZJ King, CR Cao, T Kelley, J Milne, GWA Voigt, JH Burke, TR AF Yao, ZJ King, CR Cao, T Kelley, J Milne, GWA Voigt, JH Burke, TR TI Potent inhibition of Grb2 SH2 domain binding by non-phosphate-containing ligands SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID SOLID-PHASE SYNTHESIS; SIGNAL-TRANSDUCTION; EGF RECEPTOR; O-PHOSPHOTYROSINE; PEPTIDE LIGANDS; ANALOGS; CELLS; TRANSFORMATION; SPECIFICITY; PROTEINS AB Development of Grb2 Src homology 2 (SH2) domain binding inhibitors has important implications for treatment of a variety of diseases, including several cancers. In cellular studies, inhibitors of Grb2 SH2 domain binding have to date been large, highly charged peptides which relied on special transport devices for cell membrane penetration. Work presented in the current study examines a variety of pTyr mimetics in the context of a high-affinity Grb2 binding platform. Among the analogues studied are new norm-phosphorus-containing pTyr mimetics 23a and 23b which, when incorporated into tripeptide structures 18f and 20f, are able to inhibit Grb2 SH2 domain binding with affinities among the best yet reported for non-phosphorus-containing SH2 domain inhibitors (IC50 values of 6.7 and 1.3 mu M, respectively). The present study has also demonstrated the usefulness of the Na-oxalyl group as an auxiliary which enhances the binding potency of both phosphorus- and non-phosphorus-containing pTyr mimetics. When combined with the (phosphonomethyl)phenylalanine (Pmp) residue to give analogues such as L-20d, potent inhibition of Grb2 SH2 domain binding can be achieved both in extracellular assays using isolated Grb2 SH2 domain protein and in intracellular systems measuring the association of endogenous Grb2 with its cognate p185(erbB-2) ligand. These latter effects can be achieved at micromolar to submicromolar concentrations without prodrug derivatization. The oxalyl-containing pTyr mimetics presented in this study should be of general usefulness for the development of other Grb2 SH2 domain antagonists, independent of the beta-bend-mimicking platform utilized for their display. C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. RP Burke, TR (reprint author), NCI, Med Chem Lab, Div Basic Sci, NIH, Bldg 37,Rm 5C06, Bethesda, MD 20892 USA. EM tburke@helix.nih.gov RI Burke, Terrence/N-2601-2014; Yao, Zhu-Jun/E-7635-2015 NR 49 TC 91 Z9 91 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JAN 14 PY 1999 VL 42 IS 1 BP 25 EP 35 DI 10.1021/jm980388x PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 159WL UT WOS:000078198300002 PM 9888830 ER PT J AU Turpin, JA Song, YS Inman, JK Huang, MJ Wallqvist, A Maynard, A Covell, DG Rice, WG Appella, E AF Turpin, JA Song, YS Inman, JK Huang, MJ Wallqvist, A Maynard, A Covell, DG Rice, WG Appella, E TI Synthesis and biological properties of novel pyridinioalkanoyl thiolesters (PATE) as anti-HTV-1 agents that target the viral nucleocapsid protein zinc fingers SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; REVERSE TRANSCRIPTION; NONINFECTIOUS VIRUS; IN-VITRO; ANTI-HIV; TYPE-1; INHIBITORS; BINDING; DNA AB Nucleocapsid p7 protein (NCp7) zinc finger domains of the human immunodeficiency virus type 1 (HTV-1) are being developed as antiviral targets due to their key roles in viral replication and their mutationally nonpermissive nature. On the basis of our experience with symmetrical disulfide benzamides (DIBAs; Rice et al. Science 1995, 270, 1194-1197), we synthesized and evaluated variants of these dimers, including sets of 4,4'- and 3,3'-disubstituted diphenyl sulfones and their monomeric benzisothiazolone derivatives (BITA). BITAs generally exhibited diminished antiviral potency when compared to their disulfide precursors. Novel, monomeric structures were created by linking haloalkanoyl groups to the benzamide ring through -NHC(=O)- (amide) or -S-C(=O)- (thiolester) bridges. Amide-linked compounds generally lacked antiviral activity, while haloalkanoyl thiolesters and non-halogen-bearing analogues frequently exhibited acceptable antiviral potency, thus establishing thiolester benzamides per se as a new anti-HIV chemotype. Pyridinioalkanoyl thiolesters (PATEs) exhibited superior anti-HIV-1 activity with minimal cellular toxicity and appreciable water solubility. PATEs were shown to preferentially target the NCp7 Zn finger when tested against other molecular targets, thus identifying thiolester benzamides, and PATEs in particular, as novel NCp7 Zn finger inhibitors for in vivo studies. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Lab Antiviral Drug Mech, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Lab Expt & Computat Biol, Frederick, MD 21702 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Turpin, JA (reprint author), So Res Inst, 431 Aviat Way, Frederick, MD 21701 USA. FU NCI NIH HHS [N01-CO-56000] NR 51 TC 96 Z9 100 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JAN 14 PY 1999 VL 42 IS 1 BP 67 EP 86 DI 10.1021/jm9802517 PG 20 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 159WL UT WOS:000078198300006 PM 9888834 ER PT J AU Zhan, QM Kontny, U Iglesias, M Alamo, I Yu, K Hollander, MC Woodworth, CD Fornace, AJ AF Zhan, QM Kontny, U Iglesias, M Alamo, I Yu, K Hollander, MC Woodworth, CD Fornace, AJ TI Inhibitory effect of Bcl-2 on p53-mediated transactivation following genotoxic stress SO ONCOGENE LA English DT Article DE BCL-2; GADD45; p21(CIPI/WAF1); p53; apoptosis; ionizing radiation; methylmethane sulfonate; UV radiation ID PROGRAMMED CELL-DEATH; DNA-DAMAGING AGENTS; NUCLEAR ANTIGEN; GENE-EXPRESSION; P53; PROTEIN; APOPTOSIS; INDUCTION; GROWTH; GADD45 AB In the cellular response to genotoxic stress, cell cycle checkpoint and apoptosis are considered to be two of the major biological events in maintaining genomic stability. The tumor suppressor p53 has been shown to play critical roles in these stress-induced cellular responses at least in part through the activation of its down-stream genes, such as p21(ClPl/WAFl), GADD45 and BAX. In addition, p53 has been found to down-regulate the expression of BCL-2, which is able to block apoptosis induced by both p53-dependent and independent signaling events. In this report,,ve have found that increased expression of Bcl-2 protein in the human Burkitt's lymphoma WMN cell line suppressed apoptosis induced by different DNA-damaging agents. The induction of p53-regulated genes including GADDIS, p21(ClPl/WAFl) and BAX by genotoxic stress was substantially reduced in cells expressing high levels of Bcl-2 protein. Furthermore, Bcl-2 protein was shown to specifically suppress the p53-mediated transactivation of p21(ClPl/WAFl) and PG13-CAT, which is a typical p53-binding-site reporter construct, Similarly, the inhibitory effect of Bcl-2 protein was seen in a GADD45 promoter reporter construct after treatment with methylmethane sulfonate or UV-radiation, These results indicate that in addition to its apoptosis-suppressing activity, Bcl-2 protein is able to inhibit transactivation of p53-regulated genes, which function in multiple important cellular responses to genotoxic stress, including the control of cell cycle checkpoints, cell growth suppression and DNA repair. C1 NCI, Biol Chem Lab, Bethesda, MD 20892 USA. NCI, Div Basic Sci, Biol Lab, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Div Clin Sci, Bethesda, MD 20892 USA. RP Zhan, QM (reprint author), NCI, Biol Chem Lab, Room 5CO9,Bldg 37, Bethesda, MD 20892 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 46 TC 42 Z9 53 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 14 PY 1999 VL 18 IS 2 BP 297 EP 304 DI 10.1038/sj.onc.1202310 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 159HL UT WOS:000078166500002 PM 9927186 ER PT J AU Mishra, L Cai, T Yu, P Monga, SPS Mishra, B AF Mishra, L Cai, T Yu, P Monga, SPS Mishra, B TI Elf3 encodes a novel 200-kD beta-spectrin: role in liver development SO ONCOGENE LA English DT Article DE spectrin; cloning; chromosome 11; mouse; liver; embryonic development; immunohistochemistry ID PLASMA-MEMBRANE DOMAINS; POLARIZED EPITHELIAL-CELLS; BRAIN SPECTRIN; HEPATOCYTE DIFFERENTIATION; ERYTHROCYTE SPECTRIN; SELF-ASSOCIATION; CDNA LIBRARIES; MESSENGER-RNAS; MECHANISM; SEQUENCES AB beta-spectrins are crucial for the maintenance of cell shape, the establishment of cell polarity, and the formation of distinct membrane domains. Our strategy for identifying genes important for hepatocyte polarity has been to utilize subtractive hybridization of early embryonic mouse cDNA liver libraries. As a result,,ve have cloned three isoforms of a novel beta-spectrin elf (embryonic liver beta-fodrin), and here we report the analysis of elf3, the longest isoform (8172 nt), ELF3 comprises 2154 residues with an overall similarity of 89.0% and 95.3% to mouse beta-spectrin (beta SpII Sigma 1) at the nucleotide and amino acid level, respectively. ELF3 is characterized by an actin-binding domain, a long repeat domain, and a short regulatory domain remarkable for the absence of a PH domain, Linkage analysis reveals that elf3 maps to mouse chromosome 11 between D11Bir6 and D11Xrf477, a different chromosomal locus from that of the other four spectrin genes, Northern blot analysis utilizing an elf3 3'-UTR probe demonstrates an abundant 9.0-kb transcript in brain, liver, and heart tissues. Western blot with a polyclonal antibody against ELF identifies a 200 kD protein in mouse liver, brain, kidney, and heart tissues. Immunohistochemical studies demonstrate ELF labeling of the basolateral or sinusoidal membranes surface as well as a granular cytoplasmic pattern in hepatocytes, Antisense studies utilizing cultured liver explants show a vital role of elf3 in hepatocyte differentiation and intrahepatic bile duct formation, The differential expression, tissue localization, and functional studies demonstrate the importance of elf3 in modulating interactions between various components of the cytoskeleton proteins controlling liver and bile duct development. C1 Dept Vet Affairs, Lab Dev Mol Biol, Washington, DC 20422 USA. Temple Univ, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19140 USA. Natl Human Genome Res Inst, Clin Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. RP Mishra, L (reprint author), Dept Vet Affairs, Lab Dev Mol Biol, Washington, DC 20422 USA. FU NIDDK NIH HHS [R29-DK50458-01] NR 48 TC 52 Z9 57 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 14 PY 1999 VL 18 IS 2 BP 353 EP 364 DI 10.1038/sj.onc.1202313 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 159HL UT WOS:000078166500008 PM 9927192 ER PT J AU van der Reijden, BA Dauwerse, HG Giles, RH Jagmohan-Changur, S Wijmenga, C Liu, PP Smit, B Wessels, HW Beverstock, GC Jotterand-Bellomo, M Martinet, D Muhlematter, D Lafage-Pochitaloff, M Gabert, J Reiffers, J Bilhou-Nabera, C van Ommen, GJB Hagemeijer, A Breuning, MH AF van der Reijden, BA Dauwerse, HG Giles, RH Jagmohan-Changur, S Wijmenga, C Liu, PP Smit, B Wessels, HW Beverstock, GC Jotterand-Bellomo, M Martinet, D Muhlematter, D Lafage-Pochitaloff, M Gabert, J Reiffers, J Bilhou-Nabera, C van Ommen, GJB Hagemeijer, A Breuning, MH TI Genomic acute myeloid leukemia-associated inv(16)(p13q22) breakpoints are tightly clustered SO ONCOGENE LA English DT Article DE inv(16)(p13q22); CBFB; MYH11; AML; genomic; breakpoints ID ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE MYELOMONOCYTIC LEUKEMIA; ABNORMAL MARROW EOSINOPHILS; ACUTE MYELOGENOUS LEUKEMIA; MYOSIN HEAVY-CHAIN; MOLECULAR CHARACTERIZATION; FUSION; GENE; TRANSLOCATION; CHROMOSOME-16 AB The inv(16) and related t(16;16) are found in 10% of all cases with ne novo acute myeloid leukemia. In these rearrangements the core binding factor beta (CBFB) gene on 16q22 is fused to the smooth muscle myosin heavy chain gene (MYH11) on 16p13, To gain insight into the mechanisms causing the inv(16) ne have analysed 24 genomic CBFB-MYH11 breakpoints. All breakpoints in CBFB are located in a 15-Kb intron, More than 50% of the sequenced 6.2 Kb of this intron consists of human repetitive elements. Twenty-one of the 24 breakpoints in MYH11 are located in a 370-hp intron, The remaining three breakpoints in MYH11 ape located more upstream, The localization of three breakpoints adjacent to a V(D)J recombinase signal sequence in MYH11 suggests a V(D)J recombinase-mediated rearrangement in these cases, V(D)J recombinase-associated characteristics (small nucleotide deletions and insertions of random nucleotides) were detected in six other cases. CBFB and MYH11 duplications were detected in four of six cases tested. C1 Erasmus Univ, Inst Hematol, Dept Cell Biol & Genet, Rotterdam, Netherlands. Leiden Univ, Dept Human Genet, Sylvius Labs, NL-2300 RA Leiden, Netherlands. Natl Ctr Human Genome Res, Lab Gene Transfer, NIH, Bethesda, MD USA. Erasmus Univ, Dept Cell Biol & Genet, NL-3000 DR Rotterdam, Netherlands. CHU Vaudois, Div Autonome Genet Med, CH-1011 Lausanne, Switzerland. Inst J Paoli I Calmettes, Hematol Lab, F-13009 Marseille, France. Univ Bordeaux, Lab Univ Hematol, Bordeaux, France. RP van der Reijden, BA (reprint author), Erasmus Univ, Inst Hematol, Dept Cell Biol & Genet, Rotterdam, Netherlands. RI Breuning, Martijn/E-3429-2010; Liu, Paul/A-7976-2012; Wijmenga, Cisca/D-2173-2009; van der Reijden, Bert/A-3543-2014; OI Liu, Paul/0000-0002-6779-025X; Wijmenga, Cisca/0000-0002-5635-1614 NR 33 TC 19 Z9 19 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 14 PY 1999 VL 18 IS 2 BP 543 EP 550 DI 10.1038/sj.onc.1202321 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 159HL UT WOS:000078166500027 PM 9927211 ER PT J AU Culnane, M Fowler, M Lee, SS McSherry, G Brady, M O'Donnell, K Mofenson, L Gortmaker, SL Shapiro, DE Scott, G Jimenez, E Moore, EC Diaz, C Flynn, PM Cunningham, B Oleske, J AF Culnane, M Fowler, M Lee, SS McSherry, G Brady, M O'Donnell, K Mofenson, L Gortmaker, SL Shapiro, DE Scott, G Jimenez, E Moore, EC Diaz, C Flynn, PM Cunningham, B Oleske, J CA Pediat AIDS Clin Trials Grp Protocol 219076 TI Lack of long-term effects of in utero exposure to zidovudine among uninfected children born to HIV-infected women SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; TRANSMISSION; TESTS; TRIAL; MICE AB Context With the success of zidovudine chemoprophylaxis for prevention of perinatal transmission of the human immunodeficiency virus (HIV), an increasing number of HIV-exposed but uninfected children will have in utero exposure to zidovudine and other antiretroviral drugs. Objective To evaluate the long-term effects of in utero exposure to zidovudine vs placebo among a randomized cohort of uninfected children. Design Prospective cohort study based on data collected during Pediatric AIDS Clinical Trials Group Protocol 076, a perinatal zidovudine HIV prevention trial, and Protocol 219, a long-term observational protocol. Setting Pediatric research clinics in the United States. Patients Two hundred thirty-four uninfected children born to 230 HIV-infected women enrolled in Protocol 076 and followed up through February 28, 1997, in Protocol 219 (122 in the zidovudine group and 112 in the placebo group). Main Outcome Measures Physical growth measurements, immunologic parameters, cognitive/developmental function, occurrence of neoplasms, and mortality data assessed every 6 months for children younger than 24 months and yearly thereafter or as clinically indicated. Baseline echocardiogram and funduscopic evaluations were collected before 36 months of age. Results Median age of children at time of last follow-up visit was 4.2 years (range, 3.2-5.6 years). There were no significant differences between children exposed to zidovudine and those who received placebo in terms of sequential data on lymphocyte subsets; weight, height, and head circumference z scores; and cognitive/ developmental function. No deaths or malignancies occurred. Two children (both exposed to zidovudine) are being followed up for abnormal, unexplained ophthalmic findings. One child exposed to zidovudine had a mild cardiomyopathy on echocardiogram at the age of 48 months; the child is clinically asymptomatic. Conclusions No adverse effects were observed in HIV-uninfected children with in utero and neonatal exposure to zidovudine followed up for as long as 5.6 years. Continued prospective evaluations of children born to HIV-infeded women who are exposed to antiretroviral or immunotherapeutic agents are critical to assess the longterm safety of interventions that prevent perinatal HIV transmission. C1 NIAID, Pediat Med Branch, Div AIDS, NIH, Bethesda, MD 20892 USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA. NIAID, Efficacy Trials Branch, Div AIDS, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pediat, Newark, NJ 07103 USA. Ohio State Univ, Columbus Childrens Hosp, Infect Dis Sect, Columbus, OH 43210 USA. Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. Univ Miami, Sch Med, Dept Pediat, Miami, FL USA. Univ Puerto Rico, Sch Med, Dept Pediat, San Juan, PR 00936 USA. San Juan City Hosp, Dept Pediat, San Juan, PR USA. Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA. St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA. Frontier Sci & Technol Res Fdn, Amherst, NY USA. RP Culnane, M (reprint author), NIAID, Pediat Med Branch, Div AIDS, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mc38f@nih.gov OI Mofenson, Lynne/0000-0002-2818-9808 NR 20 TC 213 Z9 221 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 13 PY 1999 VL 281 IS 2 BP 151 EP 157 DI 10.1001/jama.281.2.151 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 155VJ UT WOS:000077966800035 PM 9917118 ER PT J AU Rifkind, BM Schucker, B Gordon, DJ AF Rifkind, BM Schucker, B Gordon, DJ TI When should patients with heterozygous familial hypercholesterolemia be treated? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CORONARY HEART-DISEASE; PRAVASTATIN; PREVENTION; CHILDREN C1 NHLBI, Div Heart & Vasc Dis, Bethesda, MD 20892 USA. RP Gordon, DJ (reprint author), NHLBI, Div Heart & Vasc Dis, 6701 Rockledge Dr,Suite 9044, Bethesda, MD 20892 USA. NR 15 TC 9 Z9 9 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 13 PY 1999 VL 281 IS 2 BP 180 EP 181 DI 10.1001/jama.281.2.180 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 155VJ UT WOS:000077966800040 PM 9917123 ER PT J AU Custer, L Zajc, B Sayer, JM Cullinane, C Phillips, DR Cheh, AM Jerina, DM Bohr, VA Mazur, SJ AF Custer, L Zajc, B Sayer, JM Cullinane, C Phillips, DR Cheh, AM Jerina, DM Bohr, VA Mazur, SJ TI Stereospecific differences in repair by human cell extracts of synthesized oligonucleotides containing trans-opened 7,8,9,10-tetrahydrobenzo[a]pyrene-7,8-diol-9,10-epoxide-N-2-dG adduct stereoisomers located within the human K-ras codon 12 sequence SO BIOCHEMISTRY LA English DT Article ID DIOL EPOXIDE ADDUCTS; NUCLEOTIDE EXCISION-REPAIR; DEOXYADENOSINE N-6-AMINO GROUP; POLYCYCLIC AROMATIC-HYDROCARBONS; DIPLOID HUMAN FIBROBLASTS; STRAND-SPECIFIC REPAIR; NMR SOLUTION STRUCTURE; DG MISMATCH OPPOSITE; RNA-POLYMERASE-II; DNA-ADDUCTS AB The potent environmental carcinogen benzo[a]pyrene (BaP), following enzymatic activation to enantiomeric pairs of bay-region 7,8-diol 9,10-epoxides (the benzylic 7-hydroxyl group and epoxide oxygen are cis for DE-1 diastereomers and trans for DE-2 diastereomers), reacts with DNA to form covalent adducts predominately at the exocyclic amino groups of purines. Specific adducts, corresponding to the trans opening of each of the four optically active BaP DE isomers at C-10 by the N-2-amino group of dG, were synthesized as appropriately blocked phosphoramidites and were incorporated at either the first or second G of codon 12 within the G-rich sequence of human K-ms codons 11-13: GCT G(1)G(2)T GGC. The adducted oligonucleotides were incorporated into plasmids by primer extension, followed by purification of the covalently closed circular constructs. Adducts derived from either (+)- or (-)-DE-2, placed at either G(1) or G(2), presented strong blocks to in vitro transcription elongation by bacteriophage T3 RNA polymerase, but only moderately blocked transcription elongation by human RNA polymerase II in nuclear extracts. Adducts derived from all four DEs, placed on either G(1) or G(2), were used as substrates in a DNA repair synthesis assay using human whole cell extracts. Adducts derived from three of the DE stereoisomers exhibited significant amounts of repair synthesis, but the (-)-DE-2 adduct experienced no repair synthesis above that of the control. Constructs containing a pre-existing nick at the sixth phosphodiester bond 3' to either (+)-DE-2 or (-)-DE-2 adducts exhibited increased repair synthesis. C1 NIA, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. La Trobe Univ, Sch Biochem, Bundoora, Vic 3083, Australia. American Univ, Dept Chem, Washington, DC 20016 USA. RP Mazur, SJ (reprint author), NIA, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. NR 78 TC 23 Z9 23 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 12 PY 1999 VL 38 IS 2 BP 569 EP 581 DI 10.1021/bi9813330 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 170YY UT WOS:000078836000008 PM 9888796 ER PT J AU Ohtani, N Haruki, M Morikawa, M Crouch, RJ Itaya, M Kanaya, S AF Ohtani, N Haruki, M Morikawa, M Crouch, RJ Itaya, M Kanaya, S TI Identification of the genes encoding Mn2+-dependent RNase I-III and Mg2+-dependent RNase HIII from Bacillus subtilis: Classification of RNases H into three families SO BIOCHEMISTRY LA English DT Article ID COLI RIBONUCLEASE HI; ESCHERICHIA-COLI; REVERSE-TRANSCRIPTASE; SEQUENCE-ANALYSIS; KINETIC-ANALYSIS; DNA-SEQUENCE; RNHB GENE; DOMAIN; STABILIZATION; SUBSTRATE AB Database searches indicated that the genome of Bacillus subtilis contains three different genes encoding RNase H homologues. The ypdQ gene encodes an RNase HI homologue with 132 amino acid residues, whereas the rnh and ysgB genes encode RNase HII homologues with 255 and 313 amino acid residues, respectively. RNases HI and HII show no significant sequence similarity. These genes were individually expressed in Escherichia coli; the recombinant proteins were purified, and their enzymatic properties were compared with those of E. coli RNases HI and HII. We found that the ypdQ gene product showed no RNase H activity. The 2.2 kb pair genomic DNA containing this gene did not suppress the RNase H deficiency of an E, coli rnhA mutant, indicating that this gene product shows no RNase H activity in vivo as well. In contrast, the rnh (rnhB) gene product (RNase HII) showed a preference for Mn2+, as did E. coli RNase HII, whereas the ysgB (mhC) gene product (RNase HIII) exhibited a Mg2+-dependent RNase H activity. Oligomeric substrates digested with these enzymes indicate similar recognition of these substrates by B. subtilis and E. coli RNases HII. Likewise, B. subtilis RNase HIII and E. coli RNase HI have generated similar products. These results suggest that B. subtilis RNases HII and HIII may be functionally similar to E, coli RNases HII and HI, respectively. We propose that Mn2+-dependent RNase HII is universally present in various organisms and Mg2+-dependent RNase HIII, which may have evolved from RNase HII, functions as a substitute for RNase HI. C1 Osaka Univ, Grad Sch Engn, Dept Mat & Life Sci, Osaka 5650871, Japan. NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. Mitsubishi Kasei Inst Life Sci, Tokyo 1948511, Japan. RP Kanaya, S (reprint author), Osaka Univ, Grad Sch Engn, Dept Mat & Life Sci, 2-1 Yamadaoka, Osaka 5650871, Japan. RI Morikawa, Masaaki/L-2823-2015 NR 44 TC 116 Z9 121 U1 1 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 12 PY 1999 VL 38 IS 2 BP 605 EP 618 DI 10.1021/bi982207z PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 170YY UT WOS:000078836000012 PM 9888800 ER PT J AU Jeong, JS Kwon, SJ Kang, SW Rhee, SG Kim, K AF Jeong, JS Kwon, SJ Kang, SW Rhee, SG Kim, K TI Purification and characterization of a second type thioredoxin peroxidase (type II TPx) from Saccharomyces cerevisiae SO BIOCHEMISTRY LA English DT Article ID THIOL-SPECIFIC ANTIOXIDANT; HYDROGEN-PEROXIDE; CLONING; PROTEIN; GENE; YEAST; REDUCTASE; OXIDATION; ENZYME; BRAIN AB A yeast peroxidase that reduces H2O2 and alkyl hydroperoxides with the use of reducing equivalents provided by thioredoxin was identified previously and named thioredoxin peroxidase (TPx) [Chae, H. Z., Chung, S, J., and Rhee, S. G, (1994) J. Biol, Chem. 269, 27670-27678]. A second type thioredoxin-dependent peroxidase, named type II TPx, has now been purified from yeast, and several peptide sequences have been obtained. Using those sequences, the corresponding cDNA has been identified from the GenBank database. Comparison of the predicted sequence of 176 amino acids of type II TPx with that of the 195 residues of TPx, now renamed type I TPx, revealed no substantial homology except for a short segment preceding Cys(62) of type II TPx, Kinetic characterization of the reactions catalyzed by type I and II TPxs revealed that type I preferentially reduces H2O2 rather than alkyl hydroperoxides, whereas type II shows the reverse specificity. Type II TPx contains three cysteine residues at positions 31, 62, and 120. Experiments with mutant proteins in which these three cysteine residues were replaced individually with serine suggest that Cys(62)-SH constitutes the site of oxidation by peroxides and that the oxidized Cys(62) reacts with the Cys(120)-SH group of another type II TPx molecule to form an intermolecular disulfide linkage. The formed disulfide can then be reduced by thioredoxin, but not by glutathione. Thus, type II TPx mutants lacking Cys(62) or Cys(120) showed no detectable TPx activity, whereas mutation of Cys(31) had no effect on TPx activity. An antioxidant function of type II TPx in intact cells was demonstrated by the observation that Escherichia coli cells overexpressing wild-type protein were less sensitive to inhibition of growth by alkyl hydroperoxides than were control cells or cells overexpressing the mutant protein lacking Cys(62). C1 Chonnam Natl Univ, Coll Home Econ, Dept Food & Nutr, Kwangju 500757, South Korea. NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. RP Kim, K (reprint author), Chonnam Natl Univ, Coll Home Econ, Dept Food & Nutr, Kwangju 500757, South Korea. NR 25 TC 97 Z9 101 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 12 PY 1999 VL 38 IS 2 BP 776 EP 783 DI 10.1021/bi9817818 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 170YY UT WOS:000078836000030 PM 9888818 ER PT J AU Cardillo, C Kilcoyne, CM Cannon, RO Panza, JA AF Cardillo, C Kilcoyne, CM Cannon, RO Panza, JA TI Attenuation of cyclic nucleotide-mediated smooth muscle relaxation in blacks as a cause of racial differences in vasodilator function SO CIRCULATION LA English DT Article DE race; nitric oxide; receptors, adrenergic, beta; nucleotides, cyclic; vasodilation ID DEPENDENT VASCULAR RELAXATION; NITRIC-OXIDE PATHWAY; ESSENTIAL-HYPERTENSION; BLOOD-PRESSURE; HUMAN FOREARM; L-ARGININE; SIGNAL-TRANSDUCTION; RESPONSES; PATHOPHYSIOLOGY; ISOPROTERENOL AB Background-Vasodilator reactivity is attenuated in normotensive blacks, and this may contribute to their enhanced susceptibility to hypertension and its complications. However, the mechanisms responsible for this phenomenon are unknown. We therefore studied nitric oxide (NO)-dependent and -independent vasorelaxation in healthy blacks and whites to investigate the nature of racial differences in vasodilator function. Methods and Results-Forearm flow responses to intra-arterial infusion of increasing doses of acetylcholine (a vasodilator that stimulates endothelial release of NO), sodium nitroprusside (an exogenous NO donor), and isoproterenol (a beta-adrenergic agonist whose vasodilator effect stems from the combination of direct smooth muscle stimulation and endothelial NO release) were studied in 18 normotensive whites and 18 blacks by use of strain-gaugel plethysmography. A blunted vasodilator response to acetylcholine (7.2+/-1.1 versus 14.4+/-1.8 mL.min(-1) dL(-1); P<0,001) and sodium nitroprusside (8.2+/-1.1 versus 12.1+/-1.3 mL.min(-1).dL(-1); P<0.001) was observed in blacks compared with whites, suggesting decreased cGMP-mediated smooth muscle relaxation. The vasodilator effect of isoproterenol was lower in blacks than in whites both before (10.9+/-1.7 versus 14.9+/-1.5 mL.min(-1).dL(-1); P=0.006) and after N-G-monomethyl-L-arginine (6.1+/-1.2 versus 10.1+/-0.8 mL.min(-1).dL(-1); P<0.001), implying that cAMP-dependent vasodilator response to isoproterenol is diminished in blacks. No significant difference was observed in the hyperemic response to forearm ischemia, Conclusion-Compared with whites, healthy blacks have reduced vasodilation in response to NO-dependent and -independent stimuli. This difference seems to be related to an attenuation in cyclic nucleotide-mediated vascular smooth muscle relaxation and may play a role in the increased prevalence of hypertension and its complications in blacks. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Panza, JA (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10,Room 7B-15,10 Ctr Dr, Bethesda, MD 20892 USA. EM panzaj@gwgate.nhlbi.nih.gov NR 39 TC 69 Z9 71 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 12 PY 1999 VL 99 IS 1 BP 90 EP 95 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 156BB UT WOS:000077980600018 PM 9884384 ER PT J AU Benjamin, EJ Vasan, RS Larson, MG Levy, D Evans, JC AF Benjamin, EJ Vasan, RS Larson, MG Levy, D Evans, JC TI Assessment of LV mass by echocardiography - Response SO CIRCULATION LA English DT Letter C1 Boston Univ, NHLBI, Framingham Study, Sch Med, Framingham, MA USA. RP Benjamin, EJ (reprint author), Boston Univ, NHLBI, Framingham Study, Sch Med, Framingham, MA USA. OI Benjamin, Emelia/0000-0003-4076-2336 NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 12 PY 1999 VL 99 IS 1 BP 165 EP 166 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 156BB UT WOS:000077980600031 ER PT J AU Moore, MA Epstein, M Agodoa, L Dworkin, LD AF Moore, MA Epstein, M Agodoa, L Dworkin, LD TI Current strategies for management of hypertensive renal disease SO ARCHIVES OF INTERNAL MEDICINE LA English DT Review ID CONVERTING-ENZYME-INHIBITION; II RECEPTOR ANTAGONIST; BLOOD-PRESSURE CONTROL; DIETARY-PROTEIN RESTRICTION; RANDOMIZED CONTROLLED TRIAL; ANGIOTENSIN-II; GLOMERULAR INJURY; UNITED-STATES; DIABETIC NEPHROPATHY; CALCIUM-ANTAGONISTS AB The incidence of hypertensive end-stage renal disease continues to increase annually. To reduce this incidence, it is necessary to control systolic and diastolic hypertension. Reversible causes should always be sought in any hypertensive patient who develops renal insufficiency. Blood pressure should be reduced to 130/85 mm Hg, and in African Americans with hypertensive renal failure, reducing the blood pressure to 120/75 mm Hg may be beneficial. Any antihypertensive treatment regimen that effectively lowers blood pressure mill help slow progressive renal failure. Whenever possible, an angiotensin-converting enzyme inhibitor should be part of the treatment, since these drugs have been shown to be renoprotective beyond their antihypertensive effect in certain renal disease categories. C1 Danville Urol Clin, Danville, VA 24543 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Med, Nephrol Sect, Winston Salem, NC 27103 USA. Vet Affairs Med Ctr, Serv Nephrol, Miami, FL 33125 USA. NIDDKD, Minor Hlth Programs, NIH, Bethesda, MD USA. Rhode Isl Hosp, Div Renal Dis, Providence, RI USA. RP Moore, MA (reprint author), Danville Urol Clin, 1040 Main St,POB 1360, Danville, VA 24543 USA. NR 73 TC 18 Z9 18 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JAN 11 PY 1999 VL 159 IS 1 BP 23 EP 28 DI 10.1001/archinte.159.1.23 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 155AV UT WOS:000077924400004 PM 9892326 ER PT J AU Tapia, JA Camello, C Jensen, RT Garcia, LJ AF Tapia, JA Camello, C Jensen, RT Garcia, LJ TI EGF stimulates tyrosine phosphorylation of focal adhesion kinase (p125(FAK)) and paxillin in rat pancreatic acini by a phospholipase C-independent process that depends on phosphatidylinositol 3-kinase, the small GTP-binding protein, p21(rho), and the integrity of the actin cytoskeleton SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE epidermal growth factor; p125(FAK); paxillin; tyrosine kinase; pancreatic acini; p21(rho) ID EPIDERMAL GROWTH-FACTOR; SWISS 3T3 CELLS; EXTRACELLULAR-MATRIX; SIGNALING PATHWAYS; FACTOR RECEPTOR; ANGIOTENSIN-II; CROSS-TALK; ACTIVATION; RHO; CHOLECYSTOKININ AB Epidermal growth factor (EGF) is a potent mitogen in many cell types including pancreatic cells. Recent studies show that the effects of some growth factors on growth and cell migration are mediated by tyrosine phosphorylation of the cytosolic tyrosine kinase p125 focal adhesion kinase (p125(FAK))and the cytoskeletal protein, paxillin. The aim of the present study was to determine whether EGF activates this pathway in rat pancreatic acini and causes tyrosine phosphorylation of each of these proteins, and to examine the intracellular pathways involved. Treatment of pancreatic acini with EGF induced a rapid concentration-dependent increase in p125(FAK) and paxillin tyrosine phosphorylation, Depletion of the intracellular calcium pool or inhibition of PKC activation had no effect on the response to EGF. However, inhibition of the phosphatidylinositol 3-kinase (PI3-kinase) or inactivation of p21(rho) inhibited EGF-stimulated phosphorylation of p125(FAK) and paxillin by more than 70%. Finally, cytochalasin D, a selective disrupter of the actin filament network, completely inhibited EGF-stimulated tyrosine phosphorylation of both proteins. All these treatments did not modify EGF receptor autophosphorylation in response to EGF. These results identify p125FAK and paxillin as components of the intracellular pathways stimulated after EGF receptor occupation in rat pancreatic acini. Activation of this cascade requires activation of PI3-kinase and participation of p21(rho), but not PKC activation and calcium mobilization. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Extremadura, Dept Physiol, Caceres 10071, Spain. NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Garcia, LJ (reprint author), Univ Extremadura, Dept Physiol, Avda de la Univ S-N, Caceres 10071, Spain. RI Camello, Cristina/K-8238-2014; Garcia-Marin, Luis /L-4680-2014; Tapia, Jose/C-5181-2008 OI Camello, Cristina/0000-0003-0882-8497; Garcia-Marin, Luis /0000-0002-1795-7381; Tapia, Jose/0000-0002-3614-6867 NR 50 TC 47 Z9 47 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD JAN 11 PY 1999 VL 1448 IS 3 BP 486 EP 499 DI 10.1016/S0167-4889(98)00157-8 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 161CP UT WOS:000078271100015 PM 9990300 ER PT J AU Kioka, N Sakata, S Kawauchi, T Amachi, T Akiyama, SK Okazaki, K Yaen, C Yamada, KM Aota, S AF Kioka, N Sakata, S Kawauchi, T Amachi, T Akiyama, SK Okazaki, K Yaen, C Yamada, KM Aota, S TI Vinexin: A novel vinculin-binding protein with multiple SH3 domains enhances actin cytoskeletal organization SO JOURNAL OF CELL BIOLOGY LA English DT Article DE actin cytoskeleton; cell adhesion; focal adhesion; SH3 domain; vinculin ID INTRAMOLECULAR ASSOCIATION; CARCINOMA-CELLS; TAIL DOMAINS; ADHESION; HEAD; F9; PHOSPHORYLATION; RECOGNITION; DISRUPTION; MICROSCOPY AB Using the yeast two-hybrid system and an in vitro binding assay, we have identified a novel protein termed vinexin as a vinculin-binding protein. By Northern blotting, we identified two types of vinexin mRNA that were 3 and 2 kb in length. Screening for full-length cDNA clones and sequencing indicated that the two mRNA encode 82- and 37-kD polypeptides termed vinexin alpha and beta, respectively. Both forms of vinexin share a common carboxyl-terminal sequence containing three SH3 domains. The larger vinexin alpha contains an additional amino-terminal sequence. The interaction between vinexin and vinculin was mediated by two SH3 domains of vinexin and the proline-rich region of vinculin. When expressed, vinexin alpha and beta localized to focal adhesions in NIH 3T3 fibroblasts, and to cell-cell junctions in epithelial LLC-PK1 cells. Furthermore, expression of vinexin increased focal adhesion size. Vinexin alpha also promoted upregulation of actin stress fiber formation. In addition, cell lines stably expressing vinexin beta showed enhanced cell spreading on fibronectin. These data identify vinexin as a novel focal adhesion and cell-cell adhesion protein that binds via SH3 domains to the hinge region of vinculin, which can enhance actin cytoskeletal organization and cell spreading. C1 Biomol Engn Res Inst, Osaka 5650874, Japan. Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Kyoto Univ, Biochem Lab, Div Appl Life Sci, Kyoto 60601, Japan. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Aota, S (reprint author), Biomol Engn Res Inst, 6-2-3 Furuedai, Osaka 5650874, Japan. RI Okazaki, Kenji/H-4393-2012; Kawauchi, Takeshi/L-4770-2013 OI Kawauchi, Takeshi/0000-0002-8650-4474 NR 34 TC 130 Z9 135 U1 0 U2 8 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JAN 11 PY 1999 VL 144 IS 1 BP 59 EP 69 DI 10.1083/jcb.144.1.59 PG 11 WC Cell Biology SC Cell Biology GA 157WN UT WOS:000078084800007 PM 9885244 ER PT J AU Tsumaki, N Tanaka, K Arikawa-Hirasawa, E Nakase, T Kimura, T Thomas, JT Ochi, T Luyten, FP Yamada, Y AF Tsumaki, N Tanaka, K Arikawa-Hirasawa, E Nakase, T Kimura, T Thomas, JT Ochi, T Luyten, FP Yamada, Y TI Role of CDMP-1 in skeletal morphogenesis: Promotion of mesenchymal cell recruitment and chondrocyte differentiation SO JOURNAL OF CELL BIOLOGY LA English DT Article DE bone morphogenetic protein family; cartilage; ectopic expression; skeletal abnormalities; transgenic mice ID NUCLEOLAR ORGANIZER REGIONS; AMINO-TERMINAL PROPEPTIDE; TGF-BETA-SUPERFAMILY; II COLLAGEN GENE; MESSENGER-RNA; GROWTH-FACTOR; GROWTH/DIFFERENTIATION FACTOR-5; EMBRYONIC-DEVELOPMENT; SONIC-HEDGEHOG; EXON STRUCTURE AB Cartilage provides the template for endochondral ossification and is crucial for determining the length and width of the skeleton. Transgenic mice with targeted expression of recombinant cartilage-derived morphogenetic protein-1 (CDMP-1), a member of the bone morphogenetic protein family, were created to investigate the role of CDMP-1 in skeletal formation. The mice exhibited chondrodysplasia with expanded cartilage, which consists of the enlarged hypertrophic zone and the reduced proliferating chondrocyte zone. Histologically, CDMP-1 increased the number of chondroprogenitor cells and accelerated chondrocyte differentiation to hypertrophy. Expression of CDMP-1 in the notochord inhibited vertebral body formation by blocking migration of sclerotome cells to the notochord. These results indicate that CDMP-1 antagonizes the ventralization signals from the notochord. Our study suggests a molecular mechanism by which CDMP-1 regulates the formation, growth, and differentiation of the skeletal elements. C1 Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. Osaka Univ, Sch Med, Dept Orthopaed Surg, Suita, Osaka 5650871, Japan. Toyama Med & Pharmaceut Univ, Dept Orthopaed Surg, Toyama 9300194, Japan. RP Yamada, Y (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, 9000 Rockville Pike,Bldg 30,Room 405, Bethesda, MD 20892 USA. NR 46 TC 108 Z9 118 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JAN 11 PY 1999 VL 144 IS 1 BP 161 EP 173 DI 10.1083/jcb.144.1.161 PG 13 WC Cell Biology SC Cell Biology GA 157WN UT WOS:000078084800015 PM 9885252 ER PT J AU Szallasi, A Farkas-Szallasi, T Tucker, JB Lundberg, JM Hokfelt, T Krause, JE AF Szallasi, A Farkas-Szallasi, T Tucker, JB Lundberg, JM Hokfelt, T Krause, JE TI Effects of systemic resiniferatoxin treatment on substance P mRNA in rat dorsal root ganglia and substance P receptor mRNA in the spinal dorsal horn SO BRAIN RESEARCH LA English DT Article DE resiniferatoxin; vanilloid receptor; desensitization to vanilloid; substance P expression; tachykinin NK-1 receptor expression ID PRIMARY SENSORY NEURONS; PRIMARY AFFERENT NEURONS; NERVE GROWTH-FACTOR; ULTRAPOTENT CAPSAICIN ANALOG; GENE-RELATED PEPTIDE; ADULT-RAT; SELECTIVE DEGENERATION; INTRAVESICAL RESINIFERATOXIN; MOLECULAR CHARACTERIZATION; NEONATAL CAPSAICIN AB Capsaicin depletes the sensory neuropeptide substance P (SP) in the rat due to a combination of neuron loss and decreased synthesis in the surviving cells. Resiniferatoxin (RTX) mimics most, but not all, capsaicin actions. In the present study, the effects of RTX (300 mu g/kg, s.c.) were examined on mRNA levels for SP and its receptor in the adult rat. The percentage of dorsal root ganglia (DRG) neuronal profiles showing an in situ hybridization signal for preprotachykinin mRNAs encoding SP was not altered following RTX treatment (up to 8 weeks), though the signal became perceptibly weaker. In accord, 2 weeks after RTX administration a 60% decrease was observed in the steady-state levels of SP-encoding mRNAs using Northern blot analysis, leaving the ratio of beta- and gamma-preprotachykinin mRNAs unchanged. No change was, however, observed in mRNA levels encoding tachykinins NK-1 receptors in the dorsal horn, the spinal targets for SP. The present findings suggest that RTX does not kill SP-positive DRG neurons, though it suppresses the synthesis of SP. Since RTX treatment does not alter NK-1 receptor expression, this reduced SP synthesis is likely to play a central role in the analgesic actions of RTX. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Karolinska Inst, Dept Pharmacol, S-17177 Stockholm, Sweden. Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. RP NCI, NIH, Bldg 37,Rm 3A01,9000 Rockville Pike, Bethesda, MD 20892 USA. EM szallasi@exchange.nih.gov FU NINDS NIH HHS [NS 21937] NR 74 TC 17 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD JAN 9 PY 1999 VL 815 IS 2 BP 177 EP 184 DI 10.1016/S0006-8993(98)01168-8 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 154CH UT WOS:000077870600002 PM 9878727 ER PT J AU Elman, I Sokoloff, L Adler, CM Weisenfeld, N Breier, A AF Elman, I Sokoloff, L Adler, CM Weisenfeld, N Breier, A TI The effects of pharmacological doses of 2-deoxyglucose on cerebral blood flow in healthy volunteers SO BRAIN RESEARCH LA English DT Article DE glucose deprivation; PET; mean arterial pressure; hypothalamus; body temperature ID INSULIN-INDUCED HYPOGLYCEMIA; AUTOMATED ALGORITHM; METABOLIC STRESS; GLUCOSE-INFUSION; 2-DEOXY-D-GLUCOSE; CATECHOLAMINES; HYPOTHERMIA; TOMOGRAPHY; MECHANISMS; RECOVERY AB The effects of glucose deprivation on cerebral blood flow (CBF) have been extensively investigated during insulin-induced hypoglycemia in laboratory animals. Pharmacological doses of glucose analog, 2-deoxyglucose (2DG), is an alternative glucoprivic agent that in contrast to insulin, directly inhibits glycolysis and glucose utilization. Both glucoprivic conditions markedly increase CBF in laboratory animals. How 2DG affects CBF in humans is still undetermined. In the present study we have employed (H2O)-O-15 positron emission tomography (PET) to examine the effects of pharmacological doses of 2DG (40 mg/kg) on regional and global cerebral blood flow in 10 brain areas in 13 healthy volunteers. 2DG administration significantly raised regional CBF (rCBF) in the cingulate gyrus, sensorimotor cortex, superior temporal cortex, occipital cortex, basal ganglia, limbic system and hypothalamus. 2DG produced a trend towards elevated CBF in whole brain and frontal cortex, while no changes were observed in the corpus callosum and thalamus. In addition, 2DG significantly decreased body temperature and mean arterial pressure (MAP). Maximal percent changes in hypothalamic rCBF were significantly correlated with maximal changes in body temperature but not with MAP. These results indicate that cerebral glucoprivation produced by pharmacological doses of 2DG is accompanied by widespread activation of cortical and subcortical blood now and that the blood flow changes in the hypothalamus may be related to 2DG-induced hypothermia. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NIMH, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. NIMH, Cerebral Metab Lab, NIH, Bethesda, MD 20892 USA. RP Elman, I (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, W End House,16 Blossom St, Boston, MA 02114 USA. EM elman.igor@mgh.harvard.edu NR 38 TC 17 Z9 17 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 9 PY 1999 VL 815 IS 2 BP 243 EP 249 DI 10.1016/S0006-8993(98)01137-8 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 154CH UT WOS:000077870600010 PM 9878763 ER PT J AU Segal, JA Harris, BD Kustova, Y Basile, A Skolnick, P AF Segal, JA Harris, BD Kustova, Y Basile, A Skolnick, P TI Aminoglycoside neurotoxicity involves NMDA receptor activation SO BRAIN RESEARCH LA English DT Article DE excitotoxicity; NMDA receptor; ototoxicity; aminoglycoside; neomycin; polyamine ID D-ASPARTATE RECEPTOR; BENZODIAZEPINE BINDING-SITES; PERIPHERAL BENZODIAZEPINE; RAT-BRAIN; IN-VIVO; CHANNEL COMPLEX; GLYCINE; 7-CHLOROKYNURENATE; LOCALIZATION; ANTAGONISTS AB Previous studies have led to the hypothesis that the ototoxicity produced by aminoglycoside antibiotics involves the excitotoxic activation of cochlear NMDA receptors. If this hypothesis is correct, then these antibiotics should also injure neurons within the brain. Because aminoglycosides do not readily penetrate the blood brain barrier, we examined the effects of the aminoglycoside neomycin following intrastriatal injection. Neomycin (10-250 nmol) produced dose-dependent striatal damage manifested as an increased gliosis as measured by: (1) [H-3]PK-11195 binding, (2) staining for the astrocytic marker glial fibrillary acidic protein (GFAP) and (3) staining for OX-6, an MHC class II antigen expressed by microglia and macrophages. Go-injection of subthreshhold doses of NMDA potentiates the striatal damage produced by neomycin (10 nmol). Moreover, neomycin-induced striatal damage is attenuated by a combination of the NMDA antagonists ifenprodil and 5,7-dichlorokynurenic acid. Intrastriatal administration of compounds structurally related to neomycin, but devoid of modulatory actions at NMDA receptors (paromamine and 2-deoxystreptamine), fail to produce neuronal damage. These data support the hypothesis that aminoglycoside-induced ototoxicity is, in part, an excitotoxic process involving the activation of NMDA receptors. Moreover, aminoglycosides may damage the central nervous system in individuals with compromised blood brain barriers. (C) 1999 Published by Elsevier Science B.V. All rights reserved. C1 NIDDKD, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Segal, JA (reprint author), Lilly Res Labs, Neurosci Discovery, Bldg 48,Drop Code 0510, Indianapolis, IN 46285 USA. EM segalj@lilly.com NR 30 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 9 PY 1999 VL 815 IS 2 BP 270 EP 277 DI 10.1016/S0006-8993(98)01123-8 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 154CH UT WOS:000077870600013 PM 9878779 ER PT J AU Lloyd-Jones, DM Larson, MG Beiser, A Levy, D AF Lloyd-Jones, DM Larson, MG Beiser, A Levy, D TI Lifetime risk of developing coronary heart disease SO LANCET LA English DT Article ID GLOBAL BURDEN; POSTMENOPAUSAL WOMEN; MORTALITY; THERAPY; HEALTH; HYPERTENSION; DISABILITY; CANCER AB Background The lifetime risk of developing coronary heart disease has not been estimated in a general population. We investigated the lifetime risks of initial coronary events at different ages. Methods We assessed data for 7733 participants in the Framingham Heart Study, who had been examined at least once at age 40-94 years between 1971 and 1975, found to be free of coronary heart disease, and then followed up. We estimated the lifetime risks of coronary heart disease (angina pectoris, coronary insufficiency, myocardia[ infarction, or death from coronary heart disease) by multiple-decrement life-table methods. Findings The 7733 patients were followed up for a total of 109 948 person-years. Overall, 1157 participants developed coronary heart disease. 1312 died from noncoronary heart disease causes. Lifetime risk of coronary heart disease at age 40 years was 48.6% (95% CI 45.8-51.3) for men and 31.7% (29.2-34.2) for women. At age 70 years, lifetime risk was 34.9% (31.2-38.7) for men and 24.2% (21.4-27.0) for women. After we excluded isolated angina pectoris as an initial event, the lifetime risk of coronary artery disease events at age 40 years was 42.4% for men and 24.9% for women. Interpretation Lifetime risk at age 40 years is one in two for men and one in three for women. Even at age 70 years it is one in three for men and one in four for women. This knowledge may promote efforts in education, screening, and treatment for prevention of coronary heart disease in younger and alder patients. C1 NHLBI, Framingham Heart Study, NIH, Framingham, MA 01702 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Unit, Boston, MA USA. Boston Univ, Sch Med, Div Cardiol, Boston, MA 02118 USA. Boston Univ, Sch Med, Div Epidemiol & Prevent Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02118 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Med, Sch Med, Boston, MA 02115 USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, NIH, 5 Thurber St, Framingham, MA 01702 USA. EM dan@fram.nhlbi.nih.gov RI Lloyd-Jones, Donald/C-5899-2009 NR 28 TC 420 Z9 431 U1 2 U2 10 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JAN 9 PY 1999 VL 353 IS 9147 BP 89 EP 92 DI 10.1016/S0140-6736(98)10279-9 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 157XP UT WOS:000078087200008 PM 10023892 ER PT J AU Natarajan, V Bosche, M Metcalf, JA Ward, DJ Lane, HC Kovacs, JA AF Natarajan, V Bosche, M Metcalf, JA Ward, DJ Lane, HC Kovacs, JA TI HIV-1 replication in patients with undetectable plasma virus receiving HEART SO LANCET LA English DT Article ID THERAPY C1 NCI, SAIC Frederick, FCRDC, Frederick, MD 21701 USA. NIH, Immunoregulat Lab, Bethesda, MD 20892 USA. DuPont Circle Phys Grp PC, Washington, DC USA. NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Natarajan, V (reprint author), NCI, SAIC Frederick, FCRDC, POB B, Frederick, MD 21701 USA. FU NCI NIH HHS [N01-CO-5600] NR 5 TC 116 Z9 116 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JAN 9 PY 1999 VL 353 IS 9147 BP 119 EP 120 DI 10.1016/S0140-6736(05)76156-0 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 157XP UT WOS:000078087200019 PM 10023903 ER PT J AU Xue, Y Alford, P Shackelford, RE AF Xue, Y Alford, P Shackelford, RE TI Protein kinase C activation increases binding of transcription factor PU.1 in murine tissue macrophages SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID EXPRESSION; RECEPTOR; PHOSPHORYLATION; INHIBITION; GAMMA AB PU.1 is a transcription factor found in macrophages, B cells, neutrophils, and hemopoietic stem cells, In macrophages PU.1 regulates a number of genes, including c-fms, CD11b, CD18, and Fc gamma R1b, Previously, in primary macrophages PU.1 binding to the sequence GAGGAA was found to be induced by treatment with bacterial lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). Here we investigated the role of protein kinase C (pKC) in the induction of PU.1 binding in macrophages, We report that pharmacological activation of pKC increases PU.1 binding, while inactivation of pKC inhibits the increases in PU.1 binding by agents which activate pKC in macrophages (LPS and tumor necrosis factor-alpha), but not by an agent which does not activate pKC (IFN-gamma). pKC activation may therefore be one pathway by which PU.1 binding may be increased in primary macrophages. (C) 1999 Academic Press. C1 Duke Univ, Ctr Med, Dept Pathol, Res Triangle Pk, NC 27709 USA. RP Shackelford, RE (reprint author), NIEHS, POB 12233,F1-05111,Alexander Dr, Res Triangle Pk, NC 27709 USA. EM shackel1@niehs.nih.gov NR 16 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 8 PY 1999 VL 254 IS 1 BP 211 EP 214 DI 10.1006/bbrc.1998.9905 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 158XB UT WOS:000078141800039 PM 9920760 ER PT J AU Felzmann, T Ramsey, WJ Blaese, RM AF Felzmann, T Ramsey, WJ Blaese, RM TI Anti-tumor immunity generated by tumor cells engineered to express B7-1 via retroviral or adenoviral gene transfer SO CANCER LETTERS LA English DT Article DE tumor vaccination; gene therapy; anti-tumor immunity ID COLONY-STIMULATING FACTOR; ANTITUMOR IMMUNITY; NECROSIS-FACTOR; MURINE SARCOMA; COSTIMULATION; INTERLEUKIN-4; LYMPHOCYTES; TOLERANCE; REJECTION; CTLA-4 AB We engineered B7-1 retroviral and adenoviral gene transfer systems and studied them in four immunogenic tumor models. M-MSV tumor cells, but not K-Balb, 38.2 and 205 tumor cells, when expressing B7-1 by retroviral transduction were rejected and conferred protection against a tumor challenge. Transient expression of B7-1 after transduction with adenoviruses was less efficient. We observed enhanced cytotoxic T-lymphocyte activity accompanied by increased secretion of IL-6, IFN gamma and GMCSF. GM-CSF secretion correlated with tumor rejection. Enhanced IFN gamma but unchanged IL-4 secretion suggested a T-helper 1-mediated anti-tumor immune response. (C) 1999 Elsevier Science ireland Ltd. All rights reserved. C1 NHGRI, Clin Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. RP Felzmann, T (reprint author), St Anna Childrens Hosp, Childrens Canc Res Inst, Kinderspitalgasse 6, A-1090 Vienna, Austria. NR 25 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JAN 8 PY 1999 VL 135 IS 1 BP 1 EP 10 PG 10 WC Oncology SC Oncology GA 166AJ UT WOS:000078553800001 PM 10077215 ER PT J AU Zhu, MH John, S Berg, M Leonard, WJ AF Zhu, MH John, S Berg, M Leonard, WJ TI Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFN gamma-mediated signaling SO CELL LA English DT Article ID RECEPTOR-BETA-CHAIN; DNA-BINDING ACTIVITY; GENE-EXPRESSION; INTERFERON-ALPHA; T-LYMPHOCYTES; TRANSCRIPTION; PROTEINS; CBP; ACTIVATION; P300/CBP AB Using the coiled-coil region of Stat5b as the bait in a yeast two-hybrid screen, we identified the association of Nmi, a protein of unknown function previously reported as an N-Myc interactor. We further show that Nmi interacts with all STATs except Stat2. We evaluated two cytokine systems, IL-2 and lFN gamma, and demonstrate that Nmi augments STAT-mediated transcription in response to these cytokines. Interestingly, Nmi lacks an intrinsic transcriptional activation domain; instead, Nmi enhances the association of CBP/p300 coactivator proteins with Stall and Stat5, and together with CBP/p300 can augment IL-2- and IFN gamma-dependent transcription. Therefore, our data not only reveal that Nmi can potentiate STAT-dependent transcription, but also suggest that it can augment coactivator protein recruitment to at least some members of a group of sequence-specific transcription factors. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP NHLBI, Lab Mol Immunol, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM wjl@helix.nih.gov NR 62 TC 197 Z9 203 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD JAN 8 PY 1999 VL 96 IS 1 BP 121 EP 130 DI 10.1016/S0092-8674(00)80965-4 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 156VR UT WOS:000078023200014 PM 9989503 ER PT J AU Agarwal, SK Guru, SC Heppner, C Erdos, MR Collins, RM Park, SY Saggar, S Chandrasekharappa, SC Collins, FS Spiegel, AM Marx, SJ Burns, AL AF Agarwal, SK Guru, SC Heppner, C Erdos, MR Collins, RM Park, SY Saggar, S Chandrasekharappa, SC Collins, FS Spiegel, AM Marx, SJ Burns, AL TI Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription SO CELL LA English DT Article ID ENDOCRINE NEOPLASIA TYPE-1; C-JUN; PARATHYROID TUMORS; FOS PROTEINS; GENE; CELLS; AP-1; ONCOPROTEIN; MUTATIONS; DOMAIN AB MEN1 is a tumor suppressor gene that encodes a 610 amino acid nuclear protein (menin) of previously unknown function. Using a yeast two-hybrid screen with menin as the bait, we have identified the transcription factor JunD as a direct menin-interacting partner. Menin did not interact directly with other Jun and Fos family members. The menin-JunD interaction was confirmed in vitro and in vive. Menin repressed transcriptional activation mediated by JunD fused to the Gal4 DNA-binding domain from a Gal4 responsive reporter, or by JunD from an AP1-responsive reporter. Several naturally occurring and clustered MEN1 missense mutations disrupted menin interaction with JunD. These observations suggest that menin's tumor suppressor function involves direct binding to JunD and inhibition of JunD activated transcription. C1 NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Agarwal, SK (reprint author), NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RI Agarwal, Sunita/D-1428-2016 OI Agarwal, Sunita/0000-0002-7557-3191 NR 36 TC 398 Z9 411 U1 0 U2 10 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JAN 8 PY 1999 VL 96 IS 1 BP 143 EP 152 DI 10.1016/S0092-8674(00)80967-8 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 156VR UT WOS:000078023200016 PM 9989505 ER PT J AU Xiao, RP Avdonin, P Zhou, YY Chen, HP Akhter, SA Eschenhagen, T Lefkowitz, RJ Koch, WJ Lakatta, EG AF Xiao, RP Avdonin, P Zhou, YY Chen, HP Akhter, SA Eschenhagen, T Lefkowitz, RJ Koch, WJ Lakatta, EG TI Coupling of beta(2)-adrenoceptor to G(i) proteins and its physiological relevance in murine cardiac myocytes SO CIRCULATION RESEARCH LA English DT Article DE beta(2)-adrenergic receptor; inhibitory G protein; cardiac contractility; L-type Ca2+; current; mice, transgenic ID BETA-ADRENERGIC-RECEPTOR; RECONSTITUTED PHOSPHOLIPID-VESICLES; TRANSGENIC MICE; ADENYLATE-CYCLASE; HUMAN-HEART; OVEREXPRESSION; STIMULATION; CONTRACTION; FAILURE; ALPHA AB Transgenic mouse models have been developed to manipulate beta-adrenergic receptor (beta AR) signal transduction. Although several of these models have altered beta AR subtypes, the specific functional sequelae of beta AR stimulation in murine heart, particularly those of beta(2)-adrenergic receptor (beta(2)AR) stimulation, have not been characterized. In the present study, we investigated effects of beta(2)AR stimulation on contraction, [Ca2+](i) transient, and L-type Ca2+ currents (I-Ca) in single ventricular myocytes isolated from transgenic mice overexpressing human beta(2)AR (TG4 mice) and wild-type (WT) littermates, Baseline contractility of TG4 heart cells was increased by 3-fold relative to WT controls as a result of the presence of spontaneous beta(2)AR activation. In contrast, beta(2)AR stimulation by zinterol or isoproterenol plus a selective beta(1)-adrenergic receptor (beta(1)AR) antagonist CGP 20712A failed to enhance the contractility in TG4 myocytes, and more surprisingly, beta(2)AR stimulation was also ineffective in increasing contractility in WT myocytes, Pertussis toxin (PTX) treatment fully rescued the I-Ca, [Ca2+](i), and contractile responses to beta(2)AR agonists in both WT and TG4 cells. The PTX-rescued murine cardiac beta(2)AR response is mediated by cAMP-dependent mechanisms, because it was totally blocked by the inhibitory cAMP analog Rp-cAMPS, These results suggest that PTX-sensitive G proteins are responsible for the unresponsiveness of mouse heart to agonist-induced beta(2)AR stimulation. This was further corroborated by an increased incorporation of the photoreactive GTP analog [gamma-P-32]GTP azidoanilide into cu subunits of G(i2) and G(i3) after beta(2)AR stimulation by zinterol or isoproterenol plus the beta(1)AR blocker CGP 20712A, This effect to activate G(i) proteins was abolished by a selective beta(2)AR blocker ICI 118,551 or by PTX treatment. Thus, we conclude that (1) beta(2)ARs in murine cardiac myocytes couple to concurrent G(s) and G(i) signaling, resulting in null inotropic response, unless the G(i) signaling is inhibited; (2) as a special case, the lack of cardiac contractile response to beta(2)AR agonists in TG4 mice is not due to a saturation of cell contractility or of the cAMP signaling cascade but rather to an activation of beta(2)AR-coupled G(i) proteins; and (3) spontaneous beta(2)AR activation may differ from agonist-stimulated beta(2)AR signaling. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Russian Acad Sci, Inst Dev Biol, Moscow, Russia. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA. Univ Krankenhuas Eppendorf, Abt Allgemeine Pharmakol, Hamburg, Germany. RP NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Xiaor@GRC.NIA.NIH.Gov NR 42 TC 260 Z9 275 U1 1 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7330 EI 1524-4571 J9 CIRC RES JI Circ.Res. PD JAN 8 PY 1999 VL 84 IS 1 BP 43 EP 52 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 162RM UT WOS:000078360600005 PM 9915773 ER PT J AU Caffrey, JJ Hidaka, K Matsuda, M Hirata, M Shears, SB AF Caffrey, JJ Hidaka, K Matsuda, M Hirata, M Shears, SB TI The human and rat forms of multiple inositol polyphosphate phosphatase: functional homology with a histidine acid phosphatase up-regulated during endochondral ossification SO FEBS LETTERS LA English DT Article DE chondrocyte; inositol phosphate; bone; apoptosis; multiple inositol polyphosphate phosphatase ID SITE-DIRECTED MUTAGENESIS; ENDOPLASMIC-RETICULUM; PROTEIN; 3-PHOSPHATASE; EXPRESSION; MECHANISM; SEQUENCES; MEMBRANES AB We have derived the full-length sequences of the human and rat forms of the multiple inositol polyphosphate phosphatase (MIPP); their structural and functional comparison with a chick histidine acid phosphatase (HiPER1) has revealed new information: (1) MIPP is approximately 50% identical to HiPER1, but the ER-targeting domains are divergent; (2) MIPP appears to share the catalytic requirement of histidine acid phosphatases, namely, a C-terminal His residue remote from the RHGxRxP catalytic motif; (3) rat MIPP mRNA is upregulated during chondrocyte hypertrophy. The latter observation provides a contest for proposing that MIPP may aid bone mineralization and salvage the inositol moiety prior to apoptosis. (C) 1999 Federation of European Biochemical Societies. C1 Natl Inst Environm Hlth Sci, Inositide Signaling Grp, NIH, Res Triangle Pk, NC 27709 USA. Kyushu Univ, Fac Dent, Dept Biochem, Higashi Ku, Fukuoka 812, Japan. RP Caffrey, JJ (reprint author), Natl Inst Environm Hlth Sci, Inositide Signaling Grp, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM caffrey@niehs.nih.gov NR 24 TC 24 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JAN 8 PY 1999 VL 442 IS 1 BP 99 EP 104 DI 10.1016/S0014-5793(98)01636-6 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 156LL UT WOS:000078002600022 PM 9923613 ER PT J AU Wickner, RB Edskes, HK Maddelein, ML Taylor, KL Moriyama, H AF Wickner, RB Edskes, HK Maddelein, ML Taylor, KL Moriyama, H TI Prions of yeast and fungi - Proteins as genetic material SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID SACCHAROMYCES-CEREVISIAE; RNA VIRUSES; SUP35 GENE; PSI; URE3; INCOMPATIBILITY; MUTATION; PRODUCT; ANALOG C1 NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Wickner, RB (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bldg 8,Rm 225,,8 Ctr Dr,MSC 0830, Bethesda, MD 20892 USA. RI MADDELEIN, Marie-Lise/G-5395-2010; MORIYAMA, Hiromitsu/F-9256-2013 NR 40 TC 59 Z9 62 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 8 PY 1999 VL 274 IS 2 BP 555 EP 558 DI 10.1074/jbc.274.2.555 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 155WC UT WOS:000077968500001 PM 9872986 ER PT J AU Janulis, M Silberman, S Ambegaokar, A Gutkind, JS Schultz, RM AF Janulis, M Silberman, S Ambegaokar, A Gutkind, JS Schultz, RM TI Role of mitogen-activated protein kinases and c-Jun/AP-1 trans-activating activity in the regulation of protease mRNAs and the malignant phenotype in NIH 3T3 fibroblasts SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MATRIX METALLOPROTEINASE MATRILYSIN; HUMAN UROKINASE ENHANCER; RAT EMBRYO CELLS; C-HA-RAS; PLASMINOGEN-ACTIVATOR; SIGNALING PATHWAY; PROMOTER ACTIVITY; BINDING-SITES; CANCER CELLS; JUN AB Ras activates a multitude of downstream activities with roles in cellular proliferation, invasion and metastasis, differentiation, and programmed cell death. In this work we have evaluated the requirement of extracellular signal-regulated protein kinase (ERK), c-Jun NH2-terminal kinase kinase (JNKK), and c-Jun/AP-1 activities in transformation and extracellular matrix invasion of ras oncogene expressing NIH 3T3 fibroblasts by expressing stable mutant genes that constitutively inhibit these activities. Whereas the inhibition of ERK activity reverts the transformed and invasive phenotype, the inhibition of the JNK pathway and AP-1 transactivating activities by JNKK[K129R] and c-Jun(TAM67) had no effect on the ability of the ras oncogene-expressing cells to grow in soft agar or invade Matrigel basement membrane. Thus an elevated JNK activity and/or c-Jun/AP-1 trans-activating activity are not absolute requirements for ras transformation or invasion through basement membrane, and the dependence on AP-1 activity for transformation is cell-specific. However, inhibition of JNH kinase (JNKK) in ras-transformed cells with normally elevated JNK activity switches the protease-dependent invasive phenotype from a urokinase plasminogen activator (uPA)-dependent to a cathepsin L (CL)-dependent invasive phenotype. Conversely, treatment of ras-transformed cells of low constitutive JNK activity with the JNH stimulator, anisomycin, converts the protease mRNA levels from those characteristic of a CL-dependent to a uPA-dependent phenotype, These protease phenotypes can be duplicated in untransformed NIH 3T3 cells that express platelet-derived growth factor receptors and mi muscarinic receptors that selectively stimulate the ERK or JNK pathways, respectively. It is concluded that high ERK activity is required for both protease phenotypes, whereas the JNK pathway and c-Jun/AP-1 activity are not required for transformation but regulate a switch between uPA and CL protease phenotypes in both transformed and untransformed cells. In ras-transformed NIH 3T3 fibroblasts, the uPA- and CL-dependent protease phenotypes are redundant in their ability to invade through basement membrane. C1 Loyola Univ, Stritch Sch Med, Dept Mol & Cellular Biochem, Maywood, IL 60153 USA. Loyola Univ, Stritch Sch Med, Dept Pathol, Maywood, IL 60153 USA. NIDR, Mol Signaling Unit, Cellular Dev & Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Schultz, RM (reprint author), Loyola Univ, Stritch Sch Med, Dept Mol & Cellular Biochem, 2160 S 1st Ave, Maywood, IL 60153 USA. RI Gutkind, J. Silvio/A-1053-2009 NR 63 TC 54 Z9 61 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 8 PY 1999 VL 274 IS 2 BP 801 EP 813 DI 10.1074/jbc.274.2.801 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 155WC UT WOS:000077968500034 PM 9873019 ER PT J AU Berezhkovskii, AM Bicout, DJ Weiss, GH AF Berezhkovskii, AM Bicout, DJ Weiss, GH TI Target and trapping problems: From the ballistic to the diffusive regime SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID TELEGRAPHERS EQUATION; KINETICS; TRAPS; TIME AB The target and trapping problems refer to the reaction A+B-->B. In the target problem a single particle is fixed in space and surrounded by B's allowed to move freely, while in the trapping problem the B's are fixed and the A is able to move. Exact solutions are found for both problems in the ballistic regime, in all dimensions. We show that the solution of the target problem provides a mean-field approximation to the solution of the trapping problem, not only in the diffusive regime, but also for arbitrary noise. This approximate solution works well in the diffusive regime, but not when motion is ballistic, since it breaks down at very early times. We show that the time-dependent rate coefficients in both the target and trapping problems remain finite at t=0 for arbitrarily strong noise intensities. This behavior is in contrast to the diffusion theory prediction Chat the coefficient diverges at t=0. A recently developed model that discretizes the velocity, allowing only three values, +/-nu and 0, is used to study the reaction kinetics of both the crapping and target problems in one dimension over the entire range of noise intensities. The solutions are used to study the effects of noise intensity on the mean survival time. We show that in the target, problem this time decreases monotonically with increasing noise, while in the trapping problem this time exhibits a turnover behavior. We argue that a similar turnover occurs in the one-dimensional trapping problem when particle motion is governed by a Langevin equation. (C) 1999 American Institute of Physics. [S0021-9606(99)51902-8]. C1 NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. EM gwh@helix.nih.gov NR 22 TC 10 Z9 10 U1 0 U2 3 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 0021-9606 EI 1089-7690 J9 J CHEM PHYS JI J. Chem. Phys. PD JAN 8 PY 1999 VL 110 IS 2 BP 1112 EP 1122 DI 10.1063/1.478155 PG 11 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 153NT UT WOS:000077839700045 ER PT J AU Daly, NL Koltay, A Gustafson, KR Boyd, MR Casas-Finet, JR Craik, DJ AF Daly, NL Koltay, A Gustafson, KR Boyd, MR Casas-Finet, JR Craik, DJ TI Solution structure by NMR of circulin A: A macrocyclic knotted peptide having anti-HIV activity SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE circulin A; cyclic peptides; cystine-knot; NMR; anti-HIV activity ID NUCLEAR MAGNETIC-RESONANCE; INTERPROTON DISTANCE RESTRAINTS; PROTEIN SECONDARY STRUCTURE; RACE-SPECIFIC ELICITOR; CHEMICAL-SHIFT INDEX; X-RAY STRUCTURES; 3-DIMENSIONAL STRUCTURE; TRYPSIN-INHIBITOR; NICOTIANA-ALATA; CYSTINE KNOT AB The three-dimensional solution structure of circulin A, a 30 residue poly peptide from the African plant Chassalia parvifolia, has been determined using two-dimensional H-1-NMR spectroscopy. Circulin A was originally identified based upon its inhibition of the cytopathic effects and replication of the human immunodeficiency virus. Structural restraints consisting of 369 interproton distances inferred from nuclear Overhauser effects, and 21 backbone dihedral and nine chi(1) angle restraints from spin-spin coupling constants were used as input for simulated annealing calculations and energy minimisation in the program X-PLOR. The final set of 12 structures had mean pairwise rms differences over the whole molecule of 0.91 Angstrom for the backbone atom, and 1.68 Angstrom for all heavy atoms. For the well-defined region encompassing residues 2-12 and 18-27, the corresponding values were 0.71 and 1.66 Angstrom, respectively. Circulin A adopts a compact structure consisting of beta-turns and a distorted segment of triple-stranded beta-sheet. Fluorescence spectroscopy provided additional evidence for a solvent-exposed Trp residue. The molecule is stabilised by three disulfide bonds, two of which form an embedded loop completed by the backbone fragments connecting the cysteine residues. A third disulfide bond threads through the centre of this loop to form a "cystine-knot" motif. This motif is present in a range of other biologically active proteins, including omega-contoxin GVIA and Cucurbita maxima trypsin inhibitor. Circulin A belongs to a novel class of macrocyclic peptides which have been isolated from plants in the Rubiaceae family. The global fold of circulin A is similar to kalata B1, the only member of this class for which a structure has previously been determined. (C) 1999 Academic Press. C1 Univ Queensland, Ctr Drug Design & Dev, Brisbane, Qld 4072, Australia. Monash Univ, Victorian Coll Pharm, Parkville, Vic 3052, Australia. NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21701 USA. NCI, AIDS Vaccine Program, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. RP Craik, DJ (reprint author), Univ Queensland, Ctr Drug Design & Dev, Brisbane, Qld 4072, Australia. EM d.craik@mailbox.uq.edu.au RI Daly, Norelle/D-4302-2013; Craik, David/B-1695-2010 OI Craik, David/0000-0003-0007-6796 NR 51 TC 88 Z9 90 U1 0 U2 4 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JAN 8 PY 1999 VL 285 IS 1 BP 333 EP 345 DI 10.1006/jmbi.1998.2276 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 155VZ UT WOS:000077968200028 PM 9878410 ER PT J AU Kostenis, E Zeng, FY Wess, J AF Kostenis, E Zeng, FY Wess, J TI Structure-function analysis of muscarinic receptors and their associated G proteins SO LIFE SCIENCES LA English DT Article; Proceedings Paper CT 8th International Symposium on Subtypes of Muscarinic Receptors CY AUG 25-29, 1998 CL DANVERS, MASSACHUSETTS SP Boston Univ Sch Med DE mutagenesis studies; G protein-coupled receptors; G protein alpha-subunits; receptor G protein coupling; disulfide cross-linking studies ID AMINO-TERMINUS; ACETYLCHOLINE-RECEPTORS; COUPLING SELECTIVITY; ALPHA-SUBUNITS; BINDING; PALMITOYLATION; SITE; G(Q-ALPHA); ACTIVATION; PEPTIDE AB Each member of the muscarinic receptor family (M1-M5) can interact only with a limited subset of the many structurally closely related heterotrimeric G proteins expressed within a cell. To understand how this selectivity is achieved at a molecular level, we have used the G(i/0)-coupled M2 and the G(q/11)-coupled M3 muscarinic receptors as model systems. We developed a genetic strategy involving the coexpression of wild type or mutant muscarinic receptors with hybrid or mutant G protein a subunits to identify specific, functionally relevant receptor/G protein contact sites. This approach led to the identification of N- and C-terminal amino acids on alpha(i) and alpha(i) that are critical for maintaining proper receptor/G protein coupling. Moreover, several receptor sites were identified that are likely to be contacted by these functionally critical G alpha residues. To gain deeper insight into muscarinic receptor structure, we recently developed a cysteine disulfide cross-linking strategy, using the M3 muscarinic receptor as a model system. Among other structural modifications, this approach involves the removal of most native cysteine residues by site-directed mutagenesis, the insertion of three factor Xa cleavage sites into the third intracellular loop, and systematic 'reintroduction' of pairs of cysteine residues. Following treatment of receptor-containing membrane preparations with factor Xa and oxidizing agents, disulfide cross-linked products can be identified by immunoprecipitation and immunoblotting studies. This approach should greatly advance our knowledge of the molecular architecture of muscarinic and other G protein-coupled receptors. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Kostenis, E (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bldg 8A,Room B1A-05, Bethesda, MD 20892 USA. NR 31 TC 15 Z9 18 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JAN 8 PY 1999 VL 64 IS 6-7 BP 355 EP 362 DI 10.1016/S0024-3205(98)00574-8 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 158EV UT WOS:000078103800001 PM 10069496 ER PT J AU Landis, SC AF Landis, SC TI Development of muscarinic receptors and regulation of secretory responsiveness in rodent sweat glands SO LIFE SCIENCES LA English DT Article; Proceedings Paper CT 8th International Symposium on Subtypes of Muscarinic Receptors CY AUG 25-29, 1998 CL DANVERS, MASSACHUSETTS SP Boston Univ Sch Med DE sympathetic innervation; sweat gland secretion; transmitter plasticity ID NEUROTRANSMITTER PLASTICITY INVIVO; RAT PAROTID-GLAND; SYMPATHETIC INNERVATION; CHOLINERGIC DIFFERENTIATION; ACETYLCHOLINE; NEURONS; MOUSE; EXPRESSION; CURRENTS; AGONISTS AB Sweat glands are innervated by sympathetic neurons which undergo a change in transmitter phenotype from noradrenergic to cholinergic during development. As soon as the glands begin to differentiate, M3 muscarinic receptor mRNA and binding sites are detectable. Receptor expression appears in the absence of innervation and is maintained after denervation. While receptor expression is not responsiveness is. Muscarinic blockade during development or in adult animals results in the loss of responsiveness and its reappearance requires several days. Cholinergic muscarinic activation is most likely to regulate one or more steps in the signalling cascade that are downstream of calcium mobilization. The anterograde regulation of sweat gland responsiveness is one facet of the reciprocal interactions are required to establish a functional synapse in this system. C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Landis, SC (reprint author), NINDS, NIH, Bethesda, MD 20892 USA. NR 35 TC 13 Z9 13 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JAN 8 PY 1999 VL 64 IS 6-7 BP 381 EP 385 DI 10.1016/S0024-3205(98)00578-5 PG 5 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 158EV UT WOS:000078103800005 PM 10069500 ER PT J AU Kiesewetter, DO Carson, RE Jagoda, EM Herscovitch, P Eckelman, WC AF Kiesewetter, DO Carson, RE Jagoda, EM Herscovitch, P Eckelman, WC TI Using single photon emission tomography (SPECT) and positron emission tomography (PET) to trace the distribution of muscarinic acetylcholine receptor (mAChR) binding radioligands SO LIFE SCIENCES LA English DT Article; Proceedings Paper CT 8th International Symposium on Subtypes of Muscarinic Receptors CY AUG 25-29, 1998 CL DANVERS, MASSACHUSETTS SP Boston Univ Sch Med DE mAChR binding radioligands; SPECT; PET ID RAT-BRAIN; SELECTIVITY; M2; QNB AB Two [F-18] labeled ligands for the mAChR were prepared and evaluated in rodents and nonhuman primates. The properties of both compounds, one an agonist and the other an antagonist, were consistent with Mt subtype specificity. C1 NIH, Warren G Magnuson Clin Ctr, PET, Bethesda, MD 20892 USA. RP Eckelman, WC (reprint author), NIH, Warren G Magnuson Clin Ctr, PET, 10 Ctr Dr MSC 1180, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 17 TC 8 Z9 8 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JAN 8 PY 1999 VL 64 IS 6-7 BP 511 EP 518 DI 10.1016/S0024-3205(98)00595-5 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 158EV UT WOS:000078103800022 PM 10069517 ER PT J AU Jakubik, J Wess, J AF Jakubik, J Wess, J TI Development of a sandwich ELISA strategy to study mechanisms involved in muscarinic receptor assembly SO LIFE SCIENCES LA English DT Meeting Abstract C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JAN 8 PY 1999 VL 64 IS 6-7 MA 22 BP 565 EP 565 DI 10.1016/S0024-3205(99)90486-1 PG 1 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 158EV UT WOS:000078103800050 ER PT J AU Zeng, FY Wess, J AF Zeng, FY Wess, J TI Development of a disulfide cross-linking strategy to study muscarinic receptor structure SO LIFE SCIENCES LA English DT Meeting Abstract C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JAN 8 PY 1999 VL 64 IS 6-7 MA 21 BP 565 EP 565 DI 10.1016/S0024-3205(99)90485-X PG 1 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 158EV UT WOS:000078103800049 ER PT J AU Ventura, ON Kieninger, M Cachau, RE AF Ventura, ON Kieninger, M Cachau, RE TI Density functional theory is more accurate than coupled-cluster theory in the study of the thermochemistry of species containing the F-O bond SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID FLUORINE PEROXIDE FOOF; NITROSYL HYPOFLUORITE; THEORETICAL METHODS; ENERGY; FONO; PERTURBATION; MOLECULES; EXCHANGE; FIELD AB The standard singles and doubles coupled-cluster method including perturbational treatment of connected triple excitations, CCSD(T), and density functional methods, DFT, using a large, uncontracted, atomic natural orbital (ANO) basis set were employed for calculating the enthalpies of formation of some first-row atoms (H, N, O, F) as well as diatomic and triatomic molecules formed with them. Molecular enthalpies of formation at 298.15 K were obtained from enthalpies of reaction of the atoms, homonuclear diatomic molecules, and isodesmic reactions. It is shown that the errors are the minimum when isodesmic reactions are used. However, contrary to accepted belief, CCSD(T) gives a larger deviation from experiment than DFT in the latter case. DFT exhibits similar accuracy when using a very small basis set (6-31G*) to that with the extended basis set, while the errors obtained with CCSD(T) are much larger. It is concluded that DFT is a more accurate and convenient computational tool than CCSD(T) for the thermochemical study of species containing the F-O bond. C1 Univ Republ, Fac Quim, MTC Lab, Montevideo 11800, Uruguay. NCI, Frederick Biomed Supercomp Ctr, Frederick, MD 21702 USA. RP Ventura, ON (reprint author), Univ Republ, Fac Quim, MTC Lab, CC 1157, Montevideo 11800, Uruguay. NR 30 TC 27 Z9 27 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD JAN 7 PY 1999 VL 103 IS 1 BP 147 EP 151 DI 10.1021/jp982282j PG 5 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 174NX UT WOS:000079042200018 ER PT J AU Huster, D Arnold, K Gawrisch, K AF Huster, D Arnold, K Gawrisch, K TI Investigation of lipid organization in biological membranes by two-dimensional nuclear overhauser enhancement spectroscopy SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID MAS-NOESY SPECTRA; MAGNETIC-RESONANCE; CROSS-RELAXATION; NMR-SPECTROSCOPY; MODEL; CHOLESTEROL; DYNAMICS; VESICLES AB The cross-peaks between lipid resonances in two-dimensional nuclear Overhauser enhancement spectroscopy H-1 NMR spectra, recorded with magic-angle spinning, contain valuable information about the structure and dynamics of the lipid bilayer. We have attempted a quantitative analysis of magnetization exchange between lipid resonances in the biologically relevant liquid crystalline lamellar phase. Spectra of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) water dispersions were recorded at mixing times from 0.005 to 1 s, and all diagonal and cross-peak volumes were determined by integration. The full relaxation-rate matrix was computed for the 10 lipid resonances by a matrix equation algorithm. Results of this mathematically rigorous approach were compared with simplified approaches to calculate cross-relaxation rates. In a second series of experiments, the DMPC was mixed with increasing amounts of perdeuterated DMPC-d(67) to determine the percentage of intra- vs intermolecular magnetization transfer. With the exception of transfer between nearest neighbor protons by chemical bond, cross-relaxation in DMPC bilayers is exclusively intermolecular. There is no evidence for the transfer of magnetization over several bonds within lipid molecules by spin diffusion. Lipids exist in multiple conformations with rapid transitions between them, and, therefore, cross-relaxation rates do not represent stable molecular arrangements with fixed distances. Instead, the cross-relaxation rates reflect the probability of close approach between protons of neighboring lipid molecules. We established experimentally that cross-relaxation rates are proportional to the statistical average of lateral lipid-lipid contacts in binary mixtures. The location of lipid segments along the bilayer normal is best described by a distribution function. Segments which are located at the same depth in the bilayer approach each other with higher probability and have higher rates of magnetization transfer, compared with groups which are, on average, more distant and approach each other less frequently. The per-proton intermolecular cross-relaxation rates vary over the bilayer by only 1 order of magnitude, indicating surprisingly high probabilities of close approach even between the most distant groups, like the choline methyl groups and the terminal methyl groups of hydrocarbon chains. The results reflect the high degree of lipid motional disorder and the substantial variations in location of neighboring lipid molecules. C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. Univ Leipzig, Inst Med Phys & Biophys, D-04103 Leipzig, Germany. RP Gawrisch, K (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, 12420 Parklawn Dr,Room 158, Rockville, MD 20852 USA. NR 24 TC 114 Z9 116 U1 0 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5647 J9 J PHYS CHEM B JI J. Phys. Chem. B PD JAN 7 PY 1999 VL 103 IS 1 BP 243 EP 251 DI 10.1021/jp983428h PG 9 WC Chemistry, Physical SC Chemistry GA 174PC UT WOS:000079042700036 ER PT J AU O'Leary, DH Polak, JF Kronmal, RA Manolio, TA Burke, GL Wolfson, SK AF O'Leary, DH Polak, JF Kronmal, RA Manolio, TA Burke, GL Wolfson, SK CA Cardiovascular Hlth Study Collaborative Res Grp TI Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; CARDIOVASCULAR HEALTH; WALL THICKNESS; ATHEROSCLEROSIS RISK; SERUM-CHOLESTEROL; BLOOD-PRESSURE; PREVALENCE; ROTTERDAM; DETERMINANTS; ASSOCIATION AB Background The combined thickness of the intima and media of the carotid artery is associated with the prevalence of cardiovascular disease. We studied the associations between the thickness of the carotid-artery intima and media and the incidence of new myocardial infarction or stroke in persons without clinical cardiovascular disease. Methods Noninvasive measurements of the intima and media of the common and internal carotid artery were made with high-resolution ultrasonography in 5858 subjects 65 years of age or older. Cardiovascular events (new myocardial infarction or stroke) served as outcome variables in subjects without clinical cardiovascular disease (4476 subjects) over a median follow-up period of 6.2 years. Results The incidence of cardiovascular events correlated with measurements of carotid-artery intima-media thickness. The relative risk of myocardial infarction or stroke increased with intima-media thickness (P<0.001). The relative risk of myocardial infarction or stroke (adjusted for age and sex) for the quintile with the highest thickness as compared with the lowest quintile was 3.87 (95 percent confidence interval, 2.72 to 5.51). The association between cardiovascular events and intima-media thickness remained significant after adjustment for traditional risk factors, showing increasing risks for each quintile of combined intima-media thickness, from the second quintile (relative risk, 1.54; 95 percent confidence interval, 1.04 to 2.28), to the third (relative risk, 1.84; 95 percent confidence interval, 1.26 to 2.67), fourth (relative risk, 2.01; 95 percent confidence interval, 1.38 to 2.91), and fifth (relative risk, 3.15; 95 percent confidence interval, 2.19 to 4.52). The results of separate analyses of myocardial infarction and stroke paralleled those for the combined end point. Conclusions Increases in the thickness of the intima and media of the carotid artery, as measured noninvasively by ultrasonography, are directly associated with an increased risk of myocardial infarction and stroke in order adults without a history of cardiovascular disease. (N Engl J Med 1999;340:14-22.) (C) 1999, Massachusetts Medical Society. C1 Tufts New England Med Ctr, Dept Radiol, Boston, MA USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA. Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. RP O'Leary, DH (reprint author), CHS Coordinating Ctr, Century Sq,1501 4th Ave,Suite 2025, Seattle, WA 98101 USA. EM daniel.oleary@es.nemc.org FU NHLBI NIH HHS [N01-HC85081, N01-HC85079, N01-HC85080] NR 39 TC 2967 Z9 3066 U1 10 U2 54 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 7 PY 1999 VL 340 IS 1 BP 14 EP 22 DI 10.1056/NEJM199901073400103 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 155JQ UT WOS:000077943700003 PM 9878640 ER PT J AU Zametkin, AJ Ernst, M AF Zametkin, AJ Ernst, M TI Problems in the management of attention-deficit-hyperactivity disorder SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID LEARNING-DISABILITIES; STIMULANT MEDICATION; CHILDREN; METHYLPHENIDATE; ASSOCIATION; ADHD C1 NIMH, NIH, Bethesda, MD 20892 USA. NIDA, Brain Imaging Ctr, Baltimore, MD USA. RP Zametkin, AJ (reprint author), NIMH, NIH, Rm 3N238,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. NR 38 TC 102 Z9 108 U1 3 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 7 PY 1999 VL 340 IS 1 BP 40 EP 46 DI 10.1056/NEJM199901073400107 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 155JQ UT WOS:000077943700007 PM 9878644 ER PT J AU Walker, DR Bond, JP Tarone, RE Harris, CC Makalowski, W Boguski, MS Greenblatt, MS AF Walker, DR Bond, JP Tarone, RE Harris, CC Makalowski, W Boguski, MS Greenblatt, MS TI Evolutionary conservation and somatic mutation hotspot maps of p53: correlation with p53 protein structural and functional features SO ONCOGENE LA English DT Article DE molecular evolution; missense mutation; crystal structure; DNA binding; domain ID TUMOR-SUPPRESSOR; CRYSTAL-STRUCTURE; CELL-LINES; GENE; DOMAIN; SUBSTITUTIONS; APOPTOSIS; CANCER AB Missense mutations in p53 frequently occur at 'hotspot' amino acids which are highly conserved and represent regions of structural or functional importance. Using the p53 mutation database and the p53 DNA sequences for 11 species, we more precisely defined the relationships among conservation, mutation frequency and protein structure. We aligned the p53 sequences codon-by-codon and determined the degree of substitution among them. As a whole, p53 is evolving at an average rate for a mammalian protein-coding gene. As expected, the DNA binding domain is evolving more slowly than the carboxy and amino termini, A detailed map of evolutionary conservation shows that within the DNA binding domain there are repeating peaks and valleys of higher and lower evolutionary constraint, Mutation hotspots were identified by comparing the observed distribution of mutations to the pattern expected from a random multinomial distribution, Seventy-three hotspots were identified; these 19% of codons account for 88% of all reported p53 mutations. Both high evolutionary constraint and mutation hotspots are noted at amino acids close to the protein-DNA interface and at others more distant from DNA, often buried within the core of the folded protein but sometimes on its surface. The results indicate that targeting highly conserved regions for mutational and functional analysis may be efficient strategies for the study of cancer-related genes. C1 NCI, Natl Ctr Biotechnol Informat, Natl Lib Med, NIH, Bethesda, MD 20894 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. RP Greenblatt, MS (reprint author), Univ Vermont, Coll Med, Dept Med, Hematol Oncol Unit, Patrick 534,MCHV Campus, Burlington, VT 05401 USA. RI Makalowski, Wojciech/I-2843-2016 NR 27 TC 142 Z9 145 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 7 PY 1999 VL 18 IS 1 BP 211 EP 218 DI 10.1038/sj.onc.1202298 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 159HG UT WOS:000078166000023 PM 9926936 ER PT J AU Lin, YG AF Lin, YG TI Bridging the worlds of medicine and science: An interview with Bert I. Shapiro, MD SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 Univ Calif Irvine, Sch Med, Irvine, CA 92717 USA. Natl Inst Gen Med Sci, MSTP, Bethesda, MD 20892 USA. RP Lin, YG (reprint author), Univ Calif Irvine, Sch Med, Irvine, CA 92717 USA. NR 1 TC 2 Z9 2 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 6 PY 1999 VL 281 IS 1 BP 98 EP 99 DI 10.1001/jama.281.1.98 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 153JE UT WOS:000077829300048 ER PT J AU Ambs, S Bennett, WP Merriam, WG Ogunfusika, MO Oser, SM Harrington, AM Shields, PG Felley-Bosco, E Hussain, SP Harris, CC AF Ambs, S Bennett, WP Merriam, WG Ogunfusika, MO Oser, SM Harrington, AM Shields, PG Felley-Bosco, E Hussain, SP Harris, CC TI Relationship between p53 mutations and inducible nitric oxide synthase expression in human colorectal cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID TUMOR-SUPPRESSOR GENE; NITRATE; DNA C1 NCI, Human Carcinogenesis Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Univ Lausanne, Inst Pharmacol & Toxicol, CH-1005 Lausanne, Switzerland. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Div Basic Sci, NIH, Bldg 37,Rm 2C01,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM Curtis_Harris@nih.gov RI Felley-Bosco, Emanuela/E-7484-2017 OI Felley-Bosco, Emanuela/0000-0002-3408-0294 NR 25 TC 151 Z9 154 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 6 PY 1999 VL 91 IS 1 BP 86 EP 88 DI 10.1093/jnci/91.1.86 PG 3 WC Oncology SC Oncology GA 155BV UT WOS:000077926800018 PM 9890175 ER PT J AU Kondrashin, A Nesterova, M Cho-Chung, YS AF Kondrashin, A Nesterova, M Cho-Chung, YS TI Cyclic adenosine 3 ': 5 '-monophosphate-dependent protein kinase on the external surface of LS-174T human colon carcinoma cells SO BIOCHEMISTRY LA English DT Article ID YEAST SACCHAROMYCES-CEREVISIAE; CAMP-BINDING ECTOPROTEIN; HL-60 LEUKEMIA-CELLS; DICTYOSTELIUM-DISCOIDEUM; REGULATORY SUBUNIT; PLASMA-MEMBRANE; AMP RECEPTOR; 3T3 CELLS; DIFFERENTIATION; IDENTIFICATION AB The analysis of purified plasma membranes and the surface of intact cells revealed the presence of cyclic adenosine 3':5'-monophosphate-(cAMP) dependent protein kinase (PKA) on the external surface of LS-174T human colon carcinoma cells. Photoaffinity labeling of intact cells at confluence with 8-azido[P-32]cAMP identified the cAMP-binding proteins on the surface. Immunoprecipitation identified the photoaffinity-labeled cAMP-binding proteins as the RII alpha regulatory. subunit of PKA. During the logarithmic stage of growth, both the RI alpha and RII alpha subunits of PKA were localized on the cell surface. Intact LS-174T cells catalyzed the phosphorylation of Kemptide in a cAMP-dependent manner, upon substitution of cAMP in the medium with 8-chloroadenosine, which did not compete with cAMP for the binding on intact cells, the ecto-PKA was no longer activated. The specific inhibitory protein for PKA, PKI, abolished the stimulation of phosphorylation by cAMP. Forskolin, which elevates intracellular levels of cAMP, activated ecto-PKA. Moreover, probenecid, which blocks the export of cAMP, inhibited the forskolin-mediated activation of ecto-PKA. These results demonstrate that LS-174T colon carcinoma cells possess an ecto-PKA on the external surface. This ecto-PICA is similar, if not identical, to the soluble intracellular PKA. C1 NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, NIH, Bldg 10,Room 5B05,9000 Rockville Pike, Bethesda, MD 20892 USA. EM chochung@helix.nih.gov NR 44 TC 6 Z9 7 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 5 PY 1999 VL 38 IS 1 BP 172 EP 179 DI 10.1021/bi982090e PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 170YW UT WOS:000078835800019 PM 9890895 ER PT J AU Chen, H Cong, LN Li, YH Yao, ZJ Wu, L Zhang, ZY Burke, TR Quon, MJ AF Chen, H Cong, LN Li, YH Yao, ZJ Wu, L Zhang, ZY Burke, TR Quon, MJ TI Phosphotyrosyl mimetic peptide reverses impairment of insulin-stimulated translocation of GLUT4 caused by overexpression of PTP1B in rat adipose cells SO BIOCHEMISTRY LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASES; SOLID-PHASE SYNTHESIS; O-PHOSPHOTYROSINE; INTACT-CELLS; ESCHERICHIA-COLI; INHIBITOR DESIGN; RECEPTOR; 1B; DEPHOSPHORYLATION; PURIFICATION AB Biological actions of insulin are initiated by activation of the insulin receptor tyrosine kinase Protein tyrosine phosphatases (PTPases) PTP1B and PTP alpha are known to dephosphorylate the insulin receptor and may contribute to insulin resistance in diseases such as diabetes. We previously reported that overexpression of PTP1B in rat adipose cells significantly impairs insulin-stimulated translocation of GLUT4 [Chen, H., et al. (1997) J. Biol. Chem. 272, 8026]. in the present study, we treated adipose cells with a PTPase inhibitor containing the phosphotyrosyl mimetic difluorophosphonomethyl phenylalanine (F(2)Pmp) to determine whether we could improve the insulin resistance caused by overexpression of PTP1B or PTP alpha. Rat adipose cells transfected by electroporation with either PTP1B or PTP alpha were treated without or with the inhibitor, and effects on insulin-stimulated translocation of a cotransfected epitope-tagged GLUT4 were studied. The IC50 of the F(2)Pmp-containing inhibitor is 180 nhl for PTP1B and 10 mM for PTP alpha in vitro. As expected, in the absence of the inhibitor, overexpression of either PTP1B or PTP alpha caused a significant decrease in the amount of GLUT4 at the cell surface both in the absence and in the presence of insulin when compared with control cells transfected with epitope-tagged GLUT4 alone. Interestingly, the insulin resistance caused by overexpression of PTP1B (but not PTP alpha) was reversed by treating the transfected cells with the F(2)Pmp-containing inhibitor. Furthermore, the inhibitor blocked the insulin-stimulated association of PTP1B with the insulin receptor. We conclude that the F(2)Pmp-containing compound is a potent and specific inhibitor of overexpressed PTP1B that may be useful for designing rational therapies for treating insulin resistant diseases such as diabetes. C1 NHLBI, Hypertens Endocrine Branch, NIH, Bethesda, MD 20892 USA. NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 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; Burke, Terrence/N-2601-2014; Yao, Zhu-Jun/E-7635-2015 NR 35 TC 41 Z9 43 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 5 PY 1999 VL 38 IS 1 BP 384 EP 389 DI 10.1021/bi9816103 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 170YW UT WOS:000078835800044 PM 9890920 ER PT J AU Werbovetz, KA Brendle, JJ Sackett, DL AF Werbovetz, KA Brendle, JJ Sackett, DL TI Purification, characterization, and drug susceptibility of tubulin from Leishmania SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Leishmania; tubulin; drug discovery ID TRYPANOSOMA-BRUCEI-BRUCEI; CELL-CYCLE; ASSEMBLY INVITRO; COLCHICINE SITE; BETA-TUBULIN; INHIBITION; MECHANISM; AGENTS; PROMASTIGOTES; TRYPANOTHIONE AB Past work suggests that tubulin from kinetoplastid parasites may present an excellent drug target. To explore this possibility, tubulin was purified on a milligram scale from Leishmania mexicana amazonensis promastigotes by sonication, DEAE-Sepharose chromatography, and one cycle of assembly-disassembly. Purified leishmanial tubulin is recognized by commercially available anti-tubulin antibodies and displays concentration dependent assembly in vitro. The vinca site agents vinblastine, maytansine, and rhizoxin bind to leishmanial tubulin as assessed by the quenching of intrinsic tubulin fluorescence and the alteration of the proteins reactivity with the sulfhydryl-specific reagent 5,5'-dithiobis(2-nitrobenzoic acid). They also interfere with the assembly of leishmanial tubulin at low micromolar concentrations. Electrophilic compounds such as phenyl arsenoxide and 4-chloro-3,5-dinitro-alpha,alpha,alpha-trifluorotoluene (chloralin), which are of interest as traditional and experimental antiparasitic agents, respectively, inhibit the assembly of leishmanial tubulin in vitro as well. Colchicine-site agents and trifluralin, on the other hand, have little or no effect on leishmanial tubulin in these assays. Maytansine, taxol, and the electrophiles block the growth of Leishmania donovani amastigote-like forms in vitro at low (<1 mu M) concentrations, while colchicine site agents, trifluralin, vinblastine, and rhizoxin are at least two orders of magnitude less toxic to the parasite. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Dept Parasitol, Div Expt Therapeut, Washington, DC 20307 USA. NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Werbovetz, KA (reprint author), Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Dept Parasitol, Div Expt Therapeut, Washington, DC 20307 USA. RI Werbovetz, Karl/E-4290-2011 NR 41 TC 75 Z9 76 U1 0 U2 5 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 JAN 5 PY 1999 VL 98 IS 1 BP 53 EP 65 DI 10.1016/S0166-6851(98)00146-7 PG 13 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 163LC UT WOS:000078406100005 PM 10029309 ER PT J AU Lacourciere, GM Stadtman, TC AF Lacourciere, GM Stadtman, TC TI Catalytic properties of selenophosphate synthetases: Comparison of the selenocysteine-containing enzyme from Haemophilus influenzae with the corresponding cysteine-containing enzyme from Escherichia coli SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SELD HOMOLOG; MUTANT; IDENTIFICATION; METABOLISM; MECHANISM; SELENIUM AB The selD gene from Haemophilus influenzae has been overexpressed in Escherichia coli, The expressed protein was purified to homogeneity in a four-step procedure and then carboxymethylated by reaction with chloroacetate. N-terminal sequencing by Edman degradation identified residue 16 as carboxymethyl selenocysteine, which corresponded to the essential cysteine residue in the glycine-rich sequence of the E. coli selenophosphate synthetase. It would be expected that an ionized selenol of a selenocysteine in place of a catalytically essential cysteine residue would result in an enzyme with increased catalytic activity. To test this hypothesis we kinetically characterized the selenocysteine containing selenophosphate synthetase from H. influenzae and compared its catalytic activity to that of the cysteine containing selenophosphate synthetase from E. coli. Our characterization revealed the K-m values for the two substrates, selenide and ATP, were similar for both enzymes. However, the selenocysteine-containing enzyme did not exhibit the expected higher catalytic activity. Based on these results we suggest a role of selenocysteine in H. influenzae that is not catalytic. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Stadtman, TC (reprint author), NHLBI, Biochem Lab, NIH, Bldg 3,Room 103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 16 TC 26 Z9 30 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 5 PY 1999 VL 96 IS 1 BP 44 EP 48 DI 10.1073/pnas.96.1.44 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 156MD UT WOS:000078004400011 PM 9874769 ER PT J AU Yu, B Blaber, M Gronenborn, AM Clore, GM Caspar, DLD AF Yu, B Blaber, M Gronenborn, AM Clore, GM Caspar, DLD TI Disordered water within a hydrophobic protein cavity visualized by x-ray crystallography SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MACROMOLECULAR STRUCTURES; CRYSTAL-STRUCTURES; REFINEMENT; DIFFRACTION; RESOLUTION; INTERLEUKIN-1-BETA; PENICILLOPEPSIN; SOLVATION; ACCURACY; PROGRAM AB Water in the hydrophobic cavity of human interleukin 1 beta, which was detected by NMR spectroscopy but was invisible by high resolution x-ray crystallography, has been mapped quantitatively by measurement and phasing of all of the low resolution x-ray diffraction data from a single crystal. Phases for the low resolution data were refined by iterative density modification of an initial flat solvent model outside the envelope of the atomic model. The refinement was restrained by the condition that the map of the difference between the electron density distribution in the full unit cell and that of the atomic model be flat within the envelope of the well ordered protein structure. Care was taken to avoid overfitting the diffraction data by maintaining phases for the high resolution data from the atomic model and by a resolution-dependent damping of the structure factor differences between data and model. The cavity region in the protein could accommodate up to four water molecules. The refined solvent difference map indicates that there are about two water molecules in the cavity region. This map is compatible with an atomic model of the water distribution refined by using XPLOR. About 70% of the time, there appears to be a water dimer in the central hydrophobic cavity, which is connected to the outside by two constricted channels occupied by single water molecules approximate to 40% of the time on one side and approximate to 10% on the other. C1 Florida State Univ, Inst Mol Biophys, Tallahassee, FL 32306 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Caspar, DLD (reprint author), Florida State Univ, Inst Mol Biophys, 410 MBB-4380, Tallahassee, FL 32306 USA. EM caspar@sb.fsu.edu RI Clore, G. Marius/A-3511-2008; Blaber, Michael/E-7478-2011; OI Clore, G. Marius/0000-0003-3809-1027; Blaber, Michael/0000-0002-6856-1643 FU NCI NIH HHS [CA47439]; NIGMS NIH HHS [GM54429-01] NR 29 TC 100 Z9 101 U1 1 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 5 PY 1999 VL 96 IS 1 BP 103 EP 108 DI 10.1073/pnas.96.1.103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 156MD UT WOS:000078004400021 PM 9874779 ER PT J AU Morasso, MI Grinberg, A Robinson, G Sargent, TD Mahon, KA AF Morasso, MI Grinberg, A Robinson, G Sargent, TD Mahon, KA TI Placental failure in mice lacking the homeobox gene Dlx3 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TROPHOBLAST; EXPRESSION; MOUSE; FAMILY; DIFFERENTIATION; MUTATIONS; LETHALITY; ENCODES; EMBRYOS; MEMBER AB Dlx3 is a homeodomain transcription factor and a member of the vertebrate Distal-less family. Targeted deletion of the mouse Dlx3 gene results in embryonic death between day 9.5 and day 10 because of placental defects that alter the development of the labyrinthine layer. In situ hybridization reveals that the Dlx3 gene is initially expressed in ectoplacental cone cells and chorionic plate, and later in the labyrinthine trophoblast of the chorioallantoic placenta, where major defects are observed in the Dlx3 -/- embryos. The expression of structural genes, such as 4311 and PL-1, which were used as markers to follow the fate of different derivatives of the placenta, was not affected in the Dlx3-null embryos. However, by day 10.5 of development, expression of the paired-like homeodomain gene Esx1 was strongly downregulated in affected placenta tissue, suggesting that Dlx3 is required for the maintenance of Esx1 expression, normal placental morphogenesis, and embryonic survival. C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. RP Morasso, MI (reprint author), NIAMSD, Skin Biol Lab, NIH, Bldg 6,Room 134, Bethesda, MD 20892 USA. EM morasso@nih.gov RI Robinson, Gertraud/I-2136-2012 FU NIAMS NIH HHS [Z01 AR041124-06] NR 35 TC 166 Z9 168 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 5 PY 1999 VL 96 IS 1 BP 162 EP 167 DI 10.1073/pnas.96.1.162 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 156MD UT WOS:000078004400031 PM 9874789 ER PT J AU Kuzio, J Pearson, MN Harwood, SH Funk, CJ Evans, JT Slavicek, JM Rohrmann, GF AF Kuzio, J Pearson, MN Harwood, SH Funk, CJ Evans, JT Slavicek, JM Rohrmann, GF TI Sequence and analysis of the genome of a Baculovirus pathogenic for Lymantria dispar SO VIROLOGY LA English DT Article DE baculovirus; nuclear polyhedrosis virus; genome sequence ID NUCLEAR POLYHEDROSIS-VIRUS; LATE GENE-EXPRESSION; AUTOGRAPHA-CALIFORNICA BACULOVIRUS; ORGYIA-PSEUDOTSUGATA; RIBONUCLEOTIDE REDUCTASE; NUCLEOTIDE-SEQUENCE; DNA-REPLICATION; STRUCTURAL PROTEIN; APOPTOSIS PROTEINS; HOMOLOGOUS REGIONS AB The genome of the Lymantria dispar multinucleocapsid nucleopolyhedrovirus (LdMNPV) was sequenced and analyzed. It is composed of 161,046 bases with a G + C content of 57.5% and contains 163 putative open reading frames (ORFs) of greater than or equal to 150 nucleotides. Homologs were found to 95 of the 155 genes predicted for the Autographa californica MNPV (AcMNPV) genome. More than 9% of the LdMNPV genome was occupied by 16 repeated genes related to AcMNPV ORF2. Readily identifiable homologs of several genes that have been reported to play important roles in the AcMNPV life cycle are not present; these include ie-2, a transcriptional transactivator, and gp64, a major envelope glycoprotein of the nonoccluded form of the virus. A number of genes lacking in AcMNPV but present in other baculoviruses were identified; these include two viral enhancing factor homologs, a second copy of a conotoxin-like gene, and a dutpase homolog. Although a single gene predicted to encode a large subunit of ribonucleotide reductase was found, two different copies of the small subunit gene were present. In addition, homologs of genes not previously reported for baculoviruses were identified, including a predicted protein with homology to DNA ligases and another that has motifs most closely related to a yeast mitochondrial helicase. Thirteen homologous regions (hrs) containing 54 repeated sequences that include 30-bp imperfect palindromes were identified. The imperfect palindromes are related to those from other baculoviruses. (C) 1999 Academic Press. C1 Oregon State Univ, Dept Microbiol, Corvallis, OR 97331 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. US Forest Serv, USDA, NE Res Stn, Forestry Sci Lab, Delaware, OH 43015 USA. RP Rohrmann, GF (reprint author), Oregon State Univ, Dept Microbiol, 220 Nash Hall, Corvallis, OR 97331 USA. EM rohrmann@bcc.orst.edu FU NIGMS NIH HHS [GM 53233C] NR 81 TC 240 Z9 277 U1 0 U2 7 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 5 PY 1999 VL 253 IS 1 BP 17 EP 34 DI 10.1006/viro.1998.9469 PG 18 WC Virology SC Virology GA 158YG UT WOS:000078144600004 PM 9887315 ER PT J AU Plonsky, I Cho, MS Oomens, AGP Blissard, G Zimmerberg, J AF Plonsky, I Cho, MS Oomens, AGP Blissard, G Zimmerberg, J TI An analysis of the role of the target membrane on the Gp64-induced fusion pore SO VIROLOGY LA English DT Article ID INFLUENZA-VIRUS HEMAGGLUTININ; GP64 ENVELOPE GLYCOPROTEIN; PLANAR BILAYER-MEMBRANES; CELL-CELL FUSION; BACULOVIRUS GP64; EXPRESSING CELLS; PROTEIN; KINETICS; EXOCYTOSIS; EVENTS AB Influenza hemagglutinin (HA) and GP64 of the baculovirus Autographa californica multicapsid nuclear polyhedrosis virus induce strikingly different initial fusion pores when mediating fusion between host cells that express these fusion proteins and target cells (Plonsky and Zimmerberg, 1996; Spruce et al., 1989, 1991; Zimmerberg el al., 1994). However, in these experiments, variations in host and target membranes confounded the analysis of the role that major components of the fusion reaction play in determining initial pore characteristics. To determine the contribution of the target cell plasma membrane to the fusion pore phenotype, we studied GP64-induced fusion of stably transfected cells (Sf9(Op1D)) to either red blood cells (RBCs) or Sf9 cells. Initial fusion pores in Sf9(Op1D)/RBC and Sf9(Op1D)/Sf9 cell pairs exhibited the same conductance, and pore flickering was not observed in either combination of cells. This indicates that the target cell determines neither the size nor the reversibility of the initial pore. However, the target cell does influence the kinetics of pore formation. The waiting time between triggering and pore appearance was shorter for Sf9(Op1D)/RBC fusion than for Sf9(Op1D)/Sf9 pairs. No correlation between pore waiting lime and conductance was found. This argues against a molecular model that assumes aggregation of the pore wall from a nonfixed number of components as the rate-limiting step in GP64 fusion pore formation. (C) 1999 Academic Press. C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Cornell Univ, Boyce Thompson Inst Plant Res, Ithaca, NY 14853 USA. RP Zimmerberg, J (reprint author), NICHHD, Lab Cellular & Mol Biophys, NIH, Bldg 10,Room 10D14,10 Ctr Dr,MSC 1855, Bethesda, MD 20892 USA. RI Blissard, Gary/H-5544-2012; OI Blissard, Gary/0000-0001-9228-567X NR 43 TC 41 Z9 43 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 5 PY 1999 VL 253 IS 1 BP 65 EP 76 DI 10.1006/viro.1998.9493 PG 12 WC Virology SC Virology GA 158YG UT WOS:000078144600008 PM 9887319 ER PT J AU Murphy, EJ Edmondson, RD Russell, DH Colles, S Schroeder, F AF Murphy, EJ Edmondson, RD Russell, DH Colles, S Schroeder, F TI Isolation and characterization of two distinct forms of liver fatty acid binding protein from the rat SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Article DE liver fatty acid binding protein; isoform; conformer; mass spectral analysis; (rat) ID ESCHERICHIA-COLI; BOVINE LIVER; NUCLEOTIDE-SEQUENCE; MIXED DISULFIDE; MESSENGER-RNA; ISOFORMS; HEART; IDENTIFICATION; MITOCHONDRIAL; PURIFICATION AB Liver fatty acid binding protein (L-FABP) appears to contain several different forms that may result from posttranslational modification or bound ligand. To further assess this possibility, L-FABP was purified from rat liver homogenate and two putative isoforms separated using a sulfonyl column, a strong cation exchange resin, Fraction I eluted at 0.2 M NaCl, had a pI of 7.59, and following a final size exclusion step contained > 98% L-FABP. Fraction II eluted at 1.0 M NaCl, bird a pI of 7.59, and following a final size exclusion step contained > 99% L-FABP. Both fractions contained approx, 0.15 moles of endogenous bound fatty acid per mole of protein, while L-FABP not subjected to the cation exchange step contained 0.75 moles of fatty acid per mole of protein. Fractions I and II had a greater proportion of saturated and monounsaturated fatty acids with a large reduction in polyunsaturated fatty acids compared to L-FABP not fractionated by cation exchange. Mass spectral analysis indicated the molecular mass of Fraction I was 14 315.02 +/- 0.35 Da and Fraction II was 14 315.86 +/- 0.34 Da. The peptide map for each fraction was determined by limited digestion of each fraction with either trypsin, Asp-N, or chymotrypsin to yield overlapping peptide fragments. Mass spectral analysis of these digests indicated the two proteins had identical amino acid fragments and that Cys(69) was reduced and there were no Asn to Asp exchanges. Hence, these two forms of L-FABP were not isoforms and were not the result of differences in bound fatty acid. It is proposed that these two distinct forms of rat L-FABP were structural conformers based on two alternative folding pathways, (C) 1999 Elsevier Science B.V. All rights reserved. C1 Texas A&M Univ, Dept Physiol & Pharmacol, College Stn, TX 77843 USA. Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Murphy, EJ (reprint author), NIA, Neurosci Lab, NIH, Bldg 10,Room 6C103, Bethesda, MD 20892 USA. EM murphye@lns.nia.nih.gov RI Russell, David/C-3618-2015 OI Russell, David/0000-0003-0830-3914 FU NIDDK NIH HHS [DK41402] NR 57 TC 39 Z9 40 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 J9 BBA-MOL CELL BIOL L JI BBA-Mol. Cell. Biol. Lipids PD JAN 4 PY 1999 VL 1436 IS 3 BP 413 EP 425 DI 10.1016/S0005-2760(98)00150-7 PG 13 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 176PA UT WOS:000079159400014 PM 9989272 ER PT J AU Kino, T Gragerov, A Kopp, JB Stauber, RH Pavlakis, GN Chrousos, GP AF Kino, T Gragerov, A Kopp, JB Stauber, RH Pavlakis, GN Chrousos, GP TI The HIV-1 virion-associated protein Vpr is a coactivator of the human glucocorticoid receptor SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE nuclear receptors; AIDS; mouse mammary tumor virus; p300/CBP; steroid receptor coactivator 1 ID IMMUNODEFICIENCY-VIRUS TYPE-1; LONG TERMINAL REPEAT; CELL-CYCLE; NUCLEAR-RECEPTOR; HISTONE ACETYLTRANSFERASE; TAT PROTEIN; ACTIVATION; BINDING; COMPLEX; TRANSACTIVATION AB The HIV-1 virion-associated accessor)I protein Vpr affects both viral replication and cellular transcription, proliferation, and differentiation. We report that Vpr enhances the activity of glucocorticoids in lymphoid and muscle-derive cell Lines by interacting directly with the glucocorticoid receptor and general transcription factors, acting as a coactivator. Vpr contains the signature motif LXXLL also present in cellular nuclear receptor coactivators, such as steroid receptor coactivator 1 and p300/CREB-binding protein, which mediates their interaction with the glucocorticoid and other nuclear hormone receptors. A mutant Vpr molecule with disruption of this coactivator signature motif lost its ability to influence transcription of glucocorticoid-responsive genes and became a dominant-negative inhibitor of Vpr, possibly by retaining its general transcription factor-binding activities. The glucocorticoid coactivator activity of Vpr may contribute to increased tissue glucocorticoid sensitivity in the absence of hypercortisolism and to the pathogenesis of AIDS. C1 NICHHD, Dev Endocrinol Branch, Sect Pediat Endocrinol, NIH, Bethesda, MD 20892 USA. NIDDKD, Metab Dis Branch, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Human Retrovirus Sect, ABL, Frederick, MD 21702 USA. RP Kino, T (reprint author), NICHHD, Dev Endocrinol Branch, Sect Pediat Endocrinol, NIH, Bldg 10,Rm 10N262,10 Ctr Dr MSC 1862, Bethesda, MD 20892 USA. OI Kopp, Jeffrey/0000-0001-9052-186X; Stauber, Roland/0000-0002-1341-4523 NR 56 TC 162 Z9 164 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JAN 4 PY 1999 VL 189 IS 1 BP 51 EP 61 DI 10.1084/jem.189.1.51 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 157TL UT WOS:000078077700005 PM 9874563 ER PT J AU Nathanson, N AF Nathanson, N TI Sustaining the investment in AIDS research SO SCIENTIST LA English DT Editorial Material ID ZIDOVUDINE TREATMENT; TRANSMISSION C1 NIH, Off AIDS Res, Bethesda, MD 20892 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Nathanson, N (reprint author), NIH, Off AIDS Res, Bldg 10, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD JAN 4 PY 1999 VL 13 IS 1 BP 9 EP 9 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 155RC UT WOS:000077959300012 ER PT J AU Duncan, WC Johnson, KA Wehr, TA AF Duncan, WC Johnson, KA Wehr, TA TI 5-HT agonist-induced phase-advances of the circadian pacemaker are diminished by chronic antidepressant drug treatment SO BRAIN RESEARCH LA English DT Article DE 5-HT; 8-OH-DPAT; suprachiasmatic nucleus; 5-HT1A receptor; 5-HT7 receptor ID SUPRACHIASMATIC NUCLEUS NEURONS; WHEEL-RUNNING ACTIVITY; SYRIAN-HAMSTERS; NEUROPEPTIDE-Y; SEROTONERGIC AGONISTS; CLORGYLINE TREATMENT; RECEPTOR AGONISTS; ANTI-DEPRESSANTS; RAT; RHYTHMS AB Serotonin (5-HT) and its agonists alter the timing of the circadian pacemaker. Previous research has shown that when they are injected 4 h before or after the onset of wheel-running, they phase-advance or delay, respectively, the timing of the pacemaker. Because serotonergic interventions alter 5-HT receptor number in the hypothalamus, we asked whether chronic treatment with an antidepressant drug (AD) that modifies serotonergic function could alter the phase-shifting effects of the 5-HT agonist 8-hydroxydipropylaminotetralin (8-OH-DPAT). Hamsters were treated chronically with the monoamine oxidase inhibitor (MAOI), clorgyline, and then injected with 8-OH-DPAT or vehicle (VEH) either 4 h before or after the onset of wheel-running. MAOI treatment decreased the magnitude of both 8-OH-DPAT- and VEH-induced phase advances, but not the magnitude of 8-OH-DPAT-induced phase-delays. The results indicate that 8-OH-DPAT-induced phase-advances and delays are functionally distinct with regard to adaptive changes during chronic AD treatment. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NIMH, Sect Biol Rhythms, NIH, Bethesda, MD 20892 USA. RP Duncan, WC (reprint author), NIMH, Sect Biol Rhythms, NIH, Bethesda, MD 20892 USA. NR 38 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 2 PY 1999 VL 815 IS 1 BP 126 EP 130 DI 10.1016/S0006-8993(98)01057-9 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 153RM UT WOS:000077846400017 PM 9974132 ER PT J AU Bonassi, S Fontana, V Ceppi, M Barale, R Biggeri, A AF Bonassi, S Fontana, V Ceppi, M Barale, R Biggeri, A TI Analysis of correlated data in human biomonitoring studies. The case of high sister chromatid exchange frequency cells SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE SCE; high frequency cell; correlated data analysis; random-effects model ID REGRESSION-ANALYSIS; SCE ANALYSIS; POPULATION; LYMPHOCYTES; POLLUTANTS; HFCS AB Sister chromatid exchange (SCE) analysis in peripheral blood lymphocytes is a well established technique that aims to evaluate human exposure to toxic agents. The individual mean value of SCE per cell had been the only recommended index to measure the extent of this cytogenetic damage until the early 1980's, when the concept of high frequency cells (HFC) was introduced to increase the sensitivity of the assay. All statistical analyses proposed thus far to handle these data are based on measures which refer to the individual mean values and not to the single cell. Although this approach allows the use of simple statistical methods, part of the information provided by the distribution of SCE per single cell within the individual is lost. Using the appropriate methods developed for the analysis of correlated data, it is possible to exploit all the available information. In particular, the use of random-effects models seems to be very promising for the analysis of clustered binary data such as HFC. Logistic normal random-effects models, which allow modelling of the correlation among cells within individuals, have been applied to data from a large study population to highlight the advantages of using this methodology in human biomonitoring studies. The inclusion of random-effects terms in a regression model could explain a significant amount of variability, and accordingly change point and/or interval estimates of the corresponding coefficients. Examples of coefficients that change across different regression models and their interpretation are discussed in detail. One model that seems particularly appropriate is the random intercepts and random slopes model. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Natl Canc Inst, Dept Environm Epidemiol & Biostat, I-16132 Genoa, Italy. Univ Pisa, Dipartimento Sci Uomo & Ambiente, I-56100 Pisa, Italy. Univ Florence, Dept Stat G Parenti, I-50134 Florence, Italy. RP Bonassi, S (reprint author), Natl Canc Inst, Dept Environm Epidemiol & Biostat, Largo Rosanna Benzi 10, I-16132 Genoa, Italy. EM bonassi@hp380.ist.unige.it OI BARALE, Roberto/0000-0003-4161-2241; bonassi, stefano/0000-0003-3833-6717 NR 28 TC 34 Z9 35 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD JAN 2 PY 1999 VL 438 IS 1 BP 13 EP 21 DI 10.1016/S1383-5718(98)00153-3 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 159AQ UT WOS:000078150000002 PM 9858669 ER PT B AU Walker, FL Thoma, GR AF Walker, FL Thoma, GR BE Nixon, C Dengler, H TI Java-assisted Internet document delivery SO 14TH ANNUAL COMPUTERS IN LIBRARIES '99 PROCEEDINGS: IN COOPERATION WITH THE SPECIAL LIBRARIES ASSOCIATION LA English DT Proceedings Paper CT 14th Annual Conference on Computers in Libraries CY MAR 08-10, 1999 CL ARLINGTON, VA SP Informat Today Inc DE Java; Internet; HotMed; MedJava; document delivery; email; MIME; Ariel; DocView; World Wide Web; interlibrary loan AB An increasing number of libraries are using the Internet for document delivery, not only for interlibrary loan, but for delivering documents directly to the patron's desktop computer. This has been made possible through the widespread adoption of software such as Ariel and DocView. Ariel, a product of the Research Libraries Group, converts paper-based documents to bitmapped images, and delivers them over the Internet. The National Library of Medicine's DocView, released in January 1998 and now used by 2,000 people in over 70 countries, is primarily designed for library patrons to receive, display and manage documents received fr-om Ariel systems. Despite the relative effectiveness of such technologies, Internet document delivery to the patron's desktop remains a challenge to document delivery librarians for several reasons. First, the librarian may need to assist patrons in acquiring document-viewing software, and in helping them install it on a wide variety of computer platforms. The librarian may also need to help patrons upgrade their viewing software as new versions are released. Because a heterogeneous patron population may be expected to have a diverse range of computer skills, the document delivery librarian may indeed face the challenge of training this population in using the document viewing software. As if this were not enough, the potential problem of copyright abuse always exists when copyrighted material is distributed electronically. How does a library cope with the potential problems introduced with Internet document delivery to the patron's desktop? One potential solution to this dilemma is Java-assisted document delivery. The National Library of Medicine's Lister Hill National Center for Biomedical Communications is developing software code-named HotMed and MedJava, which provide a method of delivering library documents through the World Wide Web by using a Java applet. While HotMed is software that delivers multimedia information over the Internet, MedJava is a Java software applet that HotMed delivers with scanned documents. MedJava enables the recipient to view the documents using a Java-enabled web browser. This paper describes the prototype HotMed and MedJava software, and shows how they can significantly reduce or eliminate the problems described here that libraries face in adopting Internet document delivery to the patron's desktop. C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU INFORMATION TODAY INC PI MEDFORD PA 143 OLD MARLTON PIKE, MEDFORD, NJ 08055 USA BN 1-57387-077-3 PY 1999 BP 181 EP 190 PG 10 WC Information Science & Library Science SC Information Science & Library Science GA BP68L UT WOS:000085856800041 ER PT S AU Smith, MF AF Smith, MF GP IEEE IEEE IEEE TI The effect of contraction and twist on myocardial PET and SPECT image resolution: A mathematical phantom study SO 1999 IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD, VOLS 1-3 SE IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD LA English DT Proceedings Paper CT 1999 IEEE Nuclear Science Symposium and Medical Imaging Conference CY OCT 24-30, 1999 CL SEATTLE, WA SP IEEE, Nucl & Plasma Sci Soc, Argonne Natl Labs, Bicron Inc, Brookhaven Natl Lab, CTI PET Syst Inc, Ernest Orlando Lawrence Berkeley Natl Lab, Fermi Natl Accelerator Lab, GE Med Syst, INFN Sezione Ferrara Italy, Lawrence Livermore Natl Lab, Los Alamos Natl Lab, NASA, Natl Inst Stand & Technol, Oak Ridge Natl Lab, Picker Int, Sandia Natl Labs, Stanford Linear Accelerator Ctr, Univ Calif Irvine, Univ Washington, Seattle, Univ Ferrara Italy, Univ Utah, US DOE ID EMISSION COMPUTED-TOMOGRAPHY; MOTION; HEART AB Motion of the heart degrades cardiac PET and SPECT resolution. A mathematical phantom was constructed to model contractile and non-uniform twisting motions of the left ventricular myocardium as the heart beats. The phantom was used to estimate the effect of motion on cardiac ECT image resolution and on quantitation in regions of interest (ROIs). Cardiac motion with contraction and twist was simulated at 16 time gates. The movement of mid-myocardial points was tracked, from which motion blur was computed. Contractile motion was greater near the base and twisting motion was greater near the apex. The blur due to both motions was equivalent to 7-9 mm FWHM Gaussian smoothing. Clinical PET resolution of 7 mm was degraded to 10-11 mm FWHM and clinical SPECT resolution of 14 mm to 16-17 mm FWHM. Weighting coefficients were used to characterize how activity in short and long axis ROIs was related to activity in source model ROIs. The effect of contraction was dependent on whether short or long axis slices were used for ROIs and on the spatial location of the ROIs. The weights for short axis ROIs showed the effect of twist in blurring activity to adjacent angular sectors. This effect was not seen in long axis ROIs where the angular range encompassed by the constant thickness slices was greater. A mathematical heart phantom that models contractile and twisting motions is valuable for investigating the effect of these motions on cardiac ECT studies. C1 NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. RP Smith, MF (reprint author), NIH, Dept Nucl Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 0-7803-5697-7 J9 IEEE NUCL SCI CONF R PY 1999 BP 1255 EP 1259 PG 3 WC Engineering, Electrical & Electronic; Instruments & Instrumentation; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Instruments & Instrumentation; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA BQ74H UT WOS:000089372200258 ER PT S AU Vaquero, JJ Sassaman, MB Lang, L Seidel, J Lee, I Gandler, WR Green, MV AF Vaquero, JJ Sassaman, MB Lang, L Seidel, J Lee, I Gandler, WR Green, MV GP IEEE IEEE IEEE TI Positron projection imaging of radiopharmaceutical transport through a multi-compartment model SO 1999 IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD, VOLS 1-3 SE IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD LA English DT Proceedings Paper CT 1999 IEEE Nuclear Science Symposium and Medical Imaging Conference CY OCT 24-30, 1999 CL SEATTLE, WA SP IEEE, Nucl & Plasma Sci Soc, Argonne Natl Labs, Bicron Inc, Brookhaven Natl Lab, CTI PET Syst Inc, Ernest Orlando Lawrence Berkeley Natl Lab, Fermi Natl Accelerator Lab, GE Med Syst, INFN Sezione Ferrara Italy, Lawrence Livermore Natl Lab, Los Alamos Natl Lab, NASA, Natl Inst Stand & Technol, Oak Ridge Natl Lab, Picker Int, Sandia Natl Labs, Stanford Linear Accelerator Ctr, Univ Calif Irvine, Univ Washington, Seattle, Univ Ferrara Italy, Univ Utah, US DOE AB Estimation of the kinetic properties of radiopharmaceuticals from equilibrium data is uncertain. This situation might be improved if the kinetic transport of the compound could be visualized directly. We explored this possibility by constructing a physical device, an "H-cell", that by chemical means was made to exhibit three spatially distinct compartments. Transport of a positron-labeled compound across the interfaces and through these compartments was visualized by dynamic positron projection imaging. Results obtained in these initial experiments suggest this technique may yield useful information about tracer kinetics. C1 NIH, Dept Nucl Med, Bethesda, MD 20892 USA. RP Vaquero, JJ (reprint author), NIH, Dept Nucl Med, Bethesda, MD 20892 USA. RI Vaquero, Juan Jose/D-3033-2009 OI Vaquero, Juan Jose/0000-0001-9200-361X NR 6 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 0-7803-5697-7 J9 IEEE NUCL SCI CONF R PY 1999 BP 1337 EP 1338 PG 2 WC Engineering, Electrical & Electronic; Instruments & Instrumentation; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Instruments & Instrumentation; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA BQ74H UT WOS:000089372200276 ER PT S AU Seidel, J Vaquero, JJ Barbosa, F Lee, I Cuevas, C Gandler, WR Green, MV AF Seidel, J Vaquero, JJ Barbosa, F Lee, I Cuevas, C Gandler, WR Green, MV GP IEEE IEEE IEEE TI Performance characteristics of position-sensitive photomultiplier tubes combined through common X and Y resistive charge dividers SO 1999 IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD, VOLS 1-3 SE IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD LA English DT Proceedings Paper CT 1999 IEEE Nuclear Science Symposium and Medical Imaging Conference CY OCT 24-30, 1999 CL SEATTLE, WA SP IEEE, Nucl & Plasma Sci Soc, Argonne Natl Labs, Bicron Inc, Brookhaven Natl Lab, CTI PET Syst Inc, Ernest Orlando Lawrence Berkeley Natl Lab, Fermi Natl Accelerator Lab, GE Med Syst, INFN Sezione Ferrara Italy, Lawrence Livermore Natl Lab, Los Alamos Natl Lab, NASA, Natl Inst Stand & Technol, Oak Ridge Natl Lab, Picker Int, Sandia Natl Labs, Stanford Linear Accelerator Ctr, Univ Calif Irvine, Univ Washington, Seattle, Univ Ferrara Italy, Univ Utah, US DOE AB Combining signal channels from detector arrays can improve event throughput and minimize cost but, potentially, at the expense of other performance parameters. In this work, we evaluated a method to reduce signal number by combining the anode outputs of up to three position-sensitive photomultiplier tubes (PSPMTs) through a common X and a common Y resistive charge divider. Field flood images of these combined modules were compared to those obtained with independent detectors illuminated individually. No significant reduction in position detection accuracy was observed at low count rates when up to three tubes were combined. Event mis-positioning was also minimal for total count rates < 100,000 cps. At higher rates, pulse pileup degraded accuracy. These results suggest that this method of combining PSPMTs may be useful in reducing signal number while maintaining good event localization at reasonable count rates. C1 NIH, Bethesda, MD 20892 USA. RP Seidel, J (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. RI Vaquero, Juan Jose/D-3033-2009 OI Vaquero, Juan Jose/0000-0001-9200-361X NR 2 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 0-7803-5697-7 J9 IEEE NUCL SCI CONF R PY 1999 BP 1488 EP 1489 PG 2 WC Engineering, Electrical & Electronic; Instruments & Instrumentation; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Instruments & Instrumentation; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA BQ74H UT WOS:000089372200308 ER PT S AU Riddell, C Bacharach, SL AF Riddell, C Bacharach, SL GP IEEE IEEE IEEE TI Variable scale reprojection for iterative reconstruction: Application to PET reconstruction with OSEM SO 1999 IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD, VOLS 1-3 SE IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD LA English DT Proceedings Paper CT 1999 IEEE Nuclear Science Symposium and Medical Imaging Conference CY OCT 24-30, 1999 CL SEATTLE, WA SP IEEE, Nucl & Plasma Sci Soc, Argonne Natl Labs, Bicron Inc, Brookhaven Natl Lab, CTI PET Syst Inc, Ernest Orlando Lawrence Berkeley Natl Lab, Fermi Natl Accelerator Lab, GE Med Syst, INFN Sezione Ferrara Italy, Lawrence Livermore Natl Lab, Los Alamos Natl Lab, NASA, Natl Inst Stand & Technol, Oak Ridge Natl Lab, Picker Int, Sandia Natl Labs, Stanford Linear Accelerator Ctr, Univ Calif Irvine, Univ Washington, Seattle, Univ Ferrara Italy, Univ Utah, US DOE ID COMPUTED-TOMOGRAPHY; ORDERED SUBSETS; ALGORITHMS; PROJECTION; ROTATION; IMAGES AB Iterative reconstruction algorithms require the repetitive application of reprojection and backprojection operations. Reprojection of an image at angle theta can be decomposed into rotating the image by angle theta and summing it at angle 0. In the following paper, we show that this "rotate & sum" (RS) technique can be reduced to applying one-dimensional translations of the image rows, followed by an interpolation-free summation of the image columns. This sequence actually yields the proper reprojection magnified by a factor that depends on the angle. By pre-processing the data to match this angular variation in scale, most iterative reconstructions can be performed with this variable scale reprojection scheme (VS). The main routine is a "translate and sum" function that accesses the memory row by row. The OSEM algorithm was implemented with the VS, the RS and the line-length model, and OSEM reconstructions were performed on real PET data. The VS scheme was demonstrated to be significantly faster than RS and twice as fast as LL, without compromising image quality, and even slightly improving it. C1 NIH, Bethesda, MD 20892 USA. RP Riddell, C (reprint author), NIH, Bldg 10 Room 1C401, Bethesda, MD 20892 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 0-7803-5697-7 J9 IEEE NUCL SCI CONF R PY 1999 BP 1647 EP 1651 PG 5 WC Engineering, Electrical & Electronic; Instruments & Instrumentation; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Instruments & Instrumentation; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA BQ74H UT WOS:000089372200342 ER PT S AU Cannata, JM Zhao, JZ Ayyappan, S Ritter, TA Chen, W Shung, KK AF Cannata, JM Zhao, JZ Ayyappan, S Ritter, TA Chen, W Shung, KK BE Schneider, SC Levy, M McAvoy, BR TI Fabrication of high frequency (25-75 MHz) single element ultrasonic transducers SO 1999 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1 AND 2 SE ULTRASONICS SYMPOSIUM LA English DT Proceedings Paper CT 1999 IEEE Ultrasonics International Symposium CY OCT 17-20, 1999 CL TAHOE, NV SP IEEE Ultrason Ferroelect & Frequency Control Soc AB The design and fabrication of high frequency single element ultrasonic transducers present a multitude of challenges for the transducer engineer, from size constraints to electrical impedance matching. This paper discusses the trade-offs involved in procedures used to fabricate lithium niobate (LiNbO3) and lead titanate (PbTiO3) transducers in the 25MHz to 75MHz range. Transducers of varying dimensions were built according to an f-number range of 2-3.5. Desired focal depths were achieved with use of either an acoustic lens or a spherically focused piezoceramic. Silver epoxy backing with an acoustic impedance of approximately 5.9 MRayls was used in all designs. All transducers were designed around a 50 Omega send and receive circuit. Electrical tuning of the transducer to the receive circuitry was achieved by using an RF transformer and/or a length of coaxial cable. All transducers were tested in a pulse-echo arrangement using a Panametrics 5900PR pulser, a Wavetek function generator and a LeCroy digital oscilloscope. The bandwidth, insertion loss, and depth of focus were measured. Numerous transducers were fabricated with -6dB bandwidths ranging from 40% to 74%, and two-way insertion loss values ranging from -14dB to -28dB. C1 Penn State Univ Bioengn, NIH, Resource Ctr Med Ultrason Transducer Engn, University Pk, PA 16802 USA. RP Cannata, JM (reprint author), Penn State Univ Bioengn, NIH, Resource Ctr Med Ultrason Transducer Engn, 205 Hallowell Bldg, University Pk, PA 16802 USA. NR 6 TC 0 Z9 1 U1 2 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1051-0117 BN 0-7803-5723-X J9 ULTRASON PY 1999 BP 1099 EP 1103 PG 5 WC Acoustics; Instruments & Instrumentation; Physics, Applied SC Acoustics; Instruments & Instrumentation; Physics GA BQ43A UT WOS:000088356000236 ER PT S AU Ritter, TA Shung, KK Tutwiler, RL Shrout, TR AF Ritter, TA Shung, KK Tutwiler, RL Shrout, TR BE Schneider, SC Levy, M McAvoy, BR TI Medical imaging arrays for frequencies above 25 MHz SO 1999 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1 AND 2 SE Ultrasonics Symposium LA English DT Proceedings Paper CT 1999 IEEE Ultrasonics International Symposium CY OCT 17-20, 1999 CL TAHOE, NV SP IEEE Ultrason Ferroelect & Frequency Control Soc ID TRANSDUCER AB A fabrication method has been developed for composite linear arrays operating at a frequency of 30 MHz. The design features dual matching layers, a lens for focusing in the elevation direction, a 2-2 composite with 28 mu m wide ceramics and 5.3 mu m polymer widths, and coaxial cable for electrical impedance matching. Bandwidths exceeding 65% and crosstalk values less than -30dB were measured on prototype arrays. A non-composite 35 MHz design has also been investigated. An interconnect method using a flex circuit and sputtered metal has been tested. Properties were then measured by fitting experimental impedance data to a model using a non-linear regression technique. A k(33)' of 0.63 and an epsilon(33)(S)/epsilon(0) Of 1310 were measured for array elements operating at 35 MHz. C1 Penn State Univ, Bioengn Program, Res Ctr Med Ultrason Transducer Technol, NIH, University Pk, PA 16802 USA. RP Ritter, TA (reprint author), Penn State Univ, Bioengn Program, Res Ctr Med Ultrason Transducer Technol, NIH, 205 Hallowell Bldg, University Pk, PA 16802 USA. NR 18 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1051-0117 BN 0-7803-5722-1 J9 ULTRASON PY 1999 BP 1203 EP 1207 PG 5 WC Acoustics; Instruments & Instrumentation; Physics, Applied SC Acoustics; Instruments & Instrumentation; Physics GA BQ43A UT WOS:000088356000258 ER PT B AU Zhou, J Ng, ST Adesanya, OO Bondy, CA AF Zhou, J Ng, ST Adesanya, OO Bondy, CA BE IoannidouMousaka, L Agnantis, NJ Lopez, DM TI GH, IGF1 and mammary epithelial hyperplasia SO 22ND CONGRESS OF THE INTERNATIONAL ASSOCIATION FOR BREAST CANCER RESEARCH LA English DT Proceedings Paper CT 22nd Congress of the International-Association-for-Breast-Cancer-Research CY SEP 25-28, 1998 CL ATHENS, GREECE SP Int Assoc Breast Canc Res ID GROWTH FACTOR-I; BREAST-CANCER; HORMONE; GLAND C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Zhou, J (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-323-0925-4 PY 1999 BP 25 EP 29 PG 5 WC Oncology; Immunology; Medicine, Research & Experimental; Obstetrics & Gynecology; Pathology SC Oncology; Immunology; Research & Experimental Medicine; Obstetrics & Gynecology; Pathology GA BM89Z UT WOS:000080058900003 ER PT B AU Hussain, SP Ambs, S Harris, CC AF Hussain, SP Ambs, S Harris, CC BE Beger, HG Link, KH TI Cancer-prone oxyradical overload disease SO 2ND INTERNATIONAL CONGRESS ON GASTROENTEROLOGICAL CARCINOGENESIS LA English DT Proceedings Paper CT 2nd International Congress on Gastroenterological Carcinogenesis (ICGC) CY MAR 25-27, 1999 CL ULM, GERMANY ID NITRIC-OXIDE SYNTHASE; ENDOTHELIAL GROWTH-FACTOR; TUMOR-SUPPRESSOR GENE; HEPATITIS-B-VIRUS; INDUCED APOPTOSIS; HEPATOCELLULAR-CARCINOMA; MOUSE THYMOCYTES; MESSENGER-RNA; COLON-CANCER; IN-VIVO AB Chronic inflammation and the generation of reactive oxygen and nitrogen species have been linked with an increased risk of cancer. Oxyradical damage can cause cell death, regeneration and mutations in cancer related genes. Cancer-prone oxyradical overload disease, associated with chronic inflammation, shows a diverse etiology that may be either inherited, as in hemochromatosis and Wilsons disease, acquired, e.g., infection with hepatitis B or C virus in hepatitis and helicobactor pylorus in gastritis, or chemically induced, e.g., aid reflex in Barrett's esophagus. The alteration of the p53 tumor suppressor gene by mutations is significant in human carcinogenesis. Although a number of different exogenous carcinogens have been shown to selectively target p53, evidence supporting the endogenous insult of p53 is starting to accumulate. In this short review we will discuss the interactive effects of nitric oxide and the p53 tumor suppressor gene in colon carcinogenesis. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Hussain, SP (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. NR 71 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-323-0325-6 PY 1999 BP 9 EP 20 PG 12 WC Oncology; Gastroenterology & Hepatology SC Oncology; Gastroenterology & Hepatology GA BN43W UT WOS:000081930200002 ER PT B AU Schlessinger, D Nagaraja, R Waeltz, P Ko, M Mumm, S Pilia, G Cao, A Forabosco, A AF Schlessinger, D Nagaraja, R Waeltz, P Ko, M Mumm, S Pilia, G Cao, A Forabosco, A BE Cosmi, EV TI Premature ovarian failure: the Xq critical region and a functional genomic approach to ovarian development SO 2ND INTERNATIONAL CONGRESS ON NEW TECHNOLOGIES IN REPRODUCTIVE MEDICINE, NEONATOLOGY AND GYNECOLOGY LA English DT Proceedings Paper CT 2nd International Congress on New Technologies in Reproductive Medicine, Neonatology and Gynecology CY SEP 18-23, 1999 CL PORTO CONTE, ITALY SP Mediterranean Soc Human Reproduct & Neonatol, World Federat Scientists, European World Assoc Perinatal Med, Asia Oceania Federat Perinatal Med, Int Assoc Study Lung Srfactant Syst, Soc Investigat Early Pregnancy, New York Univ Med Sch, UMD New Jersey Med Sch, Univ Sassari, Univ Perugia, Univ La Sapienza AB Primary premature ovarian failure (PPOF) prevents or curtails female reproductive life. In contrast to a single locus identified on chromosome 3 (Pilia et al., this volume), many X/autosomal translocations are linked to PPOF. It has remained a puzzle whether these results indicate that there is a concentration of X-linked genes involved in follicle development or stability, or whether PPOF may also result from a failure of interactions that involve DNA regions during follicle development. To answer this question, we have taken two approaches: 1) the Xq critical region has been defined by mapping breakpoints of translocation. The analysis of breakpoints and the nearest genes is ongoing. 2) In a functional genomic approach, we have made a library of cDNAs from new-born mouse ovary, and have begun the systematic analysis of component cDNAs, including species unique to ovary and related tissues. C1 NIA, Genet Lab, Baltimore, MD 21224 USA. RP Schlessinger, D (reprint author), NIA, Genet Lab, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-323-0918-1 PY 1999 BP 287 EP 291 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA BQ50M UT WOS:000088538900038 ER PT B AU Kim, SJ Yang, HK Im, YH Bang, YJ Yang, HK AF Kim, SJ Yang, HK Im, YH Bang, YJ Yang, HK BE Kim, JP TI Mechanisms of TGF-beta receptor inactivation and development of resistance to TGF-beta in human gastric cancer SO 3RD INTERNATIONAL GASTRIC CANCER CONGRESS LA English DT Proceedings Paper CT 3rd International Gastric Cancer Congress CY APR 27-30, 1999 CL SEOUL, SOUTH KOREA SP Int Gastr Canc Assoc ID II RECEPTOR; MICROSATELLITE INSTABILITY; GROWTH-INHIBITION; DNA METHYLATION; CARCINOMA-CELLS; EXPRESSION; GENE; COLON; SENSITIVITY; MUTATION AB The majority of human gastric cancer cell lines have escaped from negative regulation by TGF-beta. Resistance of the majority of gastric cancer cell lines to the growth inhibitory effects of TGF-beta correlates with gross structural defects of the TGF-beta type II receptor (RII) gene in human gastric cancer cell lines. Two human gastric cancer cell lines, SNU-601 and SNU-719, display abnormal amplification of the structural gene, and two cell lines, SNU-5 and SNU-668, express truncated TGF-beta RII transcripts. Also, the genomic sequence of TGF-beta RII is truncated after exon 2 in SNU-5 and after exon 3 in SNU-668. TGF-beta RII gene mutations within a 10-bp polyadenine repeat present in the TGF-beta RII-coding region are also commonly present in gastric cancer associated with DNA microsatellite instability, a phenotypic marker for defective DNA RER (RER+). SNU-1 and SNU-638 cell lines were determined to be RER+ and to bear TGF-beta RII mutations. A subset of human gastric cancer cell lines is resistant to TGF-beta and locks TGF-beta RII mRNA expression despite evidence of a normal gene, suggesting that transcriptional repression may play an important role in controlling TGF-beta RII expression. We demonstrated that there is a strong correlation between expression patterns of TGF-beta RII mRNA and an epithelial specific ets-related transcription factor, ERT. Recently, we have identified a subset of human gastric cancer cell lines which is insensitive to TGF-beta and which expresses a low level of TGF-beta type I receptor mRNA. We show that hypermethylation of a CpG island in the 5'region of the TGF-beta RI gene provides another potentially important mechanism of escape from negative growth control by TGF-beta. C1 Natl Canc Inst, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Kim, SJ (reprint author), Natl Canc Inst, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-323-0504-6 PY 1999 BP 81 EP 90 PG 10 WC Oncology; Gastroenterology & Hepatology; Pathology; Surgery SC Oncology; Gastroenterology & Hepatology; Pathology; Surgery GA BM89J UT WOS:000080048900012 ER PT B AU Trimble, EL AF Trimble, EL BE Pecorelli, S Atlante, G Panici, RB Mancuso, S TI Clinical trials in ovarian cancer: are we doing our best? SO 7TH BIENNIAL MEETING OF THE INTERNATIONAL GYNECOLOGIC CANCER SOCIETY LA English DT Proceedings Paper CT 7th Biennial Meeting of the International-Gynecologic-Cancer-Society CY SEP 26-30, 1999 CL ROME, ITALY SP Int Gynecol Canc Soc C1 NCI, Bethesda, MD 20892 USA. RP Trimble, EL (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-323-0926-2 PY 1999 BP 31 EP 32 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA BN95N UT WOS:000083638300004 ER PT J AU Collins, FS Bochm, K AF Collins, FS Bochm, K TI Avoiding casualties in the genetic revolution: The urgent need to educate physicians about genetics SO ACADEMIC MEDICINE LA English DT Editorial Material C1 Natl Human Genome Res Inst, NIH, Bethesda, MD USA. Natl Human Genome Res Inst, Off Policy Coordinat, Bethesda, MD USA. RP Collins, FS (reprint author), Natl Human Genome Res Inst, NIH, Bethesda, MD USA. NR 0 TC 17 Z9 17 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JAN PY 1999 VL 74 IS 1 BP 48 EP 49 DI 10.1097/00001888-199901000-00017 PG 2 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 157PK UT WOS:000078070700021 PM 9934295 ER PT J AU Lopaczynski, W AF Lopaczynski, W TI Differential regulation of signaling pathways for insulin and insulin-like growth factor I SO ACTA BIOCHIMICA POLONICA LA English DT Article DE insulin; IGF-I; receptor structure; signal transduction; tyrosine phosphorylation ID TYROSINE KINASE-ACTIVITY; FIRST 3 DOMAINS; HYBRID RECEPTORS; CRYSTAL-STRUCTURE; 14-3-3 PROTEIN; C-ELEGANS; BINDING; IDENTIFICATION; DETERMINANTS; 14-3-3-PROTEINS AB The insulin receptor CIR) and the insulin-like growth factor receptor I (IGF-IR) have different functions in cell growth, apoptosis, differentiation, and transformation. Although some of these differences may be explained by the relative level of receptor expression and receptor structure (alpha and beta subunits), they may also be attributed to differences in intracellular signals generated by insulin and IGF-I. The presence of hybrid receptors (IR alpha beta subunits and IGF-IR alpha beta subunits) making up the heterotetramers has added a new dimension to our understanding of the functional roles of these receptors. However, to date the results of efforts to understand the differences between these two closely related receptors have indicated mostly similarities. For example, both receptors utilize IRS-1/IRS-2 and Shc as immediate downstream adaptors, leading to activation of the Ras, Raf, ERK kinases and PI-3 kinase pathways. We have used the yeast two hybrid system to identify proteins which bind to the activated IGF-IR but not to the IR. The cytoplasmic domain of the IGF-IR was used to screen a human fetal brain library and two isoforms of the 14-3-3 family were identified. 14-3-3 proteins are a highly conserved family of proteins which have recently been shown to interact with other components of the mitogenic and apoptotic signaling pathways, including Raf, BAD, Bcr/Bcr-Abl, middle-T antigen, Ksr, PKC, PI-3 ki-nase, ASK1 kinase, and cdc25C phosphatase. We also identified human Grb10, an adaptor protein with SH2 domain associated with the IGF-IR beta subunit. Smith's laboratory showed that Grb10 preferentially binds to the IR in intact cells. Using the interaction trap screen (active cytoplasmic domain of the IGF-IR) 55PIK and SOCS-2 proteins were also identified. However, 55PIK and SOCS-2 also interact with the IR in the yeast two hybrid system. These studies raise the possibility that 14-3-3 and Grb10 may play a role in insulin and IGF-I signal transduction suid may underlie the observed differences. C1 NCI, Endocrinol Sect, Metab Branch, Bethesda, MD 20892 USA. RP Lopaczynski, W (reprint author), NCI, Endocrinol Sect, Metab Branch, Bethesda, MD 20892 USA. EM WLX@CU.NIH.GOV NR 52 TC 24 Z9 25 U1 1 U2 6 PU ACTA BIOCHIMICA POLONICA PI WARSAW PA PASTEURA 3, 02-093 WARSAW, POLAND SN 0001-527X J9 ACTA BIOCHIM POL JI Acta Biochim. Pol. PY 1999 VL 46 IS 1 BP 51 EP 60 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 182ZU UT WOS:000079528700005 PM 10453981 ER PT J AU Lopaczynski, W Terry, C AF Lopaczynski, W Terry, C TI Insulin-like growth factor I activates insulin receptor substrate 1 and Ras in human osteosarcoma cells SO ACTA BIOCHIMICA POLONICA LA English DT Article DE IGF-I receptor; tyrosine phosphorylation; IRS-1; Ras; c-Jun; MG-63 ID PHOSPHORYLATION; IRS-1; PROTEINS; KINASES; TYROSINE; PATHWAYS; SARCOMA; MITOGEN; SIGNALS; CANCER AB Insulin-like growth factor I (IGF-I) stimulates multiplication of the human osteosarcoma cell line, MG-63, by acting through IGF-I receptor. We have characterized IGF-I stimulated phosphorylation of IRS-1, activation of Ras cycle and phosphorylation of c-Jun in this cell line. Serum starved MG-63 cells were (1) IGF-I stimulated and lysates were immunoprecipitated with polyclonal IRS-1 antibody or (2) metabolically labeled with [P-32]orthophosphoric acid and then cells were treated with IGF-I. Cell lysates were immunoprecipitated with p21Ras antibody (Y13-259) and bound nucleotides were analysed by thin-layer chromatography. We demonstrated tyrosine phosphorylation of IRS-1/2 immunoprecipitated from MG-63 cells stimulated with IGF-I. We also showed an increased level of GTP in p21Ras immunoprecipitates from IGF-I treated cells. Nuclear extracts prepared from P-32-labeled cells before and after addition of IGF-I were immunoprecipitated with c-Jun antibody. After electrophoresis and autoradiography, phosphorylation of the c-Jun band was seen to be IGF-I independent. Phosphoamino acid analysis of the c-Jun band showed that phosphoserine was the major species. C1 NCI, Endocrinol Sect, Metab Branch, Bethesda, MD 20892 USA. RP Lopaczynski, W (reprint author), NCI, Endocrinol Sect, Metab Branch, Bethesda, MD 20892 USA. NR 27 TC 2 Z9 3 U1 0 U2 1 PU ACTA BIOCHIMICA POLONICA PI WARSAW PA PASTEURA 3, 02-093 WARSAW, POLAND SN 0001-527X J9 ACTA BIOCHIM POL JI Acta Biochim. Pol. PY 1999 VL 46 IS 1 BP 117 EP 123 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 182ZU UT WOS:000079528700011 PM 10453987 ER PT J AU Lubkowski, J Wlodawer, A AF Lubkowski, J Wlodawer, A TI Decamers observed in the crystals of bovine pancreatic trypsin inhibitor SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article AB The structure of bovine pancreatic trypsin inhibitor (BPTI) has been solved at 2.1 Angstrom resolution in a new crystal form (space group P6(4)22 with unit-cell dimensions a = b = 95.0, c = 158.1 Angstrom). The asymmetric unit is a pentamer, but a decamer is created by application of crystallographic symmetry. The decamer of BPTI is only the fourth such assembly reported to date in the Protein Data Bank. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Macromol Struct Lab, Frederick, MD 21702 USA. RP Lubkowski, J (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Macromol Struct Lab, Frederick, MD 21702 USA. NR 17 TC 11 Z9 11 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD JAN PY 1999 VL 55 BP 335 EP 337 DI 10.1107/S0907444998011068 PN 1 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 161XB UT WOS:000078314000058 PM 10089443 ER PT J AU Huang, SZ Zeng, FY Chen, MJ Ren, ZR Shen, M Rodgers, GP Schechter, AN Zeng, YT AF Huang, SZ Zeng, FY Chen, MJ Ren, ZR Shen, M Rodgers, GP Schechter, AN Zeng, YT TI The delta-globin RNA transcript level in beta-thalassemia carriers SO ACTA HAEMATOLOGICA LA English DT Article DE delta-globin gene; HbA(2); heterozygote; mRNA; beta-thalassemia ID MESSENGER-RNA; MUTATIONS; HETEROZYGOTES; C->T; GENE; DNA AB Increased levels of hemoglobin A(2) (HbA(2)) are present in most beta-thalassemia carriers. The mechanism of this effect is not understood, although the increase may result from transcriptional and posttranscriptional changes. In the present study, we quantitate delta-globin mRNA levels in peripheral-blood-enriched reticulocytes and characterize the variation of delta-mRNA levels in 30 beta-thalassemia heterozygotes who individually carry one of the four common Chinese beta-thalassemia alleles [codons 41/42 (-TTCT); codon 17 (A-->T); IVS-II-654 (C-->T); -28 (A-->G)]. A sensitive and quantitative competitive reverse-transcriptase polymerase chain reaction method was developed and used to assess the absolute amounts of delta-mRNA transcripts in these peripheral erythroid cells. The results showed a large increase in delta-mRNA amounts in all the carriers examined (72.3 +/- 9.0 amol/mu g RNA) as compared with those in 12 controls (1.2 +/- 0.2 amol/mu g RNA). There was a direct correlation between the delta-mRNA levels and types of beta-thalassemia alleles; generally, the delta-mRNA levels are higher in heterozygotes for beta(0)-thalassemia mutations than beta(+)-thalassemia mutations. The delta-mRNA levels correlated inversely with hemoglobin and red cell indices but directly with HbA(2) levels in heterozygotes of each of the group of beta-thalassemia mutations. These results suggest that a greater impairment in beta-globin gene expression results in increased transcription of delta-globin gene and in a higher level of HbA(2). C1 Shanghai Childrens Hosp, Shanghai Inst Med Genet, Shanghai 200040, Peoples R China. NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. RP Zeng, FY (reprint author), Shanghai Childrens Hosp, Shanghai Inst Med Genet, 24-1400 W Beijing Rd, Shanghai 200040, Peoples R China. OI Schechter, Alan N/0000-0002-5235-9408 NR 19 TC 3 Z9 5 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5792 J9 ACTA HAEMATOL-BASEL JI Acta Haematol. PY 1999 VL 102 IS 1 BP 1 EP 6 DI 10.1159/000040959 PG 6 WC Hematology SC Hematology GA 233QK UT WOS:000082437400001 PM 10473880 ER PT J AU Onodera, M Nelson, DM Sakiyama, Y Candotti, F Blaese, RM AF Onodera, M Nelson, DM Sakiyama, Y Candotti, F Blaese, RM TI Gene therapy for severe combined immunodeficiency caused by adenosine deaminase deficiency: Improved retroviral vectors for clinical trials SO ACTA HAEMATOLOGICA LA English DT Article; Proceedings Paper CT 11th International Symposium on Molecular Biology of Hematopoiesis CY JUN 25-29, 1998 CL BORMIO, ITALY DE gene therapy; retroviral vector; severe combined immunodeficiency, adenosine deaminase; stem cells, hematopoietic; T lymphocytes, peripheral ID T-LYMPHOCYTES; CELL LINES; TRANSPLANTATION; EXPRESSION; SEQUENCE; BLOOD; CDNA; ENGRAFTMENT AB Severe combined immunodeficiency (SCID) caused by adenosine deaminase deficiency (ADA-) is the first genetic disorder to be treated with gene therapy. Since 1990 when the first trial started for 2 patients with ADA-SCID, five clinical trials enrolling 11 patients have been conducted with different clinical approaches and the results obtained from these trials have recently been reported. According to these reports, T cell-directed gene transfer was useful in the treatment of ADA- SCID whereas the retroviral-mediated gene transfer to hematopoietic stem cells was insufficient for achievement of clinical benefits. This chapter reviews several crucial problems inherent in the current retroviral technology based on the clinical data observed in these pioneering ADA gene therapy trials and presents our new retroviral vector system for the next stem cell gene therapy. C1 Hokkaido Univ, Sch Med, Dept Pediat, Sapporo, Hokkaido 060, Japan. Natl Human Genome Res Inst, Clin Gene Therapy Branch, NIH, Bethesda, MD USA. CREST, Japan Sci & Technol Corp, Tsukuba, Ibaraki, Japan. RP Onodera, M (reprint author), Univ Tsukuba, Inst Basic Med Sci, Dept Immunol, CREST, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058578, Japan. EM mk98d116@md.tsukuba.ac.jp NR 30 TC 22 Z9 22 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5792 J9 ACTA HAEMATOL-BASEL JI Acta Haematol. PY 1999 VL 101 IS 2 BP 89 EP 96 DI 10.1159/000040930 PG 8 WC Hematology SC Hematology GA 186FM UT WOS:000079718000005 PM 10202239 ER PT J AU Candotti, F Onodera, M Knazek, RA Blaese, RM AF Candotti, F Onodera, M Knazek, RA Blaese, RM TI Retroviral-mediated transfer and expression of the common gamma chain into human hematopoietic progenitors SO ACTA HAEMATOLOGICA LA English DT Article; Proceedings Paper CT 11th International Symposium on Molecular Biology of Hematopoiesis CY JUN 25-29, 1998 CL BORMIO, ITALY DE gene therapy; hematopoietic progenitors; retroviral vectors; XSCID ID SEVERE COMBINED IMMUNODEFICIENCY; BONE-MARROW TRANSPLANTATION; GENE-THERAPY; PERIPHERAL-BLOOD; STEM-CELLS; LYMPHOCYTES AB The common gamma chain (gamma(c)) of cytokine receptors is mutated in X-linked severe combined immunodeficiency, a lethal disorder characterized by the absence of both humoral and cellular immune defenses, Allogeneic bone marrow transplantation from HLA-identical siblings usually results in complete reconstitution of the immune system and is the current treatment of choice. Genetic correction and reinfusion of autologous hematopoietic stem cells represents an alternative therapeutic approach for those patients who lack suitable marrow donors. In this study, we show that retroviral-mediated transfer of the gamma(c) gene results in efficient expression in CD34+ cells and high transduction rate of colony-forming progenitors. C1 NHGRI, Clin Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. RP Candotti, F (reprint author), NHGRI, Clin Gene Therapy Branch, NIH, Bldg 10,Rm 10C103,10 Ctr Dr,MSC 1851, Bethesda, MD 20892 USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5792 J9 ACTA HAEMATOL-BASEL JI Acta Haematol. PY 1999 VL 101 IS 2 BP 106 EP 110 DI 10.1159/000040932 PG 5 WC Hematology SC Hematology GA 186FM UT WOS:000079718000007 PM 10202241 ER PT J AU Suzuki, K Mori, A Lavaroni, S Katoh, R Kohn, LD Kawaoi, A AF Suzuki, K Mori, A Lavaroni, S Katoh, R Kohn, LD Kawaoi, A TI Thyroglobulin: A master regulator of follicular function via transcriptional suppression of thyroid specific genes SO ACTA HISTOCHEMICA ET CYTOCHEMICA LA English DT Article; Proceedings Paper CT 5th Joint Meeting of the Japan-Society-of-Histochemistry-and-Cytochemistry / Histochemical-Society CY JUL 23-26, 1998 CL UNIV CALIFORNIA SAN DIEGO, LA JOLLA, CA SP Japan Soc Histochem & Cytochem, Histochem Soc, Univ Calif San Diego HO UNIV CALIFORNIA SAN DIEGO DE thyroid; thyroglobulin; autoregulation; transcription; heterogeneity ID THYROTROPIN RECEPTOR PROMOTER; CAMP RESPONSE ELEMENT; IMMUNOGOLD TECHNIQUE; FRTL-5 CELLS; RAT; EXPRESSION; HETEROGENEITY; METHIMAZOLE; GROWTH; GLAND AB lumen, is a potent regulator of follicular physiological concentrations of TG significantly suppress thyroid-specific gene expression in cultured thyrocytes and antagonizes the maximal negative feedback function. Thus, Thyroid gland function is thought to be tightly regulated by thyrotropin (TSH). However, the function of each thyroid follicle is heterogeneous despite having the same blood supply of TSH and despite homogeneous thyrocyte expression of the TSH receptor (TSHR). The nature of this heterogeneity is not fully understood. Recent studies showed that thyroglobulin (TG) protein, stored in the follicular TSH stimulation of thyroid-specific genes: thyroglobulin, thyroid peroxidase, sodium iodide symporter and TSH receptor. In vivo studies are consistent with these results. This regulation is mediated by TG suppression of thyroid-specific transcription factors: thyroid-transcription factors 1 and 2 as well as Pax-8. We propose a model of follicular activity wherein each follicle has its own cycle of thyroid hormone synthesis and secretion and wherein follicular heterogeneity reflects the asynchronous function of individual follicles. We provide evidence that this mechanism may be related to the phenotype of some thyroid diseases. C1 NIDDK, Cell Regulat Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Yamanashi Med Univ, Dept Pathol, Yamanashi 4093898, Japan. RP Suzuki, K (reprint author), NIDDK, Cell Regulat Sect, Metab Dis Branch, NIH, Bldg 10,Room 8C108, Bethesda, MD 20892 USA. NR 39 TC 17 Z9 18 U1 0 U2 0 PU JAPAN SOC HISTOCHEMISTRY & CYTOCHEMISTRY PI KYOTO PA C/O NAKANISHI PRINTING CO LTD, SHIMODACHIURI-OGAWA, KAMIGYO-KU, KYOTO, 602-8048, JAPAN SN 0044-5991 EI 1347-5800 J9 ACTA HISTOCHEM CYTOC JI Acta Histochem. Cytochem. PY 1999 VL 32 IS 2 BP 111 EP 119 PG 9 WC Cell Biology SC Cell Biology GA 201EB UT WOS:000080581100003 ER PT J AU Karasawa, N Arai, R Yamawaki, Y Shino, M Watanabe, K Onozuka, M Kawase, T Jacobowitz, DM Nagatsu, I AF Karasawa, N Arai, R Yamawaki, Y Shino, M Watanabe, K Onozuka, M Kawase, T Jacobowitz, DM Nagatsu, I TI Transient coexistence of tyrosine hydroxylase and gamma-aminobutyric acid immunoreactivities in the developing anterior olfactory nucleus of the mouse SO ACTA HISTOCHEMICA ET CYTOCHEMICA LA English DT Article DE mouse; anterior olfactory nucleus; tyrosine hydroxylase; GABA; colocalization; immunohistochemistry ID SHREW SUNCUS-MURINUS; CENTRAL-NERVOUS-SYSTEM; RAT-BRAIN; IMMUNOCYTOCHEMICAL LOCALIZATION; IMMUNOHISTOCHEMICAL LOCALIZATION; CONTAIN DOPAMINE; NEURONS; EXPRESSION; DECARBOXYLASE; GABA AB The localization of tyrosine hydroxylase (TH)-immunoreactive (IR) (TH-IR) neurons, which are transiently observed in the anterior olfactory nucleus (AON) of the mouse, was studied. A double-labelling method was used with antibodies against TH, L-3,4-dihydroxyphenylalanine (DOPA), phenylethanolamine-N-methyltransferase (PNMT). aminobutyric acid (GABA), calretinin (CR) and calbindin-D28k (CB). When the total number of TH-IR neurons observed in all regions of the AON obtained from 10- to 14-day-old mice was set at 100%, 30% of TH-IR neurons were observed in the lateral (AOL), 25% in the dorsal (AOD), 20% in the ventral (AOV), 15% in the medial (AOM) and 5% in both the posterior (AOP) and external (AOE) regions. Approximately 40% of the TH-IR neurons in the AOL to the AOV regions also exhibited GABA immunoreactivity. This corresponds to 20% of the total number of BH-IR neurons observed in all regions of the AON, and also corresponds to 12% of the total number of GABA-IR neurons observed in all regions of the AON. However, TH-IR neurons did not exhibit concomitant PNMT, CR, and CB immunoreactivities. These findings suggest that the TH-IR neurons in the AON of the mouse, a proportion of which is also GABA-IR, may function as a source of neuromodulators for the postnatal growth of GABA-IR neurons. C1 Fujita Hlth Univ, Sch Med, Dept Anat 2, Toyoake, Aichi 4701192, Japan. Fujita Hlth Univ, Sch Med, Dept Anat 1, Toyoake, Aichi 4701192, Japan. Gifu Univ, Sch Med, Dept Physiol, Gifu 5008076, Japan. Gifu Univ, Sch Med, Dept Anat, Gifu 5008076, Japan. Kanagawa Dent Coll, Dept Oral Biochem, Yokosuka, Kanagawa 2380003, Japan. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Karasawa, N (reprint author), Fujita Hlth Univ, Sch Med, Dept Anat 2, Toyoake, Aichi 4701192, Japan. NR 32 TC 3 Z9 3 U1 0 U2 0 PU JAPAN SOC HISTOCHEMISTRY & CYTOCHEMISTRY PI KYOTO PA C/O NAKANISHI PRINTING CO LTD, SHIMODACHIURI-OGAWA, KAMIGYO-KU, KYOTO, 602-8048, JAPAN SN 0044-5991 EI 1347-5800 J9 ACTA HISTOCHEM CYTOC JI Acta Histochem. Cytochem. PY 1999 VL 32 IS 4 BP 333 EP 339 PG 7 WC Cell Biology SC Cell Biology GA 232KB UT WOS:000082369000006 ER PT J AU Gordis, E Fuller, R AF Gordis, E Fuller, R TI Project MATCH SO ADDICTION LA English DT Editorial Material C1 NIAAA, NIH, Bethesda, MD 20892 USA. RP Gordis, E (reprint author), NIAAA, NIH, 6000 Execut Blvd,Willco Bldg,Ste 400, Bethesda, MD 20892 USA. NR 5 TC 5 Z9 5 U1 1 U2 1 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD JAN PY 1999 VL 94 IS 1 BP 57 EP 59 PG 3 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 159LU UT WOS:000078175300016 PM 10665095 ER PT S AU McDiarmid, R AF McDiarmid, R BE Prigogine, I Rice, SA TI On the electronic spectra of small linear polyenes SO ADVANCES IN CHEMICAL PHYSICS, VOL 110 SE Advances in Chemical Physics LA English DT Review ID DIRECT ABSORPTION-SPECTROSCOPY; ULTRAFAST INTERNAL-CONVERSION; MOLECULAR-ORBITAL THEORY; LOWER RYDBERG STATES; JET-COOLED POLYENES; EXCITED-STATES; MULTIPHOTON IONIZATION; TRANS-HEXATRIENE; METHYL-DERIVATIVES; VACUUM ULTRAVIOLET C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP McDiarmid, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NR 89 TC 20 Z9 20 U1 1 U2 11 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 3RD AVE, NEW YORK, NY 10016 USA SN 0065-2385 BN 0-471-33180-5 J9 ADV CHEM PHYS PY 1999 VL 110 BP 177 EP 214 DI 10.1002/9780470141694.ch2 PG 38 WC Physics, Atomic, Molecular & Chemical SC Physics GA BR42B UT WOS:000166343200002 ER PT S AU Bohr, VA Balajee, A Brosh, R Nehlin, J Machwe, A Evans, M Dianov, G Orren, D AF Bohr, VA Balajee, A Brosh, R Nehlin, J Machwe, A Evans, M Dianov, G Orren, D BE Dizdaroglu, M Karakaya, AE TI DNA repair and transcription in premature aging syndromes SO ADVANCES IN DNA DAMAGE AND REPAIR: OXYGEN RADICAL EFFECTS, CELLULAR PROTECTION, AND BIOLOGICAL CONSEQUENCES SE NATO ADVANCED SCIENCE INSTITUTES SERIES, SERIES A, LIFE SCIENCES LA English DT Proceedings Paper CT Conference of the NATO Advanced Study Institute on DNA Damage and Repair - Oxygen Radical Effects, Cellular Protection, and Biological Consequences CY OCT 14-24, 1997 CL TEKIROVA, TURKEY SP NATO Sci Affairs Div, Belgium ID RNA-POLYMERASE-II; NUCLEOTIDE EXCISION-REPAIR; SYNDROME CELL-LINES; COCKAYNE-SYNDROME; STIMULATED ATPASE; GENE; DEFECT; HELICASE; PROTEIN; COMPLEX AB The human progeroid disorders Cockayne syndrome (CS) and Werner syndrome (WS) exhibit several clinical features that are associated with normal aging. With the recent cloning of the Werner syndrome (WRN) gene, and with the information that this gene, the CS complementation group B (CS-B) gene, and some XP gene products are putative helicases and involved in nucleic acid metabolism, further understanding the molecular deficiency in these disorders is a high priority. Helicases are involved in a number of DNA metabolic activities including transcription, replication and DNA repair. These human disorders provide excellent model systems for studies on aging. The patients have many signs and symptoms of normal aging, but they are segmental progeroid diseases, indicating that some features of normal aging are not seen. The function of the CS-B and WRN proteins appear to be at the crossroads of aging, DNA repair, DNA replication, and transcription, and hence these studies nicely combine our mechanistic interest in basic processes with our interest in aging. CS (Group B), WRN, and other age-related disorders (Bloom, Xeroderma pigmentosum Groups B and D) carry mutations in related genes characterized by conserved motifs of sequence homology. Some proteins of this family have been demonstrated to be DNA-dependent ATPases, a subset of which have also been shown to be helicases. Proteins of this family are involved in various aspects of chromosome metabolism. The molecular defects responsible for the clinical phenotypes of these diseases remain to be determined, but presumably relate to the functional activities of these conserved proteins. In addition, specific protein-DNA and protein-protein interactions are likely to play critical roles in cellular function. Cells derived from CS patients are deficient in a special type of DNA repair, transcription coupled DNA repair, but they also appear to be defective in basal transcription. The diverse functions of the CSB protein are under intense study. Werner syndrome cells may have subtle defects in DNA repair, and possibly also in transcription. The biochemical clarification of the precise role(s) of these gene products is likely to provide very significant clues into the mechanism of aging. C1 NIA, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Mol Genet Lab, NIH, 4940 Eastern Ave, Baltimore, MD 21224 USA. NR 30 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0258-1213 BN 0-306-46042-4 J9 NATO ADV SCI I A-LIF PY 1999 VL 302 BP 27 EP 34 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA BM98E UT WOS:000080335400003 ER PT S AU Kasprzak, KS Bal, W Porter, DW Bialkowski, K AF Kasprzak, KS Bal, W Porter, DW Bialkowski, K BE Dizdaroglu, M Karakaya, AE TI Studies on oxidative mechanisms of metal-induced carcinogenesis - Recent developments SO ADVANCES IN DNA DAMAGE AND REPAIR: OXYGEN RADICAL EFFECTS, CELLULAR PROTECTION, AND BIOLOGICAL CONSEQUENCES SE NATO ADVANCED SCIENCE INSTITUTES SERIES, SERIES A, LIFE SCIENCES LA English DT Review CT Conference of the NATO Advanced Study Institute on DNA Damage and Repair - Oxygen Radical Effects, Cellular Protection, and Biological Consequences CY OCT 14-24, 1997 CL TEKIROVA, TURKEY SP NATO Sci Affairs Div, Belgium ID DNA-BASE DAMAGE; GLYCYLGLYCYL-L-HISTIDINE; HUMAN-SPERM PROTAMINES; C-G TRANSVERSION; MALE F344 RATS; HYDROGEN-PEROXIDE; MUTAGENIC SUBSTRATE; ESCHERICHIA-COLI; NICKEL COMPOUNDS; SERUM-ALBUMIN AB Two ways by which carcinogenic metals, such as Ni(II), Co(II), Cu(II), or Cd(II), may promote oxidative DNA damage, including direct effects consisting of activation of oxygen species and mediation of their attack on DNA, and indirect effects through suppression of cellular antimutagenic defenses, are discussed. The mechanisms of the direct attack may involve chelation of a metal by nuclear proteins, especially the histones and protamines, and activation of metabolic oxygen species by the resulting metal complexes at close proximity to DNA. We found that human protamine HP2 has a typical binding motif for Ni(II) and Cu(II), Arg-Thr-His-, at its N-terminus. A synthetic pentadecapeptide modeling this terminus formed strong chelates with these metals and, in addition, enhanced oxidative DNA damage by Ni(II) plus H(2)O(2), but suppressed, though not completely, the damage by Cu(II) plus H(2)O(2). Since protamines carry DNA in the sperm, the observed DNA damage may have spermicidal or transgenerational carcinogenic effects in man exposed to metals, as observed epidemiologically. The indirect effects of metals on DNA may involve inhibition of 8-oxo-dGTPases, a class of enzymes preventing incorporation of the 8-oxoguanine lesion from oxidatively-damaged deoxynucleotide pool into DNA. Cd(II) and Cu(II), and to a limited extent also Ni(II) and Co(II), were found to in vitro inhibit the enzymatic activity of a bacterial (MutT) and human (MTH1) 8-oxo-dGTPases. This may allow redox-inactive metals, such as Cd(II), to introduce the promutagenic 8-oxoguanine lesion from endogenously damaged 8-oxo-dGTP into DNA. C1 NCI, FCRDC, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Kasprzak, KS (reprint author), NCI, FCRDC, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RI Bialkowski, Karol/E-2328-2014 NR 106 TC 6 Z9 7 U1 0 U2 1 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0258-1213 BN 0-306-46042-4 J9 NATO ADV SCI I A-LIF PY 1999 VL 302 BP 193 EP 208 PG 16 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA BM98E UT WOS:000080335400016 ER PT S AU Hughes, FM Cidlowski, JA AF Hughes, FM Cidlowski, JA BE Weber, G TI Potassium is a critical regulator of apoptotic enzymes in vitro and in vivo SO ADVANCES IN ENZYME REGULATION, VOL 39 SE ADVANCES IN ENZYME REGULATION LA English DT Article; Proceedings Paper CT 39th International Symposium on Regulation of Enzyme Activity and Synthesis in Normal and Neoplastic Tissues CY OCT 05-06, 1998 CL INDIANA UNIV SCH MED, INDIANAPOLIS, INDIANA HO INDIANA UNIV SCH MED ID INDUCED THYMOCYTE APOPTOSIS; RECOMBINANT CYCLOPHILIN-A; ACID CLEAVAGE ACTIVITY; PROGRAMMED CELL-DEATH; INTERNUCLEOSOMAL FRAGMENTATION; DNA FRAGMENTATION; RAT THYMOCYTES; DEGRADATION; ACTIVATION; CHROMATIN C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, NIH, POB 12233,MD E2-02, Res Triangle Pk, NC 27709 USA. NR 39 TC 156 Z9 163 U1 1 U2 7 PU PERGAMON PRESS LTD PI OXFORD PA THE BOULEVARD LANGFORD LANE KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0065-2571 BN 0-08-043571-8 J9 ADV ENZYME REGUL PY 1999 VL 39 BP 157 EP 171 DI 10.1016/S0065-2571(98)00010-7 PG 15 WC Biochemistry & Molecular Biology; Oncology; Cell Biology SC Biochemistry & Molecular Biology; Oncology; Cell Biology GA BN54Z UT WOS:000082191200010 PM 10470372 ER PT S AU Cocco, L Capitani, S Barnabei, O Gilmour, RS Rhee, SG Manzoli, FA AF Cocco, L Capitani, S Barnabei, O Gilmour, RS Rhee, SG Manzoli, FA BE Weber, G TI Inositides in the nucleus: Further developments on phospholipase C beta(1) signalling during erythroid differentiation and IGF-I induced mitogenesis SO ADVANCES IN ENZYME REGULATION, VOL 39 SE ADVANCES IN ENZYME REGULATION LA English DT Article; Proceedings Paper CT 39th International Symposium on Regulation of Enzyme Activity and Synthesis in Normal and Neoplastic Tissues CY OCT 05-06, 1998 CL INDIANA UNIV SCH MED, INDIANAPOLIS, INDIANA HO INDIANA UNIV SCH MED ID PHOSPHOINOSITIDASE-C-BETA; PROTEIN-KINASE-C; SWISS 3T3 CELLS; FRIEND-CELLS; LIPID CYCLE; LOCALIZATION; POLYPHOSPHOINOSITIDE; TRANSLOCATION; DIACYLGLYCEROL; TRANSDUCTION C1 Univ Bologna, Inst Anat, I-40126 Bologna, Italy. Univ Ferrara, Inst Anat, I-44100 Ferrara, Italy. Univ Bologna, Dept Biol, I-40126 Bologna, Italy. NHLBI, Lab Cell Signalling, NIH, Bethesda, MD 20892 USA. Univ Auckland, Sch Med, Auckland, New Zealand. RP Cocco, L (reprint author), Univ Bologna, Inst Anat, Via Irnerio 48, I-40126 Bologna, Italy. NR 30 TC 6 Z9 6 U1 1 U2 1 PU PERGAMON PRESS LTD PI OXFORD PA THE BOULEVARD LANGFORD LANE KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0065-2571 BN 0-08-043571-8 J9 ADV ENZYME REGUL PY 1999 VL 39 BP 287 EP 297 DI 10.1016/S0065-2571(98)00025-9 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology SC Biochemistry & Molecular Biology; Oncology; Cell Biology GA BN54Z UT WOS:000082191200017 PM 10470379 ER PT S AU Chen, YD Ermolaeva, O Bittner, M Meltzer, P Trent, J Dougherty, ER Batman, S AF Chen, YD Ermolaeva, O Bittner, M Meltzer, P Trent, J Dougherty, ER Batman, S BE Lakowicz, JR Soper, SA Thompson, RB TI Clustering analysis for gene expression data SO ADVANCES IN FLUORESCENCE SENSING TECHNOLOGY IV, PROCEEDINGS OF SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Advances in Fluorescence Sensing Technology IV CY JAN 24-27, 1999 CL SAN JOSE, CA SP SPIE, Int Biomed Opt Soc, Coherent Laser Grp, ISS Inc, Molec Probes Inc, Opt Sensors Inc, Spectra Phys, Spectron Instruments Inc DE cDNA microarray; gene expression; K-mean clustering ID MICROARRAY; PATTERNS; SCALE AB The recent development of cDNA microarray allows ready access to large amount gene expression patterns for many genetic materials. Gene expression of tissue samples can be quantitatively analyzed by hybridizing fluor-tagged mRNA to targets on a cDNA microarray. Ratios of average expression level arising from co-hybridized normal and pathological samples are extracted via image segmentation, thus the gene expression pattern are obtained. The gene expression in a given biological process may provide a fingerprint of the sample development, or response to certain treatment. We propose a K-mean based algorithm in which gene expression levels fluctuate in parallel will be clustered together. The resulting cluster suggests some functional relationships between genes, and some known genes belongs to a unique functional classes shall provide indication for unknown genes in the same clusters. C1 Natl Human Genome Res Inst, NIH, Bethesda, MD USA. RP Chen, YD (reprint author), Natl Human Genome Res Inst, NIH, Bethesda, MD USA. NR 14 TC 0 Z9 0 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3072-2 J9 P SOC PHOTO-OPT INS PY 1999 VL 3602 BP 422 EP 428 DI 10.1117/12.347541 PG 7 WC Engineering, Biomedical; Medical Laboratory Technology; Optics SC Engineering; Medical Laboratory Technology; Optics GA BN09N UT WOS:000080657500045 ER PT J AU Yewdell, JW Norbury, CC Bennink, JR AF Yewdell, JW Norbury, CC Bennink, JR TI Mechanisms of exogenous antigen presentation by MHC class I molecules in vitro and in vivo: Implications for generating CD8(+) T cell responses to infectious agents, tumors, transplants, and vaccines SO ADVANCES IN IMMUNOLOGY, VOL 73 SE ADVANCES IN IMMUNOLOGY LA English DT Review ID MAJOR HISTOCOMPATIBILITY COMPLEX; HEAT-SHOCK PROTEINS; RESTRICTED EPITOPE PRESENTATION; VIRUS-LIKE PARTICLES; TOXIC LYMPHOCYTES-T; B SURFACE-ANTIGEN; PH-SENSITIVE LIPOSOMES; DNA-BASED IMMUNIZATION; MARROW-DERIVED CELLS; DENDRITIC CELLS C1 NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 216 TC 220 Z9 221 U1 4 U2 8 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 J9 ADV IMMUNOL JI Adv.Immunol. PY 1999 VL 73 BP 1 EP 77 DI 10.1016/S0065-2776(08)60785-3 PG 77 WC Immunology SC Immunology GA BP76F UT WOS:000086093500001 PM 10399005 ER PT S AU Greenwald, P AF Greenwald, P BE Zappia, V DellaRagione, F Barbarisi, A Russo, GL DelloIacovo, R TI Diet and cancer - Perspectives of prevention SO ADVANCES IN NUTRITION AND CANCER 2 SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 2nd International Symposium on Nutrition and Cancer CY OCT 20-23, 1998 CL NATL TUMOR INST FDN PASCALE, NAPLES, ITALY SP 2nd Univ Naples, Inst Biochem Macromolec, Regi Govt, Natl Res Council, Inst Food Sci & Technol, Natl Tumor Inst Fdn Pascale, 2nd Univ Naples, Italian Inst Philosoph Stud, Italian Hlth Minist, Local Govt HO NATL TUMOR INST FDN PASCALE ID POSTMENOPAUSAL BREAST-CANCER; NUTRITION INTERVENTION TRIALS; NONABSORBED FAT REPLACEMENT; DISEASE-SPECIFIC MORTALITY; BETA-CAROTENE; LUNG-CANCER; PROSTATE-CANCER; MINERAL SUPPLEMENTATION; CARDIOVASCULAR-DISEASE; CHEMOPREVENTION TRIALS C1 NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Greenwald, P (reprint author), NCI, Div Canc Prevent, NIH, Bldg 31,Room 10A52, Bethesda, MD 20892 USA. NR 108 TC 5 Z9 5 U1 0 U2 3 PU KLUWER ACADEMIC / PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46306-7 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1999 VL 472 BP 1 EP 19 PG 19 WC Oncology; Medicine, Research & Experimental; Nutrition & Dietetics SC Oncology; Research & Experimental Medicine; Nutrition & Dietetics GA BP89R UT WOS:000086535300001 PM 10736611 ER PT S AU Giacosa, A Hill, MJ AF Giacosa, A Hill, MJ CA ECP Consensus Panel BE Zappia, V DellaRagione, F Barbarisi, A Russo, GL DelloIacovo, R TI Cereals, fiber, and cancer prevention SO ADVANCES IN NUTRITION AND CANCER 2 SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 2nd International Symposium on Nutrition and Cancer CY OCT 20-23, 1998 CL NATL TUMOR INST FDN PASCALE, NAPLES, ITALY SP 2nd Univ Naples, Inst Biochem Macromolec, Regi Govt, Natl Res Council, Inst Food Sci & Technol, Natl Tumor Inst Fdn Pascale, 2nd Univ Naples, Italian Inst Philosoph Stud, Italian Hlth Minist, Local Govt HO NATL TUMOR INST FDN PASCALE ID DIET C1 Natl Canc Inst, I-16132 Genoa, Italy. Wexham Pk Hosp, ECP UK Headquarters, Slough SL2 4HL, Berks, England. RP Giacosa, A (reprint author), Natl Canc Inst, I-16132 Genoa, Italy. NR 10 TC 1 Z9 1 U1 1 U2 1 PU KLUWER ACADEMIC / PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46306-7 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1999 VL 472 BP 269 EP 272 PG 4 WC Oncology; Medicine, Research & Experimental; Nutrition & Dietetics SC Oncology; Research & Experimental Medicine; Nutrition & Dietetics GA BP89R UT WOS:000086535300023 PM 10736633 ER PT J AU Esposito, D Craigie, R AF Esposito, D Craigie, R TI HIV integrase structure and function SO ADVANCES IN VIRUS RESEARCH, VOL 52 SE ADVANCES IN VIRUS RESEARCH LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; DNA-BINDING DOMAIN; POLYNUCLEOTIDYL TRANSFER-REACTIONS; CARBOXYL-TERMINAL DOMAINS; PHOTO-CROSS-LINKING; RETROVIRAL INTEGRASE; VIRAL-DNA; CRYSTAL-STRUCTURE; CATALYTIC DOMAIN; TYPE-1 INTEGRASE C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Esposito, D (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. FU NCRR NIH HHS [RR-01081] NR 64 TC 196 Z9 205 U1 0 U2 6 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3527 J9 ADV VIRUS RES JI Adv.Virus Res. PY 1999 VL 52 BP 319 EP 333 DI 10.1016/S0065-3527(08)60304-8 PG 17 WC Virology SC Virology GA BN57C UT WOS:000082271300007 PM 10384240 ER PT J AU Wlodawer, A AF Wlodawer, A TI Crystal structures of catalytic core domains of retroviral integrases and role of divalent cations in enzymatic activity SO ADVANCES IN VIRUS RESEARCH, VOL 52 SE ADVANCES IN VIRUS RESEARCH LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; PHOTO-CROSS-LINKING; DNA-BINDING DOMAIN; HIV-1 INTEGRASE; VIRAL-DNA; ESCHERICHIA-COLI; TYPE-1 INTEGRASE; RIBONUCLEASE-H; RNASE-H; PROTEIN C1 NCI, Frederick Canc Res & Dev Ctr, Macromol Struct Lab, ABL Basic Res Program, Frederick, MD 21702 USA. RP Wlodawer, A (reprint author), NCI, Frederick Canc Res & Dev Ctr, Macromol Struct Lab, ABL Basic Res Program, Frederick, MD 21702 USA. NR 50 TC 30 Z9 32 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3527 J9 ADV VIRUS RES JI Adv.Virus Res. PY 1999 VL 52 BP 335 EP U15 DI 10.1016/S0065-3527(08)60305-X PG 19 WC Virology SC Virology GA BN57C UT WOS:000082271300008 PM 10384241 ER PT S AU Pommier, Y Neamati, N AF Pommier, Y Neamati, N BE Maramorosch, K Murphy, FA Shatkin, AJ TI Inhibitors of human immunodeficiency virus integrase SO ADVANCES IN VIRUS RESEARCH, VOL 52 SE Advances in Virus Research LA English DT Review ID HIV DNA INTEGRATION; NUCLEAR-LOCALIZATION SIGNAL; AFFINITY-BASED SELECTION; IN-VITRO INTEGRATION; SPLIT-POOL SYNTHESIS; PHOTO-CROSS-LINKING; TYPE-1 INTEGRASE; VIRAL-DNA; PREINTEGRATION COMPLEXES; INTERFACE PEPTIDES C1 NCI, Div Basic Sci, Mol Pharmacol Lab, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Div Basic Sci, Mol Pharmacol Lab, Bethesda, MD 20892 USA. NR 149 TC 92 Z9 94 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3527 BN 0-12-039852-4 J9 ADV VIRUS RES JI Adv.Virus Res. PY 1999 VL 52 BP 427 EP 458 DI 10.1016/S0065-3527(08)60310-3 PG 32 WC Virology SC Virology GA BN57C UT WOS:000082271300013 PM 10384246 ER PT J AU Collins, PL Whitehead, SS Bukreyev, A Fearns, R Teng, MN Juhasz, K Chanock, RM Murphy, BR AF Collins, PL Whitehead, SS Bukreyev, A Fearns, R Teng, MN Juhasz, K Chanock, RM Murphy, BR TI Rational design of live-attenuated recombinant vaccine virus for human respiratory syncytial virus by reverse genetics SO ADVANCES IN VIRUS RESEARCH, VOL 54 SE ADVANCES IN VIRUS RESEARCH LA English DT Review ID ENHANCED PULMONARY HISTOPATHOLOGY; TRANSCRIPTION ELONGATION-FACTOR; RNA REPLICATION; MESSENGER-RNA; L-PROTEIN; SERONEGATIVE CHIMPANZEES; GLYCOPROTEIN-G; RSV CHALLENGE; TS PHENOTYPE; M2 GENE C1 NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Collins, PL (reprint author), NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RI Teng, Michael/I-5006-2012 OI Teng, Michael/0000-0002-0722-3659 NR 53 TC 60 Z9 63 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3527 J9 ADV VIRUS RES JI Adv.Virus Res. PY 1999 VL 54 BP 423 EP 451 DI 10.1016/S0065-3527(08)60374-7 PG 29 WC Virology SC Virology GA BP54S UT WOS:000085466600012 PM 10547682 ER PT S AU Chefer, V Thompson, AC Shippenberg, TS AF Chefer, V Thompson, AC Shippenberg, TS BE McGinty, JF TI Modulation of cocaine-induced sensitization by kappa-opioid receptor agonists - Role of the nucleus accumbens and medial prefrontal cortex SO ADVANCING FROM THE VENTRAL STRIATUM TO THE EXTENDED AMYGDALA: IMPLICATIONS FOR NEUROPSYCHIATRY AND DRUG ABUSE: IN HONOR OF LENNART HEIMER SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Advancing from the Ventral Striatum to the Extended Amygdala - Implications for Neuropsychiatry and Drug Abuse-In Honor of Lennart Heimer CY OCT 18-21, 1998 CL CHARLOTTESVILLE, VIRGINIA SP NY Acad Sci, Natl Inst Mental Hlth, E Carolina Univ, Sch Med, Off Res & Grad Studies, Univ Virginia Hlth Sci Ctr, Hoechst Marion Rousell Inc, Merck Res Labs, Pfizer Inc, Pharmacia & Upjohn, Res Biochem Inc, Univ WI Hlth Emot Res Inst ID BEHAVIORAL SENSITIZATION; DOPAMINE; INITIATION; EXPRESSION C1 NIDA, Integrat Neurosci Unit, Behav Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Shippenberg, TS (reprint author), NIDA, Integrat Neurosci Unit, Behav Neurosci Lab, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NIDA NIH HHS [DA 10084] NR 9 TC 9 Z9 9 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-178-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 877 BP 803 EP 806 DI 10.1111/j.1749-6632.1999.tb09327.x PG 4 WC Substance Abuse; Multidisciplinary Sciences; Neurosciences; Psychiatry SC Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology; Psychiatry GA BN31Y UT WOS:000081586500070 PM 10415709 ER PT J AU Riley, MW Riley, JW AF Riley, MW Riley, JW TI Sociological research on age: legacy and challenge SO AGEING AND SOCIETY LA English DT Article DE changing lives; neglect of structure; interplay between lives and structures; cohort norm formation; aging and society paradigm AB The hallmark of sociology is its emphases on first, people, secondly, structures and, thirdly, their interrelationships. Similarly, we see sociological research on age as concerned with (1) people over their life course; (2) age-related structures and institutions; and (3) the dynamic interplay between people and structures as each influences the other. Guided by our 'aging and society paradigm', we review the research legacy as it has focused more on (1) than on (2), and is only now concerned with understanding the interplay between them (3) Hence our challenge to future researchers is to devise strategies for understanding and analysing this interplay and its possible contributions to the ever-accumulating research legacy. C1 NIH, Bethesda, MD 20892 USA. RP Riley, MW (reprint author), NIA, Senior Social Sci Off, Gateway Bldg Room 2C227,7201 Wisconsin Ave, Bethesda, MD 20892 USA. NR 19 TC 13 Z9 13 U1 1 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0144-686X J9 AGEING SOC JI Ageing Soc. PD JAN PY 1999 VL 19 BP 123 EP 132 PN 1 PG 10 WC Gerontology SC Geriatrics & Gerontology GA 209FZ UT WOS:000081038700006 ER PT J AU Goldman, D Lappalainen, J Knowler, WC Hanson, RL Robin, RW Urbanek, M Guenther, D Moore, E Bennett, PH Long, J Virkkunen, M Linnoila, M AF Goldman, D Lappalainen, J Knowler, WC Hanson, RL Robin, RW Urbanek, M Guenther, D Moore, E Bennett, PH Long, J Virkkunen, M Linnoila, M TI Genetic linkage of alcoholism and antisocial alcoholism SO AGGRESSIVE BEHAVIOR LA English DT Meeting Abstract C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. 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 USA SN 0096-140X J9 AGGRESSIVE BEHAV JI Aggressive Behav. PY 1999 VL 25 IS 1 BP 15 EP 15 PG 1 WC Behavioral Sciences; Psychology, Multidisciplinary SC Behavioral Sciences; Psychology GA 160JM UT WOS:000078226900022 ER PT J AU Constantino, JN Murphy, DL AF Constantino, JN Murphy, DL TI Serotonin and aggression in children SO AGGRESSIVE BEHAVIOR LA English DT Meeting Abstract C1 Washington Univ, Sch Med, Dept Psychiat, Bethesda, MD USA. Washington Univ, Sch Med, Dept Pediat, Bethesda, MD USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0096-140X J9 AGGRESSIVE BEHAV JI Aggressive Behav. PY 1999 VL 25 IS 1 BP 38 EP 38 PG 1 WC Behavioral Sciences; Psychology, Multidisciplinary SC Behavioral Sciences; Psychology GA 160JM UT WOS:000078226900059 ER PT J AU Crandall, KA Vasco, DA Posada, D Imamichi, H AF Crandall, KA Vasco, DA Posada, D Imamichi, H TI Advances in understanding the evolution of HIV SO AIDS LA English DT Article DE HIV; drug resistance; evolution; phylogeny; likelihood; model; candidate gene ID HUMAN-IMMUNODEFICIENCY-VIRUS; EFFECTIVE POPULATION-SIZE; DNA-SEQUENCE DATA; ACTIVE ANTIRETROVIRAL THERAPY; MAXIMUM-LIKELIHOOD; MUTATION-RATE; IN-VIVO; SECONDARY STRUCTURE; NUCLEOTIDE SUBSTITUTION; PHENOTYPIC ASSOCIATIONS C1 Brigham Young Univ, Dept Zool, Provo, UT 84602 USA. NCI, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Crandall, KA (reprint author), Brigham Young Univ, Dept Zool, 574 Widtsoe Bldg, Provo, UT 84602 USA. RI Posada, David/C-4502-2008 OI Posada, David/0000-0003-1407-3406 FU NICHD NIH HHS [R01 HD34350-01A1] NR 86 TC 10 Z9 10 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PY 1999 VL 13 SU A BP S39 EP S47 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 222RR UT WOS:000081799000005 PM 10885761 ER PT J AU Erickson, JW Gulnik, SV Markowitz, M AF Erickson, JW Gulnik, SV Markowitz, M TI Protease inhibitors: resistance, cross-resistance, fitness and the choice of initial and salvage therapies SO AIDS LA English DT Article DE HIV; drug resistance; selection; salvage therapy ID HUMAN-IMMUNODEFICIENCY-VIRUS; DYNAMICS IN-VIVO; HIV-1 PROTEASE; TYPE-1 PROTEASE; DRUG-RESISTANCE; REVERSE-TRANSCRIPTASE; KINETIC CHARACTERIZATION; VITRO SELECTION; VARIANTS; SENSITIVITY C1 NCI, Frederick Canc Res & Dev Ctr, SAIC, Struct Biochem Program, Frederick, MD 21702 USA. Aaron Diamond AIDS Res Ctr, New York, NY USA. RP Erickson, JW (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC, Struct Biochem Program, POB B, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 88 TC 66 Z9 67 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PY 1999 VL 13 SU A BP S189 EP S204 PG 16 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 222RR UT WOS:000081799000020 PM 10885776 ER PT J AU Gea-Banacloche, JC Lane, HC AF Gea-Banacloche, JC Lane, HC TI Immune reconstitution in HIV infection SO AIDS LA English DT Review DE HIV; CD4 T lymphocytes; immunology; opportunistic infections ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-C VIRUS; PROTEASE-INHIBITOR THERAPY; T-CELL REGENERATION; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; KAPOSIS-SARCOMA; CYTOMEGALOVIRUS RETINITIS; MOLLUSCUM CONTAGIOSUM; CMV RETINITIS C1 NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, Bethesda, MD 20892 USA. RP Lane, HC (reprint author), NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, Bldg 10,Room 11B-09,10 Ctr Dr MSCH 1876, Bethesda, MD 20892 USA. NR 163 TC 62 Z9 63 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PY 1999 VL 13 SU A BP S25 EP S38 PG 14 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 222RR UT WOS:000081799000004 PM 10885760 ER PT J AU Lundgren, J Masur, H AF Lundgren, J Masur, H TI New approaches to managing opportunistic infections SO AIDS LA English DT Article DE pneumocystis; toxoplasmosis; diarrhea; fungi; cytomegalovirus; MAC; syphilis; therapy; prevention ID HUMAN-IMMUNODEFICIENCY-VIRUS; PNEUMOCYSTIS-CARINII PNEUMONIA; ACTIVE ANTIRETROVIRAL THERAPY; CYTOMEGALOVIRUS RETINITIS; TOXOPLASMIC ENCEPHALITIS; MAINTENANCE THERAPY; CONTROLLED TRIAL; AIDS PATIENTS; INTRAVENOUS CIDOFOVIR; ORAL GANCICLOVIR C1 Univ Copenhagen, Hvidovre Hosp, EUROSIDA, Dept Infect Dis, DK-2650 Hvidovre, Denmark. NIH, Dept Crit Care Med, Bethesda, MD USA. RP Masur, H (reprint author), NIH, Ctr Clin, 7D43, Bethesda, MD 20892 USA. NR 54 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PY 1999 VL 13 SU A BP S227 EP S234 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 222RR UT WOS:000081799000023 PM 10885779 ER PT J AU Mofenson, LM Fowler, MG AF Mofenson, LM Fowler, MG TI Interruption of materno-fetal transmission SO AIDS LA English DT Article DE perinatal HIV transmission; prophylaxis; prevention ID HUMAN-IMMUNODEFICIENCY-VIRUS; TO-CHILD TRANSMISSION; VITAMIN-A-DEFICIENCY; PERINATAL HIV-1 TRANSMISSION; INFECTED WOMEN; ZIDOVUDINE PROPHYLAXIS; VERTICAL TRANSMISSION; INFANT TRANSMISSION; COST-EFFECTIVENESS; CESAREAN-SECTION C1 NICHHD, Ctr Res Mothers & Children, Adolescent & Maternal AIDS Branch, NIH, Rockville, MD 20852 USA. RP Mofenson, LM (reprint author), NICHHD, Ctr Res Mothers & Children, Adolescent & Maternal AIDS Branch, NIH, 6100 Execut Blvd,Room 4B11, Rockville, MD 20852 USA. NR 56 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PY 1999 VL 13 SU A BP S205 EP S214 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 222RR UT WOS:000081799000021 PM 10885777 ER PT J AU Nathanson, N Hirsch, VM Mathieson, BJ AF Nathanson, N Hirsch, VM Mathieson, BJ TI The role of nonhuman primates in the development of an AIDS vaccine SO AIDS LA English DT Article DE HIV; SIV; SHIV; primate models; AIDS vaccine; CTL ID SIMIAN IMMUNODEFICIENCY VIRUS; T-CELL RESPONSES; DEFICIENCY SYNDROME AIDS; LIVE ATTENUATED SIV; RHESUS MACAQUES; IMMUNE-RESPONSES; HIV-1 VACCINE; SERONEGATIVE ADULTS; RECOMBINANT GP120; SUBUNIT VACCINES C1 NIH, Off AIDS Res, US Dept Hlth & Human Serv, NIAID, Bethesda, MD 20892 USA. RP Nathanson, N (reprint author), NIH, Off AIDS Res, US Dept Hlth & Human Serv, NIAID, Room 4C02,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 74 TC 49 Z9 49 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PY 1999 VL 13 SU A BP S113 EP S120 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 222RR UT WOS:000081799000014 PM 10885770 ER PT J AU Oscherwitz, J Gotch, FM Cease, KB Berzofsky, JA AF Oscherwitz, J Gotch, FM Cease, KB Berzofsky, JA TI New insights and approaches regarding B- and T-cell epitopes in HIV vaccine design SO AIDS LA English DT Review DE AIDS vaccine; HIV; T-cell epitopes; B-cell epitopes; cytotoxic T lymphocyte; antibodies ID HUMAN-IMMUNODEFICIENCY-VIRUS; GP120 ENVELOPE GLYCOPROTEIN; HUMAN MONOCLONAL-ANTIBODY; TUMOR-ASSOCIATED ANTIGEN; CYTOTOXIC LYMPHOCYTES-T; CTL EPITOPE; V3 LOOP; SYNTHETIC PEPTIDES; IN-VIVO; ENHANCED IMMUNOGENICITY C1 NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Ann Arbor, MI USA. Vet Affairs Med Ctr, Ann Arbor, MI USA. Chelsea & Westminster Hosp, ICSM, Dept Immunol, London, England. RP Berzofsky, JA (reprint author), NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. NR 120 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PY 1999 VL 13 SU A BP S163 EP S174 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 222RR UT WOS:000081799000017 PM 10885773 ER PT J AU Strebel, K Bour, S AF Strebel, K Bour, S TI Molecular interactions of HIV with host factors SO AIDS LA English DT Review DE HIV; virus-host interactions; accessory genes; host factors ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 VPU PROTEIN; NUCLEAR-PORE COMPLEX; CD4 DOWN-REGULATION; CHIMERIC ENVELOPE GLYCOPROTEINS; PROVIRAL DNA-SYNTHESIS; CELL-CYCLE ARREST; CLASS-I MOLECULES; HUMAN T-CELLS; CYTOPLASMIC DOMAIN C1 NIAID, NIH, Mol Microbiol Lab, Bethesda, MD 20892 USA. RP Strebel, K (reprint author), NIAID, NIH, Mol Microbiol Lab, Bldg 4,Room 312,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 160 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PY 1999 VL 13 SU A BP S13 EP S24 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 222RR UT WOS:000081799000003 PM 10885759 ER PT J AU Van Damme, L Rosenberg, ZF AF Van Damme, L Rosenberg, ZF TI Microbicides and barrier methods in HIV prevention SO AIDS LA English DT Article DE microbicides; virucides; female condoms; HIV prevention ID HUMAN-IMMUNODEFICIENCY-VIRUS; SEXUALLY-TRANSMITTED DISEASES; RANDOMIZED CONTROLLED TRIAL; SEX WORKERS; FEMALE CONDOM; VAGINAL GEL; NONOXYNOL-9; INFECTION; METAANALYSIS; ACCEPTABILITY C1 Inst Trop Med, STD HIV Res & Intervent Unit, B-2000 Antwerp, Belgium. NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. RP Van Damme, L (reprint author), Inst Trop Med, STD HIV Res & Intervent Unit, Natl Str 155, B-2000 Antwerp, Belgium. NR 50 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PY 1999 VL 13 SU A BP S85 EP S92 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 222RR UT WOS:000081799000010 PM 10885766 ER PT J AU Yarchoan, R Vella, S AF Yarchoan, R Vella, S TI Clinical treatment SO AIDS LA English DT Editorial Material C1 Ist Super Sanita, Virol Lab, Retrovirus Sect, Div Antiviral Therapy & HIV Trials, I-00161 Rome, Italy. Natl Inst Hlth, Bethesda, MD USA. RP Vella, S (reprint author), Ist Super Sanita, Virol Lab, Retrovirus Sect, Div Antiviral Therapy & HIV Trials, Viale Regina Elena 299, I-00161 Rome, Italy. RI Vella, Stefano/D-4912-2015 OI Vella, Stefano/0000-0003-2347-5984 NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PY 1999 VL 13 SU A BP S175 EP S176 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 222RR UT WOS:000081799000018 PM 10885774 ER PT J AU Tsai, WP Kung, HF Nara, PL AF Tsai, WP Kung, HF Nara, PL TI The presence and absence of histocompatibility antigens in HIV type 1 produced by autologous blood-derived macrophages and peripheral blood lymphoblasts SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CLASS-I MOLECULES; CYTOMEGALOVIRUS-INFECTED CELLS; HLA CLASS-II; T-CELL; ENDOPLASMIC-RETICULUM; MEMBRANE-PROTEINS; DOWN-REGULATION; ADHESION RECEPTORS; VIRAL INFECTIVITY AB Acquisition of cellular proteins by HIV-1 virions is known to alter the physiology of the virus in vitro, Reported studies of this aspect have been largely limited to transformed T cell lines. In this study, we investigated the incorporation of major histocompatibility antigens (HLAs) on a primary macrophage-tropic isolate, HIV-1(ADA), grown from autologous monocyte-derived macrophages (MDMs) and peripheral blood mononuclear cells (PBMCs), A virus precipitation assay (VPA) demonstrated that HIV-1(ADA) grown from PBMCs incorporated substantial amounts of HLA class I (alpha chain and beta(2)m) and DR antigens, comparable with a laboratory strain, HIV-1(MN), grown from the same host cells. HIV-1(ADA), however, grown from MDMs incorporated significantly lower amounts of HLAI and -II antigens despite the fact that the infected MDMs were found to express significant amounts of HLA antigens. The lack of incorporation of these important immunomodulatory cell surface proteins may be yet another unique characteristic of macrophage-tropic isolates and suggests a possible role in their biology and or immunology. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Biochem Physiol, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Vaccine Resistant Dis Sect, Directors Lab,Off Basic Sci,Div Basic Sci, Frederick, MD 21702 USA. RP Tsai, WP (reprint author), NCI, Basic Res Lab, 37 Convent Dr,Bldg 37,Rm 6A11, Bethesda, MD 20892 USA. EM tsaiw@pop.nci.nih.gov NR 78 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JAN 1 PY 1999 VL 15 IS 1 BP 33 EP 41 DI 10.1089/088922299311682 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 157NW UT WOS:000078069400005 PM 10024050 ER PT J AU Dufour, MC AF Dufour, MC TI What is moderate drinking? Defining "drinks" and drinking levels SO ALCOHOL RESEARCH & HEALTH LA English DT Article DE moderate AOD use; standard drink; alcohol proof; wine; beer; distilled alcoholic beverage; survey; questionnaire; AOD use frequency; amount of AOD use; AOD abstinence; identification and screening for AOD use; self report; validity (research methods); reliability (research methods); AOD associated consequences; AOD impairment; risk assessment; literature review ID REPORTED ALCOHOL-CONSUMPTION; STANDARD DRINK; QUESTIONNAIRE; FREQUENCY; VALIDITY AB Although the benefits and risks associated with moderate drinking have gained increasing attention in recent years from both researchers and the general public, no universal definition of moderate drinking exists. Most currently used definitions are based on a certain number of drinks consumed in a specific time period Defining a "drink," however, also is difficult because alcoholic beverages can differ substantially in their alcohol content, even within the same beverage category (e.g., beer, wine, or distilled spirits). Because international differences in drink definitions also exist, comparing studies from different countries is difficult. The development of a universal definition of moderate drinking is hampered further by variations in de way alcohol consumption levels and drinking patterns are being assessed (i.e., the survey method and assessment modes used). Despite these problems, definitions of moderate drinking and drinking guidelines have been developed in the United States and other countries. C1 NIAAA, Bethesda, MD USA. RP Dufour, MC (reprint author), NIAAA, Bethesda, MD USA. NR 18 TC 136 Z9 138 U1 0 U2 3 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 0090-838X J9 ALCOHOL RES HEALTH JI Alochol Res. Health PY 1999 VL 23 IS 1 BP 5 EP 14 PG 10 WC Substance Abuse SC Substance Abuse GA 263CT UT WOS:000084105600001 PM 10890793 ER PT J AU Dufour, MC AF Dufour, MC TI Epidemiology: Four research perspectives SO ALCOHOL RESEARCH & HEALTH LA English DT Article C1 NIAAA, Bethesda, MD USA. RP Dufour, MC (reprint author), NIAAA, Bethesda, MD USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 0090-838X J9 ALCOHOL RES HEALTH JI Alochol Res. Health PY 1999 VL 23 IS 1 BP 8 EP 9 PG 2 WC Substance Abuse SC Substance Abuse GA 263CT UT WOS:000084105600002 ER PT J AU Fuller, RK Hiller-Sturmhofel, S AF Fuller, RK Hiller-Sturmhofel, S TI Alcoholism treatment in the United States - An overview SO ALCOHOL RESEARCH & HEALTH LA English DT Article DE addiction care; drug therapy; treatment research; United States; behavior therapy; cognitive therapy; Alcoholics Anonymous; motivational interviewing; treatment outcome; inpatient care; outpatient care; detoxification; aftercare; comparative study; patients; predictive factor; anti AOD (alcohol and other drug) craving agents; anti AOD abuse agents; intervention; literature review ID PLACEBO-CONTROLLED TRIAL; DISULFIRAM TREATMENT; RELAPSE PREVENTION; CLINICAL-TRIAL; DOUBLE-BLIND; DEPENDENCE; WITHDRAWAL; NALTREXONE; INPATIENT; FLUOXETINE AB On any given day, more than 700,000 people in the United States receive alcoholism treatment in either inpatient or outpatient settings. For many of those patients, detoxification-with or without pharmacotherapy-is the first step of treatment. The major behavioral approaches currently used in alcoholism treatment include cognitive-behavioral therapy, motivational enhancement therapy, and Alcoholics Anonymous (AA) or related 12-step programs. Clinical studies, such as the project MATCH trial, have compared the effectiveness of these approaches. Overall, that study detected no significant differences among the three treatments in patient outcome, although certain treatment methodologies may be most appropriate for patients with certain characteristics. Pharmacotherapy with aversive or anticraving medications may supplement behavioral treatment approaches. Brief interventions that are delivered by primary health care providers also have been shown to reduce drinking levels, particularly in nondependent drinkers. C1 NIAAA, Div Clin & Prevent Res, Bethesda, MD 20892 USA. RP Fuller, RK (reprint author), NIAAA, Div Clin & Prevent Res, Bethesda, MD 20892 USA. NR 33 TC 46 Z9 46 U1 6 U2 10 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 0090-838X J9 ALCOHOL RES HEALTH JI Alochol Res. Health PY 1999 VL 23 IS 2 BP 69 EP 77 PG 9 WC Substance Abuse SC Substance Abuse GA 272UG UT WOS:000084668900001 PM 10890799 ER PT J AU Hommer, DW AF Hommer, DW TI Functional imaging of craving SO ALCOHOL RESEARCH & HEALTH LA English DT Article DE AOD (alcohol and other drug) craving; single photon emission computed tomography; positron emission tomography; magnetic resonance imaging; brain imaging; blood flow measurement; cocaine; brain; basal ganglia; limbic system; brain function; neurotransmission; dopamine; glucose metabolism; literature review ID COCAINE; ACTIVATION; CIRCUITS; REWARD AB To visualize brain activity associated with mental states, such as craving for alcohol and other drugs (AODs), researchers have begun to use functional imaging techniques. Three commonly used techniques are single photon emission computed tomography (SPECT), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI). Studies using these three approaches have been reviewed in order to evaluate the validity of a proposed model of the brain regions involved in alcoholism and the craving for alcohol. This model suggests a central role for a connected group : of brain regions that include the basal:ganglia, thalamus, and orbital cortex. A study using SPECT technology in alcoholics, however, found altered brain activity in only some of those regions during craving. Additional studies in alcoholics, as well as cocaine users, identified several other brain regions whose activities appeared to change in response to :craving, These studies have led to the development of a revised model of brain regions involved in craving for AODs. Numerous questions remain, however, that must be-answered before the brain areas involved in craving can be identified conclusively. C1 NIAAA, Sect Brain Electrophysiol & Imaging, Clin Studies Lab, Div Intramural Clin & Biol Res, Bethesda, MD USA. RP Hommer, DW (reprint author), NIAAA, Sect Brain Electrophysiol & Imaging, Clin Studies Lab, Div Intramural Clin & Biol Res, Bethesda, MD USA. NR 17 TC 43 Z9 47 U1 0 U2 0 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 0090-838X J9 ALCOHOL RES HEALTH JI Alochol Res. Health PY 1999 VL 23 IS 3 BP 187 EP 196 PG 10 WC Substance Abuse SC Substance Abuse GA 276WC UT WOS:000084900500004 PM 10890814 ER PT J AU Allen, JP Sillamaukee, P Anton, R AF Allen, JP Sillamaukee, P Anton, R TI Contribution of carbohydrate deficient transferrin to gamma glutamyl transpeptidase in evaluating progress of patients in treatment for alcoholism SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE carbohydrate deficient transferrin; gamma glutamyl transpeptidase; biochemical markers; laboratory tests; relapse ID CONSUMPTION; SERUM; INCREASE; RELAPSE; MARKER AB Eight previous investigations have suggested that conjoint consideration of findings on tests for gamma glutamyl transpeptidase (GGT) and carbohydrate deficient transferrin (CDT) substantially enhances sensitivity of screening for alcohol problems while minimally diminishing specificity, Using results from a large clinical trial, the current study evaluated the two tests singly and in combination as measures of three clinically important treatment outcome criteria: any drinking, at least one day of heavy drinking, and at least three consecutive days of heavy drinking during the past month. When scored by quartile, CDT is slightly better at screening for alcohol problems in males than GGT. However, CDT seems less accurate in females than GGT, Use of the two tests in consort moderately improves the individual test accuracy in predicting drinking status for both genders. C1 NIAAA, Rockville, MD 20892 USA. Pharmacia & Upjohn Diagnost AB, Alcohol Related Dis, Uppsala, Sweden. Med Univ S Carolina, Columbia, SC USA. RP Allen, JP (reprint author), NIAAA, 6000 Execut Blvd, Rockville, MD 20892 USA. NR 23 TC 26 Z9 26 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JAN PY 1999 VL 23 IS 1 BP 115 EP 120 DI 10.1097/00000374-199901000-00016 PG 6 WC Substance Abuse SC Substance Abuse GA 162CH UT WOS:000078327500016 PM 10029211 ER PT J AU Holder, H Flay, B Howard, J Boyd, G Voas, R Grossman, M AF Holder, H Flay, B Howard, J Boyd, G Voas, R Grossman, M TI Phases of alcohol problem prevention research SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE prevention; phases; innovation; dissemination; sequence ID MINIMUM DRINKING AGE; TIME-SERIES ANALYSIS; TRAFFIC CRASHES; PEER PRESSURE; LEGISLATION; EXPERIENCE; PROGRAM; MASSACHUSETTS; RESTAURANTS; BEHAVIORS AB We build on precedents from other health research to present a phases model of research for alcohol problem prevention that accommodates the special characteristics of this research. We propose a five-level model, in which research moves along a series of relevant continua: from basic to more and more applied research; from descriptive hypothesis-generating pilot studies to full-fledged, methodologically sophisticated, hypothesis-testing studies; from smaller to larger samples for testing; from greater to lesser control of experimental conditions; from more artificial "laboratory" environments to real-world geographically defined communities; from testing the effects of single prevention strategies to more complex studies of multiple strategies integrated into intervention systems; and from research-driven outcome studies to "demonstration" projects that evaluate the capacity of various types of communities to implement prevention programs based on prior evaluations. The five phases of research are: (1) foundational research to define and determine the prevalence of specific alcohol-involved problems, establish causal factors and processes that yield the specific problems or increase the risk of a problem, and provide the foundations for the development of effective prevention interventions; (2) developmental (preliminary effectiveness) studies to develop and test the likely effectiveness, safety, and costs of new interventions or to assess the effectiveness, safety, and costs of an existing intervention; (3) efficacy studies to determine the effects, safety, and costs of an intervention under optimal conditions of implementation (or availability or enforcement) and acceptance (or adoption at the community, organizational, or group level; or participation, compliance, or adherence at the individual level); (4) effectiveness studies of the real-world effectiveness of preventive interventions with purposeful or natural variation in implementation and acceptance; and (5) demonstration studies of the effects of interventions when widely disseminated. The proposed phases model for alcohol problem prevention research presented herein differs in significant ways from the models established by other National Institutes of Health agencies. Greater emphasis is placed on natural experiments, on methods development along the whole research continuum, on collapsing or combining research phases when appropriate, on recognizing the critical importance of behavioral parameters early as well as late in the research sequence, and on extending the research continuum to embrace diffusion and dissemination (i,e., technology transfer) studies. We also include examples of phased research in existing alcohol studies and a discussion of relevant issues, including cost, special populations, methods, and dissemination. If systematically followed, this model has the potential to contribute to wider testing and dissemination of prevention interventions of known effectiveness. C1 Prevent Res Ctr, Berkeley, CA 94704 USA. Univ Illinois, Chicago, IL USA. NIAAA, Rockville, MD 20852 USA. Pacific Inst Res & Evaluat, Bethesda, MD USA. Natl Bur Econ Res, New York, NY 10003 USA. RP Holder, H (reprint author), Prevent Res Ctr, 2150 Shattuck Ave,Suite 900, Berkeley, CA 94704 USA. OI Flay, Brian/0000-0002-5209-2766 NR 65 TC 25 Z9 26 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JAN PY 1999 VL 23 IS 1 BP 183 EP 194 DI 10.1097/00000374-199901000-00027 PG 12 WC Substance Abuse SC Substance Abuse GA 162CH UT WOS:000078327500028 PM 10029222 ER PT B AU Caughey, B Chabry, J Demaimay, R Herrmann, LM Horiuchi, M Raymond, LD Raymond, GJ Caughey, WS DebBurman, SK Lindquist, S Chesebro, B AF Caughey, B Chabry, J Demaimay, R Herrmann, LM Horiuchi, M Raymond, LD Raymond, GJ Caughey, WS DebBurman, SK Lindquist, S Chesebro, B BE Iqbal, K Swaab, DF Winblad, B Wisniewski, HM TI Formation of protease-resistant prion protein in vitro: Stimulation and inhibition SO ALZHEIMER'S DISEASE AND RELATED DISORDERS: ETIOLOGY, PATHOGENESIS AND THERAPEUTICS LA English DT Proceedings Paper CT 6th International Conference on Alzheimers Disease and Related Disorders CY JUL 18-23, 1998 CL AMSTERDAM, NETHERLANDS ID CELL-FREE CONVERSION; CONGO RED; PRP ACCUMULATION; SCRAPIE; BETA; AGGREGATION; PORPHYRINS; PEPTIDES; BINDING; FORMS C1 NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Caughey, B (reprint author), NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RI Chabry, Joelle/O-2101-2016 NR 32 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 0-471-98683-6 PY 1999 BP 581 EP 587 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BM93Q UT WOS:000080188100065 ER PT J AU Jaffe, ES Krenacs, L Kumar, S Kingma, DW Raffeld, M AF Jaffe, ES Krenacs, L Kumar, S Kingma, DW Raffeld, M TI Extranodal peripheral T-cell and NK-cell neoplasms SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE T-cell lymphoma; cytotoxic T cells; NK cells; Epstein-Barr virus; extranodal lymphoma ID EPSTEIN-BARR-VIRUS; RENAL-TRANSPLANT PATIENT; ANGIOCENTRIC IMMUNOPROLIFERATIVE LESIONS; LETHAL MIDLINE GRANULOMA; NATURAL-KILLER; GAMMA-DELTA; LYMPHOMATOID GRANULOMATOSIS; CLINICOPATHOLOGICAL ENTITY; MALIGNANT HISTIOCYTOSIS; HEMOPHAGOCYTIC SYNDROME AB Mature or peripheral T-cell lymphomas are uncommon, accounting for only 10% to 15% of all non-Hodgkin lymphomas, and their classification has been controversial. In contrast to B-cell lymphomas, cytologic features have not been useful in defining disease entities, and cytologic grade has not been useful in predicting the clinical course. Similarly, many entities of T-cell or NK-cell derivation do not have a specific immunophenotype. Clinical features are of major importance, sometimes more important than the precise cell of origin, in defining T-cell and NK-cell neoplasms. Most extranodal T-cell/NK-cell lymphomas have a cytotoxic phenotype. The expression of cytotoxic molecules may predispose to apoptosis by tumor cells and normal bystander cells Three major categories of extranodal T/NK cell tumors are nasal, intestinal, and subcutaneous panniculitis-like. Hepatosplenic ya T-cell lymphoma is a more systemic disease derived from functionally immature cytotoxic cells. Many extranodal T-cell and NK-cell neoplasms are associated with Epstein-Barr virus (EBV); the association seems site dependent and shows some geographic variation. Tumors resembling any of the 3 prototypes may occur in a variety of extranodal sites. Extranodal T/NK cell lymphomas occur with increased frequency in the setting of immune suppression, especially after organ transplantation. C1 NCI, Hematopathol Sect, Pathol Lab, Bethesda, MD 20892 USA. RP Jaffe, ES (reprint author), Bldg 10,Room 2N202,MSC-1500,10 Ctr Dr, Bethesda, MD 20892 USA. RI Krenacs, Laszlo/L-8063-2014 OI Krenacs, Laszlo/0000-0001-6541-3031 NR 82 TC 81 Z9 87 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JAN PY 1999 VL 111 IS 1 SU 1 BP S46 EP S55 PG 10 WC Pathology SC Pathology GA 154MG UT WOS:000077892500005 PM 9894469 ER PT J AU Jaffe, ES Harris, NL Diebold, J Muller-Hermelink, HK AF Jaffe, ES Harris, NL Diebold, J Muller-Hermelink, HK TI World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues - A progress report SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE lymphoma; T cell; B-cell; Hodgkin's disease; non-Hodgkin's lymphoma; leukemia ID T-CELL LYMPHOMA; MONOCLONAL-ANTIBODY ALK1; NON-HODGKINS-LYMPHOMAS; CLINICOPATHOLOGICAL ENTITY; CLINICAL-SIGNIFICANCE; TRANSLOCATION; PHENOTYPE; SUBTYPE; ORIGIN AB The World Health Organization (WHO) classification has been developed under the joint auspices of the European Association for Hematopathology (EAHP) and the Society for Hematopathology (SH). First organized in 1995, the Steering Committee appointed 10 committees for T-cell and B-cell lymphomas and leukemias and myeloid and histiocytic tumors to develop a relevant list of diseases and establish definitions of each disease according to established criteria. The WHO classification uses the principles of the Revised European American Classification of Lymphoid Neoplasms (REAL), which defines each disease according to its morphologic features, immunophenotype, genetic features, postulated normal counterpart, and clinical features. The proposed classification was presented at the United States-Canadian Academy of Pathology meeting in 1997 The Steering Committee also appointed a Clinical Advisory Committee to ensure that the classification meets clinical needs and to resolve questions of clinical significance. The proposed WHO classification for lymphomas is similar to the REAL classification for lymphomas, with minor modifications and reassessment of provisional categories based on new data since 1994. C1 NCI, Hematopathol Sect, Pathol Lab, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Hotel Dieu, Serv Cent Anat & Cytol Pathol, Paris, France. Univ Wurzburg, Dept Pathol, D-8700 Wurzburg, Germany. RP Jaffe, ES (reprint author), Bldg 10,Room 2N202,MSC-1500,10 Ctr Dr, Bethesda, MD 20892 USA. NR 26 TC 180 Z9 218 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JAN PY 1999 VL 111 IS 1 SU 1 BP S8 EP S12 PG 5 WC Pathology SC Pathology GA 154MG UT WOS:000077892500002 PM 9894466 ER PT J AU Crump, AD Haynie, DL Aarons, SJ Adair, E Woodward, K Simons-Morton, BG AF Crump, AD Haynie, DL Aarons, SJ Adair, E Woodward, K Simons-Morton, BG TI Pregnancy among urban African-American teens: Ambivalence about prevention SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Article ID DECISION-MAKING; ADOLESCENTS; BEHAVIOR; CONTRACEPTIVES; TEENAGERS AB Objective: To develop a better understanding of the beliefs and influences that predispose teen females to early pregnancy. Methods: We conducted focus groups with 37 nonparenting, African-American females 14-17 years old recruited from an urban, hospital outpatient clinic. Results: Participants suggested that although pregnancy and parenting are best delayed until one is older, they American females 14-17 years old recruited from an urban, hospital outpatient clinic. Results: Participants suggested that although pregnancy and parenting are best delayed until one is older, they are common, manageable experiences, Contraceptive use was deemed as important, though contraceptive options were often perceived as ineffective, unsafe, or unpleasant. Conclusion: This study highlights the importance of developing further research to understand ambivalence and interventions to address ambivalent attitudes. C1 Univ Maryland, Dept Hlth Educ, College Pk, MD 20742 USA. NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. NIH, DC Initiat Pregnancy Prevent Protocol, Washington, DC USA. Res Triangle Inst, Rockville, MD USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. NICHD, Prevent Res Branch, DESPR, NIH, Bethesda, MD USA. RP Crump, AD (reprint author), Univ Maryland, Dept Hlth Educ, HHP Bldg Rm 2387, College Pk, MD 20742 USA. EM ac166@umail.umd.edu OI Simons-Morton, Bruce/0000-0003-1099-6617; Haynie, Denise/0000-0002-8270-6079 NR 35 TC 8 Z9 8 U1 1 U2 4 PU PNG PUBLICATIONS PI STAR CITY PA PO BOX 4593, STAR CITY, WV 26504-4593 USA SN 1087-3244 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PD JAN-FEB PY 1999 VL 23 IS 1 BP 32 EP 42 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 164YY UT WOS:000078492200004 ER PT J AU Hediger, ML Overpeck, MD Kuczmarski, RJ McGlynn, A Maurer, KR Davis, WW AF Hediger, ML Overpeck, MD Kuczmarski, RJ McGlynn, A Maurer, KR Davis, WW TI Growth at ages 3-6 years of non-Hispanic white, non-Hispanic black and Mexican-American children born small or large for gestational age. SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD USA. NCHS, CDC, Hyattsville, MD USA. PricewaterhouseCoopers, Washington, DC USA. Westat Inc, Rockville, MD USA. 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 USA SN 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PY 1999 VL 11 IS 1 MA 130 BP 114 EP 114 PG 1 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA 154HL UT WOS:000077883300042 ER PT J AU North, KE Maccluer, JW Howard, BV Welty, TK Lee, ET Fabsitz, RR AF North, KE Maccluer, JW Howard, BV Welty, TK Lee, ET Fabsitz, RR TI Heritabilities of cardiovascular disease risk factors in American Indians: The strong heart family study. SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Meeting Abstract C1 SW Fdn Biomed Res, San Antonio, TX 78284 USA. Medlant Res Inst, Washington, DC USA. Aberdeen Area Tribal Chairmens Hlth Board, Rapid City, SD USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. NHLBI, Bethesda, MD 20892 USA. 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 USA SN 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PY 1999 VL 11 IS 1 MA 157 BP 124 EP 124 PG 1 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA 154HL UT WOS:000077883300068 ER PT J AU Brown, KD Barlow, C Wynshaw-Boris, A AF Brown, KD Barlow, C Wynshaw-Boris, A TI Multiple ATM-dependent pathways: An explanation for pleiotropy SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Editorial Material ID ATAXIA-TELANGIECTASIA GENE; CELL-CYCLE CHECKPOINT; REPLICATION PROTEIN-A; DEFICIENT MICE; INDUCED PHOSPHORYLATION; IONIZING-RADIATION; DNA-DAMAGE; C-ABL; PRODUCT; P53 C1 Louisiana State Univ, Med Ctr, Dept Biochem & Mol Biol, New Orleans, LA 70112 USA. Louisiana State Univ, Med Ctr, Stanley S Scott Canc Ctr, New Orleans, LA 70112 USA. Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA. Natl Human Genome Res Inst, Genet Dis Res Branch, NIH, Bethesda, MD USA. RP Brown, KD (reprint author), Louisiana State Univ, Med Ctr, Dept Biochem & Mol Biol, 1901 Perdido St, New Orleans, LA 70112 USA. NR 36 TC 42 Z9 42 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JAN PY 1999 VL 64 IS 1 BP 46 EP 50 DI 10.1086/302223 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 164RM UT WOS:000078477400008 PM 9915942 ER PT J AU Witt, M Wang, YF Wang, SB Sun, CE Pawlik, J Rutkiewicz, E Zebrak, J Diehl, SR AF Witt, M Wang, YF Wang, SB Sun, CE Pawlik, J Rutkiewicz, E Zebrak, J Diehl, SR TI Exclusion of chromosome 7 for Kartagener syndrome but suggestion of linkage in families with other forms of primary ciliary dyskinesia SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter ID IMMOTILE CILIA; GENE; LOCALIZATION; LOCI C1 Polish Acad Sci, Inst Human Genet, PL-60479 Poznan, Poland. NIH, Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. Inst TB & Lung Dis, Rabka, Poland. RP Diehl, SR (reprint author), Polish Acad Sci, Inst Human Genet, PL-60479 Poznan, Poland. NR 28 TC 13 Z9 13 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JAN PY 1999 VL 64 IS 1 BP 313 EP 318 DI 10.1086/302203 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 164RM UT WOS:000078477400042 PM 9915976 ER PT J AU Lalwani, AK Luxford, WM Mhatre, AN Attaie, A Wilcox, ER Castelein, CM AF Lalwani, AK Luxford, WM Mhatre, AN Attaie, A Wilcox, ER Castelein, CM TI A new locus for nonsyndromic hereditary hearing impairment, DFNA17, maps to chromosome 22 and represents a gene for cochleosaccular degeneration SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter ID TEMPORAL BONE FINDINGS; MYOSIN HEAVY-CHAIN; LINKAGE; MUTATION C1 Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, Lab Mol Otol, San Francisco, CA 94143 USA. House Ear Clin, Los Angeles, CA USA. Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, Bethesda, MD USA. RP Lalwani, AK (reprint author), Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, Lab Mol Otol, San Francisco, CA 94143 USA. FU NIDCD NIH HHS [K08 DC 00112, DC00026] NR 29 TC 24 Z9 24 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JAN PY 1999 VL 64 IS 1 BP 318 EP 323 DI 10.1086/302216 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 164RM UT WOS:000078477400043 PM 9915977 ER PT J AU Roukoyatkina, NI Chefer, SI Rifkind, J Ajmani, R Talan, MI AF Roukoyatkina, NI Chefer, SI Rifkind, J Ajmani, R Talan, MI TI Cold acclimation-induced increase of systolic blood pressure in rats is associated with volume expansion SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE plasma volume; blood volume; blood viscosity; ambient temperature; body temperature; cold acclimation ID CHRONIC EXPOSURE; SEASONAL-VARIATION; INDUCED ELEVATION; PLASMA-VOLUME; TEMPERATURE; HYPERTENSION; MORTALITY; AIR; CHOLESTEROL; PREVENTION AB To investigate the mechanisms of cold-induced hypertension, the systolic blood pressure (SBP) and average daily water consumption were measured weekly in 6-month-old male Wistar rats; they were subsequently acclimated to thermoneutrality (26 degrees C for 7 weeks), to cold temperature (6 degrees C for 9 weeks), and then again reacclimated to 26 degrees C for 5 weeks. Circulating plasma volume and whole blood viscosity were measured in subgroups of rats at the end of acclimation to 26 degrees C after 2 days, after 1, 6, and 8 weeks of cold, and after 2 and 5 weeks of rewarming. The control values obtained at the end of thermoneutral period were: SEP = 130.8 +/- 18.6 mm Hg, plasma volume = 41.9 +/- 4.64 mL/kg, whole body viscosity at shear rate of 22.5 per sec = 6.7 +/- 0.48 cps, and daily water consumption = 42.25 +/- 16.81 mL. After 48 h of cold exposure there was almost a 50% increase in plasma volume that persisted to a lesser degree throughout the whole period of cold exposure (P < .05). After 2 weeks of cold exposure the daily water consumption increased and SEP began to increase. After 6 weeks of cold exposure the SEP was 30 mm Hg above that of the control level (P < .001) and was accompanied by a 25% increase in whole blood viscosity (P < .05). At the end of 8 weeks of cold exposure the plasma volume was 56.8 +/- 9.51 mL/kg and the whole blood viscosity was 8.0 +/- 1.79 cps at the 22.5 per sec shear rate. During the 5 weeks of rewarming the elevation of SEP and increased whole blood viscosity persisted, whereas the increased daily water consumption and expanded plasma volume returned to normal. Therefore, the acclimation to cold is accompanied by the development of a volume-associated hypertension, which is sustained after rewarming without volume expansion. (C) 1999 American Journal of Hypertension, Ltd. C1 NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. NIA, Gerontol Res Ctr, Behav Sci Lab, NIH, Baltimore, MD 21224 USA. NIA, Gerontol Res Ctr, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. RP Talan, MI (reprint author), NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM markt@vax.grc.nia.nih.gov NR 42 TC 10 Z9 16 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JAN PY 1999 VL 12 IS 1 BP 54 EP 62 DI 10.1016/S0895-7061(98)00213-1 PN 1 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 174ED UT WOS:000079020400009 PM 10075385 ER PT J AU Cocco, P Dosemeci, M AF Cocco, P Dosemeci, M TI Peritoneal cancer and occupational exposure to asbestos: Results from the application of a job-exposure matrix SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE peritoneal cancer; asbestos; insulation workers; epidemiology; job-exposure matrices ID MALIGNANT MESOTHELIOMA; DEATH CERTIFICATES; MORTALITY; HAZARDS; DISCORDANCE; DISEASES; WOMEN; RISK AB Background Because of the rarity of peritoneal mesothelioma, occupational risks associated with it have seldom been studied particularly among women. In this respect, death certificates databases may provide numbers large enough for analysis, although the international Classification of Diseases, 9th revision (ICD-9) does not single out mesothelioma from the rest of peritoneal cancers. The aim of this paper is twofold: to explore occupational risks of peritoneal cancer among men and women, and to test the performance of a job-exposure matrix in detecting its association with asbestos exposure using the occupation and industry reported in the death certificate. Methods From a large database containing information on the 1984-1992 death certificates of 24 U.S. states, we identified 657 deaths from peritoneal cancer and 6,570 controls who died from non-malignant diseases, 1:10 matched by region, gender race, and 5-year age group. Results Occupations at risk included insulators among men, and machine operators among women. Among men, we found a significant increase in risk associated with employment in manufacturing industries, such as industrial and miscellaneous chemicals; miscellaneous nan-metallic mineral and stone products; construction and material handling machines; and electrical machinery equipment, and supplies; as well as in services to dwellings and other buildings. Industries at increased risk among women included elementary and secondary schools; miscellaneous retail stares; and publishing and printing. Our job-exposure matrix classified 17 male cases and 3 controls in the high probability category of exposure to asbestos (OR = 61.6). Among men, risk of peritoneal cancer increased significantly by probability and intensity of exposure to asbestos. No such pattern was observed among women. The job-exposure matrix did not classify any female subjects in the high probability or intensity of asbestos exposure. Discussion This study provides evidence that death certificate data and job-exposure matrices are useful tools to observe well-established associations, such as the one existing between peritoneal cancer and asbestos exposure among men, in spite of crude information disease misclassification, and occupational misclassification. These factors are more likely to preclude meaningful results among women. Am. J. Ind. Med. 35:9-14, 1999. Published 1999 Wiley-Liss, Inc.dagger C1 NCI, Occupat Studies Sect, Bethesda, MD 20892 USA. RP Dosemeci, M (reprint author), NCI, Occupat Studies Sect, 6130 Execut Blvd,EPN Room 418, Bethesda, MD 20892 USA. EM dosemecm@epndce.nci.nih.gov NR 23 TC 24 Z9 25 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 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JAN PY 1999 VL 35 IS 1 BP 9 EP 14 DI 10.1002/(SICI)1097-0274(199901)35:1<9::AID-AJIM2>3.0.CO;2-V PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 142EW UT WOS:000077187800002 PM 9884740 ER PT J AU Gladen, BC Longnecker, MP Schecter, AJ AF Gladen, BC Longnecker, MP Schecter, AJ TI Correlations among polychlorinated biphenyls, dioxins, and furans in humans SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE polychlorinated biphenyls; dioxins; dibenzofurans; human studies, veterans ID PCB CONGENER LEVELS; HUMAN-MILK; ORGANOCHLORINE PESTICIDES; VIETNAM VETERANS; ADIPOSE-TISSUE; MONO-ORTHO; BLOOD; COPLANAR; INFANTS; PLASMA AB Background Correlations among human levels of polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans potentially complicate interpretation of studies of their individual health effects. Outcomes attributed to one may, in fact, be due to another. Methods We present correlations among dioxins, furans, and PCBs in blood collected in 1991-1992 from 44 American Vietnam veterans from Michigan. Results Correlations among specific dioxins and furans ranged from 0.26 to 0.80, with the higher-chlorinated congeners being more highly correlated Correlations among PCBs ranged from 0.06 to 0.94, with those occurring at highest concentrations being more highly correlated Correlations of PCBs with dioxins and furans ranged from -0.09 to 0.59. Correlations of individual chemicals with total dioxin toxic equivalents ranged from 0.31 to 0.76. Discussion/Conclusions If confirmed in other populations, such correlations may allow the use of simpler assays bur may also raise issues of confounding and calibration. Am. J. Ind. Med. 35:15-20, 1999. Published 1999 Wiley-Liss, Inc.dagger C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Gladen, BC (reprint author), NIEHS, Biostat Branch, Mail Drop A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. OI Longnecker, Matthew/0000-0001-6073-5322 NR 22 TC 53 Z9 53 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JAN PY 1999 VL 35 IS 1 BP 15 EP 20 DI 10.1002/(SICI)1097-0274(199901)35:1<15::AID-AJIM3>3.0.CO;2-Z PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 142EW UT WOS:000077187800003 PM 9884741 ER PT J AU Ji, BT Silverman, DT Dosemeci, M Dai, Q Gao, YT Blair, A AF Ji, BT Silverman, DT Dosemeci, M Dai, Q Gao, YT Blair, A TI Occupation and pancreatic cancer risk in Shanghai, China SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE case-control study; epidemiology; occupation; pancreatic cancer; electrical work; job exposure matrix ID CIGARETTE-SMOKING; ELECTRIC-POWER; MANUFACTURING PLANT; BREAST-CANCER; LOS-ANGELES; MORTALITY; WORKERS; INTERVIEWS; LOUISIANA; EXPOSURE AB Background Any association between occupation and pancreatic cancer risk has not been conclusively demonstrated A population-based case-control study was conducted to examine occupational risks of pancreatic cancer in Shanghai, China. Methods The study included 451 pancreatic cancer patients newly diagnosed in 1990-1993 and 1,552 controls randomly selected from Shanghai residents. Information on a lifetime job history and other factors was obtained in a face-to-face interview. Results Among men, an increased risk of pancreatic cancer was associated with employment as an electrician (OR = 7.5, CI = 2.6-21.8), and a positive trend in risk with increasing duration of employment was apparent (P for trend = 0.0003). Exposure To electric magnetic fields (EMF) as measured by a job exposure matrix also was associated with an increased risk among electricians. Threefold risks were observed for men with the highest level of intensity and for those with the highest probability of EMF exposure, although women with heavy EMF exposure did not experience increased risk. Among men, elevated risks also were found for metal workers (OR = 2.1, CI = 1.0-4.8); toolmakers (OR = 3.4, CI = 1.4-7.1); plumbers and welders (OR = 3.0 CI = 1.2-7.5); and glass manufacturers, potters, painters, and construction workers (OR = 2.6, CI = 1.1-6.3). Among women, textile workers experienced an increased risk (OR = 1.4, CI = 0.8-2.6). Conclusions Our results suggest that occupations associated with exposures to metal and textile dusts or certain chemicals may increase the risk of pancreatic cancer: The elevated risk among electricians may warrant further study to evaluate the possible role of EMF or other exposures. Am. J. Ind. Med. 35:76-81, 1999. Published 1999 Wiley-Liss, Inc.dagger C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. RP Ji, BT (reprint author), NCI, 6130 Execut Blvd,EPN 415, Rockville, MD 20852 USA. NR 36 TC 24 Z9 25 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JAN PY 1999 VL 35 IS 1 BP 76 EP 81 DI 10.1002/(SICI)1097-0274(199901)35:1<76::AID-AJIM10>3.0.CO;2-6 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 142EW UT WOS:000077187800010 PM 9884748 ER PT J AU Bloembergen, WE Hakim, RM Stannard, DC Held, PJ Wolfe, RA Agodoa, LYC Port, FK AF Bloembergen, WE Hakim, RM Stannard, DC Held, PJ Wolfe, RA Agodoa, LYC Port, FK TI Relationship of dialysis membrane and cause-specific mortality SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE cellulosic; modified cellulosic; synthetic; mortality; dialysis; cause of death ID CHRONIC-HEMODIALYSIS PATIENTS; CHRONIC-RENAL-FAILURE; HIGH-FLUX DIALYSIS; NUTRITIONAL PARAMETERS; LIPID-PEROXIDATION; BIOCOMPATIBILITY; MORBIDITY; RISK; LIPOPROTEIN AB A number of studies have suggested that type of dialysis membrane is associated with differences in long-term outcome of patients undergoing hemodialysis, both in terms of morbidity and mortality. The purpose of this study was to determine the relationship of membrane type end specific causes of death. Data from the United States Renal Data System Case Mix Adequacy Study, a national random sample of hemodialysis patients who were alive on December 31, 1990, were used. Our study was limited to patients in this data set who were undergoing dialysis for at least 1 year (n = 4,055). For the main analytic models, membrane type was classified into two categories: unmodified cellulose or MC/SYN (which combines modified cellulose [MC] and synthetic membranes [SYN]), The relationships of membrane type and major causes of mortality were analyzed using Cox proportional hazards models, which adjusted for multiple (21) covariates, including demographics, comorbidity, Kt/V, and other parameters. Patients were censored at transplantation or 60 days after a switch to peritoneal dialysis. Compared with patients dialyzed with unmodified cellulose membranes, the adjusted relative mortality risk (RR) from infection was 31% lower (RR = 0.69; P = 0.03) and from coronary artery disease was 26% lower (RR = 0.74; P = 0.07) for patients dialyzed with MC/SYN membranes. No statistically significant difference (all P > 0.1) was found in mortality risk from cerebrovascular disease (RR = 1.08), other cardiac causes (RR = 0.86), malignancy (RR = 0.90), or other known causes (RR = 0.82) between patients dialyzed with MC/SYN compared with unmodified cellulose membranes. These results offer support to reported experimental and observational clinical studies that have found that unmodified cellulose membranes may increase the risk for both infection and atherogenesis. Further studies are necessary to evaluate the possibility of confounding factors, compare more specific membrane types, and determine the pathophysiology linking membrane type to cause-specific mortality. (C) 1999 by the National Kidney Foundation, Inc. C1 US Renal Data Syst Coordinating Ctr, Ann Arbor, MI USA. Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. Vanderbilt Sch Med, Dept Med, Nashville, TN USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Bloembergen, WE (reprint author), Kidney Epidemiol & Cost Ctr, 315 W Huron St,Suite 240, Ann Arbor, MI 48103 USA. FU NHLBI NIH HHS [R01-HL-36051-15]; NIDDK NIH HHS [N01-DK-3-2202, R01 DK49531-01] NR 36 TC 86 Z9 86 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JAN PY 1999 VL 33 IS 1 BP 1 EP 10 DI 10.1016/S0272-6386(99)70251-9 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 155VH UT WOS:000077966700002 PM 9915261 ER PT J AU Depner, T Beck, G Daugirdas, J Kusek, J Eknoyan, G AF Depner, T Beck, G Daugirdas, J Kusek, J Eknoyan, G TI Lessons from the hemodialysis (HEMO) study: An improved measure of the actual hemodialysis dose SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE hemodialysis; adequacy of hemodialysis; Kt/V; HEMO study; National Institutes of Health (NIH); National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK); clinical trial ID DIALYSIS; MORBIDITY; MORTALITY; PRESCRIPTION; EFFICIENCY; ADEQUACY AB The Hemodialysis (HEMO) Study is a multicenter, prospective, randomized, 2 x 2 factorial clinical trial designed to evaluate the efficacy of the dose of dialysis delivered ("standard" v "high") and dialysis membrane flux ("low" v "high") in reducing the morbidity and mortality of patients. The study is nearly half complete. Although both patients and investigators are blinded to the overall findings, which will not be available for another 3 years, important data have been generated from which a more accurate expression has been derived for the dose of dialysis received by each patient in the trial. This new expression of the effectiveness of dialysis, eKt/V, is a two-pool approximation derived from the traditional single-pool Kt/V (spKt/V) and time on dialysis. The dialysis prescription for the HEMO Study subjects is individualized to achieve the target dose for each patient and is closely monitored by measuring the more accurate and validated expression of eKt/V. Comparisons of the HEMO Study dose of dialysis with other studies have been confused by this unique expression (eKt/V) of the dialysis dose and adequacy adopted for the HEMO Study. The target eKt/V dose in the "standard" arm of the Study Is 1.05 and in the "high" arm is 1.45 per dialysis thrice weekly. Based on data available from 426 subjects randomized to each arm, the target of 1.05 in the "standard" dose of the HEMO Study is equivalent to an spKt/V of 1.32, and that of the "high" dose, 1.67. Thus, volunteers in the "standard" arm of the Study are receiving a tightly controlled and closely monitored dose, which is above the current national mean spKt/V, and above that of the accepted minimum standard spKt/V of 1.2. When completed, the HEMO Study will show whether there are merits of a tightly controlled hemodialysis dose that is consistently delivered over a prolonged period and whether a high dose Is beneficial and safe to prescribe. (C) 1999 by the National Kidney Foundation, Inc. C1 NIDDKD, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Calif Davis, Davis, CA USA. Univ Chicago, Chicago, IL 60637 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Depner, T (reprint author), Div Nephrol, 4301 X St, Sacramento, CA 95817 USA. EM tadepner@ucdavis.edu NR 26 TC 61 Z9 62 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JAN PY 1999 VL 33 IS 1 BP 142 EP 149 DI 10.1016/S0272-6386(99)70272-6 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 155VH UT WOS:000077966700023 PM 9915282 ER PT J AU Petraglia, F Gomez, R Luisi, S Florio, P Tolosa, JE Stomati, M Romero, R AF Petraglia, F Gomez, R Luisi, S Florio, P Tolosa, JE Stomati, M Romero, R TI Increased midtrimester amniotic fluid activin A: A risk factor for subsequent fetal death SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE activin A; corticotropin-releasing factor; amniocentesis; fetal death; amniotic fluid ID CORTICOTROPIN-RELEASING FACTOR; HUMAN-PLACENTA; INHIBIN-A; MEMBRANES; SECRETION; DISEASES; BINDING; HORMONE; CELLS; LABOR AB OBJECTIVE: The objective of this study was to determine whether concentrations of activin A and corticotropin-releasing factor in amniotic fluid can identify patients at risk of fetal death. STUDY DESIGN: A retrospective case-control study of women who have had a midtrimester amniocentesis was designed. Case subjects consisted of patients who had a spontaneous fetal death after the procedure, whereas the control group consisted of patients who had a normal pregnancy outcome after midtrimester amniocentesis. Dimeric activin A was measured by a specific 2-site enzyme immunoassay, and corticotropin-releasing factor was measured by a specific and sensitive radioimmunoassay after acidic extraction. Statistical analysis was performed with Mann-Whitney U test, Fisher's exact test, and chi(2) tests and regression analysis. RESULTS: First, activin A was detectable in all amniotic fluid samples. Second, the concentration of activin A in amniotic fluid increased with advancing gestational age. Third, patients who subsequently had a fetal death had a higher median concentration of activin A than those with a normal pregnancy outcome (P < .01). Fourth, an amniotic fluid concentration of activin A greater than the 95th confidence interval for gestational age was found in 40% of patients who subsequently had a fetal death (odds ratio: 21.6; P < .005). Finally, the median concentration of corticotropin-releasing factor in amniotic fluid was not different in case subjects and control subjects. CONCLUSIONS: An elevated concentration of activin A in amniotic fluid identifies women at risk of fetal death. C1 Univ Udine, Dept Surg Sci, Chair Obstet & Gynecol, I-33100 Udine, Italy. Univ Udine, Dept Obstet & Gynecol, I-33100 Udine, Italy. Univ Pisa, Dept Surg Sci, I-56100 Pisa, Italy. Univ Pisa, Dept Obstet & Gynecol, I-56100 Pisa, Italy. NICHHD, Perinatol Res Branch, Bethesda, MD 20892 USA. RP Petraglia, F (reprint author), Univ Udine, Dept Surg Sci, Chair Obstet & Gynecol, PS Maria della Misericordia, I-33100 Udine, Italy. RI PETRAGLIA, Felice/K-6535-2016 OI PETRAGLIA, Felice/0000-0002-8851-625X NR 25 TC 16 Z9 18 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 1999 VL 180 IS 1 BP 194 EP 197 DI 10.1016/S0002-9378(99)70174-2 PN 1 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 160HJ UT WOS:000078224200036 PM 9914603 ER PT J AU Nelson, KB Grether, JK AF Nelson, KB Grether, JK TI Tight nuchal cord morbidity and mortality - Reply SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Letter C1 NINDS, Neuroepidemiol Branch, Bethesda, MD 20892 USA. Calif Dept Hlth Serv, Birth Defects Monitoring Program, Emeryville, CA 94608 USA. RP Nelson, KB (reprint author), NINDS, Neuroepidemiol Branch, Fed Bldg,Room 714,7550 Wisconsin Ave, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 1999 VL 180 IS 1 BP 251 EP 251 DI 10.1016/S0002-9378(11)70006-0 PN 1 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 160HJ UT WOS:000078224200050 ER PT J AU Chrousos, GP AF Chrousos, GP TI Reproductive placental corticotropin-releasing hormone and its clinical implications SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT Round Table Research Meeting on Hormonal Markers and Endocrine and Paracrine Pathways of Labor CY 1997 CL WASHINGTON, D.C. ID PITUITARY-ADRENAL AXIS; STRESS C1 NICHD, Sect Pediat Endocrinol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Chrousos, GP (reprint author), NICHD, Sect Pediat Endocrinol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NR 7 TC 12 Z9 13 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 1999 VL 180 IS 1 SU S BP S249 EP S250 DI 10.1016/S0002-9378(99)70710-6 PN 3 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 160HN UT WOS:000078224700010 PM 9914627 ER PT J AU Battey, JF AF Battey, JF TI Hereditary recessive progressive SNHL - What is the incidence? Reply SO AMERICAN JOURNAL OF OTOLOGY LA English DT Letter C1 Natl Inst Deafness & Other Commun Disorders, Bethesda, MD 20892 USA. RP Battey, JF (reprint author), Natl Inst Deafness & Other Commun Disorders, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD JAN PY 1999 VL 20 IS 1 BP 136 EP 137 PG 2 WC Otorhinolaryngology SC Otorhinolaryngology GA 178BC UT WOS:000079244800031 ER PT J AU Fend, F Emmert-Buck, MR Chuaqui, R Cole, K Lee, J Liotta, LA Raffeld, M AF Fend, F Emmert-Buck, MR Chuaqui, R Cole, K Lee, J Liotta, LA Raffeld, M TI Immuno-LCM: Laser capture microdissection of immunostained frozen sections for mRNA analysis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; REED-STERNBERG CELLS; TISSUE-SECTIONS; ALLELIC LOSS; IN-SITU; RT-PCR; HISTOLOGICAL SECTIONS; MOLECULAR ANALYSIS; GENE-EXPRESSION; B-CELLS AB Microdissection of routinely stained or unstained frozen sections has been used successfully to obtain purified cell populations for the analysis of cell-specific gene expression patterns in primary tissues with a complex mixture of cell types. However, the precision and usefulness of microdissection is frequently limited by the difficulty to identify different cell types and structures by morphology alone. We therefore developed a rapid immunostaining procedure for frozen sections followed by laser capture microdissection (LCM) and RNA extraction, which allows targeted mRNA analysis of immunophenotypically defined cell populations. After fixation, frozen sections are immunostained under RNAse-free conditions using a rapid three-step streptavidin-biotin technique, dehydrated and immediately subjected to LCM. RNA is extracted from captured tissue, DNAse I treated, and reverse transcribed. Acetone-, methanol-, or ethanol/acetone-fixed sections give excellent immunostaining after 12 to 25 minutes total processing time. Specificity, precision, and speed of microdissection is markedly increased due to improved identification of desired (or undesired) cell types. The mRNA recovered from immunostained tissue is of high quality. Single-step PCR is able to amplify fragments of more than 600 bp from both housekeeping genes such as beta-actin as well as cell-specific messages such as CD4 or CD19, using cDNA derived from less than 500 immunostained, microdissected cells. Immuno-LCM allows specific mRNA analysis of cell populations isolated according to their immunophenotype or expression of function-related antigens and significantly expands our ability to investigate gene expression in heterogeneous tissues. C1 NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Raffeld, M (reprint author), NCI, Hematopathol Sect, Pathol Lab, NIH, Bldg 10,Room 2N110,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Cole, Kristina/M-3922-2015 NR 27 TC 265 Z9 281 U1 0 U2 4 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 1999 VL 154 IS 1 BP 61 EP 66 DI 10.1016/S0002-9440(10)65251-0 PG 6 WC Pathology SC Pathology GA 155YF UT WOS:000077973800010 PM 9916919 ER PT J AU Hammer, MF Zegura, SL Bergen, A Long, JC Klitz, W Templeton, AR Osipova, LP Posukh, OL Karafet, TM AF Hammer, MF Zegura, SL Bergen, A Long, JC Klitz, W Templeton, AR Osipova, LP Posukh, OL Karafet, TM TI New World Y chromosome founder haplotypes and the peopling of the Americas. SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract C1 Univ Arizona, Tucson, AZ 85721 USA. NIAAA, NIH, Rockville, MD 20852 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. Monash Univ, Clayton, Vic 3168, Australia. Univ Washington, St Louis, MO 63110 USA. Inst Cytol & Genet, Novosibirsk, Russia. RI Templeton, Alan/F-5963-2011; Osipova, Ludmila/O-6480-2014; Posukh, Olga/Q-6065-2016 OI Osipova, Ludmila/0000-0001-7602-1156; Posukh, Olga/0000-0003-1352-3591 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 USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 1999 SU 28 BP 144 EP 144 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 184JE UT WOS:000079607500178 ER PT J AU Long, JC Urbanek, M Romero, FC Goldman, D AF Long, JC Urbanek, M Romero, FC Goldman, D TI DNA marker analysis for evidence of European contributions to Native American gene pools before and after Columbus. SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract C1 NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. 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 USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 1999 SU 28 BP 186 EP 186 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 184JE UT WOS:000079607500294 ER PT J AU Romero, FC Urbanek, M Goldman, D Long, JC AF Romero, FC Urbanek, M Goldman, D Long, JC TI Population genetic studies of Athabascan speaking populations in the American Southwest. SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. Univ New Mexico, Dept Anthropol, Albuquerque, NM 87131 USA. NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. 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 USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 1999 SU 28 BP 234 EP 234 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 184JE UT WOS:000079607500431 ER PT J AU Pitterle, DM Sperling, RT Myers, MG White, MF Blackshear, PJ AF Pitterle, DM Sperling, RT Myers, MG White, MF Blackshear, PJ TI Early biochemical events in insulin-stimulated fluid phase endocytosis SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE pinocytosis; signaling pathways; wortmannin; PD-98059; horseradish peroxidase ID ACTIVATED PROTEIN-KINASE; EPIDERMAL GROWTH-FACTOR; COOH-TERMINAL TRUNCATION; PHOSPHOINOSITIDE 3-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; FACTOR-I; RECEPTOR SUBSTRATE-1; GLUT4 TRANSLOCATION; SIGNAL-TRANSDUCTION; CELLS AB We examined the initial molecular mechanisms by which cells nonselectively internalize extracellular solutes in response to insulin. Insulin-stimulated fluid phase endocytosis (FPE) was examined in responsive cells, and the roles of the insulin receptor, insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3'-kinase (PI S'-kinase), Pas, and mitogen-activated protein kinase kinase (MEK) were assessed. Active insulin receptors were essential, as demonstrated by the stimulation of FPE by insulin in HIRc-B cells (Rat-l cells expressing 1.2 x 10(6) normal insulin receptors/cell) but not in untransfected Rat-1 cells or in Rat-1 cells expressing the inactive A/K1018 receptor. IRS-1 expression augmented insulin-stimulated FPE, as assessed in 32D cells, a hematopoietic precursor cell line lacking endogenous IRS-1. Insulin-stimulated FPE was inhibited in mouse brown adipose tissue (BAT) cells expressing the 17N dominant negative mutant Ras and was augmented in cells expressing wild-type Ras. The MEK inhibitor PD-98059 had little effect on insulin-stimulated FPE in BAT cells. In 32D cells, but not in HIRc-B and BAT cells, insulin-stimulated FPE was inhibited by 10 nM wortmannin, an inhibitor of PI 3'-kinase. The results indicate that the insulin receptor, IRS-1, Ras, and, perhaps in certain cell types, PI S'-kinase are involved in mediating insulin-stimulated FPE. C1 NIEHS, Off Clin Res, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr,Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Program Cell & Dev Biol, Boston, MA 02215 USA. RP NIEHS, Off Clin Res, A2-05, Res Triangle Pk, NC 27709 USA. NR 61 TC 6 Z9 6 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 EI 1522-1555 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JAN PY 1999 VL 276 IS 1 BP E94 EP E105 PG 12 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 157UL UT WOS:000078080000011 PM 9886955 ER PT J AU Pepe, S Tsuchiya, N Lakatta, EG Hansford, RG AF Pepe, S Tsuchiya, N Lakatta, EG Hansford, RG TI PUFA and aging modulate cardiac mitochondrial membrane lipid composition and Ca2+ activation of PDH SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE omega-3/omega-6 polyunsaturated fatty acids; mitochondria; calcium; pyruvate dehydrogenase; heart; rat ID DIETARY FISH-OIL; POLYUNSATURATED FATTY-ACIDS; RAT-HEART MITOCHONDRIA; PYRUVATE-DEHYDROGENASE ACTIVITY; FREE CA-2+ CONCENTRATION; RUTHENIUM RED; INTRAMITOCHONDRIAL METABOLISM; OXIDATIVE-PHOSPHORYLATION; MYOCARDIAL DYSFUNCTION; CALCIUM-TRANSPORT AB Aberrations in cell Ca2+ homeostasis have been known to parallel both changes in membrane lipid composition and aging. Previous work has shown that the lowered efficiency of work performance, which occurs in isolated hearts from rats fed a diet rich in n-6 polyunsaturated fatty acids (PUFA), relative to those fed n-3 PUFA, could be raised by mitochondrial (Mito) Ca2+ transport inhibition. We tested whether, after Ca2+-dependent stress, the Ca2+-dependent activation of pyruvate dehydrogenase (PDHA/PDHTotal) and Mite Ca2+ cycling could be manipulated by varying the ratio of n-3 to n-6 PUFA in Mite membranes in young (6 mo) and aged (24 mo) isolated rat hearts treated to n-3 or n-6 PUFA-rich diet. Inotropic stimulation by 1 mu M norepinephrine (NE) of 24-mo n-6 PUFA-rich hearts elevated total Mite Ca2+ content 38% more than in 6-mo hearts (P < 0.05). However, both the NE-induced rise in Mite Ca2+ and the difference in response between 6- and 24-mo hearts were partially abolished by n-3 PUFA treatment. NE increased the fractional activation of PDH by 44% above control levels in the 6-mo group compared with 49% in the 24-mo group after n-6 PUFA diet. However, NE stimulation of PDHA was attenuated by n-3 PUFA diet, attaining values only 29 and 23% above control levels in 6- and 24-mo mitochondria, respectively (P < 0.05). Global ischemia and reperfusion (I/R) in n-6 PUFA hearts gave rise to higher levels of total Mite Ca2+ concentration (P < 0.0001) and PDHA (P < 0.0001) compared with n-3 PUFA. Ruthenium red (3.4 mu M) abolished the effects of I/R in all groups. With aging, heart Mite membrane phosphatidylcholine was increased after n-6 PUFA-rich diet (by similar to 15%, P < 0.05), whereas cardiolipin and n-3 PUFA content were diminished by 31% (P < 0.05) and 73% (P < 0.05), respectively. These effects were prevented by n-3 PUFA-rich diet. The present study, by directly manipulating the cardiac Mite membrane n-3-to-n-6 PUFA ratio, shows that the activation of Ca2+-dependent PDH can be augmented when the n-3-to-n-6 PUFA ratio is low (n-6 PUFA-mich diet; 24-mo hearts) or attenuated when this ratio is relatively high (n-3 PUFA-rich diet). We propose that one of the consequences of dietary-induced manipulation of membrane phospholipids and PUFAs may be the altered flux of Ca2+ across the Mite membrane and thus altered intramitochondrial Ca2+-dependent processes. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Pepe, S (reprint author), NIA, Mol Genet Lab, Mitochondria & Aging Sect, Gerontol Res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 57 TC 108 Z9 109 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JAN PY 1999 VL 276 IS 1 BP H149 EP H158 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 158GX UT WOS:000078108600020 PM 9887028 ER PT J AU Leon, LR Kozak, W Rudolph, K Kluger, MJ AF Leon, LR Kozak, W Rudolph, K Kluger, MJ TI An antipyretic role for interleukin-10 in LPS fever in mice SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE acute phase response; anorexia; hypothermia; temperature regulation; sepsis; lipopolysaccharide ID CENTRAL-NERVOUS-SYSTEM; TUMOR-NECROSIS-FACTOR; RECEPTOR ANTAGONIST; LETHAL ENDOTOXEMIA; HUMAN-MONOCYTES; PROTECTS MICE; IL-10; LIPOPOLYSACCHARIDE; VASOPRESSIN; INDUCTION AB Interleukin (IL)-10 inhibits the synthesis of proinflammatory cytokines implicated in fever, including IL-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha. We hypothesized that IL-10 functions as an antipyretic in the regulation of fevers to lipopolysaccharide (LPS) and turpentine. Body temperature was measured by biotelemetry. Swiss Webster (SW) mice treated with recombinant murine IL-10 were resistant to fever induced by a low dose of LPS (100 mu g/kg ip) and to the hypothermic and febrile effects of a high (septiclike) dose of LPS (2.5 mg/kg ip). IL-10 knockout mice developed an exacerbated and prolonged fever in response to a low dose of LPS (50 mu g/kg ip) compared with their wild-type counterparts. At 4 h after injection of the low dose of LPS, plasma levels of IL-6, but not TNF-alpha, were significantly elevated in the IL-10 knockout mice compared with their wild-type controls (ANOVA, P < 0.05). After injection of the same high dose of LPS injected into SW mice, wild-type mice developed a fever at 24 h whereas IL-10 knockout mice immediately developed a profound hypothermia that lasted through 41 h (ANOVA, P < 0.05). Body weight and food intake were more significantly depressed in response to the high dose of LPS in the knockout mice compared with their wild-type controls. Only 30% of the IL-10 knockout mice survived compared with 100% of the wild-type mice (Fisher's exact test, P < 0.05). Fever in response to the injection of turpentine (100 mu l/mouse sc) did not differ between wild-type and IL-10 knockout mice. These data support the hypotheses that 1) IL-10 functions as an endogenous antipyretic following exposure to LPS, 2) a putative mechanism of the early antipyretic action of IL-10 is through the inhibition of plasma levels of IL-6, 3) IL-10 has a protective role in the lethal effects of exposure to high levels of LPS, and 4) endogenous IL-10 does not have a role in fever induced by turpentine. C1 Lovelace Resp Res Inst, Albuquerque, NM 87185 USA. RP Leon, LR (reprint author), NIDDKD, Diabet Branch, NIH, Bldg 10,Rm 8N-252,10 Ctr Dr MSC 1770, Bethesda, MD 20892 USA. RI Kozak, Wieslaw/L-5976-2014 FU NIAID NIH HHS [AI-27556] NR 38 TC 76 Z9 81 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD JAN PY 1999 VL 276 IS 1 BP R81 EP R89 PG 9 WC Physiology SC Physiology GA 157PT UT WOS:000078071400010 PM 9887180 ER PT J AU Kim, GH Ecelbarger, CA Mitchell, C Packer, RK Wade, JB Knepper, MA AF Kim, GH Ecelbarger, CA Mitchell, C Packer, RK Wade, JB Knepper, MA TI Vasopressin increases Na-K-2Cl cotransporter expression in thick ascending limb of Henle's loop SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE antidiuretic hormone; countercurrent multiplication; sodium chloride transport ID BRATTLEBORO RATS; NEPHRON SEGMENTS; NACL TRANSPORT; WATER CHANNEL; KIDNEY; MOUSE; ADH; CLONING; RECEPTOR; ATPASE AB To investigate whether the enhancement of thick ascending limb (TAL) NaCl transport in response to long-term increases in circulating vasopressin concentration is associated with increased expression levels of the apical Na-K-2Cl cotransporter in the rat TAL, we have carried out immunoblotting and immunofluorescence studies using affinity-purified, peptide-directed antibodies. Semiquantitative immunoblotting studies demonstrated a marked increase (193% of controls) in Na-K-2Cl cotransporter band density in response to restriction of water intake to 15 ml/day for 7 days. In contrast, the expression levels of two other apical proteins of the TAL (the type 3 Na/H exchanger and Tamm-Horsfall protein) were unchanged in the outer medulla. A 7-day subcutaneous infusion of the V(2) receptor-selective vasopressin analog, 1-desamino-[8-D-arginine]vasopressin (DDAVP), to Brattleboro rats also markedly increased Na-K-2Cl cotransporter expression in the outer medulla (183% of controls). Immunofluorescence localization in outer medullary tissue sections confirmed the increase in Na-K-2Cl cotransporter expression in response to DDAVP. We conclude that vasopressin strongly upregulates the expression of the Na-K-2Cl cotransporter of the TAL and that it is likely to play an important role in the long-term regulation of the countercurrent multiplication system. C1 NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. George Washington Univ, Dept Biol Sci, Washington, DC 20052 USA. Univ Maryland, Coll Med, Dept Physiol, Baltimore, MD 21201 USA. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, 10 Ctr Dr MSC 1603,Bldg 10,Rm 6N260, Bethesda, MD 20892 USA. RI chen, xuanlan/H-4158-2011 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NHLBI NIH HHS [Z01-HL-01282]; NIDDK NIH HHS [DK-32839] NR 33 TC 222 Z9 224 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JAN PY 1999 VL 276 IS 1 BP F96 EP F103 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 157AZ UT WOS:000078037800012 PM 9887085 ER PT J AU Park, JM Yang, TX Arend, LJ Schnermann, JB Peters, CA Freeman, MR Briggs, JP AF Park, JM Yang, TX Arend, LJ Schnermann, JB Peters, CA Freeman, MR Briggs, JP TI Obstruction stimulates COX-2 expression in bladder smooth muscle cells via increased mechanical stretch SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE cyclooxygenase-1; urinary tract; prostaglandins ID PEPTIDE GENE-EXPRESSION; RAT URINARY-BLADDER; REFLEX MICTURITION; ANGIOTENSIN-II; CYCLOOXYGENASE-2; PROSTANOIDS; FIBROBLASTS; INDUCTION; CAPACITY; CLONING AB Studies were performed to investigate the regulatory mechanism of bladder cyclooxygenase-2 (COX-2) expression after outlet obstruction. In situ hybridization of murine bladder tissues using COX-2-specific riboprobes demonstrated that COX-2 expression was induced predominantly in the bladder smooth muscle cells after outlet obstruction. To study the effect of increased mechanical stretch on COX isoform expression, cultured rat bladder smooth muscle cells were grown on silicone elastomer-bottomed plates coated with collagen type I and were subjected to continuous cycles of stretch/relaxation for variable duration. COX-1 mRNA levels did not change with stretch. COX-2 expression increased in a time-dependent manner after stretch, with maximal mRNA and protein levels occurring after 4 h. PGE(2) levels increased more than 40-fold in the culture media after stretch, consistent with increased COX activity, and this was reduced to near completion in the presence of a COX-2 inhibitor, NS-398. Exposure to stretch over a 48-h period induced a 4.7 +/- 0.6-fold increase in tritiated thymidine incorporation rate. This increase in DNA synthesis was markedly suppressed when the cells were stretched in the presence of NS-398. We conclude that in bladder obstruction COX-2 activation occurs predominantly in the smooth muscle cells in response to mechanical stretch. Our findings also suggest that stretch-activated COX-2 expression may participate in bladder smooth muscle cell proliferation and thereby play a role in pathological bladder wall thickening after obstruction. C1 Childrens Hosp, Dept Urol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Park, JM (reprint author), Childrens Hosp, Dept Urol, 300 Longwood Ave, Boston, MA 02115 USA. RI Briggs, Josephine/B-9394-2009 OI Briggs, Josephine/0000-0003-0798-1190 NR 34 TC 76 Z9 77 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JAN PY 1999 VL 276 IS 1 BP F129 EP F136 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 157AZ UT WOS:000078037800015 PM 9887088 ER PT J AU Lilly, AA Mehlman, PT Higley, JD AF Lilly, AA Mehlman, PT Higley, JD TI Trait-like immunological and hematological measures in female rhesus across varied environmental conditions SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Article DE Macaca mulatta; traits; individual differences; immunology; hematology; stress; CD subsets ID NONHUMAN-PRIMATES; HORMONAL RESPONSES; IMMUNE FUNCTION; MATERNAL SEPARATION; CORTISOL SECRETION; SOCIAL SEPARATION; IRON OVERLOAD; MONKEYS; STRESS; LYMPHOCYTES AB In this 2-year longitudinal study, 45 2-year-old female rhesus were observed as they were captured and removed from a free-ranging setting (Phase I), single caged for 1 year (Phase II), and housed in small, stable social groups for an additional year (Phase III). During the study, eight blood samples were taken, and hematological, immunological, and hormonal variables were assayed to determine whether I) any of the measures would exhibit trait-like, inter-individual longitudinal stability, despite fluctuations in population means induced by Phases I, II, and III; 2) plasma concentrations of cortisol, prolactin, and norepinephrine would be lowest in Phase III, and elevated during the periods of acute and chronic stress associated with Phases I and II; and 3) there would be any evidence of immunosuppression associated with Phases I and II. The results suggest that the majority of hematological/immunological variables were trait-like throughout the study in contrast to plasma cortisol, prolactin, and norepinephrine concentrations. Thus, red blood cells, hemoglobin, hematocrit, platelets, mean corpuscular volume and hemoglobin, as well as white blood cells, the absolute number of CD4+ (T-helper/ inducer) cells, the absolute number of CD8+ (T-suppressor/cytotoxic) cells, total T cells (CD2+%), total B cells (CD20+%), and the ratio of CD4+/ CD8+ cells were trait-like. The hematological measures were changed dramatically by capture and the subsequent single caging, with most not recovering to presumed baselines until after 12-28 weeks. The immune measures were depressed at capture (excepting B cells), and during 7 months of single caging failed to return to normal levels associated with social housing. We thus conclude that single housing can produce significant, long-term features of Immunosuppression. Capture produced significant increases in plasma cortisol, prolactin, and norepinephrine concentrations. Long periods of single caging produced significant increases in plasma prolactin concentrations, indicative of stress-induced anxiety, and may also have been associated with down-regulation of plasma norepinephrine and cortisol concentrations. (C) 1999 Wiley-Liss, Inc. C1 NIAAA, Clin Studies Lab, Primate Unit, Poolesville, MD 20837 USA. SUNY Stony Brook, Dept Anthropol, Stony Brook, NY 11794 USA. RP Lilly, AA (reprint author), 5843 Van Simmons, Wauchula, FL 33873 USA. FU NCRR NIH HHS [5U42RR05083, R24 RR09983] NR 67 TC 22 Z9 23 U1 2 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PY 1999 VL 48 IS 3 BP 197 EP 223 DI 10.1002/(SICI)1098-2345(1999)48:3<197::AID-AJP3>3.0.CO;2-Y PG 27 WC Zoology SC Zoology GA 201XN UT WOS:000080622600003 PM 10380995 ER PT J AU Norcross, JL Newman, JD AF Norcross, JL Newman, JD TI Effects of separation and novelty on distress vocalizations and cortisol in the common marmoset (Callithrix jacchus) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Article DE social separation; cortisol; marmosets; separation vocalizations; Callithrix jacchus ID PITUITARY-ADRENAL ACTIVITY; MONKEY CALLICEBUS-MOLOCH; SQUIRREL-MONKEYS; PHEE CALLS; PAIR-BOND; PHYSIOLOGICAL-RESPONSES; HORMONAL RESPONSES; RHESUS-MONKEYS; STRESS; MOTHER AB In socially-bonding species, separation from familiar attachment figures is widely known to stimulate a physiological. and behavioral stress response. This study investigated the hormonal and vocal responses of adult common marmosets to separation from familiar group members and to 24 hr of cohabitation with an unfamiliar opposite-sex conspecific, All subjects were removed from their home cages and placed into a novel environment for 20 min. In one group, marmosets were exposed to an unfamiliar, opposite-sex partner in the novel environment and remained paired with this partner for the 24 hr test period. In three other groups, marmosets experienced the novel environment alone and subsequently were returned to their original social- or single-housing condition, or kept separate from their social groups for a 24 h period. Blood samples were collected the day before, and at 30 min, 90 min, and at 24 h after separation. Cortisol responses were differentially affected by the length of separation and the presence of unfamiliar conspecifics. Brief separation followed by the return to the social group had minimal effect on plasma cortisol levels. All marmosets produced high levels of separation calls in the novel environment, but there was no apparent relationship between calling and cortisol levels. The lack of a temporal relationship between the production of distress vocalizations and serum cortisol has previously been noted in squirrel monkey and rhesus monkey infant separation studies; the behavioral and physiological responses to;separation appear to be similarly dissociated in the marmoset, Further, the characteristics of a separation environment can differentially affect the hormonal response by adult marmosets without differentially affecting their behavioral response. Am. J. Primatol. 47:209-222, 1999. Published 1999 Wiley-Liss, Inc.(dagger) C1 NICHD, Comparat Ethol Lab, NIH, Poolesville, MD 20837 USA. RP Norcross, JL (reprint author), NICHD, Comparat Ethol Lab, NIH, POB 529, Poolesville, MD 20837 USA. EM jn41j@nih.gov NR 53 TC 50 Z9 52 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PY 1999 VL 47 IS 3 BP 209 EP 222 PG 14 WC Zoology SC Zoology GA 172CA UT WOS:000078903700003 PM 10075435 ER PT J AU Leshner, AI AF Leshner, AI TI Science is revolutionizing our view of addiction - and what to do about it SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID COCAINE C1 Natl Inst Drug Abuse, Rockville, MD 20857 USA. RP Leshner, AI (reprint author), Natl Inst Drug Abuse, Room 10-05,5600 Fishers Lane, Rockville, MD 20857 USA. NR 10 TC 118 Z9 123 U1 0 U2 2 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 1999 VL 156 IS 1 BP 1 EP 3 PG 3 WC Psychiatry SC Psychiatry GA 153PP UT WOS:000077841700001 PM 9892289 ER PT J AU Avants, SK Margolin, A Sindelar, JL Rounsaville, BJ Schottenfeld, R Stine, S Cooney, NL Rosenheck, RA Li, SH Kosten, TR AF Avants, SK Margolin, A Sindelar, JL Rounsaville, BJ Schottenfeld, R Stine, S Cooney, NL Rosenheck, RA Li, SH Kosten, TR TI Day treatment versus enhanced standard methadone services for opioid-dependent patients: A comparison of clinical efficacy and cost SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SUBSTANCE-ABUSE TREATMENT; FORT-BRAGG; ISSUES AB Objective: This study examined the differential efficacy and relative costs of two intensities of adjunctive psychosocial services-a day treatment program and enhanced standard care-for the treatment of opioid-dependent patients maintained on methadone hydrochloride. Method: A 12-week randomized clinical trial with 6-month follow-up was conducted in a community-based methadone maintenance program. Of the 308 patients who met inclusion criteria, 291 began treatment (day treatment program: N=145; enhanced standard care: N=146), and 237 completed treatment (82% of those assigned to the day treatment program and 81% of those receiving enhanced standard care). Two hundred twenty of the patients participated in the 6-month follow-up (75% of those in the day treatment program and 73% of those in enhanced standard care provided a follow-up urine sample for screening). Both interventions were 12 weeks in duration, manual-guided, and provided by master's-level clinicians. The day treatment was an intensive, 25-hour-per-week program. The enhanced standard care was standard methadone maintenance plus a weekly skills training group and referral to on- and off-site services. Outcome measures included twice weekly urine toxicology screens, severity of addiction-related problems, prevalence of HIV risk behaviors, and program costs. Results: Although the cost of the day treatment program was significantly higher, there was no significant difference in the two groups' use of either opiates or cocaine. Over the course of treatment, drug use, drug-related problems, and HIV risk behaviors decreased significantly for patients assigned to both treatment intensities. Improvements were maintained at follow-up. Conclusions: Providing an intensive day treatment program to unemployed, inner-city methadone patients was not cost-effective relative to a program of enhanced methadone maintenance services, which produced comparable outcomes at less than half the cost. C1 Yale Univ, Sch Med, W Haven, CT 06516 USA. VA Med Ctr, W Haven, CT USA. Natl Inst Drug Abuse, Rockville, MD USA. RP Avants, SK (reprint author), Yale Subst Abuse Ctr, 34 Pk St, New Haven, CT 06519 USA. EM kelly.avants@yale.edu RI Cooney, Ned/C-5176-2014; OI Cooney, Ned/0000-0001-6698-8312; Stine, Susan/0000-0001-5426-4448 FU NIDA NIH HHS [DA-00112, DA-00277, DA-08754] NR 29 TC 65 Z9 66 U1 0 U2 2 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 1999 VL 156 IS 1 BP 27 EP 33 PG 7 WC Psychiatry SC Psychiatry GA 153PP UT WOS:000077841700006 PM 9892294 ER PT J AU Zubenko, GS Winwood, E Jacobs, B Teply, I Stiffler, JS Hughes, HB Huff, FJ Sunderland, T Martinez, AJ AF Zubenko, GS Winwood, E Jacobs, B Teply, I Stiffler, JS Hughes, HB Huff, FJ Sunderland, T Martinez, AJ TI Prospective study of risk factors for Alzheimer's disease: Results at 7.5 years SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PLATELET MEMBRANE FLUIDITY; AMYLOID PRECURSOR PROTEIN; APOLIPOPROTEIN-E GENOTYPE; E ALLELE EPSILON-4; LATE-ONSET; CHROMOSOME 14Q24.3; MISSENSE MUTATIONS; FAMILY HISTORY; TYPE-4 ALLELE; GENE AB Objective: The primary goal of this study was to evaluate increased platelet membrane fluidity as a putative risk factor for Alzheimer's disease and its relationship to the APOE epsilon 4 genotype. Method: This report describes the results of a prospective, longitudinal study of 330 initially asymptomatic, first-degree relatives of probands with Alzheimer's disease. Results: Nine incident cases of Alzheimer's disease were detected during the first 2,220 subject-years of the follow-up period. Age, increased platelet membrane fluidity, and the APOE epsilon 4 allele made significant independent contributions to the risk of developing Alzheimer's disease, while sex and years of education did not. Increased platelet membrane fluidity was associated with incident Alzheimer's disease cases between the ages of 64 and 71, while the epsilon 4 allele was associated with incident Alzheimer's disease cases from age 64 until at least age 80. Conclusions: These results indicate that increased platelet membrane fluidity is not produced by the APOE epsilon 4 allele. Instead, increased platelet membrane fluidity and the epsilon 4 allele appear to make significant independent contributions to the risk of developing Alzheimer's disease among the first-degree relatives of patients with this disorder. Moreover, the age ranges over which these risk factors operate appear to be different. C1 Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Pathol Neuropathol, Pittsburgh, PA USA. Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA. NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. RP Zubenko, GS (reprint author), Western Psychiat Inst & Clin, Rm E-1230,3811 OHara St, Pittsburgh, PA 15213 USA. FU NIA NIH HHS [AG-05133]; NIMH NIH HHS [MH-30915, MH-43261] NR 82 TC 19 Z9 20 U1 1 U2 3 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 1999 VL 156 IS 1 BP 50 EP 57 PG 8 WC Psychiatry SC Psychiatry GA 153PP UT WOS:000077841700009 PM 9892297 ER PT J AU Koo, JS Yoon, JH Gray, T Norford, D Jetten, AM Nettesheim, P AF Koo, JS Yoon, JH Gray, T Norford, D Jetten, AM Nettesheim, P TI Restoration of the mucous phenotype by retinoic acid in retinoid-deficient human bronchial cell cultures: Changes in mucin gene expression SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID TERATOCARCINOMA STEM-CELLS; VITAMIN-A-DEFICIENCY; TRACHEAL EPITHELIUM; MESSENGER-RNA; CHROMOSOMAL LOCALIZATION; RESPIRATORY SECRETIONS; MOLECULAR-CLONING; HAMSTER TRACHEA; ORGAN-CULTURES; IDENTIFICATION AB Retinoid-deficient cultures of airway epithelial cells undergo squamous differentiation. Treatment of such cultures with retinoic acid (RA) leads to restoration of the mucous phenotype. The purpose of our study was to characterize the cellular and molecular changes following RA treatment of retinoid-deficient human tracheobronchial epithelial cell cultures. Of particular interest was to determine when during the conversion of the squamous to the mucous phenotype the mucin genes MUC2, MUC5AC, and MUC5B were expressed. We used cornifin alpha and secreted mucin as markers to monitor the squamous and mucous phenotypes, respectively. Our studies showed that the RA responsiveness of the cultures progressively decreased with protracted retinoid deficiency, requiring higher RA concentrations to restore the mucous phenotype. Within 12 h after the start of RA treatment, cornifin ct expression decreased, signaling the beginning of a change in cellular phenotype. At 24 h after addition of RA to the cultures, a significant number of mucous cells appeared, and at 72 h mucin was secreted in measurable amounts. Induction of mucin gene expression occurred sequentially: MUC2, MUC5AC, and MUC5B mRNAs were upregulated at 24, 48, and 72 h, respectively. When cultures maintained in 10(-8) M RA were treated with 10(-6) M RA, MUC2 but not MUC5AC and MUC5B mRNA levels were upregulated within 6 h. Our study indicates that MUC2 mRNA is an early marker of mucous differentiation, whereas MUC5AC and MUC5B mRNAs are expressed during more advanced stages Of mucous differentiation. Our studies further suggest that each of the mucin genes is regulated by distinct mechanisms. C1 NIEHS, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. RP Nettesheim, P (reprint author), NIEHS, Pulm Pathobiol Lab, POB 12233,MD D2-01, Res Triangle Pk, NC 27709 USA. EM nettesh1@niehs.nih.gov RI Yoon, Joo-Heon/E-5781-2016; OI Jetten, Anton/0000-0003-0954-4445; Yoon, Joo-Heon/0000-0003-2404-7156 FU NHLBI NIH HHS [HL 36982] NR 46 TC 76 Z9 76 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JAN PY 1999 VL 20 IS 1 BP 43 EP 52 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 157QH UT WOS:000078072800006 PM 9870916 ER PT J AU Campo, E Miquel, R Krenacs, L Sorbara, L Raffeld, M Jaffe, ES AF Campo, E Miquel, R Krenacs, L Sorbara, L Raffeld, M Jaffe, ES TI Primary nodal marginal zone lymphomas of splenic and MALT type SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE nodal marginal zone lymphoma; monocytoid B cell lymphoma; MALT lymphoma; splenic marginal zone lymphoma ID B-CELL LYMPHOMA; PARAFOLLICULAR LYMPHOCYTES-B; CYTOGENETIC ANALYSIS; VILLOUS LYMPHOCYTES; REGION GENES; TISSUE; FEATURES; DISTINCT; NEOPLASM AB The existence of primary nodal marginal zone lymphomas (MZL) is controversial, as is their relationship to putative extranodal counterparts. Most nodal lymphomas with monocytoid B cell/marginal zone differentiation exhibit the morphologic and immunophenotypical characteristics of extranodal MALT-lymphomas. Splenic marginal zone lymphoma (SMZL) is also of putative marginal zone derivation, but it differs immunophenotypically from MALT lymphoma. To clarify the relationship between nodal and extranodal MZLs and to investigate the possible existence of a nodal variant of SMZL, 36 MZL initially considered to be primary nodal neoplasms were examined. Other low-grade lymphomas with marginal zone differentiation were excluded (small lymphocytic lymphoma/chronic lymphocytic leukemia [SLL/CLL], follicular lymphoma, and mantle cell lymphoma). Six nodal MZLs showed morphologic and phenotypic characteristics similar to those of SMZL, whereas 30 tumors were more similar to MALT-type lymphomas. The six tumors with SMZL features showed a polymorphic infiltrate surrounding residual germinal centers with absent or very attenuated mantle cuffs. These lymphomas were IgD positive (6/6) but cyclin D1 (0/5), CD5 (0/6), and CD23 (0/6) negative. Five of these patients came for treatment in stage I or II. No patient manifested splenomegaly, peripheral blood, and/or bone marrow infiltration either at diagnosis or during follow-up. Lymph nodes from 30 patients with MALT-type features showed a perisinusoidal and perivascular infiltration of monocytoid/centrocytoid cells and residual germinal centers with a relatively well-preserved mantle cuff. The neoplastic cells were negative for IgD (0/17), cyclin DI (0/8), and CD5 (0/12). Seven of 16 (44%) patients with a detailed history and clinical follow-up had evidence of extranodal lymphoma. These observations suggest that most nodal B cell lymphomas with marginal zone differentiation are of the MALT type and that they are frequently associated with an extranodal component In addition, a primary nodal counterpart of splenic MZL also exists, and may occur in the absence of splenomegaly. C1 NCI, Hematopathol Sect, Pathol Lab, Div Clin Sci,NIH, Bethesda, MD 20892 USA. RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, Div Clin Sci,NIH, Bldg 10,Room 2N202,10 Ctr Dr, Bethesda, MD 20892 USA. RI Krenacs, Laszlo/L-8063-2014; OI Krenacs, Laszlo/0000-0001-6541-3031; Campo, elias/0000-0001-9850-9793 NR 33 TC 94 Z9 96 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 1999 VL 23 IS 1 BP 59 EP 68 DI 10.1097/00000478-199901000-00006 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 154JP UT WOS:000077886000006 PM 9888704 ER PT J AU Romans, P Black, WC Sakai, RK Gwadz, RW AF Romans, P Black, WC Sakai, RK Gwadz, RW TI Linkage of a gene causing malaria refractoriness to Diphenol oxidase-A2 on chromosome 3 of Anopheles gambiae SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID PLASMODIUM-CYNOMOLGI B; DROSOPHILA-MELANOGASTER; ESTERASE LOCUS; VECTOR; ASSOCIATION; INFECTION; CLUSTER; STRAIN; SCLEROTIZATION; ENCAPSULATION AB An inbred line of the African malaria vector Anopheles gambiae is refractory to development of malaria parasites. It is homozygous for a 4.3-kb Sal I restriction fragment at the Dox-A2 locus, whereas the parent population is polymorphic at this locus, and a susceptible line is homozygous for an alternate 3.85-kb fragment. The Dox-A2 locus is located in the middle of chromosome 3R, in division 33B, and is tightly linked to a cluster of genes including Dopa decarboxylase that are involved in the production of melanin. Because the refractoriness phenotype, melanotic encapsulation of ookinete/oocysts, might involve activation of or alteration in one or more of these genes, we per formed generic crosses to determine whether a previously identified Plasmodium cynomolgi Ceylon refractoriness gene, Pif-C, is linked to Dox-A2. Backcross mosquitoes fed on one infected monkey developed infections of less than or equal to 100 oocysts. About 50% of these mosquitoes appeared phenotypically refractory, as expected for the backcross performed, but gave slight evidence of linkage between a refractoriness gene and Dox-A2. In contrast, females fed on a monkey that yielded higher infection levels, up to > 300 oocysts, showed clear evidence of linkage between a refractoriness gene and Dox-A2. We conclude that this Dox-A2-linked refractoriness gene is expressed under conditions particular to the higher infection levels, or that environmental factors obscured the generic effect of this gene at lower infection levels. C1 Univ Toronto, Dept Zool, Toronto, ON M5S 3G5, Canada. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Colorado State Univ, Dept Microbiol, Ft Collins, CO 80523 USA. RP Romans, P (reprint author), Univ Toronto, Dept Zool, Toronto, ON M5S 3G5, Canada. NR 37 TC 12 Z9 14 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JAN PY 1999 VL 60 IS 1 BP 22 EP 29 PG 8 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 163ZE UT WOS:000078436300004 PM 9988317 ER PT J AU Ferraris, JD AF Ferraris, JD TI Osmotically responsive genes: The mammalian osmotic response element (ORE). SO AMERICAN ZOOLOGIST LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC INTEGRATIVE COMPARATIVE BIOLOGY PI MCLEAN PA 1313 DOLLEY MADISON BLVD, NO 402, MCLEAN, VA 22101 USA SN 0003-1569 J9 AM ZOOL JI Am. Zool. PY 1999 VL 39 IS 5 SI SI MA 31 BP 7A EP 7A PG 1 WC Zoology SC Zoology GA 292NE UT WOS:000085800400032 ER PT J AU Flynn, KM Ferguson, SA Newbold, RR AF Flynn, KM Ferguson, SA Newbold, RR TI Estrogen mimics cause minimal behavioral alterations in rats. SO AMERICAN ZOOLOGIST LA English DT Meeting Abstract C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC INTEGRATIVE COMPARATIVE BIOLOGY PI MCLEAN PA 1313 DOLLEY MADISON BLVD, NO 402, MCLEAN, VA 22101 USA SN 0003-1569 J9 AM ZOOL JI Am. Zool. PY 1999 VL 39 IS 5 SI SI MA 145 BP 25A EP 26A PG 2 WC Zoology SC Zoology GA 292NE UT WOS:000085800400146 ER PT J AU Caughey, B Horiuchi, M Demaimay, R Raymond, GJ AF Caughey, B Horiuchi, M Demaimay, R Raymond, GJ TI Assays of protease-resistant prion protein and its formation SO AMYLOID, PRIONS, AND OTHER PROTEIN AGGREGATES SE METHODS IN ENZYMOLOGY LA English DT Review ID TRANSMISSIBLE MINK ENCEPHALOPATHY; CENTRAL-NERVOUS-SYSTEM; CELL-FREE CONVERSION; CULTURED-CELLS; SYNTHETIC PEPTIDES; SCRAPIE ISOFORM; PRP 27-30; INHIBITION; BRAIN; AGENT C1 NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Caughey, B (reprint author), NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NR 37 TC 26 Z9 26 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1999 VL 309 BP 122 EP 133 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BP32V UT WOS:000084721400009 PM 10507021 ER PT J AU Murphy, LD Zimmerman, SB AF Murphy, LD Zimmerman, SB TI A dilatancy assay for nucleoid denaturation: The centrifugation-dependent clumping of denatured spermidine nucleoids SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; SEDIMENTATION; CHROMOSOME; GENOME; DNA AB The ability of low centrifugal forces to convert denatured spermidine nucleoids from Escherichia coli into nonsedimentable macroscopic clumps is the basis of a rapid and simple, nonisotopic assay for nucleoid denaturation. C1 NIH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Murphy, LD (reprint author), NIH, Mol Biol Lab, Bldg 10, Bethesda, MD 20892 USA. NR 27 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JAN 1 PY 1999 VL 266 IS 1 BP 16 EP 22 DI 10.1006/abio.1998.2939 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 153UB UT WOS:000077850100003 PM 9887209 ER PT J AU Ghadimi, BM Heselmeyer-Haddad, K Auer, G Ried, T AF Ghadimi, BM Heselmeyer-Haddad, K Auer, G Ried, T TI Interphase cytogenetics: At the interface of genetics and morphology SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Review ID COMPARATIVE GENOMIC HYBRIDIZATION; HUMAN-CHROMOSOMES; EVENT C1 NCI, NIH, Dept Genet, Bethesda, MD 20892 USA. Karolinska Hosp & Inst, Dept Pathol & Oncol, Div Cellular & Mol Anal, Stockholm, Sweden. RP Ghadimi, BM (reprint author), NCI, NIH, Dept Genet, Bldg 49,4C24,49 Convent Dr, Bethesda, MD 20892 USA. NR 22 TC 5 Z9 5 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA VAN DIEMENSTRAAT 94, 1013 CN AMSTERDAM, NETHERLANDS SN 0921-8912 J9 ANAL CELL PATHOL JI Anal. Cell. Pathol. PY 1999 VL 19 IS 1 BP 3 EP 6 PG 4 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 276HU UT WOS:000084872800002 PM 10661620 ER PT J AU Rapallo, A Sciutto, A Geido, E Orecchia, R Infusini, E Pujic, N d'Amore, ESG Monaco, R Risio, M Rossini, FP Giaretti, W AF Rapallo, A Sciutto, A Geido, E Orecchia, R Infusini, E Pujic, N d'Amore, ESG Monaco, R Risio, M Rossini, FP Giaretti, W TI K-ras2 activation and genome instability increase proliferation and size of FAP adenomas SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Article ID ABERRANT CRYPT FOCI; GERM-LINE MUTATIONS; DNA FLOW-CYTOMETRY; K-RAS ONCOGENE; COLORECTAL-CANCER; APC GENE; POLYPOSIS PATIENTS; CYCLIN D1; APOPTOSIS; COLON AB The possible role of K-ras2 mutations and aneuploidy toward increase of proliferation and adenoma size in Familial Adenomatous Polyposis (FAP) adenomas is not known. The present study addresses these issues by investigating 147 colorectal adenomas obtained from four FAP patients. The majority of adenomas had size lower than or equal to 10 mm (86%), low grade dysplasia (63%), and were preferentially located in the right colon (60%). Normal mucosa samples were obtained from 19 healthy donors. Three synchronous adenocarcinomas were also investigated. K-ras2 mutation spectrum was analysed by PCR and Sequence Specific Oligonucleotide (SSO) hybridization, while flow cytometry (FCM) was used for evaluating degree of DNA ploidy and S-phase fraction. Overall, incidences of K-ras2 mutations, DNA aneuploidy and high S-phase values (>7.2%) were 6.6%, 5.4% and 10.5%, respectively. In particular, among the adenomas with size lower than 5 mm, K-ras2 mutation and DNA aneuploidy frequencies were only slightly above 1%. Statistically significant correlations were found between K-ras2 and size, DNA ploidy and size and K-ras2 and S-phase (p < 0.001). In particular, among the wild type K-ras2 adenomas, high S-phase values were detected in 8% of the cases versus 57% among the K-ras2 mutated adenomas (p = 0.0005). The present series of FAP adenomas indicates that K-ras2 activation and gross genomic changes play a role toward a proliferative gain and tumour growth in size. C1 Natl Canc Inst, Lab Biophys & Cytometry, I-16132 Genoa, Italy. Univ Padua, Pathol Serv, I-35100 Padua, Italy. Cardarelli Hosp, Pathol Serv, Naples, Italy. Natl Inst Canc Res & Treatment, Pathol Serv, Turin, Italy. S Giovanni Vecchio Hosp, ASLI, Gastroenterol Serv, Turin, Italy. RP Giaretti, W (reprint author), Natl Canc Inst, Lab Biophys & Cytometry, Largo Rosanna Renzi 10, I-16132 Genoa, Italy. NR 44 TC 2 Z9 2 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA VAN DIEMENSTRAAT 94, 1013 CN AMSTERDAM, NETHERLANDS SN 0921-8912 J9 ANAL CELL PATHOL JI Anal. Cell. Pathol. PY 1999 VL 19 IS 1 BP 39 EP 46 PG 8 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 276HU UT WOS:000084872800005 PM 10661623 ER PT J AU Szayna, M Zedler, L Voelkel, R AF Szayna, M Zedler, L Voelkel, R TI NMR microscopy and image processing for the characterization of flexible polyurethane foam SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE foams; materials science; microscopy; NMR spectroscopy; polyurethane C1 BASF AG, Kunststofflab, D-67056 Ludwigshafen, Germany. NIH, Baltimore, MD 21234 USA. Gesell Angew Informat, Berlin, Germany. RP Voelkel, R (reprint author), BASF AG, Kunststofflab, ZKM G201, D-67056 Ludwigshafen, Germany. NR 9 TC 2 Z9 2 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 1999 VL 38 IS 17 BP 2551 EP 2553 DI 10.1002/(SICI)1521-3773(19990903)38:17<2551::AID-ANIE2551>3.0.CO;2-J PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 234KL UT WOS:000082483700009 ER PT B AU Kaufman, JB Wang, G Zhang, W Valle, MA Shiloach, J AF Kaufman, JB Wang, G Zhang, W Valle, MA Shiloach, J BE Ikura, K Nagao, M Masuda, S Sasaki, R TI Continuous production and recovery of recombinant Ca++ binding receptor from HEK 293 cells using perfusion through a packed bed bioreactor SO ANIMAL CELL TECHNOLOGY: CHALLENGES FOR THE 21ST CENTURY LA English DT Proceedings Paper CT 1998 Joint International Meeting of the Japanese-Association-for-Animal-Cell-Technology/European-Society-for-Ani mal-Cell-Technology (JAACT/ESACT) CY JUL 26-30, 1998 CL KYOTO, JAPAN SP Japanese Assoc Anim Cell Technol, European Soc Anim Cell Technol DE perfusion; packed bed bioreactor; HEK 293 AB The extracellular domain of human parathyroid Ca++ receptor was needed for structural and clinical studies. The desired protein was produced by immobilizing the transformed HEK 293 cells in a packed bed configuration using a 2.2 liter bioreactor equipped with a vertical mixing impeller assembly and an internal basket. The production was done in two stages: a propagation stage followed by a production stage. In the first stage, which lasted approximately 140 hours, the bed was perfused with serum-containing medium, allowing the cells to grow at a constant growth rate. When the total cell population reached approximately 3x10(10), the second stage was begun. Serum-free medium replaced the serum containing medium, and the perfusion process was continued for an additional 400 hours. During this time: the medium was pumped through the packed bed at a rate of 4-6 liters per day, keeping the residual glucose concentration at 1 gl(-1). C1 NIDDK, Biotechnol Unit, LCDB, NIH, Bethesda, MD 20892 USA. RP Shiloach, J (reprint author), NIDDK, Biotechnol Unit, LCDB, NIH, Bdg 6,Rm B1-33, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-5805-8 PY 1999 BP 87 EP 91 PG 5 WC Biotechnology & Applied Microbiology; Cell Biology SC Biotechnology & Applied Microbiology; Cell Biology GA BP18F UT WOS:000084339700016 ER PT B AU Kaufman, J Cho, MW Lee, MK Shiloach, J AF Kaufman, J Cho, MW Lee, MK Shiloach, J BE Bernard, A Griffiths, B Noe, W Wurm, F TI Large scale production of HIV-1 gp120 using recombinant vaccinia virus in packed-bed bioreactor SO ANIMAL CELL TECHNOLOGY: PRODUCTS FROM CELLS, CELLS AS PRODUCTS LA English DT Proceedings Paper CT 16th Meeting of the European-Society-for-Animal-Cell-Technology (ESACT) CY APR 25-29, 1999 CL LUGANO, SWITZERLAND SP Akzo Nobel Pharma, Amersham Pharmacia Biotech, Ares Serono SA, B Braun Biotech Int GmbH, Bayer Corp, Bioengn AG, BioWhittaker Inc, Boehringer Ingelheim Pharm KG, BioInvent Prod AB, Canberra Packard SA, Cansera Int Inc, Cantone Ticino, Crossair Swissair, E Merck, Genentech Inc, Genet Inst, Genzyme Transgen Corp, Hoffmann La Roche AG, Hyclone Europe SA, Immuno AG, Div Baxter Inc, Immunex Corp, Inst Rech Pierre Fabre, Intervet Int BV, Inveresk Res Int Ltd, JRH Biosci, Life Technologies Ltd, Lonza Biol Plc, MA Bioserv, Merck Res Labs, MicroSafe BV, Novartis Pharma AG, Novo Nordisk AS, Nunc AS, Pall Europe Ltd, Pasteur Merieux Connaught, PCS Process Control Syst AG, Pharmacia & Upjohn AB, Q One Biotech Ltd, Sanofi Rech, Scharfe Syst GmbH, Schering AG, Swiss Red Cross, ZLB, SmithKline Beecham Biol, Union Bank Switzerland AB The HeLa cell-vaccinia virus system is an attractive method for producing recombinant mammalian proteins with proper post-translation modifications. This system is especially applicable to the production of the HIV-1 envelope glycoprotein, gp120, because more than half of its total mass is carbohydrates. A recombinant vaccinia virus/T7 RNA polymerase expression system to produce large amounts of gp120 was developed. The packed-bed bioreactor configuration was examined for pilot-scale production and was found to be an efficient system for both cell growth and virus infection resulting in high levels of gp120. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Shiloach, J (reprint author), NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-6075-3 PY 1999 BP 289 EP 291 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA BP71J UT WOS:000085945800064 ER PT J AU Gerin, W Bovbjerg, DH Glynn, L Davidson, K Sanders, M Sheffield, D Christenfeld, N AF Gerin, W Bovbjerg, DH Glynn, L Davidson, K Sanders, M Sheffield, D Christenfeld, N TI Comment on "Negative emotions and acute cardiovascular responses to laboratory challenges" SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Editorial Material ID REACTIVITY C1 NIH, Bethesda, MD 20892 USA. Mt Sinai Sch Med, New York, NY 10029 USA. Univ Calif Irvine, Irvine, CA USA. Univ Alabama, Tuscaloosa, AL 35487 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. E Tennessee State Univ, Johnson City, TN 37614 USA. Cornell Univ, Joan & Sanford I Weill Med Coll, Ithaca, NY 14853 USA. RP Gerin, W (reprint author), Cornell Univ, Hypertens Ctr, Joan & Sanford I Weill Med Coll, New York Presbyterian Hosp, Starr Pavil ST405,525 E 68th St, New York, NY 10021 USA. OI Sheffield, David/0000-0001-9121-1783 NR 11 TC 5 Z9 5 U1 0 U2 0 PU SOC BEHAVIORAL MEDICINE PI MIDDLETON PA 7611 ELMWOOD AVE, STE 201, MIDDLETON, WI 53562-3161 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PY 1999 VL 21 IS 3 BP 223 EP 224 DI 10.1007/BF02884837 PG 2 WC Psychology, Multidisciplinary SC Psychology GA 265GK UT WOS:000084233800005 ER PT J AU Thompson, DR Michele, JJ Cheever, EA George, DT AF Thompson, DR Michele, JJ Cheever, EA George, DT TI Selective stimulation of latissimus dorsi muscle for cardiac assist SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE electromyogram; thoracodorsal; isometric; cardiomyoplasty; aortomyoplasty ID PERIPHERAL-NERVE FIBERS; CUFF ELECTRODE; MULTICHANNEL STIMULATION; CARDIOMYOPLASTY; ANATOMY; AORTOMYOPLASTY; ACTIVATION AB The contractile power of the latissimus dorsi muscle (LDM) is used in skeletal muscle cardiac assist (SMCA) to augment the blood pumping ability of a failing heart. The LDM has three anatomically distinct, independently innervate segments-the transverse, oblique, and lateral. There are potential advantages to selectively stimulating these LDM regions. We hypothesized that (1) the three nerve branches could be stimulated selectively to activate individual muscle regions with little or no functional overlap, (2) the three muscle regions would generate similar force, and (3) nerves stimulated in combinations would generate forces corresponding to the sum of forces generated by the individual regions. In acute studies of canine LDM (n=5), regional electromyogram (EMG) and isometric force were recorded while branches of the thoracodorsal nerve were stimulated (via nerve-cuff electrodes) individually and in combinations. Analysis of regional EMG and force confirmed selective activation. Stimulation of lateral, oblique, and transverse branches of thoracodorsal nerve activated 53+/-5%, 20+/-9%, and 36+/-9% of the muscle, respectively; with corresponding developed forces of 48+/-6%, 21+/-8%, and 31+/-8% of total muscle force (R=0.98, p<0.05). Selective activation of LDM is possible with little or no functional overlap; however, the muscle regions were nonuniform. Selective stimulation may ultimately facilitate the use of performance enhancing stimulus protocols for SMCA. (C) 1999 Biomedical Engineering Society. [S0090-6964(99)01301-6]. C1 Case Western Reserve Univ, Div Cardiothorac Surg, Cleveland, OH 44106 USA. Presbyterian Med Ctr, Philadelphia Heart Inst, Philadelphia, PA 19104 USA. Swarthmore Coll, Swarthmore, PA 19081 USA. RP George, DT (reprint author), NHLBI, Rockledge Ctr 2, Room 7188,6701 Rockledge Dr,MSC 7924, Bethesda, MD 20892 USA. EM georged@nih.gov NR 27 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD JAN-FEB PY 1999 VL 27 IS 1 BP 48 EP 55 DI 10.1114/1.164 PG 8 WC Engineering, Biomedical SC Engineering GA 153VJ UT WOS:000077853400006 PM 9916760 ER PT J AU Ellsworth, DL Manolio, TA AF Ellsworth, DL Manolio, TA TI The emerging importance of genetics in epidemiologic research. I. Basic concepts in human genetics and laboratory technology SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE epidemiology; molecular genetics; human genome; polymorphism; genetic techniques; hereditary diseases ID APOLIPOPROTEIN-E POLYMORPHISM; HUMAN GENOME PROJECT; VASCULAR-DISEASE; RISK FACTOR; DNA; ATHEROSCLEROSIS; IDENTIFICATION; MUTATIONS; SEQUENCE; SAMPLES AB PURPOSE: To define a general framework of current approaches to the discovery of disease-associated genes and the role of genetic factors in influencing disease risk through the integration of genome technology and traditional epidemiologic methods. METHODS: An overview of basic concepts in human genetics, laboratory methodology for measuring genetic Variation believed to influence common diseases, and issues concerning preparation and utilization of genetic materials is provided as a foundation for genetic epidemiologic research. RESULTS: Identification and characterization of human genetic variation is providing new risk factors for disease in the form of DNA sequence variation. The availability of genetic material from participants in large epidemiologic studies and appropriate informed consent represents an invaluable resource for exploring genetic and environmental influences on disease risk. CONCLUSIONS: Advances in genome technology coupled with vast amounts of genetic data resulting from the Human Genome Project are broadening the scope of epidemiologic research and providing tools to identify individuals at increased risk of disease. Combining diverse expertise from the fields of epidemiology and human genetics provides unique opportunities to localize disease-susceptibility genes and examine molecular mechanisms of complex disease etiology. Published by Elsevier Science Inc. C1 NHLBI, Div Epidemiol & Clin Applicat, Epidemiol & Biometry Program, NIH, Bethesda, MD 20892 USA. RP Ellsworth, DL (reprint author), NHLBI, Div Epidemiol & Clin Applicat, Epidemiol & Biometry Program, NIH, 6701 Rockledge Dr,MSC 7934, Bethesda, MD 20892 USA. NR 51 TC 14 Z9 15 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JAN PY 1999 VL 9 IS 1 BP 1 EP 16 DI 10.1016/S1047-2797(98)00047-7 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 152KU UT WOS:000077777300001 PM 9915603 ER PT J AU Bergen, AW Wang, CY Tsai, J Jefferson, K Dey, C Smith, KD Park, SC Tsai, SJ Goldman, D AF Bergen, AW Wang, CY Tsai, J Jefferson, K Dey, C Smith, KD Park, SC Tsai, SJ Goldman, D TI An Asian-Native American paternal lineage identified by RPS4Y resequencing and by microsatellite haplotyping SO ANNALS OF HUMAN GENETICS LA English DT Article ID HUMAN Y-CHROMOSOME; MODERN HUMAN ORIGINS; HUMAN X-CHROMOSOME; ALLELE FREQUENCIES; HUMAN-POPULATIONS; SEX-CHROMOSOMES; HUMAN-EVOLUTION; LONG ARM; DNA; POLYMORPHISMS AB Human paternal population history was studied in 9 populations [three Native American, three Asian, two Caucasian and one African-derived sample(s)] using sequence and short tandem repeat haplotype diversity within the non-pseudoautosegmal region of the Y chromosome. Complete coding and additional flanking sequences (949 base pairs) of the RPS4Y locus were determined in 59 individuals from three of the populations, revealing a nucleotide diversity of 0.0147 %, consistent with previous estimates from Y chromosome resequencing studies. One RPS4Y sequence variant, 711C > T, was polymorphic in Asian and Native American populations, but not in African and Caucasian population samples. The RPS4Y 711C > T variant, a second unique sequence variant at DYS287 and nine Y chromosome short tandem repeat (YSTR) loci were used to analyze the evolution of Y chromosome lineages. Three unambiguous lineages were defined in Asian, Native American and Jamaican populations using sequence variants at RPX4Y and DYS287. These lineages were independently supported by the haplotypes defined solely by YSTR alleles, demonstrating the haplotypes constructed from YSTRs can evaluate population diversity, admixture and phylogeny. C1 NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. Johns Hopkins Univ, Kennedy Krieger Inst, Baltimore, MD 21205 USA. Seoul Natl Univ, Coll Med, Dept Biochem, Chongro Ku, Seoul 110799, South Korea. Taipei Blood Ctr, Taipei 100, Taiwan. RP Bergen, AW (reprint author), NCI, Genet Epidemiol Branch, DCEG, EPS 7110,6120 Execut Blvd, Rockville, MD 20852 USA. RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Bergen, Andrew/0000-0002-1237-7644 NR 77 TC 67 Z9 70 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD JAN PY 1999 VL 63 BP 63 EP 80 DI 10.1046/j.1469-1809.1999.6310063.x PN 1 PG 18 WC Genetics & Heredity SC Genetics & Heredity GA 221RF UT WOS:000081739500006 PM 10738521 ER PT J AU Shields, PG AF Shields, PG TI Molecular epidemiology of lung cancer SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT 3rd International Congress on Cancer - Chemotherapy of Non-Small-Cell Lung Cancer, New Achievements CY MAY 29-31, 1998 CL VENICE, ITALY SP UNESCO DE carcinogen metabolism; genetic susceptibility; risk assessment ID GLUTATHIONE-S-TRANSFERASE; DNA ADDUCT LEVELS; GERM-LINE POLYMORPHISMS; SQUAMOUS-CELL CARCINOMA; HEME-BINDING REGION; GSTM1 NULL GENOTYPE; CIGARETTE-SMOKING; GENETIC-POLYMORPHISM; AFRICAN-AMERICANS; 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE NNK AB Lung cancer occurs through a complex multistage process that results from the combination of carcinogen exposure and genetic susceptibilities. The primary etiology of lung cancer is tobacco smoking, but an understanding of why some smokers develop lung cancer, and others do not, remains unclear. Current studies focus on genetic susceptibilities to lung cancer, and how they modify the effects of tobacco smoke carcinogens. New assays are being developed to study other contributors to cancer risk, such as interindividual differences in DNA repair. There is current evidence to suggest that the risk of lung cancer for women, compared to men, is higher for the same level of smoking. Several biological differences for the types of lung cancer have been observed in women and men. Also, there appear to be differences in lung cancer between Caucasians and African-Americans. Molecular epidemiology tools are uniquely suited to study these biological differences. These studies will improve cancer risk assessments and focus cancer prevention strategies. Other studies also are focusing on tobacco addiction, in order to lead to improved smoking cessation strategies. C1 NCI, Mol Epidemiol Sect, Human Carcinogenesis Lab, Div Basic Sci, Bethesda, MD 20892 USA. RP Shields, PG (reprint author), NCI, Mol Epidemiol Sect, Human Carcinogenesis Lab, Div Basic Sci, Bldg 37,Room 2C16, Bethesda, MD 20892 USA. NR 68 TC 28 Z9 28 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1999 VL 10 SU 5 BP 7 EP 11 DI 10.1023/A:1008331616378 PG 5 WC Oncology SC Oncology GA 245EB UT WOS:000083092300003 ER PT J AU Del Mastro, L Gennari, A Donati, S AF Del Mastro, L Gennari, A Donati, S TI Chemotherapy of non-small-cell lung cancer: Role of erythropoietin in the management of anemia SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT 3rd International Congress on Cancer - Chemotherapy of Non-Small-Cell Lung Cancer, New Achievements CY MAY 29-31, 1998 CL VENICE, ITALY SP UNESCO DE anemia; chemotherapy; erythropoietin; lung cancer; review; toxicity ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; CISPLATIN-ASSOCIATED ANEMIA; PHASE-II; DOUBLE-BLIND; COMBINATION; TRIAL; DISEASE; GEMCITABINE; MULTICENTER; TRANSFUSION AB Main mechanisms involved in the development of chemotherapy-induced anemia are the direct bone marrow damage and the renal impairment with a secondary deficient production of erythropoietin. The first mechanism is induced by almost all cytotoxic drugs whilst the second one has been demonstrated with cisplatin treatment. NSCLC patients are generally treated with platinum-based chemotherapy and then both mechanisms are involved in the development of anemia which can be, as a consequence, more frequent and more severe compared to other cancer patients. Chemotherapy regimens such as MVP (mitomycin, vindesine, platin), cisplatin-etoposide and cisplatin-teniposide induce grade greater than or equal to 2 anemia in 64%, 46% and 83% of patients, respectively, with grade 3-4 anemia occurring in 29%, 15% and 24% of patients. New chemotherapy regimens are also associated with a high incidence of anemia. Carboplatin-paclitaxel induces grade 3-4 anemia in 34% of patients and 30% of patients need blood transfusions. Similarly, 33% of patients treated with cisplatin-gemcitabine require blood transfusions. Erythropoietin is able to correct anemia in nearly 60%-80% of patients receiving platinum-based chemotherapy and in nearly 40% of patients treated with regimens without platinum compounds, leading to a reduction in blood transfusion requirement. Moreover, erythropoietin is able to prevent anemia development in cancer patients. Due to the high incidence of anemia, erythropoietin may represent an important tool in the supportive care of NSCLC patients. Erythropoietin use is mainly limited by the economic cost and then efforts should be made to identify the subset of patients in whom this supportive therapy is cost-effective. Patient and disease characteristics, factors predicting the probability to be transfused as well as factors predicting the response to erythropoietin can be useful in selecting patients likely to benefit from erythropoietin therapy. C1 St Chiara Hosp, Dept Med Oncol, Pisa, Italy. RP Del Mastro, L (reprint author), Natl Canc Inst, L R Benzi 10, I-16132 Genoa, Italy. NR 25 TC 4 Z9 4 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1999 VL 10 SU 5 BP 91 EP 94 PG 4 WC Oncology SC Oncology GA 245EB UT WOS:000083092300019 ER PT J AU Jensen, RT AF Jensen, RT TI Pancreatic endocrine tumors: Recent advances SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT Conference on Biliopancreatic Malignancy - From Gene to Cure CY FEB 04-06, 1999 CL AMSTERDAM, NETHERLANDS SP Byk Nederland BV, Astra Pharmaceutica, Janssen Res Fdn DE apudoma; carcinoid; gastrinoma; glucagonoma; GRFoma; insulinoma; MEN1; neurofibromatosis; nonfunctional pancreatic endocrine tumor; somatostatinoma; VIPoma; von Hippel Lindau disease ID ZOLLINGER-ELLISON-SYNDROME; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; NEOPLASIA-TYPE-I; NEUROENDOCRINE TUMORS; SUPPRESSOR GENE; CHROMOGRANIN-A; LONG-TERM; METASTATIC GASTRINOMAS; DUODENAL GASTRINOMAS; CARCINOID-TUMORS AB Pancreatic endocrine tumors (PETs) can be divided on a clinical and pathologic basis into ten classes [insulinomas, gastrinomas (Zollinger-Ellison syndrome), VIPomas (Verner-Morrison syndrome, WDHA, pancreatic cholera), glucagonomas, somatostatinomas, ACTH-releasing tumors (ACTHomas), growth hormone-releasing factor secreting tumors (GRFomas), nonfunctioning or pancreatic polypeptide secreting tumors (nonfunctioning PET), PET's causing carcinoid syndrome and PET's causing hypercalcemia)]. Recent reports suggest calcitonin-secreting PET's also rarely occur but whether they cause a distinct clinical syndrome is unclear. PET's resemble carcinoid turners histologically; in their ability to synthesize and frequently secrete multiple peptides such as neuroendocrine cell markers (chromogranins); their biologic behavior and their tumor growth patterns. Both groups of tumors are highly vascular, have high densities of somatostatin receptors and similar tumor localization studies including somatostatin receptor scintigraphy are used for both. PET's, similar to carcinoids causing the carcinoid syndrome, require two separate treatment options be considered: treatment directed against the hormone-excess state and treatment directed against the tumor per se because of their malignant nature. In the last few years there have been advances in tumor diagnosis, localization methods, treatment approaches particularly related to the use of synthetic somatostatin analogues, and the definition of the role of surgical procedures in these diseases. Important other advances include insights into the long-term natural history of PET's particularly from studies of gastrinomas, which allow prognostic factors to be identified and the timing of treatment options to batter planned, as well as insights into the molecular basis of these disorders. The latter includes both a description of the molecular basis of the genetic inherited syndromes associated with PET's or carcinoid tumors, as well as an increased understanding of the molecular basis for sporadic PET's or carcinoid tumors. Each of these areas will be briefly highlighted in this presentation. C1 NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDKD, Digest Dis Branch, NIH, Bldg 10,Rm 9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. NR 53 TC 52 Z9 55 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1999 VL 10 SU 4 BP 170 EP 176 DI 10.1023/A:1008350517079 PG 7 WC Oncology SC Oncology GA 222RT UT WOS:000081799100044 PM 10436815 ER PT J AU Sindelar, WF Kinsella, TJ AF Sindelar, WF Kinsella, TJ TI Studies of intraoperative radiotherapy in carcinoma of the pancreas SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT Conference on Biliopancreatic Malignancy - From Gene to Cure CY FEB 04-06, 1999 CL AMSTERDAM, NETHERLANDS SP Byk Nederland BV, Astra Pharmaceutica, Janssen Res Fdn DE cancer; intraoperative radiotherapy; malignancy; pancreas; radiation; therapy ID RADICAL RESECTION; BEAM IRRADIATION; ADVANCED CANCERS; MORTALITY; MORBIDITY; SURVIVAL; PANCREATICODUODENECTOMY; PANCREATODUODENECTOMY; RADIATION; ADJUVANT AB Intraoperative radiotherapy (IORT) involves the administration of therapeutic radiation to malignancies during surgical procedures. IORT permits high dose delivery to tumors with the simultaneous reduction of radiation exposure to normal tissues, which may be directly shielded or operatively mobilized from the treatment volume. IORT has been investigated in various intra-abdominal malignancies, including carcinoma of the pancreas. Techniques of IORT were initially developed in Japan during the 1970's. Reports of therapeutic benefit in some patients with unresectable pancreatic cancer encouraged further examinations by various institutions in the United States. Experiences at the Massachusetts General Hospital in the early 1980's suggested that IORT enhanced survival in selected patients with locally advanced but non-metastatic disease. However, subsequent investigations studies by a variety of institutions, including the Mayo Clinic, failed to establish any conclusive evidence that IORT significantly prolonged the survival enhancement of unresectable pancreatic cancer patients. A prospective multi-institutional study carried out by the Radiation Therapy Oncology Group (RTOG) showed an 8-month median survival, similar to conventional therapy and indicating that IORT failed to prolong survival. However, the RTOG did show that IORT rapidly and consistently palliated the severe visceral pain which often accompanied pancreatic cancer. By 1990, some institutions had explored IORT as an adjunct to pancreatectomy, in patients with resectable tumors. Studies typically involved highly selected uncontrolled patients but did suggest that IORT could enhance local disease control and, in some cases, overall survival, when performed in conjunction with pancreatic resection. IORT appeared to be most conspicuously beneficial when used with extended radical resections. A small prospectively randomized trial conducted at the National Cancer Institute showed significant improvement in local disease control in patients receiving IORT compared with patients receiving conventional external beam postoperative radiotherapy after resection. Current evidence suggests that IORT may have an important palliative role in patients with unresectable pancreatic cancers, ameliorating visceral pain and promoting local control of the primary tumor; however, IORT appears to have no significant effect on overall survival. For patients with resectable disease, especially patients with locally extensive tumor, IORT appears to have benefit in enhancing disease control and in some cases survival. It is reasonable to further explore the potential role of IORT in pancreatic cancer, especially as a component of multimodal therapy, since IORT's demonstrated enhancement of local control could be an important factor in eventual disease control. C1 Case Western Reserve Univ, Sch Med, Dept Radiat Oncol, Cleveland, OH 44106 USA. NCI, NIH, Surg Branch, Bethesda, MD USA. RP Kinsella, TJ (reprint author), Case Western Reserve Univ, Sch Med, Dept Radiat Oncol, Cleveland, OH 44106 USA. NR 24 TC 48 Z9 49 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1999 VL 10 SU 4 BP 226 EP 230 DI 10.1023/A:1008395827074 PG 5 WC Oncology SC Oncology GA 222RT UT WOS:000081799100057 PM 10436828 ER PT J AU Gray, SD Bielamowicz, SA Titze, IR Dove, H Ludlow, C AF Gray, SD Bielamowicz, SA Titze, IR Dove, H Ludlow, C TI Experimental approaches to vocal fold alteration: Introduction to the minithyrotomy SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Laryngological-Association CY MAY 09-10, 1998 CL PALM BEACH, FLORIDA SP Amer Laryngol Assoc DE anatomy; lamina propria; minithyrotomy; scar; thyrotomy; vocal cord; vocal fold ID PHONOSURGERY AB Treatment of challenging laryngeal disorders, such as lamina propria loss or neuromuscular dysfunction, may require novel approaches and techniques. This paper discusses an evolution of experimental techniques for treatment of lamina propria loss and use of the minithyrotomy. These techniques have been used for surgical access for lamina propria substitution, as well as placement of stimulating electrodes. The minithyrotomy is tolerated well by patients, provides access for microscopic instruments with the surgeon's hand close to the tissue of interest, avoids intralaryngeal mucosal incisions, and lines up the direction of dissection in an anterior-to-posterior orientation. This orientation is favorable for particular situations herein discussed. We present anatomic and physiologic concepts relevant to the surgical treatment of lamina propria dysfunction, as well as presenting our clinical experience. This paper is not intended to state how these difficult problems should be handled, but rather, to present our experience in techniques that may prove useful through further development. C1 Univ Utah, Sch Med, Dept Surg, Div Otolaryngol, Salt Lake City, UT USA. George Washington Univ, Dept Surg, Div Otolaryngol, Washington, DC USA. Univ Iowa, Dept Speech Pathol & Audiol, Iowa City, IA 52242 USA. NIDCD, NIH, Bethesda, MD USA. RP Gray, SD (reprint author), 50 N Med Dr,3C120-SOM, Salt Lake City, UT 84132 USA. OI Ludlow, Christy/0000-0002-2015-6171 FU NIDCD NIH HHS [P60 DC00976-07, Z01 DC 00004-09] NR 21 TC 24 Z9 24 U1 0 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JAN PY 1999 VL 108 IS 1 BP 1 EP 9 PG 9 WC Otorhinolaryngology SC Otorhinolaryngology GA 158JG UT WOS:000078111800001 PM 9930534 ER PT J AU Kass, ES Fabian, RL Montgomery, WW AF Kass, ES Fabian, RL Montgomery, WW TI Manometric study of paranasal sinus mucoceles SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE manometry; paranasal sinus mucocele ID CHRONIC MAXILLARY ATELECTASIS; BONE-RESORPTION; PRESSURE; INTERLEUKIN-1; ACTIVATION AB A paranasal sinus mucocele is a chronic cystlike lesion characterized by slowly progressive remodeling and expansion of the surrounding osseous walls. If left untreated, it may cause significant facial deformity, ophthalmic disturbances, and, in the worst instance, intracranial complications. According to a review of the literature, there is a long-held view that positive pressure exists within paranasal sinus mucoceles; however, to our knowledge, pressure measurements have not been recorded in humans. In this study, pressure measurements were taken of 4 paranasal sinus mucoceles by means of an 18-gauge needle probe and an amplified pressure transducer. The average value was +15 cm H2O with a range of +4 to +39 cm H2O. This study confirms the long-standing assumption that positive pressure exists within paranasal sinus mucoceles. The magnitude of the pressure was comparable to that which was found to be associated with bone resorption in several previously published studies. Further studies are needed to determine whether positive pressure and osseous remodeling are causally related in this condition. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Kass, ES (reprint author), NIH, Bldg 10,Room 8B07,10 Ctr Dr MSC 1750, Bethesda, MD 20892 USA. NR 22 TC 9 Z9 9 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JAN PY 1999 VL 108 IS 1 BP 63 EP 66 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 158JG UT WOS:000078111800009 PM 9930542 ER PT J AU Martin, SE AF Martin, SE TI Police force or police service? Gender and emotional labor SO ANNALS OF THE AMERICAN ACADEMY OF POLITICAL AND SOCIAL SCIENCE LA English DT Article ID WORK AB Police work involves substantial emotional labor by officers, who must control their own emotional displays and those of citizens, who often are encountered at their worst-injured, upset, or angry. Although policing often is viewed as masculine work that focuses on lighting crime, it also requires that officers maintain order and provide diverse services, which officers tend to disdain as feminine activities. This article explores the varieties of emotional labor, the rules regulating emotional displays in policing, and the role of gender in shaping these occupational and organizational norms. It identifies variations in the norms regulating emotional labor across policing assignments, interactional situations, and the gender of both the officers and the citizens in an encounter. It also reviews coping mechanisms for regulating emotions-including socialization, organizational rituals, humor, and off-duty social activities-and the dilemmas that norms related to emotional labor pose for women officers. C1 Natl Res Council, Washington, DC 20418 USA. RP Martin, SE (reprint author), NIAAA, Res Program Alcohol & Violence, Bethesda, MD 20892 USA. NR 34 TC 83 Z9 83 U1 2 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0002-7162 J9 ANN AM ACAD POLIT SS JI Ann. Am. Acad. Polit. Soc. Sci. PD JAN PY 1999 VL 561 BP 111 EP 126 DI 10.1177/0002716299561001008 PG 16 WC Political Science; Social Sciences, Interdisciplinary SC Government & Law; Social Sciences - Other Topics GA 149PY UT WOS:000077615400008 ER PT J AU Tabor, CW Tabor, H AF Tabor, CW Tabor, H TI It all started on a streetcar in Boston SO ANNUAL REVIEW OF BIOCHEMISTRY LA English DT Review ID S-ADENOSYLMETHIONINE DECARBOXYLASE; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; SPERMIDINE BIOSYNTHESIS; 1,4-DIAMINOBUTANE PUTRESCINE; POLYAMINE REQUIREMENT; PROENZYME FORM; MUTANTS; GROWTH; GENE AB We first met on a Boston streetcar in 1940, being introduced by a mutual friend. Celia was returning from research work at the Massachusetts General Hospital as part of her senior thesis at Radcliffe College, and Herb was returning from a concert by the Boston Symphony. We were married in 1946 after Celia had finished her medical training. We started working together in 1952, and we are still actively collaborating in our studies on various aspects of the biosynthesis and function of polyamines. We are honored to have been invited by the editors of the Annual Review of Biochemistry to summarize our activities in biochemical research over the past 60 years. During most of this time we have been at the National Institutes of Health in Bethesda, hid., and we have witnessed the enormous expansion of biomedical research that has occurred during this period. In addition to summarizing our research, Herb summarizes his association with the Journal of Biological Chemistry and the remarkable developments that have occurred recently in electronic publication and dissemination of scientific literature. C1 NIDDKD, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. RP Tabor, CW (reprint author), NIDDKD, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. NR 82 TC 9 Z9 10 U1 0 U2 3 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4154 J9 ANNU REV BIOCHEM JI Annu. Rev. Biochem. PY 1999 VL 68 BP 1 EP + DI 10.1146/annurev.biochem.68.1.1 PG 33 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 238CK UT WOS:000082693200001 PM 10872442 ER PT J AU Sagui, C Darden, TA AF Sagui, C Darden, TA TI Molecular dynamics simulations of biomolecules: Long-range electrostatic effects SO ANNUAL REVIEW OF BIOPHYSICS AND BIOMOLECULAR STRUCTURE LA English DT Review DE free energies; particle mesh Ewald; fast multipole; periodic boundary conditions; Ewald summation ID PERIODIC BOUNDARY-CONDITIONS; ELECTRONIC-STRUCTURE CALCULATIONS; FAST MULTIPOLE ALGORITHM; FINITE-SIZE CORRECTIONS; PARTICLE MESH EWALD; FREE-ENERGY; COMPUTER-SIMULATIONS; IONIC HYDRATION; SYSTEMS; SUMS AB Current computer simulations of biomolecules typically make use of classical molecular dynamics methods, as a very large number (tens to hundreds of thousands) of atoms are involved over timescales of many nanoseconds. The methodology for treating short-range bonded and van der Waals interactions has matured. However, long-range electrostatic interactions still represent a bottleneck in simulations. In this article, we introduce the basic issues for an accurate representation of the relevant electrostatic interactions. In spite of the huge computational time demanded by most biomolecular systems, it is no longer necessary to resort to uncontrolled approximations such as the use of cutoffs. In particular, we discuss the Ewald summation methods, the fast particle mesh methods, and the fast multipole methods. We also review recent efforts to understand the role of boundary conditions in systems with long-range interactions, and conclude with a short perspective on future trends. C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Sagui, C (reprint author), Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. NR 73 TC 372 Z9 377 U1 3 U2 57 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1056-8700 J9 ANNU REV BIOPH BIOM JI Annu. Rev. Biophys. Biomolec. Struct. PY 1999 VL 28 BP 155 EP 179 DI 10.1146/annurev.biophys.28.1.155 PG 25 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 213KJ UT WOS:000081271400008 PM 10410799 ER PT J AU Yewdell, JW Bennink, JR AF Yewdell, JW Bennink, JR TI Mechanisms of viral interference with MHC class I antigen processing and presentation SO ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY LA English DT Review DE antigen processing; CTL; virus; MHC ID MAJOR HISTOCOMPATIBILITY COMPLEX; HUMAN-IMMUNODEFICIENCY-VIRUS; MOUSE CYTOMEGALOVIRUS GLYCOPROTEIN; CELL-SURFACE EXPRESSION; HIV-1 NEF PROTEIN; ENDOPLASMIC-RETICULUM; TRANSPLANTATION ANTIGENS; HEAVY-CHAINS; ADENOVIRUS TYPE-2; MEMBRANE-PROTEIN AB Viruses are ubiquitous and dangerous obligate intracellular parasites. To facilitate recognition of virus-infected cells by the immune system, vertebrates evolved a system that displays oligopeptides derived from viral proteins on the surface of cells in association with class I molecules of the major histocompatibility complex. Here we review the mechanisms counter-evolved by viruses to interfere with the generation of viral peptides, their intracellular trafficking, or the cell surface expression of class I molecules bearing viral peptides. This topic is important in its own right because the viruses that encode these proteins represent medically important pathogens, are potential vectors for vaccines or gene therapy, and provide strategies and tools for blocking immune recognition in transplantation, autoimmunity, and gene therapy. In addition, studies on viral interference provide unique insights into unfettered antigen processing and normal cellular functions that are exploited and exaggerated by viruses. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 87 TC 62 Z9 63 U1 0 U2 1 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1081-0706 J9 ANNU REV CELL DEV BI JI Annu. Rev. Cell Dev. Biol. PY 1999 VL 15 BP 579 EP 606 DI 10.1146/annurev.cellbio.15.1.579 PG 28 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 286UU UT WOS:000085467900019 PM 10611973 ER PT J AU Weisberg, RA Gottesman, ME Hendrix, RM Little, JW AF Weisberg, RA Gottesman, ME Hendrix, RM Little, JW TI Family values in the age of genomics: Comparative analyses of temperate bacteriophage HK022 SO ANNUAL REVIEW OF GENETICS LA English DT Review DE bacteriophage lambda; genomics; virus evolution; transcription termination; transcription antitermination; genetic switch; site-specific recombination ID SITE-SPECIFIC RECOMBINATION; TRANSCRIPTION TERMINATION FACTOR; N-ANTITERMINATION PROTEIN; COOPERATIVE DNA-BINDING; PHAGE HK022; ESCHERICHIA-COLI; NUN PROTEIN; LAMBDA-INTEGRASE; RNA-POLYMERASE; CI-REPRESSOR AB HK022 is a temperate coliphage related to phage lambda. Its chromosome has been completely sequenced, and several aspects of its life cycle have been intensively studied. In the overall arrangement, expression, and function of most of its genes, HK022 broadly resembles lambda and other members of the lambda family. Upon closer view, significant differences emerge. The differences reveal alternative strategies used by related phages to cope with similar problems and illuminate previously unknown regulatory and structural motifs. HK022 prophages protect lysogens from superinfection by producing a sequence-specific RNA binding protein that prematurely terminates nascent transcripts of infecting phage. It uses a novel RNA-based mechanism to antiterminate its own early transcription The HK022 protein shell is strengthened by a complex pattern of covalent subunit interlinking to form a unitary structure that resembles chainmail armor. Its integrase and repressor proteins are similar to those of lambda, but the differences provide insights into the evolution of biological specificity and the elements needed for construction of a stable genetic switch. C1 NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. Columbia Univ, Inst Canc Res, New York, NY 10032 USA. Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Bacteriophage Inst, Pittsburgh, PA 15260 USA. Univ Arizona, Dept Biochem, Tucson, AZ 85721 USA. Univ Arizona, Dept Mol & Cellular Biol, Tucson, AZ 85721 USA. RP Weisberg, RA (reprint author), NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. NR 125 TC 40 Z9 40 U1 0 U2 3 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4197 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 1999 VL 33 BP 565 EP 602 DI 10.1146/annurev.genet.33.1.565 PG 38 WC Genetics & Heredity SC Genetics & Heredity GA 277WM UT WOS:000084956600017 PM 10690418 ER PT J AU Waldmann, TA Tagaya, Y AF Waldmann, TA Tagaya, Y TI The multifaceted regulation of interleukin-15 expression and the role of this cytokine in NK cell differentiation and host response to intracellular pathogens SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE lymphokine; interleukin-15; IL-15 receptors; mRNA translation; NK cell development; autoimmunity ID NATURAL-KILLER-CELLS; RECEPTOR-BETA-CHAIN; IL-15 MESSENGER-RNA; BLOOD MONONUCLEAR-CELLS; DELTA T-CELLS; INTESTINAL INTRAEPITHELIAL LYMPHOCYTES; HEMATOPOIETIC PROGENITOR CELLS; GAMMA-CHAIN; RHEUMATOID-ARTHRITIS; GROWTH-FACTOR AB Interleukin-15 (IL-15) is a 14- to 15-kDa member of the 4 alpha-helix bundle family of cytokines. IL-15 expression is controlled at the levels of transcription, translation, and intracellular trafficking. In particular, IL-15 protein is posttranscriptionally regulated by multiple controlling elements that impede translation, including 12 upstream AUGs of the 5' UTR, 2 unusual signal peptides, and the C-terminus of the mature protein. IL-15 uses two distinct receptor and signaling pathways. In T and NK cells the IL-15 receptor includes IL-2/15R beta and gamma(c) subunits, which are shared with IL-2, and an IL-15-specific receptor subunit, IL-15R alpha. Mast cells respond to IL-15 with a receptor system that does not share elements with the IL-2 receptor but uses a novel 60- to 65-kDa IL-15RX subunit. In mast cells IL-15 signaling involves Jak2/STAT5 activation rather than the Jak1/Jak3 and STAT5/STAT3 system used in activated T cells. In addition to its other functional activities in immune and nonimmune cells, IL-15 plays a pivotal role in the development, survival, and function of NK cells. Abnormalities of IL-15 expression have been described in patients with rheumatoid arthritis or inflammatory bowel disease and in diseases associated with the retroviruses HIV and HTLV-I. New approaches directed toward IL-15, its receptor, or its signaling pathway may be of value in the therapy of these disorders. C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Waldmann, TA (reprint author), NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NR 142 TC 472 Z9 485 U1 1 U2 17 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 1999 VL 17 BP 19 EP 49 DI 10.1146/annurev.immunol.17.1.19 PG 31 WC Immunology SC Immunology GA 198QZ UT WOS:000080436600002 PM 10358752 ER PT J AU Yewdell, JTW Bennink, JR AF Yewdell, JTW Bennink, JR TI Immunodominance in major histocompatibility complex class I-restricted T lymphocyte responses SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE antigen processing; CTL; immunodominance; MHC ID MHC CLASS-I; EPSTEIN-BARR-VIRUS; ACUTE INFECTIOUS-MONONUCLEOSIS; HLA-A2.1 TRANSGENIC MICE; GROWTH-FACTOR-BETA; CELL RESPONSES; CTL RESPONSES; ANTIGEN PRESENTATION; PEPTIDE LIBRARIES; INFLUENZA NUCLEOPROTEIN AB Of the many thousands of peptides encoded by a complex foreign antigen that can potentially be presented to CD8+ T cells (TCD8+), only a small fraction induce measurable responses in association with any given major histocompatibility complex class I allele. To design vaccines that elicit optimal TCD8+ responses, a thorough understanding of this phenomenon, known as immunodominance, is imperative. Here we review recent progress in unraveling the molecular and cellular basis for immunodominance. Of foremost importance is peptide binding to class I molecules; only similar to 1/200 of potential determinants bind at greater than the threshold affinity(K-d > 500 nM) associated with immunogenicity. Limitations in the TCD8+ repertoire render approximately half of these peptides nonimmunogenic, and inefficient antigen processing further thins the ranks by approximately four fifths. As a result, only similar to 1/2000 of the peptides in a foreign antigen expressed by an appropriate antigen presenting cell achieve immunodominant status with a given class I allele. A roughly equal fraction of peptides have subdominant status, i.e. they induce weak-to-nondetectable primary TCD8+ responses in the context of their natural antigen. Subdominant determinants may be expressed at or above levels of immunodominant determinants, at least on antigen presenting cells in vitro. The immunogenicity of subdominant determinants is often Limited by immunodomination: suppression mediated by TCD8+ Specific for immunodominant determinants. Immunodomination is a central feature of TCD8+ responses, as it even occurs among clones responding to the same immunodominant determinant. Little is known about how immunodominant and subdominant determinants are distinguished by the TCD8+ repertoire, or how (and why) immunodomination occurs, but new tools are available to address these questions. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Yewdell, JTW (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM jyewdell@nih.gov; jbennink@nih.gov RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 115 TC 657 Z9 663 U1 1 U2 27 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 1999 VL 17 BP 51 EP 88 DI 10.1146/annurev.immunol.17.1.51 PG 38 WC Immunology SC Immunology GA 198QZ UT WOS:000080436600003 PM 10358753 ER PT J AU Lenardo, M Chan, FKM Hornung, F McFarland, H Siegel, R Wang, J Zheng, LX AF Lenardo, M Chan, FKM Hornung, F McFarland, H Siegel, R Wang, J Zheng, LX TI Mature T lymphocyte apoptosis - Immune regulation in a dynamic and unpredictable antigenic environment SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE death; cytokine; lymphokine; Fas/APO-1/CD95; Bcl-2; propriocidal; feedback; caspase; tumor necrosis factor; receptor; Autoimmune Lymphoproliferative Syndrome ID TUMOR-NECROSIS-FACTOR; FAS-MEDIATED APOPTOSIS; NF-KAPPA-B; INDUCED CELL-DEATH; ACTIVATION-INDUCED CELL; AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; HUMAN-IMMUNODEFICIENCY-VIRUS; STAPHYLOCOCCAL ENTEROTOXIN-B; MITOCHONDRIAL PERMEABILITY TRANSITION; ACUTE LYMPHOBLASTIC-LEUKEMIA AB Apoptosis of mature T lymphocytes preserves peripheral homeostasis and tolerance by countering the profound changes in the number and types of T cells stimulated by diverse antigens. T cell apoptosis occurs in at least two major forms: antigen-driven and lymphokine withdrawal. These forms of death are controlled in response to local levels of IL-2 and antigen in a feedback mechanism termed propriocidal regulation. Active antigen-driven death is mediated by the expression of death cytokines such as FasL and TNF. These death cytokines engage specific receptors that assemble caspase-activating protein complexes. These signaling complexes tightly regulate cell death but are vulnerable to inherited defects. Passive lymphokine withdrawal death may result from the cytoplasmic activation of caspases that is regulated by mitochondria and the Bcl-2 protein. The human disease, Autoimmune Lymphoproliferative Syndrome (ALPS) is due to dominant-interfering mutations in the Fas/APO-1/CD95 receptor and other components of the death pathway. The study of ALPS patients reveals the necessity of apoptosis for preventing autoimmunity and allows the genetic investigation of apoptosis in humans. Immunological, cellular, and molecular evidence indicates that throughout the life of a T cell, apoptosis may be evoked in excessive, harmful, or useless clonotypes to preserve a healthy and balanced immune system. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Lenardo, M (reprint author), NIAID, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Siegel, Richard/C-7592-2009; Chan, Francis/E-9647-2014; McFarland, Hugh/K-1503-2016; Chan, Francis K. L./F-4851-2010 OI Siegel, Richard/0000-0001-5953-9893; Chan, Francis/0000-0002-4803-8353; McFarland, Hugh/0000-0002-3322-038X; Chan, Francis K. L./0000-0001-7388-2436 NR 344 TC 724 Z9 746 U1 1 U2 8 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 1999 VL 17 BP 221 EP 253 DI 10.1146/annurev.immunol.17.1.221 PG 33 WC Immunology SC Immunology GA 198QZ UT WOS:000080436600008 PM 10358758 ER PT J AU Germain, RN Stefanova, I AF Germain, RN Stefanova, I TI The dynamics of T cell receptor signaling: Complex orchestration and the key roles of tempo and cooperation SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE kinetic proofreading; antagonists; feedback regulation ID MAJOR HISTOCOMPATIBILITY COMPLEX; MHC CLASS-II; PROTEIN-TYROSINE-PHOSPHATASE; ALTERED PEPTIDE LIGANDS; MYELIN BASIC-PROTEIN; TANDEM SH2 DOMAINS; MOTH-EATEN MICE; ANTIGEN RECEPTOR; ZETA-CHAIN; POSITIVE SELECTION AB T cells constantly sample their environment using receptors (TCR) that possess both a germline-encoded low affinity for major histocompatibility complex (MHC) molecules and a highly diverse set of CDR3 regions contributing to a range of affinities for specific peptides bound to these MHC molecules. The decision of a T cell "to sense and to respond" with proliferation and effector activity rather than "to sense, live on, but not respond" is dependent on TCR interaction with a low number of specific foreign peptide:MHC molecule complexes recognized simultaneously with abundant self peptide-containing complexes. Interaction with self-complexes alone, on the other hand, generates a signal for survival without a full activation response. Current models for how this distinction is achieved are largely based on translating differences in receptor affinity for foreign versus self ligands into intracellular signals that differ in quality, intensity, and/or duration. A variety of rate-dependent mechanisms involving assembly of molecular oligomers and enzymatic modification of proteins underlie this differential signaling. Recent advances have been made in measuring TCR:ligand interactions, in understanding the biochemical origin of distinct proximal and distal signaling events resulting from TCR binding to various ligands, and in appreciating the role of feedback pathways. This new information can be, synthesized into a model of how self and foreign ligand recognition each evoke the proper responses from T cells, how these two classes of signaling events interact, and how pathologic responses may arise as a result of the underlying properties of the system. The principles of signal spreading and stochastic resonance incorporated into this model reveal. a striking similarity in mechanisms of decision-making among T cells neurons, and bacteria. C1 NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 271 TC 320 Z9 327 U1 0 U2 9 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 1999 VL 17 BP 467 EP 522 DI 10.1146/annurev.immunol.17.1.467 PG 56 WC Immunology SC Immunology GA 198QZ UT WOS:000080436600016 PM 10358766 ER PT J AU Berger, EA Murphy, PM Farber, JM AF Berger, EA Murphy, PM Farber, JM TI Chemokine receptors as HIV-1 coreceptors: Roles in viral entry, tropism, and disease SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE AIDS; genetics; G protein-coupled receptors; pathogenesis; therapeutics ID HUMAN-IMMUNODEFICIENCY-VIRUS; GP120 ENVELOPE GLYCOPROTEIN; CD8(+) T-CELLS; INFLAMMATORY PROTEIN (MIP)-1-ALPHA; MACROPHAGE-DERIVED CHEMOKINE; AMINO-TERMINAL DOMAIN; HUMAN LYMPHOID-TISSUE; MUTANT CCR5 ALLELE; TYPE-1 INFECTION; DENDRITIC CELLS AB In addition to CD4, the human immunodeficiency virus (HIV) requires a coreceptor for entry into target cells. The chemokine receptors CXCR4 and CCR5, members of the G protein-coupled receptor superfamily, have been identified as the principal coreceptors for T cell line-tropic and macrophage-tropic HIV-1 isolates, respectively. The updated coreceptor repertoire includes numerous members, mostly chemokine receptors and related orphans. These discoveries provide a new framework for understanding critical features of the basic biology of HIV-1, including the selective tropism of individual viral variants for different CD4(+) target cells and the membrane fusion mechanism governing virus entry. The coreceptors also provide molecular perspectives on central puzzles of HIV-1 disease, including the selective transmission of macrophage-tropic variants, the appearance of T cell line-tropic variants in many infected persons during progression to AIDS, and differing susceptibilities of individuals to infection and disease progression. Genetic findings have yielded major insights into the in vivo roles of individual coreceptors and their ligands; of particular importance is the discovery of an inactivating mutation in the CCR5 gene which, in homozygous form, confers strong resistance to HIV-1 infection. Beyond providing new perspectives on fundamental aspects of HIV-1 transmission and pathogenesis, the coreceptors suggest new avenues for developing novel therapeutic and preventative strategies to combat the AIDS epidemic. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Berger, EA (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NR 230 TC 1588 Z9 1640 U1 29 U2 156 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 1999 VL 17 BP 657 EP 700 DI 10.1146/annurev.immunol.17.1.657 PG 44 WC Immunology SC Immunology GA 198QZ UT WOS:000080436600021 PM 10358771 ER PT J AU Nelms, K Keegan, AD Zamorano, J Ryan, JJ Paul, WE AF Nelms, K Keegan, AD Zamorano, J Ryan, JJ Paul, WE TI The IL-4 receptor: Signaling mechanisms and biologic functions SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE interleukin-4; interleukin-4 receptor; Stat-6; IRS-1/2; Janus kinases; phosphatase; FRIP ID STIMULATORY FACTOR-I; HUMAN INTERLEUKIN-4 RECEPTOR; NF-KAPPA-B; INDUCED TYROSINE PHOSPHORYLATION; GERMLINE EPSILON-PROMOTER; FES PROTOONCOGENE PRODUCT; HUMAN GROWTH-HORMONE; JAK-3 JANUS KINASE; COMMON GAMMA-CHAIN; IRS-1 PTB DOMAIN AB Interleukin-4 is a multifunctional cytokine that plays a critical role in the regulation of immune responses. Its effects depend upon binding to and signaling through a receptor complex consisting of the IL-4R alpha chain and the common gamma chain (gamma c), resulting in a series of phosphorylation events mediated by receptor-associated kinases. In turn, these cause the recruitment of mediators of cell growth, of resistance to apoptosis, and of gene activation and differentiation. Here we describe our current understanding of the organization of the IL-4 receptor, of the signaling pathways that are induced as a result of receptor occupancy, and of the various mechanisms through which receptor function is modulated. We particularly emphasize the modular nature of the receptor and the specialization of different receptor regions for distinct functions, most notably the independent regulation of cell growth and gene activation. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Amer Red Cross, Jerome H Holland Lab, Dept Immunol, Rockville, MD 20855 USA. RP Nelms, K (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 183 TC 955 Z9 974 U1 3 U2 40 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 1999 VL 17 BP 701 EP 738 DI 10.1146/annurev.immunol.17.1.701 PG 38 WC Immunology SC Immunology GA 198QZ UT WOS:000080436600022 PM 10358772 ER PT J AU Long, EO AF Long, EO TI Regulation of immune responses through inhibitory receptors SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE C-type lectin; immunoglobulin; MHC class I; natural killer cell ID NATURAL-KILLER-CELLS; CLASS-I MOLECULES; MAJOR HISTOCOMPATIBILITY COMPLEX; TYROSINE-PHOSPHATASE SHP-1; SST2 SOMATOSTATIN RECEPTOR; NK1.1(+) T-CELLS; HLA-G EXPRESSION; FC-GAMMA-RIIB; C-TYPE LECTIN; NK CELLS AB Major histocompatibility complex class I-specific inhibitory receptors on natural killer cells prevent the lysis of healthy autologous cells. The outcome of this negative signal is not anergy or apoptosis of natural killer cells but a transient abortion of activation signals. The natural killer inhibitory receptors fulfill this function by recruiting the tyrosine phosphatase SHP-1 through a cytoplasmic immunoreceptor tyrosine-based inhibition motif. This immunoreceptor tyrosine-based inhibition motif has become the hallmark of a growing family of receptors with inhibitory potential, which are expressed in various cell types such as monocytes, macrophages, dendritic cells, leukocytes, and mast cells. Most of the natural killer inhibitory receptors and two members of a monocyte inhibitory-receptor family bind major histocompatibility complex class I molecules. Ligands for many of the other receptors have yet to be identified. The inhibitory-receptor superfamily appears to regulate many types of immune responses by blocking cellular activation signals. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Long, EO (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 161 TC 736 Z9 754 U1 0 U2 18 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 1999 VL 17 BP 875 EP 904 DI 10.1146/annurev.immunol.17.1.875 PG 30 WC Immunology SC Immunology GA 198QZ UT WOS:000080436600026 PM 10358776 ER PT J AU Locati, M Murphy, PM AF Locati, M Murphy, PM TI Chemokines and chemokine receptors: Biology and clinical relevance in inflammation and AIDS SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE inflammation; HIV; malaria; AIDS; CCR5; leukocyte ID PROTEIN-COUPLED RECEPTOR; HIV-1 INFECTION; HOST-DEFENSE; MICE LACKING; HUMAN CYTOMEGALOVIRUS; TARGETED DISRUPTION; CELL-PROLIFERATION; CC CHEMOKINES; T-LYMPHOCYTES; INTERLEUKIN-8 AB Chemokines constitute a large family of chemotactic cytokines that act at G protein-coupled receptors to regulate diverse biological processes, including leukocyte trafficking, angiogenesis, hematopoiesis, and organogenesis. They are believed to be both beneficial in host defense against infectious agents and harmful in diseases marked by pathologic inflammation; however, actual clinical roles in these areas have not yet been established. Recently, unexpected ways have been discovered in which medically important pathogens, including HIV-I, exploit or subvert the chemokine system. These and other recent results suggest that targeting specific chemokines and chemokine receptors may have therapeutic utility in both inflammation and infectious disease. C1 Ist Ric Farmacol Mario Negri, I-20157 Milan, Italy. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Locati, M (reprint author), Ist Ric Farmacol Mario Negri, I-20157 Milan, Italy. EM locati@irfmn.mnegri.it; pmm@nih.gov RI Locati, Massimo/H-8404-2015 OI Locati, Massimo/0000-0003-3077-590X NR 81 TC 216 Z9 224 U1 0 U2 4 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1999 VL 50 BP 425 EP 440 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 170XF UT WOS:000078831800028 PM 10073287 ER PT J AU Bauer, CE Elsen, S Bird, TH AF Bauer, CE Elsen, S Bird, TH TI Mechanisms for redox control of gene expression SO ANNUAL REVIEW OF MICROBIOLOGY LA English DT Review DE SoxR; FNR; FixL; NifL; OxyR; ArcB; RegB; CrtJ; NifA ID RHIZOBIUM-MELILOTI-NIFA; AZOTOBACTER-VINELANDII NIFL; SUPEROXIDE RESPONSE REGULON; SIGNAL-TRANSDUCTION SYSTEM; TRANSCRIPTION FACTOR FNR; NITROGEN-FIXATION GENES; LEGUMINOSARUM BIOVAR TRIFOLII; DNA-BINDING CHARACTERISTICS; IN-VITRO PHOSPHORYLATION; OXIDATIVE STRESS REGULON AB This review discusses various mechanisms that regulatory proteins use to control gene expression in response to alterations in redox. The transcription factor SoxR contains stable [2Fe-2S] centers that promote transcription activation when oxidized. FNR contains [4Fe-4S] centers that disassemble under oxidizing conditions, which affects DNA-binding activity. FixL is a histidine sensor kinase that utilizes heme as a cofactor to bind oxygen, which affects its autophosphorylation activity. NifL is a flavoprotein that contains FAD as a redox responsive cofactor. Under oxidizing conditions, NifL binds and inactivates NifA, the transcriptional activator of the nitrogen fixation genes. OxyR is a transcription factor that responds to redox by breaking or forming disulfide bonds that affect its DNA binding activity. The ability of the histidine sensor kinase ArcB to promote phosphorylation of the response regulator ArcA is affected by multiple factors such as anaerobic metabolites and the redox state of the membrane. The global regulator of anaerobic gene expression in a-purple proteobacteria, RegB, appears to directly monitor respiratory activity of cytochrome oxidase. The aerobic repressor of photopigment synthesis, CrtJ, seems to contain a redox responsive cysteine. Finally, oxygen-sensitive rhizobial NifA proteins presumably bind a metal cofactor that senses redox. The functional variability of these regulatory proteins demonstrates that prokaryotes apply many different mechanisms to sense and respond to alterations in redox. C1 Indiana Univ, Dept Biol, Bloomington, IN 47405 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Bauer, CE (reprint author), Indiana Univ, Dept Biol, Bloomington, IN 47405 USA. FU NIGMS NIH HHS [GM539040, GM40941, R01 GM040941] NR 183 TC 173 Z9 180 U1 0 U2 19 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4227 J9 ANNU REV MICROBIOL JI Annu. Rev. Microbiol. PY 1999 VL 53 BP 495 EP 523 DI 10.1146/annurev.micro.53.1.495 PG 29 WC Microbiology SC Microbiology GA 247EW UT WOS:000083208500016 PM 10547699 ER PT J AU Colby, CL Goldberg, ME AF Colby, CL Goldberg, ME TI Space and attention in parietal cortex SO ANNUAL REVIEW OF NEUROSCIENCE LA English DT Review DE saccadic eye movements; spatial representation; spatial perception ID FRONTAL EYE FIELDS; LATERAL INTRAPARIETAL AREA; SACCADE-RELATED ACTIVITY; ABRUPT VISUAL ONSETS; SUPERIOR COLLICULUS; PREMOTOR CORTEX; MACAQUE MONKEY; SELECTIVE ATTENTION; PERIARCUATE NEURONS; RESPONSE PROPERTIES AB The space around us is represented not once but many times in parietal cortex. These multiple representations encode locations and objects of interest in several egocentric reference frames. Stimulus representations are transformed from the coordinates of receptor surfaces, such as the retina or the cochlea, into the coordinates of effecters, such as the eye, head, or hand. The transformation is accomplished by dynamic updating of spatial representations in conjunction with voluntary movements. This direct sensory-to-motor coordinate transformation obviates the need for a single representation of space in environmental coordinates. In addition to representing object locations in motoric coordinates, parietal neurons exhibit strong modulation by attention. Both top-down and bottom-up mechanisms of attention contribute to the enhancement of visual responses. The saliance of a stimulus is the primary factor in determining the neural response to it. Although parietal neurons represent objects in motor coordinates, visual responses are independent of the intention to perform specific motor acts. C1 Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Ctr Neural Basis Cognit, Pittsburgh, PA 15260 USA. NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. Georgetown Univ, Sch Med, Dept Neurol, Washington, DC 20007 USA. RP Colby, CL (reprint author), Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15260 USA. NR 100 TC 979 Z9 988 U1 13 U2 64 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0147-006X J9 ANNU REV NEUROSCI JI Annu. Rev. Neurosci. PY 1999 VL 22 BP 319 EP 349 DI 10.1146/annurev.neuro.22.1.319 PG 31 WC Neurosciences SC Neurosciences & Neurology GA 178LP UT WOS:000079267400014 PM 10202542 ER PT J AU Francis, NJ Landis, SC AF Francis, NJ Landis, SC TI Cellular and molecular determinants of sympathetic neuron development SO ANNUAL REVIEW OF NEUROSCIENCE LA English DT Review DE neural crest; neuronal differentiation; neurotrophic factors; cell death; neurotransmitter plasticity; synapse formation ID NERVE GROWTH-FACTOR; LEUKEMIA INHIBITORY FACTOR; CHOLINERGIC DIFFERENTIATION FACTOR; P75 NEUROTROPHIN RECEPTOR; RAT SWEAT GLANDS; BONE MORPHOGENETIC PROTEIN-4; ACHAETE-SCUTE HOMOLOG-1; AFFINITY NGF RECEPTOR; SYMPATHOADRENAL LINEAGE; MICE LACKING AB The development of the sympathetic nervous system can be divided into three overlapping stages. First, the precursors of sympathetic neurons arise from undifferentiated neural crest cells that migrate ventrally, aggregate adjacent to the dorsal aorta, and ultimately differentiate into catecholaminergic neurons. Second, cell number is refined during a period of cell death when neurotrophic factors determine the number of neuronal precursors and neurons that survive. The final stage of sympathetic development is the establishment and maturation of synaptic connections, which for sympathetic neurons can include alterations in neurotransmitter phenotype. Considerable progress has been made recently in elucidating the cellular and molecular mechanisms that direct each of these developmental decisions. We review the current understanding of each of these, focusing primarily on events in the peripheral nervous system of rodents. C1 Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Francis, NJ (reprint author), Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. EM nxf@pop.cwru.edu; slandis@codon.nih.gov NR 162 TC 134 Z9 137 U1 0 U2 2 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0147-006X J9 ANNU REV NEUROSCI JI Annu. Rev. Neurosci. PY 1999 VL 22 BP 541 EP 566 DI 10.1146/annurev.neuro.22.1.541 PG 26 WC Neurosciences SC Neurosciences & Neurology GA 178LP UT WOS:000079267400020 PM 10202548 ER PT J AU Allan, CB Lacourciere, GM Stadtman, TC AF Allan, CB Lacourciere, GM Stadtman, TC TI Responsiveness of selenoproteins to dietary selenium SO ANNUAL REVIEW OF NUTRITION LA English DT Review DE selenocysteine; glutathione peroxidases; deiodinases; thioredoxin reductase; selenoprotein P; selenoprotein W ID HYDROPEROXIDE GLUTATHIONE-PEROXIDASE; THIOREDOXIN REDUCTASE-ACTIVITY; SELENOCYSTEINE INSERTION; FINNISH MEN; RAT MUSCLE; CELL-LINE; EXPRESSION; PURIFICATION; SELENOMETHIONINE; METABOLISM AB Selenocysteine-containing enzymes that have been identified in mammals include the glutathione peroxidase family (GPX1, GPX2, GPX3, and GPX4), one or more iodothyronine deiodinases and two thioredixin reductases. Selenoprotein P, a glycoprotein that contains 10 selenocysteine residues per 43 kDa polypeptide and selenoprotein W, a 10 kDa muscle protein, are unidentified as to function. Levels of all of these selenocysteine-containing proteins in various tissues are affected to different extents by selenium availability. Increased amounts of selenoproteins observed in response to selenium supplementation were shown in several studies to correlate with increases in the corresponding mRNA levels. In general, selenoprotein levels in brain are less sensitive to dietary selenium fluctuation than the corresponding selenoprotein levels in other tissues. C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Allan, CB (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 50 TC 219 Z9 226 U1 2 U2 15 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0199-9885 J9 ANNU REV NUTR JI Annu. Rev. Nutr. PY 1999 VL 19 BP 1 EP 16 DI 10.1146/annurev.nutr.19.1.1 PG 16 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 226EL UT WOS:000082007300003 PM 10448514 ER PT J AU Okazaki, IJ Moss, J AF Okazaki, IJ Moss, J TI Characterization of glycosylphosphatidylinositiol-anchored, secreted, and intracellular vertebrate mono-ADP-ribosyltransferases SO ANNUAL REVIEW OF NUTRITION LA English DT Review DE ADP-ribosylarginine hydrolases; bacterial toxin ADP-ribosyltransferases; signal transduction; cholera toxin; nicotinamide adenine dinucleotide ID NICOTINAMIDE ADENINE-DINUCLEOTIDE; ACTIVE-SITE MUTATIONS; RIBOSYLATING BACTERIAL TOXINS; LYMPHOCYTE ALLOANTIGEN RT6.1; NAD GLYCOHYDROLASE ACTIVITY; HEAT-LABILE ENTEROTOXIN; SKELETAL-MUSCLE CELLS; GTP-BINDING PROTEINS; TURKEY ERYTHROCYTES; DIPHTHERIA-TOXIN AB Mono-ADP-ribosylation is a posttranslational modification of proteins in which the ADP-ribose moiety of nicotinamide adenine dinucleotide is transferred to an acceptor amino acid. Five mammalian ADP-ribosyltransferases (ART1-ART5) have been cloned and expression is restricted to tissues such as cardiac and skeletal muscle, leukocytes, brain, and testis. ART1 and ART2 are glycosylphosphatidylinositol (GPI)-anchored ectoenzymes. ARTS appears not to be GPI-linked and may be secreted. In skeletal muscle and lymphocytes, ART1 modifies specific members of the integrin family of adhesion molecules, suggesting that ADP-ribosylation affects cell-matrix or cell-cell interactions. In lymphocytes, ADP-ribosylation of surface proteins is associated with changes in p56(Ick) tyrosine kinase-mediated signaling. The catalytic sites of bacterial toxins and vertebrate transferases have conserved structural features, consistent with a common reaction mechanism. ADP-ribosylation can be reversed by ADP- ribosylarginine hydrolases, resulting in the regeneration of free arginine. Thus, an ADP-ribosylation cycle may play a regulatory role in vertebrate tissues. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Okazaki, IJ (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 111 TC 49 Z9 50 U1 0 U2 2 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0199-9885 J9 ANNU REV NUTR JI Annu. Rev. Nutr. PY 1999 VL 19 BP 485 EP 509 DI 10.1146/annurev.nutr.19.1.485 PG 25 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 226EL UT WOS:000082007300023 PM 10448534 ER PT J AU Sibley, DR AF Sibley, DR TI New insights into dopaminergic receptor function using antisense and genetically altered animals SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY LA English DT Review DE transgenic; knockout; homologous recombination; gene targeting; oligodeoxynucleotide ID HYPOTHALAMIC NUCLEUS LESIONS; D-1A-DEFICIENT MUTANT MICE; DEFICIENT MICE; MESSENGER-RNA; D2 RECEPTORS; IN-VIVO; GENE-EXPRESSION; MOUSE-BRAIN; OLIGODEOXYNUCLEOTIDE ANTISENSE; PROGESTERONE RECEPTORS AB Dopaminergic receptors are widespread throughout the central and peripheral nervous systems, where they regulate a variety of physiological, behavioral, and endocrine functions. These receptors are also clinically important drug targets for the treatment of a number of disorders, such as Parkinson's disease, schizophrenia, and hyperprolactinemia. To date, five different dopamine receptor subtypes have been cloned and characterized. Many of these subtypes are pharmacologically similar, making it difficult to selectively stimulate or block a specific receptor subtype in vivo. Thus, the assignment of various physiological or behavioral functions to specific dopamine receptor subtypes using pharmacological tools is difficult. In view of this, a number of investigators have-in order to elucidate functional roles-begun to use highly selective genetic approaches to alter the expression of individual dopamine receptor subtypes in vivo. This review discusses recent studies involving the use of genetic approaches for the study of dopaminergic receptor function. C1 NINDS, Mol Neuropharmacol Sect, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Sibley, DR (reprint author), NINDS, Mol Neuropharmacol Sect, Expt Therapeut Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM sibley@helix.nih.gov NR 95 TC 141 Z9 146 U1 0 U2 4 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0362-1642 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 1999 VL 39 BP 313 EP 341 DI 10.1146/annurev.pharmtox.39.1.313 PG 29 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 193YE UT WOS:000080164700014 PM 10331087 ER PT J AU Ambudkar, SV Dey, S Hrycyna, CA Ramachandra, M Pastan, I Gottesman, MM AF Ambudkar, SV Dey, S Hrycyna, CA Ramachandra, M Pastan, I Gottesman, MM TI Biochemical, cellular, and pharmacological aspects of the multidrug transporter SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY LA English DT Review DE multidrug resistance; P-glycoprotein; drug transport; ATP hydrolysis; cancer chemotherapy; chemosensitizer ID HUMAN P-GLYCOPROTEIN; STIMULATED ATPASE ACTIVITY; BLOOD-BRAIN-BARRIER; HIV-1 PROTEASE INHIBITORS; RESISTANT HUMAN-CELLS; CATALYTIC TRANSITION-STATE; NUCLEOTIDE-BINDING SITES; AMINO-ACID SUBSTITUTIONS; 6TH TRANSMEMBRANE DOMAIN; HAMSTER OVARY CELLS AB Considerable evidence has accumulated indicating that the multidrug transporter or P-glycoprotein plays a role in the development of simultaneous resistance to multiple cytotoxic drugs in cancer cells. In recent years, various approaches such as mutational analyses and biochemical and pharmacological characterization have yielded significant information about the relationship of structure and function of P-glycoprotein. However, there is still considerable controversy about the mechanism of action of this efflux pump and its function in normal cells. This review summarizes current research on the structure-function analysis of P-glycoprotein, its mechanism of action, and facts and speculations about ifs normal physiological role. C1 NCI, Cell Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RI Ambudkar, Suresh/B-5964-2008 NR 169 TC 1447 Z9 1488 U1 12 U2 120 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0362-1642 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 1999 VL 39 BP 361 EP 398 DI 10.1146/annurev.pharmtox.39.1.361 PG 38 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 193YE UT WOS:000080164700016 PM 10331089 ER PT J AU Dinse, GE Umbach, DM Sasco, AJ Hoel, DG Davis, DL AF Dinse, GE Umbach, DM Sasco, AJ Hoel, DG Davis, DL TI Unexplained increases in cancer incidence in the United States from 1975 to 1994: Possible sentinel health indicators? SO ANNUAL REVIEW OF PUBLIC HEALTH LA English DT Review DE age-period-cohort models; deviations from linearity; SEER; time trends ID PERIOD-COHORT ANALYSIS; END RESULTS PROGRAM; BREAST-CANCER; PROSTATE-CANCER; MORTALITY-RATES; DISEASE RATES; RISK-FACTORS; TRENDS; AGE; EPIDEMIOLOGY AB To search for unexplained patterns in cancer incidence, we analyzed data from 1975 to 1994 that represent similar to 10% of the population of the United States. Our analysis focused on long-term time trends in incidence and on deviations from those trends attributable to birth cohorts or to calendar periods. On average, cancer incidence rose 0.8% annually in white women and 1.8% in white men. After removing several cancers related to smoking and increased screening, average annual increases fell to 0.1% in white women but persisted at 1.7% in white men. In particular, yearly increases in non-Hodgkin's lymphoma averaged 2.4% in white women and 4.7% in white men. Among men, incidence changes attributable to cohorts grew progressively larger from one cohort to the next. Cancer incidence patterns among black men and women were similar to those among whites despite smaller population sizes. Unexplained patterns of cancer incidence may signal changes in underlying risk factors and highlight the continuing need for research on cancer etiology and prevention. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Int Agcy Res Canc, Unit Epidemiol Canc Prevent, F-69372 Lyon 08, France. Fac Med Alexis Carrel, INSERM, F-69372 Lyon 08, France. Med Univ S Carolina, Hollings Canc Ctr, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. World Resources Inst, Washington, DC 20006 USA. RP Dinse, GE (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. NR 83 TC 25 Z9 26 U1 1 U2 1 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0163-7525 J9 ANNU REV PUBL HEALTH JI Annu. Rev. Public Health PY 1999 VL 20 BP 173 EP 209 DI 10.1146/annurev.publhealth.20.1.173 PG 37 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 198RW UT WOS:000080438800013 PM 10352856 ER PT S AU Bonvini, P Hwang, SG El-Gamil, M Robbins, P Neckers, L Trepel, J AF Bonvini, P Hwang, SG El-Gamil, M Robbins, P Neckers, L Trepel, J BE Maruta, H TI Melanoma cell lines contain a proteasome-sensitive, nuclear cytoskeleton-associated pool of beta-catenin SO ANTICANCER MOLECULES: STRUCTURE, FUNCTION, AND DESIGN SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Anti-Cancer Proteins and Drugs - Structure, Function and Design CY NOV 06-09, 1998 CL NEW YORK ACAD SCI, NEW YORK, NEW YORK SP Janssen Pharmaceut, Ludwig Inst Canc Res, Melbourne Branch, NCI, NIH, Schering Plough Res Inst, AMGEN, Bayer Corp, Berlex Labs Inc, Bristol Myers Squibb, Pharmaceut Res Inst, EISAI Co Ltd, Entremed Inc, Genentech Inc, Genome Therapeut Corp, Glaxo Wellcome Inc, Hoechst Marion Roussel Inc, Merck Res Labs, Natl Neurofibromatosis Fdn Inc, Novartis Prod AG, Warner Lambert Co, Parke Davis Pharmaceut Res, Vion Pharmacuet Inc, Yakult Honsha Co Ltd, Zeneca Pharmaceut HO NEW YORK ACAD SCI ID ACTIVATION; COMPLEX C1 NCI, Dept Cell & Canc Biol, Med Branch, NIH, Rockville, MD 20850 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Dept Cell & Canc Biol, Med Branch, NIH, Bethesda, MD 20892 USA. RP Bonvini, P (reprint author), 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. NR 7 TC 1 Z9 1 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-184-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 886 BP 208 EP 211 DI 10.1111/j.1749-6632.1999.tb09418.x PG 4 WC Cell Biology; Medicine, Research & Experimental; Multidisciplinary Sciences SC Cell Biology; Research & Experimental Medicine; Science & Technology - Other Topics GA BP49D UT WOS:000085293900024 PM 10667221 ER PT S AU Russo, P Ottoboni, C Falugi, C Reinhold, W Riou, JF Parodi, S O'Connor, PM AF Russo, P Ottoboni, C Falugi, C Reinhold, W Riou, JF Parodi, S O'Connor, PM BE Maruta, H TI Cellular effects of a new farnesyltransferase inhibitor, RPR-115135, in a human isogenic colon cancer cell line model system HCT-116 SO ANTICANCER MOLECULES: STRUCTURE, FUNCTION, AND DESIGN SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Anti-Cancer Proteins and Drugs - Structure, Function and Design CY NOV 06-09, 1998 CL NEW YORK ACAD SCI, NEW YORK, NEW YORK SP Janssen Pharmaceut, Ludwig Inst Canc Res, Melbourne Branch, NCI, NIH, Schering Plough Res Inst, AMGEN, Bayer Corp, Berlex Labs Inc, Bristol Myers Squibb, Pharmaceut Res Inst, EISAI Co Ltd, Entremed Inc, Genentech Inc, Genome Therapeut Corp, Glaxo Wellcome Inc, Hoechst Marion Roussel Inc, Merck Res Labs, Natl Neurofibromatosis Fdn Inc, Novartis Prod AG, Warner Lambert Co, Parke Davis Pharmaceut Res, Vion Pharmacuet Inc, Yakult Honsha Co Ltd, Zeneca Pharmaceut HO NEW YORK ACAD SCI ID RAS; TRANSFORMATION; TARGET C1 NCI, Dept Expt Oncol, Expt Oncol Lab, I-16132 Genoa, Italy. Univ Genoa, Dept Clin & Expt Oncol, I-16132 Genoa, Italy. NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Univ Genoa, Dept Dev Biol, Genoa, Italy. Ctr Rech Rhone Poulenc Rorer, Anticanc Res Program, F-94403 Vitry, France. RP Russo, P (reprint author), NCI, Dept Expt Oncol, Expt Oncol Lab, Largo Rosanna Benzi 10, I-16132 Genoa, Italy. NR 15 TC 9 Z9 9 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-184-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 886 BP 252 EP 256 DI 10.1111/j.1749-6632.1999.tb09429.x PG 5 WC Cell Biology; Medicine, Research & Experimental; Multidisciplinary Sciences SC Cell Biology; Research & Experimental Medicine; Science & Technology - Other Topics GA BP49D UT WOS:000085293900035 PM 10667232 ER PT J AU Lee, SK Song, L Mata-Greenwood, E Kelloff, GJ Steele, VE Pezzuto, JM AF Lee, SK Song, L Mata-Greenwood, E Kelloff, GJ Steele, VE Pezzuto, JM TI Modulation of in vitro biomarkers of the carcinogenic process by chemopreventive agents SO ANTICANCER RESEARCH LA English DT Article DE chemopreventive agents; biomarker assays ID ORNITHINE DECARBOXYLASE ACTIVITY; BRONCHIAL EPITHELIAL-CELLS; GLUTATHIONE S-TRANSFERASES; ACID PHENETHYL ESTER; TUMOR PROMOTION; HUMAN-COLON; MOUSE SKIN; IN-VITRO; INDUCTION; ENZYMES AB A structurally diverse group of chemopreventive agents was evaluated using in vitro biomarkers of the carcinogenesis process. With cultured human bronchial epithelial (BEAS-2B) cells, sulfur-containing compounds such as 1,2-dithiole-3-thione and sulforaphane, and phenolic compounds such as caffeic acid phenethyl ester and genistein, showed potent inhibition of benzo(a)pyrene [B(a)P] metabolite-DNA binding. Phenolic compounds also demonstrated strong antioxidant activity. Most of the test compounds did not inhibit 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ornithine decarboxylase (ODC) activity with cultured mouse epidermal ME 308 cells, with the exception of sulfur-containing compounds, 1,2-dithiole-3-thione and sulforaphane, and a selenium compound, 1,4-phenylenebis (methylene)selenocyanate. With cultured Hepa 1c1c7 cells, sulforaphane and I, 2-dithiole-3-thione mediated strong induction of quinone reductase, and genistein and ursolic acid were moderate inducers. Chalcone, 1,4-phenylenebis (methylene)selenocyanate and caffeic acid phenethyl ester induced HL-60 cell differentiation Interestingly sulforaphane and caffeic acid phenethyl ester inhibited the total metabolism of benzo(a)pyrene with cultured BEAS-2B cells, and the distribution pattern of water-soluble metabolites was altered in comparison with the control groups. These data are suggestive of pleiotropic mechanisms that should prove beneficial when considering the chemopreventive activity of these substances. As a result, of the group of 25 agents tested, four were judged as superior cancer chemopreventive agents: caffeic acid phenethyl ester, 1,2-dithiole-3-thione, genistein, and sulforaphane. C1 Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, Program Collaborat Res Pharmaceut Sci, Chicago, IL 60612 USA. NCI, Chemoprevent Branch, NIH, Bethesda, MD 20892 USA. RP Pezzuto, JM (reprint author), Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, Program Collaborat Res Pharmaceut Sci, M-C 877,833 S Wood St, Chicago, IL 60612 USA. FU NCI NIH HHS [N01-CN-55136] NR 53 TC 37 Z9 37 U1 1 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JAN-FEB PY 1999 VL 19 IS 1A BP 35 EP 44 PG 10 WC Oncology SC Oncology GA 187KQ UT WOS:000079786100006 PM 10226522 ER PT J AU Ratnasinghe, D Tangrea, J Roth, MJ Dawsey, S Hu, N Anver, M Wang, QH Taylor, PR AF Ratnasinghe, D Tangrea, J Roth, MJ Dawsey, S Hu, N Anver, M Wang, QH Taylor, PR TI Expression of cyclooxygenase-2 in human squamous cell carcinoma of the esophagus; an immunohistochemical survey SO ANTICANCER RESEARCH LA English DT Article DE immunohistochemistry; esophageal cancer; cyclooxygenase-2; NSAIDs ID EPITHELIAL-CELLS; GENE-EXPRESSION; PHORBOL ESTER; MESSENGER-RNA; CANCER; RISK; ASPIRIN; LINXIAN; ENCODES; CHINA AB Several studies indicate that the use of non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the risk of esophageal cancer The best known function of NSAIDs action is to block the enzyme cyclooxygenase, the rate limiting enzyme in the conversion of arachidonic acid to prostaglandins. In this study we investigated the expression of cyclooxygenase-2 (Cox-2) in squamous cell cancers of the esophagus and in normal esophageal squamous epithelium. Immunohistochemical detection of Cox-2 revealed strong positive staining in the well-differentiated regions of esophageal tumors, whereas histologically normal squamous epithelium stained only weakly positive. Smooth muscle cells, some stromal and inflammatory cells were also positive. Poorly differentiated areas of the esophageal tumors were negative. Our results suggest that Cox-2 is over-expressed in well-differentiated regions of squamous cell cancers of the esophagus. C1 NCI, Canc Prevent Studies Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NCI, Pathol Histotechnol Lab, SAIC, Frederick Canc Res & Dev Ctr, Frederick, MD USA. RP Ratnasinghe, D (reprint author), NCI, Canc Prevent Studies Branch, Div Clin Sci, NIH, 6006 Execut Blvd,Suite 321, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CO-56000] NR 21 TC 84 Z9 94 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JAN-FEB PY 1999 VL 19 IS 1A BP 171 EP 174 PG 4 WC Oncology SC Oncology GA 187KQ UT WOS:000079786100023 PM 10226539 ER PT J AU Ung, A Chen, CJ Levine, PH Cheng, YJ Brinton, LA Chen, IH Goldstein, AM Hsu, MM Chhabra, SK Chen, JY Apple, RJ Yang, CS Hildesheim, A AF Ung, A Chen, CJ Levine, PH Cheng, YJ Brinton, LA Chen, IH Goldstein, AM Hsu, MM Chhabra, SK Chen, JY Apple, RJ Yang, CS Hildesheim, A TI Familial and sporadic cases of nasopharyngeal carcinoma in Taiwan SO ANTICANCER RESEARCH LA English DT Article DE nasopharyngeal carcinoma; familial; epidemiology ID EPSTEIN-BARR-VIRUS; SALTED FISH; CANCER; INFECTION; CHINESE; RISK; AGE AB Background Nasopharyngeal carcinoma (NPC) has a striking geographic/ethnic distribution with especially high rates among southern Chinese. Previous studies have indicated that a family history of NPC is associated with increased risk and noted familial clustering in low-risk populations Materials and Methods: We investigated differences between sporadic and familial cases of NPC in a case-control study, of 375 histologically confirmed NPC cases (99% response late) and 328 age-, sex-, and geographically-matched controls (88% response rate). All participants answered a derailed risk factor interview and donated blood for EBV and CYP 2E1 testing Results: Subjects with a first degree relative with NPC had an odds ratio (OR) of 7.6 (95% confidence interval (CI) =2.3-25), while those with a family history of any other cancer had only a slightly elevated risk of disease (OR=1.4; 95% CI=.93-2.2). Of the cases, 25 (6.7%) were familial-having at least one first degree relative with NPC. No significant difference was seen between familial and sporadic cases with respect to sex, age, ethnicity, histology or stage. There was a nonsignificant (p =0.16) increase in TIN2 tumors among familial cases, suggesting a more aggressive tumor. Family history of other cancers, EBV serologies, or the distribution of the Rsal c2 form of the allele of cytochrome P450 2E1 were also not significantly different between the two groups. Conclusions: In conclusion, while genetic factors ale likely to play an important role in NPC pathogenesis, our results provide little evidence that a familial form of NPC exists with characteristics notably distinct from sporadic cases. C1 NCI, DCEG, Environm Epidemiol Branch, Interdisciplinary Studies Sect, Bethesda, MD 20892 USA. Howard Hughes Res Scholars Program, Bethesda, MD 20814 USA. Natl Taiwan Univ, Inst Epidemiol, Coll Publ Hlth, Taipei, Taiwan. George Washington Univ, Sch Publ Hlth, Washington, DC 20052 USA. MacKay Mem Hosp, Dept Otolaryngol, Taipei, Taiwan. Natl Taiwan Univ Hosp, Dept Otolaryngol, Taipei, Taiwan. Natl Taiwan Univ, Coll Med, Inst Microbiol, Taipei 10018, Taiwan. NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. Roche Mol Syst, Alameda, CA USA. RP Hildesheim, A (reprint author), NCI, DCEG, Environm Epidemiol Branch, Interdisciplinary Studies Sect, EPN 443, Bethesda, MD 20892 USA. RI Chen, Chien-Jen/C-6976-2008; apple, raymond/I-4506-2012; Chen, Jen-Yang/D-2085-2010; Brinton, Louise/G-7486-2015 OI apple, raymond/0000-0002-8007-0345; Brinton, Louise/0000-0003-3853-8562 NR 21 TC 32 Z9 35 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JAN-FEB PY 1999 VL 19 IS 1B BP 661 EP 665 PG 5 WC Oncology SC Oncology GA 187KT UT WOS:000079786300007 PM 10216473 ER PT J AU de Lucca, AJ Walsh, TJ AF de Lucca, AJ Walsh, TJ TI Antifungal peptides: Novel therapeutic compounds against emerging pathogens SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Review ID EXPERIMENTAL DISSEMINATED CANDIDIASIS; PNEUMOCYSTIS-CARINII PNEUMONIA; TRACHEAL ANTIMICROBIAL PEPTIDE; RABBIT GRANULOCYTE PEPTIDES; HUMAN NEUTROPHIL DEFENSINS; SYRINGAE PV SYRINGAE; NEOFORMANS IN-VITRO; SACCHAROMYCES-CEREVISIAE; BACILLUS-SUBTILIS; CRYPTOCOCCUS-NEOFORMANS C1 ARS, So Reg Res Ctr, USDA, New Orleans, LA 70124 USA. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP de Lucca, AJ (reprint author), ARS, So Reg Res Ctr, USDA, 1100 Robert E Lee Blvd, New Orleans, LA 70124 USA. EM adelucca@nola.srrc.usda.gov NR 191 TC 176 Z9 185 U1 1 U2 16 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 1999 VL 43 IS 1 BP 1 EP 11 PG 11 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 163UD UT WOS:000078424000001 PM 9869556 ER PT J AU Frosch, BA Berquin, I Emmert-Buck, MR Moin, K Sloane, BF AF Frosch, BA Berquin, I Emmert-Buck, MR Moin, K Sloane, BF TI Molecular regulation, membrane association and secretion of tumor cathepsin B SO APMIS LA English DT Review DE cathepsin B; cysteine protease; membrane protease; secretion, molecular regulation ID BREAST-CANCER CELLS; HUMAN COLORECTAL-CARCINOMA; PROCATHEPSIN-L; SUBSTRATUM ACIDIFICATION; LIPOXYGENASE METABOLITE; EPITHELIAL-CELLS; MALIGNANT-CELLS; HUMAN-PROSTATE; EXPRESSION; GENE AB Upregulation, membrane association and secretion of cathepsin B have been shown to occur in many types of tumors and to correlate positively with their invasive and metastatic capabilities. To further understand changes in cathepsin B activity and localization, we have been examining its regulation at many levels including transcription and trafficking. Our studies indicate that there may be three promoter regions in the cathepsin B gene. Of these, continued examination of the promoter upstream of exon 1 has indicated possible control by several regulatory factors including E-box and Sp-1 binding elements. Upregulation of cathepsin B at this level may account for some of the secretion of cathepsin B found in tumors. We have also gathered evidence that endo- and exocytosis of cathepsin B may be regulated by ras and ras-related proteins in addition to previously described trafficking systems. There is also evidence that several populations of lysosomes may exist and that trafficking to different populations may determine whether cathepsin B is secreted from the tumor cell or remains intracellular. Our results indicate that membrane association and secretion of cathepsin B is not a random process in the tumor cell, but rather part of a tightly controlled system. C1 Wayne State Univ, Sch Med, Dept Pharmacol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Barbara Ann Karmanos Canc Inst, Detroit, MI 48201 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Sloane, BF (reprint author), Wayne State Univ, Sch Med, Dept Pharmacol, 540 E Canfield, Detroit, MI 48201 USA. RI Sloane, Bonnie/A-1050-2009 FU NCI NIH HHS [CA 36481, CA 56586] NR 65 TC 78 Z9 80 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0903-4641 J9 APMIS JI APMIS PD JAN PY 1999 VL 107 IS 1 BP 28 EP 37 PG 10 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 177NH UT WOS:000079215800005 PM 10190277 ER PT J AU Loeb, MJ Jaffe, H Gelman, DB Hakim, RS AF Loeb, MJ Jaffe, H Gelman, DB Hakim, RS TI Two polypeptide factors that promote differentiation of insect midgut stem cells in vitro SO ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY LA English DT Article DE differentiation factor; midgut; Heliothis virescens; Manduca sexta; stem cells ID GROWTH-FACTOR; MANDUCA-SEXTA; IN-VITRO; DROSOPHILA-MELANOGASTER; FAT-BODY; FAMILY; LARVAE; PURIFICATION; EPITHELIUM; EXTRACTS AB Isolated stem cells from the midguts of Manduca sexta and Heliothis virescens can be induced to differentiate in vitro by either of two polypeptide factors, One of the peptides was isolated from culture medium conditioned by differentiating mixed midgut cells; we used high performance liquid chromatographic separation and Edman degradation of the most prominent active peak. It is a polypeptide with 30 amino acid residues (3,244 Dal, with the sequence HVGKTPIVGQPSIPGGPVRLCPGRIR-YFKI, and is identical to the C-terminal peptide of bovine fetuin. A portion of this molecule (HVGKTPIVGQPSIPGGPVRLCPGRIR) was synthesized and was found to be very active in inducing differentiation of H. virescens midgut seem cells. It was designated Midgut Differentiation Factor 1 (MDF1), Proteolysis of bovine fetuin with chymotrypsin allowed isolation of a pentamer, Midgut Differentiation Factor 2 (MDF2) with the sequence HRAHY corresponding to a portion of the fetuin molecule near MDF1, Synthetic MDF2 was also biologically active in midgut stem cell bioassays, Dose response curves indicate activity in physiological ranges from 10(-14) to 10(-9) M for MDF1 and 10(-15) to 10(-5) M for MDF2. Published 1999 Wiley-Liss, Inc. C1 USDA, Insect Biocontrol Lab, Beltsville, MD 20705 USA. NINDS, NIH, LNC, Prot Peptide Sequencing Fac, Bethesda, MD 20892 USA. Howard Univ, Sch Med, Dept Anat, Washington, DC 20059 USA. RP Loeb, MJ (reprint author), USDA, Insect Biocontrol Lab, Bldg 011A Rm 211 BARC West, Beltsville, MD 20705 USA. NR 41 TC 29 Z9 30 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0739-4462 J9 ARCH INSECT BIOCHEM JI Arch. Insect Biochem. Physiol. PY 1999 VL 40 IS 3 BP 129 EP 140 DI 10.1002/(SICI)1520-6327(1999)40:3<129::AID-ARCH2>3.0.CO;2-B PG 12 WC Biochemistry & Molecular Biology; Entomology; Physiology SC Biochemistry & Molecular Biology; Entomology; Physiology GA 184EC UT WOS:000079596600002 PM 10207992 ER PT J AU Gelb, DJ Oliver, E Gilman, S AF Gelb, DJ Oliver, E Gilman, S TI Diagnostic criteria for Parkinson disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID PROGRESSIVE SUPRANUCLEAR PALSY; LEWY-BODY-DISEASE; RICHARDSON-OLSZEWSKI-SYNDROME; MULTIPLE SYSTEM ATROPHY; CLINICAL-DIAGNOSIS; ALZHEIMERS-DISEASE; DEMENTIA; FEATURES; ACCURACY; DEGENERATION AB The clinical diagnosis of Parkinson disease (PD) is based on the identification of some combination of the cardinal motor signs of bradykinesia, rigidity, tremor, and postural instability, but few attempts have been made to develop explicit diagnostic criteria. We propose a clinical diagnostic classification based on a comprehensive review of the literature regarding the sensitivity and specificity of the characteristic clinical features of PD. Three levels of diagnostic confidence are differentiated: Definite, Probable, and Possible. The diagnoses of Possible and Probable PD are based on clinical criteria alone. Neuropathologic confirmation is required for the diagnosis of Definite PD in patients with the clinical diagnosis of Possible or Probable PD. Criteria for histopathologic confirmation of PD are also presented. C1 Univ Michigan, Med Ctr, Dept Neurol, Ann Arbor, MI 48109 USA. NINDS, NIH, Bethesda, MD USA. RP Gilman, S (reprint author), Univ Michigan, Med Ctr, Dept Neurol, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. NR 72 TC 1437 Z9 1488 U1 7 U2 86 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JAN PY 1999 VL 56 IS 1 BP 33 EP 39 DI 10.1001/archneur.56.1.33 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 157GQ UT WOS:000078053300006 PM 9923759 ER PT J AU Schneider, C Dalakas, MC Toyka, KV Said, G Hartung, HP Gold, R AF Schneider, C Dalakas, MC Toyka, KV Said, G Hartung, HP Gold, R TI T-cell apoptosis in inflammatory neuromuscular disorders associated with human immunodeficiency virus infection SO ARCHIVES OF NEUROLOGY LA English DT Article ID INCLUSION-BODY MYOSITIS; RECEPTOR REPERTOIRE; MULTIPLE-SCLEROSIS; NERVOUS-SYSTEM; MUSCLE-FIBERS; POLYMYOSITIS; DEATH; LYMPHOCYTES; ENCEPHALOMYELITIS; DERMATOMYOSITIS AB Background: Apoptosis is one of the major mechanisms of CD4(+) T-cell depletion in human immunodeficiency virus (HIV) infection. T cells in human inflammatory myopathies in HIV-negative individuals rarely undergo apoptosis. Currently, there is no information available concerning the fate of T cells in HIV-associated myositis and polyneuropathies. Objective: To investigate whether apoptosis occurs in inflammatory lesions of muscle and nerve biopsy specimens of untreated HIV-positive patients with neuromuscular disorders. Methods: T-cell apoptosis was investigated in muscle and nerve specimens from 12 patients with HIV-associated polymyositis and 8 patients with HIV-associated inflammatory polyneuropathy. These were compared with specimens from 36 HIV-negative patients with other inflammatory myopathies and from 18 patients with inflammatory polyneuropathies. Apoptosis was assessed according to morphological criteria and with the use of in situ labeling methods. Results: In none of the HIV-associated disorders did we observe a substantial proportion of apoptotic T cells as assessed by nuclear morphological findings and in situ labeling techniques. Fas expression was up regulated only in a few inflammatory cells. Positive labeling for Fas ligand was not associated with increased apoptosis of surrounding T cells. Nuclei of degenerating muscle fibers and macrophages did not show morphological signs of apoptosis and were not labeled by the tailing reaction. Conclusions: Similar to their idiopathic counterparts, in HIV-related polymyositis and inflammatory neuropathy, T-cell inflammation is not cleared by apoptosis. The observations are consistent with the non-self-limited nature of endomysial or endoneural inflammation and suggest that in HIV-positive patients, the T-cell elimination is differentially regulated in the lymphoid organs as compared with neuromuscular tissues. C1 Univ Wurzburg, Neurol Klin, Dept Neurol, Clin Res Unit Multiple Sclerosis, D-97080 Wurzburg, Germany. NINDS, NIH, Bethesda, MD 20892 USA. CHU Bicetre, Dept Neurol, Le Kremlin Bicetre, France. RP Gold, R (reprint author), Univ Wurzburg, Neurol Klin, Dept Neurol, Clin Res Unit Multiple Sclerosis, Josef Schneider Str 11, D-97080 Wurzburg, Germany. EM r.gold@mail.uni-wuerzburg.de NR 27 TC 13 Z9 13 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JAN PY 1999 VL 56 IS 1 BP 79 EP 83 DI 10.1001/archneur.56.1.79 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 157GQ UT WOS:000078053300011 PM 9923764 ER PT J AU Scully, RE Henson, DE Nielsen, ML Ruby, SG AF Scully, RE Henson, DE Nielsen, ML Ruby, SG CA Canc Comm Coll Amer Pathologists TI Protocol for the examination of specimens from patients with carcinoma of the fallopian tube - A basis for checklists SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NCI, Early Detect Branch, Div Canc Prevent & Control, Bethesda, MD 20892 USA. Pathol Consultants, Wichita, KS USA. Hinsdale Hosp, Dept Pathol & Lab Med, Hinsdale, IL USA. RP Scully, RE (reprint author), Care Of Schramm J, Coll Amer Pathologists, 325 Waukegan Rd, Northfield, IL 60093 USA. NR 11 TC 4 Z9 4 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 1999 VL 123 IS 1 BP 33 EP 38 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 157QM UT WOS:000078073200007 PM 9923834 ER PT J AU Kingma, DW Mueller, BU Frekko, K Sorbara, LR Wood, LV Katz, D Raffeld, M Jaffe, ES AF Kingma, DW Mueller, BU Frekko, K Sorbara, LR Wood, LV Katz, D Raffeld, M Jaffe, ES TI Low-grade monoclonal Epstein-Barr virus-associated lymphoproliferative disorder of the brain presenting as human immunodeficiency virus-associated encephalopathy in a child with acquired immunodeficiency syndrome SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; IMMUNE-DEFICIENCY-SYNDROME; NON-HODGKINS-LYMPHOMA; INSITU HYBRIDIZATION; B-LYMPHOCYTES; T-LYMPHOCYTES; GRANULOMATOSIS; DISEASE; SPECTRUM; AIDS AB The association of the Epstein-Barr virus with human immunodeficiency virus-associated primary central nervous system lymphomas is well known. We describe a pediatric patient infected with human immunodeficiency virus who developed a lesion in the central nervous system that appeared to be histologically reactive and that proved to be an Epstein-Barr virus-associated monoclonal B-cell lymphoproliferative disorder by molecular analysis. An 8-year-old girl was diagnosed with vertically transmitted human immunodeficiency virus infection at age 5, for which she was treated empirically with a combination of zidovudine and didanosine. At the age of 7 years, during evaluation for entry into an antiretroviral protocol, a single hypodense frontal lobe lesion was identified by computed tomography. After unsuccessful treatment for presumed toxoplasmosis and progressive neurologic deterioration, a stereotactic brain biopsy was performed. Although the biopsy contained a polymorphic lymphoid infiltrate that appeared to be cytologically reactive, polymerase chain reaction and in situ hybridization studies revealed a monoclonal Epstein-Barr virus-associated B-cell lymphoproliferative disorder, which was reminiscent of polymorphic B-cell hyperplasia observed in the setting of immunosuppression following organ transplantation. Postoperative therapy included steroids and antiretroviral therapy. The lesion decreased slightly in size, and the child's neurologic status was relatively unremarkable for 5 months. Subsequently, she developed cytomegalovirus retinitis, progressive encephalopathy, and died with pancytopenia. This case represents a newly described manifestation of Epstein-Barr virus-associated lymphoproliferative disorder, a diagnosis that should be considered in patients with neurologic symptoms and immunodeficiency. In addition, this case exhibited histologic features reminiscent of posttransplant lymphoproliferative disease, a histologic pattern that to our knowledge has not previously been reported in the setting of acquired immunodeficiency syndrome. C1 NCI, Hematopathol Sect, Pathol Lab, Div Clin Sci,NIH, Bethesda, MD 20892 USA. NCI, HIV & AIDS Malignancy Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Kingma, DW (reprint author), NCI, Hematopathol Sect, Pathol Lab, Div Clin Sci,NIH, Bldg 10,Room 2A33, Bethesda, MD 20892 USA. NR 33 TC 7 Z9 7 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 1999 VL 123 IS 1 BP 83 EP 87 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 157QM UT WOS:000078073200016 PM 9923843 ER PT J AU Holmes, JL Kirkwood, CD Gerna, G Clemens, JD Rao, MR Naficy, AB Abu-Elyazeed, R Savarino, SJ Glass, RI Gentsch, JR AF Holmes, JL Kirkwood, CD Gerna, G Clemens, JD Rao, MR Naficy, AB Abu-Elyazeed, R Savarino, SJ Glass, RI Gentsch, JR TI Characterization of unusual G8 rotavirus strains isolated from Egyptian children SO ARCHIVES OF VIROLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; SEQUENCE-ANALYSIS; MONOCLONAL-ANTIBODIES; BOVINE ROTAVIRUSES; BRAZILIAN CHILDREN; RELATIVE FREQUENCY; VP4 SEROTYPE; PROTEIN VP4; SUBGROUP-I; IDENTIFICATION AB We report the first detection of P[14], G8 rotaviruses isolated in Egypt from the stool of children participating in a 3 year study of rotavirus epidemiology. Two strains, EGY1850 and EGY2295, were characterized by a serotyping enzyme immunoassay (EIA), virus neutralization, and sequence analysis of the genes encoding VP7 and the VP8* portion of the VP4 gene. These two strains shared a high level of homology of their VP7s (87.8% nucleotide [nt], 97.2% amino acid [aa]) and VP4s (89.6% nt, 97.1% aa) and had the highest VP7 identity to serotype G8 (>82% nt, >92% aa) and VP4 identity to genotype P[14] (greater than or equal to 81% nt, >91% aa) strains. Serological results with a VP7 G8-specific and VP4 P[14]-specific neutralizing monoclonal antibodies supported the genetic classification of EGY1850 and EGY2295 as P[14], G8. Genogroup analysis supports earlier findings that human G8 rotaviruses may be genetically related to bovine rotaviruses. These findings demonstrate that our understanding of the geographic distribution of rotavirus strains is incomplete, emphasize the need to monitor rotavirus serotypes, and extend the known distribution of serotype G8 and genotype P[14] strains in Africa. C1 Ctr Dis Control & Prevent, Viral Gastroenteritis Sect MS G04, Div Viral & Rickettsial Dis,Nat Ctr Infect Dis, Publ Hlth Serv,US Dept Hlth & Human Serv, Atlanta, GA 30333 USA. Policlin San Matteo, IRCCS, Viral Diagnost Serv, I-27100 Pavia, Italy. NICHHD, Epidemiol Branch, Bethesda, MD 20892 USA. USN, Med Res Unit 3, Cairo, Egypt. RP Holmes, JL (reprint author), Ctr Dis Control & Prevent, Viral Gastroenteritis Sect MS G04, Div Viral & Rickettsial Dis,Nat Ctr Infect Dis, Publ Hlth Serv,US Dept Hlth & Human Serv, 1600 Clifton Rd NE, Atlanta, GA 30333 USA. NR 56 TC 56 Z9 57 U1 0 U2 2 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 1999 VL 144 IS 7 BP 1381 EP 1396 DI 10.1007/s007050050594 PG 16 WC Virology SC Virology GA 221TE UT WOS:000081741700009 PM 10481744 ER PT J AU Yunus, AS Krishnamurthy, S Pastey, MK Huang, Z Khattar, SK Collins, PL Samal, SK AF Yunus, AS Krishnamurthy, S Pastey, MK Huang, Z Khattar, SK Collins, PL Samal, SK TI Rescue of a bovine respiratory syncytial virus genomic RNA analog by bovine, human and ovine respiratory syncytial viruses confirms the "functional integrity" and "cross-recognition'' of BRSV cis-acting elements by HRSV and ORSV SO ARCHIVES OF VIROLOGY LA English DT Article ID NUCLEOTIDE-SEQUENCE ANALYSIS; G-GLYCOPROTEIN GENE; MESSENGER-RNA; SYNTHETIC ANALOGS; REPORTER GENE; SENDAI VIRUS; PROTEIN; TRANSCRIPTION; REPLICATION; EXPRESSION AB The nucleotide sequences of the 3' leader and 5' trailer regions were determined for genomic RNA of bovine respiratory syncytial virus (BRSV) strain A-51908. The leader and trailer sequences are '45' and '161' nucleotides in length, respectively The functionality of BRSV leader and trailer sequences and their recognition by HRSV and ovine respiratory syncytial virus (ORSV) proteins were examined with a in vitro transcribed BRSV genomic RNA analog carrying the bacterial chloramphenicol acetyl transferase (CAT) gene under the control of BRSV transcription signals. Upon transfection into BRSV, HRSV or ORSV infected cells, the BRSV minireplicons were 'rescued' such that the reporter gene was expressed, the minigenome was replicated and packaged into micrococcal nuclease resistant-infectious minireplicons. The passage of infectious minireplicons could be blocked by a polyclonal BRSV neutralizing antiserum. Bovine parainfluenza virus-3, a heterologous paramyxovirus was inactive in rescuing BRSV genomic RNA analog. Mutational substitution of the G residue at position 4 of leader sequence in the BRSV genomic RNA analog, with an A or U residue inhibited its transcription and replication, while replacement with a C residue had no significant effect on rescue. These results show that the cis-acting elements of BRSV are functional and are also recognized by the proteins of HRSV and ORSV. The helper virus complemented rescue system developed here will be useful for characterizing the cis-acting elements of BRSV. C1 Univ Maryland, VA MD Reg Coll Vet Med, College Pk, MD 20742 USA. NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Samal, SK (reprint author), Univ Maryland, VA MD Reg Coll Vet Med, College Pk, MD 20742 USA. NR 34 TC 20 Z9 20 U1 1 U2 2 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 1999 VL 144 IS 10 BP 1977 EP 1990 DI 10.1007/s007050050719 PG 14 WC Virology SC Virology GA 253LT UT WOS:000083558600008 PM 10550670 ER PT J AU Briggs, CJ Ott, DE Coren, LV Oroszlan, S Tozser, J AF Briggs, CJ Ott, DE Coren, LV Oroszlan, S Tozser, J TI Comparison of the effect of FK506 and cyclosporin A on virus production in H9 cells chronically and newly infected by HIV-1 SO ARCHIVES OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYCLOPHILIN-A; TYPE-1; REPLICATION; PROTEIN; VIRIONS; CYCLE; INHIBITION; PATHWAY; ANALOG AB The presence of FK506-binding protein-12 was demonstrated in virions of HIV-I, although its concentration was lower than that of cyclophilin A. The effect of two inhibitors of the peptidyl-prolyl cis-trans isomerases FK506 and cyclosporin A (CsA) was studied in H9 cells that were chronically infected by HIV-I. Both drugs inhibited virus production in the infected cells in a concentration-dependent manner, by decreasing the number of the producing cells. FK506 did not have an effect on Gag processing, based on the p24 antigen content of virions produced in the presence of this drug. Furthermore, FK506 treatment of uninfected H9 cells did not diminish their susceptibility toward HIV-1 infection, whereas CsA treatment decreased the degree of HIV-1 infection with an IC50 of 1-2 mu g/ml. Also, pretreatment of the virus with CsA decreased its infectivity in HeLaCD4-LTR/beta-gal cells; in contrast, at concentrations up to 10 mu g/ml, FK506 did not have an effect. Our findings on the antiviral activity of FK506 and CsA suggest that FK506 is effective only in chronically infected cells, by selectively inhibiting the growth of HIV-1 infected cells, whereas CsA has a specific effect on virus replication. C1 Debrecen Univ Med, Sch Med, Dept Biochem & Mol Biol, H-4012 Debrecen, Hungary. ABL Basic Res Program, Mol Virol & Carcinogensis Lab, Frederick, MD USA. NCI, Frederick Canc Res & Dev Ctr, AIDS Vaccine Program, SAIC Frederick, Frederick, MD USA. RP Tozser, J (reprint author), Debrecen Univ Med, Sch Med, Dept Biochem & Mol Biol, POB 6, H-4012 Debrecen, Hungary. RI Tozser, Jozsef/A-7840-2008; OI Tozser, Jozsef/0000-0003-0274-0056; Tozser, Jozsef/0000-0001-5076-8729 FU NCI NIH HHS [N01-CO-56000] NR 25 TC 20 Z9 22 U1 0 U2 0 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 1999 VL 144 IS 11 BP 2151 EP 2160 DI 10.1007/s007050050629 PG 10 WC Virology SC Virology GA 259VT UT WOS:000083915200007 PM 10603169 ER PT J AU Chaisson, CE Zhang, YQ Sharma, L Kannel, W Felson, DT AF Chaisson, CE Zhang, YQ Sharma, L Kannel, W Felson, DT TI Grip strength and the risk of developing radiographic hand osteoarthritis - Results from the Framingham Study SO ARTHRITIS AND RHEUMATISM LA English DT Article ID PHYSICAL-ACTIVITY; CARDIOVASCULAR-DISEASE; KNEE; WOMEN; JOINT; PRESSURES; PATTERNS; FORCES AB Objective. In knees, quadriceps strength may protect against osteoarthritis (OA), Muscle activity is a major determinant of forces at the hand joints, and grip is a common task during which high muscle forces are sustained, especially at the proximal hand joints (metacarpophalangeal [MCP] joints and thumb base), This longitudinal study of radiographic hand OA examined the association between incident OA at different hand joints and maximal grip strength. Methods. Four hand joint groups were studied: distal interphalangeal (DIP), proximal interphalangeal (PIP), MCP, and the base of the thumb (carpometacarpal and scaphotrapezial combined). Subjects were members of the Framingham OA Study who had a baseline radiograph in 1967-1969 and a followup radiograph in 1992-1993 (mean followup 24 years) and had no prevalent radiographic OA in any hand joint at baseline. Incident disease was defined as development of OA defined as a modified Kellgren/Lawrence grade of greater than or equal to 2, Grip strength was measured in kilograms by dynamometer in 1958-1961 and again in 1960-1963, and the 2 measures were averaged and divided into sex-specific tertiles, Joint-based analysis was performed by adjusting for age, physical activity, and occupational category using the lowest grip strength tertile as the referent, Results, Baseline and followup radiographs were obtained from 746 subjects. Of these, 453 subjects with no prevalent OA at baseline were eligible for analysis, In men, higher maximal grip strength was associated with an increased risk of OA in the PLP (highest tertile odds ratio [OR] 2.8 compared with lowest tertile, 95% confidence interval [95% CI] 1.2-6.7), MCP (highest tertile OR 2.9, 95% CI 1.1-7.4), and thumb base joints (highest tertile OR 2.8, 95% CI 1.1-7.4), In women, there was increased risk of OA in the MCP joints (highest tertile OR 2.7, 95% CI 1.1-6.4). Conclusion. Men with high maximal grip strength are at increased risk for the development of OA in the PIP, MCP, and thumb base joints, and women, in the MCP joints. No association was found between maximal grip strength and incident OA in the DIP joints of men or women. C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Northwestern Univ, Chicago, IL 60611 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Chaisson, CE (reprint author), Boston Univ, Ctr Arthritis, 715 Albany St,A-203, Boston, MA 02215 USA. FU NHLBI NIH HHS [N01-HC-38038]; NIAMS NIH HHS [AR-20613] NR 31 TC 63 Z9 63 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JAN PY 1999 VL 42 IS 1 BP 33 EP 38 DI 10.1002/1529-0131(199901)42:1<33::AID-ANR4>3.0.CO;2-I PG 6 WC Rheumatology SC Rheumatology GA 157HU UT WOS:000078056200004 PM 9920011 ER PT J AU Lipsky, PE Maini, RN AF Lipsky, Peter E. Maini, Ravinder N. TI Arthritis Research: more than a journal SO ARTHRITIS RESEARCH LA English DT Editorial Material C1 [Lipsky, Peter E.] NIAMS, NIH, Bethesda, MD 20892 USA. [Maini, Ravinder N.] Kennedy Inst, London W6 8LH, England. RP Lipsky, PE (reprint author), NIAMS, NIH, 10-9N228, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-9913 J9 ARTHRITIS RES JI Arthritis Res. PY 1999 VL 1 IS 1 BP 1 EP 2 DI 10.1186/ar1 PG 2 WC Rheumatology SC Rheumatology GA V35OF UT WOS:000209157800001 PM 11094404 ER PT J AU El-Gabalawy, H AF El-Gabalawy, Hani TI The challenge of early synovitis: multiple pathways to a common clinical syndrome SO ARTHRITIS RESEARCH LA English DT Review C1 NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP El-Gabalawy, H (reprint author), NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. EM elgabala@exchange.nih.gov NR 65 TC 5 Z9 5 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-9913 J9 ARTHRITIS RES JI Arthritis Res. PY 1999 VL 1 IS 1 BP 31 EP 36 DI 10.1186/ar8 PG 6 WC Rheumatology SC Rheumatology GA V35OF UT WOS:000209157800008 PM 11094411 ER PT J AU Lee, J Goldbach-Mansky, R Hitchon, C Danning, C Aringer, M Hoxworth, J Smolen, J Palusuo, T Schumacher, R Smith, D Wilder, R El-Gabalawy, H AF Lee, J. Goldbach-Mansky, R. Hitchon, C. Danning, C. Aringer, M. Hoxworth, J. Smolen, J. Palusuo, T. Schumacher, R. Smith, D. Wilder, R. El-Gabalawy, Hani TI Predictors of Early Bone Erosion in Patients With Synovitis of Recent Onset SO ARTHRITIS RESEARCH & THERAPY LA English DT Meeting Abstract C1 [Lee, J.; Goldbach-Mansky, R.; Hitchon, C.; Danning, C.; Aringer, M.; Hoxworth, J.; Smolen, J.; Palusuo, T.; Schumacher, R.; Smith, D.; Wilder, R.; El-Gabalawy, Hani] NIAMSD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 1999 VL 1 SU 1 PG 1 WC Rheumatology SC Rheumatology GA V31MD UT WOS:000208886800036 ER PT J AU Marastoni, M Guerrini, R Balboni, G Salvadori, S Fantin, G Fogagnolo, M Lazarus, LH Tomatis, R AF Marastoni, M Guerrini, R Balboni, G Salvadori, S Fantin, G Fogagnolo, M Lazarus, LH Tomatis, R TI Opioid deltorphin C analogues containing cis- or trans-2- or 3- or 4-aminocyclohexanecarboxylic acid residues SO ARZNEIMITTEL-FORSCHUNG-DRUG RESEARCH LA English DT Article DE aminocyclohexanecarboxylic acid, constrained amino acids; deltorphin C analogues; opioids, peptides ID AMPHIBIAN SKIN; HIGH-AFFINITY; PEPTIDES; RECEPTOR; POTENT; SELECTIVITY; DYNORPHIN; BINDING; BRAIN; MU AB The solid phase synthesis, based on the Fmoc chemical protocol, was used to prepare ten deltorphin C (Del-C; H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2) analogues containing cis- and trans- 2 or 3- or 4- aminocyclohexanecarboxylic acid (ACCA) residues at position 3. ACCA-peptides showed high resistance to degradation by plasma or blain enzymes, negligible affinity for the kappa-binding site and modest delta- and/or mu-receptor affinities. Both [cis-3-ACCA(2)]Del-C analogues and one trans isomer are the only deltorphin analogues of this series exhibiting an appreciable delta-affinity and selectivity. These data suggest that the presence of st conformationally constrained ACCA residue in position 2 of the "message" sequence of deltorphin C is slightly tolerated. C1 Univ Ferrara, Dipartimento Sci Farmaceut, I-44100 Ferrara, Italy. Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy. Univ Ferrara, Dept Chem, I-44100 Ferrara, Italy. NIEHS, LCBRA, Res Triangle Pk, NC 27709 USA. RP Tomatis, R (reprint author), Univ Ferrara, Dipartimento Sci Farmaceut, Via Fossato Mortara 17-19, I-44100 Ferrara, Italy. OI Guerrini, Remo/0000-0002-7619-0918; SALVADORI, Severo/0000-0002-8224-2358 NR 32 TC 5 Z9 6 U1 0 U2 1 PU ECV-EDITIO CANTOR VERLAG MEDIZIN NATURWISSENSCHAFTEN PI AULENDORF PA BANDELSTOCKWEG 20, POSTFACH 1255, D-88322 AULENDORF, GERMANY SN 0004-4172 J9 ARZNEIMITTEL-FORSCH JI Arzneimittelforschung PD JAN PY 1999 VL 49 IS 1 BP 6 EP 12 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 162QZ UT WOS:000078359400002 PM 10028372 ER PT B AU Prettyman, M Antonucci, R Lynch, P Mericle, L AF Prettyman, M Antonucci, R Lynch, P Mericle, L BE Woods, L TI Electronic publication of health information in an object-oriented environment SO ASIS 99: PROCEEDINGS OF THE 62ND ASIS ANNUAL MEETING, VOL 36, 1999: KNOWLEDGE: CREATION ORGANIZATION AND USE SE PROCEEDINGS OF THE ASIS ANNUAL MEETINGS LA English DT Proceedings Paper CT 62nd Annual Meeting of the American-Society-for-Information-Science on Knowledge - Creation, Organization and Use CY OCT 31-NOV 04, 1999 CL WASHINGTON, D.C. SP Amer Soc Informat Sci ID RETRIEVAL AB The National Library of Medicine is supporting a research project on full-text search and retrieval. In addition to the research aspect, the project includes a fully deployed system, known as HSTAT, to provide access to health information. The information is all government-supported and includes practice guidelines, reference texts, evidence-based reports, clinical trial information, treatment protocols, and technology assessments. The search system depends on the SGML-encoding of the documents to provide context to the user and supports specific retrieval of pertinent sections or paragraphs of large, complex documents. The retrieval system is an object-oriented client-server model and the data is stored in an object-oriented database management system. This is a probabilistic retrieval system, providing ranked results from a natural language query. It also provides browsing and downloading capabilities, in addition to searching the entire collection or specified documents in the collection. The type of data and the perceived needs of the users have driven the development of the project. The results are measured by observation of participation and usage. C1 Natl Lib Med, Bethesda, MD 20894 USA. NR 25 TC 0 Z9 0 U1 0 U2 0 PU INFORMATION TODAY INC PI MEDFORD PA 143 OLD MARLTON PIKE, MEDFORD, NJ 08055 USA BN 1-57387-091-9 J9 P ASIS ANN PY 1999 VL 36 BP 213 EP 227 PG 15 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA BP82C UT WOS:000086299400019 ER PT J AU Banwell, MG Flynn, BL Willis, AC Hamel, E AF Banwell, MG Flynn, BL Willis, AC Hamel, E TI Synthesis, X-ray crystal structure and tubulin-binding properties of a benzofuran analogue of the potent cytotoxic agent combretastatin A4 SO AUSTRALIAN JOURNAL OF CHEMISTRY LA English DT Article ID SOLID-PHASE SYNTHESIS; PALLADIUM-CATALYZED HETEROANNULATION; NATURAL-PRODUCTS; A-4; DERIVATIVES; COLCHICINE; ANTITUBULIN; INHIBITION; MECHANISM; PRODRUGS AB The benzofuran (4), a ring-fused analogue of the potent antimitotic agent combretastatin A4 (1), has been prepared by a convergent route involving 5-endo-dig iodocyclization of o-hydroxytolan (5) as the key step. Compound (4), which has been characterized crystallographically as well as spectroscopically, is inactive as a tubulin-binding agent. C1 Australian Natl Univ, Res Sch Chem, Inst Adv Studies, Canberra, ACT 0200, Australia. NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Banwell, MG (reprint author), Australian Natl Univ, Res Sch Chem, Inst Adv Studies, Canberra, ACT 0200, Australia. RI Banwell, Martin/H-8354-2014 NR 44 TC 33 Z9 33 U1 0 U2 1 PU C S I R O PUBLISHING PI COLLINGWOOD PA 150 OXFORD ST, PO BOX 1139, COLLINGWOOD, VICTORIA 3066, AUSTRALIA SN 0004-9425 J9 AUST J CHEM JI Aust. J. Chem. PY 1999 VL 52 IS 8 BP 767 EP 774 DI 10.1071/CH99022 PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 232ZA UT WOS:000082399500007 ER PT J AU Li, QA Sun, B Matteson, DM O'Brien, TP Chan, CC AF Li, QA Sun, B Matteson, DM O'Brien, TP Chan, CC TI Cytokines and apoptotic molecules in experimental melanin-protein induced uveitis (EMIU) and experimental autoimmune uveoretinitis (EAU) SO AUTOIMMUNITY LA English DT Article DE experimental melanin-protein induced uveitis (EMIU); experimental autoimmune uveoretinitis (EAU); apoptosis; Th1 and Th2 cytokines; autoimmunity ID RETINAL-PIGMENT EPITHELIUM; ANTERIOR UVEITIS; CELL-DEATH; T-CELLS; UP-REGULATION; BCL-2; INDUCTION; ANTIGEN; FAS; INTERLEUKIN-10 AB The cytokine profile and occurrence of apoptosis during experimental melanin-protein induced uveitis (EMIU) were investigated and compared with that of experimental autoimmune uveoretinitis (EAU), EMIU or EAU was induced in Lewis rats. Eyes mere collected at different time points after immunization. Cytokine mRNA expression was identified in the inflammatory cells in the uvea of EMIU rats; IL-2, IFN-gamma and IL-12 increased at the peak of the inflammation, and then tapered off as inflammation subsided. IL-4 and IL-10 increased at the peak of ocular inflammation, and persisted with inflammation resolved, Fas and Fast were expressed consistently in ocular resident cells of EMIU, but were elevated in EAU, In EAU, Bcl-2 expression showed a sharp peak in inflammatory cells but not in the resident cells, In EMIU, high levels of Bcl-2 were present and persisted in both ocular resident and inflammatory cells. Expression of Bar was relatively stable in both EAU and EMIU. Cellular DNA fragmentation was detected in the retinal glial cells of EAU and some inflammatory cells of EMIU. In EMIU, the dynamics of Th1 cytokines were consistent with the ocular inflammation, whereas persistent expression of Th2 cytokines was consistent with their known regulatory role. The continuous high expression of Bcl-2 and the high ratio of Bcl-2 to Bar in the eyes of EMIU may possibly contribute to prevention of ocular tissue damage, and of inflammatory cells from undergoing apoptosis, thus resulting in chronic recurrent inflammation. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Chan, CC (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N103,10 Ctr Dr, Bethesda, MD 20892 USA. NR 25 TC 17 Z9 18 U1 0 U2 2 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 0891-6934 J9 AUTOIMMUNITY JI Autoimmunity PY 1999 VL 30 IS 3 BP 171 EP + DI 10.3109/08916939908993851 PG 14 WC Immunology SC Immunology GA 242UG UT WOS:000082959600005 PM 10520900 ER PT J AU Sarno, RJ Franklin, WL AF Sarno, RJ Franklin, WL TI Maternal expenditure in the polygynous and monomorphic guanaco: suckling behavior, reproductive effort, yearly variation, and influence on juvenile survival SO BEHAVIORAL ECOLOGY LA English DT Article DE Chile; guanaco; Lama guanicoe; maternal expenditure; survival ID MOUNTAIN BIGHORN SHEEP; PARENTAL INVESTMENT; DENSITY DEPENDENCE; WILD REINDEER; SEX-RATIO; DAUGHTERS; COSTS; SONS; HERD; DEER AB We investigated patterns of maternal expenditure and its influence on juvenile survival in the polygnous monomorphic guanaco (Lama guanicoe) in southern Chile from 1990 to 1994. Birth weight and growth rate (until age 1) of males and females were similar Suckling rates of males and females were not significantly different, although mothers of males rejected suckling attempts more often than mothers of females during fall and winter. Mothers with sons terminated suckling bouts in equal proportion as did mothers with daughters. Our estimated level of reproductive effort for guanacos falls within the range of species exhibiting no sex-biased maternal expenditure on offspring. Mean yearly birth weight was negatively correlated with population density;. Mean suckling time throughout the year differed among cohorts, as did the mean number of suckling attempts and rejected suckling attempts per hour throughout the year. Juvenile survival was estimated until age 1. Of the model with five covariates including juvenile sex, birth weight, adult female aggression toward taggers, mean suckling time, and population density, only mean suckling time and population density were significantly related to survival. The risk ratio for mean suckling time indicates that the risk of mortality increases as suckling time increases, whereas the risk ratio for population density indicates that the risk of mortality decreases as population density increases. Under some conditions increasing population density may be correlated with lower offspring birth weight, yet enhanced juvenile survival. This effect on survival was possibly associated with the number of predators on the studs area from year to year. C1 Iowa State Univ, Dept Anim Ecol, Ames, IA 50011 USA. RP Sarno, RJ (reprint author), NCI, FCRDC, Lab Genom Divers, Bldg 560,Room 11-12, Frederick, MD 21702 USA. NR 49 TC 24 Z9 26 U1 0 U2 17 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1045-2249 J9 BEHAV ECOL JI Behav. Ecol. PD JAN-FEB PY 1999 VL 10 IS 1 BP 41 EP 47 DI 10.1093/beheco/10.1.41 PG 7 WC Behavioral Sciences; Biology; Ecology; Zoology SC Behavioral Sciences; Life Sciences & Biomedicine - Other Topics; Environmental Sciences & Ecology; Zoology GA 161LV UT WOS:000078291200006 ER PT S AU Baum, BJ Wang, SL Cukierman, E Delporte, C Kagami, H Marmary, Y Fox, PC Mooney, DJ Yamada, KM AF Baum, BJ Wang, SL Cukierman, E Delporte, C Kagami, H Marmary, Y Fox, PC Mooney, DJ Yamada, KM BE Hunkeler, D Prokop, A Cherrington, AD Rajotte, RV Sefton, M TI Re-engineering the functions of a terminally differentiated epithelial cell in vivo SO BIOARTIFICIAL ORGANS II: TECHNOLOGY, MEDICINE, AND MATERIALS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Bioartificial Organs II - Technology, Medicine and Materials CY JUL 18-22, 1998 CL BANFF, CANADA SP Engn Fdn, Baxter Hlthcare Corp, Juvenile Diabetes Fdn, Natl Inst Hlth, Natl Sci Fdn, NY Acad Sci, Roche/Boehringer Mannheim, Whitaker Fdn ID MEDIATED GENE-TRANSFER; RAT SALIVARY-GLANDS; GROWTH-HORMONE; IN-VIVO; SECRETION; LINE; VECTORS; THERAPY; CDNA AB Because of their easy access, and important role In oral homeostasis, mammalian salivary glands provide a unique site for addressing key issues and problems in tissue engineering. This manuscript reviews studies by us in three major directions involving re-engineering functions of salivary epithelial cells, Using adenoviral-mediated gene transfer in vivo, me show approaches to i) repair damaged, hypofunctional glands and ii) redesign secretory functions to include endocrine as well as exocrine pathways. The third series of studies show our general approach to develop an artificial salivary gland for clinical situations in which all glandular tissue has been lost. C1 NIDCR, GTTB, NIH, Bethesda, MD 20892 USA. NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA. RP Baum, BJ (reprint author), NIDCR, GTTB, NIH, 10 Ctr Dr,MSC 1190,Bldg 10,Room 1N113, Bethesda, MD 20892 USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 30 TC 30 Z9 33 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-194-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 875 BP 294 EP 300 DI 10.1111/j.1749-6632.1999.tb08512.x PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials; Multidisciplinary Sciences; Transplantation SC Engineering; Materials Science; Science & Technology - Other Topics; Transplantation GA BN31W UT WOS:000081586000024 PM 10415576 ER PT B AU Cardellina, JH Fuller, RW Gamble, WR Westergaard, C Boswell, J Munro, MHG Currens, M Boyd, MR AF Cardellina, JH Fuller, RW Gamble, WR Westergaard, C Boswell, J Munro, MHG Currens, M Boyd, MR BE Bohlin, L Bruhn, JG TI Evolving strategies for the selection, dereplication and prioritization of antitumor and HIV-inhibitory natural products extracts SO BIOASSAY METHODS IN NATURAL PRODUCT RESEARCH AND DRUG DEVELOPMENT SE PROCEEDINGS OF THE PHYTOCHEMICAL SOCIETY OF EUROPE LA English DT Proceedings Paper CT International Symposium on Bioassay Methods in Natural Product Research and Drug Development CY AUG 24-27, 1997 CL UPPSALA UNIV, CTR BIOMED, UPPSALA, SWEDEN SP Photochem Soc Europe, Swedish Acad Pharmaceut Sci, Astra Lakemedel AB, BioPhausia AB, Conpharm AB, Pharm Biotech AB, Swedish Council Forestry & Agr Res, Swedish Nat Sci Res Council, Swedish Res Council Engn Sci HO UPPSALA UNIV, CTR BIOMED ID IMMUNODEFICIENCY-VIRUS TYPE-1; MARINE SPONGE; DIFFERENTIAL CYTOTOXICITY; REVERSE-TRANSCRIPTASE; CALANOLIDE-A; PALYTOXIN; MACROLIDES; PEPTIDES C1 NCI, Frederick Canc Res & Dev Ctr, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick, MD 21702 USA. RP Cardellina, JH (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diag, POB B,Bldg 1052,Room 121, Frederick, MD 21702 USA. NR 25 TC 8 Z9 9 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-5480-X J9 PR PHYT SOC PY 1999 VL 43 BP 25 EP 35 PG 11 WC Biochemistry & Molecular Biology; Plant Sciences; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Plant Sciences; Pharmacology & Pharmacy GA BP62J UT WOS:000085709000003 ER PT J AU Bohr, VA Dianov, GL AF Bohr, VA Dianov, GL TI Oxidative DNA damage processing in nuclear and mitochondrial DNA SO BIOCHIMIE LA English DT Article DE oxidative DNA damage; DNA repair; mitochondria; base excision repair; Cockayne syndrome; aging ID BASE-EXCISION-REPAIR; HAMSTER OVARY CELLS; POLYMERASE-BETA; MAMMALIAN-CELLS; HUMAN HOMOLOG; DHFR GENE; GLYCOSYLASE; CLONING; RECONSTITUTION; 8-OXOGUANINE AB Living organisms are constantly exposed to oxidative stress from environmental agents and from endogenous metabolic processes. The resulting oxidative modifications occur in proteins, lipids and DNA. Since proteins and lipids are readily degraded and resynthesized, the most significant consequence of the oxidative stress is thought to be the DNA modifications, which can become permanent via the formation of mutations and other types of genomic instability. Many different DNA base changes have been seen following some form of oxidative stress, and these lesions are widely considered as instigators for the development of cancer and are also implicated in the process of aging. Several studies have documented that oxidative DNA lesions accumulate with aging, and it appears that the major site of this accumulation is mitochondrial DNA rather than nuclear DNA. The DNA repair mechanisms involved in the removal of oxidative DNA lesions are much more complex than previously considered. They involve base excision repair (BER) pathways and nucleotide excision repair (NER) pathways, and there is currently a great deal of interest in clarification of the pathways and their interactions. We have used a number of different approaches to explore the mechanism of the repair processes, to examine the repair of different types of oxidative lesions and to measure different steps of the repair processes. Furthermore, we can measure the DNA damage processing in the nuclear DNA and separately, in the mitochondrial DNA. Contrary to widely held notions, mitochondria have efficient DNA repair of oxidative DNA damage. (C) Societe francaise de biochimie et biologie moleculaire / Elsevier, Paris. C1 NIA, Genet Mol Lab, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Genet Mol Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 46 TC 92 Z9 96 U1 1 U2 3 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0300-9084 J9 BIOCHIMIE JI Biochimie PD JAN-FEB PY 1999 VL 81 IS 1-2 BP 155 EP 160 DI 10.1016/S0300-9084(99)80048-0 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 180XP UT WOS:000079411400017 PM 10214920 ER PT J AU Kobayashi, H Wu, CC Kim, MK Paik, CH Carrasquillo, JA Brechbiel, MW AF Kobayashi, H Wu, CC Kim, MK Paik, CH Carrasquillo, JA Brechbiel, MW TI Evaluation of the in vivo biodistribution of indium-111 and yttrium-88 labeled dendrimer-1B4M-DTPA and its conjugation with anti-Tac monoclonal antibody SO BIOCONJUGATE CHEMISTRY LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 07-11, 1998 CL TORONTO, CANADA SP Soc Nucl Med ID STARBURST(TM) DENDRIMERS; OVARIAN-CANCER; IN-VIVO; T-CELL; DTPA; RADIOIMMUNOTHERAPY; STABILITY; Y-90; RADIOIMMUNODETECTION; PHARMACOKINETICS AB We evaluated the in vivo biodistribution of indium- and yttrium-labeled second-generation polyamidoamine dendrimer (PAMAM) conjugated with 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetri-aminepentaacetic acid (1B4M), a derivative of DTPA. In addition, we conjugated PAMAM-1B4M to humanized anti-Tac IgG (HuTac) and evaluated its in vitro and in vivo properties. PAMAM-1B4M was labeled with In-111 at 37-48 MBq/mg (1.0-1.3 mCi/mg) or with Y-88 at 3.7 - 4.8 MBq/mg (0.1 - 0.13 mCi/mg), and an aliquot of radiolabeled conjugate was saturated with the corresponding stable yttrium or indium. Nontumor-bearing nude mice were injected intravenously with 55.5-66.6 kBq (1.5-1.8 mu Ci) of Y-88-labeled PAMAM-1B4M or with 185 kBq (5 mu Ci) of In-111-labeled PAMAM-1B4M. The mice were then sacrificed at 15 min, 90 min, 1 day, and 4 days postinjection. Then the PAMAM-1B4M was conjugated with HuTac and labeled with 111In at 111-259 MBq/mg (3-7 mCi/mg). Another preparation of 111In-labeled HuTac-PAMAM-1B4M was saturated with stable indium. Immunoreactivity of both preparations and biodistribution in normal mice 1 h after injection and in ATAC4 and A431 tumor-bearing mice 18 h after injection were evaluated and compared with those of In-111-labeled 1B4M-HuTac. We noted significantly higher accumulations (p < 0.05) of 111In-labeled and Y-88-labeled unsaturated PAMAM-1B4M than saturated preparations in the liver, kidney, spleen, and bone at most time points. The whole-body clearance times of unsaturated preparations were significantly slower than those of saturated preparations at all time points, with the exception of 168 h for; 111In-labeled PAMAM-1B4M. The saturated preparation of 111In-labeled HuTac-PAMAM-1B4M showed lower hepatic uptake (27 +/- 2%ID/g) than the unsaturated (32 +/- 2%ID/g), but greater than the HuTac1B4M control (10 +/- 0%ID/g). The splenic uptake showed 15 +/- 1, 38 +/- 5, and 8 +/- 1%ID/g for the saturated, unsaturated, and control, respectively. The biodistribution of the dendrimer conjugated HuTac in normal organs of tumor-bearing mice was similar to nontumor bearing mice. Specific tumor (ATAC4) uptake was higher than that in nonspecific tumor (A431). In conclusion, we evaluated the biodistribution of radiolabeled PAMAM 1B4M. We noted high accumulation in the liver, kidney, and spleen, which significantly decreased when the chelates were saturated with the stable element. A similar phenomenon was observed between unsaturated and saturated 111In-labeled HuTac-PAMAM-1B4M, indicating that the PAMAM dendrimer had a detrimental effect on biodistribiution. C1 NIH, Dept Nucl Med, Bethesda, MD 20892 USA. RP Carrasquillo, JA (reprint author), NIH, Dept Nucl Med, Bldg 10,Room 1C-401,10 Ctr Dr,MSC 1180, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 43 TC 93 Z9 94 U1 1 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JAN-FEB PY 1999 VL 10 IS 1 BP 103 EP 111 DI 10.1021/bc980091d PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 171QK UT WOS:000078874800015 PM 9893971 ER PT J AU Lambert, JS Moye, J AF Lambert, JS Moye, J TI Current issues in the immunoprophylaxis of vertical transmission of HIV SO BIODRUGS LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; MOTHER-TO-CHILD; MATERNAL VIRAL LOAD; INFANT TRANSMISSION; DOUBLE-BLIND; SYNERGISTIC NEUTRALIZATION; PERINATAL TRANSMISSION; CELLULAR CYTOTOXICITY; MONOCLONAL-ANTIBODIES; ZIDOVUDINE TREATMENT AB Humoral immunity is thought to play an important role in the natural history of HIV infection, It has been hypothesised that the presence of high titre neutralising antibody may protect against the maternal-fetal transmission of HIV-I infection, HIV-Ig is a passive antibody preparation consisting of highly purified immune globulin containing high titres of antibody to HIV structural proteins, It contains considerable functional antibody in virus neutralisation and antibody dependent cytotoxicity assays, This product (and others) have undergone extensive investigation in preclinical (in vitro and animal models) and clinical trials, In a randomised, double-blind trial, pregnant women with HIV infection who were receiving antiretroviral therapy received either HIV-Ig or control intravenous Ig, While transmission rate was 5 to 6% in both treatment and control arms (sample size was too small to show a difference), infected infants who received HIV-Ig had a delayed time to culture positivity versus those receiving intravenous Ig, suggesting that HIV-Ig may have the ability to modify disease but not prevent infection, While this study did not prove an effect of HIV-Ig it did prove an effect of antiretroviral therapy in a population of women with prior zidovudine experience, Passive antibody preparations (HIV-Ig and monoclonal antibodies) may have the potential to decrease perinatal transmission in combination with anti-retroviral agents, to levels less than 5%. Special niches where immunoglobulins and HIV vaccines may play a role, include treatment of infants born to women who do not receive prenatal care, or where the diagnosis of HIV in mother and infant is made only following delivery: a post-exposure prophylaxis strategy. C1 Univ Maryland, NICHD, NIH, Inst Human Virol,Ctr Res,Div Clin Res, Baltimore, MD 21201 USA. NICHHD, Ctr Res Mothers & Children, NIH, Bethesda, MD 20892 USA. NICHHD, Pediat Adolescent & Maternal AIDS, NIH, Bethesda, MD 20892 USA. RP Lambert, JS (reprint author), Univ Maryland, NICHD, NIH, Inst Human Virol,Ctr Res,Div Clin Res, 725 W Lombard St,S521, Baltimore, MD 21201 USA. EM lambert@umbi.umd.edu OI moye, john/0000-0001-9976-8586 NR 63 TC 1 Z9 2 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1173-8804 J9 BIODRUGS JI Biodrugs PD JAN PY 1999 VL 11 IS 1 BP 31 EP 41 DI 10.2165/00063030-199911010-00004 PG 11 WC Oncology; Immunology; Pharmacology & Pharmacy SC Oncology; Immunology; Pharmacology & Pharmacy GA 157QU UT WOS:000078073800004 PM 18031113 ER PT J AU DePamphilis, ML AF DePamphilis, ML TI Replication origins in metazoan chromosomes: fact or fiction? SO BIOESSAYS LA English DT Review ID EUKARYOTIC DNA-REPLICATION; XENOPUS EGG EXTRACTS; RIBOSOMAL-RNA GENES; RECOGNITION COMPLEX; YEAST ORIGIN; SACCHAROMYCES-CEREVISIAE; TETRAHYMENA-THERMOPHILA; INITIATION SITES; NUCLEAR MATRIX; FISSION YEAST AB The process by which eukaryotic cells decide when and where to initiate DNA replication has been illuminated in yeast, where specific DNA sequences (replication origins) bind a unique group of proteins (origin recognition complex) next to an easily unwound DNA sequence at which replication can begin. The origin recognition complex provides a platform on which additional proteins assemble to form a pre-replication complex that can be activated at S-phase by specific protein kinases. Remarkably, multicellular eukaryotes, such as frogs, flies, and mammals (metazoa), have counterparts to these yeast proteins that are required for DNA replication. Therefore, one might expect metazoan chromosomes to contain specific replication origins as well, a hypothesis that has long been controversial. In fact, recent results strongly support the view that DNA replication origins in metazoan chromosomes consist of one or more high frequency initiation sites and perhaps several low frequency ones that together can appear as a nonspecific initiation zone. Specific replication origins are established during G1-phase of each cell cycle by multiple parameters that include nuclear structure, chromatin structure, DNA sequence, and perhaps DNA modification. Such complexity endows metazoa with the flexibility to change both the number and locations of replication origins in response to the demands of animal development. (C) 1999 John Wiley & Sons, Inc. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP DePamphilis, ML (reprint author), NICHHD, NIH, Bldg 6,Room 416, Bethesda, MD 20892 USA. EM depamphm@box-d.nih.gov NR 97 TC 154 Z9 155 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0265-9247 J9 BIOESSAYS JI Bioessays PD JAN PY 1999 VL 21 IS 1 BP 5 EP 16 DI 10.1002/(SICI)1521-1878(199901)21:1<5::AID-BIES2>3.0.CO;2-6 PG 12 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 163LV UT WOS:000078407900002 PM 10070250 ER PT J AU Putney, JW McKay, RR AF Putney, JW McKay, RR TI Capacitative calcium entry channels SO BIOESSAYS LA English DT Review ID INTRACELLULAR CA2+ STORES; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; DROSOPHILA TRP; XENOPUS OOCYTES; ENDOPLASMIC-RETICULUM; VESICULAR TRANSPORT; ENDOTHELIAL-CELLS; BINDING PROTEIN; T-LYMPHOCYTES; HUMAN HOMOLOG AB In the phospholipase C signaling system, Ca(2+) is mobilized from intracellular stores by an action of inositol 1,4,5-trisphosphate. The depletion of intracellular calcium stores activates a calcium entry mechanism at the plasma membrane called capacitative calcium entry. The signal for activating the entry is unknown but likely involves either the generation or release, or both, from the endoplasmic reticulum of some diffusible signal. Recent research has focused on mammalian homologues of the Drosophila TRP protein as potential candidates for capacitative calcium entry channels.. This review summarizes current knowledge about the nature of capacitative calcium entry signals, as well as the potential role of mammalian TRP proteins as capacitative calcium entry channel molecules. Published 1999 John Wiley a Sons, Inc.dagger. C1 NIEHS, Calcium Regulat Sect, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Putney, JW (reprint author), NIEHS, Calcium Regulat Sect, Lab Signal Transduct, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 75 TC 329 Z9 334 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0265-9247 J9 BIOESSAYS JI Bioessays PD JAN PY 1999 VL 21 IS 1 BP 38 EP 46 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 163LV UT WOS:000078407900005 PM 10070252 ER PT J AU Salomon, DS Bianco, C De Santis, M AF Salomon, DS Bianco, C De Santis, M TI Cripto: a novel epidermal growth factor (EGF)-related peptide in mammary gland development and neoplasia SO BIOESSAYS LA English DT Review ID HUMAN BREAST CARCINOMAS; ERBB SIGNALING NETWORK; EPITHELIAL-CELLS; TRANSGENIC MICE; FACTOR-ALPHA; IN-VIVO; GENE-EXPRESSION; MESSENGER-RNA; FACTOR FAMILY; TGF-ALPHA AB Growth and morphogenesis in the mammary gland depend on locally derived growth factors such as those in the epidermal growth factor (EGF) superfamily. Cripto-1 (CR-1, human; Cr-1, mouse)-also known as teratocarcinoma-derived growth factor-1-is a novel EGF-related protein that induces branching morphogenesis in mammary epithelial cells both in vitro and in vivo and inhibits the expression of various milk proteins. In the mouse, Cr-1 is expressed in the growing terminal end buds in the virgin mouse mammary gland and expression increases during pregnancy and lactation. Cr-1/CR-1 is overexpressed in mouse and human mammary tumors and inappropriate overexpression of Cr-1 in mouse mammary epithelial cells can lead to the clonal expansion of ductal hyperplasias. Taken together, this evidence suggests that Cr-1/CR-1 performs a role in normal mammary gland development and that it might contribute to the early stages of mouse mammary tumorigenesis and the pathobiology of human breast cancer. Published 1999 John Wiley a Sons, Inc.dagger. C1 NCI, Tumor Growth Factor Sect, LTIB, NIH, Bethesda, MD 20892 USA. RP Salomon, DS (reprint author), NCI, Tumor Growth Factor Sect, LTIB, NIH, Bethesda, MD 20892 USA. NR 71 TC 61 Z9 64 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0265-9247 J9 BIOESSAYS JI Bioessays PD JAN PY 1999 VL 21 IS 1 BP 61 EP 70 DI 10.1002/(SICI)1521-1878(199901)21:1<61::AID-BIES8>3.0.CO;2-H PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 163LV UT WOS:000078407900008 PM 10070255 ER PT J AU Rhee, SG Kang, SW Netto, LE Seo, MS Stadtman, ER AF Rhee, SG Kang, SW Netto, LE Seo, MS Stadtman, ER TI A family of novel peroxidases, peroxiredoxins SO BIOFACTORS LA English DT Article ID THIOL-SPECIFIC ANTIOXIDANT; ALKYL HYDROPEROXIDE REDUCTASE; SACCHAROMYCES-CEREVISIAE; MAMMALIAN PEROXIREDOXIN; THIOREDOXIN PEROXIDASE; HYDROGEN-PEROXIDE; SEQUENCE; CLONING; GENE C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Rhee, SG (reprint author), NHLBI, Lab Cell Signaling, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Netto, Luis/A-3783-2008 OI Netto, Luis/0000-0002-4250-9177 NR 13 TC 131 Z9 140 U1 0 U2 2 PU IOS PRESS PI AMSTERDAM PA VAN DIEMENSTRAAT 94, 1013 CN AMSTERDAM, NETHERLANDS SN 0951-6433 J9 BIOFACTORS JI Biofactors PY 1999 VL 10 IS 2-3 BP 207 EP 209 PG 3 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 284LM UT WOS:000085333900019 PM 10609884 ER PT J AU Sherman, DR Mdluli, K Hickey, MJ Barry, CE Stover, CK AF Sherman, DR Mdluli, K Hickey, MJ Barry, CE Stover, CK TI AhpC, oxidative stress and drug resistance in Mycobacterium tuberculosis SO BIOFACTORS LA English DT Article ID ALKYL HYDROPEROXIDE REDUCTASE; CATALASE-PEROXIDASE GENE; ISONIAZID RESISTANCE; SALMONELLA-TYPHIMURIUM; ESCHERICHIA-COLI; KATG; SUSCEPTIBILITIES; IDENTIFICATION; THIOREDOXIN; ANTIOXIDANT AB The Mycobacterium tuberculosis AhpC is similar to a family of bacterial and eukaryotic antioxidant proteins with alkylhydroperoxidase (Ahp) and thioredoxin-dependent peroxidase (TPx) activities. AhpC expression is associated with resistance to the front-line antitubercular drug isoniazid in the naturally resistant organisms E. coli and M. smegmatis. We identified several isoniazid-resistant M. tuberculosis isolates with ahpC promoter mutations resulting in AhpC overexpression. These strains were more resistant to cumene hydroperoxide than were wild-type strains. However, these strains were unchanged in their sensitivity to isoniazid, refuting a role for AhpC in detoxification of this drug. All the isoniazid-resistant, AhpC-overexpressing strains were also deficient in activity of the mycobacterial catalase-peroxidase KatG. KatG, the only known catalase in M. tuberculosis, is required for activation of isoniazid. We propose that compensatory ahpC promoter mutations are selected from KatG-deficient, isoniazid-resistant M. tuberculosis during infections, to mitigate the added burden imposed by organic peroxides on these strains. C1 PathoGenesis Corp, Lab TB & Res Biol, Seattle, WA 98119 USA. NIAID, Rocky Mt Labs, TB Res Unit, Intracellular Parasites Lab, Hamilton, MT 59840 USA. RP Sherman, DR (reprint author), PathoGenesis Corp, Lab TB & Res Biol, 201 Elliott Ave W, Seattle, WA 98119 USA. RI Barry, III, Clifton/H-3839-2012; OI Stover, Charles/0000-0002-7406-1696 FU Intramural NIH HHS [Z01 AI000783-11] NR 29 TC 34 Z9 36 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA VAN DIEMENSTRAAT 94, 1013 CN AMSTERDAM, NETHERLANDS SN 0951-6433 J9 BIOFACTORS JI Biofactors PY 1999 VL 10 IS 2-3 BP 211 EP 217 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 284LM UT WOS:000085333900020 PM 10609885 ER PT J AU Lacourciere, GM AF Lacourciere, GM TI Biosynthesis of selenophosphate SO BIOFACTORS LA English DT Article ID SELD GENE-PRODUCT; ESCHERICHIA-COLI; SELENOCYSTEINE SYNTHASE; SYNTHETASE; MECHANISM; ENZYME; PURIFICATION; SEQUENCE; PROTEIN; SELENIDE AB Selenophosphate synthetase, the product of the selD gene, produces the highly active selenium donor, monoselenophosphate, from selenide and ATP. Positional isotope exchange experiments have shown hydrolysis of ATP occurs by way of a phosphoryl-enzyme intermediate. Although, mutagenesis studies have demonstrated Cys(17) in the Escherichia coli enzyme is essential for catalytic activity the nucleophile in catalysis has not been identified. Recently, selenophosphate synthetase enzymes have been identified from other organisms. The human enzyme which contains a threonine residue corresponding to Cys(17) in the E. coli enzyme, has been overexpressed in E. coli. The purified enzyme shows no detectable activity in the in vitro selenophosphate synthetase assay. In contrast, when the human enzyme is expressed to complement a selD mutation in E. coli, in the presence of Se-75, incorporation of Se-75 into bacterial selenoproteins is observed. The inactive purified human enzyme together with the very low determined specific activity of the E. coli enzyme (83 nmol/min/mg) suggest an essential component for the formation of selenophosphate has not been identified. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Lacourciere, GM (reprint author), NHLBI, Biochem Lab, NIH, Bldg 3,Room 103, Bethesda, MD 20892 USA. NR 29 TC 13 Z9 14 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0951-6433 EI 1872-8081 J9 BIOFACTORS JI Biofactors PY 1999 VL 10 IS 2-3 BP 237 EP 244 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 284LM UT WOS:000085333900023 PM 10609888 ER PT J AU Molloy, AM Mills, JL Kirke, PN Weir, DG Scott, JM AF Molloy, AM Mills, JL Kirke, PN Weir, DG Scott, JM TI Folate status and neural tube defects SO BIOFACTORS LA English DT Article DE folate status; methylenetetrahydrofolate reductase; neural tube defects; thermolabile MTHFR; red cell folates; pregnancy ID METHYLENETETRAHYDROFOLATE REDUCTASE MUTATION; RISK FACTOR; 5,10-METHYLENETETRAHYDROFOLATE REDUCTASE; PREGNANCIES; DISEASE; HOMOCYSTEINE; VITAMIN-B12; PREVENTION; PLASMA; SERUM AB Periconceptional folic acid supplementation prevents approximately 70% of neural tube defects (NTDs). While most women carrying affected fetuses do not have deficient blood folate levels, the risk of having an NTD affected child is inversely correlated with pregnancy red cell folate levels. Current research is focused on the discovery of genetic abnormalities in folate related enzymes which might explain the role of folate in NTD prevention. The first candidate gene to emerge was the C677T variant of 5,10-methylenetetrahydrofolate reductase. Normal subjects who are homozygous for the mutation (TT) have red cell folate status some 20% lower than expected. It is now established that the prevalence of the TT genotype is significantly higher among spina bifida cases and their parents. Nevertheless, our studies show that the variant does not account for the reduced blood folate levels in many NTD affected mothers. We conclude that low maternal folate status may in itself be the most important risk factor for NTDs and that food fortification may be the only population strategy of benefit in the effort to eliminate NTDs. C1 Trinity Coll, Dept Biochem, Dublin 2, Ireland. Trinity Coll, Dept Clin Med, Dublin 2, Ireland. Hlth Res Board, Dublin, Ireland. NICHD, Bethesda, MD USA. RP Scott, JM (reprint author), Trinity Coll, Dept Biochem, Dublin 2, Ireland. NR 18 TC 15 Z9 16 U1 0 U2 4 PU IOS PRESS PI AMSTERDAM PA VAN DIEMENSTRAAT 94, 1013 CN AMSTERDAM, NETHERLANDS SN 0951-6433 J9 BIOFACTORS JI Biofactors PY 1999 VL 10 IS 2-3 BP 291 EP 294 PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 284LM UT WOS:000085333900031 PM 10609896 ER PT J AU Kolenbrander, PE Andersen, RN Kazmerzak, K Wu, R Palmer, RJ AF Kolenbrander, PE Andersen, RN Kazmerzak, K Wu, R Palmer, RJ TI Spatial organization of oral bacteria in biofilms SO BIOFILMS SE METHODS IN ENZYMOLOGY LA English DT Review ID ENAMEL; COLONIZATION; ACTINOMYCES; SURFACES; ADHESION; INVIVO; PLAQUE C1 Natl Inst Dental & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Univ Tennessee, Ctr Environm Biotechnol, Biofilm Imaging Facil, Knoxville, TN 37932 USA. RP Kolenbrander, PE (reprint author), Natl Inst Dental & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. NR 9 TC 30 Z9 30 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1999 VL 310 BP 322 EP 332 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BP55T UT WOS:000085490500024 PM 10547802 ER PT J AU Kasprzak, W Shapiro, BA AF Kasprzak, W Shapiro, BA TI Stem Trace: An interactive visual tool for comparative RNA structure analysis SO BIOINFORMATICS LA English DT Article ID PARALLEL GENETIC ALGORITHM; GENOMIC RNA; STRUCTURE PREDICTION; DIMERIZATION; SEQUENCE; HIV-1; REGION; PARAMETERS; UPSTREAM; HAIRPIN AB Motivation: Stem Trace is one of the latest tools available in STRUCTURELAB, an RNA structure analysis computer workbench. The paradigm used in STRUCTURELAB views RNA structure determination as a problem of dealing with a database of a large number of computationally generated structures. Stem Trace provides the capability to analyse this data set in a novel, visually driven, interactive and exploratory way In addition to providing graphs at a high level of abstraction, it is also connected with complementary visualization tools which provide orthogonal views of the same data, as well as drawing of structures represented by a stem trace. Thus, on top of being an analysis tool, Stem Trace is a graphical user interface to an RNA structural information database. Results: We illustrate Stem Trace's capabilities with several examples of the analysis of RNA folding data performed rf on 24 strains of HIV-1, HIV-2 and SIV sequences around the HIV dimerization region. This dimer linkage site has been found to play a role in encapsidation, reverse transcription, recombination, and inhibition of translation. Our examples show how Stern Trace elucidates preservation of structures in this region across the various strains of HIV. Availability: The program can be made available upon request. It runs on SUN; SGI and DEC (Compaq) Unix workstations. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramur Res Supp Progr,NIH, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Image Proc Sect, Lab Expt & Computat Biol,Div Basic Sci,NIH, Frederick, MD 21702 USA. RP Kasprzak, W (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramur Res Supp Progr,NIH, Bldg 469,Rm 150C, Frederick, MD 21702 USA. NR 32 TC 21 Z9 22 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JAN PY 1999 VL 15 IS 1 BP 16 EP 31 DI 10.1093/bioinformatics/15.1.16 PG 16 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 175JP UT WOS:000079090200003 PM 10068689 ER PT J AU McClure, ME AF McClure, ME TI Third millennium science: Reproduction research in a brave new world. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 NIEHS, Organ & Syst Toxicol Branch, Div Extramural Res & Training, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 1999 VL 60 SU 1 MA K1 BP 71 EP 71 PG 1 WC Reproductive Biology SC Reproductive Biology GA 211CA UT WOS:000081141300008 ER PT J AU Eddy, M AF Eddy, M TI Spermatogenesis and HSP70 chaperones. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 1999 VL 60 SU 1 MA M6 BP 74 EP 74 PG 1 WC Reproductive Biology SC Reproductive Biology GA 211CA UT WOS:000081141300016 ER PT J AU Dean, J AF Dean, J TI Molecular biology of the zona pellucida: Genetic mutations and fertility. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 1999 VL 60 SU 1 MA M23 BP 80 EP 80 PG 1 WC Reproductive Biology SC Reproductive Biology GA 211CA UT WOS:000081141300033 ER PT J AU Couse, J AF Couse, J TI Reproductive phenotypes in estrogen receptor knockout mice: Contrasting roles for estrogen receptor-alpha and estrogen receptor-beta. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 NIEHS, Receptor Biol Sect, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 1999 VL 60 SU 1 MA M44 BP 88 EP 88 PG 1 WC Reproductive Biology SC Reproductive Biology GA 211CA UT WOS:000081141300057 ER PT J AU Watari, H Blanchette-Mackie, EJ Dwyer, NK Pentchev, PG Glick, JM Strauss, JF AF Watari, H Blanchette-Mackie, EJ Dwyer, NK Pentchev, PG Glick, JM Strauss, JF TI The distribution and function of NPC1 protein in cholesterol trafficking in human granulosa-lutein cells. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Univ Penn, Ctr Res Reprod & Women, Philadelphia, PA 19104 USA. Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 1999 VL 60 SU 1 MA 5 BP 95 EP 95 PG 1 WC Reproductive Biology SC Reproductive Biology GA 211CA UT WOS:000081141300074 ER PT J AU Suarez-Quian, CA Smith, R Noguchi, C AF Suarez-Quian, CA Smith, R Noguchi, C TI Quantitation of androgen receptor (AR) gene expression in male reproductive tissues using real-time, fluorescence-based quantitative pcr (Q-PCR). SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Georgetown Univ, Med Ctr, Dept Cell Biol, Washington, DC 20007 USA. NIDDK, LCB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 1999 VL 60 SU 1 MA 483 BP 243 EP 243 PG 1 WC Reproductive Biology SC Reproductive Biology GA 211CA UT WOS:000081141300544 ER PT J AU Elhassan, YM Lee, CP Tasca, RJ Westhusin, ME AF Elhassan, YM Lee, CP Tasca, RJ Westhusin, ME TI The effect of NaCl-associated osmolarity changes on bovine embryo development in a completely defined culture medium supplemented with amino acids at oviductal fluid levels. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Texas A&M Univ, Dept Vet Physiol & Pharmacol, College Stn, TX USA. NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 1999 VL 60 SU 1 MA 500 BP 248 EP 248 PG 1 WC Reproductive Biology SC Reproductive Biology GA 211CA UT WOS:000081141300560 ER PT J AU Hemminki, K Palmgren, J Korhonen, P Partanen, R Brandt-Rauf, P Rautalahti, M Albanes, D Virtamo, J AF Hemminki, K Palmgren, J Korhonen, P Partanen, R Brandt-Rauf, P Rautalahti, M Albanes, D Virtamo, J TI Serum epidermal growth factor receptor and p53 as predictors of lung cancer risk in the ATBC study SO BIOMARKERS LA English DT Article DE oncoproteins; p53; lung cancer; immunoassay; prevention; treatment ID MOLECULAR EPIDEMIOLOGY; EXTRACELLULAR DOMAIN; ASBESTOSIS PATIENTS; PROTEIN; ONCOPROTEINS; ANTIBODIES; CARCINOGENESIS; CARCINOMA; ANTIGEN AB Serum samples from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study were used in a nested case control study to identify the possible association between the serum level of epidermal growth factor receptor and p53 in respect to lung cancer. The proteins were assayed for by commercial immunoassays that showed uneven, often unacceptable, quality. For EGFR there was no relationship to lung cancer. Two physiological variables appeared to modify the serum level of EGFR, age by decreasing it annually by about 4 fmol ml(-1), and stroke by increasing it by 150 fmol ml(-1). For p53, myocardial infarction appeared to cause an increase in serum levels of this protein. While the serum levels of p53 were only moderately increased in lung cancer patients, particularly those with squamous cell carcinoma, the intriguing findings related to the high frequency of p53-positive patients among those belonging to the group of patients being treated by surgery and those belonging to clinical stages 1 and 2 as compared with higher clinical stages. An untested rationalization of these results was that patients with advanced lung cancer, stages 3 and higher, develop autoantibodies against the mutant p53 and thus mask the serum levels of the mutant p53 protein. C1 Karolinska Inst, Novum, Dept Biosci, S-14157 Huddinge, Sweden. Univ Stockholm, Dept Math Stat, S-10691 Stockholm, Sweden. Univ Helsinki, Rolf Nevanlinna Inst, FIN-00014 Helsinki, Finland. Columbia Univ, Div Environm Sci, New York, NY 10032 USA. Natl Publ Hlth Inst, SF-00300 Helsinki, Finland. NCI, Bethesda, MD 20892 USA. RP Hemminki, K (reprint author), Karolinska Inst, Novum, Dept Biosci, S-14157 Huddinge, Sweden. RI Albanes, Demetrius/B-9749-2015; OI Palmgren, Juni/0000-0002-9031-8615 NR 27 TC 2 Z9 2 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-750X J9 BIOMARKERS JI Biomarkers PD JAN-FEB PY 1999 VL 4 IS 1 BP 72 EP 84 DI 10.1080/135475099231010 PG 13 WC Biotechnology & Applied Microbiology; Toxicology SC Biotechnology & Applied Microbiology; Toxicology GA 158JF UT WOS:000078111700006 PM 23898796 ER PT S AU Colarusso, P Whitley, A Levin, IW Lewis, EN AF Colarusso, P Whitley, A Levin, IW Lewis, EN BE Morris, MD TI Raman microscopy and imaging of inorganic and biological materials with liquid crystal tunable filters SO BIOMEDICAL APPLICATIONS OF RAMAN SPECTROSCOPY, PROCEEDINGS OF SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Biomedical Applications of Raman Spectroscopy CY JAN 25-26, 1999 CL SAN JOSE, CA SP SPIE, Int Biomed Opt Soc, Renishaw Inc, Instruments SA Inc, Chemicon Inc, Kaiser Opt Syst Inc DE spectroscopic imaging; chemical imaging; Raman microscopy; Raman imaging; liquid crystal tunable filters; LCTF AB The utility of Raman microscopy and imaging for the characterization of a variety of chemical and biological systems is discussed. Measurements have been carried out with an optical microscope coupled to a Raman spectrometer that contains light paths for both single point and imaging measurements. Laser irradiation and signal collection are implemented using epi-illumination through a single microscope objective. For point Raman microspectroscopy, the laser is focused to a small spot (1-3 mu m), and the Raman signal is dispersed by the spectrometer onto a CCD. It is also possible to fully integrate the imaging capability of the microscope with Raman spectroscopy. In our arrangement, the laser is defocused to provide wide-field illumination (x50 objective, maximum 40 mu m diameter). The Raman signal from within the irradiated sample area is directed through a narrow-band liquid crystal tunable filter (LCTF) and imaged onto the CCD. Spectroscopic information is obtained by recording Raman images through the LCTF (passband about 8-10 cm(-1)) over successively tuned frequencies. Raman spectra for various points within the sample thus are obtained in parallel by each pixel in the detector array. Microspectra were recorded within various samples, including bacteria. Spectroscopic features of interest were then investigated in greater spatial detail using the LCTF imaging methodology. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Lewis, EN (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3078-1 J9 P SOC PHOTO-OPT INS PY 1999 VL 3608 BP 139 EP 145 DI 10.1117/12.345395 PG 7 WC Engineering, Biomedical; Medical Laboratory Technology; Optics; Spectroscopy SC Engineering; Medical Laboratory Technology; Optics; Spectroscopy GA BN06B UT WOS:000080521500019 ER PT J AU Ramirez-Alvarado, M Kortemme, T Blanco, FJ Serrano, L AF Ramirez-Alvarado, M Kortemme, T Blanco, FJ Serrano, L TI beta-hairpin and beta-sheet formation in designed linear peptides SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE beta-hairpin; beta-sheet; peptides; protein folding; NMR ID SECONDARY STRUCTURE FORMATION; SIDE-CHAIN INTERACTIONS; NUCLEAR-MAGNETIC-RESONANCE; FREE-ENERGY DETERMINANTS; HELIX-COIL TRANSITION; DE-NOVO DESIGN; AMINO-ACIDS; AQUEOUS-SOLUTION; CHEMICAL-SHIFTS; CIRCULAR-DICHROISM AB Recent knowledge about the determinants of beta-sheet formation and stability has notably been improved by the structural analysis of model peptides with beta-hairpin structure in aqueous solution. Several experimental studies have shown that the turn region residues can not only determine the stability, but also the conformation of the beta-hairpin. Specific interstrand side-chain interactions, hydrophobic and polar, have been found to be important stabilizing interactions. The knowledge acquired in the recent years from peptide systems, together with the information gathered from mutants in proteins, and the analysis of known protein structures, has led to successful design of a folded three-stranded monomeric beta-sheet structure. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 European Mol Biol Lab, D-69117 Heidelberg, Germany. NIDDKD, NIH, Chem Phys Lab, Bethesda, MD 20892 USA. RP Serrano, L (reprint author), European Mol Biol Lab, Meyerhofstr 1, D-69117 Heidelberg, Germany. RI Blanco, Francisco/D-4401-2009; Serrano, Luis/B-3355-2013 OI Blanco, Francisco/0000-0003-2545-4319; Serrano, Luis/0000-0002-5276-1392 NR 85 TC 106 Z9 106 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JAN PY 1999 VL 7 IS 1 BP 93 EP 103 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 173QE UT WOS:000078990600011 PM 10199660 ER PT J AU Minton, AP AF Minton, AP TI Adsorption of globular proteins on locally planar surfaces. II. Models for the effect of multiple adsorbate conformations on adsorption equilibria and kinetics SO BIOPHYSICAL JOURNAL LA English DT Article ID AGGREGATION; FIBRINOGEN; SIMULATION; FERRITIN; BINDING AB Equilibrium and kinetic models for nonspecific adsorption of proteins to planar surfaces are presented. These models allow for the possibility of multiple interconvertible surface conformations of adsorbed protein. Steric repulsion resulting in area exclusion by adsorbed molecules is taken into account by treating the adsorbate as a thermodynamically nonideal two-dimensional fluid. In the equilibrium model, the possibility of attractive interactions between adsorbed molecules is taken into account in a limited fashion by permitting one of the adsorbed species to self-associate. Calculated equilibrium adsorption isotherms exhibit apparent high-affinity and low-affinity binding regions, corresponding respectively to adsorption of ligand at low fractional area occupancy in an energetically favorable side-on conformation and conversion at higher fractional area occupancy of the side-on conformation to an entropically favored end-on conformation. Adsorbate self-association may lead to considerable steepening of the adsorption isotherm, compensating to a variable extent for the broadening effect of steric repulsion. Kinetic calculations suggest that in the absence of attractive interactions between adsorbate molecules, the process of adsorption may be highly "stretched" along the time axis, rendering the attainment of adsorption equilibrium in the context of conventional experiments problematic. C1 NIDDKD, Sect Phys Biochem, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Minton, AP (reprint author), NIDDKD, Sect Phys Biochem, Lab Biochem & Genet, NIH, Bldg 8,Room 226, Bethesda, MD 20892 USA. EM minton@helix.nih.gov NR 29 TC 73 Z9 74 U1 0 U2 6 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 1999 VL 76 IS 1 BP 176 EP 187 PN 1 PG 12 WC Biophysics SC Biophysics GA 154CJ UT WOS:000077870700015 PM 9876132 ER PT J AU Adhikari, BB Wang, K AF Adhikari, BB Wang, K TI Reduction of skeletal muscle tension and stiffness by calmodulin implicates nebulin in the modulation of actin-myosin interaction. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAMS, LPB, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 1999 VL 76 IS 1 BP A165 EP A165 PN 2 PG 1 WC Biophysics SC Biophysics GA 210BU UT WOS:000081085900966 ER PT J AU Aguilella, VM Rostovtseva, TK Vodyanoy, I Bezrukov, SM Parsegian, VA AF Aguilella, VM Rostovtseva, TK Vodyanoy, I Bezrukov, SM Parsegian, VA TI Streaming potential in mitochondrial porin, VDAC. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, LPSB, NIH, Bethesda, MD 20982 USA. Univ Jaume 1, Dept Exp Sci, Castellon 12080, Spain. RI Aguilella, Vicente/B-7592-2008 OI Aguilella, Vicente/0000-0002-2420-2649 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 1999 VL 76 IS 1 BP A208 EP A208 PN 2 PG 1 WC Biophysics SC Biophysics GA 210BU UT WOS:000081085901215 ER PT J AU Bahar, I Jernigan, RL AF Bahar, I Jernigan, RL TI Subunit communication, processing and fluctuations in tryptophan synthase SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI, Lab Exp & Comp Biol, NIH, Bethesda, MD 20892 USA. Bogazici Univ, Dept Chem Engn, TR-80815 Bebek, Turkey. Bogazici Univ, Ctr Polymer Res, TR-80815 Bebek, Turkey. TUBITAK, Adv Polym Mat Res Ctr, Istanbul, Turkey. RI Jernigan, Robert/A-5421-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 1999 VL 76 IS 1 BP A115 EP A115 PN 2 PG 1 WC Biophysics SC Biophysics GA 210BU UT WOS:000081085900672 ER PT J AU Basanez, G Nechushtan, A Drozhinin, O Chanturiya, A Choe, E Tutt, S Wood, KA Hsu, YT Youle, RJ Zimmerberg, J AF Basanez, G Nechushtan, A Drozhinin, O Chanturiya, A Choe, E Tutt, S Wood, KA Hsu, YT Youle, RJ Zimmerberg, J TI Full-length Bax ruptures planar phospholipid membranes at subnanomolar concentrations SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 LCMB, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 1999 VL 76 IS 1 BP A18 EP A18 PN 2 PG 1 WC Biophysics SC Biophysics GA 210BU UT WOS:000081085900102 ER EF