FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Hsing, AW McLaughlin, JK Cocco, P Chien, HTC Fraumeni, JF AF Hsing, AW McLaughlin, JK Cocco, P Chien, HTC Fraumeni, JF TI Risk factors for male breast cancer (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE alcohol; diet; male breast cancer; obesity; tobacco; United States ID ELECTROMAGNETIC-FIELD EXPOSURE; DEAD CONTROLS; MEN; EPIDEMIOLOGY; ESTRADIOL; OBESITY AB Objectives: The etiology of male breast cancer is obscure, although an excess risk has been associated with Klinefelter syndrome, testicular disorders, benign breast disease including gynecomastia, use of exogenous estrogens, radiation, and a family history of male or female breast cancer. We conducted a case-control study to investigate risk factors further for breast cancer in men. Methods: Based on data from the 1986 National (United States) Mortality Followback Survey (NMFS) of almost 20,000 deceased adults (age 25 years or over), we compared information obtained from next-of-kin interviews of 178 men who died of breast cancer with that of 512 male controls who died of other causes. Information was obtained on selected demographic and other factors, including diet, exercise, occupation, height and weight, and use of tobacco and alcohol. Results: Increased risks were found for men who were described by their next-of-kin as very overweight (odds ratio [OR] = 2.3, 95 percent confidence interval [CI] = 1.1-5.0). The risks associated with the three upper quartiles of body mass index (BMI) (wt/ht(2)) mere 1.3, 1.6, and 2.3, respectively, with a significant dose-response relationship (P < 0.01). An excess risk was also associated with limited exercise (OR = 1.3, CI = 0.8-2.0). Consumption of red meat was associated with an increased risk, and consumption of fruits and vegetables with a decreased risk, although the trends were not significant. No association was found for tobacco or alcohol use, but an excess risk was associated with higher levels of socioeconomic status (SES) (OR = 1.8, CI = 1.1-3.0). Conclusions: Our study suggests that obesity increases the risk of male breast cancer, possibly through hormonal mechanisms, while dietary factors, physical activity, and SES indicators also deserve further investigation. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Int Epidemiol Inst, Rockville, MD USA. Westat Inc, Rockville, MD USA. RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, 6130 Execut Blvd,Room 443, Bethesda, MD 20892 USA. NR 43 TC 85 Z9 87 U1 1 U2 5 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 1998 VL 9 IS 3 BP 269 EP 275 DI 10.1023/A:1008869003012 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 110GG UT WOS:000075371400005 PM 9684707 ER PT J AU Smith, MA Simon, R Strickler, HD McQuillan, G Ries, LAG Linet, MS AF Smith, MA Simon, R Strickler, HD McQuillan, G Ries, LAG Linet, MS TI Evidence that childhood acute lymphoblastic leukemia is associated with an infectious agent linked to hygiene conditions SO CANCER CAUSES & CONTROL LA English DT Review DE acute lymphoblastic leukemia; hepatitis A virus; hygiene; Japan; socioeconomic status; United States ID CROSS-SECTIONAL SURVEYS; HEPATITIS-A ANTIGEN; SOCIAL-CLASS; CYTOMEGALOVIRUS-INFECTION; DESCRIPTIVE EPIDEMIOLOGY; BIRTH CHARACTERISTICS; STATISTICAL-ANALYSIS; VIRUS-INFECTIONS; PREVALENCE; ANTIBODY AB Objectives: The incidence of acute lymphoblastic leukemia (ALL) in children has shown temporal and geographic variation during the 20th century, with higher rates in developed nations appearing in the first half of the century, but with persisting low rates in developing nations. We sought to assess the relation of childhood ALL with hygiene conditions, an aspect of socioeconomic development affecting rates of exposure to infectious agents. Methods: Infection patterns for hepatitis A virus (HAV), an agent with a fecal-oral route of transmission, were used to indicate hygiene conditions in different populations, with emphasis on instructive United States and Japanese data. A catalytic model was fit to these data, estimating the HAV force of infection and age-specific seroprevalence rates over time. These analyses were used to assess the temporal relationship of changes in HAV infection rates to changes in childhood leukemia mortality and incidence rates. Results: We observed an inverse relationship between HAV infection prevalence and rates of childhood leukemia. Further, decreases in the HAV force of infection in the United States and Japan appear to have preceded increases in childhood leukemia rates. We describe a model based on a putative leukemia-inducing agent with a change in infection rate over time correlated with that of HAV that describes well the temporal trends in childhood leukemia rates for White children in the US and for Japanese children. Conclusion: The data suggest that improved public hygiene conditions, as measured by decreased prevalence of HAV infection, are associated with higher childhood ALL incidence rates. The model that we present supports the plausibility of the hypothesis that decreased childhood exposure to a leukemia-inducing agent associated with hygiene conditions leads to higher rates of ALL in children by increasing the frequency of in utero transmission caused by primary infection during pregnancy (or by increasing the number of individuals infected in early infancy because of lack of protective maternal antibodies). C1 NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Atlanta, GA 30333 USA. RP Smith, MA (reprint author), NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Rm 741,EPN, Bethesda, MD 20892 USA. NR 115 TC 39 Z9 40 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 1998 VL 9 IS 3 BP 285 EP 298 DI 10.1023/A:1008873103921 PG 14 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 110GG UT WOS:000075371400007 PM 9684709 ER PT J AU Cerhan, JR Cantor, KP Williamson, K Lynch, CF Torner, JC Burmeister, LF AF Cerhan, JR Cantor, KP Williamson, K Lynch, CF Torner, JC Burmeister, LF TI Cancer mortality among Iowa farmers: Recent results, time trends, and lifestyle factors (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE cancer mortality; farming; lifestyle; men; United States ID PANCREATIC-CANCER; PROSTATE-CANCER; RISK; LYMPHOMA; WORKERS AB Objectives: To update the cancer mortality patterns among Iowa (United States) farmers for the years 1987-93 and compare these results with those previously reported for 1971-86 as well as relate the PMR patterns to risk-factor survey data. Methods: We extracted usual occupation and cause of death from 88,090 Iowa death certificates for White males aged 20 and older for the years 1987-93. Proportional mortality ratios (PMR), adjusted for age, and 95 percent confidence intervals (CI) were calculated using deaths among nonfarmers to generate expected numbers. We compared lifestyle profiles for farmers and nonfarmers using male controls (n = 1,596) from a population-based case-control study conducted in Iowa from 1986-89. Results: Iowa farmers had deficit PMRs for all-cause cancer mortality (PMR = 0.92, CI = 0.90-0.94) and for lung (PMR = 0.70, CI = 0.66-0.73), liver (PMR = 0.65, CI = 0.50-0.86), and other cancer sites strongly related to smoking and alcohol use. Farmers at all ages had excess deaths for cancers of the prostate (PMR = 1.26, CI = 1.19-1.33), rectum (PMR = 1.29, CI = 1.07-1.56), brain (PMR = 1.10, CI = 0.92-1.32), multiple myeloma (PMR = 1.17, CI = 0.98-1.40), non-Hodgkin's lymphoma (PMR = 1.09, CI = 0.96-1.23), and Hodgkin's disease (PMR = 1.62, CI = 1.04-2.54). Younger farmers (aged 20 to 64 years) had excess deaths for colon cancer (PMR = 1.52, CI = 1.26-1.85) and skin melanoma (PMR = :1.60, CI = 1.07-2.38), while older farmers (aged 65+ years) had excess deaths for cancers of the pancreas (PMR = 1.18, CI = 1.04-1.34), lip (PMR = 1.58, CI = 0.59-4.21), and leukemia (PMR = 1.26, CI = 1.09-1.46). Since the 1970s, the PMR for stomach cancer has declined to expected values, while the PMRs for prostate, large intestine, pancreas, and Hodgkin's disease have increased; PMRs for other sites are consistent with earlier data. A, survey from 1986-89 showed that farmers, compared with nonfarmers, smoked less, used less alcohol, had less formal education, and consumed more total calories, and calories from protein, fat, and meat while consuming fewer calories from fruits and vegetables. Conclusions: Iowa farmers continue to be at elevated risk of mortality due to certain cancers, and, of particular interest, the risk for prostate and colon cancer appears to be increasing since 1970. C1 Univ Iowa, Coll Med, Dept Prevent Med & Environm Hlth, Iowa City, IA 52242 USA. Univ Iowa, Coll Med, Dept Prevent Med & Environm Hlth, Iowa City, IA 52242 USA. NCI, Environm Epidemiol Branch, Bethesda, MD 20892 USA. RP Cerhan, JR (reprint author), Univ Iowa, Coll Med, Dept Prevent Med & Environm Hlth, 2800 Steindler Bldg, Iowa City, IA 52242 USA. FU NCI NIH HHS [N01-CP-85614, N01-CP-51206, R21 CA/ES69838] NR 42 TC 73 Z9 74 U1 1 U2 10 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 1998 VL 9 IS 3 BP 311 EP 319 DI 10.1023/A:1008877204830 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 110GG UT WOS:000075371400009 PM 9684711 ER PT J AU Weiss, HA Troisi, R Rossing, MA Brogan, D Coates, RJ Gammon, MD Potischman, N Swanson, CA Brinton, LA AF Weiss, HA Troisi, R Rossing, MA Brogan, D Coates, RJ Gammon, MD Potischman, N Swanson, CA Brinton, LA TI Fertility problems and breast cancer risk in young women: a case-control study in the United States SO CANCER CAUSES & CONTROL LA English DT Article DE breast cancer; infertility; pregnancy; United States ID INFERTILE WOMEN; HISTORY; COHORT AB Objectives: Late age at first birth and nulliparity are established risk factors for breast cancer, yet the extent to which fertility problems contribute to these associations remains largely unexplored, Here, we examine self-reported fertility problems as a risk factor for breast cancer in young women. Methods: We used a population-based case-control study of 2,173 cases and 1,990 controls aged 20 to 54 years in the United States, Structured in-person interviews were used to elicit detailed information on established and potential breast cancer risk factors. Information was collected on pregnancy details, including difficulties becoming pregnant or maintaining a pregnancy. Results: Self-reported difficulty in becoming pregnant or maintaining a pregnancy was reported by 450 cases and 377 controls. Overall, there was little association between these fertility problems and risk of breast cancer (odds ratio [OR]=1.05), Parity was associated with a decreased risk of breast cancer in women both with (OR = 0.71) and without (OR = 0.79) fertility problems. There was little evidence of an increased risk of breast cancer with later age at first full-term birth among women without fertility problems (ORage (35+:age <20) = 1.13, 95 percent confidence interval [CI] = 0.7-1.9), but a relatively strong association among women with fertility problems (ORage (35+ :age <20) = 2.96, CI = 1.3-7.0). Among women with a first fullterm birth at age 35 or older, fertility problems were associated with a twofold risk of breast cancer. Analyses of duration of unprotected sexual intercourse prior to first pregnancy as an alternative estimate of infertility produced similar results. Conclusions: Our study suggests that the association between late age at first birth and breast cancer is stronger among women with self-reported fertility problems than among women with no fertility problems. C1 NCI, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Emory Univ, Rollins Sch Publ Hlth, Dept Biostat, Atlanta, GA 30322 USA. Columbia Univ, Sch Publ Hlth, Div Epidemiol, New York, NY USA. RP Weiss, HA (reprint author), NCI, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Execut Plaza N,Rm 443,6130 Exec Blvd, Bethesda, MD 20892 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 19 TC 14 Z9 14 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 1998 VL 9 IS 3 BP 331 EP 339 DI 10.1023/A:1008881305738 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 110GG UT WOS:000075371400011 PM 9684713 ER PT J AU Blaney, SM Takimoto, C Murry, DJ Kuttesch, N McCully, C Cole, DE Godwin, K Balis, FM AF Blaney, SM Takimoto, C Murry, DJ Kuttesch, N McCully, C Cole, DE Godwin, K Balis, FM TI Plasma and cerebrospinal fluid pharmacokinetics of 9-aminocamptothecin (9-AC), irinotecan (CPT-11), and SN-38 in nonhuman primates SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE irinotecan; 9-aminocamptothecin; CSF penetration; topotecan ID CONTINUOUS-INFUSION; DRUGS; METABOLITE; TOPOTECAN; MODEL AB Purpose: The plasma and cerebrospinal fluid (CSF) pharmacokinetics of the camptothecin analogs, 9-aminocamptothecin (9-AC) and irinotecan, were studied in a nonhuman primate model to determine their CSF penetration. Methods: 9-AC, 0.2 mg/kg (4 mg/m(2)) or 0.5 mg/kg (10 mg/m(2)), was infused intravenously over 15 min and irinotecan, 4.8 mg/kg (96 mg/m(2)) or 11.6 mg/kg (225 mg/m(2)), was infused over 30 min. Plasma and CSF samples were obtained at frequent intervals over 24 h. Lactone and total drug forms of 9-AC, irinotecan, and the active metabolite of irinotecan, SN-38, were quantified by reverse-phase HPLC. Results: 9-AC lactone had a clearance (CL) of 2.1 +/- 0.9 l/kg per h, a volume of distribution at steady state (Vd(ss)) of 1.6 +/- 0.7 l/kg and a half-life (t(1/2)) Of 3.2 +/- 0.8 h. The lactone form of 9-AC accounted for 26 +/- 7% of the total drug in plasma. The CSF penetration of 9-AC lactone was limited. CSF 9-AC lactone concentration peaked 30 to 45 min after the dose at 11 to 21 nM (0.5 mg/kg dose), and the ratio of the areas under the CSF and plasma concentration-time curves (AUC(CSF): AUC(P)) was only 3.5 +/- 2.1%. For irinotecan, the CL was 3.4 +/- 0.4 l/kg per h, the Vd(ss) was 7.1 +/- 1.3 l/kg, and the t(1/2) was 4.9 +/- 2.2 h. Plasma AUCs of the lactone form of SN-38 were only 2.0% to 2.4% of the AUCs of irinotecan lactone. The lactone form of irinotecan accounted for 26 +/- 5% of the total drug in plasma, and the lactone form of SN-38 accounted for 55 +/- 6% of the total SN-38 in plasma. The AUC(CSF): AUC(P) ratio for irinotecan lactone was 14 +/- 3%. SN-38 lactone and carboxylate could not be measured (<1.0 nM) in CSF. The AUC(CSF): AUC(P) ratio for SN-38 lactone was estimated to be less than or equal to 8%. Conclusion: Despite their structural similarity, the CSF penetration of 9-AC and SN-38 is substantially less than that of topotecan which we previously found to have an AUC(CSF): AUC(P) ratio of 32%. C1 Texas Childrens Canc Ctr, Houston, TX 77030 USA. NCI, Med Branch, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Blaney, SM (reprint author), Texas Childrens Canc Ctr, 6621 Fannin St,MC 3-3320, Houston, TX 77030 USA. NR 22 TC 46 Z9 46 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAY PY 1998 VL 41 IS 6 BP 464 EP 468 DI 10.1007/s002800050768 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA ZJ025 UT WOS:000073172000006 PM 9554590 ER PT J AU Egan, KM Stampfer, MJ Rosner, BA Trichopoulos, D Newcomb, PA Trentham-Dietz, A Longnecker, MP Mittendorf, R Greenberg, ER Willett, WC AF Egan, KM Stampfer, MJ Rosner, BA Trichopoulos, D Newcomb, PA Trentham-Dietz, A Longnecker, MP Mittendorf, R Greenberg, ER Willett, WC TI Risk factors for breast cancer in women with a breast cancer family history SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ALCOHOL-CONSUMPTION; UNITED-STATES; POSTMENOPAUSAL WOMEN; REPRODUCTIVE FACTORS; AGE; DISEASE; HEALTH; ONSET AB Family history (FH) is an important indicator of a woman's future risk of developing breast cancer, Using data collected in a large population-based case-control study (6705 cases and 9341 controls), we examined the associations of breast cancer with known risk factors in women reporting a first-degree FH (mother or sister), with an emphasis on lifestyle determinants that may be altered to reduce risk. First-degree FH was reported by 18.4% (n = 1234) of cases and 11.3% (n = 1058) of controls; the overall relative risk (RR) for breast cancer associated with a positive history was 1.70 [95% confidence interval (CI), 1.55-1.87] and 2.34 (95% CI, 1.80-3.02) for breast cancer at age 45 years or younger, Among women with a FH, statistically significant inverse associations were observed for increasing parity (RR per birth = 0.90; P < 0.0001), intake of carotene-rich foods (RR for >2000 IU/day = 0.73; P = 0.02), and strenuous activity as a young adult (RR per episode/week = 0.93; P = 0.02), Recent alcohol consumption increased risk (RR per 13 g/week = 1.21; P = 0.02), as did weight gain during adult life in postmenopausal women (RR per 5 kg = 1.08; P = 0.001), Breast-feeding for any duration was associated with a lower RR in parous, premenopausal women (RR = 0.59; P = 0.04), Associations for most risk factors with breast cancer were similar among women with and without a FH of breast cancer; however, a stronger inverse association was observed for parity in women with a positive history (P for interaction = 0.04), Based on these data, women with a FH may reduce their excess risk of breast cancer through adjustments in lifestyle and reproductive choices. The risk associated with FH of breast cancer seems to be largely independent of other known risk factors. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI 53706 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Univ Chicago, Pritzker Sch Med, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Dartmouth Coll, Hitchcock Med Ctr, Norris Cotton Canc Ctr, Hanover, NH 03756 USA. RP Egan, KM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. OI Longnecker, Matthew/0000-0001-6073-5322 NR 41 TC 43 Z9 43 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 1998 VL 7 IS 5 BP 359 EP 364 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZM687 UT WOS:000073565800001 PM 9610783 ER PT J AU Millikan, RC Pittman, GS Newman, B Tse, CKJ Selmin, O Rockhill, B Savitz, D Moorman, PG Bell, DA AF Millikan, RC Pittman, GS Newman, B Tse, CKJ Selmin, O Rockhill, B Savitz, D Moorman, PG Bell, DA TI Cigarette smoking, N-acetyltransferases 1 and 2, and breast cancer risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ENVIRONMENTAL TOBACCO-SMOKE; PASSIVE SMOKING; METABOLIC-ACTIVATION; NONSMOKING WOMEN; NAT1; EXPOSURE; POLYMORPHISM; EPIDEMIOLOGY; CARCINOGENS; BLADDER AB To examine the effects of smoking and N-acetylation genetics on breast cancer risk, we analyzed data from an ongoing, population-based, case-control study of invasive breast cancer in North Carolina. The study population consisted of 498 cases and 473 controls, with approximately equal numbers of African-American and white women, and women under the age of 50 and age 50 years or older. Among premenopausal women, there was no association between current smoking [odds ratio (OR), 0.9; 95% confidence interval (CI), 0.5-1.5] or past smoking (OR, 1.0; 95% CI, 0.6-1.6) and breast cancer risk. Among postmenopausal women, there was also no association,vith current smoking (OR, 1.2; 95% CI, 0.7-2.0); however, a small increase in risk was observed for past smoking (OR, 1.5; 95% CI, 1.0-2.4). For postmenopausal women who smoked in the past, ORs and 95% CIs were 3.4 (1.4-8.1) for smoking within the past 3 years, 3.0 (1.3-6.7) for smoking 4-9 years ago, and 0.6 (0.3-1.4) for smoking 10-19 years ago. Neither N-acetyltransferase 1 (NAT1) nor N-acetyltransferase 2 (NAT2) genotype alone was associated with increased breast cancer risk. There was little evidence for modification of smoking effects according to genotype, except among postmenopausal women. Among postmenopausal women, ORs for smoking within the past 3 years were greater for women with the NAT1*10 genotype (OR, 9.0; 95% CI, 1.9-41.8) than NAT1-non*10 (OR, 2.5; 95% CI, 0.9-7.2) and greater for NAT2-rapid genotype (OR, 7.4; 95% CI, 1.6-32.6) than NAT2-slow (OR, 2.8; 95% CI, 0.4-8.0). Future studies of NAT genotypes and breast cancer should investigate the effects of environmental tobacco smoke, diet, and other exposures. C1 Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Yale Univ, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. RP Millikan, RC (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, CB 7400, Chapel Hill, NC 27599 USA. FU NCI NIH HHS [P50-CA58223, R21-CA66201]; NIEHS NIH HHS [R01-ES07128] NR 45 TC 156 Z9 156 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 1998 VL 7 IS 5 BP 371 EP 378 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZM687 UT WOS:000073565800003 PM 9610785 ER PT J AU Khan, MA Travis, LB Lynch, CF Soini, Y Hruszkewycz, AM Delgado, RM Holowaty, EJ van Leeuwen, FE Glimelius, B Stovall, M Boice, JD Tarone, RE Bennett, WP AF Khan, MA Travis, LB Lynch, CF Soini, Y Hruszkewycz, AM Delgado, RM Holowaty, EJ van Leeuwen, FE Glimelius, B Stovall, M Boice, JD Tarone, RE Bennett, WP TI p53 mutations in cyclophosphamide-associated bladder cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NON-HODGKINS-LYMPHOMA; DNA-DAMAGE; URINARY-BLADDER; CHEMICAL CARCINOGENESIS; NITROGEN-MUSTARD; ACROLEIN; CELLS; GENE; ADDUCTS; CROTONALDEHYDE AB Cyclophosphamide is a known bladder carcinogen, with cumulative dose directly related to increased risk. There is no consensus, however, on which major cyclophosphamide metabolite (i.e., acrolein or phosphoramide mustard) drives bladder carcinogenesis. We examined 19 cyclophosphamide-related bladder tumors to test the hypothesis that they might contain somatic mutations in the p53 tumor suppressor gene that could link a specific metabolite to the etiology of these cancers. Forty-three % (9 of 19) of the cases had a mutation in p53, with a predominance at G:C bp (7 of 9, 77%), a preference for non-CpG sites (6 of 7, 86%), and frequent G:C-->A:T transitions (5 of 7, 71%). The p53 mutation spectrum of these cyclophosphamide-associated bladder cancers differed significantly from patterns reported for sporadic (P = 0.020), smoking-related (0.043), and schistosomiasis-linked (P = 0.002) tumors but not arylamine-associated neoplasms (P = 0.860). Differences between the cyclophosphamide and arylamine-associated spectra included an unusual degree of clustering of exon 6 mutations (43% versus 17%, respectively) and an absence of multiple mutations in the former. Notably lacking in our series were G:C-->T:A transversions, the principal mutation associated with acrolein, Instead, the mutation spectrum matches the phosphoramide mustard adduction sequences determined by a repetitive primer-extension assay (P = 0.024), indicating that this metabolite might be a key mutagen in cyclophosphamide-related bladder cancer. C1 City Hope Natl Med Ctr, Div Human Genet, Duarte, CA 91010 USA. NCI, Lab Human Carcinogenesis, Bethesda, MD 20892 USA. NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NIH, Dept Clin Pathol, Ctr Clin, Bethesda, MD 20892 USA. Univ Oulu, Cent Hosp, Dept Pathol, SF-90220 Oulu, Finland. Univ Iowa, Dept Prevent Med & Environm Hlth, Iowa City, IA 52242 USA. Univ Tampere, Cent Hosp, Dept Pathol, FIN-33101 Tampere, Finland. Ontario Canc Treatment & Res Fdn, Toronto, ON M5G 2L7, Canada. Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands. Univ Uppsala Hosp, Dept Oncol, S-75175 Uppsala, Sweden. Univ Texas, MD Anderson Cancer Ctr, Houston, TX 77030 USA. RP Bennett, WP (reprint author), City Hope Natl Med Ctr, Div Human Genet, Fox Plaza S,2nd Floor,1500 E Duarte Rd, Duarte, CA 91010 USA. EM BBennett@smtplink.coh.org NR 53 TC 20 Z9 20 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 1998 VL 7 IS 5 BP 397 EP 403 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZM687 UT WOS:000073565800007 PM 9610789 ER PT J AU Tokunaga, M Land, CE AF Tokunaga, M Land, CE TI Epstein-Barr virus involvement in gastric cancer: Biomarker for lymph node metastasis SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CARCINOMA AB EBV involvement in gastric cancer is characterized by episomal monoclonality, high antibody titers, EBV encoded small RNA and EBV nuclear antigen 1 expression in all tumor cells, and in the intramucosal stage, by a unique morphology. EBV involvement varies by population (similar to 7% of gastric cancers in Japan and >15% in Western countries), sex, histological type, and tumor location. The present study compares frequency of lymph node metastasis (LNM) between 170 EBV-positive and 1590 EBV-negative gastric cancer cases in Japan by level of invasiveness, Frequency of LNM increased with increasing depth of invasiveness but was consistently and significantly greater for EBV-negative cases (P = 0.0018), In particular, there were no instances of LNM among 75 EBV-positive cases as compared with 53 among 562 EBV-negative cases restricted to the mucosa and submucosa (odds ratio, 0; 95% confidence limits, 0-0.20). The finding suggests that genetic control of metastasis may differ between EBV-related and other gastric cancers, Also, the possibility that EBV-positive, noninvasive gastric cancers may not require lymph node dissection suggests that routine assay of biopsy specimens for EBV involvement could be important in populations, like that of Japan, where early gastric cancers are seen frequently. C1 Kagoshima Univ, Sch Med, Dept Publ Hlth, Kagoshima 8908520, Japan. NCI, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. RP Tokunaga, M (reprint author), Kagoshima Univ, Sch Med, Dept Publ Hlth, Sakuragaoka 8-35-1, Kagoshima 8908520, Japan. NR 5 TC 9 Z9 10 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 1998 VL 7 IS 5 BP 449 EP 450 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZM687 UT WOS:000073565800014 PM 9610796 ER PT J AU Hoshino, T Jiang, YZ Dunn, D Paul, D Qazilbash, M Cowan, K Wang, JX Barrett, J Liu, J AF Hoshino, T Jiang, YZ Dunn, D Paul, D Qazilbash, M Cowan, K Wang, JX Barrett, J Liu, J TI Transfection of interleukin-12 cDNAs into tumor cells induces cytotoxic immune responses against native tumor: implications for tumor vaccination SO CANCER GENE THERAPY LA English DT Article DE interleukin-12; cytotoxicity; tumor immunotherapy; 2008 cells; CTL; NK cells ID GENE-TRANSFER; RETROVIRAL VECTORS; STIMULATORY FACTOR; INTERFERON-GAMMA; T-CELLS; CYTOKINE; LYMPHOCYTES; THERAPY; IL-12; PURIFICATION AB Interleukin-12 (IL-12) is a heterodimeric cytokine that is central to the development of T helper 1-dependent cellular immunity. Although this cytokine has potential therapeutic application as an antineoplastic agent, the systemic infusion of IL-12 has led to toxic fatalities; hence, restriction of expression of IL-12 to the microenvironment of target tumor cells has obvious appeal. In this study, we examined whether tumor cells that were liposome-transfected with IL-12 could enhance the induction of cytolytic lymphocyte immunity to the native tumor. The plasmid expression vector that we used has several useful features including replication to high copy number as an episome and a polycistronic message enabling the production of both the p35 and p40 subunits of IL-12 without alternative splicing; up to 3 ng/mL/10(6)/48 hours of IL-12 was produced following transfection. Tumor cells transfected with IL-12 were superior to untransfected cells in the induction of lymphocyte-mediated cytolysis. IL-12 transfectants induced a heterogeneous population of natural killer, lymphokine activated killer, and cytolytic T lymphocytes, the latter of which exhibited tumor-specific activity. Our studies suggest that liposome-mediated transfection of tumor cells with an episomal, high copy number plasmid vector expressing both IL-12 subunits is a promising approach to cancer vaccination, a strategy that could be implemented ex vivo in treating malignancies such as metastatic ovarian cancer. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Liu, J (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 21 TC 12 Z9 12 U1 0 U2 1 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 USA SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD MAY-JUN PY 1998 VL 5 IS 3 BP 150 EP 157 PG 8 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA ZP536 UT WOS:000073763300003 PM 9622098 ER PT J AU Tagliaferri, P Guarrasi, R Caraglia, M Morelli, D Fabbrocini, A Correale, P Bianco, AR AF Tagliaferri, P Guarrasi, R Caraglia, M Morelli, D Fabbrocini, A Correale, P Bianco, AR TI Tumour cell resistance to non-MHC-restricted lymphocytes: molecular mechanisms and clinical implications SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Review ID NATURAL-KILLER-CELLS; HLA-CLASS-I; NK CELLS; HISTOCOMPATIBILITY COMPLEX; CARCINOMA CELLS; MONOCLONAL-ANTIBODY; DOSE INTERLEUKIN-2; CYTOLYTIC ACTIVITY; SURFACE-MOLECULE; T-LYMPHOCYTES C1 Univ Naples Federico II, Fac Med, Dipartimento Endocrinol & Oncol Mol & Clin, Cattedra Oncol Med, I-80131 Naples, Italy. NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. RP Tagliaferri, P (reprint author), Univ Naples Federico II, Fac Med, Dipartimento Endocrinol & Oncol Mol & Clin, Cattedra Oncol Med, Via S Pansini 5, I-80131 Naples, Italy. RI Caraglia, Michele/N-5670-2015; Correale, Pierpaolo/K-1640-2016 OI Caraglia, Michele/0000-0003-2408-6091; Correale, Pierpaolo/0000-0003-2154-6734 NR 65 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD MAY PY 1998 VL 46 IS 3 BP 121 EP 127 DI 10.1007/s002620050470 PG 7 WC Oncology; Immunology SC Oncology; Immunology GA ZP953 UT WOS:000073805300001 PM 9625535 ER PT J AU Neckers, LM AF Neckers, LM TI Oligodeoxynucleotide inhibitors of function: mRNA and protein interactions SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Article; Proceedings Paper CT Oncology Frontiers Conference CY OCT 15-19, 1997 CL CAYMAN ISLAND SP Hoechst Marion Roussel, Kansas City ID MYCOBACTERIUM-BOVIS BCG; MEDIATED CELL-FUSION; SINGLE-STRANDED-DNA; ANTI-SENSE RNA; PHOSPHOROTHIOATE OLIGONUCLEOTIDES; BACTERIAL-DNA; CPG MOTIFS; ADMINISTERED OLIGODEOXYNUCLEOTIDES; SYNTHETIC OLIGONUCLEOTIDES; ANTITUMOR-ACTIVITY C1 NCI, Key W Facil, NIH, Med Branch, Rockville, MD 20850 USA. RP Neckers, LM (reprint author), NCI, Key W Facil, NIH, Med Branch, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. NR 55 TC 2 Z9 2 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 USA SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD MAY PY 1998 VL 4 SU 1 BP S35 EP S42 PG 8 WC Oncology SC Oncology GA ZQ074 UT WOS:000073818800007 PM 9619269 ER PT J AU Rosenberg, SA AF Rosenberg, SA TI New opportunities for the development of cancer immunotherapies SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Article; Proceedings Paper CT Oncology Frontiers Conference CY OCT 15-19, 1997 CL CAYMAN ISLAND SP Hoechst Marion Roussel, Kansas City ID HUMAN BREAST-CANCER; T-CELL RECEPTOR; MELANOMA ANTIGEN; AUTOLOGOUS TUMOR; REACTIVE CTL; LYMPHOCYTES; INTERLEUKIN-2; PEPTIDES; INDUCTION; MART-1 C1 NCI, Surg Branch, Bethesda, MD USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, Bldg 10,Room 2B42,10 Ctr Dr,MSC 1502, Bethesda, MD USA. NR 18 TC 12 Z9 15 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 USA SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD MAY PY 1998 VL 4 SU 1 BP S1 EP S4 PG 4 WC Oncology SC Oncology GA ZQ074 UT WOS:000073818800001 PM 9619263 ER PT J AU McGarvey, CL Magnuson, WG AF McGarvey, CL Magnuson, WG TI Rehabilitation of an adolescent with medulloblastoma SO CANCER PRACTICE LA English DT Article C1 St Jude Childrens Res Hosp, Rehabil Serv, Memphis, TN 38105 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Rehabil Med, Phys Therapy Sect, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Cancer Ctr, Behav Med Sect, Houston, TX 77030 USA. RP McGarvey, CL (reprint author), St Jude Childrens Res Hosp, Rehabil Serv, 332 N Lauderdale St, Memphis, TN 38105 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1065-4704 J9 CANCER PRACT JI Cancer Pract. PD MAY-JUN PY 1998 VL 6 IS 3 BP 138 EP 142 PG 5 WC Oncology; Health Care Sciences & Services; Nursing SC Oncology; Health Care Sciences & Services; Nursing GA ZL818 UT WOS:000073474600002 ER PT J AU Suzuki, A Kushida, H Iwata, H Watanabe, M Nohmi, T Fujita, K Gonzalez, FJ Kamataki, T AF Suzuki, A Kushida, H Iwata, H Watanabe, M Nohmi, T Fujita, K Gonzalez, FJ Kamataki, T TI Establishment of a Salmonella tester strain highly sensitive to mutagenic heterocyclic amines SO CANCER RESEARCH LA English DT Article ID HUMAN CYTOCHROME-P450 1A2; HAMSTER CHL CELLS; AROMATIC-AMINES; ESCHERICHIA-COLI; N-ACETYLTRANSFERASES; STABLE EXPRESSION; METABOLIC-ACTIVATION; O-ACETYLTRANSFERASE; NONHUMAN-PRIMATES; COOKED FOODS AB Heterocyclic amines (HCAs) that are present in cooked foods require metabolic activation to exert their genotoxicity. They undergo activation via N-hydroxylation by cytochrome P450 1A2 (CYP1A2), followed by O-esterification by O-acetyltransferase (OAT). To develop a Salmonella tester strain that is highly sensitive to mutagenic HCAs, we introduced a coexpression plasmid (p1A2OR) carrying human CYP1A2 and NADPH-CYP reductase cDNAs and an expression plasmid (pOAT) carrying Salmonella OAT to Salmonella typhimurium TA1538 to yield a TA1538/ARO strain. The TA1538/ARO strain was proven to express the enzymes, as indicated by high activities of 7-ethoxyresorufin O-deethylase and isoniazid N-acetylase. The TA1538/ARO strain exhibited very high sensitivity to mutagenic HCAs 2-amino-3,4-dimethylimidazo[4,5-f]quinoline, 2-amino-3-methylimidazo[3,5-f]quinoline (IQ), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and a somewhat higher sensitivity to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine compared with the parent Ames tester strain TA1538. The minimum concentrations of 2-amino-3,3-dimethylimidazo[4,5-f]quinoline, IQ, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine giving positive results were defined by evidence that the number of colonies increased in a dose-dependent manner and reached a number two times higher than that obtained by vehicle alone as a control in the TA1538/ARO strain at concentrations of 0.3, 3, 30, and 1000 pM, respectively. When the membrane and cytosol fractions prepared from TA1358/ARO were added to a mixture containing the parental TA1538, the sensitivity of TA1538 to IQ was much lower than that seen with TA1538/ARO. These results indicate that the intracellular expression of drug-metabolizing enzymes makes the established strain of Salmonella highly sensitive to mutagenic HCAs. C1 Hokkaido Univ, Fac Pharmaceut Sci, Div Drug Metab, Sapporo, Hokkaido 060, Japan. Natl Canc Ctr, Res Inst, Div Biochem, Tokyo 104, Japan. Natl Inst Hlth Sci, Div Genet & Mutagenesis, Tokyo 158, Japan. NIH, Lab Metab, Bethesda, MD 20892 USA. RP Kamataki, T (reprint author), Hokkaido Univ, Fac Pharmaceut Sci, Div Drug Metab, Kita Ku, N12 W6, Sapporo, Hokkaido 0600812, Japan. NR 47 TC 38 Z9 38 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1998 VL 58 IS 9 BP 1833 EP 1838 PG 6 WC Oncology SC Oncology GA ZK631 UT WOS:000073344700013 PM 9581821 ER PT J AU Wink, DA Vodovotz, Y Laval, J Laval, F Dewhirst, MW Mitchell, JB AF Wink, DA Vodovotz, Y Laval, J Laval, F Dewhirst, MW Mitchell, JB TI The multifaceted roles of nitric oxide in cancer SO CARCINOGENESIS LA English DT Editorial Material ID TUMOR-NECROSIS-FACTOR; VASCULAR ENDOTHELIAL-CELLS; WOODCHUCK HEPATITIS-VIRUS; PEROXYNITRITE IN-VITRO; RIBONUCLEOTIDE REDUCTASE; ADENOCARCINOMA CELLS; SYNTHASE EXPRESSION; DNA-DAMAGE; MYOCARDIAL-ISCHEMIA; ANTITUMOR RESPONSES AB The roles of nitric oxide (NO) in numerous disease states have generated considerable discussion over the past several years. NO has been labeled as the causative agent in different pathophysiological mechanisms, yet appears to protect against various chemical species such as those generated under oxidative stress. Similarly, NO appears to exert a dichotomy of effects within the multistage model of cancer, Chronic inflammation can lead to the production of chemical intermediates, among them NO, which in turn can mediate damage to DNA, Yet, NO also appears to be critical for the tumoricidal activity of the immune system. Furthermore, NO can also have a multitude of effects on other aspects of tumor biology, including angiogenesis and metastasis, This report will discuss how the chemistry of NO may impact the initiation and progression stages of cancer. C1 NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. Inst Gustave Roussy, CNRS, URA 147, PR 2, F-94805 Villejuif, France. INSERM, U347, F-94276 Le Kremlin Bicetre, France. Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA. RP Wink, DA (reprint author), NCI, Radiat Biol Branch, Bldg 10,Room B3-B69, Bethesda, MD 20892 USA. NR 158 TC 473 Z9 491 U1 1 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1998 VL 19 IS 5 BP 711 EP 721 DI 10.1093/carcin/19.5.711 PG 11 WC Oncology SC Oncology GA ZP686 UT WOS:000073778300001 PM 9635855 ER PT J AU Takenoshita, S Tani, M Mogi, A Nagashima, M Nagamachi, Y Bennett, WP Hagiwara, K Harris, CC Yokota, J AF Takenoshita, S Tani, M Mogi, A Nagashima, M Nagamachi, Y Bennett, WP Hagiwara, K Harris, CC Yokota, J TI Mutation analysis of the Smad2 gene in human colon cancers using genomic DNA and intron primers SO CARCINOGENESIS LA English DT Article ID GROWTH-FACTOR-BETA; TUMOR-SUPPRESSOR GENE; MAD-RELATED PROTEIN; IN-VIVO ALTERATIONS; HUMAN LUNG CANCERS; 3' SPLICE SITE; MICROSATELLITE INSTABILITY; COLORECTAL CANCERS; MESSENGER-RNA; POLYPYRIMIDINE TRACT AB In mammals, one of the Mad homologues, Smad2, was reported to be a mediator of TGF-beta signaling, and was found mutated in some cases of colon and lung cancers. To extend the analysis of this gene, we previously investigated the genomic organization of the human Smad2 gene and defined the structure of 12 exons and flanking introns, In this study, we designed 11 sets of intron-based primers to examine the entire coding region of the Smad2 gene. By the PCR-SSCP method using these primers, we screened genomic DNA sequences of colorectal cancers for mutations of the Smad2 gene, Though there was no mutation within all exons of the Smad2 gene, two of 60 sporadic colorectal cancers displayed deletions in the polypyrimidine tract preceding exon 4, Deletions of this region were also detected in colon cancer cell lines, and were clustered within cells exhibiting microsatellite instability. Deletions in the polypyrimidine tract had various effects on pre-mRNA splicing, but had no effect on the splicing of the Smad2 gene in these cases. However, our data support the idea that the polypyrimidine tract in the splicing acceptor site is a target of mutations in mismatch repair-deficient tumors. C1 Natl Canc Ctr, Res Inst, Div Biol, Tokyo 104, Japan. Gunma Univ, Sch Med, Dept Surg 1, Gunma 371, Japan. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Yokota, J (reprint author), Natl Canc Ctr, Res Inst, Div Biol, Tokyo 104, Japan. NR 52 TC 27 Z9 28 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1998 VL 19 IS 5 BP 803 EP 807 DI 10.1093/carcin/19.5.803 PG 5 WC Oncology SC Oncology GA ZP686 UT WOS:000073778300012 PM 9635866 ER PT J AU Li, JJ Colburn, NH Oberley, LW AF Li, JJ Colburn, NH Oberley, LW TI Maspin gene expression in tumor suppression induced by overexpressing manganese-containing superoxide dismutase cDNA in human breast cancer cells SO CARCINOGENESIS LA English DT Article ID DNA-BINDING ACTIVITY; MOUSE EPIDERMAL-CELLS; NF-KAPPA-B; REDOX REGULATION; HYDROGEN-PEROXIDE; LUNG FIBROBLASTS; INTRACELLULAR PH; CIS-FOS; ACTIVATION; INDUCTION AB We have reported the tumor suppressive effects of manganese-containing superoxide dismutase (MnSOD) in human breast cancer cells. In order to understand the molecular mechanism of this anti-tumor effect, we asked whether tumor suppressor gene(s), especially the ones inhibiting tumor invasion and motility, are involved in MnSOD-induced tumor suppression. Maspin is one of the serpin family of protease inhibitors that has been shown to function as a tumor-suppressor in human breast epithelium, In the present study, we demonstrated that maspin expression was up-regulated in human breast cancer MCF-7 cells that overexpress a normal MnSOD gene. The induced maspin transcripts were detected by RT-PCR and Northern blot and identified by sequencing. Maspin gene expression was induced in parallel with the level of exogenous MnSOD protein, which was induced by transfection with varied amounts of cDNA, In order to analyze cell invasion ability, which may be related to the induced maspin gene expression, MnSOD stable transfectants were tested using a matrigel invasion chamber. The invasion ability was reduced to 24% and 36% in the cloned (MCF + SOD) and pooled MnSOD-transfectants (MCF + SODp) respectively, compared with the wild-type MCF-7 cell line, In conclusion, these results suggest that overexpression of a normal MnSOD cDNA in human breast cancer cells up-regulates the gene expression of the protease inhibitor, maspin, which may play a role in the inhibitory function of MnSOD on tumor invasion. C1 NCI, Frederick Canc Res & Dev Ctr, Gene Regulat Sect, Lab Biochem Physiol, Frederick, MD 21702 USA. Univ Iowa, Dept Radiat Biol, Radiat Res Lab, Iowa City, IA 52242 USA. RP Li, JJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Gene Regulat Sect, Lab Biochem Physiol, Frederick, MD 21702 USA. EM Lij@ncifcrf.gov NR 54 TC 48 Z9 48 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1998 VL 19 IS 5 BP 833 EP 839 DI 10.1093/carcin/19.5.833 PG 7 WC Oncology SC Oncology GA ZP686 UT WOS:000073778300017 PM 9635871 ER PT J AU Mauthe, RJ Snyderwine, EG Ghoshal, A Freeman, SPHT Turteltaub, KW AF Mauthe, RJ Snyderwine, EG Ghoshal, A Freeman, SPHT Turteltaub, KW TI Distribution and metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in female rats and their pups at dietary doses SO CARCINOGENESIS LA English DT Article ID ACCELERATOR MASS-SPECTROMETRY; FOOD-DERIVED CARCINOGEN; HETEROCYCLIC AMINES; COOKED BEEF; MUTAGEN PHIP; BREAST-MILK; CHLOROPHYLLIN; EXPOSURE; INHIBITION; PRODUCTS AB 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mammary carcinogen in female rats and is present in a wide variety of cooked meats. We address here the excretion of PhIP and its metabolites into the breast-milk of lactating rats and the ability of chlorophyllin, a food product derivative with chemopreventive properties, to affect these levels at low PhIP doses. Lactating female F344 rats with suckling pups were orally administered 50, 500 and 1000 ng [C-14]PhIP/kg body weight. The excretion of the [C-14]PhIP into milk and its distribution among the mammary tissue, liver and blood of the dam, as well as among stomach contents and liver of their suckling pups was measured using accelerator mass spectrometry (AMS), PhIP, PhIP-4'-sulfate, 4'-hydroxy-PhIP, and N-2-hydroxy-PhIP-N-3-glucuronide were found in the milk at all doses. The chlorophyllin (500 mu g/kg) co-administration with PhIP (500 ng/kg) caused increased levels of [C-14]PhIP in the milk (32%) and stomach contents (35%) of the pups relative to the animals not receiving chlorophyllin at these low PhIP doses. In contrast, lower [C-14]PhIP levels in the chlorophyllin treated animals were observed in the blood (47%) and mammary tissue (68%) of the dam, as well as the pup's liver tissue (37%) compared to the animals receiving only PhIP, Chlorophyllin co-administration resulted in an increased amount of N-2-hydroxy-PhIP-N-3-glucuronide (42%), increased PhIP (79%) and decreased levels of PhIP-4'-sulphate (77%) relative to the animals not receiving chlorophyllin. These results suggest that PhIP and PhIP metabolites are present in the breast-milk of lactating rats at human dietary PhIP exposures and that PhIP is absorbed by the newborn. Furthermore, these results suggest that other dietary components can affect the dosimetry of PhIP in breast-feeding offspring. C1 Univ Calif Lawrence Livermore Natl Lab, Mol & Struct Biol Div, Livermore, CA 94551 USA. Univ Calif Lawrence Livermore Natl Lab, Ctr Accelerator Mass Spectrometry, Livermore, CA 94551 USA. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Turteltaub, KW (reprint author), Univ Calif Lawrence Livermore Natl Lab, Mol & Struct Biol Div, Livermore, CA 94551 USA. RI Freeman, Stewart/C-3290-2012 OI Freeman, Stewart/0000-0001-6148-3171 FU NCI NIH HHS [CA55861] NR 47 TC 23 Z9 23 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1998 VL 19 IS 5 BP 919 EP 924 DI 10.1093/carcin/19.5.919 PG 6 WC Oncology SC Oncology GA ZP686 UT WOS:000073778300029 PM 9635883 ER PT J AU Chen, HJC Gonzalez, FJ Shou, MG Chung, FL AF Chen, HJC Gonzalez, FJ Shou, MG Chung, FL TI 2,3-epoxy-4-hydroxynonanal, a potential lipid peroxidation product for etheno adduct formation, is not a substrate of human epoxide hydrolase SO CARCINOGENESIS LA English DT Article ID VACCINIA VIRUS; HUMAN-LIVER; DNA; EXPRESSION; RAT; DEOXYGUANOSINE; ACRYLONITRILE; METABOLITES; MICROSOMES; RODENTS AB Our previous studies have shown that 2,3-epoxy-4-hydroxynonanal, a reactive epoxy aldehyde capable of forming etheno adducts with DNA bases, is mutagenic and tumorigenic (Carcinogenesis, 14, 2073), The epoxy aldehyde can be generated from trans-4-hydroxy-2-nonenal, a lipid peroxidation product of omega-6 polyunsaturated fatty acids, by autoxidation or by incubation with fatty acid hydroperoxides or hydrogen peroxides (Chem. Res. Toxicol., 9, 306), These are plausible in vivo pathways for the formation of 2,3-epoxy-4-hydroxynonanal. The possibility that 2,3-epoxy-4-hydroxynonanal is a tumorigen of endogenous origin is suggested by recent observations that etheno bases are detected as background DNA lesions in untreated rodents and humans. A metabolic pathway critical for detoxification of 2,3-epoxy-4-hydroxynonanal involves the ring-opening by epoxide hydrolase, which abolishes its ability to form cyclic etheno DNA adducts, In this study, we examined whether 2,3-epoxy-4-hydroxynonanal is a substrate of cDNA expressed human epoxide hydrolase, Human epoxide hydrolase was expressed in TK-143 cells (thymidine kinase-deficient human embryoblast) infected with recombinant vaccinia virus encoding human epoxide hydrolase cDNA, Controls consisted of the cells infected with vaccinia virus in the absence of human epoxide hydrolase cDNA, No hydrolysis occurred when [2,3-H-3]2,3-epoxy-4-hydroxynonanal was incubated at 37 degrees C for 30 min at pH 7.4 with cells expressing human epoxide hydrolase, as indicated by the presence of a pair of radioactive peaks in reversed-phase HPLC chromatography, which comigrated with the UV standards of the two diastereomers of the epoxy aldehyde, The identity of these compounds as the intact epoxy aldehyde was further supported by derivatization to the 2,4-dinitrophenylhydrazones followed by reversed phase HPLC analysis, Similar results were observed with the control cells or with the heat deactivated human epoxide hydrolase, The epoxide hydrolase activity in the expressed cells was demonstrated by their ability to convert benzo[a]pyrene-4,5-dihydroepoxide to benzo[a]pyrene-trans-4,5-dihydrodiol under the same conditions. These results clearly indicate that 2,3-epoxy-4-hydroxynonanal is not a substrate of human epoxide hydrolase, and, thus strengthen its possible endogenous role in the formation of promutagenic exocyclic etheno adducts in vivo. C1 NCI, Mol Carcinogenesis Lab, Bethesda, MD 20892 USA. Amer Hlth Fdn, Div Carcinogenesis & Mol Epidemiol, Valhalla, NY 10595 USA. RP Chen, HJC (reprint author), Natl Chung Cheng Univ, Dept Chem, Chiayi, Taiwan. RI Chen, Hauh-Jyun/G-4879-2010 FU NCI NIH HHS [CA 43159] NR 36 TC 14 Z9 15 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1998 VL 19 IS 5 BP 939 EP 943 DI 10.1093/carcin/19.5.939 PG 5 WC Oncology SC Oncology GA ZP686 UT WOS:000073778300032 PM 9635886 ER PT J AU Wang, XC Strauss, KI Ha, QN Nagula, S Wolpoe, ME Jacobowitz, DM AF Wang, XC Strauss, KI Ha, QN Nagula, S Wolpoe, ME Jacobowitz, DM TI Chymotrypsin gene expression in rat peripheral organs SO CELL AND TISSUE RESEARCH LA English DT Article DE pancreas; stomach; duodenum; ribonuclease protection assay; immunocytochemistry; protease; rat; (Sprague Dawley) ID PROTEOLYTIC-ENZYMES; MONOCLONAL-ANTIBODY; CALRETININ; SEQUENCE; GRANULES; PEPTIDE; CLONING; CELLS AB Prior studies have revealed the presence of chymotrypsinlike protease in peripheral organs, although no definitive evidence for the synthesis of this enzyme in tissue other than the pancreas is available. In an attempt to detect chymotrypsinogen mRNA in peripheral organs, a fragment of the pancreatic chymotrypsin mRNA from rat was amplified using PCR. The sequence was identified as a portion of the rat chymotrypsin B gene overlapping exon 5 through exon 7. It was subcloned into the pGEM-4Z vector and used as a template for the vitro transcription of an antisense riboprobe. Using ribonuclease protection and Northern blot analyses,chymotrypsin mRNA was detected in the rat pancreas, stomach, duodenum, ovary, and spleen. Monoclonal and polyclonal antisera against chymotrypsin detected chymotrypsinlike immunoreactivity in rat and human pancreas, rat stomach, duodenum and jejunum. Electrophoresis and immunoblotting revealed chymotrypsin-chymotrypsinogen bands (25-29 kDa) in the stomach and duodenum. Synthesis of a potent protease such as chymotrypsin in tissue other than pancreas is significant, suggesting a potential physiological and/or pathological role in these tissues. high enzyme activity of this organ. Subsequently, numerous studies have demonstrated the presence of chymotrypsinlike proteases elsewhere in the periphery (e.g., Kaiser and Hoskin 1992; King et al. 1987). All of these chymotrypsinlike proteases had the common property of cleaving chymotrypsin substrates, but were unaffected by chymotrypsin-specific inhibitors. No evidence has been presented to indicate that chymotrypsin itself is expressed in any tissue other than the exocrine glands of the pancreas. The field of molecular biology has dramatically expanded the array of techniques available for detection of gene expression. In the present paper we surveyed peiripheral tissues from rats for chymotrypsin mRNA using a sensitive ribonuclease protection analysis (RPA) and Northern blot analysis. Chymotrypsin mRNA was detected in the pancreas, stomach, intestine, ovary and spleen. Immunohistochemistry confirmed the presence of chymotrypsin immunoreactivity in cells of the pancreas and gastrointestinal tract. In addition, immunoprecipitation Western blot analysis identified chymotrypsin proteins in the pancreas, stomach and intestine. C1 NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Wang, XC (reprint author), NIMH, Clin Sci Lab, Bldg 10,Room 3D-48,10 Ctr Dr,MSC 1266, Bethesda, MD 20892 USA. EM dwj@helix.nih.gov NR 27 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD MAY PY 1998 VL 292 IS 2 BP 345 EP 354 DI 10.1007/s004410051065 PG 10 WC Cell Biology SC Cell Biology GA ZQ431 UT WOS:000073860900017 PM 9560477 ER PT J AU Montesano, R Soriano, JV Malinda, KM Ponce, ML Bafico, A Kleinman, HK Bottaro, DP Aaronson, SA AF Montesano, R Soriano, JV Malinda, KM Ponce, ML Bafico, A Kleinman, HK Bottaro, DP Aaronson, SA TI Differential effects of hepatocyte growth factor isoforms on epithelial and endothelial tubulogenesis SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID FACTOR SCATTER FACTOR; MET PROTOONCOGENE PRODUCT; CAPILLARY-LIKE STRUCTURES; RECEPTOR TYROSINE KINASE; C-MET; FACTOR/SCATTER FACTOR; ANGIOGENESIS INVITRO; BIOLOGICAL-ACTIVITY; MOLECULAR-CLONING; BASEMENT-MEMBRANE AB Hepatocyte growth factor (HGF)/scatter factor (SF) is a pleiotropic cytokine that acts as a mitogen, motogen, and morphogen for a variety of cell types. HGF/NK1 and HGF/NK2 are two naturally occurring truncated variants of HGF/SF, which extend from the NH, terminus through the first and second kringle domain, respectively. Although these variants have been reported to have agonistic or antagonistic activity relative to HGF/SF in assays of cell proliferation and motility, their potential morphogenic activity has not been investigated, To address this issue, we assessed the ability of HGF/NK1 and HGF/NK2 to induce tube formation by (a) MCF-10A mammary epithelial cells grown within collagen gels and (b) human umbilical vein endothelial (HUVE) cells grown on Matrigel, We found that HGF/NK1 stimulated tubulogenesis by both MCF-10A and HUVE cells, whereas HGF/NK2 did not stimulate tubulogenesis, but efficiently antagonized the morphogenic effect of full-length HGF/SF. HGF/NK1 and HGF/NK2 also had agonistic and antagonistic effects, respectively, on MCF-10A cell proliferation and HUVE cell migration. These results demonstrate that HGF/NK1, which only consists of the NH(2)-terminal hairpin and first kringle domain, is sufficient to activate the intracellular signaling pathways required to induce morphogenic responses in epithelial and endothelial cells, In contrast, HGF/NK2, which differs from HGF/NK1 by the presence of the second kringle domain, is devoid of intrinsic activity but opposes the effects of HGF/SF, The differential properties of the two HGF/SF isoforms provide a basis for the design of more potent HGF/SF agonists and antagonists. C1 Univ Geneva, Med Ctr, Dept Morphol, CH-1211 Geneva 4, Switzerland. NIDR, Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Mt Sinai Med Ctr, Derald H Ruttenberg Canc Ctr, New York, NY 10029 USA. RP Montesano, R (reprint author), Univ Geneva, Med Ctr, Dept Morphol, 1 Rue Michel Servet, CH-1211 Geneva 4, Switzerland. EM roberto.montesano@medecine.unige.ch RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 FU NCI NIH HHS [IROI-CA 71672-O1A1] NR 69 TC 51 Z9 51 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD MAY PY 1998 VL 9 IS 5 BP 355 EP 365 PG 11 WC Cell Biology SC Cell Biology GA ZM949 UT WOS:000073592500001 PM 9607557 ER PT J AU Carrillo, C Cafferata, EGA Genovese, J O'Reilly, M Roberts, AB Santa-Coloma, TA AF Carrillo, C Cafferata, EGA Genovese, J O'Reilly, M Roberts, AB Santa-Coloma, TA TI TGF-beta 1 up-regulates the mRNA for the Na+/Ca2+ exchanger in neonatal rat cardiac myocytes SO CELLULAR AND MOLECULAR BIOLOGY LA English DT Article DE TGF-beta 1; Na+/Ca2+ exchanger; cardiac myocytes ID GROWTH-FACTOR-BETA; PROTEIN-KINASE-C; TRANSFORMING GROWTH-FACTOR-BETA-1; SELECTIVE INHIBITOR; PHOSPHOLIPASE-C; GENE-EXPRESSION; LEUKEMIA-CELLS; SMOOTH-MUSCLE; CALCIUM; GENISTEIN AB Northern analyses of neonatal cardiac myocytes demonstrated that TGF-beta 1 (5 ng/ml) stimulates and IL-1 beta (5 ng/ml) decreases the steady-state levels of the mRNA coding for the Na+/Ca2+ exchanger. This is in agreement with the effects of TGF-beta 1 and IL-1 beta on beating rate and calcium uptake, suggesting that such effects might be mediated, at least partially, through up-regulation of the Na+/Ca2+ exchanger. Basal and TGF-beta 1 stimulated mRNA levels were inhibited by the PKC inhibitors H7 (10 mu M) and GF109203X (250 nhl). In addition, apigenin (12.5 mu M), a MAP kinase inhibitor, was able to inhibit basal mRNA levels for the exchanger. Cycloheximide (35.5 mu M) had no effect on basal mRNA levels for the exchanger but steady-state levels were diminished in cells treated with TGF-beta 1. Finally, actinomycin D (10 mu M) inhibited both basal and TGF-beta 1 stimulated mRNA levels, though with a more pronounced effect in the presence of TGF-beta 1. These results suggest that a complex mechanism of regulation exists for the exchanger and that PKC and possibly MAP kinases might be involved. The up-regulation of this important protein for calcium extrusion, induced by TGF-beta 1, might prepare cells to better overcome the calcium overload which occurrs under cellular stress and might explain some of the cytoprotective effects of TGF-beta 1. C1 Fdn Campomar, Inst Invest Bioquim, RA-1405 Buenos Aires, DF, Argentina. Ctr Nacl Genet Med, Buenos Aires, DF, Argentina. NCI, Chemoprevent Lab, NIH, Bethesda, MD 20892 USA. RP Santa-Coloma, TA (reprint author), Fdn Campomar, Inst Invest Bioquim, Patricias Argentinas 435, RA-1405 Buenos Aires, DF, Argentina. NR 39 TC 15 Z9 15 U1 0 U2 0 PU CELLULAR & MOLECULAR BIOLOGY PI NOISY-LE-GRAND PA PROF R WEGMANN RESIDENCE HAUSSMANN 1 AVENUE DU PAVE NEUF, 93160 NOISY-LE-GRAND, FRANCE SN 0145-5680 J9 CELL MOL BIOL JI Cell. Mol. Biol. PD MAY PY 1998 VL 44 IS 3 BP 543 EP 551 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 102GK UT WOS:000074915900019 PM 9620452 ER PT J AU Pospisil, R Mage, RG AF Pospisil, R Mage, RG TI B-cell superantigens may play a role in B-cell development and selection in the young rabbit appendix SO CELLULAR IMMUNOLOGY LA English DT Article ID PROTEIN TYROSINE PHOSPHORYLATION; STAPHYLOCOCCUS-AUREUS; ANTIBODY REPERTOIRE; REGION SEQUENCES; GENE CONVERSION; STIMULATION; MATURATION; EXPRESSION; BINDING; RECEPTOR AB In order to develop protective antibodies against a wide range of potentially infectious pathogens, the young rabbit must diversify a limited initial repertoire by somatic mechanisms (the high copy number primary repertoire). The majority of rabbit B cells produce heavy chain variable regions by rearranging the V(H)a allotype-encoding V(H)1 gene. Thus in normal rabbits the majority of serum immunoglobulins bear V(H)a allotype (due to V(H)1 FR1 and FR3 sequences). The young rabbit appendix is a site of diversification of rearranged V-H genes by gene-conversion-like and somatic hypermutation mechanisms. The newly generated B cells probably undergo selection processes that involve foreign and self-antigens and superantigens. We find preferential expansion and survival of B cells in normal and V-H-mutant ali/ali rabbits based on their heavy chain FR1 and FR3 sequences (V(H)a allotype). This selection may involve "superantigen"-like interactions with endogenous as well as exogenous ligands. (C) 1998 Academic Press. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20982 USA. RP Mage, RG (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr MSC 1892, Bethesda, MD 20982 USA. RI Pospisil, Richard/B-7467-2012 NR 40 TC 16 Z9 18 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD MAY 1 PY 1998 VL 185 IS 2 BP 93 EP 100 DI 10.1006/cimm.1998.1288 PG 8 WC Cell Biology; Immunology SC Cell Biology; Immunology GA ZU247 UT WOS:000074177100002 PM 9636687 ER PT J AU Mosnaim, AD Kulaga, H Adams, AJ Wolf, ME Puente, J Freitag, F Diamond, S AF Mosnaim, AD Kulaga, H Adams, AJ Wolf, ME Puente, J Freitag, F Diamond, S TI Flow cytometric analysis of lymphocyte subsets in migraine patients during and outside of an acute headache attack SO CEPHALALGIA LA English DT Article DE CD3/CD16/CD56 triple positive lymphocytes; flow cytometry; lymphocyte subsets; migraine ID TENSION-TYPE HEADACHE; KILLER-CELL ACTIVITY; CLUSTER HEADACHE; CHALLENGE; INVITRO; EPISODE; BLOOD AB We have conducted flow cytometric studies of two subsets of lymphocyte markers in groups of migraineurs during (n = 12; group B) and outside (n = 10; group C) of a migraine without aura attack (total n = 22; group A), including a group of patients tested in both of these phases (n=5; group D), and compared these results with those obtained from a population of age-comparable, sex- and race-matched healthy volunteers (n=12; group E). Comparison of the first set of lymphocytes (CD3(+)CD16+56(+), CD3(-)CD16+56(+), CD3(-)CD19(+), CD3(+)CD19(+), and CD3(+)HLA-DR+) between the patients in group A and the controls (group E) showed differences, reflecting greater group A percentages of CD3(+)CD16+CD56(+) and CD3(-)CD19(+) lymphocytes. Furthermore, these differences reached statistical significance only for the CD3(+)CD16+CD56(+) lymphocytes, and then solely for the patients in group C (Scheffe's test, p<0.05). Paired analysis of the above lymphocyte markers for subjects in group D failed to show significant differences between patients when they were having and not having a migraine attack, raising the possibility that results from a larger study could show meaningful increases in percentages of CD3(+)CD16+CD56(+) lymphocytes as one of the immune parameters useful for differentiating migraineurs from controls. Comparison of a second set of lymphocyte markers (CD19(+)CD5(+), CD20(+)CD72(-), CD20(-)CD72(+), CD20(+)CD72(+)) among either the different groups of patients or between the patients and controls failed, however, to show statistically significant differences, emphasizing the apparent specificity of the findings described above for CD3(+)CD16+CD56(+) lymphocytes. Our results, albeit of a preliminary nature, suggest the occurrence of significant, differential changes in lymphocyte subset immunophenotyping between groups of pain-free migraineurs and patients during an acute migraine episode or controls. Corroboration of these findings may prove useful in clinical laboratory practice to identify changes in immunological parameters specifically associated with migraineurs, and help towards a better understanding of the etiology and pathophysiology of this condition. C1 Finch Univ Hlth Sci Chicago Med Sch, Dept Mol Biol & Pharmacol, N Chicago, IL 60064 USA. NIMH, St Elizabeths Hosp, NRC, Mol Neurobiol Unit, Washington, DC 20032 USA. Loyola Univ, Sch Med, Dept Psychiat, New Orleans, LA 70118 USA. Univ Chile, Fac Chem & Pharmaceut Sci, Dept Biochem & Mol Biol, Santiago, Chile. Diamond Headache Clin, Chicago, IL USA. RP Mosnaim, AD (reprint author), Finch Univ Hlth Sci Chicago Med Sch, Dept Mol Biol & Pharmacol, 3333 Green Bay Rd, N Chicago, IL 60064 USA. NR 30 TC 14 Z9 14 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD MAY PY 1998 VL 18 IS 4 BP 197 EP 201 DI 10.1046/j.1468-2982.1998.1804197.x PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA ZV038 UT WOS:000074262100009 PM 9642494 ER PT J AU Erve, JCL Amarnath, V Graham, DG Sills, RC Morgan, AL Valentine, WM AF Erve, JCL Amarnath, V Graham, DG Sills, RC Morgan, AL Valentine, WM TI Carbon disulfide and N,N-diethyldithiocarbamate generate thiourea cross-links on erythrocyte spectrin in vivo SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID IN-VIVO; EXPOSURE; PROTEINS; ACID; CS2 AB CS2, a known neurotoxicant, is used in the viscose production of rayon and is also a decomposition product of N,N-diethyldithiocarbamate, a metabolic product of the drug disulfiram used in alcohol aversion therapy. Previous in vitro investigations have demonstrated the ability of CS2 to cross-link proteins through thiourea, dithiocarbamate ester, and disulfide structures. Although in vivo studies have supported protein cross-linking as both a mechanism of neurotoxicity and a potential biomarker of effect, the chemical structures responsible far CS2-mediated protein cross-linking in vivo have not been elucidated. In the present study, the structure of one type of stable protein cross-link produced on erythrocyte spectrin by CS2 in vivo is determined. Rats were exposed to 50, 500, and 800 ppm CS2 for 13 weeks by inhalation or to 3 mmol/kg N,N-diethyldithiocarbamate administered orally on alternating days for 8 weeks. Erythrocyte spectrin preparations from control and exposed rats were hydrolyzed using 6 N HCl and separated by size-exclusion chromatography. The fraction that coeluted with the synthetic deuterated lysine-lysine thiourea internal standard was derivatized with 3-[4'-[(N,N,N-trimethylamino)ethylene]phenyl] 2-isothiocyanate and analyzed by liquid chromatography tandem mass spectrometry using selected reaction monitoring detection. Lysine-lysine thiourea was detected in spectrin preparations obtained from CS2-treated rats at 500 and 800 ppm and N,N-diethyldithiocarbamate-treated rats, but not from controls. These results establish that CS2-mediated protein cross-linking occurs in vivo through the generation of Lys-Lys thiourea and that diethyldithiocarbamate can, through in vivo release of CS2, produce the same cross-linking structure. This observation supports the utility of cross-linking of peripheral proteins as a specific dosimeter of internal exposure for CS2 and provides a mechanistic explanation to account for the high-molecular-weight neurofilament protein species isolated from rats exposed to CS2 or N,N-diethyldithiocarbamate. C1 Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Ctr Mol Toxicol, Nashville, TN 37232 USA. NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Erve, JCL (reprint author), Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. FU NIEHS NIH HHS [P30 ES00267, ES06387, ES05764] NR 16 TC 10 Z9 10 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAY PY 1998 VL 11 IS 5 BP 544 EP 549 DI 10.1021/tx980007i PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA ZP385 UT WOS:000073747000018 PM 9585486 ER PT J AU Mundy, LM Oldach, D Auwaerter, PG Gaydos, CA Moore, RD Bartlett, JG Quinn, TC AF Mundy, LM Oldach, D Auwaerter, PG Gaydos, CA Moore, RD Bartlett, JG Quinn, TC CA Hopkins CAP Team TI Implications for macrolide treatment in community-acquired pneumonia SO CHEST LA English DT Article DE atypical pathogen; Chlamydia species; community-acquired legionella; macrolide; Mycoplasma pneumoniae; pneumonia ID POLYMERASE CHAIN-REACTION; REACTION-ENZYME-IMMUNOASSAY; CHLAMYDIA-PNEUMONIAE; MYCOPLASMA-PNEUMONIAE; LEGIONNAIRES-DISEASE; BACTERIAL PNEUMONIA; INITIAL MANAGEMENT; INFECTION; THERAPY; ADULTS AB Study objectives: To identify associated clinical parameters, concurrent respiratory tract infections, and the association between macrolide-based therapy and mortality in patients with community-acquired pneumonia ascribed to atypical. Design: Secondary analysis of prospective, cross-sectional study. Setting: Tertiary care hospital. Patients: Three hundred eighty-five consecutive patients who were admitted to the Johns Hopkins Hospital from November 11, 1990, through November 10, 1991, and treated for community-acquired pneumonia. Results: An atypical pathogen was identified in 29 of 385 adults (7.5%). A second pathogen was detected in 16 of 29 patients (55.2%) in whom an atypical pathogen was detected, compared with 13 of 137 patients (9.5%) in whom conventional bacterial pathogens were detected (odds ratio, 10.22; 95% confidence interval, 3.1 to 28.8; p<0.0001). During hospitalization, only four patients (13.8%) with detection of an atypical pathogen received at least 7 days of either a macrolide or tetracycline. No patient identified to have an atypical pathogen died. For patients who either provided paired sera or who died, 24 of 197 (12.2%) had atypical pathogens detected. Conclusions: Despite vigorous study methods, atypical pathogens were uncommon in our hospitalized population. A second concurrent respiratory pathogen was identified for most patients with atypical pneumonia. Although macrolide use was rare in this patient population, mortality was zero for patients in whom an atypical pathogen was detected, affirming that macrolide-based therapy need not be routine in the therapeutic management of community-aquired pneumonia. C1 Washington Univ, Sch Med, Div Infect Dis, St Louis, MO 63110 USA. Washington Univ, Sch Med, Div Gen Med Sci, St Louis, MO 63110 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Johns Hopkins Sch Med, Baltimore, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Mundy, LM (reprint author), Washington Univ, Sch Med, Div Infect Dis, 660 S Euclid, St Louis, MO 63110 USA. RI Gaydos, Charlotte/E-9937-2010 NR 40 TC 59 Z9 61 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 1998 VL 113 IS 5 BP 1201 EP 1206 DI 10.1378/chest.113.5.1201 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA ZM939 UT WOS:000073591500015 PM 9596295 ER PT J AU Menchaca, G Padilla-Noriega, L Mendez-Toss, M Contreras, JF Puerto, FI Guiscafre, H Mota, F Herrera, I Cedillo, R Munoz, O Ward, R Hoshino, Y Lopez, S Arias, CF AF Menchaca, G Padilla-Noriega, L Mendez-Toss, M Contreras, JF Puerto, FI Guiscafre, H Mota, F Herrera, I Cedillo, R Munoz, O Ward, R Hoshino, Y Lopez, S Arias, CF TI Serotype specificity of the neutralizing-antibody response induced by the individual surface proteins of rotavirus in natural infections of young children SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; VACCINE DEVELOPMENT; SEROLOGIC RESPONSE; BOVINE ROTAVIRUS; IMMUNE-RESPONSES; VP4 GENOTYPES; PROTECTION; INFANTS; GASTROENTERITIS; EPITOPES AB The relative contribution of the rotavirus surface proteins, VP4 and VP7, to the induction of homotypic as weal as heterotypic neutralizing antibodies (NtAbs) in natural infections,vas studied. The NtAb titers of paired sera from 70 infants with serologically defined primary rotavirus infections were determined with a panel of rotavirus reassortants having one surface protein from a human rotavirus (serotypes G1 to G4 for VP7 and P1A and P1B for VP4) and the other surface protein from a heterologous animal rotavirus strain. A subset of 37 children were evaluated for epitope-specific antibodies to the two proteins by an epitope-blocking assay. The infants mere found to seroconvert more frequently to VP4 than to VP7 by both methods, although the titers of the seroconverters were higher to VP7 than to VP4, Both proteins induced homotypic as well as heterotypic NtAbs. G1 VP7 frequently induced a response to both G1 and G3 VP7s, while G3 VP7 and P1A VP4 induced mostly homotypic responses. C1 Univ Nacl Autonoma Mexico, Inst Biotechnol, Cuernavaca 62250, Morelos, Mexico. Univ Autonoma Nuevo Leon, Fac Ciencias Biol, Monterrey, Nuevo Leon, Mexico. Univ Autonoma Yucatan, Ctr Invest Reg Hideyo Noguchi, Merida, Yucatan, Mexico. Inst Mexicano Seguro Social, Mexico City, DF, Mexico. Hosp Infantil Mexico, Unidad Rehidratac Oral, Mexico City, DF, Mexico. Univ Autonoma San Luis Potosi, Fac Med, San Luis Potosi, Mexico. Childrens Hosp, Med Ctr, Div Clin Virol, Cincinnati, OH 45229 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Arias, CF (reprint author), Univ Nacl Autonoma Mexico, Inst Biotechnol, AP 510-3,Colonia Miraval, Cuernavaca 62250, Morelos, Mexico. NR 67 TC 9 Z9 10 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD MAY PY 1998 VL 5 IS 3 BP 328 EP 334 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZL785 UT WOS:000073471300013 PM 9605987 ER PT J AU Lenz, HJ Danenberg, KD Leichman, CG Florentine, B Johnston, PG Groshen, S Zhou, LY Xiong, YP Danenberg, PV Leichman, LP AF Lenz, HJ Danenberg, KD Leichman, CG Florentine, B Johnston, PG Groshen, S Zhou, LY Xiong, YP Danenberg, PV Leichman, LP TI p53 and thymidylate synthase expression in untreated stage II colon cancer: Associations with recurrence, survival, and site SO CLINICAL CANCER RESEARCH LA English DT Article ID FLUOROURACIL PLUS LEVAMISOLE; NEGATIVE BREAST-CANCER; PROGNOSTIC-SIGNIFICANCE; PROTEIN EXPRESSION; COLORECTAL-CANCER; ADJUVANT THERAPY; BLADDER-CANCER; GENE; ADENOCARCINOMA; OVEREXPRESSION AB We initiated a retrospective study to determine whether p53 status and thymidylate synthase (TS) protein expression in primary colon tumors influence recurrence and survival for patients with stage II colon cancer. Tumor specimens from 45 consecutive untreated patients with stage II colon cancer were examined for p53 and TS protein expression using immunohistochemistry. The median follow-up was 5.1 years. Eighteen patients had left-sided tumors, and 27 had right-sided tumors. Fourteen of 45 patients (31%) developed recurrence. p53 overexpression was detected in the tumors of 18 patients (40%); 10 patients (55%) with p53 overexpression recurred; and 4 of 27 (15%) without evidence of p53 overexpression recurred (P = 0.002), High TS expression was detected in the tumors of 16 patients (36%): 8 patients (50%) with high TS expression recurred, and 6 patients (21%) with low TS expression recurred (P = 0.027), Patients with p53 overexpression had a significantly poorer survival than did those patients without p53 overexpression (P < 0.001). High TS expression was associated with poor survival (P = 0.004), p53 overexpression and high TS expression were significantly associated with left-sided tumors (P = 0.003 and P = 0.022), Thirteen of 16 patients (81%) with high TS expression also overexpressed p53, and 24 of 29 patients (81%) with low TS expression did not manifest p53 overexpression (P < 0.001), p53 and TS expression in primary stage LI colon cancer are associated and appear to influence recurrence and survival. In this pilot study, left-sided tumors demonstrate significantly more p53 overexpression and significantly higher TS expression than do right-sided tumors, which may explain the significantly poorer survival for patients with left-sided tumors. C1 Univ So Calif, Norris Comprehens Canc Ctr, Canc Res Lab 218, Sch Med,Div Med Oncol, Los Angeles, CA 90033 USA. Univ So Calif, Norris Comprehens Canc Ctr, Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. Univ So Calif, Norris Comprehens Canc Ctr, Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA. Univ So Calif, Norris Comprehens Canc Ctr, Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. USN, NCI, Med Oncol Branch, Bethesda, MD 20089 USA. RP Lenz, HJ (reprint author), Univ So Calif, Norris Comprehens Canc Ctr, Canc Res Lab 218, Sch Med,Div Med Oncol, 1303 N Mission Rd, Los Angeles, CA 90033 USA. EM lenz@hsc.usc.edu FU NCI NIH HHS [CA-60108, CA-70802, P30CA14089] NR 42 TC 124 Z9 126 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 1998 VL 4 IS 5 BP 1227 EP 1234 PG 8 WC Oncology SC Oncology GA ZL982 UT WOS:000073493000018 PM 9607581 ER PT J AU Lianes, P Charytonowicz, E Cordon-Cardo, C Fradet, Y Grossman, HB Hemstreet, GP Waldman, FM Chew, K Wheeless, LL Faraggi, D AF Lianes, P Charytonowicz, E Cordon-Cardo, C Fradet, Y Grossman, HB Hemstreet, GP Waldman, FM Chew, K Wheeless, LL Faraggi, D CA Natl Canc Inst Bladder Tumor Marker Network TI Biomarker study of primary nonmetastatic versus metastatic invasive bladder cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID TRANSITIONAL-CELL CARCINOMA; P53 NUCLEAR OVEREXPRESSION; LYMPH-NODE METASTASES; FLOW-CYTOMETRY; GENETIC ALTERATIONS; TUMOR PROGRESSION; PROGNOSTIC VALUE; URINARY-BLADDER; ALLELIC LOSSES; ANGIOGENESIS AB A cohort of 109 patients with primary transitional cell carcinomas, stages T-2-T-3, grade 2 or higher, was identified and further divided into two groups based on lymphatic metastasis at the time of cystectomy (n = 57 cases) or absence of detectable metastatic disease over a minimum of 5 years of follow-up after cystectomy (n = 52). Blocks corresponding to the primary tumor lesions were sectioned and distributed to different laboratories to be analyzed, Immunohistochemistry on deparaffinized tissue sections was conducted for evaluation of p53 nuclear overexpression (monoclonal antibody PAb1801), assessment of proliferative index (Ki-67 antigen-monoclonal antibody MIB1), and microvascular counts (factor VIII-related antigen). DNA content/ploidy studies were performed on material obtained from thick sections. A double-blinded strategy was used for the evaluation of laboratory data versus clinical parameters. The cutoff value for p53 nuclear overexpression was greater than or equal to 20% of tumor cells displaying nuclear staining. The median values for MIB1 (greater than or equal to 18% of tumor nuclear cell staining) and microvascular counts (greater than or equal to 40 microvessels/area screened) were used as cutoff points for these two variables. The assessment of DNA content was conducted by classifying cases as diploid, tetraploid, or aneuploid, Statistical analyses were performed using the Fisher's Exact Test (2-tailed). Results revealed that none of the markers studied had a statistically significant correlation with the end point of the study, i.e., the presence of lymph node metastatic disease, in the cohort of patients studied, although an obvious trend for p53 was noted, It is concluded that alterations of p53, Ki-67 proliferative index, microvascular counts, and ploidy are not strongly associated with lymph node status in patients affected with high-stage, high-grade bladder cancer. C1 Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Univ Laval, Dept Urol, Laval, PQ G1R 2J6, Canada. Univ Texas, MD Anderson Cancer Ctr, Houston, TX 77030 USA. Univ Oklahoma, Dept Urol, Ctr Hlth Sci, Oklahoma City, OK 73104 USA. Univ Calif San Francisco, Div Mol Cytometry, San Francisco, CA 94143 USA. Univ Rochester, Dept Pathol, Rochester, NY 14642 USA. NCI, Div Canc Diag & Treatment, Bethesda, MD 20892 USA. RP Cordon-Cardo, C (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA. EM cordon-c@mskcc.org FU NCI NIH HHS [CA-47538, CA-56973, CA-47526] NR 30 TC 26 Z9 26 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 1998 VL 4 IS 5 BP 1267 EP 1271 PG 5 WC Oncology SC Oncology GA ZL982 UT WOS:000073493000023 PM 9607586 ER PT J AU Herrera, AH Xiang, LB Martin, SG Lewis, J Wilson, JG AF Herrera, AH Xiang, LB Martin, SG Lewis, J Wilson, JG TI Analysis of complement receptor type 1 (CRI) expression on erythrocytes and of CR1 allelic markers in Caucasian and African American populations SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article DE human; complement; cell surface molecules; molecular biology ID SYSTEMIC LUPUS-ERYTHEMATOSUS; HUMAN C3B/C4B RECEPTOR; FRAGMENT-LENGTH-POLYMORPHISM; IMMUNE-COMPLEXES BIND; C3B RECEPTOR; CR-1 GENE; CODING REGION; CLEARANCE; IDENTIFICATION; MEMBRANE AB CR1 expression on erythrocytes (E) is regulated by an element that is tightly linked in Caucasians to the site of an RFLP of the CR1 gene. Genomic HindIII fragments of 7.4 and 6.9 kb identify alleles that are expressed in high (H allele) or low (L allele) amounts, respectively. When age-fractionated E of donors heterozygous for both the H and L alleles and for CR1 allotypes of differing molecular weights were analyzed in Western blots, the product of the L allele appeared to have an increased rate of loss during cell aging A coding sequence polymorphism of CR1 predicted to cause a Pro --> Arg substitution in its proximal extramembranous region was tightly linked in Caucasians to the site of the HindIII RFLP. However, neither this polymorphism nor the HindlII RFLP correlated with CR1 expression among African Americans, Relative instability of CR1 encoded by the L allele thus may derive from another coding sequence polymorphism, or may require both the Pro --> Arg substitution and epistatic effects of another polymorphic gene. (C) 1998 Academic Press. C1 Vet Affairs Med Ctr, Dept Med, Jackson, MS 39216 USA. Univ Mississippi, Med Ctr, Dept Microbiol, Jackson, MS 39216 USA. Tougaloo Coll, Dept Biol, Tougaloo, MS 39174 USA. RP Herrera, AH (reprint author), NIAMSD, NIH, Bldg 6,Room 113,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 60 TC 48 Z9 53 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD MAY PY 1998 VL 87 IS 2 BP 176 EP 183 DI 10.1006/clin.1998.4529 PG 8 WC Immunology; Pathology SC Immunology; Pathology GA ZR487 UT WOS:000073982200010 PM 9614933 ER PT J AU O'Grady, NP Barie, PS Bartlett, JG Bleck, T Garvey, G Jacobi, J Linden, P Maki, DG Nam, M Pasculle, W Pasquale, MD Tribett, DL Masur, H AF O'Grady, NP Barie, PS Bartlett, JG Bleck, T Garvey, G Jacobi, J Linden, P Maki, DG Nam, M Pasculle, W Pasquale, MD Tribett, DL Masur, H TI Practice guidelines for evaluating new fever in critically ill adult patients SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID VENTILATOR-ASSOCIATED PNEUMONIA; CATHETER-RELATED INFECTION; PARA-NASAL SINUSITIS; INTENSIVE-CARE UNIT; CORE TEMPERATURE-MEASUREMENT; PROTECTED SPECIMEN BRUSH; SURGICAL WOUND-INFECTION; BLOOD CULTURES; CLOSTRIDIUM-DIFFICILE; NOSOCOMIAL INFECTIONS AB Objective: The development of practice guidelines for evaluating adult patients who develop new fever in the intensive care unit (ICU) for the purpose of guiding clinical practice. Participants: A task force of 13 experts in disciplines related to critical care medicine, infectious diseases. and surgery was convened from the membership of the Society of Critical Care Medicine and the infectious Disease Society of America. Evidence: The task force members provided personal experience and determined the published literature (articles retrieved with use of MEDLINE or textbooks) from which consensus would be sought. The published literature was reviewed and classified into one of four categories, according to study design and scientific value. Consensus process: The task force met several times in person and twice monthly by teleconference over a 1-year period to identify the pertinent literature and arrive at consensus recommendations. Consideration was given to the relationship between the weight of scientific evidence and the experts' opinions. Draft documents were composed and debated by the task force until consensus was reached by nominal group process. Conclusions: The panel concluded that because fever can have many infectious and noninfectious etiologies, a new fever in an adult patient in the ICU should trigger a careful clinical assessment rather than automatic orders for laboratory and radiological tests. A cost-conscious approach to obtaining diagnostic studies should be undertaken if they are indicated after a clinical evaluation. The goal of such an approach is to determine. in a directed manner, whether infection is present so that additional testing can be avoided and therapeutic options can be identified. C1 NIH, Bethesda, MD 20892 USA. Johns Hopkins Hosp, Baltimore, MD 21287 USA. St Agnes Hosp, Baltimore, MD USA. New York Hosp, New York, NY 10021 USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Univ Virginia, Charlottesville, VA USA. Infect Dis Physicians Inc, Annandale, VA USA. Methodist Hosp Indiana, Indianapolis, IN 46202 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Lehigh Valley Hosp, Allentown, PA USA. RP O'Grady, NP (reprint author), NIH, Bldg 10,Room 7D43,10 Ctr Dr MSC 1662, Bethesda, MD 20892 USA. NR 106 TC 59 Z9 60 U1 2 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY PY 1998 VL 26 IS 5 BP 1042 EP 1059 DI 10.1086/520308 PG 18 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZM239 UT WOS:000073518600003 PM 9597223 ER PT J AU El-Sadr, WM Perlman, DC Matts, JP Nelson, ET Cohn, DL Salomon, N Olibrice, M Medard, F Chirgwin, KD Mildvan, D Jones, BE Telzak, EE Klein, O Heifets, L Hafner, R AF El-Sadr, WM Perlman, DC Matts, JP Nelson, ET Cohn, DL Salomon, N Olibrice, M Medard, F Chirgwin, KD Mildvan, D Jones, BE Telzak, EE Klein, O Heifets, L Hafner, R CA Terry Beirn Community Programs Clinical Res AI TI Evaluation of an intensive intermittent-induction regimen and duration of short-course treatment for human immunodeficiency virus-related pulmonary tuberculosis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID MULTIDRUG-RESISTANT TUBERCULOSIS; SHORT-COURSE CHEMOTHERAPY; HIV-INFECTED PATIENTS; MYCOBACTERIUM-TUBERCULOSIS; CONTROLLED TRIAL; THERAPY; LEVOFLOXACIN; OFLOXACIN; CIPROFLOXACIN AB This study examined whether adding levofloxacin to a standard four-drug regimen improved the 8-week culture response and compared effectiveness of 9 versus 6 months of intermittent therapy for human immunodeficiency virus-related pansusceptible pulmonary tuberculosis. Patients were randomized to receive either four or five drugs, the fifth being levofloxacin, Patients who completed induction therapy were randomized to complete 9 versus 6 months of intermittent therapy with isoniazid and rifampin. In the randomized induction phase, 97.3% of patients in the four-drug group and 95.8% in the five-drug group had sputum culture conversion at 8 weeks (P = 1.00). In the continuation phase, one patient (2%) assigned to 9 months and two patients (3.9%) assigned to 6 months of therapy had treatment failure/relapse (P = 1.00), In conclusion, this study showed that levofloxacin added no benefit to a highly effective, largely intermittent, four-drug induction regimen; Both 9 and 6 months of intermittent therapy were associated with low treatment failure/relapse rates. C1 Columbia Univ, Coll Phys & Surg, Harlem Hosp Ctr, Div Infect Dis, New York, NY 10037 USA. Columbia Univ, Coll Phys & Surg, Harlem Hosp Ctr, Div Pulm Med, New York, NY 10037 USA. Beth Israel Med Ctr, Div Infect Dis, New York, NY 10003 USA. SUNY Hlth Sci Ctr, Div Infect Dis, Brooklyn, NY 11203 USA. Bronx Lebanon Hosp Ctr, Bronx, NY 10456 USA. Univ Minnesota, Sch Publ Hlth, Div Biostat, Ctr Stat, Minneapolis, MN 55455 USA. Denver Publ Hlth Dept, Denver CPCRA, Denver, CO USA. Natl Jewish Med & Res Ctr, Denver, CO USA. Univ So Calif, Med Ctr, Div Internal Med, Los Angeles, CA USA. NIAID, Div Aids, Washington, DC USA. RP El-Sadr, WM (reprint author), Columbia Univ, Coll Phys & Surg, Harlem Hosp Ctr, Div Infect Dis, MLK Pavilion,Room 3107,506 Lenox Ave, New York, NY 10037 USA. FU NIAID NIH HHS [U01 AI046370] NR 43 TC 86 Z9 89 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY PY 1998 VL 26 IS 5 BP 1148 EP 1158 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZM239 UT WOS:000073518600024 PM 9597244 ER PT J AU Rasmusson, DX Zonderman, AB Kawas, C Resnick, SM AF Rasmusson, DX Zonderman, AB Kawas, C Resnick, SM TI Effects of age and dementia on the trail making test SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article ID NEUROPSYCHOLOGICAL TESTS; NORMATIVE DATA; FRONTAL-LOBE; EDUCATION; BRAIN AB Trail Making Test (TMT) performance was investigated in 765 elderly volunteers (age range 60 to 96 years), 58 of whom met DSM-III-R criteria for dementia and 40 dementia "suspects," who showed mild changes in one or two cognitive domains. Cross-sectional analyses of the 667 nondemented participants, revealed significant age effects in completion times for both Parts A and B. Prevalence of errors increased with age on Part B, but not on Part A. Two-year longitudinal changes were examined in a subset of the nondemented sample (n = 385). Significant slowing was found for Part B, but not for Part A, with older age groups showing the greatest change. Error rates did not increase. Dementia status accounted for a significant proportion of the variance in completion times after accounting for age, education, and gender. Receiver operating characteristic analyses suggest that the TMT may be useful in screening for cognitive dysfunction. C1 NIA, Intramural Res Program, Gerontol Res Ctr, Lab Personal & Cognit, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD USA. RP Rasmusson, DX (reprint author), NIA, Intramural Res Program, Gerontol Res Ctr, Lab Personal & Cognit, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM xeno@mvx.grc.nia.nih.gov OI Zonderman, Alan B/0000-0002-6523-4778 NR 33 TC 32 Z9 33 U1 0 U2 4 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0920-1637 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD MAY PY 1998 VL 12 IS 2 BP 169 EP 178 PG 10 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 113VH UT WOS:000075574200005 ER PT J AU Litvan, I Paulsen, JS Cummings, J Mega, M AF Litvan, I Paulsen, JS Cummings, J Mega, M TI Neurobehavioral dissociations in movement disorders: Utility of the NPI SO CLINICAL NEUROPSYCHOLOGIST LA English DT Meeting Abstract C1 NINDS, MNB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0920-1637 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD MAY PY 1998 VL 12 IS 2 BP 280 EP 280 PG 1 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 113VH UT WOS:000075574200118 ER PT J AU Jeng, JJ Kallarakal, AT Kim, SF Popov, KM Song, BJ AF Jeng, JJ Kallarakal, AT Kim, SF Popov, KM Song, BJ TI Pyruvate dehydrogenase E1 alpha isoform in rat testis: cDNA cloning, characterization, and biochemical comparison of the recombinant testis and liver enzymes SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article DE rat testis; pyruvate dehydrogenase; tissue-specific isozyme; cDNA cloning; sequence variation; gene expression; recombinant protein characterization; phosphorylation ID MOLECULAR-CLONING; ESCHERICHIA-COLI; SUBUNIT GENES; EXPRESSION; COMPLEXES; KINASE; MOUSE; SEQUENCE; DEFICIENCY; COMPONENT AB Previous data indicated a tissue-specific regulation of mitochondrial pyruvate dehydrogenase (PDH) complex, especially in the brain and testis. The lack of biochemical data on the rat testis PDH limits comparative analysis between testis and liver enzymes. Therefore, we have isolated a cDNA clone encoding rat testis PDK E1 alpha isoform, determined its nucleotide sequence, studied the tissue-specific expression, and characterized the recombinant protein produced in bacteria, compared to the liver counterpart. Our cDNA clone (2.2 kb) contained the identical open reading frame (from nt 974 to 2149) with that previously reported (Cullingford et al., 1993 Biochim Biophys Acta 1216:149-153) but contained a long 5' untranslated region, which has little identity to the other clone. Northern blot confirmed testis-specific expression of this isoform. Genomic DNA analyses by PCR amplification suggested this clone is a gene product distinct from its X-linked somatic counterpart. Our biochemical and kinetic analyses revealed that the purified recombinant rat testis PDH EI (containing both E1 alpha and E1 beta subunits) was enzymatically active and phosphorylated in vitro by purified PDH-kinase p48 or p45, similar to the recombinant human liver enzyme. Our current data thus indicate that the differential regulation of testis PDH observed in the animal model may result from differential modulation of PDH-kinase or -phosphatase in this tissue rather than the presence of functionally different PDH E1subunit. (C) 1998 Elsevier Science Inc. All rights reserved. C1 NIAAA, Lab Membrane Biochem & Biophys, Rockville, MD 20852 USA. Indiana Univ, Sch Med, Dept Biochem, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Mol Biol, Indianapolis, IN 46202 USA. RP Song, BJ (reprint author), NIAAA, Lab Membrane Biochem & Biophys, 12501 Washington Ave, Rockville, MD 20852 USA. NR 44 TC 7 Z9 10 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0305-0491 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD MAY PY 1998 VL 120 IS 1 BP 205 EP 216 DI 10.1016/S0305-0491(98)10010-X PG 12 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA 116UA UT WOS:000075742200020 PM 9787790 ER PT J AU Freeman, BD Zeni, F Banks, SM Eichacker, PQ Bacher, JD Garvey, EP Tuttle, JV Jurgensen, CH Natanson, C Danner, RL AF Freeman, BD Zeni, F Banks, SM Eichacker, PQ Bacher, JD Garvey, EP Tuttle, JV Jurgensen, CH Natanson, C Danner, RL TI Response of the septic vasculature to prolonged vasopressor therapy with N-omega-monomethyl-L-arginine and epinephrine in canines SO CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT Meeting on Molecular Basis of Sepsis CY OCT 08-11, 1996 CL WOODS HOLE, MA DE nitric oxide; sepsis; septic shock; hemodynamics; endotoxin; tumor necrosis factor; epinephrine; survival ID NITRIC-OXIDE SYNTHASE; TUMOR-NECROSIS-FACTOR; METHYL-L-ARGININE; CARDIAC MYOCYTES; ENDOTOXIN-SHOCK; BLOOD-PRESSURE; FACTOR-ALPHA; CARDIOVASCULAR PERFORMANCE; BARORECEPTOR REFLEX; SYNTHESIS IMPROVES AB Objective: To investigate the effect of blocking nitric oxide production on cardiovascular function and survival in canine septic shock treated with or without a conventional vasopressor. Design: Randomized, controlled trial. Setting: An animal research laboratory at the National Institutes of Health. Subjects: Sixty purpose-bred beagles. Interventions: Fibrin clots containing Escherichia coli were surgically placed into the peritoneal cavity. N-omega-monomethyl-L-arginine (L-NMMA) 10 mg/kg followed by 0.5, 1.0, or 4.0 mg/kg/hr), epinephrine (1 mu g/kg/min), both, or neither were infused for 24 hrs beginning 6 hrs after the onset of infection. All animals received fluid and antibiotic therapy. Measurements and Main Results: Serum nitric oxide metabolites, nitrite and nitrate, increased with infection (p=.024) and decreased with L-NMMA (p=.004, all doses combined). Myocardial nitric oxide synthase activity was ranked as follows: nonsurvivors > survivors > noninfected controls (p < .01). Other tissues examined showed the same pattern. L-NMMA produced sustained increases in systemic vascular resistance index and mean arterial pressure 9 and 24 hrs after the onset of infection (p less than or equal to .04). Left ventricular ejection fraction was depressed by septic shock (p=.01) and further decreased by L-NMMA (p=.02). However, control and L-NMMA cardiac index values were similar (p>.4), perhaps because L-NMMA increased pulmonary artery occlusion pressure (p=.02). From 9 to 24 hrs, epinephrine, in the absence or presence of L-NMMA, blunted recovery of cardiac index (p<.02) and had a diminishing vasopressor effect (p=.05). Neither L-NMMA nor epinephrine, individually or combined, significantly altered survival rates at the doses investigated (p greater than or equal to .69). Conclusions: The tested doses showed that nitric oxide production was inhibited by L-NMMA in canine septic shock, but mortality and myocardial depression were unaffected. These results suggest that if L-NMMA has a beneficial effect on survival rates in septic shock, it is small. C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Surg Serv, Vet Resource Program, Bethesda, MD 20892 USA. Glaxo Wellcome Inc, Glaxo Wellcome Res Labs, Res Triangle Pk, NC 27709 USA. RP Danner, RL (reprint author), NIH, Dept Crit Care Med, Bldg 10,Room 7D43, Bethesda, MD 20892 USA. NR 76 TC 14 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 1998 VL 26 IS 5 BP 877 EP 886 DI 10.1097/00003246-199805000-00022 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA ZL791 UT WOS:000073471900018 PM 9590318 ER PT J AU Watson, ML Grix, SP Jordan, NJ Place, GA Dodd, S Leithead, J Poll, CT Yoshimura, T Westwick, J AF Watson, ML Grix, SP Jordan, NJ Place, GA Dodd, S Leithead, J Poll, CT Yoshimura, T Westwick, J TI Interleukin 8 and monocyte chemoattractant protein 1 production by cultured human airway smooth muscle cells SO CYTOKINE LA English DT Article DE airway smooth muscle; chemokines; IL-1; TNF ID TUMOR-NECROSIS-FACTOR; ALVEOLAR MACROPHAGES; GENE-EXPRESSION; RECOMBINANT CYTOKINES; ASTHMA; LUNG; ACCUMULATION; PATHOGENESIS; INTERFERON; INHIBITION AB Leukocyte accumulation and activation are key events in the pathogenesis of inflammatory lung disease. The ability of human airway smooth muscle cells (HASM) to contribute to the inflammatory process by its ability to produce the chemokines interleukin (IL) 8, monocyte chemotactic protein (MCP-1) and regulated on activation, normal T cell expressed and secreted (RANTES) was investigated. Cultured HASM, when stimulated with the pro-inflammatory cytokines IL-1 alpha (0.01-1 ng/ml) or tumour necrosis factor alpha(TNF-alpha, 0.3-30ng/ml), synthesize and release substantial amounts of IL-8, as assessed by specific immunoassay, bioasssay (elevation of intracellular free calcium in human nentrophils), and upregulation of mRNA. These stimuli also increased MCP-1 production and mRNA expression, but RANTES mRNA expression was not detected at 24 h. The smooth muscle spasmogen endothelin 1 (1 mu M) was unable to stimulate IL-8 or MCP-1 release or mRNA expression. These data indicate that HASM may constitute an important source of leukocyte attractants in the inflamed lung, where the inducing stimuli, IL-1 alpha and TNF-alpha, are also likely to be present. (C) Academic Press Limited. C1 Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England. Bayer PLC, Stoke Poges SL2 4LY, Bucks, England. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. RP Watson, ML (reprint author), Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England. RI Jordan, Nicola/B-3341-2013 FU Wellcome Trust NR 36 TC 35 Z9 37 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1043-4666 J9 CYTOKINE JI Cytokine PD MAY PY 1998 VL 10 IS 5 BP 346 EP 352 DI 10.1006/cyto.1997.0350 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA ZQ860 UT WOS:000073910300004 PM 9619372 ER PT J AU Kostrouchova, M Krause, M Kostrouch, Z Rall, JE AF Kostrouchova, M Krause, M Kostrouch, Z Rall, JE TI CHR3: a Caenorhabditis elegans orphan nuclear hormone receptor required for proper epidermal development and molting SO DEVELOPMENT LA English DT Article DE nuclear hormone receptor; Caenorhabditis elegans; molting; hormone response element; epidermis; CHR3 ID DNA-BINDING PROPERTIES; REV-ERBA-ALPHA; C-ELEGANS; COLLAGEN GENES; SUPERFAMILY MEMBERS; ECDYSONE RECEPTOR; CELL LINEAGE; ROR-ALPHA; FAMILY; EXPRESSION AB CHR3 is a Caenorhabditis elegans orphan nuclear hormone receptor highly homologous to Drosophila DHR3, an ecdysone-inducible gene product involved in metamorphosis, Related vertebrate factors include RORalpha/RZRalpha, RZRbeta and RevErb, Gel-shift studies show that CHR3 can bind the DRS-type hormone response sequence. CHR3 is a nuclear protein present in all blastomeres during early embryogenesis. During morphogenesis, both CHR3 protein and zygotically active reporter genes are detectable in epidermal cells and their precursors, Inhibition of the gene encoding CHR3 results in several larval defects associated with abnormal epidermal cell function, including molting and body size regulation, suggesting that CHR3 is an essential epidermal factor required for proper postembryonic development. C1 NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Krause, M (reprint author), NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. OI Krause, Michael/0000-0001-6127-3940 NR 73 TC 80 Z9 82 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 0950-1991 J9 DEVELOPMENT JI Development PD MAY PY 1998 VL 125 IS 9 BP 1617 EP 1626 PG 10 WC Developmental Biology SC Developmental Biology GA ZQ557 UT WOS:000073880000006 PM 9521900 ER PT J AU Takahashi, K Nuckolls, GH Tanaka, O Semba, I Takahashi, I Dashner, R Shum, L Slavkin, HC AF Takahashi, K Nuckolls, GH Tanaka, O Semba, I Takahashi, I Dashner, R Shum, L Slavkin, HC TI Adenovirus-mediated ectopic expression of Msx2 in even-numbered rhombomeres induces apoptotic elimination of cranial neural crest cells in ovo SO DEVELOPMENT LA English DT Article DE cranial neural crest; cell migration; chick; microinjection; fusion protein; whole mount immunostaining; explant culture; pattern formation; cell determination; craniofacial development ID BETA SIGNAL-TRANSDUCTION; CHICK-EMBRYO; DEATH; HINDBRAIN; MIGRATION; ORIGIN; IDENTIFICATION; EMBRYOGENESIS; GENERATION; RECEPTORS AB Distinct cranial neural crest-derived cell types (a number of neuronal as well as non-neuronal cell lineages) are generated at characteristic times and positions in the rhombomeres of the hindbrain in developing vertebrate embryos, To examine this developmental process, we developed a novel strategy designed to test the efficacy of gain-of-function Msx2 expression within rhombomeres in ovo prior to the emigration of cranial neural crest cells (CNCC), Previous studies indicate that CNCC from odd-numbered rhombomeres (r3 and r5) undergo apoptosis in response to exogenous BMP4. We provide evidence that targeted infection in ovo using adenovirus containing Msx2 and a reporter molecule indicative of translation can induce apoptosis in either even-or odd-numbered rhombomeres, Furthermore, infected lacZ-control explants indicated that CNCC emigrated, and that 20% of these cells were double positive for crest cell markers HNK-1 and P-gal, In contrast, there were no HNK-1 and Msx2 double positive cells emigrating from Msx2 infected explants, These results support the hypothesis that apoptotic elimination of CNCC can be induced by 'gain-of-function' Msx2 expression in even-numbered rhombomeres. These inductive interactions involve qualitative, quantitative, positional and temporal differences in TGF-beta-related signals, Msx2 expression and other transcriptional control. C1 NIAMSD, Craniofacial Dev Sect, NIH, Bethesda, MD 20892 USA. RP Takahashi, K (reprint author), NIAMSD, Craniofacial Dev Sect, NIH, Bethesda, MD 20892 USA. FU NIAMS NIH HHS [Z01-AR41114-02] NR 52 TC 44 Z9 45 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 0950-1991 J9 DEVELOPMENT JI Development PD MAY PY 1998 VL 125 IS 9 BP 1627 EP 1635 PG 9 WC Developmental Biology SC Developmental Biology GA ZQ557 UT WOS:000073880000007 PM 9521901 ER PT J AU Knezevic, V De Santo, R Mackem, S AF Knezevic, V De Santo, R Mackem, S TI Continuing organizer function during chick tail development SO DEVELOPMENT LA English DT Article DE gastrulation; tail organizer; neural induction; neural regionalization; Gnotl; Brachyury; T-box genes; chick embryo ID SECONDARY NEURULATION; NEURAL INDUCTION; PRIMITIVE STREAK; RETINOIC ACID; HOMEOBOX GENE; AVIAN EMBRYO; MOUSE; BUD; NODE; GASTRULATION AB Development of the posterior body (lumbosacral region and tail) in vertebrates is delayed relative to gastrulation. In amniotes, it proceeds with the replacement of the regressed node and primitive streak by a caudal blastema-like mass of mesenchyme known as the tail bud. Despite apparent morphological dissimilarities, recent results suggest that tail development in amniotes is in essence a continuation of gastrulation, as is the case in Xenopus. However, this has been inferred primarily from the outcome of fate mapping studies demonstrating discrete, regionalized cell populations in the tail bud, like those present at gastrulation, Our analysis of the tail bud distribution of several molecular markers that are expressed in specific spatial domains during chick gastrulation confirms these results. Furthermore, we present evidence that gastrulation-like ingression movements from the surface continue in the early chick tail bud and that the established tail bud retains organizer activity. This 'tail organizer' has the expected properties of being able to recruit uncommitted host cells into a new embryonic axis and induce host neural tissue with posteriorly regionalized gene expression when grafted to competent host cells that are otherwise destined to form only extra-embryonic tissue. Together, these results indicate that chick tail development is mechanistically continuous with gastrulation and that the developing tail in chick may serve as a useful experimental adjunct to investigate the molecular basis of inductive interactions operating-during gastrulation, considering that residual tail organizing activity is still present at a surprisingly late stage. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Mackem, S (reprint author), NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. FU NICHD NIH HHS [N01-HD-7-3263] NR 68 TC 55 Z9 56 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 0950-1991 J9 DEVELOPMENT JI Development PD MAY PY 1998 VL 125 IS 10 BP 1791 EP 1801 PG 11 WC Developmental Biology SC Developmental Biology GA ZT589 UT WOS:000074103000001 PM 9550712 ER PT J AU Kordon, EC Smith, GH AF Kordon, EC Smith, GH TI An entire functional mammary gland may comprise the progeny from a single cell SO DEVELOPMENT LA English DT Article DE stem cell; mammary; transplantation; mouse ID TUMOR VIRUS-DNA; IN-VIVO; MOUSE; INTEGRATION; MICE; EXPRESSION; TUMORIGENESIS; SEQUENCES; INT-3; GENES AB Any epithelial portion of a normal mouse mammary gland can reproduce an entire functional gland when transplanted into an epithelium-free mammary fat pad. Mouse mammary hyperplasias and tumors are clonal dominant populations and probably represent the progeny of a single transformed cell. Our study provides evidence that single multipotent stem cells positioned throughout the mature fully developed mammary gland have the capacity to produce sufficient differentiated progeny to recapitulate an entire functional gland. Our evidence also demonstrates that these stem cells are self-renewing and are found with undiminished capacities in the newly regenerated gland. We have taken advantage of an experimental model where mouse mammary tumor virus infects mammary epithelial cells and inserts a deoxyribonucleic acid copy(ies) of its genome during replication. The insertions occur randomly within the somatic genome. CzechII mice have no endogenous nucleic acid sequence homology with mouse mammary tumor virus; therefore all viral insertions may be detected by Southern analysis provided a sufficient number of cells contain a specific insertional event. Transplantation of random fragments of infected CzechII mammary gland produced clonal-dominant epithelial populations in epithelium-free mammary fat pads. Serial transplantation of pieces of the clonally derived outgrowths produced second generation glands possessing the same viral insertion sites providing evidence for self-renewal of the original stem cell. Limiting dilution studies with cell cultures derived from third generation clonal outgrowths demonstrated that three multipotent but distinct mammary epithelial progenitors were present in clonally derived mammary epithelial populations. Estimation of the potential number of multipotent epithelial cells that may be evolved from an individual mammary-specific stem cell by self-renewal is in the order of 10(12)-10(13). Therefore, one stem cell might easily account for the renewal of mammary epithelium over several transplant generations. C1 NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. RP Smith, GH (reprint author), NCI, Tumor Immunol & Biol Lab, Bldg 10,Room 8B07,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 32 TC 362 Z9 376 U1 2 U2 7 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD MAY PY 1998 VL 125 IS 10 BP 1921 EP 1930 PG 10 WC Developmental Biology SC Developmental Biology GA ZT589 UT WOS:000074103000013 PM 9550724 ER PT J AU Hastings, PD Grusec, JE AF Hastings, PD Grusec, JE TI Parenting goals as organizers of responses to parent-child disagreement SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID BEHAVIOR; SOCIALIZATION; ATTRIBUTION; STRATEGIES; MOTHERS; BELIEFS; AGE; DISCIPLINE; CONFLICT; OUTCOMES AB Parenting goals are outcomes that parents hope to achieve during interactions with children. Three studies involving 138 men (78 fathers) and 158 women (110 mothers) examined the causes and consequences of parents' focusing on various goals during disagreements with young children. Women were more likely than men to focus on relationship-centered (RC) goals, public situations increased concern for short-term parent-centered (PC) goals, and empathy was predictive of long term child-centered (CC) and RC goals. PC goals were associated with power assertion, CC goals with reasoning, and RC goals with warm, negotiating, and cooperative parenting behavior. Attributions of intentionality and dispositional causation were possible mediators of the link between power assertion and PC and CC goals. Instructions to focus on PC goals increased negative affective states and decreased sympathy for children, whereas instructions to focus on RC goals had the opposite effects. C1 Univ Toronto, Dept Psychol, Toronto, ON M5S 1A1, Canada. RP Hastings, PD (reprint author), NIMH, NIH, Bldg 15-K, Bethesda, MD 20892 USA. EM Paul_D_Hastings@nih.gov NR 43 TC 114 Z9 114 U1 3 U2 13 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD MAY PY 1998 VL 34 IS 3 BP 465 EP 479 DI 10.1037//0012-1649.34.3.465 PG 15 WC Psychology, Developmental SC Psychology GA ZM034 UT WOS:000073498100008 PM 9597357 ER PT J AU Imperatore, G Hanson, RL Pettitt, DJ Kobes, S Bennett, PH Knowler, WC AF Imperatore, G Hanson, RL Pettitt, DJ Kobes, S Bennett, PH Knowler, WC CA Pima Diabet Genes Grp TI Sib-pair linkage analysis for susceptibility genes for microvascular complications among Pima Indians with type 2 diabetes SO DIABETES LA English DT Article ID CONVERTING-ENZYME GENE; STAGE RENAL-DISEASE; ALDOSE REDUCTASE GENE; PROLIFERATIVE RETINOPATHY; ANGIOTENSINOGEN GENE; URINE SAMPLES; IDDM PATIENTS; RISK-FACTORS; HUMAN GENOME; NEPHROPATHY AB The aim of this study was to identify loci influencing susceptibility to microvascular complications (nephropathy and retinopathy) in Pima Indians with type 2 diabetes. Affected sib-pair linkage analyses were performed on 98 diabetic sibling pairs with nephropathy in both members and on 103 sibling pairs with retinopathy in both members. Four chromosomal regions with some evidence of linkage (P < 0.01; logarithm of odds [LOD] > 1.18) with nephropathy were identified. The strongest evidence for linkage with nephropathy was on chromosome 7, where two adjacent markers, D7S500 and D7S1804, were linked both by two-point analysis (LOD = 2.73 and LOD = 2.28; respectively) and by multipoint analysis (LOD = 2.04). Additional loci potentially linked to nephropathy were found on chromosome 3, near D3S3053 (multipoint LOD = 1.48); on chromosome 9, near D9S910 (multipoint LOD = 1.12) and D9S302 (two-point LOD = 1.28); and on chromosome 20, near D20S115 (multipoint LOD = 1.83) and GATA65E01 (two-point LOD 1.89). Multipoint analyses showed two regions with some evidence for linkage to retinopathy: chromosome 3 between D3S3053 and D3S2427 (LOD = 1.36), and chromosome 9 between D9S1120 and D9S910 (LOD 1.46). These linkage analyses suggest that a genetic element on chromosome 7 and possibly one on chromosome 20 influence susceptibility to diabetic nephropathy but not retinopathy. Genetic elements on chromosome 3 and 9 may determine susceptibility to both these complications. These loci could presumably influence susceptibility to the complications by influencing the microvasculature directly, by influencing the severity of hyperglycemia, or by other unknown mechanisms. C1 NIDDKD, Diabet & Arthrit Epidemiol Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85014 USA. RP Imperatore, G (reprint author), NIDDKD, Diabet & Arthrit Epidemiol Sect, Phoenix Epidemiol & Clin Res Branch, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU NCRR NIH HHS [1 P41 RR03655] NR 75 TC 234 Z9 255 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 1998 VL 47 IS 5 BP 821 EP 830 DI 10.2337/diabetes.47.5.821 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZL168 UT WOS:000073405600017 PM 9588456 ER PT J AU Tack, CJJ Ong, MKE Lutterman, JA Smits, P AF Tack, CJJ Ong, MKE Lutterman, JA Smits, P TI Insulin-induced vasodilatation and endothelial function in obesity/insulin resistance. Effects of troglitazone SO DIABETOLOGIA LA English DT Article DE insulin resistance; troglitazone; insulin sensitisers; vasodilatation; obesity; endothelial function ID DEPENDENT DIABETES-MELLITUS; MUSCLE BLOOD-FLOW; SYMPATHETIC NEURAL ACTIVATION; HYPOGLYCEMIC AGENT CS-045; SKELETAL-MUSCLE; NITRIC-OXIDE; GLUCOSE-UPTAKE; HUMANS; SENSITIVITY; NIDDM AB Insulin resistance is associated with a decreased vasodilator response to insulin. Because insulin's vasodilator effect is nitric oxide dependent, this impairment may reflect endothelial dysfunction. Troglitazone, an insulin-sensitiser, might thus improve insulin-dependent and/or endothelium-dependent vascular function in insulin resistant obese subjects. For 8 weeks, fifteen obese subjects were treated with either 400 mg troglitazone once daily or placebo, in a randomised, double-blind, cross-over design. At the end of each treatment period, we measured forearm vasodilator responses (plethysmography) to intra-arterial administered acetylcholine and sodium nitroprusside; insulin sensitivity and insulin-induced vascular and neurohumoral responses (clamp); vasoconstrictor responses to N-G-monomethyl-L-arginine (L-NMMA) during hyperinsulinaemia; and ambulatory 24-h blood pressure (ABPM). Baseline data (placebo) of obese subjects were compared with those obtained in lean control subjects. Obese subjects were insulin resistant compared with leans (whole-body glucose uptake: 26.8 +/- 3.0 vs. 53.9 +/- 4.3 mu mol.kg(-1).min(-1), p < 0.001). Troglitazone improved whole-body glucose uptake (to 31.9 +/- 3.3 mu mol.kg(-1).min(-1), p = 0.028), and forearm glucose uptake (from 1.09 +/- 0.54 to 2.31 +/- 0.69 mu mol.dL(-1).min(-1), p = 0.006). Insulin-induced vasodilatation was blunted in obese subjects (percent increase in forearm blood flow (FBF) in lean 66.5 +/- 23.0%, vs. 10.1 +/- 11.3 % in obese, p = 0.04), but did not improve during troglitazone. Vascular responses to acetylcholine, sodium nitroprusside and L-NMMA did not differ between the obese and lean group, nor between both treatment periods in the obese individuals. In conclusion, in insulin resistant obese subjects, endothelial vascular function is normal despite impaired vasodilator responses to insulin. Troglitazone improved insulin sensitivity but it had no effects on endothelium-dependent and-independent vascular responses. These data do not support an association between insulin resistance and endothelial function. C1 Univ Nijmegen Hosp, Dept Internal Med, Div Gen Internal Med, NL-6500 HB Nijmegen, Netherlands. Univ Nijmegen Hosp, Dept Pharmacol, NL-6500 HB Nijmegen, Netherlands. RP Tack, CJJ (reprint author), NINDS, Clin Neurosci Branch, NIH, Bldg 10,Room 6N252,9000 Rockville Pike MSC-1424, Bethesda, MD 20892 USA. RI Tack, Cees/A-2368-2014 NR 39 TC 142 Z9 148 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD MAY PY 1998 VL 41 IS 5 BP 569 EP 576 DI 10.1007/s001250050948 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZM524 UT WOS:000073548800012 PM 9628275 ER PT J AU Yajima, S Lee, SH Minowa, T Mouradian, MM AF Yajima, S Lee, SH Minowa, T Mouradian, MM TI Sp family transcription factors regulate expression of rat D-2 dopamine receptor gene SO DNA AND CELL BIOLOGY LA English DT Article ID BOX-BINDING-PROTEINS; ACTIVATION DOMAINS; MOLECULAR-CLONING; PROMOTER REGION; MEMBERS; CELLS; D1; TRANSACTIVATION; SEQUENCE; AFFINITY AB The rat D-2 dopamine receptor gene is transcribed from a TATA-less promoter that has an initiator-like sequence and several putative Sp1 binding sites. We previously reported that a negative modulator is located between nucleotides -116 and -76 (D(2)Neg-B) in this gene and that Sp1 as well as another unknown factor bind to this region (Minowa et al., J. Biol. Chem. 269, 11656, 1994). In the present investigation employing the in situ filter detection method, we identified this factor as Sp3, Anti-Sp3 antiserum used in gel-shift assays also revealed that Sp3 binds to the D(2)Neg-B sequence. Cotransfection of Drosophila Schneider's SL2 cells with Sp3 or Sp1 expression plasmids in the presence of CAT reporter plasmids containing D-2 promoter regions demonstrated that Sp1 increased CAT activity in a dose-dependent manner, whereas Sp3, either alone or in the presence of Sp1, failed to activate or repress transcription. On the other hand, using the TATA-containing reporter plasmid BCAT-2, Sp3 coexpression significantly repressed Sp1-induced trans-activation, although Sp3 alone was ineffective. Thus, the transcriptional activity of Sp3 is dependent on the promoter context, and the negative regulation of D-2 gene expression appears quite complex and mag not depend simply an known DNA-protein interactions involving only Sp1 and Sp3. C1 NINDS, Expt Therapeut Branch, Genet Pharmacol Unit, NIH, Bethesda, MD 20892 USA. RP Mouradian, MM (reprint author), Bldg 10,Room 5C116,10 Ctr Dr MSC 1406, Bethesda, MD 20892 USA. NR 48 TC 31 Z9 33 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD MAY PY 1998 VL 17 IS 5 BP 471 EP 479 DI 10.1089/dna.1998.17.471 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA ZT236 UT WOS:000074064300008 PM 9628590 ER PT J AU Gasior, M Beekman, M Carter, RB Goldberg, SR Witkin, JM AF Gasior, M Beekman, M Carter, RB Goldberg, SR Witkin, JM TI Antiepileptogenic effects of the novel synthetic neuroactive steroid, ganaxolone, against pentylenetetrazol-induced kindled seizures: Comparison with diazepam and valproate SO DRUG DEVELOPMENT RESEARCH LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the American-Epilepsy-Society CY DEC 05-10, 1997 CL BOSTON, MASSACHUSETTS SP Amer Epilepsy Soc DE neuroactive steroids; antiepileptic drugs; kindling; convulsions; epilepsy; locomotor activity ID NMDA-RECEPTOR ANTAGONIST; GAMMA-AMINOBUTYRIC-ACID; CHLORIDE IONOPHORE; CHILDHOOD EPILEPSY; ANIMAL-MODELS; ANTICONVULSANT; NEUROSTEROIDS; GABA; COMPLEX; DRUGS AB Pharmacological treatment of epilepsy is often unsatisfactory due to side effects and the lack of drugs that control the progressive epileptogenic process. Modulation of inhibitory gamma-aminobutyric acid (GABA)-ergic neurotransmission by synthetic agonists of the neuroactive steroid binding site on the GABAA receptor complex is one approach toward the identification of improved antiepileptic agents. In this study, antiepileptogenic and anticonvulsive effects of the novel synthetic neuroactive steroid, ganaxolone (3 alpha-hydroxy-3 beta-methyl-5 alpha-piegnan-20-one) were evaluated in comparison with diazepam and valproate against pentylenetetrazol (PTZ)-induced kindled seizures in mice. Kindled seizures provide a model of the progressive epileptogenic process. Successive administration of 45 mg/kg PTZ on days 1, 3, 5, 8, and 10 resulted in the rapid development of kindled seizures and significant reductions in thresholds for clonic convulsions, tonic convulsions, and lethality induced by PTZ on day 10. Ganaxolone, diazepam, and valproate dose-dependently protected against clonic convulsions induced by acute submaximal dose of PTZ (70 mg/kg). The compounds also dose-dependently suppressed fully kindled seizures and blocked the expression of kindled seizures over successive treatments with PTZ (45 mg/kg). Relative to acute anticonvulsive potencies against 70 mg/kg PTZ, however, ganaxolone was more potent than valproate or diazepam against fully kindled seizures and in blocking the expression of kindled seizures over successive treatments with PTZ. Importantly, only ganaxolone demonstrated antiepileptogenic activity by blocking the development of kindling, as evidenced when PTZ was administered in the absence of anticonvulsant treatments. Both diazepam and valproate failed to prevent development of kindled seizures even at doses that fully suppressed motor expression of seizures during kindling acquisition.Unlike diazepam and valproate, ganaxolone did not impair ambulatory activity within the dose range used in this study. These data, taken in conjunction with other findings on the unique pharmacological actions of ganaxolone, predict an improvement in the pharmacological management of epilepsy with this synthetic neuroactive steroid. (C) 1998 Wiley-Liss, Inc. C1 NIDA, Drug Dev Grp, Preclin Pharmacol Lab, Addict Res Ctr,NIH, Baltimore, MD 21224 USA. Univ Groningen, Ctr Pharm, Dept Med Chem, NL-9713 AW Groningen, Netherlands. CoCensys Inc, Dept Pharmacol, Irvine, CA USA. RP Gasior, M (reprint author), NIDA, Drug Dev Grp, Preclin Pharmacol Lab, Addict Res Ctr,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mgasior@irp.nida.nih.gov NR 54 TC 9 Z9 9 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 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD MAY PY 1998 VL 44 IS 1 BP 21 EP 33 DI 10.1002/(SICI)1098-2299(199805)44:1<21::AID-DDR4>3.0.CO;2-R PG 13 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 112BT UT WOS:000075474800004 ER PT J AU Nakatsuka, M Nakatsuka, K Osawa, Y AF Nakatsuka, M Nakatsuka, K Osawa, Y TI Metabolism-based inactivation of penile nitric oxide synthase activity by guanabenz SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID METHYL-L-ARGININE; IRREVERSIBLE INHIBITION; CYTOCHROME-P-450 HEME; CORPUS CAVERNOSUM; BRAIN; LIVER; RAT; MACROPHAGE; PHENCYCLIDINE; DEGRADATION AB Guanabenz (Wytensin) was shown to inactivate nitric oxide synthase (NOS) activity in vitro and in vivo. In in vitro studies with the use of a cytosolic fraction from penile tissue, the inactivation was found to depend on NADPH, time, and the concentration of guanabenz. The L-, but not the D-, isomer of arginine could protect from the inactivation, suggesting an active site-directed event. The kinetics of inactivation could be described by an apparent dissociation constant for the initial reversible complex (K-i) and a pseudo first-order inactivation constant (k(intact)) of 38.5 mu M and 0.179 min(-1), respectively. In in vivo studies, guanabenz was shown to inhibit penile cytosolic NOS activity in a dose-and time-dependent manner. Treatment of rats with guanabenz (5 mg/kg/day) for 4 days caused a decrease of approximately one-half in the NOS activity of the penile cytosolic fraction with a concomitant loss in the amount of immunodetectable NOS protein. Treatment for 4 days at a dose of 0.5 mg/kg/day showed a similar decrease in activity, whereas a dose of 0.05 mg/kg/day showed no effects. Due to the multitude of processes that are regulated by NO, the inactivation of NOS is a potential mechanism to be considered in a variety of biological effects associated with drugs. C1 Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. NHLBI, Lab Mol Immunol, NIH, Bethesda, MD USA. RP Osawa, Y (reprint author), Univ Michigan, Sch Med, Dept Pharmacol, 1301 Med Sci Res Bldg 3,1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA. FU NIEHS NIH HHS [ES08365] NR 40 TC 25 Z9 26 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD MAY PY 1998 VL 26 IS 5 BP 497 EP 501 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZM966 UT WOS:000073594400015 PM 9571232 ER PT J AU Siegel, H Frei, K Greenfield, J Schiffmann, R Sato, S AF Siegel, H Frei, K Greenfield, J Schiffmann, R Sato, S TI Electroencephalographic findings in patients with mucolipidosis type IV SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE mucolipidosis; spike; synchrony; background; EEG; seizure ID NATURAL-HISTORY AB Objective: To describe the electroencephalographic findings in mucolipidosis type IV (ML IV), a lysosomal storage disease of unknown etiology characterized clinically by corneal clouding, retinal degeneration and severe psychomotor retardation. Most patients are of Ashkenazi-Jewish ancestry. The EEG findings in this syndrome have not been characterized. Methods: We analyzed the EEGs of 10 patients with the diagnosis of ML IV, aged between of 2.5 and 21 years. All patients had 21 channel recordings in the international 10/20 system without sedation. Results: Six of the 10 patients had slowing of the background in the theta frequency range, and 4 had excessive beta frequency activity without the administration of medications. Two patients were able to reach stage 2 sleep, and were noted to have both synchronous and asynchronous spindles and vertex waves. Of the 10 patients, 6 had epileptiform spikes, all of which were noted frequently. The location of the spikes varied, from the frontal and temporal regions to the central regions, although location was consistent in each patient. Only one patient with epileptiform spikes had a history of clinical seizures. None of the other patients had a history of seizures. Conclusions: These findings imply that epileptiform discharges are common in patients with ML IV, but are infrequently associated with clinical seizures. (C) 1998 Elsevier Science Ireland Ltd. C1 NINDS, EEG Sect, NIH, Bethesda, MD 20892 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Siegel, H (reprint author), NINDS, EEG Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 11 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0013-4694 J9 ELECTROEN CLIN NEURO JI Electroencephalogr. Clin. Neurophysiol. PD MAY PY 1998 VL 106 IS 5 BP 400 EP 403 DI 10.1016/S0013-4694(98)00013-3 PG 4 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA ZR304 UT WOS:000073960700003 PM 9680151 ER PT J AU Latour, S Zhang, J Siraganian, RP Veillette, A AF Latour, S Zhang, J Siraganian, RP Veillette, A TI A unique insert in the linker domain of Syk is necessary for its function in immunoreceptor signalling SO EMBO JOURNAL LA English DT Article DE linker; hemopoietic cells; Syk; tyrosine protein kinase ID PROTEIN-TYROSINE KINASE; CELL ANTIGEN RECEPTOR; MOLECULAR-CLONING; ZAP-70; ACTIVATION; TCR; PHOSPHORYLATION; PROTEOLYSIS; P72(SYK); BINDING AB Accumulating data indicate that the 'linker' region of Syk, which lies between its tandem Src homology 2 (SH2) domains and kinase region, provides a critical function for the biological activity of Syk, This importance has been ascribed to the presence of tyrosine phosphorylation sites capable of mediating the recruitment of cellular effecters, We and others previously identified an alternatively spliced variant of Syk, termed SykB, which lacks a 23 amino acid sequence in the linker domain, As this 'linker insert' is also not present in the closely related enzyme Zap-70, it seems plausible that Syk possesses this unique sequence for functional reasons, To understand its role better, we have compared the abilities of Syk and SykB to participate in immunoreceptor-triggered signal transduction, The results of our experiments revealed that, unlike Syk, SykB was inefficient at coupling stimulation of Fc epsilon RI on basophils or the antigen receptor on T cells to the early and late events of cellular activation, Further studies showed that the functional defect in SykB was not caused by the absence of crucial tyrosine phosphorylation sites, or by a reduced intrinsic kinase activity, Rather, it correlated with the reduced ability of SykB to bind phosphorylated immunoreceptor tyrosine-based activation moths (ITAMs) in vitro and in viva. In combination, these results demonstrated that the unique insert in the linker domain of Syk is crucial for its capacity to participate in immunoreceptor signalling. Furthermore, they provided evidence that the linker region can regulate the ability of Syk to hind ITAMs, thus identifying a novel function for this domain. C1 McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada. McGill Univ, Dept Med, Montreal, PQ H3G 1Y6, Canada. McGill Univ, Dept Oncol, Montreal, PQ H3G 1Y6, Canada. McGill Univ, McGill Canc Ctr, Montreal, PQ H3G 1Y6, Canada. Montreal Gen Hosp, Dept Med, Montreal, PQ H3G 1A4, Canada. Montreal Gen Hosp, Dept Oncol, Montreal, PQ H3G 1A4, Canada. NIDR, Receptors & Signal Transduct Sect, OIIB, NIH, Bethesda, MD 20892 USA. RP Veillette, A (reprint author), McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada. EM veillette@medcor.mcgill.ca NR 42 TC 57 Z9 60 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 1 PY 1998 VL 17 IS 9 BP 2584 EP 2595 DI 10.1093/emboj/17.9.2584 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZN307 UT WOS:000073632800014 PM 9564041 ER PT J AU Balducci-Silano, PL Suzuki, K Ohta, M Saito, J Ohmori, M Montani, V Napolitano, G Shong, M Taniguchi, SI Pietrarelli, M Lavaroni, S Mori, A Singer, DS Kohn, LD AF Balducci-Silano, PL Suzuki, K Ohta, M Saito, J Ohmori, M Montani, V Napolitano, G Shong, M Taniguchi, SI Pietrarelli, M Lavaroni, S Mori, A Singer, DS Kohn, LD TI Regulation of major histocompatibility (MHC) class II human leukocyte antigen-DR alpha gene expression in thyrocytes by single strand binding protein-1, a transcription factor that also regulates thyrotropin receptor and MHC class I gene expression SO ENDOCRINOLOGY LA English DT Article ID COMPLEX CLASS-I; AUTOIMMUNE THYROID-DISEASE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CAMP RESPONSE ELEMENT; Y-BOX PROTEIN; PRESENTING CELLS; MAMMALIAN-CELLS; FRTL-5 CELLS; PROMOTER; INTERFERON AB The single strand binding protein (SSBP-1) is a positive regulator of TSH receptor gene expression and binds to an element with a GXXXXG motif The S box of the mouse major histocompatibility class II: gene has multiple GXXXXG motifs and can also bind SSBP-1. The S box is one of four highly conserved elements on the 5'-flanking region of class II genes that are necessary for interferon-gamma (IFN gamma) to overcome the normally suppressed state of the gene and induce aberrant class II expression. In this report are show that SSBP-1, when overexpressed in FRTL-5 thyroid cells, is a positive regulator of human leukocyte antigen (HLA)-DR alpha class II gene expression, as is IFN gamma or the class II trans-activator (CIITA). This is evidenced by increased exogenous promoter activity, increased endogenous RNA levels, and increased endogenous antigen expression after transfecting full-length SSBP-1 complementary DNA together with a HLA-DR alpha promoter-reporter gene chimera into TSH-treated FRTL-5 thyroid cells whose endogenous SSBP-1 levels are low. IFN gamma reverses the ability of TSH to decrease endogenous SSBP-1 RNA levels. Also, whereas SSBP-1 transfection does not cause any increase in IFN?induced exogenous promoter activity;, transfection of SSBP-1 and CIITA additively increases endogenous class II RNA levels to levels measured in cells treated with IFN gamma. Further, competition studies show that SSBP-1 binding is necessary for format-ion of the double strand protein/ DNA complexes that are seen in electrophoretic mobility shift assays when the class II 5'-flanking region is incubated with extracts from IFN gamma-treated FRTL-5 cells and that have been previously associated with IFN gamma-induced aberrant class II expression. These data suggest that SSBP-1 is involved in the action of IFN gamma to overcome the normally suppressed state of the class II gene; it functions together with CIITA, whose expression is independently increased by IFN gamma. The effect of SSBP-1 as a positive regulator of class II promoter activity is lost in cells maintained without TSH, in which endogenous SSBP-1 RNA levels are already high in the absence of aberrant class LI gene expression. These data suggest that high levels of endogenous SSBP-1 are insufficient to cause aberrant class II expression, but, rather, TSH or IFN gamma treatment additionally modulates the cell, albeit differently, such that transfected or endogenous SSBP-1, respectively, can express its positive regulatory activity. The effect of TSH is consistent with reports indicating that TSH enhances the ability of IFN gamma to increase class II gene expression despite the fact IFN gamma increases endogenous SSBP-1 to only the same levels as in cells untreated with TSH. Finally, the effect of SSBP-1 as a positive regulator is lost when GXXXXG motifs, which exist on both the coding and noncoding strands of the S box, are mutated. Consistent with this, mutation and oligonucleotide competition studies show that GXXXXG motifs are necessary for either strand of the S box to bind protein/DNA complexes containing SSBP-1. in FRTL-5 cell extracts or to bind to recombinant SSBP-1. They also suggest that the SSBP-1-binding sites on either strand of the HLA-DR alpha S box are functionally distinct. We conclude from these data that the positive regulatory action of SSBP-1 on class LT gene expression involves GXXXXG motifs on each strand of the highly conserved S box of the class II 5'-flanking region. As SSBP-1 is modulated by IFN gamma and is involved in class I and TSH receptor as iveII as class Il gene expression in FRTL-5 cells, the sum of the data supports the hypotheses that common transcription factors regulate all three genes, and their altered activities may contribute to the development of autoimmunity. C1 NIDDKD, Metab Dis Branch, Cell Regulat Sect, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Kohn, LD (reprint author), NIDDKD, Metab Dis Branch, Cell Regulat Sect, NIH, Bldg 10,Room 9C101B, Bethesda, MD 20892 USA. EM lenk@bdg10.niddk.nih.gov NR 66 TC 13 Z9 14 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 1998 VL 139 IS 5 BP 2300 EP 2313 DI 10.1210/en.139.5.2300 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZK821 UT WOS:000073367100017 PM 9564838 ER PT J AU Landi, MT Consonni, D Patterson, DG Needham, LL Lucier, G Brambilla, P Cazzaniga, MA Mocarelli, P Pesatori, AC Bertazzi, PA Caporaso, NE AF Landi, MT Consonni, D Patterson, DG Needham, LL Lucier, G Brambilla, P Cazzaniga, MA Mocarelli, P Pesatori, AC Bertazzi, PA Caporaso, NE TI 2,3,7,8-tetrachlorodibenzo-p-dioxin plasma levels in seveso 20 years after the accident SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE accident; dioxin; fat; gender; hormones; TCCD ID HIGHER CHLORINATED DIOXINS; SOFT-TISSUE SARCOMA; CANCER MORTALITY; POTENTIAL EXPOSURE; CHEMICAL WORKERS; TUMOR PROMOTION; 2,3,7,8-TCDD; SERUM; HERBICIDES; VIETNAM AB In 1976, near Seveso, Italy, an industrial accident caused the release of large quantities of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) into the atmosphere, resulting in the highest levels of the toxicant ever recorded in humans. The contaminated area was divided into three zones (A, B, R) corresponding to decreasing TCDD level in soil, and a cohort including all residents was enumerated The population of the surrounding noncontaminated area (non-ABR) was chosen as referent population Two decades after the accident, plasma TCDD level were measured in 62 subjects randomly sampled from the highest exposed zones (A and B) and 59 subjects from non-ABR, frequency matched for age, gender, and cigarette smoking status. Subjects living in the exposed areas have persistently elevated plasma TCDD level (range = 1.2-89.9 ppt; geometric mean = 53.2 and 11.0 ppt for Zone A and Zone B, respectively). Levels significantly decrease by distance from the accident sim (p = 0.0001), down to general population values (4.9 ppt) in non-ABR, thus validating the original zone classification based on environmental measurements. Women have higher TCDD levels than men in the entire study area (p = 0.0003 in Zone B; p = 0.007 in non-ABR). This gender difference persists after adjustment for location within the zone, consumption of meat derived from locally raised animals, age, body mass index, and smoking. There is no evidence for a gender difference in exposure, so variation in metabolism or elimination due to body fat or hormone-related factors may explain this finding. Elevated TCDD levels in women may contribute to adverse reproductive, developmental, and cancer outcomes. C1 NCI, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. Univ Milan, Epidemiol Res Ctr, EPOCA, I-20122 Milan, Italy. Ist Clin Perfezionamento, Inst Occupat Hlth, Milan, Italy. Ctr Dis Control & Prevent, Atlanta, GA 30341 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Milan, Desio Hosp, Milan, Italy. RP Landi, MT (reprint author), NCI, Genet Epidemiol Branch, NIH, EPN 400A,6130 Execut Blvd, Bethesda, MD 20892 USA. RI Needham, Larry/E-4930-2011; bertazzi, pietro alberto/D-5039-2017; OI bertazzi, pietro alberto/0000-0003-3475-2449; pesatori, angela/0000-0002-0261-3252 NR 43 TC 55 Z9 57 U1 0 U2 2 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 1998 VL 106 IS 5 BP 273 EP 277 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 111UX UT WOS:000075457600021 PM 9520360 ER PT J AU Hatch, EE Linet, MS Kleinerman, RA Tarone, RE Severson, RK Hartsock, CT Haines, C Kaune, WT Friedman, D Robison, LL Wacholder, S AF Hatch, EE Linet, MS Kleinerman, RA Tarone, RE Severson, RK Hartsock, CT Haines, C Kaune, WT Friedman, D Robison, LL Wacholder, S TI Association between childhood acute lymphoblastic leukemia and use of electrical appliances during pregnancy and childhood SO EPIDEMIOLOGY LA English DT Article DE magnetic fields; appliances; leukemia; childhood; case-control study ID FREQUENCY MAGNETIC-FIELDS; CONTROL SELECTION; CANCER; EXPOSURE; CHILDREN; BLANKETS; RISK AB As part of a comprehensive study of residential magnetic field exposure in nine midwestern and mid-Atlantic stares, we evaluated the use of appliances by 640 patients with acme lymphoblastic leukemia, 0-14 years of age, diagnosed between 1989 and 1993, and 640 matched control children, Mothers were interviewed regarding use of electrical appliances during their pregnancy with the subject and the child's postnatal use, The risk of acute lymphoblastic leukemia was elevated in children whose mothers reported use of an electric blanket or mattress pad during pregnancy [odds ratio (OR) = 1.59; 95%;; confidence interval (CI) = 1.11-2.29] but was reduced for use of sewing machines during pregnancy (OR = 0.76; 95% CI = 0.59-0.98), The risk of acute lymphoblastic leukemia was increased with children's use of electric blankets or mattress Fads (OR = 2.75; 95% CI = 1.52-4.98) and three other electrical appliances (hair dryers, video machines in arcades, and video games connected to a television), but the patterns of risk for duration in years of use and frequency of use were inconsistent for most appliances used by children, Risks rose viith increasing number of hours per day children spent watching television, but risks were similar regardless of the usual distance from the television The inconsistency; in the dose-response patterns far many appliances, reporting and selection bias, and the lack of an effect for measured 60 Hertz. magnetic fields or wire codes in our companion study must be considered before ascribing these associations to exposures from magnetic fields. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Minnesota, Sch Med, Div Pediat Epidemiol & Clin Res, Minneapolis, MN 55455 USA. Informat Management Syst Inc, Rockville, MD USA. Westat Inc, Rockville, MD USA. EM Factors, Richland, WA USA. RP Hatch, EE (reprint author), NCI, Div Canc Epidemiol & Genet, 6130 Execut Blvd,MSC7362, Bethesda, MD 20892 USA. OI Kleinerman, Ruth/0000-0001-7415-2478 FU NCI NIH HHS [N01-CP-95608, R01 CA48051] NR 30 TC 42 Z9 46 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 1998 VL 9 IS 3 BP 234 EP 245 DI 10.1097/00001648-199805000-00006 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZJ384 UT WOS:000073209400006 PM 9583414 ER PT J AU Mace, K Bowman, ED Vautravers, P Shields, PG Harris, CC Pfeifer, AMA AF Mace, K Bowman, ED Vautravers, P Shields, PG Harris, CC Pfeifer, AMA TI Characterisation of xenobiotic-metabolising enzyme expression in human bronchial mucosa and peripheral lung tissues SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE cytochrome P450; phase I enzymes; phase II enzymes; gene expression; lung; carcinogens ID PULMONARY CARCINOMAS; HUMAN-LIVER; CELL-LINE; CANCER; CYTOCHROMES-P450; GENE AB The human respiratory epithelium is in direct contact with chemical carcinogens and toxins in inhaled air. Therefore, the activities of xenobiotic-metabolising enzymes in this epithelium could modulate respiratory toxicity and carcinogenesis. We determined the expression of several xenobiotic-metabolising enzymes, including phase I and phase II enzymes, in human bronchial mucosa and peripheral lung tissues. Reverse transcription-polymerase chain reaction (RT-P CR) analysis of phase I enzymes showed CYP1A1 and CYP2C (CYP2C8 and CYP2C18) mRNA expression in all of the 14 bronchial mucosa specimens. CYP2A6 and CYP2B6 mRNAs were found in 85% of the samples, whereas 50 and 90% of the tissues displayed CYP2E1 and CYP3A5 expression, respectively. However, CYP1A2, CYP2D6 and CYP3A4 mRNAs were not detected in all samples analysed. Normal human bronchial epithelial cells (NHBE cells) cultured in serum-free conditions showed reduced P450 expression in comparison with the bronchial mucosal samples. Similar to the bronchial mucosa, the peripheral lung tissues expressed CYP1A1, CYP2A6, CYP2B6, CYP2C (CYP2C8 and CYP2C18), CYP2E1 and CYP3A5 mRNAs, but did not show detectable levels of CYP2D6. Additional P450s, such as CYP1A2 and CYP3A4, were detected. The expression of CYP1A1, CYP1A2, CYP2B6, CYP2E1 and CYP3A4/5 in peripheral lung tissues was confirmed at the protein level, whereas CYP2A6 protein was undetectable. The use of specific primers for the detection of the phase II isoenzymes belonging to the glutathione S-transferase mu (GST mu) and N-acetyl transferase (NAT) families showed that GSTM1 was expressed in 40% of the bronchial mucosa and 25% of the peripheral lung tissues, whereas GSTM3 and NAT1 mRNAs were found in all bronchial and lung samples. Finally, NAT2 expression was detected in all peripheral lung tissues, but was not detected in the bronchus. In conclusion, these results describing the diversity of the xenobiotic-metabolising enzymes expressed in the bronchus and lung tissues indicate that the human respiratory system could significantly and specifically contribute to the activation and metabolism of several environmental procarcinogens. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Nestle Res Ctr, Dept Life Sci, CH-1000 Lausanne 26, Switzerland. NCI, Div Basic Sci, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Mace, K (reprint author), Nestle Res Ctr, Dept Life Sci, POB 44, CH-1000 Lausanne 26, Switzerland. RI Shields, Peter/I-1644-2012 NR 27 TC 142 Z9 150 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD MAY PY 1998 VL 34 IS 6 BP 914 EP 920 DI 10.1016/S0959-8049(98)00034-3 PG 7 WC Oncology SC Oncology GA ZU616 UT WOS:000074215900029 PM 9797707 ER PT J AU Alvarez, LM Cullinan, AE Siwkowski, A Hampel, A DiPaolo, JA AF Alvarez, LM Cullinan, AE Siwkowski, A Hampel, A DiPaolo, JA TI Ribozyme-mediated inhibition of HPV-16 E6/E7 immortalization of human keratinocytes. SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI, Div Basic Sci, Bethesda, MD 20892 USA. No Illinois Univ, Dept Biol Sci, De Kalb, IL 60115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD MAY PY 1998 VL 34 SU 2 MA OP168 BP S37 EP S37 PG 1 WC Oncology SC Oncology GA ZV719 UT WOS:000074334200168 ER PT J AU Niklinski, J Rusin, M Chyczewski, L Sipowicz, M Shiao, YE Niklinska, WE Laudanski, J Furman, M Chorazy, M AF Niklinski, J Rusin, M Chyczewski, L Sipowicz, M Shiao, YE Niklinska, WE Laudanski, J Furman, M Chorazy, M TI p53 mutations in non-small cell lung cancer in Poland SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 Bialystok Med Univ, Dept Thorac Surg Pathol & Histol, Bialystok, Poland. Inst Oncol, Dept Tumor Biol, Gliwice, Poland. NCI, Carcinogenesis Lab, Frederick, MD 21702 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 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD MAY PY 1998 VL 34 SU 2 MA PP139 BP S30 EP S30 PG 1 WC Oncology SC Oncology GA ZV719 UT WOS:000074334200140 ER PT J AU Kirschbaum, T Pourrajabi, S Zocher, I Schwendinger, J Heim, V Roschenthaler, F Kirschbaum, V Zachau, HG AF Kirschbaum, T Pourrajabi, S Zocher, I Schwendinger, J Heim, V Roschenthaler, F Kirschbaum, V Zachau, HG TI The 3 ' part of the immunoglobulin kappa locus of the mouse SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE immunoglobulin V kappa genes; mouse; contig ID INFLUENZA-VIRUS HEMAGGLUTININ; VARIABLE GENE SEGMENTS; ANTI-DNA ANTIBODIES; SOMATIC MUTATION; REGION GENES; DIVERSITY; REARRANGEMENT; SPECIFICITY; HYBRIDOMAS; FAMILIES AB A detailed restriction map of a 430-kb contig comprising the single C kappa, the 5 JH and the adjoining 22 V kappa gene segments is presented. The first 12 V kappa genes following the J kappa C kappa region belong to the V kappa 21 family, the subsequent ones to the closely related families V kappa 8 and V kappa 19/28. Previous difficulties in cloning all V kappa 21 genes can now be explained by the presence of a duplicated region in this part of the locus. The structure was established by analysis of yeast artificial chromosome, bacterial artificial chromosome and cosmid clones and by the so-called long template PCR technique. The distance between C kappa and the proximal V kappa 21 gene is 22 kb and the average distances between the V kappa genes are about 20 kb. Of the 12 V kappa 21 genes 5 were sequenced for the first time and 8 of the 12 genes were found to be expressed. Of the 10 V kappa 8 and V kappa 19/28 germline genes 9 are new; expression products of 8 of the 10 genes were known. The known 5', 3' polarities allow to specify for the 22 V kappa genes whether they are rearranged to the J kappa C kappa element by a deletion or an inversion mechanism. Also the formation of interesting rearrangement products in classical cell lines as MPC11, MOPC41 and PC7043 can be explained now. The non-V kappa sequence L10 whose rearrangement by inversion has been described earlier (Hoechtl and Zachau, Nature 1983. 302: 260-263) was now localized downstream of J kappa C kappa. C1 NIH, Fogarty Int Ctr Adv Study Hlth Sci, Bethesda, MD 20892 USA. RP Zachau, HG (reprint author), Univ Munich, Adolf Butenandt Inst Physiol Chem, Marchioninistr 15, Munich, Germany. EM Zachau@bio.med.uni-muenchen.de NR 40 TC 27 Z9 27 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAY PY 1998 VL 28 IS 5 BP 1458 EP 1466 DI 10.1002/(SICI)1521-4141(199805)28:05<1458::AID-IMMU1458>3.0.CO;2-5 PG 9 WC Immunology SC Immunology GA ZM963 UT WOS:000073594100003 PM 9603450 ER PT J AU Gressens, P Paindaveine, B Hill, JM Evrard, P Brenneman, DE AF Gressens, P Paindaveine, B Hill, JM Evrard, P Brenneman, DE TI Vasoactive intestinal peptide shortens both G1 and S phases of neural cell cycle in whole postimplantation cultured mouse embryos SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE growth factor; neuroepithelium; neurogenesis; pituitary adenylate cyclase activating polypeptide ID BRAIN-DEVELOPMENT; MESSENGER-RNA; MATRIX CELLS; SPINAL-CORD; RAT-BRAIN; RECEPTOR; POLYPEPTIDE; EXPRESSION; VIP; REPLICATION AB Vasoactive intestinal peptide, a trophic and mitogenic factor, stimulates growth in whole cultured mouse embryos. Inhibition of this growth function between embryonic days 9 and 11 induces growth retardation accompanied by severe microcephaly. In the present study, to determine the effects of this peptide on the different phases of the cell cycle of neural cells, embryonic day 9.5 cultured mouse embryos were cumulatively labelled with bromodeoxyuridine. Vasoactive intestinal peptide (10(-7)M) shortened S phase and G1 phase of neuroepithelial cells by 50% (4.8-2.4 h) and 58% (1.9-0.8 h), respectively, compared with controls. G2 and M phases were not modified by vasoactive intestinal peptide treatment. Total cell cycle length was consequently reduced by 43% (8.2-4.7 h) in vasoactive intestinal peptide treated embryos, compared with controls. In contrast, vasoactive intestinal peptide did not modify the rate of neuroepithelial cell death as assessed by the proportion of nuclei containing fragmented DNA. These data suggest that vasoactive intestinal peptide stimulates growth in premigratory stages of nervous system development by shortening S and G1 phases of the cell cycle and that S phase duration can be regulated by a physiological peptide. C1 Hop Robert Debre, Serv Neuropediat, F-75019 Paris, France. Hop Robert Debre, INSERM CRI 9701, F-75019 Paris, France. Fac Xavier Bichat, F-75019 Paris, France. NIH, Sect Dev & Mol Pharmacol, Bethesda, MD 20892 USA. RP Gressens, P (reprint author), Hop Robert Debre, Serv Neurol Pediat, 48 Blvd Serurier, F-75019 Paris, France. NR 41 TC 40 Z9 40 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAY PY 1998 VL 10 IS 5 BP 1734 EP 1742 DI 10.1046/j.1460-9568.1998.00172.x PG 9 WC Neurosciences SC Neurosciences & Neurology GA ZN166 UT WOS:000073616500020 PM 9751145 ER PT J AU Serafini, R Ma, W Maric, D Maric, I Lahjouji, F Sieghart, W Barker, JL AF Serafini, R Ma, W Maric, D Maric, I Lahjouji, F Sieghart, W Barker, JL TI Initially expressed early rat embryonic GABA(A) receptor Cl- ion channels exhibit heterogeneous channel properties SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE GABA(A) receptors; dorsal spinal cord; embryonic receptors; proliferative cells ID SUBUNIT MESSENGER-RNAS; SPINAL-CORD NEURONS; A RECEPTORS; CALCIUM TRANSIENTS; CELLS; BRAIN; IMMUNOREACTIVITY; CURRENTS AB We have studied the earliest expression of GABA-induced Cl- channels in the rat embryonic dorsal spinal cord (DSC) using in situ hybridization, immunocytochemistry, flow cytometry and electrophysiology. At embryonic day 13 (E13) cells in the dorsal region are still proliferating. In situ hybridization consistently showed transcripts encoding only three GABA(A) receptor subunits (alpha(4), beta(1) and gamma(1)); immunocytochemistry both in tissue sections and in acutely isolated cells in suspension demonstrated the expression of the corresponding proteins and also revealed staining for other subunits (alpha(2), alpha(3), beta(3), gamma(2)) In patch-recordings performed in cells acutely isolated from the dorsal cord, responses to GABA were detected in 356 out of 889 cells. GABA-evoked responses, which often displayed the opening of a few channels, were mediated by Cl- ions, were inhibited by bicuculline and picrotoxin, and potentiated by benzodiazepines. Taken together, these observations indicate that Cl- channels likely involve GABAA type receptors. Fluctuation analysis revealed channel kinetics consisting of three exponential components (tau s: approximate to 1, 9 and 90 ms) and a wide variety of inferred unitary conductance values, ranging between 4 and 40 pS. A comparison of these results with observations in other, later embryonic cell types and recombinant receptors suggests that most of the earliest E13 DSC GABAA receptors may include alpha(3) subunit. These GABAA receptor Cl- channels may be activated physiologically as both GABA synthesizing enzymes and GABA are present in the E13 dorsal cord. C1 NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. Univ Vienna, Psychiat Clin, Dept Biochem Psychiat, A-1090 Vienna, Austria. RP Maric, D (reprint author), NINDS, Neurophysiol Lab, NIH, Bldg 36,Room 2602, Bethesda, MD 20892 USA. EM Dragan@codon.nih.gov RI Sieghart, Werner/A-4877-2013 OI Sieghart, Werner/0000-0002-0443-0302 NR 32 TC 23 Z9 23 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAY PY 1998 VL 10 IS 5 BP 1771 EP 1783 DI 10.1046/j.1460-9568.1998.00187.x PG 13 WC Neurosciences SC Neurosciences & Neurology GA ZN166 UT WOS:000073616500024 PM 9751149 ER PT J AU Sills, TL Onalaja, AO Crawley, JN AF Sills, TL Onalaja, AO Crawley, JN TI Mesolimbic dopaminergic mechanisms underlying individual differences in sugar consumption and amphetamine hyperlocomotion in Wistar rats SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE D-1; D-2; feeding; locomotion; quinpirole; SKF-38393 ID INDUCED LOCOMOTOR-ACTIVITY; NUCLEUS-ACCUMBENS; EXTRACELLULAR DOPAMINE; INGESTIVE BEHAVIOR; 6-OHDA LESIONS; MICRODIALYSIS; VULNERABILITY; COCAINE; PREDICT; SENSITIZATION AB Individual differences within strains of rats have been demonstrated for dopamine-mediated behaviours and responses to dopaminergic drugs. Differences in mesolimbic dopamine function may underlie individual differences in some of these behaviours, including sugar consumption and amphetamine hyperlocomotion. The present study addressed two potential mechanisms for these differences in dopamine-mediated behaviours. The possibility of functional differences in dopamine receptor subtypes was tested in LOW and HIGH sugar feeders. LOW and HIGH feeders did not differ in their response to the partial D-1 agonist SKF-38393. The highest dose (2.5 mg/kg) of the D-2 agonist quinpirole stimulated locomotor activity to a greater degree in a subset of HIGH sugar feeders as compared with LOW feeders. AII doses of amphetamine induced a greater locomotor response in HIGH feeders as compared with LOW feeders, and HIGH feeders exhibited higher levels of extracellular dopamine in the nucleus accumbens than LOW feeders following exposure to sugar and treatment with amphetamine. These results support the interpretation that LOW and HIGH feeders exhibit differences in presynaptic nucleus accumbens dopamine function that account for the expression of individual differences in sugar consumption and response to amphetamine treatments. A subset of HIGH feeders may also exhibit greater D-2 receptor function. C1 NIMH, Sect Behav Neuropharmacol, Expt Therapeut Branch, Bethesda, MD 20892 USA. RP Sills, TL (reprint author), Clarke Inst Psychiat, Biopsychol Sect, 250 Coll St, Toronto, ON M5T 1R8, Canada. NR 30 TC 12 Z9 12 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAY PY 1998 VL 10 IS 5 BP 1895 EP 1902 DI 10.1046/j.1460-9568.1998.00201.x PG 8 WC Neurosciences SC Neurosciences & Neurology GA ZN166 UT WOS:000073616500034 PM 9751159 ER PT J AU Milenic, DE Roselli, M Brechbiel, MW Pippin, CG McMurray, TJ Carrasquillo, JA Colcher, D Lambrecht, R Gansow, OA Schlom, J AF Milenic, DE Roselli, M Brechbiel, MW Pippin, CG McMurray, TJ Carrasquillo, JA Colcher, D Lambrecht, R Gansow, OA Schlom, J TI In vivo evaluation of a lead-labeled monoclonal antibody using the DOTA ligand SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE monoclonal antibody; radioimmunotherapy; radioimmunoscintigraphy; lead chelates; B72.3; DOTA ID COLON CARCINOMA XENOGRAFTS; SINGLE-CHAIN FV; INTRAPERITONEAL RADIOIMMUNOTHERAPY; CANCER; B72.3; STABILITY; BINDING; BIODISTRIBUTION; COMPLEXES; DTPA AB The aim of this study was to assess the utility of a radioimmunoconjugate containing a lead radionuclide for therapy and scintigraphy applications. The radioimmunoconjugate evaluated consisted of a bifunctional DOTA ligand and monoclonal antibody (MAb) B72.3 using athymic mice bearing LS-174T tumors, human colon carcinoma xenografts. In the studies reported here, the lead-203-DOTA complex itself was first demonstrated to have in vivo stability. MAb B72.3 was then conjugated with the DOTA ligand and labeled with Pb-203, and the immunoreactivity of B72.3 was maintained. The localization of the radioimmunoconjugate to tumor tissue and other select organs paralleled that of DOTA-I-125-B72.3, suggesting a similar metabolic pattern of the two radioimmunoconjugates. Thus, the DOTA-metal complex does not alter the behavior of the radioimmunoconjugate. Tumor localization of the Pb-203-DOTA-B72.3 conjugate was demonstrated with biodistribution studies as well as immunoscintigraphy studies. Such data highlight the stability of a lead radionuclide in the DOTA ligand. The suitability of this chelation chemistry for labeling radioimmunoconjugates with a lead radionuclide now makes its application in nuclear medicine a feasible proposition. C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Dept Nucl Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, 9000 Rockville Pike,Bldg 10 Room 8B07, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 51 TC 15 Z9 15 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6997 J9 EUR J NUCL MED JI Eur. J. Nucl. Med. PD MAY PY 1998 VL 25 IS 5 BP 471 EP 480 DI 10.1007/s002590050246 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZR257 UT WOS:000073956000003 PM 9575242 ER PT J AU Ghezzi, F Gomez, R Romero, R Yoon, BH Edwin, SS David, C Janisse, J Mazor, M AF Ghezzi, F Gomez, R Romero, R Yoon, BH Edwin, SS David, C Janisse, J Mazor, M TI Elevated interleukin-8 concentrations in amniotic fluid of mothers whose neonates subsequently develop bronchopulmonary dysplasia SO EUROPEAN JOURNAL OF OBSTETRICS GYNECOLOGY AND REPRODUCTIVE BIOLOGY LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the Society-of-Perinatal-Obstetricians CY JAN 20-26, 1997 CL ANAHEIM, CALIFORNIA SP Soc Perinatal Obstetricians DE amniotic fluid; interleukin 8; bronchopulmonary dysplasia; intraamniotic infection; cytokines ID CHRONIC LUNG-DISEASE; RESPIRATORY-DISTRESS SYNDROME; PREMATURE-INFANTS; INFECTION; RISK; PATHOPHYSIOLOGY; PATHOGENESIS; INFLAMMATION; ASSOCIATION; PREVENTION AB Objective: To determine if an intrauterine sub-clinical inflammatory process is a risk factor for the development of bronchopulmonary dysplasia. Methods: A cohort study was conducted in patients who met the following criteria: (1) Singleton gestation; (2) preterm labor or preterm premature rupture of the membranes, (3) amniocentesis for microbiologic studies of the amniotic fluid and (41 delivery between 24 and 28 weeks of gestation. Bronchopulmonary dysplasia was defined as the need for supplemental oxygen fur 78 days or longer after birth, associated with compatible chest radiographic findings. Amniotic fluid interleukin-8, was measured using a specific immunoassay. Logistic regression analysis and bootstrap procedure were used for statistical purposes. Results: Forty-seven patients met the inclusion criteria for this study. Among these patients, the prevalence of bronchopulmonary dysplasia was 23.4% (11/47). Amniotic fluid culture was positive in 21 out of 47 (44.7%) patients. Median (range) amniotic fluid interleukin-8 concentration was higher in patients whose neonates subsequently developed bronchopulmonary dysplasia than in those who did not (17 [9.8-583.7] ng ml(-1) versus 9.6 [0.91-744] ng ml(-1), P = 0.057). An amniotic fluid IL-8 level greater than 11.5 ng ml(-1) was far more common in mothers whose fetuses went on to develop bronchopulmonary dysplasia than in those who did not (10/11 [90.9%] versus 17/36 [47%]; P = 0.01). This relationship remained significant even after correcting for the effect of gestational age and birthweight (Odds ratio: 11.9; P < 0.05), Conclusion: Sub-clinical intrauterine inflammation is a risk factor for the subsequent development of bronchopulmonary dysplasia. We propose that in utero aspiration of fluid with high concentration of pro-inflammatory mediators may contribute to the lune injury responsible for the development of bronchopulmonary dysplasia. (C) 1998 Elsevier Science ireland Ltd. C1 NICHHD, Perinatol Res Branch, Bethesda, MD 20892 USA. Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, Detroit, MI USA. Wayne State Univ, Ctr Hlth Care Effect Res, Detroit, MI USA. RP Romero, R (reprint author), Hutzel Hosp, Dept Obstet & Gynecol, NICHD, Perinatol Res Branch, 4707 St Antoine Blvd, Detroit, MI 48201 USA. RI Yoon, Bo Hyun/H-6344-2011; OI Ghezzi, Fabio/0000-0003-3949-5410 NR 31 TC 111 Z9 111 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0301-2115 J9 EUR J OBSTET GYN R B JI Eur. J. Obstet. Gynecol. Reprod. Biol. PD MAY PY 1998 VL 78 IS 1 BP 5 EP 10 DI 10.1016/S0301-2115(97)00236-4 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA ZJ635 UT WOS:000073236500002 PM 9605441 ER PT J AU Hauser, W Johren, O Saavedra, JM AF Hauser, W Johren, O Saavedra, JM TI Characterization and distribution of angiotensin II receptor subtypes in the mouse brain SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE angiotensin AT(1) receptors; angiotensin AT(2) receptors; locus coeruleus; caudate putamen; candesartan; losartan; CGP 42112; PD 123319 ID MOLECULAR-CLONING; TYPE-2 RECEPTOR; BLOOD-PRESSURE; RAT-BRAIN; BINDING-SITES; EXPRESSION; GENE; CV-11974; AUTORADIOGRAPHY; LOCALIZATION AB We localized and characterized angiotensin II receptor subtypes (AT, and AT,) in the mouse brain, with the use of autoradiography after incubation with [I-125][Sar(1)]-angiotensin II or [I-125]CGP 42112 and displacement with selective angiotensin AT(1) (losartan and candesartan) or angiotensin AT(2) (CGP 42112(1) and PD 123319(2)) receptor ligands. In the mouse, the receptor subtype affinity for the different ligands was similar to that of the rat. The receptor subtype distribution was also similar to that in the rat, with some notable exceptions, such as the presence of angiotensin AT(1) but not AT(2) receptors in the locus coeruleus, and the expression of angiotensin AT(1) receptors in the caudate putamen. These results confirm that careful consideration of the specific distribution of receptor subtypes in different species, even those closely related such as the mouse and the rat, should be conducted before meaningful comparisons could be proposed. Our data also form the basis for future studies of mouse models such as those with angiotensin receptor gene deficiencies. Published by Elsevier Science B.V. 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. RI Johren, Olaf/G-6967-2011 NR 30 TC 61 Z9 61 U1 0 U2 1 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 MAY 1 PY 1998 VL 348 IS 1 BP 101 EP 114 DI 10.1016/S0014-2999(98)00134-4 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZR744 UT WOS:000074009400013 PM 9650837 ER PT J AU Gurguis, GNM Turkka, J Linnoila, M AF Gurguis, GNM Turkka, J Linnoila, M TI Effects of serotonin and metergoline on (125)[I]-iodocyanopindolol binding parameters to beta-adrenergic receptors in rat brain SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE beta-adrenergic receptors (beta AR); serotonin; metergoline; 5-HT1B receptors; iodocyanopindolol; antidepressants ID ADENYLATE-CYCLASE; 5-HYDROXYTRYPTAMINE RELEASE; I-125 IODOCYANOPINDOLOL; DIHYDROALPRENOLOL BINDING; ANTIDEPRESSANT TREATMENTS; ADRENOCEPTOR ANTAGONISTS; I125 IODOCYANOPINDOLOL; H-3 DIHYDROALPRENOLOL; DESIPRAMINE TREATMENT; MEDIATING INHIBITION AB Most ligands which have been employed to investigate the regulation of beta-adrenergic receptors (beta AR) under pathophysiological conditions and in response to pharmacological manipulations have also been shown to have affinity for 5-HT1B receptors. We examined the effects of serotonin and metergoline (10 mu M) on I-125-iodocyanopindolol (ICYP, 5-100 pM) binding to beta AR in rat frontal cortex and hippocampus membranes. In both brain regions, the presence of either serotonin or metergoline significantly lowered iodocyanopindolol dissociation constant (K-d) and maximum binding capacity (B-max). Isoproterenol displacement curves showed that the decrease in receptor density was primarily due to a significant decrease in the receptors in the low-conformational state. Thus, a significant fraction of the apparent ICYP binding to beta AR in the low-conformational state was due to binding to 5-HT1B receptors. Neither serotonin nor metergoline had an effect on the agonist isoproterenol dissociation constant from beta AR in either conformational state. Published by Elsevier Science B.V./ECNP. C1 NIAAA, Clin Studies Lab, DICBR, NIH, Bethesda, MD 20892 USA. Dept Vet Affairs Med Ctr, Psychiat Serv 116A, Lab Clin Neurosci & Autonom Pharmacol, Dallas, TX 75216 USA. Univ Oulu, Dept Neurol, Oulu, Finland. RP Linnoila, M (reprint author), NIAAA, Clin Studies Lab, DICBR, NIH, 10-RM,3C103,10 Ctr Dr,MSC 1256, Bethesda, MD 20892 USA. NR 60 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD MAY PY 1998 VL 8 IS 2 BP 131 EP 140 DI 10.1016/S0924-977X(97)00059-X PG 10 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA ZM540 UT WOS:000073550400008 PM 9619692 ER PT J AU Denisova, NA Erat, SA Kelly, JF Roth, GS AF Denisova, NA Erat, SA Kelly, JF Roth, GS TI Differential effect of aging on cholesterol modulation of carbachol-stimulated low-K-m GTPase in striatal synaptosomes SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE aging; synaptosomes; cholesterol; G-protein; microviscosity ID MEMBRANE LIPID-COMPOSITION; HETEROTRIMERIC G-PROTEINS; EVOKED DOPAMINE RELEASE; FATTY-ACID COMPOSITION; AGE-RELATED-CHANGES; RAT FRONTAL-CORTEX; SIGNAL-TRANSDUCTION; CEREBRAL-CORTEX; SPHINGOMYELIN DEGRADATION; ALZHEIMERS-DISEASE AB Previous research has suggested that age-related decline in physiological functions may be the result of substantial alterations in membrane molecular structure. The purpose of the present experiments was to elucidate the role of cholesterol domains in the age-related decline in receptor-G-protein interactions in striatal synaptosomes. We observed a significant age-related deficit in muscarinic cholinergic stimulated Low-K-m GTPase activity and its age-related susceptibility to cholesterol treatment in range of 10(-10)-10(-5) M. Treatment of synaptosomes from old rats with cholesterol in range of 10(-8)-10(-6) M restored the Low-K-m, GTPase activity up to the level seen in young animals and reached a maximum at 10(-7) M. In synaptosomes from young rats, however, cholesterol treatment did not have any effect on striatal Low-K-m GTPase activity. We observed significant alterations in the membrane lipid composition of striatal synaptosomes as a function of age. Our results suggested a significant interaction of age and cholesterol treatment on physical properties of striatal synaptosomes. Thus, the present results of experiments in vitro support our previous results of experiments in vivo and suggested an interaction of cholesterol domains with muscarinic-cholinergic receptor G-protein alpha subunit coupling/uncoupling through regulation of physical properties of striatal synaptosomes. Published by Elsevier-Science Inc. C1 Tufts Univ, Human Nutr Res Ctr Aging, USDA ARS, Boston, MA 02111 USA. NIA, Gerontol Res Ctr, Johns Hopkins Bayview Med Ctr, Mol Physiol & Genet Sect,Lab Cellular & Mol Biol, Baltimore, MD 21224 USA. RP Tufts Univ, Human Nutr Res Ctr Aging, USDA ARS, Boston, MA 02111 USA. EM denissova_ne@hnrc.tufts.edu NR 71 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 0531-5565 EI 1873-6815 J9 EXP GERONTOL JI Exp. Gerontol. PD MAY PY 1998 VL 33 IS 3 BP 249 EP 265 DI 10.1016/S0531-5565(97)00096-X PG 17 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA ZJ863 UT WOS:000073261300006 PM 9615923 ER PT J AU Norford, D Koo, JS Gray, T Alder, K Nettesheim, P AF Norford, D Koo, JS Gray, T Alder, K Nettesheim, P TI Expression of nitric oxide synthase isoforms in normal human tracheobronchial epithelial cells in vitro: Dependence on retinoic acid and the state of differentiation SO EXPERIMENTAL LUNG RESEARCH LA English DT Article DE nitric oxide synthase; tracheobronchial epithelium; retinoic acid; airway differentiation ID MOLECULAR-CLONING; LUNG; KERATINOCYTES; PURIFICATION; GROWTH; GENE; BETA AB The retinoic and (RA) and differentiation dependence of constitutive expression of the nitric oxide synthase (NOS) isoforms, iNOS, eNOS, and bNOS, was examined by reverse transcriptase polymerase chain recitation (RT-PCR) in cultured, normal, human, tracheobronchial epithelial (NHTBE) cells. In the presence of RA (RA(+)), early passage NHTBE cells grown in air-liquid interface (ALI) cultures undergo mucous differentiation; in the absence of RA (RA(-)), they undergo metaplastic squamous differentiation. Under both conditions the respective differentiated phenotype develops around day 10 of culture. We found that iNOS mRNA levels were much higher in RA(+) cultures, expressing the mucous phenotype, than in RA(-) cultures, expressing the metaplastic squamous phenotype. In contrast, eNOS mRNA tenets were much higher in RA(-) cultures than in RA(+) cultures. Expression of bNOS was not significantly affected by the RA status. The pattern of expression of NOS isoforms was then studied during the course of development of the two cellular phenotypes. During the early stages of differentiation, expression of iNOS (RA(+)) and eNOS (RA(-)) was very low, indicating that the expression of these two isoforms was not only dependent an the presence or absence of RA, but also on the degree of differentiation. The differentiation dependence of bNOS mRNA was less obvious. Four days of RA treatment of RA(-) cultures, which reverses the squamous phenotype and restores mucous differentiation, induced iNOS expression in a concentration-dependent manner. eNOS expression was depressed by 10(-8) M RA, while bNOS mRNA levels were slightly reduced by 10(-6) M RA. No NOS proteins were detected in unstimulated RA(+) and RA(-) cultures. iNOS protein was induced by cytokine treatment in RA(+) cultures, in contrast to eNOS and bNOS protein levels, which were unaffected. Our studies show that constitutive expression of the NOS isoforms is differentially regulated and that iNOS and eNOS mRNA levels are dependent on the stage of mucous and squamous differentiation, respectively. bNOS expression was only marginally affected by the RA or differentiation status. C1 NIEHS, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Coll Vet Med, Dept Anat Physiol Sci & Radiol, Raleigh, NC 27606 USA. RP Nettesheim, P (reprint author), NIEHS, Pulm Pathobiol Lab, POB 12233,MD D2-01, Res Triangle Pk, NC 27709 USA. FU NHLBI NIH HHS [HL 36982] NR 32 TC 16 Z9 16 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 USA SN 0190-2148 J9 EXP LUNG RES JI Exp. Lung Res. PD MAY-JUN PY 1998 VL 24 IS 3 BP 355 EP 366 PG 12 WC Respiratory System SC Respiratory System GA ZT331 UT WOS:000074074100009 PM 9635256 ER PT J AU Hallett, M AF Hallett, M TI Plasticity of the human motor system SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. NR 0 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 1998 VL 151 IS 1 BP 146 EP 146 PG 1 WC Neurosciences SC Neurosciences & Neurology GA ZM959 UT WOS:000073593600017 ER PT J AU Mamounas, LA Blue, ME Lyons, WE AF Mamounas, LA Blue, ME Lyons, WE TI Neurotrophin-stimulated plasticity of serotonergic neurons in the mature and aging brain SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 NIA, Mol Neurobiol Unit, Mol Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD USA. Kennedy Krieger Res Inst, Baltimore, MD USA. NR 0 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 1998 VL 151 IS 1 BP 161 EP 161 PG 1 WC Neurosciences SC Neurosciences & Neurology GA ZM959 UT WOS:000073593600074 ER PT J AU Shahabuddin, M Fields, I Bulet, P Hoffmann, JA Miller, LH AF Shahabuddin, M Fields, I Bulet, P Hoffmann, JA Miller, LH TI Plasmodium gallinaceum: Differential killing of some mosquito stages of the parasite by insect defensin SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE antibacterial peptide; malaria; transmission; vector ID INDUCIBLE ANTIBACTERIAL PEPTIDE; AEDES-AEGYPTI; SPOROGONIC DEVELOPMENT; SEQUENCE HOMOLOGY; MALARIA PARASITES; INNATE IMMUNITY; VECTOR MOSQUITO; PURIFICATION; SPOROZOITES; DROSOPHILA AB We examined several insect antimicrobial peptides to study their effect on Plasmodium gallinaceum zygotes, ookinetes, oocysts, and sporozoites. Only two insect defensins-Aeschna cyanea (dragon fly) and Phormia terranovae (flesh fly)-had a profound toxic effect on the oocysts in Aedes aegypti and on isolated sporozoites. The defensins affected the oocysts in a time-dependent manner. Injecting the peptide into the hemolymph 1 or 2 days after an infectious blood meal had no significant effect on prevalence of infection or relative oocyst density per mosquito. When injected 3 days after parasite ingestion, the relative oocyst density was significantly reduced. Injection on day 4 or later damaged the developing oocysts, although the oocysts density per mosquito was not significantly different when examined on day 8. The oocysts were swollen or had extensive internal vacuolization. The peptides had no detectable effect on the early stages of the parasite: the zygotes and ookinetes tested in vitro. Both the defensins were highly toxic to isolated sporozoites in vitro as indicated by disruption of the membrane permeability barrier, a change in morphology, and loss of motility. In contrast to the toxicity of cecropin and magainin for mosquitoes, defensin, at concentrations that kill parasites, is not toxic to mosquitoes, suggesting that defensin should be studied further as a potential molecule to block sporogonic development of Plasmodium. (C) 1998 Academic Press. C1 NIAID, Med Entomol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. CNRS, Inst Biol Mol & Cellulaire, F-67084 Strasbourg, France. RP Shahabuddin, M (reprint author), NIAID, Med Entomol Sect, Parasit Dis Lab, NIH, Bldg 4,Room 126, Bethesda, MD 20892 USA. NR 28 TC 116 Z9 124 U1 1 U2 12 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD MAY PY 1998 VL 89 IS 1 BP 103 EP 112 DI 10.1006/expr.1998.4212 PG 10 WC Parasitology SC Parasitology GA ZN503 UT WOS:000073652400014 PM 9603495 ER PT J AU Maucher, C Weissinger, EM Kremmer, E Baccarini, M Procyk, K Henderson, DW Wolff, L Kolch, W Kaspers, B Mushinski, JF Mischak, H AF Maucher, C Weissinger, EM Kremmer, E Baccarini, M Procyk, K Henderson, DW Wolff, L Kolch, W Kaspers, B Mushinski, JF Mischak, H TI Activation of bcl-2 suppressible 40 and 44 kDa p38-like kinases during apoptosis of early and late B lymphocytic cell lines SO FEBS LETTERS LA English DT Article DE apoptosis; bcl-2; interleukin 1 beta converting enzyme; kinase; p38; lymphocyte ID PROTEIN-KINASE; DEATH; MECHANISMS; PATHWAY; GROWTH; LIFE AB Activation of several different kinases characterizes the induction of apoptosis, Abelson virus transformed pre-B lymphocytes undergo apoptosis within 24 h of serum deprivation, PKA activation or gamma-irradiation, and the activity of two kinases of ca, 40 and 44 kDa is specifically induced during this apoptotic process. Bcl-2 expression prevents both apoptosis and the induction of these kinases, Immunologic and substrate similarities indicate that these kinases are related to the p38 family of MAP kinases, More mature cells of the B lymphocytic lineage, plasmacytomas, also exhibit induction of these kinases when apoptosis is induced by withdrawal of serum or IL-6, Treatment of the pre-B cells with ICE protease inhibitors when apoptotic stimuli are delivered prevents induction of the kinase activity, and partially inhibits apoptosis, These findings indicate that the induction of these 40 and 44 kDa p38 related kinases is a common feature of apoptosis in mouse B lymphocytic cells and may represent a step downstream of ICE proteases in the signal cascade that leads to programmed cell death. (C) 1998 Federation of European Biochemical Societies. C1 NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. GSF, Inst Klin Mol Biol & Tumorgenet, D-81377 Munich, Germany. GSF, Inst Klin hamatol, D-81377 Munich, Germany. GSF, Inst Immunol, D-81377 Munich, Germany. Univ Vienna, Inst Mikrobiol & Genet, A-1030 Vienna, Austria. Univ Munich, Inst Terphysiol, D-80539 Munich, Germany. RP Mushinski, JF (reprint author), NCI, Genet Lab, NIH, Bldg 37,Room 2B26,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. RI Mischak, Harald/E-8685-2011; Baccarini, Manuela/B-6481-2014; OI Baccarini, Manuela/0000-0002-3033-391X; Kolch, Walter/0000-0001-5777-5016 NR 26 TC 3 Z9 3 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 MAY 1 PY 1998 VL 427 IS 1 BP 29 EP 35 DI 10.1016/S0014-5793(98)00387-1 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA ZM745 UT WOS:000073571600007 PM 9613594 ER PT J AU Yoo, SH Lewis, MS AF Yoo, SH Lewis, MS TI Interaction between an intraluminal loop peptide of the inositol 1,4,5-trisphosphate receptor and the near N-terminal peptide of chromogranin A SO FEBS LETTERS LA English DT Article DE chromogranin A; inositol 1,4,5-triphosphate receptor; N-terminal peptide ID PH-DEPENDENT INTERACTION; VESICLE MATRIX PROTEINS; MEMBRANE; BINDING; CA2+; GRANULES; SEQUENCE; RELEASE; REGION AB The near N-terminal region of chromogranin A (CGA) has been shown to be the secretory vesicle membrane binding region, and tetrameric chromogranin A has been demonstrated to bind four molecules of an intraluminal loop peptide of the inositol 1,4,5-trisphosphate (IP3) receptor. It was therefore necessary to determine whether the conserved near N-terminal region of CGA interacts with the intraluminal loop region of the IP3 receptor. In the present study, we found that the proposed anchor region of CGA, the conserved near N-terminal region, does indeed interact with the intraluminal loop region of the IP3 receptor at the intravesicular pH of 5.5, further strengthening the case for the potential interaction between tetrameric chromogranins and tetrameric IP3 receptors in the cell. (C) 1998 Federation of European Biochemical Societies. C1 Korea Adv Inst Sci & Technol, Biomed Res Ctr, Secretory Granule Res Grp, Taejon 305701, South Korea. NIH, Biomed Engn & Instrumentat Program, NCRR, Bethesda, MD 20892 USA. RP Yoo, SH (reprint author), Korea Adv Inst Sci & Technol, Biomed Res Ctr, Secretory Granule Res Grp, 373-1 Gusong Dong, Taejon 305701, South Korea. EM shyoo@cais.kaist.ac.kr NR 25 TC 14 Z9 14 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 MAY 1 PY 1998 VL 427 IS 1 BP 55 EP 58 DI 10.1016/S0014-5793(98)00393-7 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA ZM745 UT WOS:000073571600012 PM 9613599 ER PT J AU Simpson, JL Carson, SA Chesney, C Conley, MR Metzger, B Aarons, J Holmes, LB Jovanovic-Peterson, L Knopp, R Mills, JL AF Simpson, JL Carson, SA Chesney, C Conley, MR Metzger, B Aarons, J Holmes, LB Jovanovic-Peterson, L Knopp, R Mills, JL TI Lack of association between antiphospholipid antibodies and first-trimester spontaneous abortion: prospective study of pregnancies detected within 21 days of conception SO FERTILITY AND STERILITY LA English DT Article DE antiphospholipid antibodies; anticardiolipin antibodies; pregnancy loss; cohort study design ID RECURRENT SPONTANEOUS-ABORTIONS; ANTICARDIOLIPIN ANTIBODIES; LUPUS ANTICOAGULANT; IMMUNOLOGICAL ASPECTS; CLINICAL-SIGNIFICANCE; DIABETIC MOTHERS; NUCLEAR ANTIGENS; FETAL DEATH; WOMEN; PREVALENCE AB Objective: To determine the role of antiphospholipid antibodies and anticardiolipin antibodies in first-trimester losses, addressing experimental pitfalls that preclude excluding the possibility that these antibodies reflect merely the selection bias of studying couples only after they have already experienced losses. Design: Given that retrospective studies cannot exclude the possibility that such antibodies arise as a result of the fetal death, blood samples were obtained either before pregnancy or very early in pregnancy. Sera were obtained within 21 days of conception. Setting: Multicenter university-based hospitals (National Institute of Child Health and Human Development collaborative study). Patient(s): Subjects for the current study were 93 women who later experienced pregnancy loss (48 diabetic; 45 nondiabetic), matched 2:1 with 190 controls (93 diabetic and 97 nondiabetic) who subsequently had normal live-born offspring. Intervention(s): Sera from these 283 women were analyzed for antiphospholipid antibodies by enzyme immunoassay. In 260 of the 283 women (87 with pregnancy losses; 173 with live-born infants), sera were also available to perform assays for anticardiolipin antibodies by enzyme immunoassay. Main Outcome Measure(s): Pregnancy losses. Result(s): No association was observed between pregnancy loss and the presence of antiphospholipid antibodies or anticardiolipin antibodies. Levels of antiphospholipid antibodies were 6-19 PL/mL in 62.4% of the pregnancies that ended in losses and greater than or equal to 20 PL/mL in 5.4%; among pregnancies resulting in live-born infants, the percentages were 56.8% and 6.8%, respectively. Of the pregnancies that ended in a loss, 5.7% had anticardiolipin antibodies greater than or equal to 16 GPL/mL, compared with 5.2% of those ending in a live birth. Conclusion(s): This prospective study suggests that anticardiolipin antibodies and antiphospholipid antibodies are not associated with an increased risk for first-trimester pregnancy loss. (C) 1998 by American Society for Reproductive Medicine. C1 Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. Univ Tennessee, Dept Obstet & Gynecol, Memphis, TN 38103 USA. Baptist Mem Hosp, Dept Pathol, Memphis, TN 38146 USA. NICHHD, Epidemiol Branch, Bethesda, MD 20892 USA. Northwestern Univ, Dept Med, Chicago, IL 60611 USA. Univ Pittsburgh, Magee Womens Hosp, Dept Med, Pittsburgh, PA 15213 USA. Sansum Med Res Fdn, Santa Barbara, CA 93105 USA. Univ Washington, Seattle, WA 98195 USA. RP Simpson, JL (reprint author), Baylor Coll Med, Dept Obstet & Gynecol, 6550 Fannin,Suite 729A, Houston, TX 77030 USA. NR 50 TC 21 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAY PY 1998 VL 69 IS 5 BP 814 EP 820 DI 10.1016/S0015-0282(98)00054-5 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA ZJ796 UT WOS:000073254100004 PM 9591485 ER PT J AU Rauhala, P Khaldi, A Mohanakumar, KP Chiueh, CC AF Rauhala, P Khaldi, A Mohanakumar, KP Chiueh, CC TI Apparent role of hydroxyl radicals in oxidative brain injury induced by sodium nitroprusside SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE dopamine; iron; lipid peroxidation; nitric oxide; oxidative stress; S-nitrosothiols; sodium nitroprusside; substantia nigra; free radical ID LOW-DENSITY-LIPOPROTEIN; NITRIC-OXIDE PROTECTS; LIPID-PEROXIDATION; HYDROGEN-PEROXIDE; FATTY-ACIDS; SUPEROXIDE; PRODUCTS; PEROXYNITRITE; CYTOTOXICITY; GENERATION AB Sodium nitroprusside (disodium nitroferricyanide) has been suggested to cause cytotoxicity through either the release of cyanide and/or nitric oxide. The present study investigated a possible mechanism that after a brief release of nitric oxide, iron moiety of breakdown products of sodium nitroprusside could cause a lone lasting oxidative stress, such as hydroxyl radical generation, lipid peroxidation and cytotoxicity. Intranigral administration of sodium nitroprusside (0-16.8 nmol) to rats induced an acute increase in lipid peroxidation in the substantia nigra and a chronic dopamine depletion in the caudate nucleus. Photodegraded (nitric oxide-exhibited) sodium nitroprusside, however, still produced lipid peroxidation and neurotoxicity in the midbrain. Moreover, non-iron containing nitric oxide-donor compounds, such as S-nitroso-N-acetylpenicillamine, did not cause oxidative brain injury in vivo suggesting that nitric oxide may not mediate neurotoxicity induced by sodium nitroprusside. Additional in vitro studies demonstrated that both freshly prepared (nitric oxide donor) and photodegraded (nitric oxide-exhausted) sodium nitroprusside generated hydroxyl radicals in the presence of ascorbate and also increased lipid peroxidation in brain homogenates. These pro-oxidative effects of sodium nitroprusside were blocked by nitric oxide, S-nitroso-N-acetylpenicillamine, oxyhemoglobin, and deferoxamine (iron chelator). The present results suggest that iron moiety, rather than nitric oxide, may mediate the pro-oxidative properties of sodium nitroprusside. With this new information in mind, the misuse of sodium nitroprusside as a selective nitric oxide donor in both basic and clinical uses should be urgently addressed. Published by Elsevier Science, Inc. C1 NIMH, LCS, Clin Ctr,Unit Neurodegenerat & Neuroprotect, NIH, Bethesda, MD 20892 USA. RP Chiueh, CC (reprint author), NIMH, LCS, Clin Ctr,Unit Neurodegenerat & Neuroprotect, NIH, Bldg 10,Rm 3D-41, Bethesda, MD 20892 USA. OI Rauhala, Pekka/0000-0003-2036-3522 NR 39 TC 78 Z9 79 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAY PY 1998 VL 24 IS 7-8 BP 1065 EP 1073 DI 10.1016/S0891-5849(97)00386-9 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA ZP915 UT WOS:000073801200001 PM 9626559 ER PT J AU Sokal, EM Conjeevaram, HS Roberts, EA Alvarez, F Bern, EM Goyens, P Rosenthal, P Lachaux, A Shelton, M Sarles, J Hoofnagle, J AF Sokal, EM Conjeevaram, HS Roberts, EA Alvarez, F Bern, EM Goyens, P Rosenthal, P Lachaux, A Shelton, M Sarles, J Hoofnagle, J TI Interferon alfa therapy for chronic hepatitis B in children: A multinational randomized controlled trial SO GASTROENTEROLOGY LA English DT Article ID VIRUS-INFECTION; CARRIER CHILDREN; E-ANTIGEN; CLEARANCE AB Background & Aims: Treatment of chronic hepatitis B with interferon alfa is not approved in children. The aim of this study was to evaluate the safety and efficacy of interferon alfa (IFN-alpha) in children with chronic hepatitis B and increased transaminase levels. Methods: Children were given either IFN-alpha 2b (6 megaunits/m(2) thrice weekly for 24 weeks) or no treatment. Clearance of markers of viral replication was evaluated 24 weeks after therapy and after 48 weeks of observation in controls. Results: Of 149 children enrolled, 144 were evaluable (70 treated and 74 controls). Serum hepatitis B e antigen and viral DNA became negative in 26% of treated children and 11% of controls (P < 0.05), Serum aminotransferase levels normalized and liver histology improved among responders, Hepatitis B surface antigen became undetectable in 10% of treated patients and 1% of controls, Female gender and interferon treatment were the only significant predictors of response. Ethnic origin, baseline aminotransferase level, initial DNA levels, and histology did not correlate with response, Most adverse reactions were mild or moderate, and dose was reduced in 24% of children. Conclusions: In children with chronic hepatitis B, INF-alpha promotes loss of viral replication markers and surface antigen and improves aminotransferases and histology. C1 Univ Catholique Louvain, Dept Pediat, Clin St Luc, B-1200 Brussels, Belgium. Univ Chicago Hosp, Chicago, IL 60637 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Hop St Justine, Montreal, PQ H3T 1C5, Canada. New England Med Ctr, Boston, MA 02111 USA. Hop Enfants Reines Fabiola, Brussels, Belgium. Univ Calif San Francisco, San Francisco, CA 94143 USA. Hop Edouard Herriot, Lyon, France. Cook Childrens Med Ctr, Ft Worth, TX USA. Hop Enfants La Timone, Marseille, France. NIH, Bethesda, MD 20892 USA. RP Sokal, EM (reprint author), Univ Catholique Louvain, Dept Pediat, Clin St Luc, 10-1301 Ave Hippocrate, B-1200 Brussels, Belgium. EM sokal@pedi.ucl.ac.be NR 24 TC 134 Z9 152 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 1998 VL 114 IS 5 BP 988 EP 995 DI 10.1016/S0016-5085(98)70318-X PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZJ817 UT WOS:000073256500021 PM 9558288 ER PT J AU Debelenko, LV Emmert-Buck, MR Lubensky, IA Jensen, RT AF Debelenko, LV Emmert-Buck, MR Lubensky, IA Jensen, RT TI Gastrin is the most important factor in ECL tumorigenesis - Reply SO GASTROENTEROLOGY LA English DT Letter ID ZOLLINGER-ELLISON SYNDROME; MULTIPLE ENDOCRINE NEOPLASIA; CELL CARCINOIDS; TYPE-1; HYPERGASTRINEMIA; RAT C1 Natl Canc Inst, Pathol Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Digest Dis Branch, NIH, Bethesda, MD USA. RP Debelenko, LV (reprint author), Natl Canc Inst, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 13 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 1998 VL 114 IS 5 BP 1114 EP 1115 DI 10.1016/S0016-5085(98)70347-6 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZJ817 UT WOS:000073256500043 ER PT J AU Li, Z Rakkar, A Katayose, Y Kim, M Shanmugam, N Srivastava, S Moul, JW McLeod, DG Cowan, KH Seth, P AF Li, Z Rakkar, A Katayose, Y Kim, M Shanmugam, N Srivastava, S Moul, JW McLeod, DG Cowan, KH Seth, P TI Efficacy of multiple administrations of a recombinant adenovirus expressing wild-type p53 in an immune-competent mouse tumor model SO GENE THERAPY LA English DT Article DE adenovirus; p53; gene therapy; apoptosis; bystander effect ID GENE-THERAPY; IN-VIVO; GROWTH SUPPRESSION; GLIOBLASTOMA CELLS; CANCER CELLS; LUNG-CANCER; CARCINOMA; ANGIOGENESIS; INHIBITOR; APOPTOSIS AB Infection of Renca cells in vitro with a recombinant adenovirus expressing a marker gene beta-galactosidase resulted in high level of the transgene expression. Renca tumors grown in Balb/C mice were also infectable with this recombinant adenovirus. The transgene expression in the tumors of Ad-beta gal, on day 7 produced beta-galactosidase for about 7 days, however, administration of another dose of AD-beta gal, on day 7 produced beta-galactosidase expression. To investigate the effect of antibodies to adenovirus were injected with multiple doses of adenovirus to produce neutralizing antibodies. To these animals Renca cells were injected and tumors formed. Interestingly, when Ad beta-gal was administered into these tumors, a high level of transgene expression was still observed. We next explored the utility of a recombinant adenovirus expressing p53 (AdWTp53) in the Renca tumor model. Renca cells when exposed to an adenovirus expressing p53 (AdWTp53) produced a high level of p53 protein, a p53-inducible gene p21/WAF1/Cip1 and underwent apoptosis. A single injection of AdWTp53 (10(9) plaque forming units) resulted in significant inhibition of tumor growth. However, multiple administrations (four doses of 2.5 x 10(8) plaque forming units) of AdWTp53 were needed for tumor cures. Mixing uninfected and AdWTp53-infected cells showed a bystander effect of AdWTp53-infected Renca cells. Based on these results we believe that an appropriate dose scheduling of AdWTp53 can be efficacious for cancer gene therapy in immune-competent tumor-bearing animals. C1 NCI, Med Branch, Med Breast Canc Sect, NIH, Bethesda, MD 20892 USA. USUHS, Dept Surg, Ctr Prostate Dis Res, Bethesda, MD USA. RP Seth, P (reprint author), NCI, Med Branch, Med Breast Canc Sect, NIH, Bldg 10,Room 12N226, Bethesda, MD 20892 USA. NR 36 TC 38 Z9 38 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD MAY PY 1998 VL 5 IS 5 BP 605 EP 613 DI 10.1038/sj.gt.3300636 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA ZN010 UT WOS:000073598700005 PM 9797864 ER PT J AU Kleiman, SE Pastan, I Puck, JM Gottesman, MM AF Kleiman, SE Pastan, I Puck, JM Gottesman, MM TI Characterization of an MDR1 retroviral bicistronic vector for correction of X-linked severe combined immunodeficiency SO GENE THERAPY LA English DT Article DE XSCID; MDR1; gene transfer; retroviral vectors ID RECEPTOR-GAMMA-CHAIN; IL-2 RECEPTOR; MULTIDRUG TRANSPORTER; MONOCLONAL-ANTIBODIES; P-GLYCOPROTEIN; GENE-TRANSFER; CELL-LINES; EXPRESSION; INSERTION; MODEL AB X-linked severe combined immunodeficiency (XSCID) is a hereditary disorder characterized by severe T cell lymphopenia and abnormal B cell function. The disease is caused by mutations in IL2RG, the gene encoding the interleukin-2 receptor common gamma chain (gamma C) shared by several interleukin receptors. A Harvey retroviral bicistronic vector containing an IL2RG cDNA and cDNA encoding the multidrug transporter (MDR1) was constructed to investigate the correction of XSCID. Translation of the MDR1 cDNA is achieved from an internal ribosome entry site (IRES). Mouse fibroblasts transfected or transduced with the vector expressed both membrane proteins as detected with specific monoclonal antibodies by fluorescence activated cell sorting. Two human SXCID B cell lines were transduced using a filter concentration method in combination with phosphate depletion. Significant expression of both proteins was detected by Western blot analysis. This construct might be particularly useful if high expression of gamma c is required, as might be achievable through in vivo selection for drug resistance of recipient lymphocytes. 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. NHGRI, Lab Gene Transfer, NIH, Bethesda, MD USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, Div Basic Sci, NIH, Bldg 37,Room 1A09,37 Convent Dr MSC4255, Bethesda, MD 20892 USA. NR 35 TC 8 Z9 14 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD MAY PY 1998 VL 5 IS 5 BP 671 EP 676 DI 10.1038/sj.gt.3300651 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA ZN010 UT WOS:000073598700013 PM 9797872 ER PT J AU Wildner, O Candotti, F Krecko, EG Xanthopoulos, KG Ramsey, WJ Blaese, RM AF Wildner, O Candotti, F Krecko, EG Xanthopoulos, KG Ramsey, WJ Blaese, RM TI Generation of a conditionally neo(r)-containing retroviral producer cell line: effects of neo(r) on retroviral titer and transgene expression SO GENE THERAPY LA English DT Article DE single gene retroviral vectors; Cre/IoxP; GFP; neo(r) ID SITE-SPECIFIC RECOMBINATION; MURINE HEMATOPOIETIC-CELLS; HUMAN ADENOSINE-DEAMINASE; LONG-TERM EXPRESSION; GENE-EXPRESSION; ADENOVIRUS VECTORS; MAMMALIAN-CELLS; DNA-SEQUENCES; THERAPY; LOXP AB We have developed a method for generating high-titer retroviral producer cell lines conditionally containing a neomycin resistance gene (neo(r)) based on the Cre/loxP system. For this, a bicistronic retroviral splicing vector carrying the green fluorescence protein (GFP) and a marker gene cassette consisting of internal ribosome entry site (IRES) and neo flanked by loxP sites, was constructed and conveniently used to generate a G418 resistant vector produced cell line. Following titer determination and verification of the biological activity of the retroviral supernatants, the selectable expression cassette which was no longer required was excised from the provirus by transient Cre expression using an adenoviral vector. This strategy led to precise excision of neo(r) and generation of retroviral supernatants containing functional 'neo-less' retroviral particles without detrimental effects on the high vector titers found in the parental neo(r)-containing producer lines. GFP expression was significantly increased after the excision of neo, in both the producer lines and retrovirally transduced target cells. Reintroduction of neo did not alter GFP expression, suggesting that the neo gene and/or its gene product per se are not acting as a transcriptional silencer. C1 NHGRI, Clin Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. RP Wildner, O (reprint author), NHGRI, Clin Gene Therapy Branch, NIH, Bldg 10,Room 10C103,10 Ctr Dr,MSC 1851, Bethesda, MD 20892 USA. NR 53 TC 14 Z9 14 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD MAY PY 1998 VL 5 IS 5 BP 684 EP 691 DI 10.1038/sj.gt.3300654 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA ZN010 UT WOS:000073598700015 PM 9797874 ER PT J AU Gottesman, S Roche, E Zhou, YN Sauer, RT AF Gottesman, S Roche, E Zhou, YN Sauer, RT TI The ClpXP and ClpAP proteases degrade proteins with carboxy-terminal peptide tails added by the SsrA-tagging system SO GENES & DEVELOPMENT LA English DT Article DE 10Sa RNA; lambda repressor; Escherichia coli; intracellular proteolysis; molecular recognition; ATP-dependent degradation ID ESCHERICHIA-COLI K-12; SMALL STABLE RNA; 10SA RNA; LAMBDA-REPRESSOR; MU-REPRESSOR; PHAGE; GENE; SEQUENCE; TSP; IDENTIFICATION AB Interruption of translation in Escherichia coli can lead to the addition of an Ii-residue carboxy-terminal peptide tail to the nascent chain. This modification is mediated by SsrA RNA (also called 10Sa RNA and tmRNA) and marks the tagged polypeptide for proteolysis. Degradation in vivo of lambda repressor amino-terminal domain variants bearing this carboxy-terminal SsrA peptide tag is shown here to depend on the cytoplasmic proteases ClpXP and ClpAP. Degradation in vitro of SsrA-tagged substrates was reproduced with purified components and required a substrate with a wild-type SsrA tail, the presence of both ClpP and either ClpA or ClpX, and ATP. Clp-dependent proteolysis accounts for most degradation of SsrA-tagged amino-domain substrates at 32 degrees C, but additional proteases contribute to the degradation of some of these SsrA-tagged substrates at 39 degrees C. The existence of multiple cytoplasmic proteases that function in SsrA quality-control surveillance suggests that the SsrA tag is designed to serve as a relatively promiscuous signal for proteolysis. Having diverse degradation systems able to recognize this tag may increase degradation capacity, permit degradation of a wide variety of different tagged proteins, or allow SsrA-tagged proteins to be degraded under different growth conditions. C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Gottesman, S (reprint author), NCI, Mol Biol Lab, Bethesda, MD 20892 USA. EM susang@helix.nih.gov OI , /0000-0002-1719-5399 FU NIAID NIH HHS [AI-16897] NR 46 TC 503 Z9 507 U1 1 U2 22 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 1 PY 1998 VL 12 IS 9 BP 1338 EP 1347 DI 10.1101/gad.12.9.1338 PG 10 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA ZN219 UT WOS:000073621800011 PM 9573050 ER PT J AU DeMarini, DM Shelton, ML Abu-Shakra, A Szakmary, A Levine, JG AF DeMarini, DM Shelton, ML Abu-Shakra, A Szakmary, A Levine, JG TI Spectra of spontaneous frameshift mutations at the hisD3052 allele of Salmonella typhimurium in four DNA repair backgrounds SO GENETICS LA English DT Article ID COLI LACI GENE; ESCHERICHIA-COLI; IN-VIVO; SACCHAROMYCES-CEREVISIAE; SPONTANEOUS MUTAGENESIS; SEQUENCE-ANALYSIS; MAMMALIAN-CELLS; HISTIDINOL DEHYDROGENASE; SLIPPAGE-MISALIGNMENT; MOLECULAR NATURE AB To characterize the hisD3052-1 frameshift allele of Salmonella typhimurium, we analyzed similar to 6000 spontaneous revertants (rev) for a 2-base deletion hotspot within the sequence (CG)(4), and we sequenced similar to 500 nonhotspot rev. The reversion target is a minimum of 76 bases (nucleotides 843-918) that code for amino acids within a nonconserved region of the histidinol dehydrogenase protein. Only 0.4-3.9% were true rev. Of the following classes, 182 unique second-site mutations were identified: hotspot, complex frameshifts requiring Delta uvrB + pKM101 (TA98-specific) or not (concerted), I-base insertions, duplications, and nonhotspot deletions. The percentages of hotspot mutations were 13.8% in TA1978 (wild type), 24.5% in UTH8413 (pKM101), 31.6% in TA1538 (Delta uvrB), and 41.0% in TA98 (Delta uvrB, pKM101). The Delta uvrB allele decreased by three times the mutant frequency (MF, rev/10(8) survivors) of duplications and increased by about two times the MF of deletions. Separately, the Delta uvrB allele or pKM101 plasmid increased by two to three times the MF of hotspot mutations; combined, they increased this IMF by five times. The percentage of 1-base insertions was not influenced by either Delta uvrB or pKM101. Hotspot deletions and TA98-specific complex frameshifts are inducible by some mutagens; concerted complex frameshifts and 1-base insertions are not; and there is little evidence for mutagen-induced duplications and nonhotspot deletions. Except for the base substitutions in TA98-specific complex frameshifts, all spontaneous mutations of the hisD3052 allele are likely templated. The mechanisms may involve (I) the potential of direct and inverted repeats to undergo slippage and misalignment and to form quasi-palindromes and (2) the interaction of these sequences with DNA replication and repair proteins. C1 US EPA, Div Environm Carcinogenesis MD68, Res Triangle Pk, NC 27711 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. RP DeMarini, DM (reprint author), US EPA, Div Environm Carcinogenesis MD68, Res Triangle Pk, NC 27711 USA. EM demarini.david@epamail.epa.gov NR 100 TC 27 Z9 27 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD MAY PY 1998 VL 149 IS 1 BP 17 EP 36 PG 20 WC Genetics & Heredity SC Genetics & Heredity GA ZN696 UT WOS:000073672500003 PM 9584083 ER PT J AU Guyer, M AF Guyer, M TI Statement on the rapid release of genomic DNA sequence SO GENOME RESEARCH LA English DT Editorial Material C1 Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. RP Guyer, M (reprint author), Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. NR 0 TC 14 Z9 14 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1054-9803 J9 GENOME RES JI Genome Res. PD MAY PY 1998 VL 8 IS 5 BP 413 EP 413 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA ZP398 UT WOS:000073748300001 PM 9582183 ER PT J AU Pruitt, KD AF Pruitt, KD TI WebWise: Guide to McDermott Center for Human Growth and Development at University of Texas Southwest Web site SO GENOME RESEARCH LA English DT Article C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Pruitt, KD (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1054-9803 J9 GENOME RES JI Genome Res. PD MAY PY 1998 VL 8 IS 5 BP 422 EP 426 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA ZP398 UT WOS:000073748300005 PM 9582187 ER PT J AU Ben-Porath, I Kozak, CA Benvenisty, N AF Ben-Porath, I Kozak, CA Benvenisty, N TI Chromosomal mapping of TMP (EMP1), XMP (EMP2), and YMP (EMP3), genes encoding membrane proteins related to PMP22 SO GENOMICS LA English DT Article ID PERIPHERAL MYELIN PROTEIN-22; MARIE-TOOTH DISEASE; MOUSE; IDENTIFICATION; REGIONS; GENOME; FAMILY; DNA AB We have recently characterized a novel mammalian gene family, encoding membrane glycoproteins with four trans-membrane domains. This gene family includes the previously studied PMP22, which is involved in the Charcot-Marie-Tooth neuropathy, and three novel genes: TMP, XMP, and YMP (HGMW-approved symbols EMP1, EMP2 and EMP3, respectively). The Tmp (tumor-associated membrane protein) gene was isolated from a c-myc induced mouse brain tumor and is expressed in several highly proliferative cell types. We have now isolated cDNAs of the mouse Xmp and Ymp genes and determined the chromosomal localization of mouse Tmp, Xmp, and Ymp. Tmp was mapped to mouse chromosome 6, Xmp was mapped to chromosome 16, and Ymp was mapped to chromosome 7. Tmp and Ymp map to paralogous chromosomal regions, whereas Xmp maps to a chromosomal region that is putatively paralogous to a region on chromosome 11, to which Pmp22 was previously mapped. These data suggest that this family of membrane glycoproteins evolved as a result of chromosomal duplications, (C) 1998 Academic Press. C1 Hebrew Univ Jerusalem, Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel. NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. RP Benvenisty, N (reprint author), Hebrew Univ Jerusalem, Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel. NR 23 TC 25 Z9 29 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD MAY 1 PY 1998 VL 49 IS 3 BP 443 EP 447 DI 10.1006/geno.1998.5238 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA ZQ212 UT WOS:000073834000013 PM 9615230 ER PT J AU Burwinkel, B Miglierini, G Jenne, DE Gilbert, DJ Copeland, NG Jenkins, NA Ring, HZ Francke, U Kilimann, MW AF Burwinkel, B Miglierini, G Jenne, DE Gilbert, DJ Copeland, NG Jenkins, NA Ring, HZ Francke, U Kilimann, MW TI Structure of the human paralemmin gene (PALM), mapping to human chromosome 19p13.3 and mouse chromosome 10, and exclusion of coding mutations in grizzled, mocha, jittery, and hesitant mice SO GENOMICS LA English DT Article ID LINKAGE MAP; RADIATION AB Paralemmin is a newly identified protein that is associated with the plasma membrane and with intracellular membranes through a lipid anchor. It is abundant in brain, is expressed at intermediate levels in the kidney and in endocrine cells, and occurs at low levels in many other tissues. As it is a candidate for genetic disorders that affect membrane functions, we have determined the structure of the human paralemmin gene, PALM showing that it is organized into nine exons. Moreover, we have performed chromosomal assignments of the human and mouse paralemmin genes, localizing them to regions of homology at human 19p13.3 and the central mouse chromosome 10. Finally, mutation analysis using RNA from mice homozygous for the mutant genes grizzled (gr), mocha (mh), mocha 2J (mh(2J)), jittery (ji) and hesitant (ji(hes)), which map to this area, excluded mutations in their Palm coding sequences. (C) 1998 Academic Press. C1 Ruhr Univ Bochum, Inst Physiol Chem, D-44780 Bochum, Germany. Max Planck Inst Psychiat, Abt Neuroimmunol, D-82152 Planegg Martinsried, Germany. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. Stanford Univ, Med Ctr, Dept Genet, Stanford, CA 94305 USA. Stanford Univ, Med Ctr, Howard Hughes Med Inst, Stanford, CA 94305 USA. RP Kilimann, MW (reprint author), Ruhr Univ Bochum, Inst Physiol Chem, D-44780 Bochum, Germany. NR 8 TC 6 Z9 8 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD MAY 1 PY 1998 VL 49 IS 3 BP 462 EP 466 DI 10.1006/geno.1998.5276 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA ZQ212 UT WOS:000073834000017 PM 9615234 ER PT J AU Krishnan, R Goodman, B Jin, DY Jeang, KT Collins, C Stetten, G Spencer, F AF Krishnan, R Goodman, B Jin, DY Jeang, KT Collins, C Stetten, G Spencer, F TI Map location and gene structure of the Homo sapiens mitotic arrest deficient 2 (MAD2L1) gene at 4q27 SO GENOMICS LA English DT Article ID SPINDLE ASSEMBLY CHECKPOINT; HEPATOCELLULAR-CARCINOMA; PIMA-INDIANS C1 Johns Hopkins Univ, Sch Med, Ctr Med Genet, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Gynecol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Obstet, Baltimore, MD 21205 USA. Johns Hopkins Univ, Program Human Genet, Baltimore, MD 21205 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Spencer, F (reprint author), Johns Hopkins Univ, Sch Med, Ctr Med Genet, Ross 1167,720 Rutland Ave, Baltimore, MD 21205 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 19 TC 14 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD MAY 1 PY 1998 VL 49 IS 3 BP 475 EP 478 DI 10.1006/geno.1998.5233 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA ZQ212 UT WOS:000073834000020 PM 9615237 ER PT J AU Ensoli, B Monini, P Colombini, S Goletti, D Cafaro, A Butto, S Sgadari, C Leone, P Franco, M Leone, P Sturzl, M Verani, P AF Ensoli, B Monini, P Colombini, S Goletti, D Cafaro, A Butto, S Sgadari, C Leone, P Franco, M Leone, P Sturzl, M Verani, P TI Role of HHV-8 in the pathogenesis of Kaposi's sarcoma SO HAEMATOLOGICA LA English DT Article; Proceedings Paper CT Workshop of the Italian-Society-for-Experimental-Hematology CY JUL 03, 1997 CL FLORENCE, ITALY SP Italian Soc Exptl Hematol C1 Ist Super Sanita, Virol Lab, I-00161 Rome, Italy. NCI, Tumor Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Max Planck Inst, Abt Virusforsch, Martinsried, Germany. RP Ensoli, B (reprint author), Ist Super Sanita, Virol Lab, Viale Regina Elena 299, I-00161 Rome, Italy. RI Sturzl, Michael/B-3019-2015; Sgadari, Cecilia/H-4302-2016; Ensoli, Barbara/J-9169-2016; Monini, Paolo/K-1429-2016; Cafaro, Aurelio/K-5314-2016 OI Sturzl, Michael/0000-0002-9276-2824; Sgadari, Cecilia/0000-0003-0364-4912; Ensoli, Barbara/0000-0002-0545-8737; Monini, Paolo/0000-0002-4941-6854; NR 0 TC 0 Z9 0 U1 0 U2 3 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD MAY PY 1998 VL 83 IS 5 BP 467 EP 468 PG 2 WC Hematology SC Hematology GA ZR236 UT WOS:000073953900015 ER PT J AU Boyce, WT O'Neill-Wagner, P Price, CS AF Boyce, WT O'Neill-Wagner, P Price, CS TI Crowding stress and violent injuries among behaviorally inhibited rhesus macaques SO HEALTH PSYCHOLOGY LA English DT Article DE stress; injury; behavioral inhibition; crowding ID MONKEYS AB Environmental stressors and stable individual differences in human behavior have both been implicated etiologically in injuries. Because stress-related injuries are difficult to study experimentally in humans, the authors examined injury incidence in a troop of 21 male and 15 female free-ranging rhesus macaques (Macaca mulatta) before, during, and after a 6-month group confinement. Individual differences in behavioral inhibition to novelty were assessed, using multiple, quantified observations of behavior by 3 independent raters during 3 previous years. Incidence and severity of medically attended injuries were ascertained from veterinary records over a 2-year study period. A 5-fold increase in the incidence of injuries was documented during confinement stress, and an interaction was found between the stressor and behavioral inhibition in the prediction of injury incidence. Highly inhibited animals had significantly higher injury rates during confinement, compared with their uninhibited peers, but equal or lower rates in the low stress periods that preceded and followed confinement. Inhibited individuals appeared to have been specifically targeted for violence during the group stressor but were protected under normative, more predictable conditions. C1 Univ Calif Berkeley, Hlth & Med Sci Program, Inst Human Dev, Berkeley, CA 94720 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. NICHHD, Comparat Ethol Lab, Bethesda, MD 20892 USA. RP Boyce, WT (reprint author), Univ Calif Berkeley, Hlth & Med Sci Program, Inst Human Dev, 570 Univ Hall 1190, Berkeley, CA 94720 USA. NR 21 TC 27 Z9 28 U1 1 U2 8 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD MAY PY 1998 VL 17 IS 3 BP 285 EP 289 DI 10.1037//0278-6133.17.3.285 PG 5 WC Psychology, Clinical; Psychology SC Psychology GA ZN008 UT WOS:000073598500011 PM 9619479 ER PT J AU Rapola, JM Virtamo, J Ripatti, S Haukka, JK Huttunen, JK Albanes, D Taylor, PR Heinonen, OP AF Rapola, JM Virtamo, J Ripatti, S Haukka, JK Huttunen, JK Albanes, D Taylor, PR Heinonen, OP TI Effects of alpha tocopherol and beta carotene supplements on symptoms, progression, and prognosis of angina pectoris SO HEART LA English DT Article DE antioxidants; angina pectoris; prevention; vitamin supplements ID ANTIOXIDANT VITAMIN INTAKE; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; CORONARY-DISEASE; CONTROLLED TRIAL; E CONSUMPTION; RISK; MALES; MEN AB Objective-To evaluate the effects of alpha tocopherol and beta carotene supplements on recurrence and progression of angina symptoms, and incidence of major coronary events in men with angina pectoris. Design-Placebo controlled clinical trial. Setting-The Finnish alpha tocopherol beta carotene cancer prevention study primarily undertaken to examine the effects of a tocopherol and beta carotene on cancer. Subjects-Male smokers aged 50-69 years who had angina pectoris in the Rose chest pairs questionnaire at baseline (n = 1795). Interventions-alpha tocopherol (vitamin E) 50 mg/day, beta carotene 20 mg/day or both, or placebo in 2 x 2 factorial design. Main outcome measures-Recurrence of angina pectoris at annual follow up visits when the questionnaire was readministered; progression from mild to severe angina; incidence of major coronary events (non-fatal myocardial infarction and fatal coronary heart disease). Results-There were 2513 recurrences of angina pectoris during follow up (median 4 years). Compared to placebo, the odds ratios for recurrence in the active treatment groups were: alpha tocopherol only 1.06 (95% confidence interval (CI) 0.85 to 1.33), alpha tocopherol and beta carotene 1.02 (0.82 to 1.27), beta carotene only 1.06 (0.84 to 1.33). There were no significant differences in progression to severe angina among the groups given supplements or placebo. Altogether 314 major coronary events were observed during follow up (median 5.5 years) and the risk for them did not differ significantly among the groups given supplements or placebo. Conclusions-There was no evidence of beneficial effects for a tocopherol or beta carotene supplements in male smokers with angina pectoris, indicating no basis for therapeutic or preventive use of these agents in such patients. C1 Natl Publ Hlth Inst, Dept Nutr, FIN-00300 Helsinki, Finland. NCI, Bethesda, MD 20892 USA. Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. RP Rapola, JM (reprint author), Natl Publ Hlth Inst, Dept Nutr, Mannerheimintie 166, FIN-00300 Helsinki, Finland. EM Janne.Rapola@ktl.fi RI Albanes, Demetrius/B-9749-2015; Ripatti, Samuli/H-9446-2014; Haukka, Jari/G-1484-2014 OI Ripatti, Samuli/0000-0002-0504-1202; Haukka, Jari/0000-0003-1450-6208 FU NCI NIH HHS [N01-CN-45165] NR 34 TC 49 Z9 50 U1 1 U2 4 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD MAY PY 1998 VL 79 IS 5 BP 454 EP 458 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZM543 UT WOS:000073550700009 PM 9659191 ER PT J AU Yu, MS Emerson, SU Cote, P Shapiro, M Purcell, RH AF Yu, MS Emerson, SU Cote, P Shapiro, M Purcell, RH TI The GDPAL region of the pre-S1 envelope protein is important for morphogenesis of woodchuck hepatitis virus SO HEPATOLOGY LA English DT Article ID B SURFACE-ANTIGEN; AVIAN HEPADNAVIRUS; DNA-SYNTHESIS; VIRAL-DNA; REPLICATION; EXPRESSION; INFECTION; SELECTION; SEQUENCE; DOMAIN AB The pre-S envelope protein of duck hepatitis B virus (DHBV) contains a region, Asp-Asp-Pro-Leu-Leu (DDPLL), that is specifically required for virus assembly and secretion (Lenhoff and Summers, J Virol 1994;68:4565-4571). We found that amino acids 201 to 205 of the pre-S envelope protein of woodchuck hepatitis virus (WHV) form a conserved amino acid cluster, Gly-Asp-Pro-Ala-Leu (GDPAL), which resembles the DDPLL sequence of DHBV, To determine whether the GDPAL region was functionally equivalent to the DDPLL region, we deleted this region from the pre-S protein of WHV or mutated individual amino acids within the region. The mutant DNA was transfected into human hepatoma cell line Huh7, and the medium was assayed for virion production by immunoprecipitation and Southern blot analysis. We found that an in-frame deletion of this small region inhibited virion formation, suggesting that the GDPAL region of the pre-S envelope protein was required for virus assembly and/or secretion of WHV. Individual replacement of alanine 204, leucine 205, or serine 206 with other amino acid residues did not affect virus production. However, substitution of either aspartic acid 202 with valine or proline 203 with leucine dramatically inhibited WHV production. Furthermore, the GDPAL mutants were individually tested for their abilities to complement a pre-S1 defective genome. The results showed that the GDPAL region functioned as part of the pre-S1 protein but was not required to function as part of the pre-S2 protein. C1 NIAID, Infect Dis Lab, Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Sch Med, Div Mol Virol & Immunol, Rockville, MD USA. Bioqual Inc, Rockville, MD USA. RP Yu, MS (reprint author), NCI, Expt Carcinogenesis Lab, Chem Carcinogenesis Sect, NIH, Bethesda, MD 20892 USA. NR 28 TC 2 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 1998 VL 27 IS 5 BP 1408 EP 1414 DI 10.1002/hep.510270531 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZK414 UT WOS:000073318500031 PM 9581699 ER PT J AU Fortin, E AF Fortin, E TI Neurovisual complications of interferon-alpha therapy SO HEPATOLOGY LA English DT Editorial Material ID HEPATITIS TYPE-C; ALFA; HEMORRHAGE C1 NEI, NIH, Bethesda, MD 20892 USA. RP Fortin, E (reprint author), NEI, NIH, 10 Ctr Dr,Bldg 10,Rm 10 N 112, Bethesda, MD 20892 USA. NR 20 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 1998 VL 27 IS 5 BP 1441 EP 1442 DI 10.1002/hep.510270536 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZK414 UT WOS:000073318500036 PM 9581704 ER PT J AU Lippincott-Schwartz, J Cole, NB Donaldson, JG AF Lippincott-Schwartz, J Cole, NB Donaldson, JG TI Building a secretory apparatus: role of ARF1/COPI in Golgi biogenesis and maintenance SO HISTOCHEMISTRY AND CELL BIOLOGY LA English DT Review ID ADP-RIBOSYLATION FACTOR; ENDOPLASMIC-RETICULUM; BREFELDIN-A; BETA-COP; INTERMEDIATE COMPARTMENT; GUANINE-NUCLEOTIDE; PROTEIN-TRANSPORT; PHOSPHOLIPASE-D; VESICLE TRAFFICKING; MEMBRANE-PROTEIN AB The secretory apparatus within all eukaryotic cells comprises a dynamic membrane system with bidirectional membrane transport pathways and overlapping compartmental boundaries. Membrane traffic and organelle biogenesis/maintenance are fundamentally linked within this system, with perturbations in membrane traffic quickly leading to changes in organelle structure and identity. Dissection of the molecular basis of these properties in yeast and mammalian cells has revealed a crucial role for the cytoplasmic protein complex ARF1/COPI, which undergoes regulated assembly and disassembly with membranes. ARF1/COPI appears to be involved in the formation and maintenance of the Golgi complex, which is the receiving and delivery station for all secretory traffic. ARF1-GTP, through assembly of COPI to membranes and, possibly, through activation of PLD, is likely to promote the formation and maturation of pre-Golgi intermediates into Golgi elements, whereas ARF-GDP causes COPI dissociation and stimulates the formation of retrograde transport structures that recycle Golgi membrane back to the ER. These processes are appear to underlie the coupling of organelle biogenesis and membrane trafficking within cells, allowing the size and shape of secretory organelles to be altered in response to changing cellular needs. Future work needs to address how the activation and localization of ARF1/COPI to membranes as well as other related factors are temporally and spatially regulated, and by what mechanism they transform membrane shape and dynamics to facilitate protein transport and compartmental functioning. C1 NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Lippincott-Schwartz, J (reprint author), NICHD, Cell Biol & Metab Branch, NIH, Bldg 18T,Room 101,18 Lib Dr, Bethesda, MD 20892 USA. EM jlippin@helix.nih.gov NR 118 TC 67 Z9 67 U1 2 U2 6 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0301-5564 J9 HISTOCHEM CELL BIOL JI Histochem. Cell Biol. PD MAY-JUN PY 1998 VL 109 IS 5-6 BP 449 EP 462 DI 10.1007/s004180050247 PG 14 WC Cell Biology; Microscopy SC Cell Biology; Microscopy GA ZW657 UT WOS:000074433600004 PM 9681627 ER PT J AU Orban, Z Bornstein, SR Chrousos, GP AF Orban, Z Bornstein, SR Chrousos, GP TI The interaction between leptin and the hypothalamic-pituitary-thyroid axis SO HORMONE AND METABOLIC RESEARCH LA English DT Review DE leptin; hypothalamic; pituitary; thyroid axis ID WHITE ADIPOSE-TISSUE; PARAVENTRICULAR NUCLEUS; HYPERTHYROID PATIENTS; COPULSATILE RELEASE; SECRETION RATE; HYPOTHYROIDISM; HORMONE; THYROTROPIN; GENE; NOREPINEPHRINE AB The description of the adipose tissue hormone leptin has led to important discoveries. Leptin plays a role not only in the regulation of metabolic efficiency, energy expenditure, food intake and adiposity, but also contributes greatly to the adaptation of the organism to starvation, Much of the literature has focused on the physiologic roles of leptin-driven processes as diverse as feeding behavior, body weight, defense to starvation and reproduction, The following discussion summarizes knowledge that has accumulated regarding the interaction between leptin and the hypothalamic-pituitary-thyroid axis. C1 NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Orban, Z (reprint author), NICHHD, Dev Endocrinol Branch, Bldg 10,Room 10N262,10 Ctr Dr, Bethesda, MD 20892 USA. NR 64 TC 33 Z9 35 U1 0 U2 1 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD MAY PY 1998 VL 30 IS 5 BP 231 EP 235 DI 10.1055/s-2007-978872 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZU903 UT WOS:000074247900001 PM 9660078 ER PT J AU Stratakis, CA AF Stratakis, CA TI The familial lentiginosis syndromes are emerging from the obscurity imposed by rarity: New genes and genetic loci for multiple tumors and developmental defects SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE lentigines; Peutz-Jeghers Syndrome; LEOPARD Syndrome; myxomas; Cowden Disease; Carney Complex; adrenal gland AB Lentigines (similar but not identical to "ephelides" or "freckles") are common skin lesions, which, in a small number of patients, can be of great interest to endocrinologists and other nondermatological specialists. In these cases, lentigines constitute part of genetic syndromes that are associated with inherited forms of neoplasias or other pathologic processes of the cardiovascular, endocrine, and gastrointestinal systems. The familial lentiginoses, as these syndromes are collectively known, include the Leopard and Peutz-Jeughers syndromes, Carney complex, and the newly described "syndrome of arterial dissections with lentiginosis". Additional disorders, like Cowden's disease, Bannayan-Ruvalcaba-Riley syndrome and others, have phenotypes that overlap with the lentiginoses, Macronodular adrenocortical hyperplasia is a special case in the cohort of diseases reported here, because it is not associated with any skin lesions; however, the bilateral nature of adrenocortical defects and the new molecular insights into its pathophysiology make it a disorder particularly interesting to the researchers that investigate primary pigmented adrenocortical disease (PPNAD), the adrenal pathology seen in Carney complex. In the majority of the reported kindreds with lentiginosis and related syndromes, the lesions are inherited in an autosomal dominant manner. The genetic loci and specific genes for these syndromes are now under intense investigation. These genes appear not only to participate in the pleiotropy of human pigmentation, but also to be involved in the function, growth and proliferation of other neural crest and mesenchymal cells. The abstracts that follow describe the most recent advances in the field of familiar lentiginosis as well as provide us with some insight from the pioneers in the field: Dr. McCusick (Peutz-Jeghers syndrome), Dr. Gorlin (LEOPARD syndrome), Dr. Carney (Carney complex). This represents a unique blend of clinical and basic research, medical history and molecular biology, made possible by a generous grant from the Office of Rare Diseases (ORD), Office of the Director (OD), National Institutes of Health (NIH), which funded the "1(st) International Meeting on Carney complex and related disorders" held at the NIH on May 1(st), 1998. The abstracts are listed in the order they were presented at the meeting. C1 NICHHD, Unit Genet & Endocrinol, Sect Pediat Endocrinol, Dev Endocrinol Branch,NICHD,NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Pediat, Div Genet & Ped Endocrinol, Washington, DC 20057 USA. RP Stratakis, CA (reprint author), NICHHD, Unit Genet & Endocrinol, Sect Pediat Endocrinol, Dev Endocrinol Branch,NICHD,NIH, Blg 10,Room 10 N 262,10 Ctr Dr,MSC 1852, Bethesda, MD 20892 USA. NR 0 TC 8 Z9 8 U1 0 U2 1 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD MAY PY 1998 VL 30 IS 5 BP 285 EP 290 DI 10.1055/s-2007-978885 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZU903 UT WOS:000074247900014 ER PT J AU Maass, G Bogedain, C Scheer, U Michl, D Horer, M Braun-Falco, M Volkenandt, M Schadendorf, D Wendtner, CM Winnacker, EL Kotin, RM Hallek, M AF Maass, G Bogedain, C Scheer, U Michl, D Horer, M Braun-Falco, M Volkenandt, M Schadendorf, D Wendtner, CM Winnacker, EL Kotin, RM Hallek, M TI Recombinant adeno-associated virus for the generation of autologous, gene-modified tumor vaccines: Evidence for a high transduction efficiency into primary epithelial cancer cells SO HUMAN GENE THERAPY LA English DT Article ID HEMATOPOIETIC PROGENITOR CELLS; ADENOASSOCIATED VIRUS; PHENOTYPIC CORRECTION; NONDIVIDING CELLS; T-LYMPHOCYTES; VECTORS; EXPRESSION; THERAPY; SUPPRESSION; REJECTION AB To explore the potential of recombinant vectors based on recombinant adeno-associated virus (rAAV) for cancer vaccination, we investigated the transduction efficiency of rAAV into cancer cells ex vivo. Infection of human epithelial cancer cell lines with rAAV carrying reporter genes encoding beta-galactosidase (rAAV/LacZ) or luciferase (rAAV/Luc) resulted in high levels of reporter gene expression (> 90% positive cells). In marked contrast, rAAV poorly transduced all murine tumor cell lines, as well as human hematopoietic cell lines. Either irradiation or adenovirus infection of tumor cells prior to rAAV infection induced a 10- to 100-fold increase of reporter gene expression. To determine the transduction efficiency of rAAV into primary cancer cells, freshly isolated, irradiated tumor cells from malignant melanoma and ovarian carcinoma patients were infected with rAAV/Luc, resulting in up to 6.9-fold higher levels of gene expression than in a HeLa tumor cell line. Time course experiments with freshly isolated tumor cells infected with rAAV/Luc showed maximal levels of luciferase expression between days 3 and 9 posttransduction. Simultaneous infection of primary tumor cells with up to three rAAV vectors containing genes encoding the immunostimulatory proteins B7-2 (CD86), p35 subunit of IL-12, and p40 subunit of IL-12 resulted in high expression of B7-2 in more than 90% of the tumor cells and in the secretion of high levels of IL-12. Taken together, our results demonstrate that rAAV efficiently transduces freshly isolated human, epithelial tumor cells and might therefore be a potent tool to produce improved, gene-modified cancer vaccines. C1 MediGene AG, Munich, Germany. Univ Munich, Genzentrum, Munich, Germany. Univ Munich, Dermatol Klin & Poliklin, D-8000 Munich, Germany. Univ Heidelberg, Heidelberg, Germany. Univ Munich, Klinikum Innenstadt, Med Klin, D-8000 Munich, Germany. NHLBI, Mol Hematol Branch, Bethesda, MD 20892 USA. RP Bogedain, C (reprint author), MediGene AG, Lochhamer Str 11, D-82152 Martinsried, Germany. RI kotin, robert/B-8954-2008 NR 40 TC 33 Z9 35 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAY 1 PY 1998 VL 9 IS 7 BP 1049 EP 1059 DI 10.1089/hum.1998.9.7-1049 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA ZM551 UT WOS:000073551500010 PM 9607416 ER PT J AU Sterman, DH Treat, J Litzky, LA Amin, KM Coonrod, L Molnar-Kimber, K Recio, A Knox, L Wilson, JM Albelda, SM Kaiser, LR AF Sterman, DH Treat, J Litzky, LA Amin, KM Coonrod, L Molnar-Kimber, K Recio, A Knox, L Wilson, JM Albelda, SM Kaiser, LR TI Adenovirus-mediated herpes simplex virus thymidine kinase/ganciclovir gene therapy in patients with localized malignancy: Results of a phase I clinical trial in malignant mesothelioma SO HUMAN GENE THERAPY LA English DT Article ID HUMAN CFTR CDNA; CYSTIC-FIBROSIS; PLEURAL MESOTHELIOMA; BRAIN-TUMORS; KINASE GENE; LUNG-CANCER; RECOMBINANT ADENOVIRUS; EXPERIMENTAL GLIOMAS; NASAL EPITHELIUM; VECTOR AB Malignant pleural mesothelioma is a fatal neoplasm that is unresponsive to standard modalities of cancer therapy. We conducted a phase I dose-escalation clinical trial of adenoviral (Ad)-mediated intrapleural herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) gene therapy in patients with mesothelioma as a model for treatment of a localized malignancy. The goals of this phase I trial were to assess the safety, toxicity, and maximally tolerated dose of intrapleural Ad.HSVtk, to examine patient inflammatory response to the viral vector, and to evaluate the efficiency of intratumoral gene transfer. Twenty-one previously untreated patients were enrolled in this single-arm, dose-escalation study with viral doses ranging from 1 X 10(9) plaque-forming units (pfu) to 1 X 10(12) pfu. A replication-incompetent recombinant adenoviral vector containing the HSVtk gene under control of the Rous sarcoma virus (RSV) promoter-enhancer was introduced into the pleural cavity of patients with malignant mesothelioma followed by 2 weeks of systemic therapy with GCV at a dose of 5 mg/kg twice a day. The initial 15 patients underwent thoracoscopic pleural biopsy prior to, and 3 days after, vector delivery. The last six patients underwent only the post-vector instillation biopsy. Dose-limiting toxicity was not reached. Side effects were minimal and included fever, anemia, transient liver enzyme elevations, and bullous skin eruptions, as well as a temporary systemic inflammatory response in those receiving the highest dose. Strong intrapleural and intratumoral immune responses were generated. Using RNA PCR, in situ hybridization, immunohistochemistry, and immunoblotting, HSVtk gene transfer was documented in 11 of 20 evaluable patients in a dose-related fashion. This study demonstrates that intrapleural administration of an adenoviral vector containing the HSVtk gene is well tolerated and results in detectable gene transfer when delivered at high doses. Further development of therapeutic trials for treatment of localized malignancy using this vector is thus warranted. C1 Univ Penn, Med Ctr, Div Pulm & Crit Care Med, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, Div Hematol Oncol, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, Dept Pathol, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, Dept Surg, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, NIH, Gen Clin Res Ctr, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, Dept Mol & Cellular Engn, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, Inst Human Gene Therapy, Philadelphia, PA 19104 USA. RP Kaiser, LR (reprint author), Hosp Univ Penn, Dept Surg, 6 Silverstein Bldg,3400 Spruce St, Philadelphia, PA 19104 USA. RI Wilson, James/F-9220-2011; OI Wilson, James/0000-0002-9630-3131; Sterman, Daniel/0000-0003-1249-0804 FU NCI NIH HHS [P01 CA66726]; NCRR NIH HHS [MO1-RR00040] NR 38 TC 255 Z9 264 U1 1 U2 1 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 MAY 1 PY 1998 VL 9 IS 7 BP 1083 EP 1092 DI 10.1089/hum.1998.9.7-1083 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA ZM551 UT WOS:000073551500013 PM 9607419 ER PT J AU DeStefano, AL Cupples, LA Arnos, KS Asher, JH Baldwin, CT Blanton, S Carey, ML da Silva, EO Friedman, TB Greenberg, J Lalwani, AK Milunsky, A Nance, WE Pandya, A Ramesar, RS Read, AP Tassabejhi, M Wilcox, ER Farrer, LA AF DeStefano, AL Cupples, LA Arnos, KS Asher, JH Baldwin, CT Blanton, S Carey, ML da Silva, EO Friedman, TB Greenberg, J Lalwani, AK Milunsky, A Nance, WE Pandya, A Ramesar, RS Read, AP Tassabejhi, M Wilcox, ER Farrer, LA TI Correlation between Waardenburg syndrome phenotype and genotype in a population of individuals with identified PAX3 mutations SO HUMAN GENETICS LA English DT Article ID SYNDROME TYPE-I; HUP2 PAIRED DOMAIN; SYNDROME WS; DOMINANT INHERITANCE; MISSENSE MUTATION; SPLOTCH MOUSE; HUMAN HOMOLOG; GENE; HETEROGENEITY; DISEASE AB Waardenburg syndrome (WS) type 1 is an autosomal dominant disorder characterized by sensorineural hearing loss, pigmentary abnormalities of the eye, hair, and skin, and dystopia canthorum. The phenotype is variable and affected individuals may exhibit only one or a combination of several of the associated features. To assess the relationship between phenotype and gene defect, clinical and genotype data on 48 families (271 WS individuals) collected by members of the Waardenburg Consortium were pooled. Forty-two unique mutations in the PAX3 gene, previously identified in these families, were grouped in five mutation categories: amino acid (AA) substitution in the paired domain, AA substitution in the homeodomain, deletion of the Ser-Thr-Pro-rich region, deletion of the homeodomain and the Ser-Thr-Pro-rich region, and deletion of the entire gene. These mutation classes are based on the structure of the PAX3 gene and were chosen to group mutations predicted to have similar defects in the gene product. Association between mutation class and the presence of hearing loss, eye pigment abnormality, skin hypopigmentation, or white forelock was evaluated using generalized estimating equations, which allowed for incorporation of a correlation structure that accounts for potential similarity among members of the same family. Odds for the presence of eye pigment abnormality, white forelock, and skin hypopigmentation were 2, 8, and 5 times greater, respectively, for individuals with deletions of the homeodomain and the Pro-Ser-Thr-rich region compared to individuals with an AA substitution in the homeodomain. Odds ratios that differ significantly from 1.0 for these traits may indicate that the gene products resulting from different classes of mutations act differently in the expression of WS. Although a suggestive association was detected for hearing loss with an odds ratio of 2.6 for AA substitution in the paired domain compared with AA substitution in the homeodomain, this odds ratio did not differ significantly from 1.0. C1 Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Epidemiol & Biostat, Boston, MA 02118 USA. Boston Univ, Sch Med, Ctr Human Genet, Boston, MA 02118 USA. Gallaudet Univ, Washington, DC 20002 USA. Michigan State Univ, Dept Zool, E Lansing, MI 48824 USA. Michigan State Univ, Grad Program Genet, E Lansing, MI 48824 USA. Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA 23298 USA. Univ Fed Pernambuco, Dept Genet, Recife, PE, Brazil. Univ Cape Town, Dept Human Genet, ZA-7925 Cape Town, South Africa. Univ San Francisco, Dept Otorhinolaryngol, San Francisco, CA 94117 USA. Univ Manchester, Manchester, Lancs, England. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. RP Farrer, LA (reprint author), Boston Univ, Sch Med, Dept Neurol, 80 E Concord St, Boston, MA 02118 USA. RI Ramesar, Raj/I-6941-2015; OI Ramesar, Raj/0000-0001-5688-1634; Farrer, Lindsay/0000-0001-5533-4225 FU NIDCD NIH HHS [R01 DC01160, R01 DC01848, R01 DC02407]; Wellcome Trust NR 36 TC 33 Z9 35 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAY PY 1998 VL 102 IS 5 BP 499 EP 506 DI 10.1007/s004390050732 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA ZU188 UT WOS:000074171100001 PM 9654197 ER PT J AU Chang, S Rosenberg, MJ Morton, H Francomano, CA Biesecker, LG AF Chang, S Rosenberg, MJ Morton, H Francomano, CA Biesecker, LG TI Identification of a mutation in liver glycogen phosphorylase in glycogen storage disease type VI SO HUMAN MOLECULAR GENETICS LA English DT Article ID DEFICIENCY MCARDLES-DISEASE; MYOPHOSPHORYLASE DEFICIENCY; LINKAGE ANALYSIS; STRATEGIES; HUMANS; CODON AB Glycogen storage disease type VI (GSD6) defines a group of disorders that cause hepatomegaly and hypoglycemia with reduced liver phosphorylase activity. The course of these disorders is generally mild, but definitive diagnosis requires invasive procedures. We analyzed a Mennonite kindred with an autosomal recessive form of GSD6 to determine the molecular defect and develop a non-invasive diagnostic test. Linkage analysis was performed using genetic markers flanking the liver glycogen phosphorylase gene (PYGL), which was suspected to be the cause of the disorder on biochemical grounds. Mennonite GSD6 was linked to the PYGL locus with a multipoint LOD score of 4.7. The PYGL gene was analyzed for mutations by sequencing genomic DNA. Sequencing of genomic DNA revealed a splice site abnormality of the intron 13 splice donor. Confirmation of the genomic mutation was performed by sequencing RT-PCR products, which showed heterogeneous PYGL mRNA lacking all or part of exon 13 in affected persons. This study is the first to demonstrate that a mutation in the PYGL gene can cause GSD6. This mutation is estimated to be present on 3% of Mennonite chromosomes and the disease affects 0.1% of that population. Determination of this mutation provides a basis for the development of a simple and non-invasive diagnostic test for the disease and the carrier state in this population and confirms biochemical data showing the importance of this gene in glucose homeostasis. C1 Natl Human Genome Res Inst, Lab Genet Dis Res, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Clin Special Children, Strasbourg, PA 17579 USA. Johns Hopkins Univ, Ctr Med Genet, Baltimore, MD 21287 USA. RP Biesecker, LG (reprint author), 49 Convent Dr,Room 4A80, Bethesda, MD 20892 USA. RI Chang, Susie/E-2870-2011 NR 26 TC 16 Z9 17 U1 2 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY PY 1998 VL 7 IS 5 BP 865 EP 870 DI 10.1093/hmg/7.5.865 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA ZN549 UT WOS:000073657000013 PM 9536091 ER PT J AU Fogt, F Vargas, MP Zhuang, ZP Merino, MJ AF Fogt, F Vargas, MP Zhuang, ZP Merino, MJ TI Utilization of molecular genetics in the differentiation between adrenal cortical adenomas and carcinomas SO HUMAN PATHOLOGY LA English DT Article DE adrenal cortical tumors; loss of heterozygosity ID ADRENOCORTICAL CARCINOMA; P53 MUTATIONS; TUMORS; HETEROZYGOSITY; NEOPLASMS; CANCERS; GENES; LOCI; 9P21 AB Distinction between benign adrenal cortical proliferative lesions and adrenal cortical carcinoma has been approached by a combination of histological, immunohistochemical, and macroscopical parameters. Modern imaging studies allow detection of small adrenal cortical lesions that may be incorrectly diagnosed. Differentiation between benign and malignant tumors of the adrenal cortex nas attempted by microdissection of nine cases of adrenal cortical hyperplasia, 10 cortical adenomas, and 18 adrenalcortical carcinomas with subsequent polymerase chain reaction (PCR) amplification for loss of heterozygosity (LOH) of five microsatellites of putative tumor suppressor gene loci: p53 gene (17p), the neuroblastoma candidate gene (Ip), the p16 gene (9p), the von Hippel Lindau gene (3p), and the retinoblastoma gene (13q). None of the hyperplastic lesions or cortical adenomas showed LOH of any of the gene markers used. Conversely, genetic changes were observed in 61% (11 of 18) of the cases of carcinoma. Forty-four percent of the lesions showed LO for p53 (7 of 16). LOH of Ip, 3p, and 9p ic ere seen in 22%, 22%, and 26%, respectively LOH of the retinoblastoma gene was seen in 80% or four of five of the informative cases studied. We conclude that LOH studies may be used to distinguish malignant from nonmalignant adrenal cortical proliferations. Relative infrequency of LOH in 3p may furthermore help to differentiate adrenal lesions from clear cell carcinomas of the kidney. Copyright (C) 1998 by W.B. Saunders Company. C1 NIH, Pathol Lab, Bethesda, MD 20892 USA. RP Fogt, F (reprint author), Univ Penn, Presbyterian Med Ctr, Dept Pathol, 39th & Market St, Philadelphia, PA 19104 USA. NR 22 TC 10 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 1998 VL 29 IS 5 BP 518 EP 521 DI 10.1016/S0046-8177(98)90069-7 PG 4 WC Pathology SC Pathology GA ZM542 UT WOS:000073550600014 PM 9596277 ER PT J AU Anasti, JN Kalantaridou, SN Kimzey, LM George, M Nelson, LM AF Anasti, JN Kalantaridou, SN Kimzey, LM George, M Nelson, LM TI Human follicle fluid vascular endothelial growth factor concentrations are correlated with luteinization in spontaneously developing follicles SO HUMAN REPRODUCTION LA English DT Article DE dominant follicle; follicle fluid; human; luteinization; vascular endothelial growth factor ID OVARIAN HYPERSTIMULATION SYNDROME; PERMEABILITY FACTOR; GRANULOSA-CELLS; GRAAFIAN-FOLLICLES; MENSTRUAL-CYCLE; FACTOR VEGF; EXPRESSION; ANGIOGENESIS; MISCARRIAGE; INVITRO AB Vascular endothelial growth factor (VEGF) is a cytokine that induces angiogenesis. Angiogenesis is a prominent histologic component of the luteinization process. Luteinization is also characterized by granulosa cell progesterone secretion in response to the luteinizing hormone (LH) surge. Local VEGF production in human pre-ovulatory follicles, induced by LH, was postulated to be a luteinization mediator in women. To investigate this hypothesis, serum and fluid from the dominant follicle of 31 healthy regularly cycling multiparous women undergoing laparoscopic sterilization were obtained. VEGF was measured by enzyme-linked immunosorbent assay, and LH and progesterone were measured by radioimmunoassay, Follicle aspiration was performed at a median of 13 days from the last menstrual period (range 11-17 days). The median preovulatory follicle diameter was 16 mm (range 11-23 mm), Follicle fluid VEGF concentrations (mean 6900 pg/ml, range 1200-17 100 pg/ml) were correlated positively with follicle fluid progesterone concentrations (mean 10 176 nmol/l, range 636-66 780 nmol/l, r = 0.62, P = 0.002), This correlation was even tighter (r = 0.87, P < 0.0001) when only samples from the 22 women in the earliest stages of follicle luteinization were considered. In these women serum LH concentrations were also correlated with follicle fluid VEGF concentrations (r = 0.51, P = 0.02), Our findings demonstrate the close dynamic relationship between VEGF production and early luteinization in human follicles during normal non-stimulated cycles. C1 NICHHD, Sect Womens Hlth, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Clin Ctr Nursing Dept, NIH, Bethesda, MD 20892 USA. RP Nelson, LM (reprint author), NICHHD, Sect Womens Hlth, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NR 35 TC 39 Z9 42 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD MAY PY 1998 VL 13 IS 5 BP 1144 EP 1147 DI 10.1093/humrep/13.5.1144 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA ZT614 UT WOS:000074105500014 PM 9647535 ER PT J AU Bagrov, AY Fedorova, OV Dmitrieva, RI Howald, WN Hunter, AP Kuznetsova, EA Shpen, VM AF Bagrov, AY Fedorova, OV Dmitrieva, RI Howald, WN Hunter, AP Kuznetsova, EA Shpen, VM TI Characterization of a urinary bufodienolide Na+,K+-ATPase inhibitor in patients after acute myocardial infarction SO HYPERTENSION LA English DT Article; Proceedings Paper CT 11th Meeting of the American-Society-of-Hypertension CY MAY 15-18, 1996 CL NEW YORK, NEW YORK SP Amer Soc Hypertens DE Na+-K+-ATPase; bufodienolides; myocardial infarction; digitalis-like factors ID DIGITALIS-LIKE FACTORS; DIGOXIN-LIKE IMMUNOREACTIVITY; VENTRICULAR ARRHYTHMIAS; NATRIURETIC HORMONE; HUMAN-PLASMA; ISCHEMIA; OUABAIN; MARINOBUFAGENIN; COMPOUND; SODIUM AB Recent evidence suggests the existence of several endogenous Na+,K+-ATPase inhibitors in mammals. Previously, we have shown that the amphibian Na+,K+-ATPase inhibitor marinobufagenin (3,5-dihydroxy-14,15-epoxy bufodienolide) acts as a vasoconstrictor in isolated rat and human arteries. Mammalian plasma was shown to contain marinobufagenin-like immunoreactive material, which is responsive to saline volume expansion. The present study describes purification of a bufodienolide, which is similar to marinobufagenin, from the urine of patients after acute myocardial infarction with the use of thin-layer chromatography and reverse-phase high-performance liquid chromatography (HPLC). The purified substance cross-reacted with marinobufagenin antibody, demonstrated maximal UV absorbance at 300 nm characteristic of bufodienolides, and eluted from HPLC columns with the same retention time as marinobufagenin. Mass spectrometry of purified material revealed the presence of a substance indistinguishable from amphibian marinobufagenin and having molecular mass of 400 D. The present studies show that one of the human digitalis-like factors may have a bufodienolide structure and is likely to represent marinobufagenin or its isomer, and they suggest a role for this substance in the pathogenesis of myocardial ischemia. C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. IM Sechenov Evolutionary Physiol & Biochem Inst, Pharmacol Lab, St Petersburg, Russia. Verta Peptides Inc, St Petersburg, Russia. Univ Washington, Mass Spectrometry Ctr, Dept Med Chem, Seattle, WA 98195 USA. RP Bagrov, AY (reprint author), NIA, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM BagrovA@grc.nia.nih.gov OI Dmitrieva, Renata/0000-0002-3073-7914 NR 47 TC 101 Z9 104 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAY PY 1998 VL 31 IS 5 BP 1097 EP 1103 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ZM283 UT WOS:000073523000008 PM 9576120 ER PT J AU Lee, C Eden, M Unser, M AF Lee, C Eden, M Unser, M TI High-quality image resizing using oblique projection operators SO IEEE TRANSACTIONS ON IMAGE PROCESSING LA English DT Article DE B-spline models; image scaling (magnification and reduction); oblique projection; orthogonal projection; resampling ID SPLINE FILTERS; INTERPOLATION; WAVELETS; REPRESENTATION; APPROXIMATION; DESIGN; L(2) AB The standard interpolation approach to image resizing is to fit the original picture with a continuous model and resample the function at the desired rate. However, one can obtain more accurate results if one applies a filter prior to sampling, a fact well known from sampling theory, The optimal solution corresponds to an orthogonal projection onto the underlying continuous signal space. Unfortunately, the optimal projection prefilter is difficult to implement when sine or high order spline functions are used. In this paper, we propose to resize the image using an oblique rather than an orthogonal projection operator in order to make use of faster, simpler, and more general algorithms. We show that we can achieve almost the same result as with the orthogonal projection provided that we use the same approximation space. The main advantage is that it becomes perfectly feasible to use higher order models (e.g, splines of degree n greater than or equal to 3), We develop the theoretical background and present a simple and practical implementation procedure using B-splines, Our experiments show that the proposed algorithm consistently outperforms the standard interpolation methods and that it provides essentially the same performance as the optimal procedure (least squares solution) with considerably fewer computations. The method works for arbitrary scaling factors and is applicable to both image enlargement and reduction. C1 Yonsei Univ, Dept Elect Engn, Seoul 120749, South Korea. NIH, BEIP, NCRR, Bethesda, MD 20892 USA. Swiss Fed Inst Technol, IOA, DMT, EPFL, CH-1015 Lausanne, Switzerland. RP Yonsei Univ, Dept Elect Engn, Seoul 120749, South Korea. EM chulhee@bubble.yonsei.ac.kr; edenm@helix.nih.gov; Michael.Unser@epfl.ch RI Unser, Michael/A-1550-2008 NR 27 TC 42 Z9 46 U1 1 U2 8 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1057-7149 EI 1941-0042 J9 IEEE T IMAGE PROCESS JI IEEE Trans. Image Process. PD MAY PY 1998 VL 7 IS 5 BP 679 EP 692 DI 10.1109/83.668025 PG 14 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA ZK247 UT WOS:000073300100005 PM 18276284 ER PT J AU Martin, MP Harding, A Chadwwick, R Kronick, M Cullen, M Lin, L Mignot, E Carrington, M AF Martin, MP Harding, A Chadwwick, R Kronick, M Cullen, M Lin, L Mignot, E Carrington, M TI Characterization of 12 microsatellite loci of the human MHC in a panel of reference cell lines (vol 47, pg 131, 1998) SO IMMUNOGENETICS LA English DT Correction C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. Perkin Elmer Corp, Appl Biosyst Div, Foster City, CA USA. Stanford Univ, Ctr Marcolepsy Res, Dept Psychiat, Sch Med, Palo Alto, CA 94304 USA. RP Carrington, M (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. NR 1 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD MAY PY 1998 VL 47 IS 6 BP 503 EP 503 DI 10.1007/s002510050392 PG 1 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA ZN220 UT WOS:000073621900014 ER PT J AU Paul, WE Ben-Sasson, SZ AF Paul, WE Ben-Sasson, SZ TI Time for a new science of vaccinology - A challenge to immunologists SO IMMUNOLOGIST LA English DT Editorial Material C1 NIAID, Immunol Lab, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Hadassah Med Sch, Lautenberg Ctr Gen & Tumor Immunol, IL-911120 Jerusalem, Israel. RP Paul, WE (reprint author), NIAID, Immunol Lab, Bldg 10,Room 11N311, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU HOGREFE & HUBER PUBLISHERS PI KIRKLAND PA PO BOX 2487, KIRKLAND, WA 98083-2487 USA SN 1192-5612 J9 IMMUNOLOGIST JI Immunologist PD MAY-JUN PY 1998 VL 6 IS 3 BP 100 EP + PG 4 WC Immunology SC Immunology GA 127PY UT WOS:000076360800001 ER PT J AU Shearer, WT Mofenson, L AF Shearer, WT Mofenson, L TI HIV and women and pregnancy - Preface SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Texas Childrens Hosp, Dept Allergy & Immunol, Houston, TX 77030 USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, Rockville, MD 20852 USA. RP Shearer, WT (reprint author), Texas Childrens Hosp, Dept Allergy & Immunol, 6621 Fannin St,MC 1-3291, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD MAY PY 1998 VL 18 IS 2 BP XI EP XII PG 2 WC Allergy; Immunology SC Allergy; Immunology GA ZP743 UT WOS:000073784000001 ER PT J AU Mofenson, L AF Mofenson, L TI Antiretroviral therapy and interruption of HIV perinatal transmission SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TO-CHILD TRANSMISSION; ZIDOVUDINE TREATMENT; VERTICAL TRANSMISSION; VIRAL LOAD; TYPE-1; PREGNANCY; TOXICOLOGY; METABOLISM; RESISTANCE AB In the United States in 1994, a regimen of zidovudine (ZDV)-administered during pregnancy, labor, and to the newborn for the first 6 weeks of life-reduced the risk of HIV perinatal transmission by two-thirds. In general clinical practice, this regimen has been associated with dramatic declines in perinatal transmission in the United States and other industrialized countries. The complexity and cost of the ZDV regimen, however, limits its applicability in many developing countries, in which the majority of perinatal transmission occurs. Modified antiretrovirals and other interventions are currently being tested. Over the next few years, the results of these tests should advance our understanding of the pathogenesis of perinatal HIV-1 transmission, as well as provide alternative interventions to reduce the burden of pediatric HIV infection. C1 NICHHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, Rockville, MD 20852 USA. RP Mofenson, L (reprint author), NICHHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, 6100 Execut Blvd,Room 4B11E, Rockville, MD 20852 USA. EM LM65D@nih.gov OI Mofenson, Lynne/0000-0002-2818-9808 NR 65 TC 10 Z9 10 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 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD MAY PY 1998 VL 18 IS 2 BP 441 EP + DI 10.1016/S0889-8561(05)70013-8 PG 25 WC Allergy; Immunology SC Allergy; Immunology GA ZP743 UT WOS:000073784000011 ER PT J AU Horton, WE Udo, I Precht, P Balakir, R Hasty, K AF Horton, WE Udo, I Precht, P Balakir, R Hasty, K TI Cytokine inducible matrix metalloproteinase expression in immortalized rat chondrocytes is independent of nitric oxide stimulation SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE cartilage; cytokines; gelatinase; cell culture ID HUMAN ARTICULAR-CARTILAGE; MESSENGER-RNA EXPRESSION; TISSUE INHIBITOR; GROWTH-FACTOR; GENE-EXPRESSION; GELATINASE-A; COLLAGENASE; STROMELYSIN; ACTIVATION; PROTEOGLYCAN AB The objective of this study was to determine if an immortalized mammalian chondrocyte cell line had a profile of matrix metalloproteinase (MMP) expression that was consistent with what has been reported for primary chondrocytes in vitro and in, vivo. A combination of zymography, Western, and Northern analysis was used to examine the expression of MMPs that are relevant to cartilage degradation. Both interleukin-1 beta and tumor necrosis factor alpha induced a 4- to B-fold increase in the level of MMP-9 expression in conditioned media, and a 17- to 24-fold increase in MMP-3 mRNA. Other compounds such as basic fibroblast growth factor and staurosporine each increased MMP-9 expression individually and potentiated the effects of the two cytokines. Transforming growth factor beta had no positive or inhibitory effects. N-methyl arginine blocked the increase in nitric oxide observed following treatment with the cytokines but did not prevent the increased expression of MMPs. The pattern of metalloproteinase expression observed in IRC cells and the response to cytokines is very similar to what has been reported during the pathogenesis of osteoarthritis. The IRC cells should be useful as a model system to study basic mechanisms controlling chondrocyte MMP expression and to identify pharmacological modulators of this process. C1 NIA, Gerontol Res Ctr, Biol Chem Lab, Baltimore, MD 21224 USA. Univ Tennessee, Dept Anat & Neurobiol, Memphis, TN 38104 USA. RP Horton, WE (reprint author), NIA, Gerontol Res Ctr, Biol Chem Lab, Mailbox 12,4940 Eastern Ave, Baltimore, MD 21224 USA. FU NIAMS NIH HHS [AR-39166] NR 50 TC 34 Z9 34 U1 0 U2 1 PU SOC IN VITRO BIOLOGY PI LARGO PA 9315 LARGO DR WEST, STE 25, LARGO, MD 20774 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD MAY PY 1998 VL 34 IS 5 BP 378 EP 384 PG 7 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA ZQ625 UT WOS:000073886800007 PM 9639100 ER PT J AU Rahimi, N Tremblay, E McAdam, L Roberts, A Elliott, B AF Rahimi, N Tremblay, E McAdam, L Roberts, A Elliott, B TI Autocrine secretion of TGF-beta 1 and TGF-beta 2 by pre-adipocytes and adipocytes: A potent negative regulator of adipocyte differentiation and proliferation of mammary carcinoma cells SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE TGF-beta; adipocytes; proliferation; differentiation; breast cancer ID TRANSFORMING GROWTH-FACTOR; ANCHORAGE-INDEPENDENT GROWTH; BETA TGF-BETA; GENE-EXPRESSION; TRANSGENIC MICE; CYCLE ARREST; FACTOR-ALPHA; C-MET; RECEPTOR; GROWTH-FACTOR-BETA-1 AB We have developed an in, vitro system to examine the influence of adipocytes, a major mammary stromal cell type, on the growth of a murine mammary carcinoma, SP1. Previously, we have shown that 3T3-L1 adipocytes release a mitogenic factor, hepatocyte growth factor, which strongly stimulates proliferation of SP1 cells. We now show that 3T3-L1 preadipocytes secrete active inhibitory molecules which inhibit DNA synthesis in SP1 cells. In addition, latent inhibitory activity is present in conditioned media (CM) from both pre-adipocytes and adipocytes, and is activated following acid treatment. CM also inhibited DNA synthesis in Mv1Lu wild type epithelial cells, but not DR27 mutant epithelial cells which lack TGF-beta type II receptor. Inhibitory activity of CMs was partially abrogated by neutralizing anti-TGF-beta 1 and anti-TGF-beta 2 antibodies, and was removed following ultrafiltration through membranes of 10 000 M-s but not 30 000 M-r pore size. These results show that the inhibitory effect on DNA synthesis is mediated by TGF-beta 1-like and TGF-beta 2-like molecules. In addition, acid-treated CM as well as purified TGF-beta inhibited differentiation of pre-adipocytes. Untreated pre-adipocyte CM, but not mature adipocyte CM, spontaneously inhibited adipocyte differentiation. Together, these findings indicate that pre-adipocytes spontaneously activate their own secreted TGF-beta, whereas mature adipocytes do not, and suggest that activation of TGF-beta has a potent negative regulatory effect on adipocyte differentiation and tumor growth. Thus, TGF-beta may be an important modulator of tumor growth and adipocyte differentiation via both paracrine and autocrine mechanisms. These findings emphasize the importance of adipocyte-tumor interactions in the regulation of tumor microenvironment. C1 Queens Univ, Dept Pathol, Canc Res Labs, Kingston, ON K7L 3N6, Canada. NCI, Chemoprevent Lab, NIH, Bethesda, MD 20892 USA. RP Queens Univ, Dept Pathol, Canc Res Labs, Kingston, ON K7L 3N6, Canada. NR 41 TC 40 Z9 40 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-2690 EI 1543-706X J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD MAY PY 1998 VL 34 IS 5 BP 412 EP 420 PG 9 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA ZQ625 UT WOS:000073886800011 PM 9639104 ER PT J AU Gu, XX Chen, J Barenkamp, SJ Robbins, JB Tsai, CM Lim, DJ Battey, J AF Gu, XX Chen, J Barenkamp, SJ Robbins, JB Tsai, CM Lim, DJ Battey, J TI Synthesis and characterization of lipooligosaccharide-based conjugates as vaccine candidates for Moraxella (Branhamella) catarrhalis SO INFECTION AND IMMUNITY LA English DT Article ID NONTYPABLE HAEMOPHILUS-INFLUENZAE; OUTER-MEMBRANE PROTEIN; OTITIS-MEDIA; SEROTYPE-A; LIPOPOLYSACCHARIDE ANTIGENS; IMMUNOLOGICAL PROPERTIES; PROTECTIVE ANTIBODIES; OLIGOSACCHARIDE; INFECTION; CHILDREN AB Moraxella (Branhamella) catarrhalis is an important cause of otitis media and sinusitis in children and of lower respiratory tract infections in adults, Lipooligosaccharide (LOS) is a major surface antigen of the bacterium and elicits bactericidal antibodies. Treatment of the nos from strain ATCC 25238 with anhydrous hydrazine reduced its toxicity 20,000-fold. as assayed in the Limulus amebocyte lysate (LAL) test. The detoxified LOS (dLOS) was coupled to tetanus toroid (TT) or high-molecular-weight proteins (HMP) from nontypeable Haemophilus influenzae through a linker of adipic acid dihydrazide to form dLOS-TT or dLOS-HMP. The molar ratios of dLOS to TT and HMP conjugates were 19:1 and 31:1, respectively. The antigenicity of the two conjugates was similar to that of the nos, as determined by double immunodiffusion. Subcutaneous or intramuscular injection of both conjugates elicited a 50- to 100-fold rite in the geometric mean of immunoglobulin G (IgG) to the homologous LOS in mice after three injections and a 350- to 700-fold rise of anti-nos IgG in rabbits after two injections. The immunogenicity of the conjugate was enhanced by formulation with monophosphoryl lipid A plus trehalose dimycolate. In rabbits, conjugate-induced antisera had complement-mediated bactericidal activity against the homologous strain and heterologous strains of M. catarrhalis. These results indicate that a detoxified LOS-protein conjugate is a candidate for immunization against M. catarrhalis diseases. C1 NIDCD, NIH, Immunol Lab, Rockville, MD 20850 USA. St Louis Univ, Sch Med, Dept Pediat, St Louis, MO 63104 USA. House Ear Inst, Los Angeles, CA 90057 USA. NICHD, Bethesda, MD 20892 USA. US Food & Drug Adm, Bethesda, MD 20892 USA. RP Gu, XX (reprint author), NIDCD, NIH, Immunol Lab, 5 Res Court,2A31, Rockville, MD 20850 USA. EM xgu@pop.nidcd.nih.gov OI Barenkamp, Stephen/0000-0002-3054-8910 NR 61 TC 59 Z9 62 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1998 VL 66 IS 5 BP 1891 EP 1897 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZL243 UT WOS:000073413100012 PM 9573066 ER PT J AU Yan, SZ Rodrigues, RG Roberts, DD AF Yan, SZ Rodrigues, RG Roberts, DD TI Hemoglobin-induced binding of Candida albicans to the cell-binding domain of fibronectin is independent of the Arg-Gly-Asp sequence SO INFECTION AND IMMUNITY LA English DT Article ID EPITHELIAL ADHESION; RECEPTOR; MATRIX; TROPICALIS; SYSTEMS; LIGAND; SITE AB Hemoglobin specifically induces fibronectin (FN) binding to the pathogenic yeast Candida albicans, Where grown in the complex medium Sabouraud broth, C, albicans expresses receptors that bind to several domains of FN. Growth id defined medium supplemented with 0.1% hemoglobin, however, enhanced the binding of FN to a single class of receptors, with a K-d = 4.6 x 10(-8) M. Competitive binding assays using recombinant and proteolytic fragments of FN revealed that the cell-binding domain mediated this interaction. A recombinant 40-kDa fragment of FN consisting of type III repeats 9 to 13 had an inhibitory activity similar to that of the entire 120-kDa cell-binding domain, indicating that the C-terminal portion of the cell-binding domain contains the binding site. A recombinant 33-kDa fragment of the cell-binding domain and a 33-kDa fragment with the RGD sequence deleted had the same inhibitory activities, demonstrating that the RGD sequence recognized by some mammalian integrins is not required. The addition of hemoglobin to the culture medium also enhanced Candida cell adhesion to immobilized FN and to 120- and 40-kDa fragments of FN but not to the collagen-binding or fibrin I domains. Using ligand protection, we identified a surface protein from C, albicans with an apparent molecular mass of 55 kDa that was protected by both FN and the 40-kDa fragment derived from the cell-binding domain, Therefore, hemoglobin both induces FN binding and changes the relative affinities of C, albicans for the cell- and collagen-binding domains of FN. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Roberts, DD (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A33,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. EM droberts@helix.nih.gov RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 25 TC 17 Z9 17 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1998 VL 66 IS 5 BP 1904 EP 1909 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZL243 UT WOS:000073413100014 PM 9573068 ER PT J AU Sack, DA Tacket, CO Cohen, MB Sack, RB Losonsky, GA Shimko, J Nataro, JP Edelman, R Levine, MM Giannella, RA Schiff, G Lang, D AF Sack, DA Tacket, CO Cohen, MB Sack, RB Losonsky, GA Shimko, J Nataro, JP Edelman, R Levine, MM Giannella, RA Schiff, G Lang, D TI Validation of a volunteer model of cholera with frozen bacteria as the challenge SO INFECTION AND IMMUNITY LA English DT Article ID ABO BLOOD-GROUPS; ANTIBODY-RESPONSES; VIBRIO-CHOLERAE; ORAL VACCINES; B-SUBUNIT; EFFICACY; BANGLADESH; DURATION; IMMUNITY; HUMANS AB To evaluate a standardized inoculum of Vibrio cholerae for volunteer challenge studies, 40 healthy adult volunteers were challenged at three different institutions with a standard inoculum prepared directly from dials of frozen, virulent, Fl Tor Inaba V. cholerae N16961, with no further incubation. Groups of 5 volunteers, with each group including 2 volunteers with blood group O, were given a dose of 10(5) CFU, and 34 of the 40 volunteers developed diarrhea (mean incubation time, 28 h), Transient fevers occurred in 15 (37.5%) of the volunteers. V. cholerae was excreted by 36 of 40 volunteers. Five additional volunteers received 10(4) CFU, and four developed diarrhea but with a lower average purging rate than required for the model. Of the 40 volunteers, 37 developed rises in their vibriocidal and antitoxin titers similar to those in previous groups challenged with freshly harvested bacteria, We conclude that challenge with frozen bacteria results in a reproducible illness similar to that induced by freshly harvested bacteria. Use of this model should minimize differences in attack rates or severity when groups are challenged at different times and in different institutions. C1 Johns Hopkins Univ, Vaccine Testing Unit, Dept Int Hlth, Baltimore, MD 21205 USA. Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. NIAID, Bethesda, MD 20892 USA. Univ Cincinnati, Cincinnati, OH USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. RP Sack, DA (reprint author), Johns Hopkins Univ, Vaccine Testing Unit, Dept Int Hlth, 550 N Broadway,Suite 1001, Baltimore, MD 21205 USA. EM dsack@jhsph.edu OI Cohen, Mitchell/0000-0002-4412-350X FU NCRR NIH HHS [RR-00035, M01 RR008084, MO1-RR08084]; NIAID NIH HHS [N01-AI 45252] NR 17 TC 37 Z9 42 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1998 VL 66 IS 5 BP 1968 EP 1972 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZL243 UT WOS:000073413100023 PM 9573077 ER PT J AU Hanson, MS Cassatt, DR Guo, BP Patel, NK McCarthy, MP Dorward, DW Hook, M AF Hanson, MS Cassatt, DR Guo, BP Patel, NK McCarthy, MP Dorward, DW Hook, M TI Active and passive immunity against Borrelia burgdorferi decorin binding protein A (DbpA) protects against infection SO INFECTION AND IMMUNITY LA English DT Article ID OUTER SURFACE-PROTEIN; LYME-DISEASE AGENT; IMMUNOLOGICAL CHARACTERIZATION; RECOMBINANT OSPA; FULL-LENGTH; MICE; ANTIBODY; VACCINE; GENE; IMMUNOGENICITY AB Borrelia burgdorferi, the spirochete that causes Lyme disease, binds decorin, a collagen-associated extracellular matrix proteoglycan found in the skin (the site of entry For the spirochete) and in many other tissues. Two borrelial adhesins that recognize this proteoglycan, decorin binding proteins A and B (DbpA and DbpB, respectively), have recently been identified. Infection of mice by low-dose B. burgdorferi challenge elicited antibodies against DbpA and DbpB that were sustained at high levels, suggesting that these antigens are expressed in vivo. Scanning immunoelectron microscopy showed that DbpA was surface accessible on intact borreliae. Passive administration of DbpA antiserum protected mice from infection following challenge with heterologous B. burgdorferi sensu stricto isolates, even where serum administration was delayed for up to 4 days after challenge. DbpA is the first antigen target identified that is capable of mediating immune resolution of early, localized B. burgdorferi infections. DbpA immunization also protected mice from B. burgdorferi challenge; DbpB immunization was much less effective. DbpA antiserum inhibited in vitro growth of many B. burgdorferi sensu late isolates of diverse geographic, phylogenetic and clinical origins. In combination, these findings support a role for DbpA in the immunoprophylaxis of Lyme disease and suggest that DbpA vaccines have the potential to eliminate early-stage B. burgdorferi infections. C1 Medimmune Inc, Gaithersburg, MD 20878 USA. Texas A&M Univ, Albert B Alkek Inst Biosci & Technol, Dept Biochem & Biophys, Ctr Extracellular Matrix Biol, Houston, TX 77030 USA. NIAID, Rocky Mt Labs, Microscopy Branch, NIH, Hamilton, MT 59840 USA. RP Hanson, MS (reprint author), Medimmune Inc, 35 W Watkins Mill Rd, Gaithersburg, MD 20878 USA. EM hansonm@medimmune.com FU NIAID NIH HHS [AI39865] NR 65 TC 108 Z9 111 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1998 VL 66 IS 5 BP 2143 EP 2153 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZL243 UT WOS:000073413100047 PM 9573101 ER PT J AU Chang, YC Kwon-Chung, KJ AF Chang, YC Kwon-Chung, KJ TI Isolation of the third capsule-associated gene, CAP60, required for virulence in Cryptococcus neoformans SO INFECTION AND IMMUNITY LA English DT Article ID SEROTYPE-A; AGARICUS-BISPORUS; TRANSFORMATION; PROTEIN; MUTANTS; POLYSACCHARIDES; CELLULOSE; GROWTH; URA5 AB polysaccharide capsule is one of the most important virulence factors for the pathogenic fungus Crytococcus neoformans. We previously characterized two capsule-associated genes, CAP59 and CAP64. To further dissect the molecular mechanism of capsule synthesis, 16 acapsular mutants induced by 4-nitroquinoline-1-oxide were obtained. The acapsular phenotype of one of these mutants was complemented. The cloned gene was designated CAP60, and deletion of this newly described capsule-associated gene resulted in an acapsular phenotype, The proposed 67-kDa Cap60p contains 592 amino acids and appears to have a putative transmembrane domain close to the N terminus. DNA sequence analysis revealed that CAP60 has similarity to CAP59 at the center portion of its coding regions. Contour-clamped homogeneous electric field blot analysis suggested that these two genes are on the same chromosome. CAP60 and CAP59, however, could not be functionally substituted for each other by direct complementation or by domain swap experiments, In addition, CAP60 is closely linked to a gene which is similar to a cellulose growth-specific gene of Agaricus bisporus, CEL1, Immunogold electron microscopy studies of the epitope-tagged CAP60 gene revealed that Cap60p was primarily localized to the nuclear membrane. Animal model studies indicated that CAP60 is essential for virulence. Thus, CAP60 is required for both capsule format-ion and virulence. C1 NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP NIAID, Clin Invest Lab, NIH, Bldg 10,Room 11C304, Bethesda, MD 20892 USA. EM June_Kwon-chung@nih.gov FU NIAID NIH HHS [5 R01-AI24912, R01 AI024912] NR 29 TC 136 Z9 149 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1998 VL 66 IS 5 BP 2230 EP 2236 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZL243 UT WOS:000073413100058 PM 9573112 ER PT J AU Kantorow, M Piatigorsky, J AF Kantorow, M Piatigorsky, J TI Phosphorylations of alpha A- and alpha B-crystallin SO INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES LA English DT Article DE phosphorylation; crystallin; small heat shock protein; vertebrate lens ID HEAT-SHOCK PROTEINS; CREUTZFELDT-JAKOB DISEASE; NON-LENTICULAR TISSUES; NIH 3T3 FIBROBLASTS; BOVINE LENS; POSTTRANSLATIONAL MODIFICATIONS; INVIVO PHOSPHORYLATION; NONLENTICULAR TISSUES; IMMUNOREACTIVE ALPHA; SKELETAL-MUSCLE AB In addition to being refractive proteins in the vertebrate lens, the two alpha-crystallin polypeptides (alpha A and alpha B) are also molecular chaperones that can protect proteins from thermal aggregation. The alpha B-crystallin polypeptide, a functional member of the small heat shock family, is expressed in many tissues in a developmentally regulated fashion, is stress-inducible, and is overexpressed in many degenerative diseases and some tumors indicating that it plays multiple roles. One possible clue to alpha-crystallin functions is the fact that both polypeptides are phosphorylated on serine residues by cAMP-dependent and cAMP-independent mechanisms. The cAMP-independent pathway is an autophosphorylation that has been demonstrated in vitro, depends on magnesium and requires cleavage of ATP. Disaggregation of alpha A-, but not alpha B-crystallin into tetramers results in an appreciable increase in autophosphorylation activity, reminiscent of other heat shock proteins, and suggests the possibility that changes in the aggregation state of alpha A-crystallin are involved in yet undiscovered signal transduction pathways. The alpha-crystallin polypeptides differ with respect to their abilities to undergo cAMP-dependent phosphorylation, with preference given to the alpha B-crystallin chain. These differences and complexities in alpha-crystallin phosphorylations, coupled with the differences in expression patterns of the two alpha-crystallin polypeptides, are consistent with the idea that each polypeptide has distinctive structural and metabolic roles. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Piatigorsky, J (reprint author), NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NR 86 TC 40 Z9 41 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0141-8130 J9 INT J BIOL MACROMOL JI Int. J. Biol. Macromol. PD MAY-JUN PY 1998 VL 22 IS 3-4 BP 307 EP 314 DI 10.1016/S0141-8130(98)00028-2 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Applied; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA ZU691 UT WOS:000074223800017 PM 9650085 ER PT J AU Simone, G Mangia, A Petroni, S Trotti, I Paradiso, A Marzullo, F De Lena, M Leone, A AF Simone, G Mangia, A Petroni, S Trotti, I Paradiso, A Marzullo, F De Lena, M Leone, A TI nm23 expression in human breast cancer: correlation with cell proliferation (S-phase) as observed with a double-labeling immunocytochemical-autoradiographic technique SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE breast cancer; nm23; TLI; immunochemistry; autoradiography ID NUCLEOSIDE DIPHOSPHATE KINASE; METASTASIS-RELATED NM23-H1; MESSENGER-RNA EXPRESSION; TUMOR-METASTASIS; PROTEIN EXPRESSION; OVARIAN CARCINOMAS; BASEMENT-MEMBRANE; GENE-EXPRESSION; OVEREXPRESSION; ASSOCIATION AB In 51 unselected breast cancer samples, a double-labeling immunocytochemical technique was utilized to observe the phenotypic expression of the nm23 gene during S-phase. The feasibility of the method was confirmed by comparison with routine evaluations for both thymidine-labeling index and nm23 (p<0.001). No correlation was found between the two parameters in the overall series or when subgroups regarding menopausal status, nodal involvement, tumor size, hormone receptor content were considered. Tumors with a higher nuclear grade showed a significant correlation only with TLI (p=0.02). A trend for an inverse relationship between the two parameters was noted but was not statistically significant. A significant association between TLI and nm23 expression was found by Chi-square test using median values as cut-off. Our data based on morphological and in situ observations do not confirm a correlation between nm23 and cell proliferation, even if this correlation cannot be completely excluded. Multicentric trials of high power with these same techniques are still necessary to definitely establish the prognostic role of nm23 in breast cancer. C1 Inst Oncol, Anat & Cytodiagnost Lab, Anat & Cytodiagnost Pathol Unit, I-70126 Bari, Italy. Inst Oncol, Expt & Clin Oncol Lab, I-70126 Bari, Italy. Inst Oncol, Div Med Oncol, I-70126 Bari, Italy. NCI, Bethesda, MD 20892 USA. RP Simone, G (reprint author), Inst Oncol, Anat & Cytodiagnost Lab, Anat & Cytodiagnost Pathol Unit, Via Amendola 209, I-70126 Bari, Italy. RI Leone, Alvaro/K-6410-2016 OI Leone, Alvaro/0000-0003-3815-9052 NR 40 TC 40 Z9 42 U1 0 U2 2 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAY PY 1998 VL 12 IS 5 BP 1055 EP 1059 PG 5 WC Oncology SC Oncology GA ZJ067 UT WOS:000073176200012 PM 9538128 ER PT J AU Zahn, TP Roberts, BR Schooler, C Cohen, R AF Zahn, TP Roberts, BR Schooler, C Cohen, R TI Manual and saccadic reaction time with constant and variable preparatory intervals in schizophrenia SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID SMOOTH-PURSUIT; EYE-MOVEMENTS; INFORMATION; DEFICIT AB Saccadic reaction time (RT) has been shown to be unimpaired in schizophrenia. Could this be due to its not requiring controlled information processing? The authors gave 49 schizophrenia patients and 34 controls manual and saccadic RT tasks with preparatory intervals of 1, 3, and 5 s given in regular and irregular sequences. If saccades require mainly automatic processes, they should not be affected by variations in the preparatory interval that are mediated by controlled processing. The manual task showed typical slower RT and larger preparatory interval effects in patients than in controls. Although the saccadic task showed significant effects of both the preparatory interval and the preparatory interval on the preceding trial similar in kind to those in manual RT, there were no group differences in these or in RT. The results are attributed to greater stimulus-response compatibility in the saccadic task, which puts fewer demands on working memory. C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. NIMH, Sect Socioenvironm Studies, Bethesda, MD 20892 USA. Univ Konstanz, Dept Psychol, D-7750 Constance, Germany. RP Zahn, TP (reprint author), NIMH, Lab Brain & Cognit, Bldg 10,Room 4C104,10 Ctr Dr,MSC 1366, Bethesda, MD 20892 USA. EM ted_zahn@nih.gov NR 33 TC 3 Z9 3 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD MAY PY 1998 VL 107 IS 2 BP 328 EP 337 DI 10.1037/0021-843X.107.2.328 PG 10 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA ZM672 UT WOS:000073564300015 PM 9604562 ER PT J AU Kalish, LA Boyer, K Brown, G Burns, D Diaz, C Hanson, C Landesman, S Matzen, E Tuomala, R AF Kalish, LA Boyer, K Brown, G Burns, D Diaz, C Hanson, C Landesman, S Matzen, E Tuomala, R CA Women Infants Transmiss Study Grp TI Cigarette smoking and maternal-child HIV transmission SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Letter ID HUMAN-IMMUNODEFICIENCY-VIRUS; PREGNANCY; REDUCTION; CULTURE C1 New England Res Inst, Watertown, MA 02172 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. NICHHD, Bethesda, MD 20892 USA. Univ Puerto Rico, San Juan, PR 00936 USA. Baylor Coll Med, Houston, TX 77030 USA. SUNY Brooklyn, Brooklyn, NY USA. NIAID, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kalish, LA (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02172 USA. FU PHS HHS [U01 A1-34842, U01 A1-34858, U01 A1-34856] NR 7 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAY 1 PY 1998 VL 18 IS 1 BP 86 EP 88 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZM282 UT WOS:000073522900013 PM 9593463 ER PT J AU McElroy, SL Frye, M Denicoff, K Altshuler, L Nolen, W Kupka, R Suppes, T Keck, PE Leverich, GS Kmetz, GF Post, RM AF McElroy, SL Frye, M Denicoff, K Altshuler, L Nolen, W Kupka, R Suppes, T Keck, PE Leverich, GS Kmetz, GF Post, RM TI Olanzapine in treatment-resistant bipolar disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE olanzapine; bipolar disorder ID CLOZAPINE AB Background: We evaluated the response to olanzapine in 14 consecutive patients with bipolar I disorder who were inadequately responsive to standard psychotropic agents. Methods: Fourteen patients with bipolar I disorder by DSM-IV criteria experiencing persistent affective symptoms inadequately responsive to at least one standard mood stabilizer were treated with open-label olanzapine by one of the authors. Response was assessed with the Clinical Global Impression Scale modified for use in bipolar disorder (CGI-BP). Results: The 14 patients received olanzapine at a mean (SD dosage of 14.1+/-7.2 (range 5-30) mg/day for a mean+/-SD of 101.4 + 56.3 (range 30-217) days of treatment. Of the 14 patients; 8 (57%) displayed much or very much overall improvement in their illness. In general, olanzapine was well tolerated. The most common side effects were sedation, tremor, dry mouth, and appetite stimulation with weight gain. Limitations: Data were obtained nonblindly and without a randomized control group, and olanzapine was added to ongoing psychotropic regimens. Conclusion: Olanzapine may have antimanic and mood-stabilizing effects in some patients with bipolar disorder, and is generally well tolerated. Controlled studies of olanzapine in bipolar disorder appear warranted. (C) 1998 Elsevier Science B.V. C1 Univ Cincinnati, Coll Med, Stanley Fdn Bipolar Treatment Outcome Network, Biol Psychiat Program,Dept Psychiat, Cincinnati, OH 45267 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Vet Adm Med Ctr, Los Angeles, CA 90073 USA. HC Rumke Grp, NL-3500 AB Utrecht, Netherlands. Univ Texas, SW Med Ctr Dallas, Dallas, TX 75235 USA. RP McElroy, SL (reprint author), Univ Cincinnati, Coll Med, Stanley Fdn Bipolar Treatment Outcome Network, Biol Psychiat Program,Dept Psychiat, 231 Bethesda Ave, Cincinnati, OH 45267 USA. RI Nolen, Willem/E-9006-2014 NR 10 TC 82 Z9 86 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD MAY PY 1998 VL 49 IS 2 BP 119 EP 122 DI 10.1016/S0165-0327(98)00002-0 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZK956 UT WOS:000073384500004 PM 9609675 ER PT J AU Pegg, AE Kanugula, S Edara, S Pauly, GT Moschel, RC Goodtzova, K AF Pegg, AE Kanugula, S Edara, S Pauly, GT Moschel, RC Goodtzova, K TI Reaction of O-6-benzylguanine-resistant mutants of human O-6-alkylguanine-DNA alkyltransferase with O-6-benzylguanine in oligodeoxyribonucleotides SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN O6-METHYLGUANINE-DNA METHYLTRANSFERASE; HUMAN O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; ESCHERICHIA-COLI; ALKYLATING-AGENTS; DNA-REPAIR; CRYSTAL-STRUCTURE; INACTIVATION; O6-BENZYLGUANINE; SENSITIVITY; PROTEIN AB Inactivation of the human DNA repair protein, O-6-alkylguanine-DNA alkyltransferase (AGT), by O-6-benzylguanine renders tumor cells susceptible to killing by alkylating agents, AGT mutants resistant to O-6-benzylguanine can be made by converting Pro(140) to an alanine (P140A) or Gly(156) to an alanine (G156A), These mutations had a much smaller effect on the reaction with O-6-benzylguanine when it was incorporated into a short single-stranded oligodeoxyribonucleotide. Such oligodeoxyribonucleotides could form the basis for the design of improved AGT inhibitors. AGT and mutants P140A and G156A preferentially reacted with O-6-benzylguanine when incubated with a mixture of two 16-mer oligodeoxyribonucleotides, one containing O-6-benzylguanine and the other, O-6-methylguanine. When the 6 amino acids located in positions 159-164 in AGT were replaced by the equivalent sequence from the Escherichia coli Ada-C protein (mutant AGT/6ada) the preference for benzyl repair was eliminated. Further mutation incorporating the P140A change into AGT/6ada giving mutant P140A/6ada led to a protein that resembled Ada-C in preference for the repair of methyl groups, but P140A/6ada did not differ from P140A in reaction with the free base O-6-benzylguanine. Changes in the AGT active site pocket can therefore affect the preference for repair of O-6-benzyl or -methyl groups when present in an oligodeoxyribonucleotide without altering the reaction with free O-6-benzylguanine. C1 Penn State Univ, Milton S Hershey Med Ctr, Dept Cellular & Mol Physiol, Coll Med, Hershey, PA 17033 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Pegg, AE (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Dept Cellular & Mol Physiol, Coll Med, POB 850,500 Univ Dr, Hershey, PA 17033 USA. NR 40 TC 21 Z9 21 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 1 PY 1998 VL 273 IS 18 BP 10863 EP 10867 DI 10.1074/jbc.273.18.10863 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZL064 UT WOS:000073395200012 PM 9556560 ER PT J AU Yan, ZH Karam, WG Staudinger, JL Medvedev, A Ghanayem, BI Jetten, AM AF Yan, ZH Karam, WG Staudinger, JL Medvedev, A Ghanayem, BI Jetten, AM TI Regulation of peroxisome proliferator-activated receptor alpha-induced transactivation by the nuclear orphan receptor TAK1/TR4 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RETINOID-X-RECEPTOR; RESPONSIVE ELEMENT UPSTREAM; RAT HYDRATASE-DEHYDROGENASE; HORMONE-RECEPTOR; THYROID-HORMONE; DIFFERENTIAL EXPRESSION; TRANSCRIPTION FACTOR; LIPID-METABOLISM; ACID RECEPTORS; CO-REPRESSOR AB Recently, Re reported the cloning of the nuclear orphan receptor TAK1. In this study, we characterized the sequence requirements for optimal TAK1 binding and analyzed the repression of the peroxisome proliferator-activated receptor alpha (PPAR alpha) signaling pathway by TAK1. Site selection analysis showed that TAK1 has the greatest affinity for direct repeat-1 response elements (RE) containing AGGTCAAAGGTCA (TAK1-RE) to which it binds as a homodimer, TAK1 is a very weak inducer of TAK1-RE-dependent transcriptional activation. We observed that TAK1, as PPAR alpha; is expressed within rat hepatocytes and is able to bind the peroxisome proliferator response elements (PPREs) present in the promoter of the PPAR alpha target genes rat enoyl-CoA hydratase (HD) and peroxisomal fatty acyl-CoA oxidase (ACOX). TAK1 is unable to induce PPRE-dependent transcriptional activation and represses PPAR alpha-mediated transactivation through these elements in a dose-dependent manner. Two-hybrid analysis showed that TAK1 does not form heterodimers with either PPAR alpha or retinoid X receptor (RXR alpha), indicating that this repression does not involve a mechanism by which TAK1 titrates out PPAR alpha or RXR alpha from PPAR.RXR complexes. Further studies demonstrated that the PPAR alpha Ligand 8(S)-hydroxyeicosatetraenoic acid strongly promotes the interaction of PPAR alpha with the co-activator RIP-140 but decreases the interaction of PPAR alpha with the corepressor SMRT. In contrast, TAK1 interacts with RIP-140 but not with SMRT and competes with PPAR alpha for RIP-140 binding. These observations indicated that the antagonistic effects of TAK1 on PPAR alpha.RXR alpha transactivation act at least at two levels in the PPAR alpha signaling pathway: competition of TAK1 with PPAR alpha.RXR for binding to PPREs as well as to common co-activators, such as RIP-140. Our results suggest an important role for TAK1 in modulating PPAR alpha-controlled gene expression in hepatocytes. C1 NIEHS, Cell Biol Sect, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Glaxo Wellcome Res & Dev Ltd, Dept Mol Endocrinol, Res Triangle Pk, NC 27709 USA. RP Jetten, AM (reprint author), NIEHS, Cell Biol Sect, Pulm Pathobiol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. OI Jetten, Anton/0000-0003-0954-4445 NR 75 TC 55 Z9 59 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 1 PY 1998 VL 273 IS 18 BP 10948 EP 10957 DI 10.1074/jbc.273.18.10948 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZL064 UT WOS:000073395200025 PM 9556573 ER PT J AU Weiler, S Gruschus, JM Tsao, DHH Yu, L Wang, LH Nirenberg, M Ferretti, JA AF Weiler, S Gruschus, JM Tsao, DHH Yu, L Wang, LH Nirenberg, M Ferretti, JA TI Site-directed mutations in the vnd/NK-2 homeodomain - Basis of variations in structure and sequence-specific DNA binding SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RESONANCE SOLUTION STRUCTURE; CENTRAL-NERVOUS-SYSTEM; NK-2 HOMEOBOX GENE; CRYSTAL-STRUCTURE; ANTENNAPEDIA HOMEODOMAIN; DROSOPHILA-MELANOGASTER; FUNCTIONAL SPECIFICITY; TRANSCRIPTION FACTORS; RECOGNITION CODE; COMPLEX AB Secondary structures, DNA binding properties, and thermal denaturation behavior of six site-directed mutant homeodomains encoded by the vnd/NK-2 gene from Drosophila melanogaster are described. Three single site H52R, Y54M, and T56W mutations, two double site H52R/T56W and Y54M/T56W mutations, and one triple site H52R/Y54M/T56W mutation were investigated. These positions were chosen based on their variability across homeodomains displaying differences in secondary structure and DNA binding specificity. Multidimensional NMR, electrophoretic mobility shift assays, and circular dichroism spectropolarimetry studies were carried out on recombinant 80-amino acid residue proteins containing the homeodomain, Position 56, but more importantly position 56 in combination with position 52, plays an important role in determining the length of the recognition helix. The H52R mutation alone does not affect the length of this helix but does increase the thermal stability. introduction of site mutations at positions 52 and 56 in vnd/NK-2 does not modify their high affinity binding to the 18-base pair DNA fragment containing the vnd/NK-2 consensus binding sequence, CAAGTG, Site mutations involving position 54 (Y54M, Y54M/T56W, and H52R/Y54M/T56W) all show a decrease of 1 order of magnitude in their binding affinity. The roles in structure and sequence specificity of individual atom-atom interactions are described. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. RP Ferretti, JA (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM jafer@helix.nih.gov NR 52 TC 39 Z9 39 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 MAY 1 PY 1998 VL 273 IS 18 BP 10994 EP 11000 DI 10.1074/jbc.273.18.10994 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZL064 UT WOS:000073395200031 PM 9556579 ER PT J AU Prasad, R Beard, WA Chyan, JY Maciejewski, MW Mullen, GP Wilson, SH AF Prasad, R Beard, WA Chyan, JY Maciejewski, MW Mullen, GP Wilson, SH TI Functional analysis of the amino-terminal 8-kDa domain of DNA polymerase beta as revealed by site-directed mutagenesis - DNA binding and 5 '-deoxyribose phosphate lyase activities SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BASE EXCISION-REPAIR; RESIDUES; IDENTIFICATION; MECHANISM; ENDONUCLEASE; 5'-PHOSPHATE; PATHWAY AB The amino-terminal 8-kDa domain of DNA polymerase beta functions in binding single-stranded DNA (ssDNA), recognition of a 5'-phosphate in gapped DNA structures, and as a 8'-deoxyribose phosphate (dRP) lyase, NMR and x-ray crystal structures of this domain have suggested several residues that may interact with ssDNA or play a role in the dRP lyase reaction. Nine of these residues were altered by site-directed mutagenesis. Each mutant was expressed in Escherichia coli, and the recombinant protein was purified to near homogeneity. CD spectra of these mutant proteins indicated that the alteration did not adversely affect the global protein structure, Single-stranded DNA binding was probed by photochemical cross-linking to oligo(dT)(16). Several mutants (F25W, K35A, K60A, and K68A) were impaired in ssDNA binding activity, whereas other mutants (H34G, E71Q, K72A, E75A, and K84A) retained near wild-type binding activity. The 5'-phosphate recognition activity of these mutants was examined by UV cross-linking to a 5-nucleotide gap DNA where the 5' terminus in the gap was either phosphorylated or unphosphorylated, The results indicate that Lys(35) is involved in 5'-phosphate recognition of DNA polymerase beta. Finally, the dRP lyase activity of these mutants was evaluated using a preincised apurinic/apyrimidinic DNA, Alanine mutants of Lys(35) and Lys(60) are significantly reduced in dRP lyase activity, consistent with the lower ssDNA binding activity. More importantly, alanine substitution for Lys(72) resulted in a greater than 90% loss of dRP lyase activity, without affecting DNA binding. Alanine mutants of Lys(68) and Lys(84) had wild-type dRP lyase activity. The triple alanine mutant, K35A/K68A/K72A, was devoid of dRP lyase activity, suggesting that the effects of the alanine substitution at Lys(72) and Lys(35) were additive. The results suggest that Lys(72) is directly involved in formation of a covalent imino intermediate and are consistent with Lys(72) as the predominant Schiff base nucleophile in the dRP lyase beta-elimination catalytic reaction. C1 NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. Univ Texas, Med Branch, Sealy Ctr Mol Sci, Galveston, TX 77555 USA. Univ Connecticut, Ctr Hlth, Dept Biochem, Farmington, CT 06032 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, POB 12233,111 TW Alexander Dr,Bldg 101,Rm B246, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov NR 30 TC 118 Z9 120 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 1 PY 1998 VL 273 IS 18 BP 11121 EP 11126 DI 10.1074/jbc.273.18.11121 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZL064 UT WOS:000073395200050 PM 9556598 ER PT J AU Klutch, M Woerner, AM Marcus-Sekura, CJ Levin, JG AF Klutch, M Woerner, AM Marcus-Sekura, CJ Levin, JG TI Generation of HIV-1/HIV-2 cross-reactive peptide antisera by small sequence changes in HIV-1 reverse transcriptase and integrase immunizing peptides SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE HIV-1; HIV-2; synthetic peptides; peptide antisera; cross-reactive response; chimeric peptides; reverse transcriptase; integrase; enzyme assays; peptide diagnostics ID IMMUNODEFICIENCY-VIRUS TYPE-1; DNA-BINDING DOMAIN; MONOCLONAL-ANTIBODIES; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; ANGSTROM RESOLUTION; NATURAL PROTECTION; HTLV-III; H DOMAIN; PROTEIN AB We have generated peptide antisera against selected regions in HIV-1 and HIV-2 reverse transcriptase (RT) and integrase (IN) to investigate the specificity of determinants governing the immune response, Peptides representing homologous regions (>50%) in the N- and C-termini and central portions of HIV-2 these proteins were synthesized and injected into rabbits. HIV-1 and HIV-2 IN peptide antisera inhibited IN-mediated cleavage of an HIV-1 DNA oligonucleotide substrate in a 3' processing assay, while anti-RT or normal sera had no effect. None of the RT sera inhibited RT activity. In Western blots, HIV-2 antisera directed against RT or IN peptides recognized HIV-2. RT and IN proteins, respectively, as expected, but also cross-reacted with the corresponding HIV-1 proteins. By contrast, corresponding HIV-1 antisera were type-specific. In some cases, HIV-1 cross-reactive antisera could be generated by immunization with HIV-1 chimeric peptides with as few as two residues in the HIV-1 sequence changed to the corresponding HIV-2 amino acids. The finding that a type-specific response can be converted to a cross-reactive response suggests alternate strategies for developing new diagnostic reagents which detect HIV-1 and HIV-2. In addition, our results provide a general model for generating HIV peptide vaccines with dual specificity against HIV-1 and HIV-2. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD USA. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Levin, JG (reprint author), NICHD, Mol Genet Lab, NIH, Bldg 6B,Room 216,9000 Rockville Pike, Bethesda, MD 20892 USA. EM judith.levin@nih.gov NR 42 TC 6 Z9 6 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD MAY-JUN PY 1998 VL 5 IS 3 BP 192 EP 202 DI 10.1007/BF02253469 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA ZY858 UT WOS:000074668700005 PM 9678490 ER PT J AU Harvat, BL Wang, A Seth, P Jetten, AM AF Harvat, BL Wang, A Seth, P Jetten, AM TI Up-regulation of p27(Kip1), p21(WAF1/Cip1) and p16(Ink4a) is associated with, but not sufficient for, induction of squamous differentiation SO JOURNAL OF CELL SCIENCE LA English DT Article DE squamous differentiation; p27; p16; p130; growth arrest; cornifin ID CYCLIN-DEPENDENT KINASES; HUMAN EPIDERMAL-KERATINOCYTES; NORMAL HUMAN FIBROBLASTS; CELL-CYCLE; TERMINAL DIFFERENTIATION; RETINOBLASTOMA PROTEIN; NEURONAL DIFFERENTIATION; TRANSFORMING GROWTH-FACTOR-BETA-1; REPLICATIVE SENESCENCE; EPITHELIAL-CELLS AB Irreversible growth arrest is an early and integral part of squamous cell differentiation in normal human epidermal keratinocytes (NHEKs) and is assumed to be linked to the control of expression of differentiation-specific genes. In this study, we examine the link between the molecular events associated with growth arrest and the expression of differentiation genes. NHEKs that have been induced to undergo growth arrest and differentiation by suspension culture contain populations in both G(1) and G(2)/M of the cell cycle. The irreversible growth arrest state in NHEKs is characterized by an accumulation of the hypophosphorylated forms of Rb and p130, with subsequent down-regulation of levels of Rb, up-regulation of p130 and associated down-regulation of E2F-regulated genes such as cyclin A. These events correlate with an inhibition of G(1) cdk activity, mediated in part by an increase in the cdk inhibitors p21(WAF1/Cip1), p27(Kip1) and p16(Ink4a). Flow cytometric and immunoblot analysis demonstrated that the timing of the up-regulation of p27, p16 and p130 corresponds closely with the induction of the squamous-specific genes cornifin Phi (SPRR-1) and transglutaminase type I, suggesting a close link between control of growth arrest and differentiation. However, growth arrest induced by over-expression of p27, p21 or p16 by recombinant adenovirus is not sufficient to induce expression of the differentiation genes, or to invoke the pattern of cell cycle regulatory protein expression characteristic of the differentiation-specific irreversible growth arrest. We conclude that growth arrest mediated by activation of the Rb pathway is not sufficient to trigger terminal squamous differentiation and additional signals which can be generated during suspension culture are required to promote the complete differentiation program. C1 NIEHS, Cell Biol Sect, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIH, Med Branch, Bethesda, MD 20892 USA. RP Jetten, AM (reprint author), NIEHS, Cell Biol Sect, Pulm Pathobiol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. OI Jetten, Anton/0000-0003-0954-4445 NR 78 TC 67 Z9 68 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 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAY PY 1998 VL 111 BP 1185 EP 1196 PN 9 PG 12 WC Cell Biology SC Cell Biology GA ZQ623 UT WOS:000073886600005 PM 9547295 ER PT J AU Lafrenie, RM Bernier, SM Yamada, KM AF Lafrenie, RM Bernier, SM Yamada, KM TI Adhesion to fibronectin or collagen I gel induces rapid, extensive, biosynthetic alterations in epithelial cells SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID SIGNAL-TRANSDUCTION; GENE-EXPRESSION; EXTRACELLULAR-MATRIX; INTEGRIN; FIBROBLASTS; KINASE; DIFFERENTIATION; PATHWAYS; CYTOSKELETAL; PROTEINS AB Extracellular matrix influences many cellular events. In this study, we demonstrate that adhesion of human salivary gland (HSG) epithelial cells to fibronectin-or collagen I gel-coated substrates, mediated by beta(1) integrins, results in substantial alterations in protein and RNA expression profiles. The large numbers of changes in expression suggest that simply changing the adhesive substrate has basic effects on the regulation of cellular biosynthesis. Two-dimensional electrophoresis of [S-35] methionine-labeled HSG cell proteins identified significant differences in the patterns of protein expression by cells cultured on nonprecoated substrates, collagen I gels or fibronectin. Thirty-two differentially expressed cDNA clones, which included both novel and previously sequenced genes, were up-regulated within 6 hr by culturing HSG cells on fibronectin or collagen I gels. Therefore, adhesion to collagen I or fibronectin resulted in rapid, widespread changes in cellular biosynthetic control. Expression of some genes was induced by ligation of beta(1) integrins with antifunctional antibodies, whereas the expression of other genes was not induced. Most of the differentially expressed genes were upregulated by adhesion to both fibronectin- and collagen I gel-coated substrates, but a few genes were selectively up-regulated on only one substrate. Furthermore, the up-regulated expression of some genes was detected within 3 hr, whereas changes in others required 6 hr. Discrete adhesive substrates and integrin molecules differentially affected the expression of a significant number of genes, suggesting that the cellular responses to adhesion were triggered through several signaling pathways. (C) 1998 Wiley-Liss, Inc.dagger. C1 NIDR, Div Intramural Res, Cranofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Lafrenie, RM (reprint author), NIDR, Div Intramural Res, Cranofacial Dev Biol & Regenerat Branch, NIH, Bldg 30,Room 421,30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 50 TC 20 Z9 22 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAY PY 1998 VL 175 IS 2 BP 163 EP 173 DI 10.1002/(SICI)1097-4652(199805)175:2<163::AID-JCP6>3.0.CO;2-M PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA ZD091 UT WOS:000072650500006 PM 9525475 ER PT J AU Lucia, MS Sporn, MB Roberts, AB Stewart, LV Danielpour, D AF Lucia, MS Sporn, MB Roberts, AB Stewart, LV Danielpour, D TI The role of transforming growth factor-beta 1, -beta 2, and -beta 3 in androgen-responsive growth of NRP-152 rat prostatic epithelial cells SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID RAPID COLORIMETRIC ASSAY; TGF-BETA RECEPTOR; VENTRAL PROSTATE; CANCER-CELLS; NONSTEROIDAL ANTIANDROGEN; ENDOCRINE THERAPY; CELLULAR RECEPTOR; STEROID-HORMONES; LNCAP; GROWTH-FACTOR-BETA-1 AB We have investigated the role of autocrine/paracrine TGF-beta secretion in the regulation of cell growth by androgens as demonstrated by its inhibition by two androgen response modifiers; the nonsteroidal antiandrogen hydroxyflutamide (OHF), believed to act by inhibiting androgen binding to androgen receptors, or finasteride, an inhibitor of 5 alpha-reductase, the enzyme necessary for the conversion of testosterone to 5 alpha-dihydrotestosterone (DHT), using the nontumorigenic rat prostatic epithelial cell line NRP-152. Growth of these cells was stimulated three- to sixfold over control by either testosterone or DHT under serum-free culture conditions. This was accompanied by a two- to threefold decrease in the secretion rate of TGF-beta 1, -beta 2, and -beta 3. Finasteride reversed the ability of testosterone but not DHT to stimulate growth and downregulate expression of TGF-beta 1, -beta 2, and -beta 3 in a dose-dependent fashion, suggesting that this activity of testosterone required its conversion to DHT. OHF antagonized the stimulatory effects of DHT on NRP-152 cell growth but could reverse the inhibitory effects of DHT only on TGF-beta 2 and TGF-beta 3 and not TGF-beta 1 secretion. This suggests that either TGF-beta 1 regulation by DHT or the androgen antagonism of OHF occurs independent of androgen receptor binding. Neutralizing antibodies to TGF-beta (pantropic and isoform-specific) were able to block the ability of finasteride to antagonize the effects of testosterone nearly completely while only partially inhibiting the antiandrogenic effects of OHF. Thus, the ability of androgens to stimulate growth of NRP-152 cells involves the downregulation of the production of TGF-beta 1, -beta 2, and -beta 3 in addition to other growth-stimulatory mechanisms. (C) 1998 Wiley-Liss, Inc.dagger. C1 NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD USA. RP Lucia, MS (reprint author), Univ Colorado, Med Ctr, Dept Pathol, Box B-216, Denver, CO 80262 USA. NR 43 TC 30 Z9 33 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAY PY 1998 VL 175 IS 2 BP 184 EP 192 DI 10.1002/(SICI)1097-4652(199805)175:2<184::AID-JCP8>3.0.CO;2-K PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA ZD091 UT WOS:000072650500008 PM 9525477 ER PT J AU Gorman, JST Jones, TH Spande, TF Snelling, RR Torres, JA Garraffo, HM AF Gorman, JST Jones, TH Spande, TF Snelling, RR Torres, JA Garraffo, HM TI 3-hexyl-5-methylindolizidine isomers from thief ants, Solenopsis (Diplorhoptrum) species SO JOURNAL OF CHEMICAL ECOLOGY LA English DT Article DE venom; alkaloids; Solenopsis (Diplorhoptrum); indolizidine; chemotaxonomy ID VENOM ALKALOIDS; FIRE ANTS; HYMENOPTERA; FORMICIDAE; CHEMISTRY AB The venom alkaloids from the workers of nine collections of Solenopsis (Diplorhoptrum) from California contain either (5E,9E)-3-hexyl-5-methylindolizidine (Ic) or (5Z,9E)-3-hexyl-5-methylindolizidine (Id) along with cis-2-methyl-6-nonylpiperidine. The structures of these compounds were determined from their mass spectra and by comparison of their GC-FTIR spectra with those of a synthetic mixture. In view of the facts that a third diastereomer of 3-hexyl-5-methylindolizidine had been reported in previous collections of Solenopsis (Diplorhoptrum) queens from Puerto Rico, and that indolizidines along with other ant venom alkaloids are sequestered by amphibians, the determination of species in this difficult group of ants is significant. In particular, the chemotaxonomic value of the stereochemistry of these venom alkaloids is discussed. C1 Virginia Mil Inst, Dept Chem, Lexington, VA 24450 USA. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Los Angeles Cty Museum Nat Hist, Los Angeles, CA USA. Univ Puerto Rico, Dept Biol, Rio Piedras, PR 00931 USA. US Forest Serv, IITF, Rio Piedras, PR 00928 USA. RP Jones, TH (reprint author), Virginia Mil Inst, Dept Chem, Lexington, VA 24450 USA. NR 22 TC 11 Z9 11 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0098-0331 J9 J CHEM ECOL JI J. Chem. Ecol. PD MAY PY 1998 VL 24 IS 5 BP 933 EP 943 DI 10.1023/A:1022381719471 PG 11 WC Biochemistry & Molecular Biology; Ecology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology GA ZM260 UT WOS:000073520700010 ER PT J AU Bogusz, S Cheatham, TE Brooks, BR AF Bogusz, S Cheatham, TE Brooks, BR TI Removal of pressure and free energy artifacts in charged periodic systems via net charge corrections to the Ewald potential SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID PARTICLE MESH EWALD; MOLECULAR-DYNAMICS SIMULATIONS; CALCULATING ELECTROSTATIC INTERACTIONS; COMPUTER-SIMULATIONS; BOUNDARY-CONDITIONS; IONIC HYDRATION; WATER; SUMS; TRANSFERABILITY; PROTEINS AB A uniform neutralizing background plasma is employed by default in standard Ewald calculations for net-charged systems. We show here that this plasma leads to serious artifacts in both system energy and pressure, which lead to unrealistic behavior. These artifacts are especially critical to simulations where either net charge or volume is allowed to change. To correct these problems we institute a net-charge correction term that consists of subtracting off the Ewald sum for a single particle with charge equal to the net charge of the full system and an optional Born or Poisson-Boltzmann term. This correction decreases pressure artifacts by three orders of magnitude and allows rapid energy convergence as the cell size increases. The correction term is general, in that it applies to systems of any shape or net charge. The net-charge correction was tested for systems in all three phases of matter: gas, solid and liquid, and found to be markedly superior to standard Ewald in all three cases. In the gas phase, isolated molecular energies are quickly achieved as the cell size increases. In the solid phase the vaporization energy of the NaCl crystal is reproduced using free energy perturbation techniques where a single atom is removed. In the liquid phase, the solvation free energy of Na+ was investigated. It is demonstrated that both the net-charge correction and an energy term twice the size of a Born term is required to obtain optimal free energies of ionic hydration. (C) 1998 American Institute of Physics. C1 NIH, Struct Biol Lab, Div Comp Res & Technol, Bethesda, MD 20892 USA. RP Bogusz, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Rockville, MD 20852 USA. NR 42 TC 101 Z9 103 U1 2 U2 23 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD MAY 1 PY 1998 VL 108 IS 17 BP 7070 EP 7084 DI 10.1063/1.476320 PG 15 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA ZK384 UT WOS:000073315200006 ER PT J AU Yanovski, JA Nieman, LK Doppman, JL Chrousos, GP Wilder, RL Gold, PW Kalogeras, KT AF Yanovski, JA Nieman, LK Doppman, JL Chrousos, GP Wilder, RL Gold, PW Kalogeras, KT TI Plasma levels of corticotropin-releasing hormone in the inferior petrosal sinuses of healthy volunteers, patients with Cushing's syndrome, and patients with pseudo-Cushing states SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HYPOPHYSEAL PORTAL BLOOD; PITUITARY VENOUS-BLOOD; ARGININE-VASOPRESSIN; CEREBROSPINAL-FLUID; MAJOR DEPRESSION; ADRENOCORTICOTROPIN SECRETION; CLINICAL-IMPLICATIONS; ANOREXIA-NERVOSA; FACTOR CRF; DISEASE AB The objective of this study was to determine whether measurements of human CRH in the inferior petrosal sinuses could distinguish patients with Cushing's syndrome from those with pseudo-Cushing states or normal physiology. Twenty-five patients with Cushing's disease, 17 patients with the syndrome of ectopic ACTH, 7 patients with Cushing's syndrome of adrenal origin, 6 patients with pseudo-Cushing states, and 11 volunteers believed to have normal hypothalamic-pituitary-adrenal axes were studied. Basal plasma human CRH and ACTH were measured at two time points in the petrosal sinuses and in a peripheral vein. Most subjects were studied after the administration of intravenous diazepam or midazolam and fentanyl, hut because of the known inhibitory effects of such sedation on CRH secretion; 2 normal volunteers and 3 patients with pseudo-Cushing states were studied without sedation. Human CRH levels were near or below the detection Limit of the assay in all subjects. Although the normal volunteers and patients with pseudo-Cushing states who were studied without sedation had significantly greater inferior petrosal sinus ACTH levels than those who received sedation, there were no differences in measured human CRH levels for any of the groups. We conclude that inferior petrosal sinus human CRH levels are not easily measured in the inferior petrosal sinuses and cannot be used to determine whether individual patients may have hypersecretion of CRH causing their ACTH secretion. C1 NICHHD, Off Director, NIH, Bethesda, MD 20892 USA. NICHHD, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. NIAMSD, Arthritis & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. Univ Mississippi, Med Ctr, Sch Med, Dept Psychiat & Human Behav, Jackson, MS 39216 USA. RP Yanovski, JA (reprint author), NICHHD, Off Director, NIH, 10 Ctr Dr,MSC 1862,Bldg 10,Room 10N262,9000 Rockv, Bethesda, MD 20892 USA. EM jy15@nih.gov OI Yanovski, Jack/0000-0001-8542-1637 NR 29 TC 6 Z9 6 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1998 VL 83 IS 5 BP 1485 EP 1488 DI 10.1210/jc.83.5.1485 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZM396 UT WOS:000073535300015 PM 9589643 ER PT J AU Torpy, DJ Bornstein, SR Cizza, G Chrousos, GP AF Torpy, DJ Bornstein, SR Cizza, G Chrousos, GP TI The effects of glucocorticoids on leptin levels in humans may be restricted to acute pharmacologic dosing SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Letter ID CUSHINGS-SYNDROME; OBESE SUBJECTS; DEXAMETHASONE; SECRETION; CORTISOL C1 NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Torpy, DJ (reprint author), NICHHD, Dev Endocrinol Branch, Bldg 10,Room 10 N262,10 Ctr Dr, Bethesda, MD 20892 USA. NR 17 TC 24 Z9 24 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1998 VL 83 IS 5 BP 1821 EP 1822 DI 10.1210/jc.83.5.1821 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZM396 UT WOS:000073535300074 PM 9589701 ER PT J AU Bild, DE Sholinksy, PD Schreiner, PJ Hilner, JE Swanson, CA AF Bild, DE Sholinksy, PD Schreiner, PJ Hilner, JE Swanson, CA TI Validity of self-reported fat distribution in young adults: The CARDIA study SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE self-report; fat distribution; risk factors; HDL-cholesterol; insulin ID CORONARY HEART-DISEASE; BODY-FAT; CARDIOVASCULAR-DISEASE; DIABETES-MELLITUS; HIP CIRCUMFERENCE; ADIPOSE-TISSUE; PLASMA-INSULIN; BREAST-CANCER; RISK; OBESITY AB To determine the validity of self-reported information on body fat distribution, relationships between reported location of weight gain and measured waist-to-hip ratio (WHR), high density lipoprotein cholesterol (HDL-C), and fasting insulin were analyzed in 5115 black and white men and women aged 18-30 years. In black men, WHR adjusted for age and body mass index (BMI) ranged from 0.833 among those reporting upper and central weight gain to 0.812 among those reporting lower body weight gain (trend across five reported fat distribution categories, P = 0.0004). Corresponding values were, for white men, 0.852 to 0.831; for black women, 0.777 to 0.721; and for white women, 0.172 to 0.701 teach P < 0.0001). Reported fat distribution was associated with HDL-C in women, but not in men, and with fasting insulin in all groups. While these associations were somewhat weaker than with measured WHR, self-reported fat distribution does provide valid information about body fat distribution in young adults, particularly women. Published 1998 Elsevier Science Inc. C1 NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. Univ Alabama, CARDIA Coordinating Ctr, Birmingham, AL USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Bild, DE (reprint author), NHLBI, Div Epidemiol & Clin Applicat, 2 Rockledge Ctr,6701 Rockledge Dr, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [N01-HC-48049, N01-HC-48047, N01-HC-48048] NR 28 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD MAY PY 1998 VL 51 IS 5 BP 407 EP 413 DI 10.1016/S0895-4356(98)00009-2 PG 7 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA ZK149 UT WOS:000073290300006 PM 9619968 ER PT J AU Kim, KS Takeda, K Sethi, R Pracyk, JB Tanaka, K Zhou, YF Yu, ZX Ferrans, VJ Bruder, JT Kovesdi, I Irani, K Goldschmidt-Clermont, P Finkel, T AF Kim, KS Takeda, K Sethi, R Pracyk, JB Tanaka, K Zhou, YF Yu, ZX Ferrans, VJ Bruder, JT Kovesdi, I Irani, K Goldschmidt-Clermont, P Finkel, T TI Protection from reoxygenation injury by inhibition of rac1 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE reoxygenation; signal transduction; rac; ras; adenovirus ID FREE-RADICAL GENERATION; ACTIVATED PROTEIN-KINASES; SIGNAL-TRANSDUCTION; HYDROGEN-PEROXIDE; ADENOVIRUS TYPE-5; TERMINAL KINASES; NADPH OXIDASE; CELL-DEATH; KAPPA-B; REPERFUSION AB We demonstrate that adenoviral-mediated gene transfer of a dominant negative rad gene product (N17rac1) inhibits the intracellular burst of reactive oxygen species (ROS) that occurs after reoxygenation of vascular smooth muscle cells. In contrast, expression of a dominant negative ras gene (N17ras) had no effect. Challenge of control cells and cells expressing N17rac1 with a direct oxidant stress produced an equivalent increase in intracellular ROS levels and subsequent cell death. This suggests that N17rac1 expression appears to block production of harmful oxygen radicals and does not act directly or indirectly to scavenge ROS generated during reoxygenation. Expression of N17rac1 results in protection from hypoxia/reoxygenation-induced cell death in a variety of cell types including vascular smooth muscle cells, fibroblasts, endothelial cells, and ventricular myocytes. These results suggest that reoxygenation injury requires the activation of rac proteins, and that inhibition of rac-dependent pathways may be a useful strategy for the prevention of reperfusion injury in ischemic tissues. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. GenVec Inc, Rockville, MD 20852 USA. Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD 21205 USA. Ohio State Univ, Heart & Lung Inst, Columbus, OH 43210 USA. Hanyang Univ, Div Cardiol, Seoul 133791, South Korea. RP Finkel, T (reprint author), NHLBI, Cardiol Branch, NIH, 10 Center Dr,MSC 1650,Bldg 10,Room 7B-15, Bethesda, MD 20892 USA. NR 42 TC 118 Z9 119 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY 1 PY 1998 VL 101 IS 9 BP 1821 EP 1826 DI 10.1172/JCI1830 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZN286 UT WOS:000073630700003 PM 9576744 ER PT J AU Asai, O Longo, DL Tian, ZG Hornung, RL Taub, DD Ruscetti, FW Murphy, WJ AF Asai, O Longo, DL Tian, ZG Hornung, RL Taub, DD Ruscetti, FW Murphy, WJ TI Suppression of graft-versus-host disease and amplification of graft-versus-tumor effects by activated natural killer cells after allogeneic bone marrow transplantation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE NK cell; graft-versus-host disease; bone marrow transplantation; immunotherapy; cytokines ID LEUKEMIA; MICE; ENGRAFTMENT; ANTIBODIES; PROTECTION; DEPLETION; INVIVO; GROWTH; BETA; GVHD AB Bone marrow transplantation (BMT) is currently used for the treatment of a variety of neoplastic diseases. However, significant obstacles limiting the efficacy of allogeneic BMT are the occurrence of graft-versus-host disease (GvHD) and tumor relapse. Natural killer (NK) cells exert a variety of immunologic and homoeostatic functions. We examined whether adoptive transfer of activated NK cells of donor type would prevent GvHD after allogeneic BMT in mice. Lethally irradiated C57BL/6 (H-2(b)) mice, were transplanted with MHC incompatible BALB/c (H-2(d)) bone marrow cells and spleen cells and rapidly succumbed to acute GvHD. In contrast, mice that also received activated NK cells of donor type exhibited significant increases in survival. In determining the mechanism by which the NK cells prevented GvHD, mice were concurrently treated with a neutralizing antibodies to the immunosuppressive cytokine TGF beta. Anti-TGF beta completely abrogated the protective effects of the activated donor NK cells indicating that TGF beta plays an important role in the prevention of GvHD by NK cells. We then examined whether activated NK cells of donor type after allogeneic BMT would induce graft-versus-tumor (GvT) effects without GvHD in mice bearing a murine colon adenocarcinoma (MCA-38). 10 d after receiving the tumor, in which the mice had demonstrable lung metastases, recipients received an allogeneic BMT with or without activated NK cells. Administration of activated NK cells resulted in significant GvT effects after allogeneic BMT as evidenced by increases in median survival and fewer lung metastasis. No evidence of GVHD was detected compared with recipients receiving spleen cells alone which also developed fewer lung metastases but in which all had succumbed to GVHD. Thus, our findings suggest that adoptive immunotherapy using activated donor NK cells combined with allogeneic BMT inhibits GvHD and promotes GvT in advanced tumor-bearing mice. These results also suggest that GvT and GvHD can be dissociable phenomena. C1 NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. NCI, Lab Leukocyte Biol, SAIC Frederick, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Murphy, WJ (reprint author), NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Bldg 567,Room 209, Ft Detrick, MD 21702 USA. RI Tian, Zhigang/J-3512-2013 NR 24 TC 183 Z9 196 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY 1 PY 1998 VL 101 IS 9 BP 1835 EP 1842 DI 10.1172/JCI1268 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZN286 UT WOS:000073630700005 PM 9576746 ER PT J AU Chang, YC Segal, BH Holland, SM Miller, GF Kwon-Chung, KJ AF Chang, YC Segal, BH Holland, SM Miller, GF Kwon-Chung, KJ TI Virulence of catalase-deficient Aspergillus nidulans in p47(phox-/-) mice - Implications for fungal pathogenicity and host defense in chronic granulomatous disease SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE catalase; catA; catB; CGD; p47(phox) ID REGULATED CATALASE; HYDROGEN-PEROXIDE; HUMAN-NEUTROPHILS; GAMMA-INTERFERON; OXIDATIVE STRESS; FUMIGATUS HYPHAE; DAMAGE; GENE; ITRACONAZOLE; PHAGOCYTE AB Chronic granulomatous disease (CGD) is a rare genetic disorder in which phagocytes fail to produce superoxide because of defects in one of several components of the NADPH oxidase complex. As a result, patients develop recurrent life-threatening bacterial and fungal infections. The organisms to which CGD patients are most susceptible produce catalase, regarded as an important factor for microbial pathogenicity in CGD. To test the role of pathogen-derived catalase in CGD directly, we have generated isogenic strains of Aspergillus nidulans in which one or both of the catalase genes (catA and catB), have been deleted. We hypothesized that catalase negative mutants would be less virulent than the wild-type strain in experimental animal models. CGD mice were produced by disruption of the p47(phox) gene which encodes the 47-kD subunit of the NADPH oxidase. Wild-type A. nidulans inoculated intranasally caused fatal infection in CGD mice, but did not cause disease in wild-type littermates. Surprisingly, wild-type A. nidulans and the catA, catB, and catA/catB mutants were equally virulent in CGD mice. Histopathological studies of fatally infected CGD mice showed widely distributed lesions in the lungs regardless of the presence or absence of the catA and catB genes. Similar to the CGD model, catalase-deficient A. nidulans was highly virulent in cortisone-treated BALB/c mice. Taken together, these results indicate that catalases do not play a significant role in pathogenicity of A. nidulans in p47(phox-/-) mice, and therefore raise doubt about the central role of catalases as a fungal virulence factor in CGD. C1 NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NIH, Natl Ctr Res Resources, Vet Resources Program, Bethesda, MD 20892 USA. RP Kwon-Chung, KJ (reprint author), NIAID, Clin Invest Lab, NIH, Bldg 10,Room 11C304, Bethesda, MD 20892 USA. NR 36 TC 80 Z9 85 U1 1 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY 1 PY 1998 VL 101 IS 9 BP 1843 EP 1850 DI 10.1172/JCI2301 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZN286 UT WOS:000073630700006 PM 9576747 ER PT J AU Margolis, LB Glushakova, S Grivel, JC Murphy, PM AF Margolis, LB Glushakova, S Grivel, JC Murphy, PM TI Blockade of CC chemokine receptor 5 (CCR5)-tropic human immunodeficiency virus-1 replication in human lymphoid tissue by CC chemokines SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE AIDS; HIV; chemokine; leukocyte; receptor ID HIV-1 INFECTION; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; MIP-1-ALPHA; MIP-1-BETA; RANTES; GENE; PATHOGENESIS; PROGRESSION; INDIVIDUALS AB The CC chemokines MIP-1 alpha, MIP-1 beta, and RANTES suppress replication of certain HIV-1 strains in cultured PBMC and T cell lines by blocking interaction of gp120 with CC chemokine receptor 5 (CCR5). However, the same chemokines can enhance HIV-1 replication in cultured macrophages. The net effect of chemokines on HIV-1 infection in intact lymphoid tissue, the major reservoir of HIV-1 in vivo, is unknown and unpredictable since the tissue contains both T lymphocytes and macrophages. Here we show that exogenous MIP-1 alpha, MIP-1 beta, and RANTES markedly suppressed replication of CCR5-tropic HIV-1 strains in blocks of human lymphoid tissue infected ex vivo. Moreover, endogenous MIP-1 alpha, MIP-1 beta, and RANTES were upregulated in tissues infected ex vivo with CXC chemokine receptor C-tropic but not CCR5-tropic HIV-1. Such an upregulation may contribute to the virus phenotype shift in the course of HIV disease in vivo. C1 NICHHD, Lab Mol & Cellular Biophys, NIH, Bethesda, MD 20892 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Margolis, LB (reprint author), NICHHD, Lab Mol & Cellular Biophys, NIH, Bldg 10,Room 10D14, Bethesda, MD 20892 USA. EM pmm@nih.gov NR 26 TC 41 Z9 42 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY 1 PY 1998 VL 101 IS 9 BP 1876 EP 1880 DI 10.1172/JCI2015 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZN286 UT WOS:000073630700010 PM 9576751 ER PT J AU Norflus, F Tifft, CJ McDonald, MP Goldstein, G Crawley, JN Hoffmann, A Sandhoff, K Suzuki, K Proia, RL AF Norflus, F Tifft, CJ McDonald, MP Goldstein, G Crawley, JN Hoffmann, A Sandhoff, K Suzuki, K Proia, RL TI Bone marrow transplantation prolongs life span and ameliorates neurologic manifestations in Sandhoff disease mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE beta-N-acetylhexosaminidase metabolism; gangliosidoses physiopathology; blood-brain barrier; Tay-Sachs disease metabolism; disease models, animal ID CENTRAL-NERVOUS-SYSTEM; MUCOPOLYSACCHARIDOSIS TYPE-VII; LYSOSOMAL STORAGE DISEASE; TWITCHER MICE; MOUSE; PHENOTYPE; MICROGLIA; CELLS AB The G(M2) gangliosidoses are a group of severe, neurodegenerative conditions that include Tay-Sachs disease, Sandhoff disease, and the G(M2) activator deficiency. Bone marrow transplantation (BMT) was examined as a potential treatment for these disorders using a Sandhoff disease mouse model. BMT extended the life span of these mice from similar to 4.5 mo to up to 8 mo and slowed their neurologic deterioration. BMT also corrected biochemical deficiencies in somatic tissues as indicated by decreased excretion of urinary oligosaccharides, and lower glycolipid storage and increased levels of beta-hexosaminidase activity in visceral organs. Even with neurologic improvement, neither clear reduction of brain glycolipid storage nor improvement in neuronal pathology could be detected, suggesting a complex pathogenic mechanism. Histological analysis revealed beta-hexosaminidase-positive cells in the central nervous system and visceral organs with a concomitant reduction of colloidal iron-positive macrophages. These results may be important for the design of treatment approaches for the G(M2) gangliosidoses. C1 NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Med Genet, Washington, DC 20010 USA. NIMH, Sect Behav Neuropharmacol, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. Univ Bonn, Kekule Inst Organ Chem & Biochem, D-53121 Bonn, Germany. Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. RP Proia, RL (reprint author), NIDDKD, Genet & Biochem Branch, NIH, Bldg 10,Room 9D-20,10 Center Dr,MSC 1810, Bethesda, MD 20892 USA. EM proia@nih.gov RI Proia, Richard/A-7908-2012 FU NICHD NIH HHS [P30-HD 03110]; NINDS NIH HHS [R01-NS 24453] NR 28 TC 101 Z9 103 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY 1 PY 1998 VL 101 IS 9 BP 1881 EP 1888 DI 10.1172/JCI2127 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZN286 UT WOS:000073630700011 PM 9576752 ER PT J AU Gaydos, CA Howell, MR Quinn, TC Gaydos, JC McKee, KT AF Gaydos, CA Howell, MR Quinn, TC Gaydos, JC McKee, KT TI Use of ligase chain reaction with urine versus cervical culture for detection of Chlamydia trachomatis in an asymptomatic military population of pregnant and nonpregnant females attending Papanicolaou smear clinics SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID RISK-FACTORS; INFECTION; WOMEN; SPECIMENS; DIAGNOSIS; PREVALENCE; ASSAY; MEN AB Ligase chain reaction (LCR) (Abbott Laboratories, Abbott Park, Ill.) with first-catch urine specimens was used to detect Chlamydia trachomatis infections in 465 asymptomatic military women attending clinics for routine Papanicolaou smear tests. Results were compared to results of cervical culture to determine the sensitivity of the urine LCR and the possible presence of inhibitors of amplification in pregnant and nonpregnant women. Discrepant results for LCR and culture were resolved by direct fluorescent antibody staining of culture sediments, two different PCR assays, and LCR for the outer membrane protein 1 gene. The prevalence of Chlamydia in specimens by urine LCR was 7.3% compared to 5% by culture. For 434 women with matching specimens, there were 11 more specimens positive by LCR than were positive by culture, of which all but one were determined to be true positives. There were four culture-positive, LCR-negative specimens, all from nonpregnant women. The sensitivity, specificity, and positive and negative predictive values of urine LCR after discrepant results were resolved were 88.6, 99.7, 96.9, and 99.0%, respectively. The sensitivity of culture was 71.4%. From the 148 pregnant women (prevalence by LCR, 6.8%), there were no patients who were cervical culture positive and urine LCR-negative to indicate the presence in pregnant women of inhibitors of LCR. Additionally, a subset of 55 of the LCR-negative frozen urine specimens from pregnant women that had been previously processed in LCR buffer were inoculated with 5 cell culture inclusion forming units of C. trachomatis each and retested by LCR; all tested positive, indicating the absence of inhibitors of LCR in urine from these pregnant women. The use of LCR testing of urine specimens from asymptomatic women, whether pregnant or not, offers a sensitive and easy method to detect C. trachomatis infection in women. C1 Johns Hopkins Univ, Div Infect Dis, Baltimore, MD 21205 USA. NIAID, NIH, Bethesda, MD 20892 USA. USA, Ctr Hlth Promot & Prevent Med, Aberdeen Proving Ground, MD USA. Womac Army Med Ctr, Prevent Med Serv, Ft Bragg, NC USA. RP Gaydos, CA (reprint author), Johns Hopkins Univ, Div Infect Dis, 1159 Ross Res Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. RI Gaydos, Charlotte/E-9937-2010 NR 37 TC 43 Z9 46 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 1998 VL 36 IS 5 BP 1300 EP 1304 PG 5 WC Microbiology SC Microbiology GA ZJ084 UT WOS:000073177900026 PM 9574695 ER PT J AU Granovsky, MO Mueller, BU Nicholson, HS Rosenberg, PS Rabkin, CS AF Granovsky, MO Mueller, BU Nicholson, HS Rosenberg, PS Rabkin, CS TI Cancer in human immunodeficiency virus-infected children: A case series from the Children's Cancer Group and the National Cancer Institute SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; SMOOTH-MUSCLE TUMORS; LYMPHOID NEOPLASIA; SYNDROME AIDS; ASSOCIATION; LEIOMYOSARCOMAS; EXPERIENCE; TISSUE; TYPE-1; MALT AB Purpose: To describe the spectrum of malignancies in human immunodeficiency virus (HIV)-infected children and the clinical outcome of patients with these tumors. Methods: We retrospectively surveyed the Children's Cancer Group (CCG) and the National Cancer institute (NCI) for cases of cancer that occurred between July 1982 and February 1997 in children who were HIV seropositive before or at the time of cancer diagnosis, We used Kaplan-Meier survivorship curves, hazard function estimates, and Cox proportional hazards models to evaluate survival. Results: Sixty-four children (39 boys, 25 girls) with 65 tumors were reported, Thirty-seven children (58%) acquired HN infection vertically (median age at cancer diagnosis, 4.3 years); 22 children (34%) acquired HIV through transfusion of blood or blood products (median age at cancer diagnosis, 13.4 years). Forty-two children (65%) had non-Hodgkin's lymphoma (NHL), Eleven children (17%) had leiomyosarcomas (or leiomyomas), which are otherwise exceptionally rare in children. Other malignancies included acute leukemia (five children), Kaposi's sarcoma (KS; three children), Hodgkin's disease (two children), vaginal carcinoma in situ (one child), and tracheal neuroendocrine carcinoma (one child), Median survival after NHL diagnosis was 6 months (range, 1 day to 89 months) and after leiomyosarcoma was 12 months (range, 10 days to 19 months), The average monthly death rate after NHL diagnosis was 12% in the first 6 months, which decreased to about 2% thereafter In contrast, the monthly death rate after leiomyosarcoma diagnosis increased from 5% in the first 6 months to about 20% thereafter. Conclusion: After NHL, leiomyosarcoma is the sec and reading cancer in children with HIV infection, Bath cancers have high mortality rates; improved outcome for NHL, in particular, may depend on earlier diagnosis and therapy. (C) 1998 by American Society of Clinical Oncology. C1 NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA. RP Granovsky, MO (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6130 Execut Blvd,EPN-434, Rockville, MD 20852 USA. FU NCI NIH HHS [CA 13539] NR 37 TC 72 Z9 75 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1998 VL 16 IS 5 BP 1729 EP 1735 PG 7 WC Oncology SC Oncology GA ZL271 UT WOS:000073415900014 PM 9586885 ER PT J AU Hoffman, MP Roque, E Nomizu, M Yamada, Y Kleinman, HK AF Hoffman, MP Roque, E Nomizu, M Yamada, Y Kleinman, HK TI Laminin peptides promote differentiation of salivary gland cells. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAY PY 1998 VL 77 IS 5 BP 1131 EP 1131 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA ZL730 UT WOS:000073464700197 ER PT J AU Yuspa, SH AF Yuspa, SH TI The pathogenesis of squamous cell cancer: lessons learned from studies of skin carcinogenesis SO JOURNAL OF DERMATOLOGICAL SCIENCE LA English DT Review DE skin cancer; protein kinase C; fos; EGF receptor ID PROTEIN-KINASE-C; NEOPLASTIC MOUSE KERATINOCYTES; TERMINAL DIFFERENTIATION; MALIGNANT CONVERSION; TUMOR PROGRESSION; TYROSINE PHOSPHORYLATION; HIGH-RISK; V-RAS; EXPRESSION; STAUROSPORINE AB This study used the induction of squamous cell carcinomas on mouse skin as an experimental model to evaluate molecular and biochemical changes that contribute to the neoplastic phenotype. The study was facilitated by the development of keratinocyte cell culture assays that reproduce each stage of the carcinogenesis process, by discoveries of stage-specific genetic and epigenetic changes and by application of pharmacological and molecular tools that modify each step. An early event in the transformation of keratinocytes involves mutation and activation of the ras(Ha) gene, producing a benign tumor. The phenotypic consequences of ras mutations are mediated by activation of the epidermal growth factor receptor (EGFR), upregulation of protein kinase C (PKC)alpha and AP-1 mediated transcriptional activity and inactivation of PKC delta through tyrosine :phosphorylation. These changes in benign tumors are manifested by hyperproliferation (EGFR), aberrant expression of keratinocyte genes (PKC alpha and AP-1) and delayed terminal differentiation (PKC delta). Accumulated chromosomal abnormalities, multifocal phenotypic changes and alterations in gene expression are associated with premalignant progression. Upregulation of the fos gene and AP-1 transcriptional activity causes malignant conversion of benign keratinocytes. In the absence of c-fos, benign tumor cells fail to upregulate secreted angiogenic and proteolytic factors and this may prevent malignant conversion. These pathways provide targets for preventive strategies to interrupt the process of carcinogenesis prior to the evolution of the fully malignant tumor. (C) 1998 Published by Elsevier Science Ireland Ltd. All rights reserved. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. RP Yuspa, SH (reprint author), Bldg 37,Room 3B25,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. NR 30 TC 127 Z9 128 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0923-1811 J9 J DERMATOL SCI JI J. Dermatol. Sci. PD MAY PY 1998 VL 17 IS 1 BP 1 EP 7 DI 10.1016/S0923-1811(97)00071-6 PG 7 WC Dermatology SC Dermatology GA ZR508 UT WOS:000073984600001 PM 9651822 ER PT J AU Murakami, H Nishioka, S Setterfield, J Bhogal, BS Black, MM Zillikens, D Yancey, KB Balding, SD Giudice, GJ Diaz, LA Nishikawa, T Kiyokawa, C Hashimoto, T AF Murakami, H Nishioka, S Setterfield, J Bhogal, BS Black, MM Zillikens, D Yancey, KB Balding, SD Giudice, GJ Diaz, LA Nishikawa, T Kiyokawa, C Hashimoto, T TI Analysis of antigens targeted by circulating IgG and IgA autoantibodies in 50 patients with cicatricial pemphigoid SO JOURNAL OF DERMATOLOGICAL SCIENCE LA English DT Article DE autoantigen; bullous pemphigoid antigen; cicatricial pemphigoid; fusion protein; immunoblot ID EPIDERMOLYSIS-BULLOSA-ACQUISITA; BASEMENT-MEMBRANE; IMMUNOBLOT ANALYSIS; BMZ ANTIBODIES; SKIN; IDENTIFICATION; BP180; IMMUNOFLUORESCENCE; MICROSCOPY; EPILIGRIN AB In this study we investigated sera from 50 typical cicatricial pemphigoid (CP) patients. By indirect immunofluorescence on 1 M NaCl-split human skin sections, IgG of 17 sera and IgA of 22 sera reacted with the epidermal side of the split, while IgG of two sera reacted with the dermal side. These latter two sera were later confirmed to be anti-epiligrin CP. By immunoblotting of epidermal extracts, IgG of 14 sera reacted with the 230 kD bullous pemphigoid (BP) antigen (BP230). IgG of 15 sera and IgA of 11 sera reacted with the 180 kD BP antigen (BP180). Interestingly, a bacterial fusion protein containing the BP180 NC16a domain was recognized by IgG of 18 sera but not by IEA of any sera. Fusion proteins containing the C-terminal region of BP180 were recognized by IgG of 20 sera, but it was detected by IEA of only two sera. Our results suggest that, although CP sera show very low titers of autoantibodies, a considerable number of sera contain IgG antibodies to BP180 (either NC16a or C-terminal domain), confirming previous studies. In addition, we showed that greater numbers of IgA antibodies react with BP180, seemingly with different types of epitopes from those for IgG antibodies. Because the specificity of IgG antibodies is not very different from those in BP, IgA antibodies may play a specific role for the development of characteristic clinical features in CP. Future studies should elucidate the pathogenic role of the IgA antibodies in CP. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Kurume Univ, Sch Med, Dept Dermatol, Kurume, Fukuoka 830, Japan. Keio Univ, Sch Med, Dept Dermatol, Tokyo 160, Japan. United Med & Dent Sch Guys & St Thomas Hosp, Dept Immunofluorescence, St Johns Inst Dermatol, London SE1 7EH, England. Univ Wuerzburg, Dept Dermatol, D-97080 Wuerzburg, Germany. NCI, Dermatol Branch, Bethesda, MD 20892 USA. Med Coll Wisconsin, Dept Dermatol, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Dept Biochem, Milwaukee, WI 53226 USA. Med Coll Wisconsin, VA Med Ctr, Milwaukee, WI 53226 USA. RP Hashimoto, T (reprint author), Kurume Univ, Sch Med, Dept Dermatol, 67 Asahimachi, Kurume, Fukuoka 830, Japan. RI Zillikens, Detlef/C-8572-2011 FU NIAMS NIH HHS [R01-AR32081, R01-AR32599, R01-AR40410] NR 30 TC 61 Z9 61 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0923-1811 J9 J DERMATOL SCI JI J. Dermatol. Sci. PD MAY PY 1998 VL 17 IS 1 BP 39 EP 44 DI 10.1016/S0923-1811(97)00067-4 PG 6 WC Dermatology SC Dermatology GA ZR508 UT WOS:000073984600006 PM 9651827 ER PT J AU Piver, WT Duval, LA Schreifer, JA AF Piver, WT Duval, LA Schreifer, JA TI Evaluating health risks from ground-water contaminants SO JOURNAL OF ENVIRONMENTAL ENGINEERING-ASCE LA English DT Article AB A method is proposed to evaluate changes in health risks from ground water drawn from specified locations in the subsurface as a result of the transport of contaminant chemicals from buried waste sites. To evaluate the health risk, a stochastic one-dimensional contaminant transport model is solved with Monte Carlo simulation. The risk at a specified location is equal to the number of times that contaminant concentrations exceed the health standard concentration divided by the number of iterations in the Monte Carlo simulation. The method is used on a simulated aquifer to demonstrate how health risks vary with time and location in the subsurface. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Duke Univ, Dept Civil & Environm Engn, Durham, NC 27708 USA. RP Piver, WT (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 10 TC 4 Z9 4 U1 0 U2 0 PU ASCE-AMER SOC CIVIL ENGINEERS PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2398 USA SN 0733-9372 J9 J ENVIRON ENG-ASCE JI J. Environ. Eng.-ASCE PD MAY PY 1998 VL 124 IS 5 BP 475 EP 478 DI 10.1061/(ASCE)0733-9372(1998)124:5(475) PG 4 WC Engineering, Environmental; Engineering, Civil; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA ZJ416 UT WOS:000073213300013 ER PT J AU Territo, PR Burggren, WW AF Territo, PR Burggren, WW TI Cardio-respiratory ontogeny during chronic carbon monoxide exposure in the clawed frog Xenopus laevis SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE ontogeny; development; Xenopus laevis; carbon monoxide; oxygen consumption; lactate; heart rate; stroke volume; cardiac output; O-2 consumption/transport quotient ID BULLFROGS RANA-CATESBEIANA; RAINBOW-TROUT; OXYGEN-CONSUMPTION; GAS-EXCHANGE; WHOLE-BLOOD; HEART-RATE; HYPOXIA; LARVAE; TRANSPORT; FISH AB The present study investigates the ontogeny of cardiorespiratory physiology in Xenopus laevis where Oz transport is obstructed. Animals were raised from eggs (NF stage 1) to metamorphic climax (NF stage 63), while maintained either in air or in chronic 2 kPa CO, which functionally ablates O-2 transport by hemoglobin (Hb), Whole-animal rate of oxygen consumption ((M)over dot (O2)), whole-body lactate concentration, individual mass, heart rate (fn) and stroke volume (Vs) were measured. Additionally, cardiac output ((Q)over dot) and the ratio of the rate of oxygen consumption to the total rate at which oxygen is transported in the blood ((M)over dot (O2)/(Q)over dot (O2)) were calculated to determine limitations imparted when O-2 transport is impaired. Our data on early development suggest that the onset of convective blood pow occurs prior to the absolute need for convection to supplement diffusive transport, Values for (M)over dot (O2), whole-body lactate concentration, mass and fH did not differ significantly between controls and CO-exposed animals. However, CO-exposed animals showed a significant (P<0.05) increase in Vs, (M)over dot (O2)/(Q)over dot (O2) and (Q)over dot compared with controls. These results indicate that limiting blood O-2 transport is not deleterious to metabolism and development as a whole and that convective oxygen transport via Hb is not essential for normal cardiovascular or respiratory function during larval development. C1 Univ Nevada, Dept Biol Sci, Las Vegas, NV 89154 USA. RP Territo, PR (reprint author), NHLBI, NIH, Cardiac Energet Lab, Bldg 1,Room B3-07,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Burggren, Warren/A-1561-2016 OI Burggren, Warren/0000-0001-8023-420X NR 65 TC 49 Z9 50 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD MAY PY 1998 VL 201 IS 9 BP 1461 EP 1472 PG 12 WC Biology SC Life Sciences & Biomedicine - Other Topics GA ZT233 UT WOS:000074063900019 PM 9547325 ER PT J AU Cupp, MS Ribeiro, JMC Champagne, DE Cupp, EW AF Cupp, MS Ribeiro, JMC Champagne, DE Cupp, EW TI Analyses of cDNA and recombinant protein for a potent vasoactive protein in saliva of a blood-feeding black fly, Simulium vittatum SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE erythema; vasoactive protein; Simulium vittatum; black fly; salivary gland; cDNA ID LUTZOMYIA-LONGIPALPIS; FINDING STRATEGY; GLAND EXTRACT; AEDES-AEGYPTI; FLIES DIPTERA; RESPONSES; MODULATION; ARTHROPODS; MAXADILAN AB A cDNA was cloned from the salivary glands of a blood-feeding black fly Simulium vittatum. The encoded protein has been given the name Simulium vittatum erythema protein or SVEP, because of its ability to increase blood perfusion in skin capillaries, resulting in the well-characterized erythema of black fly bites. The full-length cDNA contains 548 base pairs which encode 152 amino acid residues of the nascent protein. Post-translational processing produces a mature, secreted protein of 133 residues with a molecular mass of 15.4 kDa. Recombinant SVEP (rSVEP) was produced in a baculovirus expression system and purified by a one-step reversed-phase HPLC procedure. Analyses of physical properties and biological potency demonstrated fidelity of rSVEP to the native protein. Recombinant SVEP relaxed rabbit aorta preparations when preconstricted with 2 mu mol l(-1) phenylephrine or 25 mmol l(-1) K+ but not with 60 mmol l(-1) K+. Further, the rSVEP-induced relaxation response of phenylephrine-constricted aorta was inhibited by glibenclamide (10 mu mol l(-1)), suggesting that at least part of its action to relax smooth muscle may result from the opening of ATP-dependent K(+)channels. SVEP is a novel salivary-gland-derived vasoactive protein that may be essential for blood feeding by black flies and could potentially enhance transmissionof filarial parasites. C1 Univ Arizona, Dept Entomol, Tucson, AZ 85721 USA. Auburn Univ, Dept Entomol, Auburn, AL 36849 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Georgia, Dept Entomol, Athens, GA 30602 USA. RP Univ Arizona, Dept Entomol, Tucson, AZ 85721 USA. EM mcupp@acesag.auburn.edu OI Ribeiro, Jose/0000-0002-9107-0818 FU NIAID NIH HHS [AI-31075, AI-18694, AI-35591] NR 28 TC 31 Z9 31 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0022-0949 EI 1477-9145 J9 J EXP BIOL JI J. Exp. Biol. PD MAY PY 1998 VL 201 IS 10 BP 1553 EP 1561 PG 9 WC Biology SC Life Sciences & Biomedicine - Other Topics GA ZU570 UT WOS:000074211300005 PM 9556538 ER PT J AU Agostini, HT Shishido-Hara, Y Baumhefner, RW Singer, EJ Ryschkewitsch, CF Stoner, GL AF Agostini, HT Shishido-Hara, Y Baumhefner, RW Singer, EJ Ryschkewitsch, CF Stoner, GL TI JC virus type 2: definition of subtypes based on DNA sequence analysis of ten complete genomes SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; CEREBROSPINAL-FLUID; BRAIN; PCR; AMPLIFICATION; INDIVIDUALS; VARIANTS; STRAIN; URINE; AIDS AB Five major genotypes of JC virus (JCV) have been defined based on nucleotide differences in the VP1 gene of the DNA sequence. These types are probably a result of virus evolution in geographically isolated population groups. One of the first genotypes identified, Type 2, was found to represent strains of Asian origin. In order to further define the spectrum within Type 2 strains, the entire 5.1 kb genome of nine urinary strains of ICV was amplified by PCR with one pair of primers. These urine samples were obtained in the USA (California and New Mexico) from three European Americans, three Native Americans, two African Americans and one Hispanic American. The complete genome of an Asian ICV strain (Tokyo-1) isolated from progressive multifocal leukoencephalopathy (PML) brain in Japan was also sequenced. Here, we report the analysis of these ten DNA sequences and their deduced protein translations. Two phylogenetically distinct subtypes of Type 2 were found, 2A and 2B, which differ from each other by 0.8-1.1% of the coding region sequence. A 215 bp product amplified with primers in the VP1 gene contains enough sequence information to distinguish the major types and subtypes of JCV and is suitable for application in viral epidemiological studies. The investigation of these genomic variations is of special interest because JCV Type 2 strains are found at a significantly higher frequency in brain tissue of patients with PML than would be predicted from their excretion in a control population. C1 NINDS, Neurotoxicol Sect, NIH, Bethesda, MD 20892 USA. W Los Angeles Vet Affairs Med Ctr, Neurol Serv, Los Angeles, CA 90073 USA. RP Stoner, GL (reprint author), NINDS, Neurotoxicol Sect, NIH, Bldg 36,Room 4A-29, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA 90073] NR 32 TC 43 Z9 43 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD MAY PY 1998 VL 79 BP 1143 EP 1151 PN 5 PG 9 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA ZL473 UT WOS:000073436400020 PM 9603329 ER PT J AU Johnson, WE Culver, M Iriarte, JA Eizirik, E Seymour, KL O'Brien, SJ AF Johnson, WE Culver, M Iriarte, JA Eizirik, E Seymour, KL O'Brien, SJ TI Tracking the evolution of the elusive Andean mountain cat (Oreailurus jacobita) from mitochondrial DNA SO JOURNAL OF HEREDITY LA English DT Article ID PHYLOGENETIC ANALYSIS; NUCLEOTIDE-SEQUENCES; FELIDAE; TREES AB Rarely observed in the wild, the existence of the Andean mountain cat (Oreailurus jacobita) has been established based on only 3 skulls and 14 museum skins. The Andean mountain cat's evolutionary relationship to other felids based on morphological characters is largely contradictory, with evidence aligning it with South American small spotted cats (ocelot lineage) or alternatively with pantherine lineage felids, Here we describe the phylogenetic distinctiveness and placement of the Andean mountain cat using DNA extracted from pieces of nine independent pelt specimens, including one confiscated from a trapper in 1995, A phylogenetic analysis of DNA sequences from three rapidly evolving mitochondrial genes (16S rRNA, NADH-5, and ATP-8) indicate that the Andean mountain cat is a distinct species belonging to the ocelot lineage. Our findings suggest that the Andean mountain cat diverged from a common ancestor with the ocelot (Leopardus pardalis) and margay (L. wiedii) and exhibits moderate levels of genetic variation. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Gen Divers, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Program Resources Inc Dyncorp, Biol Carcinogenesis & Dev Program, Frederick, MD 21702 USA. Serv Agricola & Ganadero, Santiago, Chile. Univ Fed Rio Grande do Sul, Dept Genet, Porto Alegre, RS, Brazil. Royal Ontario Museum, Dept Palaeobiol, Toronto, ON M5S 2C6, Canada. RP Johnson, WE (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Gen Divers, Frederick, MD 21702 USA. RI Eizirik, Eduardo/K-8034-2012; Johnson, Warren/D-4149-2016 OI Eizirik, Eduardo/0000-0002-9658-0999; Johnson, Warren/0000-0002-5954-186X NR 50 TC 34 Z9 41 U1 2 U2 17 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1503 EI 1465-7333 J9 J HERED JI J. Hered. PD MAY-JUN PY 1998 VL 89 IS 3 BP 227 EP 232 DI 10.1093/jhered/89.3.227 PG 6 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA ZU606 UT WOS:000074214900006 PM 9656464 ER PT J AU Martinez, A Farr, A Vos, MD Cuttitta, F Treston, AM AF Martinez, A Farr, A Vos, MD Cuttitta, F Treston, AM TI Peptide-amidating enzymes are expressed in the stellate epithelial cells of the thymic medulla SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE thymus; stellate epithelial cells; amidation; oxytocin; immunohistochemistry; in situ hybridization; enzyme assays ID MESSENGER-RNA; ALPHA-AMIDATION; GROWTH-FACTOR; MONOOXYGENASE; LYMPHOCYTES; ANTIGENS; LINES; PAM; LOCALIZATION; BIOACTIVITY AB C-terminal amidation is a post-translational processing step necessary to convey biological activity to a large number of regulatory peptides. In this study we have demonstrated that the peptidyl-glycine alpha-amidating monooxygenase enzyme complex (PAM) responsible for this activity is located in the medullary stellate epithelial cells of the thymus and in cultured epithelial cells bearing a medullary phenotype, using Northern blot, immunocytochemistry, in situ hybridization, and enzyme assays. Immunocytochemical localization revealed a granular pattern in the cytoplasm of the stellate cells, which were also positive for cytokeratins and a B-lymphocyte-associated antigen. The presence of PAM activity in medium conditioned by thymic epithelial cell lines suggests that PAM is a secreted product of these cells. Among the four epithelial cell lines examined, there was a direct correlation between PAM activity and content of oxytocin, an amidated peptide. Taken together, these data provide convincing evidence that thymic epithelial cells have the capacity to generate amidated peptides that may influence T-cell differentiation and suggest that the amidating enzymes could play an important role in the regulation of thymic physiology. C1 NCI, Cell & Canc Biol Dept, Div Clin Sci, NIH, Rockville, MD 20850 USA. Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA. RP Martinez, A (reprint author), NCI, Cell & Canc Biol Dept, Div Clin Sci, NIH, 9610 Med Ctr Dr, Rockville, MD 20850 USA. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 FU NIA NIH HHS [AG 04360]; NIAID NIH HHS [AI 24137] NR 38 TC 7 Z9 7 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD MAY PY 1998 VL 46 IS 5 BP 661 EP 668 PG 8 WC Cell Biology SC Cell Biology GA ZK585 UT WOS:000073339900011 PM 9562574 ER PT J AU Surman, DR Irvine, KR Shulman, EP Allweis, TM Rosenberg, SA Restifo, NP AF Surman, DR Irvine, KR Shulman, EP Allweis, TM Rosenberg, SA Restifo, NP TI Generation of polyclonal rabbit antisera to mouse melanoma associated antigens using gene gun immunization SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE melanoma antigen; recombinant anti-cancer vaccines; gene gun immunization; polyclonal antisera ID NUCLEIC-ACID IMMUNIZATION; MONOCLONAL-ANTIBODIES; TYROSINASE CDNA; CELLS; EXPRESSION; VACCINE; DNA; PIGMENTATION; MELANOCYTES; RESPONSES AB Lymphocytes from patients with melanoma have been used to clone melanoma associated antigens which are, for the most part, nonmutated melanocyte tissue differentiation antigens. To establish a mouse model for the use of these 'self' antigens as targets for anti-tumor immune responses, we have employed the mouse homologues of the human melanoma antigens Tyrosinase, Tyrosinase Related Protein-1 (TRP-1), gp100, and MART-1. We sought to generate antisera against these proteins for use in the construction of experimental recombinant and synthetic anti-cancer vaccines, and for use in biologic studies. Using genes cloned from the B16 mouse melanoma or from murine melanocytes, we immunized rabbits with plasmid DNAs coated onto microscopic gold beads that were then delivered using a hand-held, helium-driven 'gene gun'. This strategy enabled us to generate polyclonal rabbit sera containing antibodies that specifically recognized each antigen, as measured by immunostaining of vaccinia Virus infected cells. The sera that we generated specifically for TRP-1, gp100, and MART-1 recognized extracts of the spontaneous murine melanoma, B16. The identities of the recognized proteins was confirmed by Western blot analysis. The titers and specificities of these antisera were determined using ELISA. Interestingly, serum samples generated against murine MART-1 and gp100 developed antibodies that were cross-reactive with the corresponding human homologues. Recognition of human gp100 and murine Tyrosinase appeared to be dependent upon conformational epitopes since specificity was lost upon denaturation of the antigens. These antisera may be useful in the detection, purification and characterization of the mouse homologues of recently cloned human tumor associated antigens and may enable the establishment of an animal model of the immune consequences of vaccination against 'self' antigens. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Restifo, NP (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B46,10 Ctr Dr, Bethesda, MD 20892 USA. EM restifo@nih.gov RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01] NR 30 TC 12 Z9 12 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD MAY 1 PY 1998 VL 214 IS 1-2 BP 51 EP 62 DI 10.1016/S0022-1759(98)00036-2 PG 12 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 101GY UT WOS:000074862300006 PM 9692858 ER PT J AU Mason, LH Willette-Brown, J Anderson, SK Gosselin, P Shores, EW Love, PE Ortaldo, JR McVicar, DW AF Mason, LH Willette-Brown, J Anderson, SK Gosselin, P Shores, EW Love, PE Ortaldo, JR McVicar, DW TI Characterization of an associated 16-kDa tyrosine phosphoprotein required for Ly-49D signal transduction SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; MOLECULES; RECEPTORS; WELL AB Ly-49D is an activating receptor on NK cells that does not become tyrosine phosphorylated upon activation. This report demonstrates that immunoprecipitation of Ly-49D, following pervanadate treatment or specific Ab cross-linking, coprecipitates a 16-kDa tyrosine-phosphorylated protein (pp16), Immunoblotting experiments and data from TCR-zeta/FceRI gamma double knockout mice confirm that pp16 is not TCR-zeta, TCR-eta, or FceRI gamma, Association of pp16 with Ly-49D involves a transmembrane arginine since mutation to leucine (Ly-49D(R54L)) abolishes association with pp16 in transfected P815 cells. In addition, Ly-49D(R54L) transfectants fail to mediate Ca2+ mobilization following Ab cross-linking. Therefore, signaling through Ly-49D on NK cells depends on association with a distinct tyrosine phosphoprotein (pp16) in a manner analogous to that of TCR and FcR. Expression of this novel signaling peptide in both the NK and myeloid lineages indicates that pp16 is likely involved in the signal transduction cascade of additional receptor families. C1 NCI, Expt Immunol Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. US FDA, Div Hematol Prod, Ctr Biol Evaluat & Res, Washington, DC 20204 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Mason, LH (reprint author), NCI, Expt Immunol Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Bldg 560,Room 31-93, Frederick, MD 21702 USA. EM MASON@MAIL.NCIFCRF.GOV RI Anderson, Stephen/B-1727-2012; McVicar, Daniel/G-1970-2015 OI Anderson, Stephen/0000-0002-7856-4266; NR 20 TC 80 Z9 80 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 MAY 1 PY 1998 VL 160 IS 9 BP 4148 EP 4152 PG 5 WC Immunology SC Immunology GA ZJ528 UT WOS:000073225800002 PM 9574512 ER PT J AU Bamford, RN DeFilippis, AP Azimi, N Kurys, G Waldmann, TA AF Bamford, RN DeFilippis, AP Azimi, N Kurys, G Waldmann, TA TI The 5 ' untranslated region, signal peptide, and the coding sequence of the carboxyl terminus of IL-15 participate in its multifaceted translational control SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MESSENGER-RNA TRANSLATION; ACTIVATED KILLER-CELLS; BETA-CHAIN; PROLIFERATION; ELONGATION; INDUCTION; RECEPTOR; CYTOKINE; PROTEIN; BIOSYNTHESIS AB We previously reported that the AUG-burdened 5' untranslated region (UTR) of IL-15 mRNA impedes its translation. Here we demonstrate that the nucleotide or protein sequences of the IL-15 signal peptide and carboxyl terminus also contribute to the poor translation of IL-15 transcripts. In particular, the exchange of the IL-15 signal peptide coding sequence with that of IL-2 increased cellular and secreted levels of IL-15 protein 15- to 20-fold in COS cells, while IL-2 transcripts with the IL-15 signal peptide generated 30- to 50-fold less IL-2 protein than wild-type IL-2, Furthermore, the addition of an artificial epitope tag to the 3' coding sequence of IL-15 increased its protein production 5- to 10-fold. Combining these two IL-15 message modifications, in addition to removing the 5' UTR, increased IL-15 synthesis 250-fold compared with a wild-type construct with an intact 5' UTR, These data suggest that IL-15 mRNA, unlike IL-2 mRNA, may exist in translationally inactive pools. By storing translationally quiescent IL-15 mRNA, cells might respond to intracellular infections or other stimuli by rapidly transforming IL-15 message into one that can be efficiently translated. C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Bamford, RN (reprint author), NCI, Metab Branch, NIH, Bldg 10,Room 4N115, Bethesda, MD 20892 USA. NR 32 TC 115 Z9 122 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1998 VL 160 IS 9 BP 4418 EP 4426 PG 9 WC Immunology SC Immunology GA ZJ528 UT WOS:000073225800036 PM 9574546 ER PT J AU Toda, M Martuza, RL Kojima, H Rabkin, SD AF Toda, M Martuza, RL Kojima, H Rabkin, SD TI In situ cancer vaccination: An IL-12 defective vector replication-competent herpes simplex virus combination induces local and systemic antitumor activity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CARCINOMA CELL-LINES; IN-VIVO; ESTABLISHED TUMORS; RECOMBINANT IL-12; MURINE MELANOMA; INTERLEUKIN-12; CYTOKINE; EXPRESSION; ANTIGEN; IMMUNOTHERAPY AB Intratumoral inoculation of replication-competent, attenuated herpes simplex virus (HSV) mutants inhibits tumor growth by direct cytotoxic viral replication and induction of a tumor-specific immune response. To boost the antitumor response, we describe a defective HSV vector encoding IL-12 as an adjuvant to in situ vaccination by the replication-competent HSV helper virus. The defective HSV vector system consists of defective particles containing tandem repeats of the cytokine genes (p40 and p35) in combination with a HSV helper virus. Heterodimeric IL-12 was expressed and secreted after IL-12 defective vector infection of tumor cells. In a syngeneic, bilateral established tumor model with CT26 murine colon carcinoma, unilateral intratumoral inoculation with an IL-12 defective/replication-competent HSV vector combination significantly reduced tumor growth of the inoculated and noninoculated contralateral tumors. This antitumor effect was significantly greater than with a lacZ-defective/replication-competent HSV vector combination, which itself was significantly greater than the mock inoculation. Efficacy is associated with enhancement of tumor-specific CTL activity, including specificity against the CT26 immunodominant MHC class I restricted Ag AH1, and IFN-gamma production. There was no significant tumor growth inhibition after intratumoral inoculation of s.c. CT26 tumors in athymic mice. We conclude that this defective HSV vector system is an effective method for cytokine gene delivery to tumors in situ and IL-12 expression in tumors synergizes the antitumor activity mediated by the replication-competent HSV helper virus. C1 Georgetown Univ, Med Ctr, Dept Neurosurg, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Georgetown Brain Tumor Ctr, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20007 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Rabkin, SD (reprint author), Georgetown Univ, Med Ctr, Dept Neurosurg, 3970 Reservoir Rd NW, Washington, DC 20007 USA. RI rabkin, samuel/C-2443-2012; Toda, Masahiro/L-2268-2013 OI rabkin, samuel/0000-0003-2344-2795; FU NINDS NIH HHS [NS32677, NS33342] NR 49 TC 116 Z9 116 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1998 VL 160 IS 9 BP 4457 EP 4464 PG 8 WC Immunology SC Immunology GA ZJ528 UT WOS:000073225800041 PM 9574551 ER PT J AU Wynn, TA Cheever, AW Williams, ME Hieny, S Caspar, P Kuhn, R Muller, W Sher, A AF Wynn, TA Cheever, AW Williams, ME Hieny, S Caspar, P Kuhn, R Muller, W Sher, A TI IL-10 regulates liver pathology in acute murine Schistosomiasis mansoni but is not required for immune down-modulation of chronic disease SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GRANULOMA-FORMATION; CELL RESPONSES; INFECTED MICE; TH2 CYTOKINES; T-CELLS; EXPRESSION; HELMINTH; EGGS; INFLAMMATION; FIBROSIS AB We have used IL-10 gene knockout mice (IL-10T) to examine the role of endogenous DL-IO in the down-modulation of hepatic granuloma formation and lymphocyte responses that occurs in chronic infection with the helminth parasite Schistosoma mansoni, Although IL-10-deficient animals showed 20 to 30% mortality between 8 and 14 wk postinfection, they displayed no alterations in their susceptibility to infection and produced similar numbers of eggs as their wild-type littermates. The IL-10T mice displayed a significant increase in hepatic granuloma size at the acute stage of infection, which was associated with increased IFN-gamma, IL-2, IL-1 beta, and TNF-alpha mRNA expression in liver and elevated Th1-type cytokine production by lymphoid cells, Despite developing an enhanced Th1-type cytokine response, the IL-10T mice showed no consistent decrease in their Th2-type cytokine profile, Surprisingly, although granulomatous inflammation was enhanced at the acute stage of infection, the livers of IL-10T mice displayed no significant increase in fibrosis and underwent normal immune down-modulation at the chronic stage of infection, Moreover, the down-modulated state could be induced in IL-10T mice by sensitizing the animals to schistosome eggs before infection, further demonstrating that the major down-regulatory mechanism is not dependent upon IL-10. We conclude that while IL-10 plays an important role in controlling acute granulomatous inflammation, it plays no essential role in the process of immune down-modulation in chronic schistosome infection. C1 NIAID, Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Biomed Res Inst, Rockville, MD 20852 USA. Univ Cologne, Genet Inst, Cologne, Germany. RP Wynn, TA (reprint author), NIAID, Immunol Sect, Parasit Dis Lab, NIH, Bldg 4,Room 126,9000 Rockville Pike, Bethesda, MD 20892 USA. EM twynn@atlas.niaid.nih.gov RI Wynn, Thomas/C-2797-2011; Muller, Werner/B-9044-2008 OI Muller, Werner/0000-0002-1297-9725 NR 38 TC 125 Z9 130 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1998 VL 160 IS 9 BP 4473 EP 4480 PG 8 WC Immunology SC Immunology GA ZJ528 UT WOS:000073225800043 PM 9574553 ER PT J AU Bei, R Guptill, V Masuelli, L Kashmiri, SVS Muraro, R Frati, L Schlom, J Kantor, J AF Bei, R Guptill, V Masuelli, L Kashmiri, SVS Muraro, R Frati, L Schlom, J Kantor, J TI The use of a cationic liposome formulation (DOTAP) mixed with a recombinant tumor-associated antigen to induce immune responses and protective immunity in mice SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE liposome; recombinant human CEA; immunogenicity; Baculovirus; boost ID CARCINOEMBRYONIC-ANTIGEN; MONOCLONAL-ANTIBODIES; IMMUNOLOGICAL ADJUVANTS; ANTITUMOR-ACTIVITY; PROTEIN ANTIGENS; VACCINIA-CEA; CARRIERS; GENE; CARCINOMA; EPITOPES AB The cationic liposome DOTAP is a well-known transfection reagent. It has been manufactured and approved for clinical use, is readily available, and can be easily used as an adjuvant. These characteristics prompted us to investigate the effectiveness of DOTAP as an adjuvant to induce immune responses and protective immunity in mice using baculovirus-derived carcinoembryonic antigen (bV-CEA) as a model antigen. Two routes of administration and a dose-response study of bV-CEA were used in BALB/c mice to define the magnitude of the immune response as well as the most effective route of immunization. The results demonstrate differences in antibody titers, immunoglobulin (Ig)G isotype, and T-cell responses between the intravenous (i.v.) or subcutaneous (s.c.) route of immunization. The titer of the anti-CEA antibodies induced by the s.c. immunization was greater than the response by i.v. immunization. The s.c. route enhanced the IgG2a/2b isotype, whereas i.v. immunization elicited primarily IgG1. T-cell proliferation responses and cytokine production paralleled the humoral response (i.e., production was higher in the s.c. immunized animals). No differences in immunological responses were seen using either 25 or 10 mu g of bV-CEA three times. An amount of 25 mu g of bV-CEA/DOTAP given by s.c. immunization was sufficient in protecting mice from the transplant of syngeneic tumor cells transduced with the human CEA gene. We conclude that the cationic liposome DOTAP may be a useful immunoadjuvant for active anti-tumor immunotherapy in future clinical trials. This study will help to define the most effective way to use such an adjuvant. C1 Univ La Sapienza, Dipartimento Med Sperimentale & Patol, I-00161 Rome, Italy. NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. Univ G DAnnunzio, Dept Oncol & Neurosci, Chieti, Italy. RP Bei, R (reprint author), Univ La Sapienza, Dipartimento Med Sperimentale & Patol, Viale Regina Elena 324, I-00161 Rome, Italy. NR 46 TC 28 Z9 28 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAY PY 1998 VL 21 IS 3 BP 159 EP 169 DI 10.1097/00002371-199805000-00001 PG 11 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA ZM391 UT WOS:000073534600001 PM 9610907 ER PT J AU Maeda, Y Venzon, DJ Mitsuya, H AF Maeda, Y Venzon, DJ Mitsuya, H TI Altered drug sensitivity, fitness, and evolution of human immunodeficiency virus type 1 with pol gene mutations conferring multi-dideoxynucleoside resistance SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID REVERSE-TRANSCRIPTASE; COMBINATION THERAPY; ZIDOVUDINE; INVITRO; INHIBITORS; SELECTION; VARIANTS; REPLICATION; INFECTIVITY; STRAINS AB Investigations were done to determine whether the replication kinetics of human immunodeficiency virus (HIV)-1 were altered when the virus acquired a set or subsets of five mutations (A62V, V75I, F77L, F116Y, and Q151M) in the pol gene conferring resistance to multiple dideoxynucleosides. In the absence of drugs, the replication rate of all infectious clones generated was comparable to that of wild type HIV-1. However, in the presence of zidovudine or didanosine, the comparative order for replication was HIV-1(62/75/77/116/151) > HIV-1(77/116/151) > HIV-1(75/77/116/151) approximate to HIV-1(151), whereas that for drug resistance was HIV-1(75/77/116/151) > HIV-1(62/75/77/116/151) greater than or equal to HIV-1(77/116/151) > HIV-1(151). The virologic features of these infectious mutants suggest that HIV-1 develops drug resistance through one or more mutations, which, however, sacrifice replicative capability; then it finally acquires optimal replication competence by additional mutations when the multi-dideoxynucleoside-resistant mutant emerges. C1 NCI, Expt Retrovirol Sect, Med Branch, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Mitsuya, H (reprint author), NCI, Expt Retrovirol Sect, Med Branch, NIH, Bldg 10,Room 5A11, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 28 TC 106 Z9 110 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1998 VL 177 IS 5 BP 1207 EP 1213 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZM264 UT WOS:000073521100010 PM 9593005 ER PT J AU Clements-Mann, ML Weinhold, K Matthews, TJ Graham, BS Gorse, GJ Keefer, MC McElrath, MJ Hsieh, RH Mestecky, J Zolla-Pazner, S Mascola, J Schwartz, D Siliciano, R Corey, L Wright, PF Belshe, R Dolin, R Jackson, S Xu, S Fast, P Walker, MC Stablein, D Excler, JL Tartaglia, J Duliege, AM Sinangil, F Paoletti, E AF Clements-Mann, ML Weinhold, K Matthews, TJ Graham, BS Gorse, GJ Keefer, MC McElrath, MJ Hsieh, RH Mestecky, J Zolla-Pazner, S Mascola, J Schwartz, D Siliciano, R Corey, L Wright, PF Belshe, R Dolin, R Jackson, S Xu, S Fast, P Walker, MC Stablein, D Excler, JL Tartaglia, J Duliege, AM Sinangil, F Paoletti, E CA NIAID AIDS Vaccine Evaluation Grp TI Immune responses to human immunodeficiency virus (HIV) type 1 induced by canarypox expressing HIV-1(MN) gp120, HIV-1(SF2) recombinant gp120, or both vaccines in seronegative adults SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Annual Meeting of the Institute-of-Human-Virology CY SEP, 1996 CL BALTIMORE, MARYLAND SP Inst Human Virol ID T-LYMPHOCYTE RESPONSES; NEUTRALIZING ANTIBODIES; PASSIVE-IMMUNIZATION; RABIES GLYCOPROTEIN; CYNOMOLGUS MONKEYS; CANDIDATE VACCINE; PERIPHERAL-BLOOD; CLONAL ANALYSIS; NAIVE ADULTS; INFECTION AB A safety and immunogenicity trial was conducted in vaccinia-immune and vaccinia-naive human immunodeficiency virus (HIV)-uninfected adults who were randomized to receive 10(6) or 10(7) TCID50 of canarypox (ALVAC) vector expressing HIV-1(MN) gp160 or 10(5.5) TCID50 of ALVAC-rabies virus glycoprotein control at 0 and 1 or 2 months and ALVAC-gp160 or 50 mu g of HIV-1(SF2) recombinant (r) gp12O in microfluidized emulsion at 9 and 12 months; others received rgp120 at 0, 1, 6, and 12 months. All vaccines were well-tolerated. Neither vaccinia-immune status before vaccination nor ALVAC dose affected HIV immune responses. HIV-1(MN) and HIV-1(SF2) neutralizing antibodies were detected more often (100%) in ALVAC-gp160/rgp120 recipients than in recipients of ALVAC-gp160 (<65%) or rgp120 (89%) alone. ALVAC-gp160/rgp120 also elicited more frequent HIV V3-specific and fusion-inhibition antibodies, antibody-dependent cellular cytotoxicity, lymphoproliferation, and cytotoxic CD8(+) T cell activity than did either vaccine alone. Trials with ALVAC expressing additional HIV components and rgp120 are underway. C1 Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. EMMES Corp, Potomac, MD USA. NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. Duke Univ, Sch Med, Durham, NC USA. Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. St Louis Univ, Sch Med, St Louis, MO USA. Vet Adm Med Ctr, St Louis, MO USA. Univ Rochester, Sch Med & Dent, Rochester, NY USA. Vet Adm Med Ctr, New York, NY 10010 USA. NYU Med Ctr, New York, NY 10016 USA. Virogenet Corp, Troy, NY 12180 USA. Univ Washington, Sch Med, Seattle, WA USA. Walter Reed Army Inst Res, Washington, DC USA. Chiron Vaccines, Emeryville, CA USA. Pasteur Merieux Connaught, Marnes la Coquette, France. RP Clements-Mann, ML (reprint author), Johns Hopkins Univ, Ctr Immunizat Res, Hampton House 117,624 N Broadway, Baltimore, MD 21205 USA. FU NIAID NIH HHS [AI-45207, AI-45208, AI-45211] NR 79 TC 171 Z9 173 U1 1 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1998 VL 177 IS 5 BP 1230 EP 1246 PG 17 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZM264 UT WOS:000073521100013 PM 9593008 ER PT J AU Goletti, D Weissman, D Jackson, RW Collins, F Kinter, A Fauci, AS AF Goletti, D Weissman, D Jackson, RW Collins, F Kinter, A Fauci, AS TI The in vitro induction of human immunodeficiency virus (HIV) replication in purified protein derivative-positive HIV-infected persons by recall antigen response to Mycobacterium tuberculosis is the result of a balance of the effects of endogenous interleukin-2 and proinflammatory and antiinflammatory cytokines SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 4th Conference on Retroviruses and Opportunistic Infections CY JAN 22-31, 1997 CL WASHINGTON, D.C. ID TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR-BETA; ACTIVE TUBERCULOSIS; IMMUNE ACTIVATION; FACTOR-ALPHA; TRANSFORMING GROWTH-FACTOR-BETA-1; PULMONARY TUBERCULOSIS; MONOCYTIC CELLS; TGF-BETA; EXPRESSION AB Coinfection with Mycobacterium tuberculosis and human immunodeficiency virus (HIV) is a serious problem, particularly in developing countries. Recently, M. tuberculosis and purified protein derivative (PPD) were demonstrated to induce HIV replication in CD8 T cell-depleted peripheral blood mononuclear cells from HIV-positive, PPD-positive persons but not in cells from PPD-negative persons. The role of endogenous and exogenous cytokines in modulating M. tuberculosis-induced HIV replication was evaluated. M. tuberculosis-induced HIV replication decreased following simultaneous inhibition of endogenous interleukin (IL)-2, IL-1 beta, and tumor necrosis factor-alpha by the addition of soluble receptors and receptor antagonists or following exogenous IL-10 and transforming growth factor (TGF)-beta. In contrast, neutralization of endogenous IL-10 and TGF-beta augmented M. tuberculosis-induced HIV replication by increasing cellular activation. Thus, the balance between IL-2 and proinflammatory and antiinflammatory cytokines plays a major role in,II. tuberculosis-induced replication of HIV. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Rockville, MD 20857 USA. RP Fauci, AS (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 31,Room 7A03, Bethesda, MD 20892 USA. EM afl03@nih.gov OI Goletti, Delia/0000-0001-8360-4376 NR 44 TC 35 Z9 36 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1998 VL 177 IS 5 BP 1332 EP 1338 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZM264 UT WOS:000073521100026 PM 9593021 ER PT J AU Cohen, JI AF Cohen, JI TI Infection of cells with varicella-zoster virus down-regulates surface expression of class I major histocompatibility complex antigens SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID LYMPHOCYTES-T; IMMUNITY AB In vitro assays indicate that both major histocompatibility complex (MHC) class I and II-restricted cytotoxic T lymphocytes are important for recognition of varicella-zoster virus (VZV)infected cells. This study demonstrates that infection of human fibroblasts with wild-type or recombinant-derived strain Oka VZV results in down-regulation of surface expression of class I MHC heavy chains. Radioactive labeling of infected cells indicated that the amount of newly synthesized class I antigen was similar in uninfected and VZV-infected cells. In addition, immunoblotting showed that the amount of total cellular class I MHC heavy chains was unaffected by VZV infection. These results suggest that the reduction of class I heavy chains on the surface of VZV-infected cells is due to a defect in posttranslational processing. The down-regulation of class I MHC antigens in VZV-infected cells may provide a mechanism for the virus to escape the host immune response. C1 NIAID, Clin Invest Lab, Med Virol Sect, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIAID, Clin Invest Lab, Med Virol Sect, Bldg 10,Room 11N214, Bethesda, MD 20892 USA. NR 16 TC 48 Z9 49 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1998 VL 177 IS 5 BP 1390 EP 1393 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZM264 UT WOS:000073521100036 PM 9593031 ER PT J AU Coleman, AB Lugo, TG AF Coleman, AB Lugo, TG TI Normal human melanocytes that express a bFGF transgene still require exogenous bFGF for growth in vitro SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE melanoma; retroviral vectors ID MALIGNANT SKIN MELANOMA; ENDOTHELIAL-CELLS; TUMOR PROGRESSION; FACTOR RNA; FIBROBLAST; PHENOTYPE; GENE; TRANSFORMATION; LESIONS; PROLIFERATION AB The expression of basic fibroblast growth factor (bFGF) has been implicated as an important factor in the development of malignant melanoma. The timing of this expression suggests that bFGF plays a role early in melanoma tumor progression. Benign nevi produce bFGF, and cells cultured from these lesions show a loss of dependence on exogenous bFGF for growth. We have examined the effects of constitutive bFGF expression on the in vitro growth requirements of normal human melanocytes. bFGF was overexpressed in normal human epidermal melanocytes through genomic insertion of a human bFGF cDNA in a retroviral vector. These melanocytes produced the 18 kDa bFGF isoform as well as the higher molecular weight isoforms. The bFGF was not released into. the culture medium, but it was present in the cell nucleus. The bFGF produced by these cells was mitogenic for 3T3 fibroblasts and therefore possessed functional activity; however, melanocytes producing bFGF had the same appearance and growth patterns as those infected with control virus or uninfected melanocytes. Expression of bFGF did not confer independence from the exogenous mitogen, nor would these cells form colonies in a soft-agar medium. These results indicate that expression of bFGF alone is not enough to cause aberrant growth of normal human melanocytes. C1 Univ Calif Riverside, Div Biomed Sci, Riverside, CA 92521 USA. RP Lugo, TG (reprint author), NCI, Canc Diagnosis Program, 6130 Execut Blvd,Suite EPN 700, Bethesda, MD 20892 USA. NR 45 TC 15 Z9 15 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 1998 VL 110 IS 5 BP 793 EP 799 DI 10.1046/j.1523-1747.1998.00166.x PG 7 WC Dermatology SC Dermatology GA ZJ401 UT WOS:000073211600014 PM 9579548 ER PT J AU Uitto, J Boyd, CD Lebwohl, MG Moshell, AN Rosenbloom, J Terry, S AF Uitto, J Boyd, CD Lebwohl, MG Moshell, AN Rosenbloom, J Terry, S TI International centennial meeting on pseudoxanthoma elasticum: Progress in PXE research SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material ID FIBERS; GENE C1 Thomas Jefferson Univ, Jefferson Med Coll, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA. Univ Hawaii, Pacific Biomed Res Ctr, Honolulu, HI 96822 USA. Mt Sinai Sch Med, Dept Dermatol, New York, NY USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Dent Med, Philadelphia, PA 19104 USA. PXE Int, Sharon, MA USA. RP Uitto, J (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Dermatol & Cutaneous Biol, 233 S 10th St,Suite 450 BLSB, Philadelphia, PA 19107 USA. FU NIAMS NIH HHS [1R13 AR44826-01] NR 19 TC 39 Z9 39 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 1998 VL 110 IS 5 BP 840 EP 842 DI 10.1046/j.1523-1747.1998.00188.x PG 3 WC Dermatology SC Dermatology GA ZJ401 UT WOS:000073211600023 PM 9579557 ER PT J AU Fukumoto, T Matsukawa, A Yoshimura, T Edamitsu, S Ohkawara, S Takagi, K Yoshinaga, M AF Fukumoto, T Matsukawa, A Yoshimura, T Edamitsu, S Ohkawara, S Takagi, K Yoshinaga, M TI IL-8 is an essential mediator of the increased delayed-phase vascular permeability in LPS-induced rabbit pleurisy SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE inflammation; neutrophil infiltration; tumor necrosis factor alpha ID TUMOR-NECROSIS-FACTOR; ATTRACTANT ACTIVATION PROTEIN-1; AMINO-ACID-SEQUENCE; NEUTROPHIL ACCUMULATION; POLYMORPHONUCLEAR LEUKOCYTES; SELECTIVE DEPLETION; MONOCLONAL-ANTIBODY; PLASMA LEAKAGE; TNF-ALPHA; IN-VIVO AB We investigated use involvement of IL-8 in the delayed vascular permeability (VP) in rabbit lipopolysaccharide (LPS)-pleurisy. Maximal level of interleukin-8 (IL-8) was detected in pleural fluid at 2 h after LPS injection and anti-IL-8 inhibited the delayed VP by 90%. Injection of homologous IL-8 induced VP, the time-course of which preceded that of LPS-induced delayed VP. Production of IL-8 in LPS-pleurisy was inhibited with anti-tumor necrosis factor alpha (TNF-alpha), whereas the production of TNF-alpha was not affected with anti-IL-8. Injection of IL-8 did not induce TNF-alpha production and anti-TNF-alpha had no effect on IL-8-induced VP. injection of homologous TNF-alpha induced IL-8 production and VP, and TNF-alpha induced delayed VP was blocked with anti-IL-8. These results indicate important roles of IL-8 in LPS-induced delayed VP and that TNF-alpha causes the delayed VP through the production of IL-8. C1 Kumamoto Univ, Sch Med, Dept Pathol, Kumamoto 860, Japan. Kumamoto Univ, Sch Med, Dept Orthoped, Kumamoto 860, Japan. Natl Canc Inst, Frederick Canc Res & Dev Ctr, Immunol Lab, Immunopathol Sect, Frederick, MD USA. RP Yoshinaga, M (reprint author), Kumamoto Univ, Sch Med, Dept Pathol, 2-2-1 Honjo, Kumamoto 860, Japan. NR 38 TC 17 Z9 17 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAY PY 1998 VL 63 IS 5 BP 584 EP 590 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA ZK602 UT WOS:000073341600008 PM 9581802 ER PT J AU Bruce, C Sharp, DS Tall, AR AF Bruce, C Sharp, DS Tall, AR TI Relationship of HDL and coronary heart disease to a common amino acid polymorphism in the cholesteryl ester transfer protein in men with and without hypertriglyceridemia SO JOURNAL OF LIPID RESEARCH LA English DT Article DE cholesteryl ester transfer protein; lipid transfer protein; high density lipoproteins; hypertriglyceridemia; coronary heart disease ID HIGH-DENSITY-LIPOPROTEIN; TRANSGENIC MICE; PLASMA; GENE; MUTATION; DEFICIENCY; ATHEROSCLEROSIS; DETERMINANTS; LIVER; LOCI AB Plasma triglyceride (TG) levels are inversely related to HDL-cholesterol levels and subjects with high TG and low HDL cholesterol have increased coronary heart disease (CHD) risk. Plasma cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from HDL to TG-rich lipoproteins. In this study we determined the relationship between a common CETP amino acid polymorphism (I405V) and CETP and HDL levels and CHD prevalence in 576 men of Japanese ancestry in the Honolulu Heart Program cohort. This conservative substitution was associated with altered plasma CETP concentration (1.95 +/- 0.54, 1.91 +/- 0.57, and 1.77 +/- 0.57 mu g/ml for the II, Nand VV genotypes, respectively), The distribution of plasma CETP concentrations among the VC:but not LI, men appeared bimodal (P < 0.01), suggesting the presence of a functionally significant CETP gene mutation(s) in a subset of V alleles, HDLC levels were higher in VV than IV for II men (55.4 +/- 17.4, 51.3 +/- 16.6, 51.1 +/- 17.0 mg/dl, P < 0.04), However, the increase in HDL was only significant in VV men with plasma TG > 165 mg/dl, Although CHD prevalence was not significantly different among the three genotypes in this population, in the subpopulation with high plasma TG, CHD prevalence appeared higher among VV than Nor II subjects (38% vs. 27% vs. 18%, P < 0.05 for an interaction of genotype and plasma TG levels). In fresh plasma from a separate group of normolipidemic subjects, the V/I polymorphism was not associated with any change in plasma CETP specific activity.ir The data suggest that a widespread and common CETP gene mutation(s) in linkage disequilibrium with 405V causes low CETP. Among hypertriglyceridemic men this is associated with higher HDL and possibly with increased CHD. C1 Columbia Univ, Div Mol Med, New York, NY 10032 USA. NHLBI, Div Epidemiol & Clin Applicat, Epidemiol & Biometry Program, NIH, Bethesda, MD 20892 USA. RP Tall, AR (reprint author), Columbia Univ, Div Mol Med, New York, NY 10032 USA. FU NHLBI NIH HHS [HL22682, HL56984, N01-HC-02901] NR 37 TC 106 Z9 112 U1 0 U2 1 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAY PY 1998 VL 39 IS 5 BP 1071 EP 1078 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZM678 UT WOS:000073564900016 PM 9610775 ER PT J AU Duyn, JH Yang, YH Frank, JA van der Veen, JW AF Duyn, JH Yang, YH Frank, JA van der Veen, JW TI Simple correction method for k-space trajectory deviations in MRI SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE fast MRI; gradient hardware; k-space; correction methods AB A method is presented to correct for the imperfections of spatial encoding gradients in MRI. The approach is simple and fast, can be performed with standard scanner hardware, and does not require separate measurements with reference phantoms. The new method, using the MR signal to accurately measure the k-space trajectory of the imaging sequence, allows for correction of gradient hardware imperfections and eddy-current effects. Initial measurements are presented which demonstrate the efficacy of the method to correct images acquired with spiral and EPI scan techniques. C1 NIH, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. NIH, CBDB, Bethesda, MD 20892 USA. RP Duyn, JH (reprint author), NIH, Lab Diagnost Radiol Res, Bldg 10,Room B1N-256, Bethesda, MD 20892 USA. RI Duyn, Jozef/F-2483-2010 NR 6 TC 166 Z9 168 U1 7 U2 17 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD MAY PY 1998 VL 132 IS 1 BP 150 EP 153 DI 10.1006/jmre.1998.1396 PG 4 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA ZR481 UT WOS:000073981300019 PM 9615415 ER PT J AU Malkov, VA Camerini-Otero, RD AF Malkov, VA Camerini-Otero, RD TI Dissociation kinetics of RecA protein-three-stranded DNA complexes reveals a low fidelity of RecA-assisted recognition of homology SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE dissociation kinetics; fidelity; RecA; three-stranded DNA ID ESCHERICHIA-COLI RECA; HUMAN RAD51 PROTEIN; WATSON-CRICK BONDS; CRYSTAL-STRUCTURE; ATP HYDROLYSIS; BASE TRIPLETS; BRANCH MIGRATION; HELIX FORMATION; IN-VITRO; RECOMBINATION AB We determined that the incorporation of one mismatch into RecA mediated synaptic complexes between oligonucleotide single-stranded DNAs and target duplex DNAs destabilizes the complex by 0.8 to 1.9 kcal/mol. This finding supports our previous result, that RecA binding per se can significantly decrease the loss in free energy associated with mismatch incorporation even in the absence of ATP hydrolysis. We show that the specificity is mostly driven by the dissociation process. We found that the relative destabilization induced by different mismatches depends on their position. Thus, while there is a good correlation between the ranking order of mismatches at the 5' end of synaptic complexes and mismatches in heteroduplexes (D-loops), there is no correlation between the ranking order for mismatches at the 3' end and mismatches in various DNA structures. This difference between the 5' and 3' ends of synaptic complexes agrees well with the established 5' to 3' polarity of the strand exchange promoted by RecA protein. The lack of a correlation between mismatches at the 3' end of synaptic complexes and mismatches in D-loops suggests the intermediate is probably not a canonical protein-free D-loop. C1 NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Camerini-Otero, RD (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bldg 10,Room 9D15,10 Ctr Dr,MSC 1810, Bethesda, MD 20892 USA. NR 57 TC 17 Z9 18 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 MAY 1 PY 1998 VL 278 IS 2 BP 317 EP 330 DI 10.1006/jmbi.1998.1706 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZN917 UT WOS:000073696500004 PM 9571054 ER PT J AU Kultz, D AF Kultz, D TI Phylogenetic and functional classification of mitogen- and stress-activated protein kinases SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE extracellular signal-regulated kinase; mitogen-activated protein kinase; stress-activated protein kinase; phosphorylation; signature sequence; signal transduction; structure; evolution ID SIGNAL-TRANSDUCTION PATHWAYS; MAP KINASE; SACCHAROMYCES-CEREVISIAE; REGULATED KINASE; MAMMALIAN-CELLS; HOMOLOG; TYROSINE; PHOSPHORYLATES; GROWTH; EXPRESSION AB All currently sequenced stress-activated protein kinases (SAPKs), extracellular signal-regulated kinases (ERKs), and other mitogen-activated protein kinases (MAPKs) were analyzed by sequence alignment, phylogenetic tree construction, and three-dimensional structure modeling in order to classify members of the MAPK family. Based on this analysis the MAPK family was divided into three subgroups (SAPKs, ERKs, and MAPK3) that consist of at least nine subfamilies. Members of a given subfamily were exclusively from animals, plants, or yeast/fungi. A single signature sequence, [LIVM][TS]XX[LIVM]XT[RK][WY]YRXPX[LIVM][LIVM], was identified that is characteristic for all MAPKs and sufficient to distinguish MAPKs from other members of the protein kinase superfamily. This signature sequence contains the phosphorylation site and is located on loop 12 of the three-dimensional structure of MAPKs. I also identified signature sequences that are characteristic for each of the nine subfamilies of MAPKs. By modeling the three-dimensional structure of three proteins for each MAPK subfamily based on the resolved atomic structures of rat ERK2 and murine p38, it is demonstrated that amino acids conserved in all MAPKs are located primarily in the center of the protein around the catalytic cleft. I conclude that these residues are important for maintaining proper folding into the gross structure common to all MAPKs. On the other hand, amino acids conserved in a given subfamily are located mainly in the periphery of MAPKs, indicating their possible importance for defining interactions with substrates, activators, and inhibitors. Within these subfamily-specific regions. amino acids were identified that represent unique residues occurring in only a single subfamily and their location was mapped in three-dimensional structure models. These unique residues are likely to be crucial for subfamily-specific interactions of MAPKs with substrates, inhibitors, or activators and, therefore, represent excellent targets for site-directed mutagenesis experiments. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Kultz, D (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, 10 Ctr Dr,MSC 1603,Bldg 10,Room 6N260, Bethesda, MD 20892 USA. NR 89 TC 135 Z9 141 U1 0 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD MAY PY 1998 VL 46 IS 5 BP 571 EP 588 DI 10.1007/PL00006338 PG 18 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA ZH748 UT WOS:000073143700008 PM 9545468 ER PT J AU Zupan, V Hill, JM Brenneman, DE Gozes, I Fridkin, M Robberecht, P Evrard, P Gressens, P AF Zupan, V Hill, JM Brenneman, DE Gozes, I Fridkin, M Robberecht, P Evrard, P Gressens, P TI Involvement of pituitary adenylate cyclase-activating polypeptide II vasoactive intestinal peptide 2 receptor in mouse neocortical astrocytogenesis SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE activity-dependent neurotrophic factor; 5-bromo-2 '-deoxyuridine; cyclic AMP; glial fibrillary acidic protein; growth factor; Ro 25-1553 ID DEVELOPING MURINE BRAIN; FUNCTIONAL EXPRESSION; RAT-BRAIN; INDUCED DISTURBANCES; CORTICAL ASTROCYTES; NEURONAL SURVIVAL; VIP RECEPTORS; ANTAGONIST; CLONING; PACAP AB At the end of neuronal migration, the neopallial germinative zone produces glial cells destined to colonize the upper layers of neocortex. High densities of binding sites for vasoactive intestinal peptide (VIP) have been found in the rodent germinative zone just after completion of neuronal migration, suggesting a possible role of VIP in neocortical astrocytogenesis. In the present study, administration of a VIP antagonist at embryonic days 17 and 18 to pregnant mice was followed by a dramatic depletion of astrocytes in the upper cortical layer of the offspring. The depletion of astrocytes was dose-dependent, with a 42% reduction in the density of astrocytes observed with 50 mu g of antagonist. The antagonist effect was reversed by cotreatment with VIP or pituitary adenylate cyclase-activating polypeptide (PACAP), suggesting the involvement of a receptor common to these two neuropeptides. VIP antagonist-induced inhibition of astrocytogenesis was also blocked by Po 25-1553, a long-acting cyclic VIP analogue selective for the PACAP II VIP2 receptor subclass. Our results demonstrate that VIP and/or PACAP play a crucial physiological role in neocortical astrocytogenesis, possibly through interaction with PACAP II VIP2 receptors. C1 Hop Robert Debre, Serv Neuropediat, F-75019 Paris, France. Hop Robert Debre, INSERM CRI9701, F-75019 Paris, France. Fac Xavier Bichat, Paris, France. NICHHD, Dev Neurobiol Lab, Sect Dev & Mol Pharmacol, Bethesda, MD 20892 USA. Weizmann Inst Sci, Dept Organ Chem, IL-76100 Rehovot, Israel. Tel Aviv Univ, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. Univ Brussels, Sch Med, Lab Chim Biol & Nutr, Brussels, Belgium. RP Gressens, P (reprint author), Hop Robert Debre, Serv Neuropediat, 48 Blvd Serurier, F-75019 Paris, France. NR 49 TC 51 Z9 53 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 1998 VL 70 IS 5 BP 2165 EP 2173 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA ZJ393 UT WOS:000073210500044 PM 9572304 ER PT J AU Ochedalski, T Rabadan-Diehl, C Aguilera, G AF Ochedalski, T Rabadan-Diehl, C Aguilera, G TI Interaction between glucocorticoids and corticotropin releasing hormone (CRH) in the regulation of the pituitary CRH receptor in vivo in the rat SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE pituitary; CRH receptor; glucocorticoids; CRH ID MESSENGER-RIBONUCLEIC-ACID; CHRONIC STRESS; ANTERIOR-PITUITARY; GENE-TRANSCRIPTION; SUPRAOPTIC NUCLEI; ADRENAL AXIS; EXPRESSION; SECRETION; RESPONSES; BRAIN AB Acute stress causes biphasic changes in corticotropin releasing hormone (CRH) receptor mRNA expression with an early decrease followed by an increase. However, in the absence of glucocorticoids in adrenalectomized rats, stress results in prolonged CRH receptor (CRH-R) mRNA loss, suggesting that interactions between glucocorticoids and hypothalamic factors are critical for regulation of CRH receptor mRNA. To address this question, CRH binding, type-1 CRH-R mRNA, POMC mRNA and POMC hnRNA expression were measured by binding autoradiography and in situ hybridization in pituitaries from intact and adrenalectomized rats. CRH-R mRNA decreased by 59% 5 h after injection of corticosterone (10 mg sc) and returned to basal levels by 18 h, a time when plasma corticosterone concentrations were still elevated, and CRH binding and POMC hnRNA were significantly reduced. Elevations in plasma corticosterone in the range of acute stress by injection of 2 mg sc caused CRH-R mRNA expression to return to near basal values by 6 h, after a 52% and 39% decrease at 2 h and 4 h. More transient changes were seen after a single injection of CRH (1 mu g), with a 44% decrease in CRH-R mRNA and a 175% increase in POMC hnRNA by 2 h, returning to basal values by 4 h, The transient effect of CRH was not due to clearance of CRH from the circulation or receptor desensitization since CRH receptor mRNA expression also recovered after injection of a higher dose (10 mu g) or repeated injections of CRH which caused sustained increases in plasma CRH and pituitary POMC hnRNA levels. CRH injection in adrenalectomized rats decreased CRH-R mRNA for up to 6 h, suggesting that glucocorticoids ale permissive for the recovery of CRH-R mRNA, Supporting this hypothesis, simultaneous injection of corticosterone and CRH restored CRH-R mRNA expression by 4 h, and increased CRH binding 4 h and 6 h after injection. The data show that interaction between CRH and glucocorticoids counteracts individual inhibitory effects of these regulators alone, and that such effects are likely to contribute to the regulatory pattern of pituitary CRH receptors during acute stress. C1 NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Aguilera, G (reprint author), NICHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bldg 10,Room 10,N 262,10 Ctr Dr, Bethesda, MD 20892 USA. NR 38 TC 23 Z9 23 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD MAY PY 1998 VL 10 IS 5 BP 363 EP 369 DI 10.1046/j.1365-2826.1998.00212.x PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA ZR936 UT WOS:000074031200006 PM 9663650 ER PT J AU Jeohn, GH Kong, LY Wilson, B Hudson, P Hong, JS AF Jeohn, GH Kong, LY Wilson, B Hudson, P Hong, JS TI Synergistic neurotoxic effects of combined treatments with cytokines in murine primary mixed neuron/glia cultures SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE cytokine; glia; neurons; neurotoxicity; nitric oxide; lipopolysaccharide ID NITRIC-OXIDE SYNTHASE; CENTRAL-NERVOUS-SYSTEM; HUMAN-IMMUNODEFICIENCY-VIRUS; CORTICAL CULTURES; NEURONAL INJURY; GLUTAMATE NEUROTOXICITY; ACTIVATED MICROGLIA; ALZHEIMERS-DISEASE; INTERFERON-GAMMA; IMMUNE-SYSTEM AB Activation of brain glial cells with the bacterial endotoxin lipopolysaccharide (LPS), the HIV-1 coat protein gp120, or beta-amyloid-derived peptides, stimulates the expression of several cytokines, including tumor necrosis factor-alpha (TNF alpha), interleukin-1 (IL-1) and IL-6, and nitric oxide (NO) which have been proposed as causes of neurodegeneration in the brain. In the present study, the neurotoxic effects of several cytokines, alone or in various combinations, and the correlations of the release of lactate dehydrogenase, the loss of neurons, and the secretion of NO in brain neuronal cell injury were investigated in murine primary mixed neuronal/glial cell cultures. A specific combination of cytokines, i.e., IL-1 (1 ng/ml) + TNF alpha (10 ng/ml)/interferon-gamma (IFN gamma) (200 u/ml), induced a dramatic neuronal cell injury in the neuron/glia cultures, and its cytotoxic profile was very similar to that seen with the LPS/IFN gamma-induced neuron injury. This indicates that among the many toxic immune mediators secreted in response to LPS, IL-1 and TNF alpha can mimic LPS as the triggering signals and primary mediators for glia-mediated neuron injury in the presence of IFN gamma. This study provides new insights about the cytotoxic mechanism(s) for cytokine-mediated neuron injury. (C) 1998 Published by Elsevier Science B.V. C1 NIEHS, Lab Pharmacol Chem, Neuropharmacol Sect, NIH, Res Triangle Pk, NC 27709 USA. RP Hong, JS (reprint author), NIEHS, Lab Pharmacol Chem, Neuropharmacol Sect, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 40 TC 147 Z9 148 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD MAY 1 PY 1998 VL 85 IS 1 BP 1 EP 10 DI 10.1016/S0165-5728(97)00204-X PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA ZR945 UT WOS:000074032100001 PM 9626992 ER PT J AU Filippi, M Comi, G McFarland, HF Miller, DH AF Filippi, M Comi, G McFarland, HF Miller, DH TI Magnetic Resonance Techniques in Multiple Sclerosis - First Advanced Course - Proceedings of a symposium held in Milan, Italy, 15-17 May 1997. Introduction SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Editorial Material C1 Univ Milan, Sci Inst Osped San Raffaele, Dept Neurol, MS Biosignal Anal Ctr, I-20122 Milan, Italy. NIH, Neuroimmunol Branch, Bethesda, MD 20892 USA. Inst Neurol, NMR Res Unit, London, England. RP Filippi, M (reprint author), Univ Milan, Sci Inst Osped San Raffaele, Dept Neurol, MS Biosignal Anal Ctr, I-20122 Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD MAY PY 1998 VL 64 SU 1 BP S1 EP S1 PG 1 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA ZW086 UT WOS:000074372500001 ER PT J AU McFarland, HF AF McFarland, HF TI The lesion in multiple sclerosis: clinical, pathological, and magnetic resonance imaging considerations SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article; Proceedings Paper CT Meeting on the Magnetic Resonance Techniques in Multiple Sclerosis CY MAY 15-17, 1997 CL MILAN, ITALY DE multiple sclerosis lesion; magnetic resonance imaging ID DISEASE-ACTIVITY; MRI AB Despite the cause of multiple sclerosis remaining elusive, recent studies of the disease using magnetic resonance imaging (MRI) and detailed pathological analysis have provided new insights into the events involved in the evolution of the lesion in multiple sclerosis. Most evidence points to disruption of the blood-brain barrier as the initial event in development of the lesion in multiple sclerosis. It is thought that antigen specific T cells enter the nervous system, recognise antigen, and begin a cytokine cascade that mediates disruption of the blood-brain barrier seen on contrast enhanced MRI. Subsequently, the inflammatory response is amplified and the effector stage leading to myelin damage is initiated. The mechanism(s) causing myelin damage is uncertain. MRI and pathological studies now indicate that damage to the axon may occur earlier in lesion development than generally thought. Although T2 weighted MRI techniques lack pathological specificity, considerable attention is now focused on studying newer techniques that should provide greater insight into lesion development. These include studies of hypointensities on T1 weighted images, proton spectroscopy, magnetisation transfer imaging, and diffusion imaging. Hopefully, these new techniques will provide a better understanding of events involved in the multiple sclerosis lesion as well as an improved understanding of the relation between disease as measured on MRI and that seen clinically. C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP McFarland, HF (reprint author), NINDS, Neuroimmunol Branch, NIH, Bld 10,Room 5B16,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 19 TC 23 Z9 23 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD MAY PY 1998 VL 64 SU 1 BP S26 EP S30 PG 5 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA ZW086 UT WOS:000074372500006 PM 9647281 ER PT J AU Miller, DH Frank, JA AF Miller, DH Frank, JA TI Magnetic resonance imaging techniques to monitor short term evolution of multiple sclerosis and to use in preliminary trials SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article; Proceedings Paper CT Meeting on the Magnetic Resonance Techniques in Multiple Sclerosis CY MAY 15-17, 1997 CL MILAN, ITALY DE multiple sclerosis; short term evolution; magnetic resonance imaging ID DISEASE-ACTIVITY; GADOLINIUM ENHANCEMENT; RELAPSING PATIENTS; SPINAL-CORD; MRI; LESIONS; SERIAL; BRAIN; SPECTROSCOPY; SENSITIVITY AB Short term serial magnetic resonance imaging (MRT) studies have provided major new insights into the natural history of multiple sclerosis, and are providing an excellent tool for preliminary assessment of therapeutic effect. In early relapsing-remitting and secondary progressive multiple sclerosis, monthly T2-weighted and gadolinium enhanced scanning discloses, on average, about 10 new or enhancing lesions for each clinical relapse. This approach relies largely on the detection of acute inflammatory (MRI) activity with blood-brain barrier break down--as the importance of this for long term disability remains uncertain, these methods for the present should not be used as the definitive assessment of treatment outcome. C1 Inst Neurol, Dept Clin Neurol, NMR Res Unit, London WC1N 3BG, England. NIH, Lab Diagnost Radiol, Bethesda, MD 20892 USA. RP Miller, DH (reprint author), Inst Neurol, Dept Clin Neurol, NMR Res Unit, Queen Sq, London WC1N 3BG, England. NR 47 TC 6 Z9 6 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD MAY PY 1998 VL 64 SU 1 BP S44 EP S46 PG 3 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA ZW086 UT WOS:000074372500009 PM 9647284 ER PT J AU Paty, DW McFarland, H AF Paty, DW McFarland, H TI Magnetic resonance techniques to monitor the long term evolution of multiple sclerosis pathology and to monitor definitive clinical trials SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article; Proceedings Paper CT Meeting on the Magnetic Resonance Techniques in Multiple Sclerosis CY MAY 15-17, 1997 CL MILAN, ITALY DE magnetic resonance imaging; multiple sclerosis evolution; axonal loss; clinical trials ID QUANTITATIVE MRI; DISEASE-ACTIVITY; LESION; MS; ENHANCEMENT; TIME AB Magnetic resonance has provided a literal window on the brain to visualise the actual pathology of MS as it evolves in the living patient. Natural history studies disclosed that MRI visualised pathological activity was seen at 5 to 10 x the rate of clinical relapses. Utilising that knowledge, systematic MRI monitoring has been used to supplement clinical monitoring to show the treatment effect in several clinical trials. This chapter explains how MR techniques can be used to further explore the evolution of in vivo pathology both in clinical trials and natural history studies. C1 Vancouver Gen Hosp, Dept Med, Div Neurol, Vancouver, BC V6T 2B5, Canada. NIH, Dept Neuroimmunol, Bethesda, MD 20892 USA. RP Paty, DW (reprint author), Vancouver Gen Hosp, Dept Med, Div Neurol, Vancouver, BC V6T 2B5, Canada. NR 27 TC 26 Z9 26 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD MAY PY 1998 VL 64 SU 1 BP S47 EP S51 PG 5 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA ZW086 UT WOS:000074372500010 PM 9647285 ER PT J AU Li, W Quigley, L Yao, DL Hudson, LD Brenner, M Zhang, BJ Brocke, S McFarland, HF Webster, HD AF Li, W Quigley, L Yao, DL Hudson, LD Brenner, M Zhang, BJ Brocke, S McFarland, HF Webster, HD TI Chronic relapsing experimental autoimmune encephalomyelitis: Effects of insulin-like growth factor-I treatment on clinical deficits, lesion severity, glial responses, and blood brain barrier defects SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE demyelination; growth factor; multiple sclerosis; inflammation ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; GENE-EXPRESSION; BINDING-PROTEIN; IGF-I; DEMYELINATION; MYELINATION; RECEPTOR; MOUSE; MICE AB Chronic relapsing experimental autoimmune encephalomyelitis (crEAE), a model for multiple sclerosis, was used to test 2 regimens of insulin-like growth factor-I (IGF-I) treatment. We induced crEAE by injecting 3x0(7) myelin basic protein-(MBP) sensitized lymph node cells into adult female SJL/J mice. Fifty-one mice, divided randomly into 4 groups, were used in the first trial. Two groups received IGF-I (a gift of Cephalon, Inc.) 0.6 mg/kg/d subcutaneously from day 7 to day 16 and the other two groups received placebo injections. IGF-I treatment reduced clinical deficits during the first attack and during 2 subsequent relapses. Image analysis of immunostained and histological sections showed that IGF-I treatment reduced BBB defects and both the numbers and sizes of inflammatory, demyelinating, and demyelinated lesions. Twelve mice that had recovered from their first attack were used in our second trial to evaluate possible adverse effects of prolonged treatment with a higher dose of IGF-I. Six received 1.2 mg/kg/d for 6 weeks (days 19-63). No adverse effects of IGF-I treatment were identified. The eyes, hearts, livers, and kidneys of IGF-I-treated mice were normal histologically and their spleens also appeared normal except for mild to moderate microscopic increases in lymphopoesis. Our results suggest that prolonged IGF-I treatment is well tolerated and that the anti-inflammatory effects of IGF-I have a major role in reducing clinical deficits and lesion severity in crEAE. These effects, if present in multiple sclerosis, may benefit patients with this disease. C1 NINDS, Expt Neuropathol Lab, NIH, Bethesda, MD 20892 USA. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Lab Dev Neurogenet, NIH, Bethesda, MD 20892 USA. NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Webster, HD (reprint author), NINDS, Expt Neuropathol Lab, NIH, Bldg 36,Rm 4A-29, Bethesda, MD 20892 USA. NR 44 TC 34 Z9 36 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1998 VL 57 IS 5 BP 426 EP 438 PG 13 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA ZN115 UT WOS:000073611400006 PM 9596413 ER PT J AU Sandberg, GD Wong, K Morrison, AL Colegial, CH Mena, H Schiffmann, R AF Sandberg, GD Wong, K Morrison, AL Colegial, CH Mena, H Schiffmann, R TI Neuropathologic clues to laminar neuronal cell loss in neuronopathic Gaucher disease. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1998 VL 57 IS 5 MA 60 BP 484 EP 484 DI 10.1097/00005072-199805000-00071 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA ZN115 UT WOS:000073611400071 ER PT J AU Paltan-Ortiz, JD Bobo, LD Heyes, MP Zito, MA Herman, MM Velasco, H Briggs, NC Webster, MJ Yolken, RH Torrey, EF AF Paltan-Ortiz, JD Bobo, LD Heyes, MP Zito, MA Herman, MM Velasco, H Briggs, NC Webster, MJ Yolken, RH Torrey, EF TI Correlation of histopathologic and epidemiologic variables with elevated CNS interleukin-2 receptor alpha and quinolinic acid levels in psychiatric disorders SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 NIMH, Stanley Fdn, Ctr Neurosci, IRP,NIH, Washington, DC USA. NIMH, Clin Brain Disorders Branch, Ctr Neurosci, IRP,NIH, Washington, DC USA. Analyt Chem Lab, Bethesda, MD USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1998 VL 57 IS 5 MA 70 BP 486 EP 486 DI 10.1097/00005072-199805000-00080 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA ZN115 UT WOS:000073611400080 ER PT J AU Brett, FM Cervenakova, L Collinge, J Farrell, MA Gibbs, CJ Traynor, B Staunton, H AF Brett, FM Cervenakova, L Collinge, J Farrell, MA Gibbs, CJ Traynor, B Staunton, H TI Sporadic fatal dementia with thalamic gliosis and D178N PrP genotype but with absence of spongiform change and negative PrP immunocytochemistry. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Beaumont Hosp, Dublin 9, Ireland. NIH, Bethesda, MD 20892 USA. Imperial Coll Sci Technol & Med, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1998 VL 57 IS 5 MA 93 BP 492 EP 492 DI 10.1097/00005072-199805000-00103 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA ZN115 UT WOS:000073611400103 ER PT J AU Duda, J Lippa, CF Croul, S Nee, L Flanders, K AF Duda, J Lippa, CF Croul, S Nee, L Flanders, K TI Estrogen and Alzheimer's disease: Could the TGF-beta system be involved? SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Allegheny Univ Hlth Sci, Philadelphia, PA 19102 USA. NIA, NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1998 VL 57 IS 5 MA 106 BP 495 EP 495 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA ZN115 UT WOS:000073611400116 ER PT J AU Tresser, N Quezado, M Whitney, L Becker, K Bonner, R Emmert-Buck, M Liotta, L AF Tresser, N Quezado, M Whitney, L Becker, K Bonner, R Emmert-Buck, M Liotta, L TI Laser capture microdissection: Applications in neuropathology SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Bonner, Robert/C-6783-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1998 VL 57 IS 5 MA 146 BP 505 EP 505 DI 10.1097/00005072-199805000-00164 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA ZN115 UT WOS:000073611400156 ER PT J AU Wong, K Armstrong, RC Gyure, KA Morrison, AL Colegial, CH Rodriguez, D Schiffman, R AF Wong, K Armstrong, RC Gyure, KA Morrison, AL Colegial, CH Rodriguez, D Schiffman, R TI Foamy oligodendroglia containing multilaminar and multilocular structures a distinctive feature in childhood ataxia with diffuse central nervous system hypomyelination syndrome. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Armed Forces Inst Pathol, Washington, DC 20306 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIH, Bethesda, MD 20892 USA. INSERM, U342, Paris, France. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1998 VL 57 IS 5 MA 148 BP 506 EP 506 DI 10.1097/00005072-199805000-00166 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA ZN115 UT WOS:000073611400158 ER PT J AU Darvish, N Russell, JT AF Darvish, N Russell, JT TI Neurotransmitter-induced novel modulation of a nonselective cation channel by a cAMP-dependent mechanism in rat pineal cells SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID ACTIVATING POLYPEPTIDE PACAP; CYCLIC-AMP; N-ACETYLTRANSFERASE; PROTEIN-KINASE; CALCIUM; GLAND; NOREPINEPHRINE; STIMULATION; PEPTIDE; INFLUX AB In the rat, circadian rhythm in melatonin is regulated by noradrenergic and neuropeptide inputs to the pineal via adenosine 3',5'-cyclic monophosphate (cAMP)- and Ca2+ dependent mechanisms. We have identified a large conductance (170 pS), voltage-dependent, nonselective cation channel on rat pineal cells in culture that shows a novel mode of modulation by cAMP. Pituitary adenylate cyclase activating peptide (PACAP), norepinephrine, or 8-Br-cAMP increase channel open probability (P-o) with a hyperpolarizing shift in voltage dependence such that the channel becomes active at resting membrane potentials. The increase in P-o was accompanied by a change in current rectification properties such that the channel was transformed from being inactive at rest to an inwardly rectifying cation conductance in the presence of agonist, which depolarizes the cell. This channel is calcium insensitive, is blocked by Cs', and shows a permeability sequence: K+ > Na+ greater than or equal to NH4+ > Li+. The data suggest that PACAP and norepinephrine acting through a cAMP-dependent mechanism modulate this nonselective cation channel, resulting in a slow onset depolarization that may be important in regulation of pineal cell excitability. C1 NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. RP Russell, JT (reprint author), NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. NR 43 TC 19 Z9 20 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 1998 VL 79 IS 5 BP 2546 EP 2556 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA ZP587 UT WOS:000073768400027 PM 9582227 ER PT J AU Morsli, H Choo, D Ryan, A Johnson, R Wu, DK AF Morsli, H Choo, D Ryan, A Johnson, R Wu, DK TI Development of the mouse inner ear and origin of its sensory organs SO JOURNAL OF NEUROSCIENCE LA English DT Article DE inner ear development; sensory organs; lunatic fringe; BMP4; NT-3; Brn3.1 ID MESSENGER-RNA; EXPRESSION AB The molecular mechanisms dictating the morphogenesis and differentiation of the mammalian inner ear are largely unknown. To better elucidate the normal development of this organ, two approaches were taken. First, the membranous labyrinths of mouse inner ears ranging from 10.25 to 17 d postcoitum (dpc) were filled with paint to reveal their gross development. Particular attention was focused on the developing utricle, saccule, and cochlea. Second, we used bone morphogenetic protein 4 (BMP4) and lunatic fringe (Fng) as molecular markers to identify the origin of the sensory structures. Our data showed that BMP4 was an early marker for the superior, lateral, and posterior cristae, whereas Fng served as an early marker for the macula utriculi, macula sacculi, and the sensory portion of the cochlea. The posterior crista was the first organ to appear at 11.5 dpc and was followed by the superior crista, the lateral crista, and the macula utriculi at 12 dpc. The macula sacculi and the cochlea were present at 12 dpc but became distinguishable from each other by 13 dpc. Based on the gene expression patterns, the anterior and lateral cristae may share a common origin. Similarly, three sensory organs, the macula utriculi, macula sacculi, and cochlea, seem to arise from a single region of the otocyst. C1 Natl Inst Deafness & Other Commun Disorders, Rockville, MD 20850 USA. Univ Calif San Diego, Sch Med, Dept Surg Otolaryngol, La Jolla, CA 92093 USA. Univ Calif San Diego, Sch Med, Dept Neurosci, La Jolla, CA 92093 USA. Univ Texas, Md Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA. RP Wu, DK (reprint author), Natl Inst Deafness & Other Commun Disorders, 5 Res Ct,Room 2B34, Rockville, MD 20850 USA. FU NIDCD NIH HHS [DC00139] NR 38 TC 307 Z9 314 U1 1 U2 14 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 MAY 1 PY 1998 VL 18 IS 9 BP 3327 EP 3335 PG 9 WC Neurosciences SC Neurosciences & Neurology GA ZJ036 UT WOS:000073173100021 PM 9547240 ER PT J AU Chen, R Corwell, B Yaseen, Z Hallett, M Cohen, LG AF Chen, R Corwell, B Yaseen, Z Hallett, M Cohen, LG TI Mechanisms of cortical reorganization in lower-limb amputees SO JOURNAL OF NEUROSCIENCE LA English DT Article DE amputation; motor reorganization; mechanisms of plasticity; human; transcranial magnetic stimulation; motor cortex ID HUMAN MOTOR CORTEX; TRANSCRANIAL MAGNETIC STIMULATION; SOMATOSENSORY CORTEX; NERVE INJURY; FUNCTIONAL REORGANIZATION; REPRESENTATION PATTERNS; ELECTRICAL-STIMULATION; MOTONEURON PLASTICITY; DYNAMIC ORGANIZATION; RAPID REORGANIZATION AB The human motor system undergoes reorganization after amputation, but the site of motor reorganization and the mechanisms involved are unknown. We studied the site and mechanisms of motor reorganization in 16 subjects with traumatic lower-limb amputation. Stimulation at different levels in the CNS was used to determine the site of reorganization. The mechanisms involved were evaluated by measuring the thresholds for transcranial magnetic stimulation (TMS) and by testing intracortical inhibition and facilitation. With TMS, the threshold for muscle activation on the amputated side was lower than that of the intact side, but with transcranial electrical stimulation there was no difference in motor threshold between the two sides. TMS at the maximal output of the stimulator activated a higher percentage of the motor neuron pool (%MNP) on the amputated side than on the intact side. The %MNP activated by spinal electrical stimulation was similar on the two sides. Paired TMS study showed significantly less intracortical inhibition on the amputated side. Our findings suggest that motor reorganization after lower-limb amputation occurs predominately at the cortical level. The mechanisms involved are likely to include reduction of GABAergic inhibition. C1 NINDS, Human Cort Physiol Unit, NIH, Bethesda, MD 20892 USA. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol Unit, NIH, Bldg 10,Room 5N234,10 Ctr Dr,MSC-1430, Bethesda, MD 20892 USA. RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 NR 71 TC 204 Z9 205 U1 4 U2 13 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 MAY 1 PY 1998 VL 18 IS 9 BP 3443 EP 3450 PG 8 WC Neurosciences SC Neurosciences & Neurology GA ZJ036 UT WOS:000073173100032 PM 9547251 ER PT J AU Scherer, SE Gallo, V AF Scherer, SE Gallo, V TI Expression and regulation of kainate and AMPA receptors in the rat neural tube SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE glutamate receptors; nestin; gene regulation; neurons; glia; cell differentiation ID FUNCTIONAL GLUTAMATE RECEPTORS; CENTRAL-NERVOUS-SYSTEM; STEM-CELLS; CELLULAR DIVERSITY; PROGENITOR-CELL; NMDA RECEPTORS; CHANNELS; BRAIN; NEURONS; SUBUNIT AB We analyzed the expression and regulation of glutamate receptor subunits in the rat neural tube (10 day embryos) and in cell cultures derived from this tissue. In the cultures, all cells were stained with antibodies against the neural progenitor marker nestin, More than 50% of the cells were also stained by the monoclonal antibodies LB1 or A2B5, which bind to neuronal and glial progenitors. Approximately 6% of the cells were stained with antibodies for the low affinity NGF receptor, a neural crest cell marker. A small percentage of cells differentiated to neurons or astrocytes, as determined by staining with anti-neurofilament and anti-GFAP antibodies, respectively, RT-PCR analysis of neural tube tissue and culture mRNAs demonstrated that the AMPA receptor subunits GluR3 and 4 and the kainate receptor subunits GluR6, 7, KA1 and KA2 were detectable at E10, The kainate receptor subunits GluR6 and KA2 were upregulated by culture conditions which stimulated cell differentiation, as determined by concomitant downregulation of nestin mRNA, Both in neural tube tissue and in cultured cells, GluR6 was 100% unedited. Finally, both GluR6 and KA2 proteins could be detected in subpopulations of neural progenitors and differentiated neurons. Our data indicate that kainate receptor genes are expressed in undifferentiated progenitor cells of the neural tube at E10, and are upregulated during neural cell differentiation. (C) 1998 Wiley-Liss, Inc.dagger. C1 NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. RP Gallo, V (reprint author), NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bldg 49,Room 5A-78,49 Convent Dr, Bethesda, MD 20892 USA. NR 61 TC 23 Z9 24 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAY 1 PY 1998 VL 52 IS 3 BP 356 EP 368 DI 10.1002/(SICI)1097-4547(19980501)52:3<356::AID-JNR12>3.0.CO;2-4 PG 13 WC Neurosciences SC Neurosciences & Neurology GA ZM121 UT WOS:000073506800012 PM 9590444 ER PT J AU Lonser, RR Heiss, JD Oldfield, EH AF Lonser, RR Heiss, JD Oldfield, EH TI Tumor devascularization by intratumoral ethanol injection during surgery - Technical note SO JOURNAL OF NEUROSURGERY LA English DT Article DE ethanol; hemostasis; injection; surgery; tumor ID ABSOLUTE ETHANOL; VERTEBRAL HEMANGIOMA; THYROID-NODULES AB Preoperative reduction in tumor vascularity has been accomplished previously by selective catheterization of tumor vessels and delivery of occlusive materials. The results of percutaneous infusion of vertebral hemangiomas and other vascular lesions led the authors to speculate that rapid devascularization of tumors by direct injection of ethanol (ETOH) could be used to reduce bleeding and facilitate resection during surgery. Thus, the use of intratumoral injection of ETOH and its effects on tumor hemostasis and resectability were examined. Four patients received direct injection of ETOH into either a spinal epidural (two renal cell carcinomas and one rhabdomyosarcoma) or a large cerebellar neoplasm (hemangioblastoma). Intraoperative perfusion of the tumors with ETOH produced immediate blanching and devascularization and enhanced visualization and resection. Incremental tumor devascularization is achieved by careful injection of small amounts of ETOH directly into the lesion, producing immediate and complete regional tumor devascularization. Use of this technique reduces intratumoral bleeding and enhances the ease and effectiveness of resection. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,5D37 MSC 1414, Bethesda, MD 20892 USA. NR 10 TC 28 Z9 29 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD MAY PY 1998 VL 88 IS 5 BP 923 EP 924 DI 10.3171/jns.1998.88.5.0923 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA ZJ709 UT WOS:000073244500022 PM 9576266 ER PT J AU de Vries, G AF de Vries, G TI Multiple bifurcations in a polynomial model of bursting oscillations SO JOURNAL OF NONLINEAR SCIENCE LA English DT Article DE bursting oscillations; classification of bursting oscillations; multiple bifurcation theory; codimension ID HUXLEY EQUATIONS; SYSTEM; HODGKIN; CELLS AB Bursting oscillations are commonly seen to be the primary mode of electrical behaviour in a variety of nerve and endocrine cells, and have also been observed in some biochemical and chemical systems. There are many models of bursting. This paper addresses the issue of being able to predict the type of bursting oscillation that can be produced by a model. A simplified model capable of exhibiting a wide variety of bursting oscillations is examined. By considering the codimension-2 bifurcations associated with Hopf, homoclinic, and saddle-node of periodics bifurcations, a bifurcation map in two-dimensional parameter space is coated. Each region on the map is characterized by a qualitatively distinct bifurcation diagram and, hence, represents one type of bursting oscillation. The map elucidates the relationship between the various types of bursting oscillations. In addition, the map provides a different and broader view of the current classification scheme of bursting oscillations. C1 NIDDKD, Math Res Branch, NIH, Bethesda, MD 20892 USA. RP de Vries, G (reprint author), NIDDKD, Math Res Branch, NIH, BSA Bldg,Suite 350, Bethesda, MD 20892 USA. NR 31 TC 32 Z9 32 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8974 J9 J NONLINEAR SCI JI J. Nonlinear Sci. PD MAY-JUN PY 1998 VL 8 IS 3 BP 281 EP 316 PG 36 WC Mathematics, Applied; Mechanics; Physics, Mathematical SC Mathematics; Mechanics; Physics GA ZK978 UT WOS:000073386700003 ER PT J AU Lang, L Jagoda, E Schmall, B Vuong, BK Adams, HR Nelson, DL Carson, RE Eckelman, WC AF Lang, L Jagoda, E Schmall, B Vuong, BK Adams, HR Nelson, DL Carson, RE Eckelman, WC TI The development of F-18 labeled 5-HT1A silent antagonists. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, PET Dept, Bethesda, MD 20892 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 132 BP 36P EP 36P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300133 ER PT J AU Jones, DW Gorey, JG Zajicek, K Das, B Urbina, RA Lee, KS Heinz, A Knable, MB Higley, D Weinberger, DR Linnoila, M AF Jones, DW Gorey, JG Zajicek, K Das, B Urbina, RA Lee, KS Heinz, A Knable, MB Higley, D Weinberger, DR Linnoila, M TI Depletion-restoration studies reveal the impact of endogenous dopamine and serotonin on [I-123]beta-CIT SPECT imaging in primate brain. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIMH, CBDB, Ctr Neurosci, Washington, DC USA. NIAAA, Bethesda, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 158 BP 42P EP 42P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300159 ER PT J AU Ferrand, SK Carson, JM Brigger, P Bacharach, SL Davis, CM Dilsizian, V AF Ferrand, SK Carson, JM Brigger, P Bacharach, SL Davis, CM Dilsizian, V TI Evidence for post-exercise stunning in patients with abnormal lung : heart ratio by gated thallium SPECT SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 172 BP 46P EP 46P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300173 ER PT J AU Watabe, H Endres, CJ Carson, RE AF Watabe, H Endres, CJ Carson, RE TI Measurement of dopamine release with [C-11]raclopride and continuous infusion: Optimization and signal-to-nose considerations. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 208 BP 55P EP 55P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300208 ER PT J AU Caraco, C Aloj, L Chou, LY Eckelman, WC AF Caraco, C Aloj, L Chou, LY Eckelman, WC TI The glucose-6-phosphatase catalytic unit requires other factors to promote FDG release from cells. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NICHD, PET, Dept Nucl Med, NIH, Bethesda, MD USA. NICHD, PET, HDB Dept, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 259 BP 67P EP 67P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300259 ER PT J AU Kim, LS Kim, MK Kobayashi, H Le, N Paik, DS Rajagopal, V Kreitman, RJ Pastan, I Carrasquillo, JA Paik, CH AF Kim, LS Kim, MK Kobayashi, H Le, N Paik, DS Rajagopal, V Kreitman, RJ Pastan, I Carrasquillo, JA Paik, CH TI Acylation by succinic anhydride improves renal clearance of anti-Tac scdsFv labeled with Tc-99m MAG3. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 295 BP 76P EP 76P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300295 ER PT J AU Riddell, C Jousse, F Aloj, L Mansour, P Whatley, M Carrasquillo, JA Daube-Witherspoon, ME Libutti, SK Danforth, DN Bacharach, SL AF Riddell, C Jousse, F Aloj, L Mansour, P Whatley, M Carrasquillo, JA Daube-Witherspoon, ME Libutti, SK Danforth, DN Bacharach, SL TI Noise reduction in oncology FDG PET images by iterative reconstruction: A quantitative assessment. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 2 Z9 2 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 308 BP 80P EP 80P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300308 ER PT J AU Herscovitch, P Kiesewetter, DO Carson, RE Eckelman, WC AF Herscovitch, P Kiesewetter, DO Carson, RE Eckelman, WC TI Biodistribution and radiation dose estimates for [F-18]Fluoropropyl-TZTP, a new muscarinic cholinergic ligand. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, PET Dept, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 329 BP 85P EP 85P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300329 ER PT J AU Wilbur, DS Hamlin, DK Tingey, JM Bray, LA Egorov, OB Pathare, PM Brechbiel, MW Sandmaier, BM AF Wilbur, DS Hamlin, DK Tingey, JM Bray, LA Egorov, OB Pathare, PM Brechbiel, MW Sandmaier, BM TI Studies of labeling proteins with the alpha-emitting radionuclide Bi-213. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. Pacific NW Natl Lab, Richland, WA USA. NIH, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 355 BP 91P EP 91P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300355 ER PT J AU Riddell, C Jousse, F Aloj, L Mansour, P Whatley, M Carrasquillo, JA Daube-Witherspoon, ME Libutti, SK Danforth, DN Bacharach, SL AF Riddell, C Jousse, F Aloj, L Mansour, P Whatley, M Carrasquillo, JA Daube-Witherspoon, ME Libutti, SK Danforth, DN Bacharach, SL TI Attenuation correction vs. no attenuation correction: A signal to noise analysis in FDG PET wholebody images. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 383 BP 98P EP 98P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300383 ER PT J AU Bencherif, B Gorelick, D Nelson, R Stauffer, R Ravert, HT Mathews, WB Musachio, JL Dannals, RF Frost, JJ AF Bencherif, B Gorelick, D Nelson, R Stauffer, R Ravert, HT Mathews, WB Musachio, JL Dannals, RF Frost, JJ TI Brain mu opioid receptor binding changes in chronic cocaine users following prolonged abstinence correlate with time to relapse using region of interest (ROI) and statistical parametric mapping (SPM). SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NIDA, DIR, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 387 BP 99P EP 99P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300387 ER PT J AU Bencherif, B Gorelick, D Nelson, R Stauffer, R Ravert, HT Mathews, WB Musachio, JL Dannals, RF Frost, JJ AF Bencherif, B Gorelick, D Nelson, R Stauffer, R Ravert, HT Mathews, WB Musachio, JL Dannals, RF Frost, JJ TI Brain mu opioid receptor binding changes in chronic cocaine users following early monitored abstinence. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIDA, DIR, Baltimore, MD USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 386 BP 99P EP 99P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300386 ER PT J AU Heinz, A Ragan, P Mazzanti, C Goldman, D Jones, DW Gorey, JG Knable, MB Hommer, D Lee, KS Weinberger, DR Linnoila, M AF Heinz, A Ragan, P Mazzanti, C Goldman, D Jones, DW Gorey, JG Knable, MB Hommer, D Lee, KS Weinberger, DR Linnoila, M TI Effects of gender genetics, and serotonin turnover on availability of brainstem serotonin transporters in alcoholism: An [I-123]beta-CIT SPECT study. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIMH, Ctr Neurosci, CBDB, Washington, DC 20032 USA. NIAAA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 390 BP 100P EP 100P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300390 ER PT J AU Ferrand, SK Carson, JM Brigger, P Bacharach, SL Davis, CM Dilsizian, V AF Ferrand, SK Carson, JM Brigger, P Bacharach, SL Davis, CM Dilsizian, V TI Effect of left ventricular valve plane selection on computation of left ventricular ejection fraction from gated thallium SPECT. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 404 BP 103P EP 104P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300404 ER PT J AU Karp, JS Smith, RJ Muehllehner, G Daube-Witherspoon, ME Hines, H AF Karp, JS Smith, RJ Muehllehner, G Daube-Witherspoon, ME Hines, H TI Image quality measurement for evaluation of PET scanner performance SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. ADAC Labs, Milpitas, CA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 525 BP 133P EP 134P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300524 ER PT J AU Carson, RE Lang, L Watabe, H Der, MG Adams, HR Jagoda, E Endres, CJ Herscovitch, P Eckelman, WC AF Carson, RE Lang, L Watabe, H Der, MG Adams, HR Jagoda, E Endres, CJ Herscovitch, P Eckelman, WC TI Evaluation of a new F-18 labeled analog of the 5-HT1A antagonist way 100635 for PET. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, PET Dept, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 2 Z9 2 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 533 BP 135P EP 136P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300532 ER PT J AU Watabe, H Channing, MA Der, MG Adams, HR Jagoda, E Herscovitch, P Eckelman, WC Carson, RE AF Watabe, H Channing, MA Der, MG Adams, HR Jagoda, E Herscovitch, P Eckelman, WC Carson, RE TI Kinetic analysis of the 5-HT2A ligand [C-11]MDL 100,907. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 536 BP 136P EP 136P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300535 ER PT J AU Buvat, I Kitsiou, AN Carson, JM Dilsizian, V Bacharach, SL AF Buvat, I Kitsiou, AN Carson, JM Dilsizian, V Bacharach, SL TI Rest and low dose dobutamine N-13 ammonia gated cardiac PET: Simultaneous assessment of function, blood flow and uptake. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 INSERM, U494, Paris, France. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 557 BP 141P EP 141P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300556 ER PT J AU Barker, WC Srinivasan, G Dilsizian, V Bacharach, SL AF Barker, WC Srinivasan, G Dilsizian, V Bacharach, SL TI Myocardial SPECT noise reduction through iterative OSEM reconstruction. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 733 BP 160P EP 160P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300628 ER PT J AU Yao, R Johnson, CA Riddell, C Bacharach, SL Daube-Witherspoon, ME AF Yao, R Johnson, CA Riddell, C Bacharach, SL Daube-Witherspoon, ME TI Attenuation correction and iterative reconstruction for PET. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 809 BP 179P EP 179P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300707 ER PT J AU Morris, ED Chefer, SI Lane, MA Muzic, RF Wong, DF Dannals, RF Matochik, JA Bonab, AA Villemagne, VL Grant, SJ Ingram, DK Roth, GS London, ED AF Morris, ED Chefer, SI Lane, MA Muzic, RF Wong, DF Dannals, RF Matochik, JA Bonab, AA Villemagne, VL Grant, SJ Ingram, DK Roth, GS London, ED TI Effect of age on D2 dopamine receptor binding measured with 11-C-raclopride and PET in rhesus monkeys. Partial volume correction reduces the apparent rate of decline with age. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIDA, Baltimore, MD USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 924 BP 207P EP 207P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300822 ER PT J AU Kim, MK Pie, JE Kobayashi, H Le, N Paik, DS Waldmann, TA Carrasquillo, JA Paik, CH AF Kim, MK Pie, JE Kobayashi, H Le, N Paik, DS Waldmann, TA Carrasquillo, JA Paik, CH TI Renal uptake of F(ab ')2 can be decreased by lowering of its pI by acylation with glycolate. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 980 BP 221P EP 221P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300880 ER PT J AU McDevitt, MR Finn, RD Larson, SM Curcio, MJ Bander, N Brechbiel, MW Sgouros, G Geerlings, MW Barendswaard, E Scheinberg, DA AF McDevitt, MR Finn, RD Larson, SM Curcio, MJ Bander, N Brechbiel, MW Sgouros, G Geerlings, MW Barendswaard, E Scheinberg, DA TI Bismuth labeled antibodies for therapy of prostate carcinomas: Preclinical studies. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Cornell Univ, Coll Med, New York, NY USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 3 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 990 BP 223P EP 224P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300890 ER PT J AU John, CS Geyer, BC Vilner, BJ Lim, BB Bowen, WD AF John, CS Geyer, BC Vilner, BJ Lim, BB Bowen, WD TI Comparative biodistributions of a radioiodinated benzamide in nude mice and C57 black mice bearing B16 melanoma xenografts. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 1003 BP 227P EP 227P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300903 ER PT J AU Magata, Y Lang, L Channing, M Schmall, B Jagoda, E Eckelman, WC AF Magata, Y Lang, L Channing, M Schmall, B Jagoda, E Eckelman, WC TI Development of stable [F-18] labeled benzylfluoride derivatives. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, PET Dept, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 1016 BP 230P EP 230P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300916 ER PT J AU Kobayashi, H Wu, C Kim, MK Paik, CH Waldmann, TA Carrasquillo, JA Brechbiel, MW AF Kobayashi, H Wu, C Kim, MK Paik, CH Waldmann, TA Carrasquillo, JA Brechbiel, MW TI Evaluation of the biodistribution of indium-111 and yttrium-88 labeled dendrimer-1B4M-DTPA alone or conjugated with a monoclonal antibody. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 1027 BP 232P EP 233P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300927 ER PT J AU Karamychev, VN Panyutin, IG Kim, MK Reed, MW Le, N Paik, CH Carrasquillo, JA Neumann, RD AF Karamychev, VN Panyutin, IG Kim, MK Reed, MW Le, N Paik, CH Carrasquillo, JA Neumann, RD TI DNA cleavage by decay of Auger-emitting isotopes attached to oligonucleotides through linkers. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 1041 BP 236P EP 236P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300941 ER PT J AU Aloj, L Caraco, C Eckelman, WC Neumann, RD AF Aloj, L Caraco, C Eckelman, WC Neumann, RD TI Glucose tranSporter proteins and hexokinase activity: Which is more important for FDG uptake in cancer cells? SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Dept Nucl Med, Bethesda, MD 20892 USA. NIH, PET Dept, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 1104 BP 251P EP 251P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560301003 ER PT J AU Aloj, L Caraco, C Eckelman, WC Neumann, RD AF Aloj, L Caraco, C Eckelman, WC Neumann, RD TI 2-fluoro-2-deoxyglucose is preferentially taken up over 2-deoxyglucose by cancer cells: Implications for the mechanism of FDG retention in tumors. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Dept Nucl Med, Bethesda, MD 20892 USA. NIH, PET Dept, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 1105 BP 251P EP 251P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560301004 ER PT J AU Kim, MK Seidel, J Paik, DS Le, N Pie, JE Kohayashi, H Green, MV Carrasquillo, JA Paik, CH AF Kim, MK Seidel, J Paik, DS Le, N Pie, JE Kohayashi, H Green, MV Carrasquillo, JA Paik, CH TI Uptake inhibition study of two Tc-99m-labeled hepatobiliary imaging agents using biotin and biocytin. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 1192 BP 272P EP 272P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560301089 ER PT J AU Brunetti, A Fulham, MJ Aloj, L De Souza, B Nieman, L Oldfield, EH Di Chiro, G AF Brunetti, A Fulham, MJ Aloj, L De Souza, B Nieman, L Oldfield, EH Di Chiro, G TI Decreased brain glucose utilization in patients with Cushing's disease SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE Cushing's disease; cerebral glucose metabolism; PET; glucocorticoids ID NERVOUS-SYSTEM; CEREBRAL ATROPHY; PLASMA-MEMBRANE; METABOLIC-RATE; HUMANS; MANIFESTATIONS; DEOXYGLUCOSE; TOMOGRAPHY; DEPRESSION; CORTISOL AB Glucocorticoid hormones affect glucose use in different tissues, and the results of several experimental studies have suggested that glucocorticoids have a central action on cerebral metabolism. PET, using the radiotracer F-18-fluorodeoxyglucose (FDG), permits the measurement of cerebral glucose metabolism. Methods: To investigate whether cerebral glucose metabolism would be altered in patients with increased plasma glucocorticoid levels, we analyzed the FDG PET studies that were done on 13 patients with Cushing's disease and compared the results with those obtained in 13 age-matched normal control subjects. A second FDG PET scan was performed on 4 patients after surgical removal of the pituitary adenoma. Results: Patients with Cushing's disease had a significant reduction in cerebral glucose metabolism compared with normal controls. In the patients on whom a second PET scan was performed, there was a trend toward increased glucose metabolism on the second scan when comparing pre-and postsurgery values for each patient. Conclusion: We suggest that the decreased cerebral glucose metabolism we observed in Cushing's disease is attributable to increased glucocorticoid levels, and we speculate that abnormal cerebral glucose metabolism might contribute to the cognitive and psychiatric abnormalities that are frequently observed in patients with Cushing's disease. C1 Univ Naples Federico II, CNR, Ctr Nucl Med, I-80131 Naples, Italy. NICHHD, NINDS, Neuroimaging Branch,Surg Neurol Branch, Nucl Med Dept,Clin Ctr,Dev Endocrinol Branch,NIH, Bethesda, MD USA. RP Brunetti, A (reprint author), Univ Naples Federico II, CNR, Ctr Nucl Med, Via Pansini 5, I-80131 Naples, Italy. NR 35 TC 24 Z9 28 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 BP 786 EP 790 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZL912 UT WOS:000073486000017 PM 9591575 ER PT J AU Kobayashi, H Wu, CC Yoo, TM Sun, BF Drumm, D Pastan, I Paik, CH Gansow, OA Carrasquillo, JA Brechbiel, MW AF Kobayashi, H Wu, CC Yoo, TM Sun, BF Drumm, D Pastan, I Paik, CH Gansow, OA Carrasquillo, JA Brechbiel, MW TI Evaluation of the in vivo biodistribution of yttrium-labeled isomers of CHX-DTPA-conjugated monoclonal antibodies SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE DTPA; chelates; stereoisomers; enantiomers; antibody ID BIFUNCTIONAL CHELATE TECHNIQUES; BINDING-SITE BARRIER; CARCINOMA XENOGRAFTS; OVARIAN-CANCER; NUDE-MICE; RADIOIMMUNOTHERAPY; Y-90; THERAPY; TUMOR; AGENT AB We evaluated the in vivo stability and biodistribution of four isomers (CHX-A', CHA-A ", CHX-B' and CHX-B ") of 2-(p-isothiocyanato-benzyl)-cyclo hexyl-diethylenetriaminepentaacetic acid (CHX-DTPA), a recently developed backbone-substituted derivative of DTPA, Methods: The ligands were conjugated to monoclonal antibody B3, a murine IgG1 kappa, and labeled with Y-88 at 55.5-66.6 MBq/mg (1.5-1.8 mCi/mg). Nontumor-bearing nude mice were injected intravenously with 55.5-66.6 kBq (1.5-1.8 mu Ci) of Y-88- labeled B3 conjugates and with I-125-labeled B3 as an internal control. The mice were then killed at 6, 24, 48, 96 and 168 hr postinjection. Results: At 168 hr, the concentration of Y-88 in processed bone of either CHX-A' [4.6% injected dose (ID)/g] or CHX-A " (4.0%ID/g) was less than that of either the CHX-B' (21.9%ID/g) or B " (12.1%ID/g) ligands. The two ligands CHX-B " and CHX-B' were not acceptable for yttrium labeling of antibody because of their high and progressive bone accumulation. The accumulation of Y-88 in bone of CHX-B' was five times greater than that of CHX-A' al 168 hr. The CHX-A " cleared from the circulation slightly faster than CHX-A' without releasing the yttrium and showed the lowest uptake by bone of any of the four isomers. The accumulation in the other normal organs was similar for all four isomers of Y-88-CHX-B3 conjugates. Conclusion: Although the CHX-B " and CHX-B' were not acceptable for labeling with yttrium, the CHX-A' and CHX-A " were suitable, indicating that differences in stereochemistry can greatly influence stability of radionuclide in the chelate. C1 NCI, Dept Nucl Med, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NCI, Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Carrasquillo, JA (reprint author), Bldg 10,Room 1C-401,10 Ctr Dr,MSC1180, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 41 TC 39 Z9 41 U1 0 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 BP 829 EP 836 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZL912 UT WOS:000073486000027 PM 9591585 ER PT J AU Smith, MF Gilland, DR Coleman, RE Jaszczak, RJ AF Smith, MF Gilland, DR Coleman, RE Jaszczak, RJ TI Quantitative imaging of iodine-131 distributions in brain tumors with pinhole SPECT: A phantom study SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE pinhole collimator; SPECT; iodine-131 imaging; brain tumor; radioimmunotherapy ID RADIOLABELED MONOCLONAL-ANTIBODIES; MALIGNANT GLIOMAS; HIGH-RESOLUTION; GAMMA-CAMERA; PHASE-I; I-131; RADIOIMMUNOTHERAPY; ATTENUATION; QUANTIFICATION; COLLIMATOR AB method of quantitatively imaging I-131 distributions in brain tumors from intratumoral administration of activity was developed and investigated using pinhole SPECT of brain tumor phantoms, Methods: Pinhole SPECT sensitivity and resolution were characterized using I-131 point-source acquisitions with high-resolution lead (1.4-mm diameter aperture) and tungsten (1.0-mm diameter aperture) pinhole inserts. SPECT scans were obtained from brain tumor phantoms in a water-filled cylinder. The tumor phantoms consisted of spheres filled with an I-131 solution to model intratumoral administration of radiolabeled monoclonal antibodies. Two spheres were 20.5 and 97 mi, and two other concentric spheres modeled a tumor with a high-activity shell (71.5 ml) and a low-activity core (21 ml). The collimator focal length was 16 cm and the distance from the pinhole to the center of rotation was 13 cm, The filtered backprojection reconstruction algorithm incorporated scatter and attenuation compensation. SPECT tumor activities and concentrations were estimated using scaling factors from reference point-source scans. Results: System sensitivities for point sources at the center of rotation were 28.4 cts/sec(-1) MBq(-1) (lead insert) and 13.6 cts/sec(-1) MBq(-1) (tungsten insert). SPECT resolutions (FWHM) at the center of rotation were 8.1-11.9 mm (lead) and 6.7-10.3 mm (tungsten). Total tumor activity estimates from SPECT were within 17% of the true activities. SPECT activity concentration estimates in small regions of interest (ROIs) averaged -20% for the 20.5-ml sphere, -11 % for the 97-ml sphere, -39% for the shell and +20% for the core of the shell-core phantom. Activity spillover due to limited spatial resolution and the tails of the system response functions biased the estimates. The shell-to-core activity concentration ratio of 4.1 was better estimated with the tungsten insert (2.3) than with the lead insert (1.9) due to better resolution. Conclusion: Pinhole SPECT is a promising technique for imaging and quantifying total I-131 activity in regions the size of brain tumors. Relative errors were greater for activity concentration estimates in small ROIs than for total activity estimates. C1 Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biomed Engn, Durham, NC 27710 USA. RP Smith, MF (reprint author), NIH, Dept Nucl Med, Bldg 10,Rm 1C401,10 Ctr Dr,MSC 1180, Bethesda, MD 20892 USA. FU NCI NIH HHS [R01-CA33541]; NHLBI NIH HHS [R29-HL52162] NR 29 TC 21 Z9 21 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 BP 856 EP 864 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZL912 UT WOS:000073486000031 PM 9591589 ER PT J AU Panyutin, IG Neumann, RD AF Panyutin, IG Neumann, RD TI Gene radiotherapy; Gene targeted versus targeted by gene product SO JOURNAL OF NUCLEAR MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Panyutin, IG (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 7 TC 7 Z9 7 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 BP 928 EP 929 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZL912 UT WOS:000073486000052 PM 9591608 ER PT J AU Facchetti, F Blanzuoli, L Vermi, W Notarangelo, LD Giliani, S Fiorini, M Fasth, A Stewart, DM Nelson, DL AF Facchetti, F Blanzuoli, L Vermi, W Notarangelo, LD Giliani, S Fiorini, M Fasth, A Stewart, DM Nelson, DL TI Defective actin polymerization in EBV-transformed B-cell lines from patients with the Wiskott-Aldrich syndrome SO JOURNAL OF PATHOLOGY LA English DT Article DE Wiskott-Aldrich syndrome ID LIGAND-INDUCED ASSOCIATION; X-LINKED THROMBOCYTOPENIA; ALPHA-ACTININ; SYNDROME PROTEIN; T-CELLS; SURFACE-IMMUNOGLOBULIN; TYROSINE KINASES; MUTATIONS; GENE; SRC AB The Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive disorder characterized by eczema, thrombocytopenia, and immunodeficiency. An allelic variant of the disease is characterized by isolated thrombocytopenia (XLT), The gene responsible for WAS/XLT (WASP) encodes for a 502 amino acid protein (WASP) that is possibly involved in actin binding and cytoskeleton organization. The expression of WASP and the distribution of F-actin and alpha-actinin (which binds to and stabilizes actin filaments) have been analysed in lymphoblastoid cell lines from six patients with WAS and one with XLT, Western blot and immunocytochemistry did not reveal WASP expression in four WAS patients, whereas two WAS patients (with a moderate clinical course) expressed trace amounts of mutant WASP. In contrast, the XLT patient expressed normal amounts of WASP, Furthermore, cell lines from WAS and XLT patients also markedly differed in F-actin polymerization and alpha-actinin distribution, In particular, severe defects of cytoplasmic F-actin expression and of F-actin-positive microvillus formation, and impaired capping of alpha-actinin, mere observed in all patients who lacked WASP. As a whole, the degree of impairment of WASP protein expression in WAS/XLT seems to correlate with anomalies of cytoskeletal organization, strongly supporting a role for WASP in the regulation of F-actin polymerization, (C) 1998 John Wiley & Sons, Ltd. C1 Univ Brescia, Spedali Civili, Dept Pathol, I-25124 Brescia, Italy. Univ Brescia, Dept Paediat, Brescia, Italy. Univ Gothenburg, Dept Paediat, Gothenburg, Sweden. NCI, Immunopathol Sect, Metab Branch, NIH, Bethesda, MD USA. RP Facchetti, F (reprint author), Univ Brescia, Spedali Civili, Dept Pathol, I-25124 Brescia, Italy. RI Facchetti, Fabio/E-7190-2010; Notarangelo, Luigi/F-9718-2016 OI Facchetti, Fabio/0000-0003-4975-2388; Notarangelo, Luigi/0000-0002-8335-0262 NR 53 TC 41 Z9 43 U1 1 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD MAY PY 1998 VL 185 IS 1 BP 99 EP 107 DI 10.1002/(SICI)1096-9896(199805)185:1<99::AID-PATH48>3.0.CO;2-L PG 9 WC Oncology; Pathology SC Oncology; Pathology GA ZP268 UT WOS:000073735300015 PM 9713366 ER PT J AU Parker, RI Siegel, RS Ratajczak, MZ Gewirtz, AM AF Parker, RI Siegel, RS Ratajczak, MZ Gewirtz, AM TI Deficient in vitro megakaryocytopoiesis and decreased in vivo platelet turnover in children and young adults with chronic thrombocytopenia SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE ITP; platelet turnover; megakaryocyte growth; myelodysplasia ID BONE-MARROW; PURPURA; KINETICS; GLYCOCALICIN; MECHANISMS; CLEARANCE; DISORDERS; INVITRO AB Purpose: Chronic thrombocytopenia is uncommon in children and frequently thought to be secondary to chronic idiopathic thrombocytopenic purpura (ITP), which is considered an immune disorder. However, not all children with chronic ITP respond to immunosuppressive therapy. Platelet survival and megakaryocyte growth were studied to determine if there is a failure of platelet production in children with chronic thrombocytopenia who carry a presumptive diagnosis of chronic ITP. Patients and Methods: In vitro megakaryocyte growth using a plasma clot system and in vivo survival of In-111-labeled autologous platelets were studied in seven patients (aged 2 days to 17 years at diagnosis; aged 2 to 28 years at time of megakaryocyte study) with chronic isolated thrombocytopenia (range 1,000 to 130,000/mu l). Results: All seven patients exhibited elevated platelet-associated immunoglobulin G early in the course of their disease and showed normal marrow morphology with normal numbers of morphologically typical megakaryocytes on initial marrow biopsy. Occasional dysplastic-appearing megakaryocytes were noted in three of the seven patients at diagnosis and all patients were noted to have dysplastic megakaryocytes, reduced megakary ocytes, or both during follow-up (range 5 to 16 years). Either morphologic or karyotypic abnormalities indicative of myelodysplasia subsequently developed in three patients. No patient exhibited any significant megakaryocyte colony growth under basal conditions. In one patient, megakaryocytic colonies significantly increased when grown in the presence of serum from aplastic patients and growth factors (granulocyte-macrophage colony-simulating factor, interleukin-3, and interleukin-6). Erythroid colony growth was markedly deficient in four of five patients studied and myeloid colonies were normal in two of three patients studied. Five of the seven patients underwent platelet survival studies. Platelet survival was < 6 days in the 4 patients with platelet counts < 100,000/mu l (range 2 to 60,000/mu l; survival range 92 to 137 hours) and was normal in the patient whose platelet count was > 100,000/mu l (platelets 132,000/mu l; survival 253 hours). All five patients had either overtly low or inappropriately low platelet turnovers (range 100 to 1423 platelets/mu l per hour; normal range 1200 to 1600 platelets/mu l per hour). The patient with the lowest platelet count and platelet turnover had previously undergone a splenectomy without benefit. Conclusions: Megakaryocyte dysfunction resulting in subnormal production of platelets may play a significant role in the thrombocytopenia noted in some patients who have an isolated thrombocytopenia and a clinical picture that suggests ITP. Determination of platelet turnover may help to identify these patients. These data suggest the presence of a stem cell defect which may progress to myelodysplasia or overt marrow failure in these patients. C1 NIH, Dept Clin Pathol, Bethesda, MD 20892 USA. George Washington Univ, Dept Med, Div Hematol, Washington, DC USA. Univ Penn, Sch Med, Dept Pathol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Hematol, Philadelphia, PA 19104 USA. RP Parker, RI (reprint author), SUNY Stony Brook, Dept Pediat, HSC T-11,060, Stony Brook, NY 11794 USA. RI Ratajczak, Mariusz Zdzislaw/N-1599-2014 NR 21 TC 4 Z9 4 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD MAY-JUN PY 1998 VL 20 IS 3 BP 196 EP 201 DI 10.1097/00043426-199805000-00003 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA ZR947 UT WOS:000074032300003 PM 9628429 ER PT J AU Kaufman, HL Roden, M Nathanson, D Basso, TM Schwartzentruber, DJ Holland, SM AF Kaufman, HL Roden, M Nathanson, D Basso, TM Schwartzentruber, DJ Holland, SM TI Splenectomy in a child with chronic Mycobacterium avium complex infection and splenic sequestration SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE mycobacteria; interferon-gamma; neutropenia; splenectomy; splenomegaly ID INTERFERON-GAMMA; PROPHYLAXIS; DISEASE AB Mycobacterium avium complex infections (MAC) are being reported with increasing frequency in immunocompromised patients. When these infections become resistant to standard antibiotic therapy, treatment with interferon-gamma (IFN-gamma) can be helpful. Pain, fever, splenic enlargement, and cytopenias caused by splenic sequestration developed during IFN-gamma treatment in a 9-year-old boy and were successfully treated by splenectomy. The development of IFN-gamma-induced splenic sequestration and cytopenias in MAC-infected patients represents a new indication for splenectomy. Copyright (C) 1998 by W.B. Saunders Company. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Kaufman, HL (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, Dept Surg, 111 E 210th St, Bronx, NY 10467 USA. NR 14 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD MAY PY 1998 VL 33 IS 5 BP 761 EP 763 DI 10.1016/S0022-3468(98)90212-3 PG 3 WC Pediatrics; Surgery SC Pediatrics; Surgery GA ZM669 UT WOS:000073564000028 PM 9607493 ER PT J AU Cooper, ER Hanson, C Diaz, C Mendez, H Abboud, R Nugent, R Pitt, J Rich, K Rodriguez, EM Smeriglio, V AF Cooper, ER Hanson, C Diaz, C Mendez, H Abboud, R Nugent, R Pitt, J Rich, K Rodriguez, EM Smeriglio, V CA Women Infants Transmission Study Grp TI Encephalopathy and progression of human immunodeficiency virus disease in a cohort of children with perinatally acquired human immunodeficiency virus infection SO JOURNAL OF PEDIATRICS LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; HIV-INFECTION; ABNORMALITIES; TRANSMISSION; TYPE-1 AB Objective: To describe the incidence, predictors, and survival of children with human immunodeficiency virus (HIV) encephalopathy followed in the Women and Infants Transmission Study cohort. Study design: Retrospective review of clinical and immunologic staging of perinatally HIV-infected infants, based on the 1994 Centers for Disease Control and Prevention Classification System. Results: Data were available for 128 HIV-infected children, with a median follow-up of 24 months. HIV encephalopathy was diagnosed in 27 (21%) of children. Median survival after diagnosis was 14 months. Of children with encephalopathy, 74% had at least moderate immunosuppression by the time of diagnosis. Encephalopathy represented the first acquired immunodeficiency syndrome-defining condition in 67%, and the only one in 26% of children. Hepatosplenomegaly or lymphadenopathy during the first 3 months of life was diagnosed in 63%, in contrast to 29% of those without encephalopathy (p value = 0.001). Cardiomyopathy was present in 30% of the children with encephalopathy versus 2% of those without encephalopathy. High viral load in infancy was associated with increased risk of encephalopathy but was not predictive of age at onset. Conclusions: Encephalopathy in children with HIV is common and is associated with high viral load, immunodeficiency, and shortened survival. Encephalopathy was more likely to develop in infants with early signs and symptoms of HIV, although age at onset could not be predicted. C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Puerto Rico, Sch Med, Dept Pediat, San Juan, PR 00936 USA. SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. New England Res Inst, Watertown, MA 02172 USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD 20892 USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. NIAID, Div Aids, Bethesda, MD 20892 USA. NIDA, Rockville, MD USA. RP Cooper, ER (reprint author), Boston Med Ctr, Finland Lab, 774 Albany St, Boston, MA 02118 USA. FU NIAID NIH HHS [U01 AI 34858, U01 AI 34842]; NICHD NIH HHS [HD-82913] NR 20 TC 79 Z9 83 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAY PY 1998 VL 132 IS 5 BP 808 EP 812 DI 10.1016/S0022-3476(98)70308-7 PG 5 WC Pediatrics SC Pediatrics GA ZN105 UT WOS:000073610400014 PM 9602190 ER PT J AU Nomeir, AA McComish, MF Ferrala, NF Silveira, D Covey, JM Chadwick, M AF Nomeir, AA McComish, MF Ferrala, NF Silveira, D Covey, JM Chadwick, M TI Liquid chromatographic analysis in mouse, dog and human plasma; stability, absorption, metabolism and pharmacokinetics of the anti-HIV agent 2-chloro-5-(2-methyl-5,6-dihydro-1,4-oxathiin-3-yl carboxamido)isopropylbenzoate (NSC 615985, UC84) SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE reversed phase LC; absorption; metabolism; anti-HIV agent; NSC 615985; UC84; NNRTI ID OXATHIIN CARBOXANILIDE; DERIVATIVES; ESTER AB NSC 615985 (UC 84) has demonstrated anti-HIV activity in the NCI-AIDS antiviral screen and aias under consideration as an anti-AIDS drug. The compound was subsequently shown to be a non-nucleoside reverse transcriptase inhibitor (NNRTI). An HPLC method was developed for the analysis of NSC 615985 in mouse, dog and human plasma; and was used to study its stability in plasma and blood as well as its absorption and metabolism in mice. The method involved precipitation of plasma protein with three volumes of methanol followed by HPLC analysis of the supernatant. The HPLC analysis was carried out on a reversed-phase Nova-Pak C-18 column with a mobile phase of KH2PO4 (0.01 M; pH 4.8)-acetonitrile (52:48, v/v) at a flow rate of 1 ml min(-1) and quantification with a UV detector set at 259 nm. The lower limit of quantitation was 0.05 mu g ml(-1) in 1 ml of dog or human plasma or 0.1 mu g ml(-1) in 0.5 ml of mouse plasma. NSC 615985 was more stable in dog and human plasma than in mouse plasma, and was less stable in blood than in plasma of the three species investigated. Following bolus intravenous (IV) administration at 10 mg kg(-1) to male CDF, mice, NSC 615985 elimination followed biexponential kinetics with half-lives of 1 and 7 min; and was extensively metabolized. NSC 615985 was very poorly absorbed following oral (PO) administration as a suspension in water or in 20% lipid emulsion (Liposyn II). Following bolus subcutaneous (SC) administration of [C-14]NSC 615985 at 10 mg kg(-1), relatively low concentrations of the parent compound were observed in three of 36 mice. One metabolite was tentatively identified in plasma of both the IV- and SC-treated animals as the sulfoxide of the parent compound. No parent compound was detected in the urine of NSC 615985 dosed mice. At least seven metabolites were present in urine, one metabolite (constituting 8-14%, of urinary radioactivity) was tentatively identified as the carboxylic acid resulting from the hydrolysis of the isopropyl group from the parent compound. In summary, NSC 615985 was poorly absorbed following oral administration and extensively metabolized and eliminated following IV or SC administration. This unfavorable pharmacokinetic profile of NSC 615985 as well as its pattern of activity against NNRTI-resistant strains of HIV-1 precluded its progression to clinical trial; however, other members of the general chemical class are currently being evaluated by the NCI. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Arthur D Little Inc, Cambridge, MA 02140 USA. NCI, Bethesda, MD 20892 USA. RP Nomeir, AA (reprint author), Schering Plough Corp, Res Inst, Dept Drug Metab & Pharmacokinet, Mail Stop 2880,2015 Galloping Hill Rd, Kenilworth, NJ 07033 USA. FU NCI NIH HHS [N01-CM-87284] NR 14 TC 1 Z9 1 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD MAY PY 1998 VL 17 IS 1 BP 27 EP 38 DI 10.1016/S0731-7085(97)00159-3 PG 12 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA ZK988 UT WOS:000073387700004 PM 9608423 ER PT J AU Soldner, A Spahn-Langguth, H Palm, D Mutschler, E AF Soldner, A Spahn-Langguth, H Palm, D Mutschler, E TI A radioreceptor assay for the analysis of AT(1)-receptor antagonists - Correlation with complementary LC data reveals a potential contribution of active metabolites SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE AT(1)-receptor; losartan; EXP 3174; UP 269-6; SL 91.0102-90 DL; radioreceptor assay ID II RECEPTOR ANTAGONIST; BINDING-SITES; RAT LUNG; ANGIOTENSIN; ENALAPRIL; SUBTYPES; LIVER AB A reliable and sensitive radioreceptor assay based on rat lung homogenate as receptor preparation was developed to determine the angiotensin-II antagonistic profile of losartan and its main active metabolite EXP 3174 as well as its congeners exemplified by UP 269-6 and SL 91.0102-90 DL. This method proved to De precise with an intra-and interday variability of less than 10% and a limit of quantification less than or equal to 1 ng ml(-1). The analysis of the K-i values in protein-free Hepes-buffer versus blank human or rat plasma revealed the distinct high plasma-protein binding of EXP 3174 which consequently caused a dramatic drop of potency from 10-15-fold in the buffer to only about 2-fold in control plasma, when compared to the parent compound losartan and the two congeners investigated. Upon evaluation of clinical samples by both the reported radioreceptor assay (RRA) and the established high-performance liquid chromatography (HPLC), the correlation of the normalized data pairs (concentration equivalents) suggested the contribution of active metabolites to the angiotensin-II antagonistic effect of SL 91.0102-90 DL, but not to the effect of UP 269-6. In the context of an extended preclinical study in rats, the correlation of RRA with the respective HPLC concentration equivalents of losartan and its main active metabolite EXP 3174 confirmed previous findings that only losartan and EXP 3174 exert the angiotensin-II-AT(1) receptor blockade without the contribution of other metabolites (P.C. Wong, W.A. Price, A.T. Chiu et al., J. Pharmacol. Exp. Ther. 255 (1990) 211-217). Published by Elsevier Science B.V. All rights reserved. C1 Univ Frankfurt, Bioctr Niederursel, Dept Pharmacol, D-60439 Frankfurt, Germany. Univ Halle Wittenberg, Dept Pharmaceut Chem, D-06120 Halle, Germany. Hosp Univ Frankfurt, Ctr Pharmacol, D-60509 Frankfurt, Germany. RP Soldner, A (reprint author), NIDDK, NIH, Bioorgan Chem Lab, 8A-BIA-09, Bethesda, MD 20892 USA. NR 22 TC 11 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD MAY PY 1998 VL 17 IS 1 BP 111 EP 124 DI 10.1016/S0731-7085(97)00240-9 PG 14 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA ZK988 UT WOS:000073387700015 PM 9608433 ER PT J AU Fariello, RG McArthur, RA Bonsignori, A Cervini, MA Maj, R Marrari, P Pevarello, P Wolf, HH Woodhead, JW White, HS Varasi, M Salvati, P Post, C AF Fariello, RG McArthur, RA Bonsignori, A Cervini, MA Maj, R Marrari, P Pevarello, P Wolf, HH Woodhead, JW White, HS Varasi, M Salvati, P Post, C TI Preclinical evaluation of PNU-151774E as a novel anticonvulsant SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ANTIEPILEPTIC DRUGS; SEIZURE MODELS; EPILEPSY; LAMOTRIGINE; MECHANISMS; CLASSIFICATION; MICE AB PNU-151774E [(S)-(+)-2-(4-(3-fluorobenzyloxy) benzylamino) propanamide, methanesulfonate] is a structurally novel anticonvulsant having Naf channel-blocking and glutamate release-inhibiting properties, as well as being a MAO(B), inhibitor. Its anticonvulsant activity was evaluated in the maximal electroshock (MES) test and in chemically induced seizures (bicuculline, BIG; picrotoxin, PIG; 3-mercaptopropionic acid, 3-MPA; pentylenetetrazole, PTZ; strychnine, STRYC). Behavioral toxicity was evaluated in the rotorod test with measurements of spontaneous locomotor activity and passive avoidance responding. The anti-MES activity of PNU-151774E in both mice and rats, respectively, produced ED50 values of 4.1 mg/kg and 6.9 mg/kg after i.p. administration or 8.0 mg/kg and 11.8 mg/kg after p.o. administration. Oral anti-MES activity in rats peaked between 1 and 2 h after administration and was evident up to 4 h. This activity was related to brain levels of unchanged drug which peaked at 37 mM within 1 h. Oral ED50 values (mg/kg) effective in blocking tonic extension seizures by chemical convulsants in mice were: BIC (26.9), PIC (60.6), 3-MPA (21.5), STRYC (104.1) and PTZ (26.8). This potency was associated with high therapeutic indices relative to: MES (78.2), BIC (23.3), PIC (10.3), 3-MPA (29.1) and STRYC (6.0). No evidence of tolerance to anti-MES activity after repeated dosing was observed. PNU-151774E did not show anti-absence seizure activity as assessed by i.v. infusion of PTZ. PNU-151774E impaired spontaneous activity in rats only at the oral rotorod ED50 dose of 700 mg/kg p.o. PNU-151774E did not impair passive avoidance responding at doses up to 40 times the oral MES ED50 dose in rats. These results indicate that PNU-151774E is an anticonvulsant effective in various seizure models with a wide therapeutic window, and with a low potential to induce tolerance and locomotor or cognitive side effects. C1 Thomas Jefferson Univ, Dept Neurol, Philadelphia, PA 19107 USA. Pharmacia & Upjohn Inc, CNS Preclin Res, I-20014 Nerviano, MI, Italy. Pharmacia & Upjohn Inc, Pharmacokinet & Metab, I-20014 Nerviano, MI, Italy. Pharmacia & Upjohn Inc, Dept Med Chem, I-20014 Nerviano, MI, Italy. Univ Utah, NIH, NINDS,Dept Pharmacol & Toxicol, Anticonvulsant Screening Project, Salt Lake City, UT 84112 USA. Ist Clin Perfezionamento, Dept Neurosci, Milan, Italy. RP McArthur, RA (reprint author), Pharmacia & Upjohn Inc, CNS Discovery Res, 725-209-407,301 Henrietta St, Kalamazoo, MI 49007 USA. NR 44 TC 43 Z9 43 U1 1 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 MAY PY 1998 VL 285 IS 2 BP 397 EP 403 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZM874 UT WOS:000073585000002 PM 9580576 ER PT J AU Viu, E Zapata, A Capdevila, JL Fossom, LH Skolnick, P Trullas, R AF Viu, E Zapata, A Capdevila, JL Fossom, LH Skolnick, P Trullas, R TI Glycine site antagonists and partial agonists inhibit N-methyl-D-aspartate receptor-mediated [(3)H]arachidonic acid release in cerebellar granule cells SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID 1-AMINOCYCLOPROPANE CARBOXYLIC-ACID; ARACHIDONIC-ACID; RAT-BRAIN; NMDA RECEPTOR; RECOGNITION SITES; MODULATORY SITE; PRIMARY CULTURES; 7-CHLOROKYNURENIC ACID; SUBUNIT COMPOSITION; XENOPUS-OOCYTES AB Activation of N-methyl-D-aspartate (NMDA) receptors is known to produce arachidonic acid release, which has been implicated in excitotoxicity. Antagonists and partial agonists at the glycine site of the NMDA receptor, despite exhibiting functional differences in electrophysiological studies, inhibit glutamate-induced neurotoxicity and ischemia-induced neurodegeneration. The objective of this study was to investigate the effects of both glycine site antagonists and partial agonists on NMDA receptor-mediated [(3)H]arachidonic acid (AA) release evoked by glutamate, NMDA or a competitive inhibitor of the glutamate/aspartate uptake carrier. The [(3)H]AA release evoked by a maximally effective concentration of glutamate (100 mu M) was blocked by the glycine site antagonists 7-chlorokynurenic acid (7-CKYN) and 5,7-dichlorokynurenic acid (5,7-DCKYN) and by a low intrinsic efficacy glycine partial agonist (+)-1-hydroxy-3-aminopyrrolid-2-one [(+)-HA-966], 1-Aminocyclopropanecarboxylic acid (ACPC), a high intrinsic efficacy glycine partial agonist, did not modify [(3)H]AA release evoked by 100 mu M glutamate. However, ACPC blocked (in a glycine reversible manner) the [(3)H]AA release induced by NMDA (100 mu M) with an IC(50) of 131 +/- 2 mu M. Furthermore, L-trans-pyrrolidine-2,4-dicarboxylate (PDC), a competitive inhibitor of the glutamate transporter, also released [(3)H]AA (E(max) and EC(50) of 127 +/- 4% and 30 +/- 1 mu M, respectively). ACPC, 7-CKYN and (+)-2-amino-7-phosphonoheptanoic acid (AP-7), a competitive NMDA receptor antagonist, inhibited [(3)H]AA release evoked by PDC. These results demonstrate that both glycine site antagonists and partial agonists can inhibit NMDA receptor-mediated [(3)H]AA release in cerebellar granule cells, an action consistent with the neuroprotective effects of these compounds. C1 CSIC, IIBB, Unitat Neurobiol, Dept Bioanalit Med, ES-08034 Barcelona, Spain. NIDDKD, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Trullas, R (reprint author), CSIC, IIBB, Unitat Neurobiol, Dept Bioanalit Med, Jordi Girona 18-26, ES-08034 Barcelona, Spain. EM rtonbi@cid.csis.es RI Trullas, Ramon/D-2197-2016 OI Trullas, Ramon/0000-0001-7951-9881 NR 61 TC 20 Z9 20 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 1998 VL 285 IS 2 BP 527 EP 532 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZM874 UT WOS:000073585000019 PM 9580593 ER PT J AU Brenneman, DE Hauser, J Neale, E Rubinraut, S Fridkin, M Davidson, A Gozes, I AF Brenneman, DE Hauser, J Neale, E Rubinraut, S Fridkin, M Davidson, A Gozes, I TI Activity-dependent neurotrophic factor: Structure-activity relationships of femtomolar-acting peptides SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID VASOACTIVE-INTESTINAL-PEPTIDE; RECEPTOR-MEDIATED ENDOCYTOSIS; NEURONAL SURVIVAL; ELECTRICAL-ACTIVITY; HIPPOCAMPAL-NEURONS; ENVELOPE PROTEIN; OXIDATIVE STRESS; CEREBRAL-CORTEX; CELL-CULTURES; INHIBITORS AB Activity-dependent neurotrophic factor (ADNF) is a glia-derived protein that is neuroprotective at femtomolar concentrations. A 14-amino acid peptide of ADNF (ADNF-14) has been reported that protects cultured neurons from multiple neurotoxins. Structure-activity relationships of peptides related to ADNF-14 now have been determined, A 9-amino acid core peptide (ADNF-9) has been identified that has greater potency and a broader effective concentration range (10(-16) to 10(-13) M) than ADNF or ADNF-14 in preventing cell death associated with tetrodotoxin treatment of cerebral cortical cultures. Deletions or conservative amino acid substitutions to ADNF-9 resulted in reduced potency, narrower effective concentration range and/or decreased efficacy. Removal of the N-terminal serine or the COOH-terminal isoleucine-proline-alanine from ADNF-9 produced a significant reduction in survival-promoting activity. Comparative studies of ADNF-9 action in mixed (glia plus neurons) vs, glia-depleted neuronal cultures indicated that ADNF-9 can act directly on neurons, although the potency of the peptide was 10,000-fold greater in mixed cultures. Kinetic studies showed that exposure to ADNF-9 for only 2 hr was sufficient to produce a 4-day protection against the cell-killing action of tetrodotoxin. Treatment with bafilomycin Al (an inhibitor of receptor-mediated endocytosis) for 2 hr prevented the ADNF- and ADNF-9-mediated neuroprotection. ADNF-9, like ADNF-14, was neuroprotective against N-methyl-D-aspartate and the beta-amyloid peptide (amino acids 25-35), and had a much broader range of effective concentrations than ADNF-14. These studies identify ADNF-9 as an attractive lead compound for the development of therapeutic agents against neurodegenerative diseases. C1 NICHHD, Sect Dev & Mol Pharmacol, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Sect Cell Biol, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Weizmann Inst Sci, Dept Organ Chem, IL-76100 Rehovot, Israel. Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. RP Brenneman, DE (reprint author), NICHHD, Sect Dev & Mol Pharmacol, Dev Neurobiol Lab, NIH, Bldg 49,Room 5A38, Bethesda, MD 20892 USA. NR 49 TC 113 Z9 119 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 MAY PY 1998 VL 285 IS 2 BP 619 EP 627 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZM874 UT WOS:000073585000032 PM 9580606 ER PT J AU Grauert, M Rho, JM Subramaniam, S Rogawski, MA AF Grauert, M Rho, JM Subramaniam, S Rogawski, MA TI N-methyl-D-aspartate receptor channel block by the enantiomeric 6,7-benzomorphans BIII 277 CL and BIII 281 CL SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID HIPPOCAMPAL-NEURONS; MK-801; ANTAGONISTS; RESPONSES; MECHANISM; CURRENTS; CULTURE AB BIII 277 CL {(-)-2R-[2 alpha,3(R*),6 alpha]-3-(2-methoxypropyl-6,11,11-trimethyl-2,6-methano-1,2,3,4,5,6-hexahydro-3-benzazocin-9-ol hydrochloride) is a novel benzomorphan with neuroprotective and anticonvulsant properties that exhibits high affinity binding to the N-methyl-D-aspartate (NMDA) receptor but, in contrast to other structurally related benzomorphans, low affinity for mu opiate and sigma sites. Whole-cell voltage-clamp and single-channel recording were used to study the interaction of BIII 277 CL and its enantiomer BIII 281 CL with native NMDA receptors in cultured hippocampal neurons. Bill 277 CL and Bill 281 CL produced a slow use-dependent block of whole-cell NMDA receptor currents. Once block was established, recovery was slow (<50% in greater than or equal to 40 min). The steady-state IC50 (n(H) values derived from logistic fits to concentration-block isotherms obtained at -60 mV were 5.3 nM (0.67) and 58 nM (1.2), respectively. The benzomorphans had no effect on currents evoked by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and gamma-aminobutyric acid but minimally inhibited kainate-evoked currents at high (greater than or equal to 30 mu M) concentrations. Bill 277 CL and Bill 281 CL failed to bind and block closed NMDA receptor channels, and the block was occluded by Mg++ consistent with an open channel-blocking mechanism. Steady-state block was diminished by depolarization; analysis of the voltage-dependence of block indicated that BIII 281 CL binds within the channel at a site that senses 46% of the transmembrane electric field. Recordings of single NMDA receptor channels in outside-out membrane patches confirmed the slow, persistent blocking action obtained in whole-cell recordings. In addition, at high concentrations, flickering of the unitary currents was observed consistent with a low-affinity channel-blocking action. Taking the present data in conjunction with previously obtained structure-activity information for N-substituted benzomorphans, a three-mode-blocking model was developed in which there are three interaction sites for binding of the high-affinity ligand BIII 277 CL. In this model, the drug can bind in one of three modes by docking at one, two or all three interaction points but cannot transition between modes. The model further proposes that the lower-affinity enantiomer Bill 281 CL binds in modes with one and two but not all three interaction points docked. We conclude that Bill 277 CL and Bill 281 CL are potent and selective, use-dependent (uncompetitive) channel-blocking NMDA receptor antagonists. The substantially higher affinity that BIII 277 CL exhibits for the NMDA receptor in comparison with its enantiomer and other benzomorphans appears to be due to stabilization of binding at three sites within the channel. 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 17 TC 6 Z9 6 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 MAY PY 1998 VL 285 IS 2 BP 767 EP 776 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZM874 UT WOS:000073585000051 PM 9580625 ER PT J AU Wyatt, RJ Henter, ID AF Wyatt, RJ Henter, ID TI The effects of early and sustained intervention on the long-term morbidity of schizophrenia SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article ID FOLLOW-UP; NEUROLEPTIC TREATMENT; TREATMENT RESPONSE; 1ST ADMISSIONS; NATURAL COURSE; FIRST-EPISODE; 1ST-ADMISSION; MAINTENANCE; HYPOTHESIS; PREDICTORS AB By examining the literature concerning early intervention with antipsychotic medications, and how it affects long-term morbidity, this article will review the concept that early intervention with antipsychotic medications improves the long-term course of schizophrenia. It also looks at the potential long-term effects of discontinuing antipsychotic medications early in the course of schizophrenia. It appears that early intervention with antipsychotic medications decreases some of the long-term morbidity associated with schizophrenia. Some of the implications of this finding are discussed in the context of both clinical practice and clinical research. Published by Elsevier Science Ltd. C1 NIMH, Neurosci Ctr St Elizabeths, Neuropsychiat Branch, NIH, Washington, DC 20032 USA. RP Wyatt, RJ (reprint author), NIMH, Neurosci Ctr St Elizabeths, Neuropsychiat Branch, NIH, Washington, DC 20032 USA. FU Intramural NIH HHS [Z99 MH999999] NR 82 TC 52 Z9 53 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD MAY-AUG PY 1998 VL 32 IS 3-4 BP 169 EP 177 DI 10.1016/S0022-3956(97)00014-9 PG 9 WC Psychiatry SC Psychiatry GA 118WZ UT WOS:000075865100007 PM 9793870 ER PT J AU Arayssi, TK Schumacher, HR AF Arayssi, TK Schumacher, HR TI Evaluation of a modified needle for small joint biopsies SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE synovial biopsy; rheumatoid arthritis; psoriasis; small joints; fingers AB Objective. To assess the value of a new short biopsy needle modified from the Parker-Pearson needle in obtaining adequate synovial tissue from small joints. Methods. The short needle is 2.5 cm in length with a repositioned hooked biopsy notch closer to the end of the needle to allow better specimen retrieval. It can be used to obtain synovial biopsies from small joints of the hand using the usual arthrocentesis approaches. Results. Ten patients underwent 12 synovial biopsies with a success rate of 92%. No complications from the procedure were observed. Samples obtained were adequate for a variety of studies including synovial histopathological evaluation, electron microscopy, and DNA extraction. Conclusion. The new modified short needle expands the spectrum of joints that con be biopsied for diagnostic and research purposes in an outpatient setting. C1 Vet Adm Med Ctr, Philadelphia, PA 19104 USA. NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA. RP Schumacher, HR (reprint author), Vet Adm Med Ctr, Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM Schumacher.ralph@philadelphia.va.gov OI Arayssi, Thurayya/0000-0003-2469-0272 NR 6 TC 8 Z9 8 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 MAY PY 1998 VL 25 IS 5 BP 876 EP 878 PG 3 WC Rheumatology SC Rheumatology GA ZK991 UT WOS:000073388000009 PM 9598883 ER PT J AU Anderson, DW Bowland, BJ Cartwright, WS Bassin, G AF Anderson, DW Bowland, BJ Cartwright, WS Bassin, G TI Service-level costing of drug abuse treatment SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE substance abuse treatment; managed care; economic-actuarial costing AB This payer presents a methodology far estimating costs of delivering specific substance abuse treatment services. Data collected from 13 programs indicate that the mean cost of residential treatment is $2,773 per patient per month, and outpatient treatment costs average $636 per patient per month. Data are presented on the cost per patient per month for individual treatment and nontreatment services, average number of services, cost PET unit of service, and intensity of services. III addition to their application to insurance benefit cost estimation, these data illustrate the costing of best-practice adolescent treatment consistent with a Center for Substance Abuse Treatment (CSAT) Treatment Improvement Protocol. In the emerging policy environment, derailed cost estimates like these will aid the design of cost-effective treat ment programs, and serve the development of the substance abuse benefit in a health care reform insurance package. (C) 1998 Elsevier Science Inc. C1 Ctr Econ Res, Res Triangle Inst, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Agr & Resource Econ, Grad Program, Raleigh, NC 27695 USA. NIDA, Serv Res Branch, Clin & Serv Res Div, Rockville, MD 20852 USA. Johnson Bassin & Shaw Inc, Silver Spring, MD USA. RP Anderson, DW (reprint author), Ctr Econ Res, Res Triangle Inst, 3040 Cornwallis Rd,POB 12194, Res Triangle Pk, NC 27709 USA. EM dwa@rti.org NR 9 TC 45 Z9 45 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD MAY-JUN PY 1998 VL 15 IS 3 BP 201 EP 211 DI 10.1016/S0740-5472(97)00189-X PG 11 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA ZT276 UT WOS:000074068300005 PM 9633032 ER PT J AU Zametkin, AJ Ernst, M Silver, R AF Zametkin, AJ Ernst, M Silver, R TI Laboratory and diagnostic testing in child and adolescent psychiatry: A review of the past 10 years SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE laboratory tests; pediatrics; assessment ID DEFICIT HYPERACTIVITY DISORDER; CEREBROSPINAL-FLUID NEUROCHEMISTRY; DEXAMETHASONE SUPPRESSION TEST; FRAGILE-X-SYNDROME; OBSESSIVE-COMPULSIVE DISORDER; DISRUPTIVE BEHAVIOR DISORDERS; THYROID STIMULATING HORMONE; MAJOR DEPRESSIVE DISORDER; ATTENTION-DEFICIT; MONOAMINE METABOLITES AB Objective: To review in a critical fashion the literature of the past decade covering diagnostic and laboratory testing in the field of child and adolescent psychiatry. Method: A computerized search of articles published during the past decade was made, and selected articles are presented. Because of the paucity of articles specifically relating to minors, selected articles from adult psychiatry are cited. Results: With a few notable exceptions, few controlled studies an the specificity and sensitivity of any laboratory test for any specific disorder of behavior presenting in children have been conducted in children and adolescents. A high index of suspicion will remain the clinician's best ally in utilizing laboratory measures in the assessment of psychopathology. Nonetheless, studies have appeared that will guide the clinician as to what tests are not clinically useful. Conclusion: indications and the lack of indications for specific laboratory studies are an integral part of the knowledge base that child psychiatrists must have. Much more empirical data will need to be collected prospectively to inform the field and to move the judicious use of the laboratory from an art to a science. C1 NIMH, Off Clin Director, NIH, Bethesda, MD 20892 USA. NIDA, Brain Imaging Ctr, NIH, Baltimore, MD USA. RP Zametkin, AJ (reprint author), NIMH, Off Clin Director, NIH, Room 3N238,Bldg 10,Ctr Dr MSC 1276, Bethesda, MD 20892 USA. EM zametkin@box-z.nih.gov NR 62 TC 9 Z9 10 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 1998 VL 37 IS 5 BP 464 EP 472 DI 10.1097/00004583-199805000-00007 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA ZJ953 UT WOS:000073270300008 PM 9585646 ER PT J AU Yellowitz, J Horowitz, AM Goodman, HS Canto, MT Farooq, NS AF Yellowitz, J Horowitz, AM Goodman, HS Canto, MT Farooq, NS TI Knowledge, opinions and practices of general dentists regarding oral cancer: A pilot survey SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article AB The authors mailed a pilot survey to 500 randomly selected general dentists. Although most dentists reported their knowledge of oral cancer to be current, their actual knowledge of oral cancer risk factors and signs and symptoms was inconsistent. Conflicting data were also found between their level of knowledge and their provision of oral cancer examinations. Most respondents agreed that patients should undergo an oral cancer examination annually, yet many do not provide this service. C1 NIDR, Off Sci Policy & Anal, Off Director, Bethesda, MD 20892 USA. Dept Hlth & Mental Hyg, Baltimore, MD USA. Univ Maryland, Coll Dent Surg, Pediat Dent Postgrad Program, Baltimore, MD 21201 USA. RP Yellowitz, J (reprint author), NIDR, Off Sci Policy & Anal, Off Director, Bethesda, MD 20892 USA. NR 11 TC 46 Z9 47 U1 0 U2 1 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 MAY PY 1998 VL 129 IS 5 BP 579 EP 583 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA ZM424 UT WOS:000073538800015 PM 9601170 ER PT J AU Slavkin, HC AF Slavkin, HC TI And we all lived happily ever after: Understanding the biological controls of aging SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article C1 NIDR, Bethesda, MD 20892 USA. RP Slavkin, HC (reprint author), NIDR, 31 Ctr Dr,MSC 2290,Bldg 31,Room 2C39, Bethesda, MD 20892 USA. NR 6 TC 1 Z9 1 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 MAY PY 1998 VL 129 IS 5 BP 629 EP 633 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA ZM424 UT WOS:000073538800024 PM 9601178 ER PT J AU Subar, AF Krebs-Smith, SM Cook, A Kahle, LL AF Subar, AF Krebs-Smith, SM Cook, A Kahle, LL TI Dietary sources of nutrients among US adults, 1989 to 1991 SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID UNITED-STATES POPULATION; NHANES-II SURVEY; FOOD SOURCES; QUANTITATIVE DATA; AMERICAN DIET; FIBER; MACRONUTRIENTS; WOMEN AB Objective To identify major food sources of 27 nutrients and dietary constituents for US adults. Design Single 24-hour dietary recalls were used to assess intakes. From 3,970 individual foods reported, 112 groups were created on the basis of similarities in nutrient content or use. Food mixtures were disaggregated using the US Department of Agriculture (USDA) food grouping system. Subjects/setting A nationally representative sample of adults aged 19 years or older (n=10,638) from USDA's 1989-91 Continuing Survey of Food Intakes by Individuals. Analyses performed For each of 27 dietary components, the contribution of each food group to intake was obtained by summing the amount provided by the food group for all respondents and dividing by total intake from all food groups for all respondents. Results This article updates previous work and is, to the authors' knowledge, the first to provide such data for carotenes, vitamin B-12, magnesium, and copper. Beef, yeast bread, poultry, cheese, and milk were among the top 10 sources of energy, fat, and protein. The following other major sources also contributed more than 2% to energy intakes: carbohydrate: yeast bread, soft drinks/soda, cakes/cookies/quick breads/doughnuts, sugars/syrups/jams, potatoes (white), ready-to-eat cereal, and pasta; protein: pasta; and fat: margarine, salad dressings/mayonnaise, and cakes/cookies/quick breads/doughnuts. Ready-to-eat cereals, primarily because of fortification, were among the top 10 food sources for 18 of 27 nutrients. Applications/conclusions These analyses are the most current regarding food sources of nutrients and, because of disaggregation of mixtures, provide a truer picture of contributions of each food group. C1 NCI, Appl Res Branch, Bethesda, MD 20892 USA. USDA ARS, Riverdale, MD USA. Informat Management Serv, Silver Spring, MD USA. RP Subar, AF (reprint author), NCI, Appl Res Branch, 6130 Execut Blvd,MSC 7344,EPN 313, Bethesda, MD 20892 USA. NR 18 TC 162 Z9 164 U1 1 U2 7 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD MAY PY 1998 VL 98 IS 5 BP 537 EP 547 DI 10.1016/S0002-8223(98)00122-9 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZL506 UT WOS:000073440300011 PM 9597026 ER PT J AU Wilbur, WJ AF Wilbur, WJ TI A comparison of group and individual performance among subject experts and untrained workers at the document retrieval task SO JOURNAL OF THE AMERICAN SOCIETY FOR INFORMATION SCIENCE LA English DT Article ID INFORMATION-RETRIEVAL; TEXT RETRIEVAL; SYSTEM; KNOWLEDGE AB Useful retrieval depends on the ability to predict which documents a user will find helpful in answer to a query. Our interest is the common case when no information is provided about the user other than the query and the query is in natural language. In this setting it is well accepted that a human can make useful predictions in the form of judgments about what will likely prove useful to another human. We present data showing that when the predictions of a group of humans are averaged, the result is a better predictor. If performance is measured as a precision, the group performance increases with the size of the group and approaches a limit of approximately 50% improvement over average individual performance on our data. Superior performance by groups raises the question of how. The groups we studied were subject experts and a natural question was whether the superior performance resulted from the pooling of their subject knowledge. In order to answer this question we studied also a group of untrained individuals. to our surprise we found that while untrained individuals had a somewhat inferior performance compared to trained individuals, the group of untrained individuals together performed better than any single trained individual and almost at the level of the trained group. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Wilbur, WJ (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NR 34 TC 6 Z9 6 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0002-8231 J9 J AM SOC INFORM SCI JI J. Am. Soc. Inf. Sci. PD MAY 1 PY 1998 VL 49 IS 6 BP 517 EP 529 DI 10.1002/(SICI)1097-4571(19980501)49:6<517::AID-ASI4>3.0.CO;2-W PG 13 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA ZG613 UT WOS:000073021400003 ER PT J AU Terris, J Ecelbarger, CA Sands, JM Knepper, MA AF Terris, J Ecelbarger, CA Sands, JM Knepper, MA TI Long-term regulation of renal urea transporter protein expression in rat SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID DUCT WATER PERMEABILITY; COLLECTING DUCT; BRATTLEBORO RAT; VASOPRESSIN; CLONING; KIDNEY; IMCD AB To test the hypothesis that the abundance of the apical urea transporter of the inner medullary collecting duct (IMCD) is regulated in vivo by factors associated with altered water balance, immunoblots of rat inner medullary membrane fractions were probed with rabbit polyclonal antibodies against the renal urea transporter (RUT) gene product. In inner medullas of Brattleboro rats, which manifest severe chronic water diuresis, a 117-kD band was seen, in addition to the previously described 97-kD band. These two bands were detectable by antibodies directed against two different regions of the RUT sequence. When Brattleboro rats were treated with a 5-d infusion of arginine vasopressin (AVP) by osmotic minipump, the 117-kD band was markedly diminished, whereas the 97-kD band was unchanged. Simultaneous infusion of the diuretic agent furosemide prevented the AVP-induced decrease in the 117-kD band. In AVP-infused Sprague Dawley rats, the 117-kD band was barely perceptible. However, when AVP treated rats were infused with furosemide for 5 d, the 117-kD band was markedly accentuated, whereas the 97-kD band was unchanged. The abundance of the 117-kD RUT protein in the renal papilla was inversely correlated with dietary protein intake. Further immunoblotting studies revealed that the 117-kD protein is heavily expressed in IMCD cells and not in non-collecting duct components of the inner medulla, and is present in low-density microsome fractions from inner medulla. From this study, the following conclusions can be made: (I) The collecting duct urea transporter is present in at least two forms (97 and 117 kD) in the IMCD. (2) The expression level of the 117-kD urea transporter protein is regulated and is inversely correlated with medullary osmolality and urea concentration, but does not correlate with circulating AVP level. (3) Although AVP regulates RUT function on a short-term basis, long-term changes in AVP levels do not increase RUT abundance. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. Emory Univ, Sch Med, Div Nephrol, Atlanta, GA USA. Uniformed Serv Univ Hlth Sci, Dept Physiol, Bethesda, MD 20814 USA. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bldg 10,Room 6N260,10 Ctr Dr,MSC 1603, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [R01 DK041707] NR 24 TC 63 Z9 63 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAY PY 1998 VL 9 IS 5 BP 729 EP 736 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA ZK785 UT WOS:000073363300001 PM 9596069 ER PT J AU Kato, A Naruse, M Knepper, MA Sands, JM AF Kato, A Naruse, M Knepper, MA Sands, JM TI Long-term regulation of inner medullary collecting duct urea transport in rat SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 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 LOW-PROTEIN DIET; WATER CHANNEL; KIDNEY; VASOPRESSIN; EXPRESSION; CLONING; PERMEABILITY; MEMBRANE; DIURESIS AB Facilitated urea transport is regulated acutely by arginine vasopressin (AVP) and hyperosmolality in rat terminal inner medullary collecting duct (IMCD). This study tested whether chronic diuresis or antidiuresis regulates facilitated urea transport. Basal and AVP-stimulated urea permeabilities (P-urea) were measured in perfused IMCD subsegments, Rats were made: (1) diuretic by giving them sugar water (with or without food) or furosemide; or (2) antidiuretic by water deprivation. They were then compared with untreated rats given food and water ad libitum. Terminal TMCD from untreated rats had a high basal P-urea that was significantly increased by AVP. Diuresis significantly increased basal P-urea in terminal IMCD in all five diuresis protocols. Water deprivation for 1 or 3 d bad no effect on basal or AVP-stimulated P-urea in the IMCD2 subsegment of the terminal IMCD, In contrast, 3 d of water deprivation significantly increased both basal and AVP-stimulated P-urea in the IMCD, subsegment; 1 d of water deprivation had no effect on basal or AVP-stimulated P-urea. Next, initial IMCD (IMCD1) were studied. Initial IMCD from untreated rats had a low basal P-urea that was not increased by AVP (10 nM). Water diuresis (with or without food) for 3 to 5 d had no effect on basal P-urea but significantly increased AVP-stimulated P-urea. Furosemide diuresis and water diuresis for 1 or 7 d had no effect on either basal or AVP-stimulated P-urea in initial IMCD. Water deprivation for 2 to 3 d, but not for 1 d, significantly increased basal P-urea in initial IMCD, whereas water deprivation for 1 d increased AVP-stimulated P-urea. It is concluded that chronic changes in hydration cause heterogeneous changes in facilitated urea transport in rat IMCD subsegments. C1 Emory Univ, Sch Med, Div Renal, Dept Med, Atlanta, GA 30322 USA. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Sands, JM (reprint author), Emory Univ, Sch Med, Div Renal, Dept Med, WMRB Room 338,1639 Pierce Dr NE, Atlanta, GA 30322 USA. FU NIDDK NIH HHS [R01 DK041707, P01-DK50268, R01-DK41707] NR 39 TC 35 Z9 35 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAY PY 1998 VL 9 IS 5 BP 737 EP 745 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA ZK785 UT WOS:000073363300002 PM 9596070 ER PT J AU Parent, C Rozanski, E AF Parent, C Rozanski, E TI What is your diagnosis? Pneumopericardium and pulmonary alveolar disease SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article C1 Univ Penn, Vet Hosp, Ctr Vet Crit Care, Philadelphia, PA 19104 USA. RP Parent, C (reprint author), NIH, Bldg 10,Room 7 D43,10 Ctr Dr MSC 1662, Bethesda, MD 20892 USA. NR 2 TC 6 Z9 6 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD MAY 1 PY 1998 VL 212 IS 9 BP 1377 EP 1378 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA ZL306 UT WOS:000073419400024 PM 9589120 ER PT J AU Arankalle, VA Chadha, MS Dama, BM Tsarev, SA Purcell, RH Banerjee, K AF Arankalle, VA Chadha, MS Dama, BM Tsarev, SA Purcell, RH Banerjee, K TI Role of immune serum globulins in pregnant women during an epidemic of hepatitis E SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE efficacy; hepatitis E; ISG; pregnant women ID NON-B-HEPATITIS; E VIRUS-INFECTION; WATERBORNE NON-A; VIRAL-HEPATITIS; RHESUS-MONKEYS; INDIA; HEV AB The efficacy of an Indian preparation of immune serum grobulins (ISG) was evaluated among pregnant women during an epidemic of hepatitis E in Karad, Western India from January to March 1993. Ten of 55 women receiving ISG developed immunoglobulin M (IgM) antibodies to hepatitis E virus (anti-HEV) during the 1 month of follow-up compared with 18 out of 53 control subjects. Although the total number of recent HEV infections was significantly less in the ISG-treated group, no significant difference could be shown in the proportion of clinical hepatitis E cases because of the very small numbers of patients who developed clinical disease. The observed marginal beneficial effect of ISG might be the result of a low immunoglobulin G (IgG) anti-HEV IgG titre (1:500) of the ISG preparation used. Preparation and testing of high-titred ISG should be a high priority for protecting pregnant women during epidemics of hepatitis E. C1 Natl Inst Virol, Hepatitis Div, Pune 411001, Maharashtra, India. Govt Maharashtra, Off Addit Director Communicable Dis, Pune, Maharashtra, India. NIH, Hepatitis Viruses Sect, Bethesda, MD 20892 USA. RP Arankalle, VA (reprint author), Natl Inst Virol, Hepatitis Div, 20-A Dr Ambedkar Rd,PB No 11, Pune 411001, Maharashtra, India. NR 18 TC 37 Z9 39 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD MAY PY 1998 VL 5 IS 3 BP 199 EP 204 DI 10.1046/j.1365-2893.1998.00096.x PG 6 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA ZR933 UT WOS:000074030900009 PM 9658374 ER PT J AU Graff, J Ehrenfeld, E AF Graff, J Ehrenfeld, E TI Coding sequences enhance internal initiation of translation by hepatitis A virus RNA in vitro SO JOURNAL OF VIROLOGY LA English DT Article ID PYRIMIDINE-RICH TRACT; RIBOSOMAL ENTRY SITE; CAP-INDEPENDENT TRANSLATION; 5' NONTRANSLATED REGION; A VIRUS; POLIOVIRUS RNA; C VIRUS; PICORNAVIRUS RNAS; NONCODING REGION; MESSENGER-RNA AB Hepatitis A virus (HAV), unlike other picornaviruses, has a stow-growth phenotype in permissive cell lines and in general does not induce host cell cytopathology. Although there are no published reports of productive infection of HeLa cells by HAV, HAV RNA appears to be readily translated in HeLa cells when transcribed by T7 RNA polymerase provided by a recombinant vaccinia virus. The 5' noncoding region of HAV was fused to poliovirus (PV) coding sequences to determine the effect on translation efficiency in HeLa cell extracts in vitro, Conditions were optimized for utilization of the HAV internal ribosome entry segment (IRES), Transcripts from chimeric constructs fused precisely at the initiation codon were translated very poorly. However, chimeric RNAs which included 114 or more nucleotides from the HAV capsid coding sequences downstream of the initiation codon were translated much more efficiently than those lacking these sequences, making HAV-directed translation efficiency similar to that directed by the PV IRES. Sixty-six nucleotides were insufficient to confer increased translation efficiency. The most 5'-terminal HAV 138 nucleotides, previously determined to be upstream of the IRES, had an inhibitory effect on translation efficiency. Constructs lacking these terminal sequences, or those in which the PV 5'-terminal sequences replaced those from HAV, translated three- to fourfold better than those with the intact HAV 5'-terminal end. C1 Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA. RP Graff, J (reprint author), NIAID, NIH, LID, Hepatitis Virus Sect, Bldg 7,Room 200,7 Ctr Dr,MSC 0740, Bethesda, MD 20892 USA. FU NIAID NIH HHS [AI26350, AI12387] NR 45 TC 24 Z9 24 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 MAY PY 1998 VL 72 IS 5 BP 3571 EP 3577 PG 7 WC Virology SC Virology GA ZH268 UT WOS:000073090100010 PM 9557637 ER PT J AU Baumert, TF Ito, S Wong, DT Liang, TJ AF Baumert, TF Ito, S Wong, DT Liang, TJ TI Hepatitis C virus structural proteins assemble into viruslike particles in insect cells SO JOURNAL OF VIROLOGY LA English DT Article ID NON-B-HEPATITIS; NON-A; FULMINANT-HEPATITIS; ENVELOPE PROTEIN; E2-NS2 REGION; LOW-DENSITY; EXPRESSION; GENOME; IDENTIFICATION; GLYCOPROTEIN AB Hepatitis C virus (HCV) is a leading cause of chronic hepatitis in the world. The study of HCV has been hampered by the low level of viral particles in infected individuals, the inability to propagate efficiently the virus in cultured cells, and the lack of a convenient animal model. Due to these obstacles, neither the structure of the virus nor the prerequisites for its assembly have been clearly defined. In this report, we describe a model for the production and purification of HCV-like particles in insect cells using a recombinant baculovirus containing the cDNA of the HCV structural proteins. In insect cells, expressed HCV structural proteins assembled into enveloped viruslike particles (40 to 60 nm in diameter) in large cytoplasmic cisternae, presumably derived from the endoplasmic reticulum. Biophysical characterization of viruslike particles by CsCl and sucrose gradient centrifugation revealed biophysical properties similar to those of putative virions isolated from infected humans. The results suggested that HCV core and envelope proteins without p7 were sufficient for viral particle formation. Analysis of particle-associated nucleic acids demonstrated that HCV RNAs were selectively incorporated into the particles over non-HCV transcripts. The synthesis of HCV-like particles in insect cells may provide an important tool to determine the structural requirements for HCV particle assembly as well as to study viral genome encapsidation and virus-host interactions. The described system may also represent a potential approach toward vaccine development. C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Stanford Univ, Sch Med, Dept Med, Div Gastroenterol, Palo Alto, CA 94304 USA. RP Liang, TJ (reprint author), NIDDK, Liver Dis Sect, NIH, 10 Ctr Dr,Rm 9B16, Bethesda, MD 20892 USA. EM JLiang@nih.gov FU NCI NIH HHS [CA-54525]; NIDDK NIH HHS [DK-01952, VF-DK-14361] NR 49 TC 268 Z9 286 U1 3 U2 13 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 MAY PY 1998 VL 72 IS 5 BP 3827 EP 3836 PG 10 WC Virology SC Virology GA ZH268 UT WOS:000073090100039 PM 9557666 ER PT J AU Strockbine, LD Cohen, JI Farrah, T Lyman, SD Wagener, F DuBose, RF Armitage, RJ Spriggs, MK AF Strockbine, LD Cohen, JI Farrah, T Lyman, SD Wagener, F DuBose, RF Armitage, RJ Spriggs, MK TI The Epstein-Barr virus BARF1 gene encodes a novel, soluble colony-stimulating factor-1 receptor SO JOURNAL OF VIROLOGY LA English DT Article ID FACTOR-I RECEPTOR; HUMAN B-CELLS; BAMHI-A; NASOPHARYNGEAL CARCINOMA; CSF-1 RECEPTOR; BIOLOGICAL CHARACTERIZATION; EXTRACELLULAR DOMAIN; MOLECULAR-CLONING; HUMAN MONOCYTES; POINT MUTATION AB Epstein-Barr virus (EBV) is a ubiquitous herpesvirus associated with infectious mononucleosis and several tumors. The BARF1 gene is transcribed early after EBV infection from the BamHI A fragment of the EBV genome. Evidence shown here indicates that the BARF1 protein is secreted into the medium of transfected cells and from EBV-carrying B cells induced to allow lytic replication of the virus. Expression cloning identified colony-stimulating factor-1 (CSF-1) as a ligand for BARF1, Computer-assisted analyses indicated that subtle amino acid sequence homology exists between BARF1 and c-fms, the cellular proto-oncogene that is the receptor for CSF-1. Recombinant BARF1 protein was found to be biologically active, and it neutralized the proliferative effects of human CSF-1 in a dose-dependent fashion when assayed in vitro. Since CSF-1 is a pleiotropic cytokine best known for its differentiating effects on macrophages, these data suggest that BARF1 may function to modulate the host immune response to EBV infection. C1 Immunex Res & Dev Corp, Mol Biol, Seattle, WA 98101 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Spriggs, MK (reprint author), Immunex Res & Dev Corp, Mol Biol, 51 Univ St, Seattle, WA 98101 USA. NR 60 TC 98 Z9 104 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 MAY PY 1998 VL 72 IS 5 BP 4015 EP 4021 PG 7 WC Virology SC Virology GA ZH268 UT WOS:000073090100062 PM 9557689 ER PT J AU Kiernan, RE Ono, A Englund, G Freed, EO AF Kiernan, RE Ono, A Englund, G Freed, EO TI Role of matrix in an early postentry step in the human immunodeficiency virus type 1 life cycle SO JOURNAL OF VIROLOGY LA English DT Article ID ENDOGENOUS REVERSE TRANSCRIPTION; NUCLEAR-LOCALIZATION SIGNAL; PROVIRAL DNA-SYNTHESIS; NONDIVIDING CELLS; VIRAL-DNA; ENVELOPE GLYCOPROTEIN; PARTICLE-PRODUCTION; GAG PROTEINS; C-TERMINUS; INFECTION AB The matrix protein of human immunodeficiency virus type 1 (HIV-1) has been reported to play a crucial role in the targeting of the Gag polyprotein precursor to the plasma membrane and in the incorporation of viral envelope glycoproteins into budding virions. In this report, we present evidence that mutation of a highly conserved Leu at matrix amino acid 20 blocks or markedly delays virus replication in a range of cell types, including T-cell lines, primary human peripheral blood mononuclear cells, and monocyte-derived macrophages. These mutations do not impair virus assembly and release, RNA encapsidation, or envelope glycoprotein incorporation into virions but rather cause significant defects in an early step in the virus life cycle, as measured by single-cycle infectivity assays and the analysis of viral DNA synthesis early postinfection. This infectivity defect is independent of the type of envelope glycoprotein carried on mutant virions; similar results are obtained in pseudotyping experiments using wild-type or truncated HIV-1 envelope glycoproteins, the amphotropic murine leukemia virus envelope, or the vesicular stomatitis G protein, Intriguingly, matrix residue 20 mutations also increase the apparent binding of Gag to membrane, accelerate the kinetics of Gag processing, and induce defects in endogenous reverse transcriptase activity without affecting virion density or morphology, These results help elucidate the function of matrix in HIV-1 replication. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Freed, EO (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Rm 307, Bethesda, MD 20892 USA. EM EFreed@nih.gov NR 79 TC 109 Z9 110 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1998 VL 72 IS 5 BP 4116 EP 4126 PG 11 WC Virology SC Virology GA ZH268 UT WOS:000073090100074 PM 9557701 ER PT J AU Benson, J Chougnet, C Robert-Guroff, M Montefiori, D Markham, P Shearer, G Gallo, RC Cranage, M Paoletti, E Limbach, K Venzon, D Tartaglia, J Franchini, G AF Benson, J Chougnet, C Robert-Guroff, M Montefiori, D Markham, P Shearer, G Gallo, RC Cranage, M Paoletti, E Limbach, K Venzon, D Tartaglia, J Franchini, G TI Recombinant vaccine-induced protection against the highly pathogenic simian immunodeficiency virus SIVmac251: Dependence on route of challenge exposure SO JOURNAL OF VIROLOGY LA English DT Article ID ENHANCING ANTIBODY-RESPONSES; CELL STIMULATORY FACTOR; IMMUNE-RESPONSES; RHESUS MACAQUES; FOWLPOX VIRUS; T-CELLS; INFECTION; SIV; IMMUNIZATION; SEQUENCE AB Vaccine protection from infection and/or disease induced by highly pathogenic simian immunodeficiency virus (SIV) strain SIVmac251 in the rhesus macaque model is a challenging task Thus far, the only approach that has been reported to protect a fraction of macaques from infection following intravenous challenge with SIVmac251 was the use of a live attenuated SIV vaccine. In the present study, the gag, pol, and env genes of SIVK6W were expressed in the NYVAC vector, a genetically engineered derivative of the vaccinia virus Copenhagen strain that displays a highly attenuated phenotype in humans. In addition, the genes for the alpha and beta chains of interleukin-12 (IL-12), as well as the IL-2 gene, were expressed in separate NYVAC vectors and inoculated intramuscularly, in conjunction with or separate from the NYVAC-SIV vaccine, in 40 macaques. The overall cytotoxic T-lymphocyte (CTL) response was greater, at the expense of proliferative and humoral responses, in animals immunized with NYVAC-SIV and NYVAC-IL-12 than in animals immunized with the NYVAC-SIV vaccine alone. At the end of the immunization regimen, half of the animals were challenged with SIVmac251 by the intravenous route and the other half were exposed to SIVmac251 intrarectally. Significantly, five of the eleven vaccinees exposed mucosally to SIVmac251 showed a transient peak of viremia 1 week after viral challenge and subsequently appeared to clear viral infection. In contrast, all 12 animals inoculated intravenously became infected, but 5 to 6 months after viral challenge, 4 animals were able to control viral expression and appeared to progress to disease more slowly than control animals. Protection did not appear to be associated with any of the measured immunological parameters, Further modulation of immune responses by coadministration of NYVAC-cytokine recombinants did not appear to influence the outcome of viral challenge. The fact that the NYVAC-SIV recombinant vaccine appears to be effective per se in the animal model that best mirrors human AIDS supports the idea that the development of a highly attenuated poxvirus-based vaccine candidate can be a valuable approach to significantly decrease the spread of human immunodeficiency virus (HIV) infection by the mucosal route. C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Ctr AIDS Res, Dept Surg, Durham, NC 27710 USA. Adv Biosci Labs Inc, Kensington, MD 20895 USA. Publ Hlth Lab Serv, Ctr Appl Microbiol & Res, Div Pathol, Salisbury SP4 0JG, Wilts, England. Virogenet Corp, Troy, NY 12180 USA. Univ Med, Inst Human Virol, Baltimore, MD 21201 USA. RP Franchini, G (reprint author), NCI, Basic Res Lab, 37 Convent Dr,Bldg 37,Rm 6A11, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 50 TC 142 Z9 142 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 MAY PY 1998 VL 72 IS 5 BP 4170 EP 4182 PG 13 WC Virology SC Virology GA ZH268 UT WOS:000073090100079 PM 9557706 ER PT J AU Roper, RL Wolffe, EJ Weisberg, A Moss, B AF Roper, RL Wolffe, EJ Weisberg, A Moss, B TI The envelope protein encoded by the A33R gene is required for formation of actin-containing microvilli and efficient cell-to-cell spread of vaccinia virus SO JOURNAL OF VIROLOGY LA English DT Article ID ESCHERICHIA-COLI; LAC REPRESSOR; GLYCOPROTEIN; RELEASE; MEMBRANE; HEMAGGLUTININ; EXPRESSION; DISSEMINATION; SEQUENCE; FUSION AB The vaccinia virus (VV) A33R gene encodes a highly conserved 23- to 28-kDa glycoprotein that is specifically incorporated into the viral outer envelope. The protein is expressed early and late after infection, consistent with putative early and late promoter sequences. To determine the role of the protein, two inducible A33R mutants were constructed, one with the late promoter and one with the early and late A33R promoter elements. Decreased A33R expression was associated with small plaques that formed comets in liquid medium. Using both an antibiotic resistance gene and a color marker, an A33R deletion mutant, vA33 Delta, was isolated, indicating that the A33R gene is not essential for VV replication. The plaques formed by vA33 Delta, however, were tiny, indicating that the A33R protein is necessary for efficient cell-to-cell spread. Rescue of the large-plaque phenotype was achieved by inserting a new copy of the A33R gene into the thymidine kinase locus, confirming the specific genetic basis of the phenotype. Although there was a reduction in intracellular virus formed in cells infected with vA33 Delta, the amount of infectious virus in the medium was increased. The virus particles in the medium had the buoyant density of extracellular enveloped viruses (EEV). Additionally, amounts of vA33 Delta cell-associated extracellular enveloped viruses (CEV) were found to be normal. Immunogold electron microscopy of cells infected with vA33 Delta demonstrated the presence of the expected F13L and B5R proteins in wrapping membranes and EEV; however, fully wrapped vA33 Delta intracellular enveloped viruses (IEV) were rare compared to partially wrapped particles. Specialized actin tails that propel IEV particles to the periphery and virus-tipped microvilli (both common in wild-type-infected cells) were absent in cells infected with vA33 Delta. This is the first deletion mutant in a VV envelope gene that produces at least normal amounts of fully infectious EEV and CEV and yet has a small-plaque phenotype. These data support a new model for VV spread, emphasizing the importance of virus-tipped actin tails. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 4,Room 229 4,Ctr Dr,MSC 0445, Bethesda, MD 20892 USA. NR 58 TC 103 Z9 105 U1 1 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 MAY PY 1998 VL 72 IS 5 BP 4192 EP 4204 PG 13 WC Virology SC Virology GA ZH268 UT WOS:000073090100081 PM 9557708 ER PT J AU Tsai, CC Emau, P Follis, KE Beck, TW Benveniste, RE Bischofberger, N Lifson, JD Morton, WR AF Tsai, CC Emau, P Follis, KE Beck, TW Benveniste, RE Bischofberger, N Lifson, JD Morton, WR TI Effectiveness of postinoculation (R)-9-(2-Phosphonylmethoxypropyl) adenine treatment for prevention of persistent simian immunodeficiency virus SIVmne infection depends critically on timing of initiation and duration of treatment SO JOURNAL OF VIROLOGY LA English DT Article ID INFANT RHESUS MACAQUES; PROPHYLAXIS; 9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE; LENTIVIRUS; INVITRO; THERAPY; POTENT AB (R)-9-(2-Phosphonylmethoxypropyl) adenine (PMPA), an acyclic nucleoside phosphonate analog, is one of a new class of potent antiretroviral agents. Previously, we showed that PMPA treatment for 28 days prevented establishment of persistent simian immunodeficiency virus (SIV) infection in macaques even when therapy was initiated 24 h after intravenous virus inoculation. In the present study, we tested regimens involving different intervals between intravenous inoculation with SIV and initiation of PMPA treatment, as well as different durations of treatment, for the ability to prevent establishment of persistent infection. Twenty-four cynomolgus macaques (Macaca fascicularis) were studied for 46 weeks after inoculation with SIV, All mock-treated control macaques showed evidence of productive infection within 2 weeks postinoculation (p.i.). All macaques that were treated with PMPA for 28 days beginning 24 h p.i. showed no evidence of viral replication following discontinuation of PMPA treatment. However, extending the time to initiation of treatment from 24 to 48 or 72 h p.i. or decreasing the duration of treatment reduced effectiveness in preventing establishment of persistent infection. Only half of the macaques treated for 10 days, and none of those treated for 3 days, were completely protected when treatment was initiated at 24 h. Despite the reduced efficacy of delayed and shortened treatment, all PMPA-treated macaques that were not protected showed delays in the onset of cell-associated and plasma viremia and antibody responses compared with mock controls. These results clearly show that both the time between virus exposure and initiation of PMPA treatment as well as the duration of treatment are crucial factors for prevention of acute SIV infection in the macaque model. C1 Univ Washington, Reg Primate Res Ctr, Seattle, WA 98195 USA. NCI, Viral Carcinogenesis Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Lab Retroviral Pathogenesis, AIDS Vaccine Program, SAIC Frederick,FCRDC, Frederick, MD 21702 USA. Gilead Sci Inc, Foster City, CA 94404 USA. RP Tsai, CC (reprint author), Pacific Med Ctr, UW Res Lab, 11th Floor,1200 12th Ave S, Seattle, WA 98144 USA. EM cctsai@bart.rprc.washington.edu FU NCRR NIH HHS [P51 RR000166, RR00166]; NIAID NIH HHS [N01-AI-15120, N01-AI-65311] NR 34 TC 214 Z9 220 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1998 VL 72 IS 5 BP 4265 EP 4273 PG 9 WC Virology SC Virology GA ZH268 UT WOS:000073090100089 PM 9557716 ER PT J AU Mulloy, JC Migone, TS Ross, TM Ton, N Green, PL Leonard, WJ Franchini, G AF Mulloy, JC Migone, TS Ross, TM Ton, N Green, PL Leonard, WJ Franchini, G TI Human and simian T-Cell leukemia viruses type 2 (HTLV-2 and STLV-2(pan-p)) transform T cells independently of Jak/STAT activation SO JOURNAL OF VIROLOGY LA English DT Article ID RECEPTOR-BETA-CHAIN; JAK-3 JANUS KINASE; CONSTITUTIVE ACTIVATION; IL-2 RECEPTOR; STAT PROTEINS; TYROSINE PHOSPHORYLATION; CYTOPLASMIC DOMAINS; LYMPHOTROPIC VIRUS; MYELOID CELLS; INTERLEUKIN-2 AB Human T-lymphotropic virus type 1 (HTLV-1) and HTLV-2 differ in pathogenicity in vivo. HTLV-1 causes leukemia and neurologic and inflammatory diseases, whereas HTLV-2 is less clearly associated with human disease. Both retroviruses transform human T cells in vitro, and transformation by HTLV-1 was found to be associated with the constitutive activation of the Jak/STAT pathway. To assess whether HTLV-2 transformation may also result in constitutive activation of the Jak/STAT pathway, six interleukin-2-independent, HTLV-2-transformed T-cell lines were analyzed for the presence of activated Jak and STAT proteins by electrophoretic mobility shift assay. In addition, the phosphorylation status of Jak and STAT proteins was assessed directly by immunoprecipitation and immunoblotting with an antiphosphotyrosine antibody. Jak/STAT proteins were not found to be constitutively activated in any of the T-cell lines infected by the type 2 human and nonhuman primate viruses, suggesting that HTLV-2 and the cognate virus simian T-lymphotropic virus type 2 from Pan paniscus transform T cells in vitro by mechanisms at least partially different from those used by HTLV-1. C1 NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Mol Immunol, Bethesda, MD 20892 USA. Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37212 USA. RP Mulloy, JC (reprint author), NCI, Basic Res Lab, NIH, Bldg 37,Room 6A09,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA59581] NR 41 TC 33 Z9 33 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 MAY PY 1998 VL 72 IS 5 BP 4408 EP 4412 PG 5 WC Virology SC Virology GA ZH268 UT WOS:000073090100105 PM 9557732 ER PT J AU Whitehead, SS Juhasz, K Firestone, CY Collins, PL Murphy, BR AF Whitehead, SS Juhasz, K Firestone, CY Collins, PL Murphy, BR TI Recombinant respiratory syncytial virus (RSV) bearing a set of mutations from cold-passaged RSV is attenuated in chimpanzees SO JOURNAL OF VIROLOGY LA English DT Article ID SERONEGATIVE CHIMPANZEES; MESSENGER-RNA; VACCINE; TRANSCRIPTION; DETERMINANTS; PHENOTYPE; MUTANTS; PROTEIN; GENES; TS AB A set of five missense mutations previously identified by nucleotide sequence analysis of subgroup A cold-passaged (cp) respiratory syncytial virus (RSV) has been introduced into a recombinant wild-type strain of RSV. This recombinant virus, designated rA2cp, appears to replicate less efficiently in the upper and lower respiratory tracts of seronegative chimpanzees than either biologically derived or recombinant wild-type RSV. Infection with rA2cp also resulted in significantly less rhinorrhea and cough than infection with wild-type RSV. These findings confirm the role of the cp mutations in attenuation of RSV and identify their usefulness for inclusion in future live attenuated recombinant RSV vaccine candidates. C1 NIAID, Infect Dis Lab, Resp Viruses Sect, Bethesda, MD 20892 USA. RP Whitehead, SS (reprint author), NIAID, Infect Dis Lab, Resp Viruses Sect, 7 Ctr Dr,MSC 0720, Bethesda, MD 20892 USA. FU NIAID NIH HHS [AI-000030, AI-000087] NR 26 TC 63 Z9 74 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 MAY PY 1998 VL 72 IS 5 BP 4467 EP 4471 PG 5 WC Virology SC Virology GA ZH268 UT WOS:000073090100116 PM 9557743 ER PT J AU Bazan, HA Alkhatib, G Broder, CC Berger, EA AF Bazan, HA Alkhatib, G Broder, CC Berger, EA TI Patterns of CCR5, CXCR4, and CCR3 usage by envelope glycoproteins from human immunodeficiency virus type 1 primary isolates SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL LINES; MOLECULAR-CLONING; PRIMARY MACROPHAGES; VACCINIA VIRUS; HIV-1 ENTRY; FUSION COFACTORS; FOREIGN GENES; RECEPTOR; INFECTION; REPLICATION AB Coreceptor usage by Envs from diverse primary human immunodeficiency virus type 1 isolates was analyzed by a vaccinia virus-based expression and assay system. Usage of recombinant CCR5 and CXCR4 correlated closely with fusogenicity toward macrophages and T-cell lines expressing endogenous coreceptors. Surprisingly, recombinant CCR3 was utilized by most primary and T-cell-line-adapted Envs. Endogenous CXCR4 in macrophages was functional as a coreceptor. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Microbiol, Bethesda, MD 20814 USA. RP Berger, EA (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 4,Room 236, Bethesda, MD 20892 USA. EM edward_berger@nih.gov RI Bazan, Hernan/D-4923-2011 NR 53 TC 73 Z9 76 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 MAY PY 1998 VL 72 IS 5 BP 4485 EP 4491 PG 7 WC Virology SC Virology GA ZH268 UT WOS:000073090100119 PM 9557746 ER PT J AU O'Connor, KG Tobin, JD Harman, SM Plato, CC Roy, TA Sherman, SS Blackman, MR AF O'Connor, KG Tobin, JD Harman, SM Plato, CC Roy, TA Sherman, SS Blackman, MR TI Serum levels of insulin-like growth factor-I are related to age and not to body composition in healthy women and men SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID BONE-MINERAL DENSITY; CLINICAL RESEARCH-CENTER; FACTOR-BINDING-PROTEIN; POSTMENOPAUSAL WOMEN; ELDERLY WOMEN; IGF-I; TRANSDERMAL ESTROGEN; FAT DISTRIBUTION; SOMATOMEDIN-C; NORMAL ADULTS AB Background. Aging is accompanied by decreased bone and lean body mass, increased fat mass, and reduced growth hormone (GH) axis function, reflected in diminished levels of insulin-like growth factor-I (IGF-I). Similar changes in body composition occur in nonelderly, GH-deficient adults and are reversible with GH administration, suggesting that diminished GH/IGF-I axis activity may contribute to such age-related changes. To determine the precise pattern of IGF-I decline with age, and to test the hypothesis that this decline is related to concomitant changes in body composition and bone metabolism independent of age, we conducted a cross-sectional survey in 351 healthy participants in the Baltimore Longitudinal Study of Aging. Methods. We evaluated relationships among IGF-I, age, and total and regional adiposity, as assessed by body mass index (BMI) and waist-to-hip ratio (WHR); lean body mass, as estimated from urinary creatinine excretion (Crex/ht); bone mineral density (BMD), as assessed by single and dual photon absorptiometry scanning; and circulating levels of parathyroid hormone (PTH), 1,25-(OH)(2) D-3, 25-OHD, and osteocalcin. Results. Serum ICF-I levels declined with age (p < .0001) in both men (r = -.51) and women (r = -.67). Ln men, the decline was Linear, whereas IGF-I levels decreased faster in women < 45 years of age than in older women (p < .01) or in men (p < .001). IGF-I was inversely related to BMI (p < .005), WHR (p < .001), and PTH (p < .01) in women. IGF-I was positively related to BMD of the hip and radius in both genders (p < .0003) and to Crex/ht (p < .0005) and osteocalcin (p < .0001) in men. With increasing age, Crex/ht and BMD decreased (p < .0001) and WHR, PTH, and osteocalcin increased (p < .005) in both genders, whereas BMI increased only in women (p < .005). After adjustment for age, IGF-I was not significantly related to BMI, WHR, Crex/ht, or BMD in either gender. IGF-I was positively related to 1,25-(OH)(2) D-3 (p < .01) independently of age in women. Conclusions. Advancing age, rather than declining serum levels of IGF-I, appears to be a major determinant of lifetime changes in body composition and BMD in women and men. C1 Johns Hopkins Bayview Med Ctr, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21224 USA. Johns Hopkins Bayview Med Ctr, Div Endocrinol & Metab, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NIA, Gerontol Res Ctr, Endocrine Sect, NIH, Baltimore, MD 21224 USA. NIA, Gerontol Res Ctr, Appl Physiol Sect, NIH, Baltimore, MD 21224 USA. RP Blackman, MR (reprint author), Johns Hopkins Bayview Med Ctr, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21224 USA. NR 43 TC 69 Z9 70 U1 1 U2 2 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 1998 VL 53 IS 3 BP M176 EP M182 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA ZM037 UT WOS:000073498400012 PM 9597048 ER PT J AU Visser, M Harris, TB Langlois, J Hannan, MT Roubenoff, R Felson, DT Wilson, PWF Kiel, DP AF Visser, M Harris, TB Langlois, J Hannan, MT Roubenoff, R Felson, DT Wilson, PWF Kiel, DP TI Body fat and skeletal muscle mass in relation to physical disability in very old men and women of the Framingham Heart Study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID X-RAY ABSORPTIOMETRY; NURSING-HOME ADMISSION; ELDERLY PEOPLE; RISK-FACTORS; WEIGHT-LOSS; NHANES-I; STRENGTH; MORTALITY; PERFORMANCE; PREDICTORS AB Background. Low muscle mass has been assumed to be associated with disability, but no studies confirming this association have been published. High body weight and high body mass index, both rough indicators of body fatness, have been shown to increase the risk for disability: however, the specific role of body fatness has not been studied. Methods. The relations of skeletal muscle mass and percent body fat with self-reported physical disability were studied in 753 men and women aged 72 to 95 years. Cross-sectional data from biennial examination 22 (1992-1993) of the Framingham Heart Study were used. Body composition was assessed by dual-energy x-ray absorptiometry. Disability was scored as any versus none on a 9-item questionnaire. Results. Total body and lower extremity muscle mass were not associated with disability in either men or women. However, a strong positive association between percent body fat and disability was observed. The odds ratio for disability in those in the highest tertile of body fatness was 2.69 (95% confidence interval 1.45-5.00) for women and 3.08 (1.22-7.81) for men compared to those in the lowest tertile. The increased risk could not be explained by age, education, physical activity, smoking, alcohol use, estrogen use (women only), muscle mass, and health status. Analyses restricting disability to mobility items gave similar results. Conclusions. In contrast to current assumptions, low skeletal muscle mass was not associated with self-reported physical disability. Persons with a high percent body fat had high levels of disability. Because it cannot be ruled out that persons with low skeletal muscle mass dropped out earlier in the study, prospective studies are needed to further assess the relationship between body composition and physical disability. C1 NIA, Epidemiol Demogr & Biometr Program, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Hebrew Rehabil Ctr Aged, Res & Training Inst, Boston, MA 02115 USA. Tufts Univ, Sch Med, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Boston Univ, Sch Med, Ctr Arthritis, Boston, MA 02118 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Harvard Univ, Sch Med, Div Aging, Boston, MA 02115 USA. RP Visser, M (reprint author), NIA, Epidemiol Demogr & Biometr Program, Bethesda, MD 20892 USA. NR 47 TC 149 Z9 150 U1 1 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 1998 VL 53 IS 3 BP M214 EP M221 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA ZM037 UT WOS:000073498400018 PM 9597054 ER PT J AU Leveille, SG Guralnik, JM Ferrucci, L Corti, MC Kasper, J Fried, LP AF Leveille, SG Guralnik, JM Ferrucci, L Corti, MC Kasper, J Fried, LP TI Black/white differences in the relationship between MMSE scores and disability: The women's health and aging study SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article ID MINI-MENTAL-STATE; COGNITIVE IMPAIRMENT; PHYSICAL-DISABILITY; COMMUNITY RESIDENTS; EXAM SCORES; EDUCATION; AGE; PERFORMANCE; PREDICTORS; DEMENTIA AB The purpose of this article is to examine Black/White differences among older women in the relationship between physical functional difficulties and variations in cognitive status, measured,within the low to high normal range of the Mini-Mental State Examination (MMSE). We studied 3,585 women with MMSE scores of 18 and above from a population-based random sample of 3,841 community-dwelling women aged 65 and older living in East Baltimore, Maryland. Trained interviewers administered the MMSE and obtained information on demographics, medical conditions, and functional difficulties. Prevalence of any functional difficulty was 43.3% in Whites and 48.5% in Blacks, who were 25% of the study sample. After adjusting for age and education, a significant trend for increasing functional difficulty with decreasing MMSE scores was found in White women but not in Black women. Since no explanation for these racial differences could be identified, these findings suggest that the MMSE may not be a valid predictor of functional difficulty in Black women who score greater than or equal to 18 on the instrument. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Hosp I Fraticini, Dept Geriatr, INRCA, Florence, Italy. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Leveille, SG (reprint author), NIA, Epidemiol Demog & Biometry Program, 7201 Wisconsin Ave,Suite 3C-309, Bethesda, MD 20892 USA. NR 32 TC 20 Z9 20 U1 3 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD MAY PY 1998 VL 53 IS 3 BP P201 EP P208 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA ZM872 UT WOS:000073584800006 PM 9602835 ER PT J AU Jylha, M Guralnik, JM Ferrucci, L Jokela, J Heikkinen, E AF Jylha, M Guralnik, JM Ferrucci, L Jokela, J Heikkinen, E TI Is self-rated health comparable across cultures and genders? SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article ID PERCEIVED HEALTH; FOLLOW-UP; MORTALITY; POPULATION; RATINGS; ADULTS; WOMEN; MEN AB Self-rated health is a frequently used health indicator, but there is little data on its comparability across cultures. Ne employed samples from Tampere, Finland, and Florence, Italy, of the European Longitudinal Study on Aging to examine the cultural and gender differences in self-rated health;lr. Personal interview data was used and vital status ascertained after 7 years. After adjusting for several health-related variables, we found no substantial difference in self-rated health between genders, although women in Florence were three times and melt in Florence four limes more likely to report good self-rated health than men in Tampere. The correlational structure of self-rated health was similar bl befit areas. The significant graded association between self-rated health and mortality ill both areas was mostly explained by other health indicators included in a multivariate model. Results suggest that self-rated health is a useful summary of physical health but it may predict mortality better in men than in women and be sensitive to cultural environment. Therefore, direct gender and cultural comparisons of self-rated health should be made with caution. C1 Tampere Univ, Sch Publ Hlth, FIN-33101 Tampere, Finland. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. INRCA, Geriatr Dept I Fraticini, Natl Res Inst, Florence, Italy. Univ Jyvaskyla, Dept Hlth Sci, Jyvaskyla, Finland. Univ Jyvaskyla, Ctr Interdisciplinary Gerontol, Jyvaskyla, Finland. RP Jylha, M (reprint author), Tampere Sch Publ Hlth, POB 607, FIN-33101 Tampere, Finland. NR 39 TC 165 Z9 167 U1 2 U2 11 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD MAY PY 1998 VL 53 IS 3 BP S144 EP S152 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA ZM872 UT WOS:000073584800010 PM 9602839 ER PT J AU Fernandez-Llama, P Andrews, P Nielsen, S Ecelbarger, CA Knepper, MA AF Fernandez-Llama, P Andrews, P Nielsen, S Ecelbarger, CA Knepper, MA TI Impaired aquaporin and urea transporter expression in rats with adriamycin-induced nephrotic syndrome SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the American-Society-of-Nephrology CY NOV 02-06, 1997 CL SAN ANTONIO, TEXAS SP Amer Soc Nephrol DE collecting duct; water permeability; vasopressin; water channels ID WATER CHANNEL EXPRESSION; INDUCED DOWN-REGULATION; COLLECTING DUCT; ADENYLYL CYCLASES; KIDNEY MEDULLA; VASOPRESSIN; LOCALIZATION AB Nephrotic syndrome is associated with abnormal regulation of renal water excretion. To investigate the role of collecting duct watts channels and solute transporters in this process, we have carried out semiquantitative immunoblotting of kidney tissues from rats dth adriamycin-induced nephrotic syndrome. These experiments demonstrated that adriamycin-induced nephrotic syndrome is associated with marked decreases in expression of aquaporin-2, aquaporin-3, aquaporin-4, and the vasopressin-regulated urea transporter in renal inner medulla, indicative of a suppression of the capacity for water and urea absorption by the inner medullary collecting duct. In contrast, expression of the alpha(1)-subunit of the Na,K-ATPase in the inner medulla was unaltered. Light and electron microscopy of perfusion-fixed kidneys demonstrated that the collecting ducts are morphologically normal and unobstructed. Inner medullary; expression of the descending limb water channel, aquaporin-1. was not significantly altered, pointing to a selective effect on the collecting duel. Aquaporin-2 and aquaporin-3 expression was also markedly diminished in the renal cortex, indicating that the effect is nut limited tu the inner medullary collecting duct. Differential centrifugation studies and immunocytochemistry in inner medullary thin sections demonstrated increased targeting of aquaporin-2 to the plasma membrane, consistent with the expected short-term action of vasopressin an aquaporin-2 trafficking. The extensive down-regulation of aquaporin and urea transporter expression may represent an appropriate renal response to the extracellular volume expansion observed in nephrotic syndrome, but may occur at the expense of decreased urinary concentrating and diluting capacity. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Sch Med, Dept Cell Biol, Washington, DC USA. Univ Aarhus, Inst Anat, Dept Cell Biol, Aarhus, Denmark. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bldg 10,Room 6N260,10 Ctr Dr,MSC 1603, Bethesda, MD 20892 USA. NR 34 TC 55 Z9 55 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 1998 VL 53 IS 5 BP 1244 EP 1253 DI 10.1046/j.1523-1755.1998.00878.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA ZH989 UT WOS:000073168500016 PM 9573539 ER PT J AU Tritten, JJ Haefliger, JM Delouche, D Bovey, E Chan, CC Guex-Crosier, Y Herbort, CP AF Tritten, JJ Haefliger, JM Delouche, D Bovey, E Chan, CC Guex-Crosier, Y Herbort, CP TI Interleukin-10 found in the vitreous, in uveitis associated to cerebral lymphom SO KLINISCHE MONATSBLATTER FUR AUGENHEILKUNDE LA German DT Article; Proceedings Paper CT 90th Annual Congress of the Schweizerischen-Ophthalmologischen-Gesellschaft (SOG/SSO) CY SEP 10-13, 1997 CL LUGANO, SWITZERLAND SP Schweizer Ophthalmolog Gesell DE interleukin-10; vitritis; cerebral lymphoma AB The authors report on a 36 year-old patient who presented with a chronic unilateral vitritis. A diagnosis of cerebral lymphoma was made 4 years earlier and a maxillary sinus recurrence was treated with chemotherapy and radiotherapy. A vitrectomy was performed and the level of Interleukin-10, a lymphoma cells growth factor, was found very high, giving a clue for the lymphomatous cause of the vitritis. C1 Hop Ville, Serv Ophtalmol, CH-2300 La Chaux De Fonds, Switzerland. Hop Jules Gonin, Lausanne, Switzerland. NEI, Bethesda, MD 20892 USA. RP Tritten, JJ (reprint author), Hop Ville, Serv Ophtalmol, Chasseral 20, CH-2300 La Chaux De Fonds, Switzerland. NR 3 TC 3 Z9 3 U1 0 U2 0 PU FERDINAND ENKE VERLAG PI STUTTGART PA POSTFACH 30 03 66, D-70443 STUTTGART, GERMANY SN 0023-2165 J9 KLIN MONATSBL AUGENH JI Klinische Monatsblat. Augenheilkunde PD MAY PY 1998 VL 212 IS 5 BP 416 EP 417 DI 10.1055/s-2008-1034924 PG 2 WC Ophthalmology SC Ophthalmology GA ZV562 UT WOS:000074317500054 PM 9677597 ER PT J AU Groll, AH Muller, FMC AF Groll, AH Muller, FMC TI Advances in prevention and treatment of infectious complications in children and adolescents with cancer SO KLINISCHE PADIATRIE LA German DT Article DE infections; cancer; treatment; prevention; neutropenia; mycoses ID NEUTROPENIC PATIENTS; EMPIRIC TREATMENT; RANDOMIZED TRIAL; FEVER; CEFTAZIDIME; THERAPY; VANCOMYCIN; EPIDEMIOLOGY; BACTEREMIA; MANAGEMENT AB Due to the high dose-intensity of most current treatment protocols, the growing number of marrow transplantations, the routine use of aggressive supportive care and certain pathogen-related problems, infections remain an important cause for morbidity and mortality in children and adolescents with cancer. Over the last decade, however, considerable progress has been made in diagnosis, prevention and treatment of infectious complications in the immunocompromised host. This article first delineates both clinical approach and current treatment strategies in the pediatric cancer patient presenting with neutropenia and fever of unknown origin. It then reviews diagnosis and treatment of the most common specific infections and concludes with a discussion of preventive measures in the setting of anticancer treatment. C1 NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bethesda, MD 20892 USA. RP Groll, AH (reprint author), NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bldg 10,Rm 13N240,10 Ctr Dr, Bethesda, MD 20892 USA. NR 34 TC 6 Z9 6 U1 0 U2 0 PU FERDINAND ENKE VERLAG PI STUTTGART PA POSTFACH 30 03 66, D-70443 STUTTGART, GERMANY SN 0300-8630 J9 KLIN PADIATR JI Klinische Padiatr. PD MAY-JUN PY 1998 VL 210 IS 3 BP 106 EP 114 DI 10.1055/s-2008-1043860 PG 9 WC Pediatrics SC Pediatrics GA ZN832 UT WOS:000073687100003 PM 9629543 ER PT J AU Matsukawa, A Yoshimura, T Maeda, T Takahashi, T Ohkawara, S Yoshinaga, M AF Matsukawa, A Yoshimura, T Maeda, T Takahashi, T Ohkawara, S Yoshinaga, M TI Analysis of the cytokine network among tumor necrosis factor alpha, interleukin-1 beta, interleukin-8, and interleukin-1 receptor antagonist in monosodium urate crystal-induced rabbit arthritis SO LABORATORY INVESTIGATION LA English DT Article ID LIPOPOLYSACCHARIDE-INDUCED ARTHRITIS; IL-1; INFLAMMATION; MEDIATOR; CELLS; PURIFICATION; ACTIVATION; KINETICS; ANTIBODY; DISEASE AB In the present study, we analyzed the cytokine network among TNF alpha, IL-1 beta, IL-8, and IL-1 receptor antagonist (IL-1Ra) in a rabbit experimental model of acute gout. The production of TNF alpha in synovial fluids reached the peak at 2 hours after the intra-articular injection of monosodium urate (MSU) crystals. The production of IL-1 beta and IL-8 reached the first peak at 2 hours and the second peak at 9 and 12 hours, respectively. The production of endogenous IL-1Ra reached the peak at 9 hours. The source of TNF alpha and the first phase of IL-8 was synovial cells, whereas infiltrating leukocytes were the source of the second phase of IL-8 and also of IL-1 beta and IL-1Ra. The production of TNF alpha was not altered by either anti-IL-8 IgG or IL-1Ra. The first IL-1 beta peak was reduced only with a combination of anti-TNF alpha mAb and anti-IL-8 IgG, whereas the second peak was significantly reduced by either inhibitor. The first IL-8 peak was not altered with anti-TNF alpha mAb or IL-1Ra, whereas the second IL-8 peak was reduced with IL-1Ra. Anti-TNF alpha mAb or anti-IL-8 IgG significantly reduced the peak level of endogenous IL-1Ra. These cytokine inhibitors also attenuated the maximal leukocyte accumulation at 9 hours, but not the initial phase, which occurred within 2 hours. These results provide evidence that IL-8 and TNF alpha were responsible for the production of IL-1 beta and IL-1Ra, and that IL-1 beta was responsible for the second phase of IL-1 beta and IL-8 production. Our data also suggest that the initial and the maximal phases of leukocyte influx are differently regulated. Finally, the intravenous injection of colchicine inhibited neutrophil infiltration without affecting the production of TNF alpha or the first peak of IL-8, suggesting that colchicine inhibits MSU crystal-induced arthritis by directly inhibiting the migration of neutrophils. C1 Kumamoto Univ, Sch Med, Dept Pathol, Kumamoto 860, Japan. NCI, Immunopathol Sect, Immunol Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Matsukawa, A (reprint author), Kumamoto Univ, Sch Med, Dept Pathol, 2-2-1 Honjo, Kumamoto 860, Japan. NR 39 TC 53 Z9 61 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAY PY 1998 VL 78 IS 5 BP 559 EP 569 PG 11 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA ZP326 UT WOS:000073741100006 PM 9605181 ER PT J AU Emanuel, EJ Emanuel, LL AF Emanuel, EJ Emanuel, LL TI The promise of a good death SO LANCET LA English DT Article ID PHYSICIAN-ASSISTED SUICIDE; OF-LIFE QUESTIONNAIRE; ADVANCE DIRECTIVES; TERMINAL CARE; CANCER PAIN; EUTHANASIA; ATTITUDES; ILLNESS; HOSPICE; NEEDS C1 NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Amer Med Assoc, Div Eth Stand, Chicago, IL 60610 USA. RP Emanuel, EJ (reprint author), NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bldg 10 Room 1C118, Bethesda, MD 20892 USA. EM eemanuel@nih.gov NR 60 TC 203 Z9 207 U1 3 U2 15 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAY PY 1998 VL 351 SU 2 BP 21 EP 29 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA ZP168 UT WOS:000073724100005 ER PT J AU Rozemuller, H Rombouts, EJC Touw, IP FitzGerald, DJP Kreitman, RJ Hagenbeek, A Martens, ACM AF Rozemuller, H Rombouts, EJC Touw, IP FitzGerald, DJP Kreitman, RJ Hagenbeek, A Martens, ACM TI In vivo targeting of leukemic cells using diphtheria toxin fused to murine GM-CSF SO LEUKEMIA LA English DT Article DE diphtheria toxin mGM-CSF fusion protein; GM-CSF receptor; BNML/LT12; leukemia model ID COLONY-STIMULATING FACTOR; ACUTE MYELOCYTIC-LEUKEMIA; NONHEMATOPOIETIC TUMOR-CELLS; HEMATOPOIETIC STEM-CELLS; RAT BONE-MARROW; PSEUDOMONAS EXOTOXIN; GRANULOCYTE-COLONY; ENDOTHELIAL-CELLS; FACTOR RECEPTORS; FUSION PROTEIN AB We have previously demonstrated that diphtheria toxin (DT) fused to human GM-CSF effectively eliminates human longterm leukemia initiating cells in SCID mice. However, because huGM-CSF does not react with the murine GM-CSF receptor possible side-effects to nonleukemic tissues could not be ana analyzed in the AML/SCID model. To overcome this problem, we used murine GM-CSF fused to DT and studied the therapeutic index in the rat leukemia model BNML/LT12. In DT-mGM-CSF dose escalation experiments, severe dose-dependent toxicity to organs such as liver, kidney and lung was observed. Therefore, the antileukemic effects were evaluated with the lower doses. Daily intraperitoneal bolus injections of 75 mu g/kg/day for 7 days induced a 3 log leukemic cell kill. The dose of 75 mu g/kg/day had no effect on the hemopoietic progenitor cell subsets. These in vivo studies show that the DT-GM-CSF fusion protein can be used for specifically targeting leukemic cells and thus has potential as a therapeutic agent in the treatment of AML. C1 Erasmus Univ, Inst Hematol, Rotterdam, Netherlands. Dr Daniel Den Hoed Canc Ctr, NL-3008 AE Rotterdam, Netherlands. NCI, Mol Biol Lab, DCBDC, Bethesda, MD 20892 USA. RP Martens, ACM (reprint author), Univ Utrecht Hosp, Dept Haematol, POB 85500,Room G03-647, NL-3508 GA Utrecht, Netherlands. NR 51 TC 4 Z9 4 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 1998 VL 12 IS 5 BP 710 EP 717 DI 10.1038/sj.leu.2400990 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA ZM558 UT WOS:000073552200011 PM 9593269 ER PT J AU Qi, CF Chattopadhyay, SK Lander, M Kim, Y Fredrickson, TN Hartley, JW Morse, HC AF Qi, CF Chattopadhyay, SK Lander, M Kim, Y Fredrickson, TN Hartley, JW Morse, HC TI Expression of cyclin D1 in mouse B cell lymphomas of different histologic types and differentiation stages SO LEUKEMIA RESEARCH LA English DT Article DE B cell lymphoma; Bcl-1; cyclin D1; PCNA ID MURINE LEUKEMIA-VIRUS; CENTROCYTIC LYMPHOMA; PUTATIVE ONCOGENE; PRAD1/CYCLIN D1; SQUAMOUS-CELL; GENE; OVEREXPRESSION; CANCER; FIBROBLASTS; PROGRESSION AB The G1 cyclin, cyclin D1, has been implicated in the development of human and mouse tumors. Here we describe immunohistochemical analyses of cyclin D1 for a large panel of mouse B cell tumors. In addition, we characterize cyclin D1 expression in a series of cultured cell lines that represent transformed B cells at different stages of development. Immunohistochemical analysis showed that for low-grade lymphomas, cyclin D1 was expressed by 83% of centroblastic-centrocytic (CBCC) and 14% of small lymphocytic lymphomas (SLL). For high-grade tumors, 28% of B lymphoblastic and 23% of centroblastic tumors expressed cyclin D1, while all immunoblastic lymphomas were negative. Studies of RNA and protein prepared from cultured B lineage tumors showed that cyclin D1 was expressed by all pre-B and most B cell tumors but not by cell lines representative of late B cell differentiation or by plasma cells. Expression of cyclin D1 in the lymphomas was not associated with alterations in the genomic structure of the Fis-1 (Bcl-1) common proviral integration site or cyclin D1 itself or with cell growth activity as assessed by expression of proliferating cell nuclear antigen (PCNA). (C) 1998 Published by Elsevier Science Ltd. C1 NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Registry Expt Canc, NIH, Bethesda, MD 20892 USA. RP Qi, CF (reprint author), NIAID, Immunopathol Lab, NIH, 7 Ctr Dr, Bethesda, MD 20892 USA. OI Morse, Herbert/0000-0002-9331-3705 FU NIAID NIH HHS [N01-AI-45203] NR 37 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD MAY PY 1998 VL 22 IS 5 BP 395 EP 404 DI 10.1016/S0145-2126(97)00189-6 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA ZU635 UT WOS:000074217800002 PM 9652725 ER PT J AU Cheson, BD AF Cheson, BD TI Standard and low-dose chemotherapy for the treatment of myelodysplastic syndromes SO LEUKEMIA RESEARCH LA English DT Article DE myelodysplastic syndromes; cytarabine; 5-azacytidine; topotecan ID CHRONIC MYELOMONOCYTIC LEUKEMIA; TOPOISOMERASE-I-INHIBITOR; ARABINOSIDE ARA-C; ACUTE NONLYMPHOBLASTIC LEUKEMIA; ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; REFRACTORY ACUTE-LEUKEMIA; CYTOSINE-ARABINOSIDE; PHASE-I; PRELEUKEMIC SYNDROMES AB The myelodysplastic syndromes (MDS) are a heterogeneous group of disorders with an invariably fatal outcome. Other than bone marrow transplantation, no treatment has been able to alter the natural history of MDS. As a result, there has been an interest in identifying new and more effective chemotherapeutic agents. Many of the drugs that have been evaluated in an attempt to increase remissions and prolong survival were selected because of their activity in acute myeloid leukemia. Thus cytarabine has been the most widely studied drug. Although numerous studies suggested activity for low-dose cytarabine (LoDAC), a careful analysis of the data identified a complete remission (CR) rate of less than 20%, without meaningful clinical benefit. The issue of LoDAC was finally put to rest by a randomized trial in which survival was no better than with supportive care. 5-Azacytidine induces cellular differentiation by hypomethylation of DNA. Phase II trials noted CRs in fewer than 10% of patients, with response rates under 30%, although additional patients appeared to experience hematologic and clinical benefit. A randomized trial of 5-azacytidine versus supportive care failed to demonstrate a survival benefit. One of the most promising new agents is the topoisomerase inhibitor topotecan, which achieves CRs in more than 30% of patients. Combinations of this drug with other active agents are in development. Obviously, new treatment strategies are needed to improve the outcome of MDS patients. Combination approaches incorporating new, active agents should have sound scientific rationale, targeting biological differences among the various MDS subtypes. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NCI, Med Sect, Clin Invest Branch,Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20852 USA. RP Cheson, BD (reprint author), NCI, Med Sect, Clin Invest Branch,Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Execut Plaza N,Room 741, Bethesda, MD 20852 USA. NR 49 TC 21 Z9 23 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD MAY PY 1998 VL 22 SU 1 BP S17 EP S21 DI 10.1016/S0145-2126(98)00039-3 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 116MA UT WOS:000075727800005 PM 9734695 ER PT J AU Virta, A Komu, M Lundbom, N Jaaskelainen, S Kalimo, H Airio, A Alanen, A Kormano, M AF Virta, A Komu, M Lundbom, N Jaaskelainen, S Kalimo, H Airio, A Alanen, A Kormano, M TI Low field T(1)p imaging of myositis SO MAGNETIC RESONANCE IMAGING LA English DT Article DE myositis; muscle; spin-lock; T-1p ID MAGNETIC-RESONANCE; MUSCLE; RELAXATION; DERMATOMYOSITIS; TISSUE; WATER; POLYMYOSITIS; RELAXOMETRY; DISPERSION; DYSTROPHY AB The purpose of this study was to evaluate 1/T(1)p in relation to 1/T-1 and 1/T-2 in characterizing normal and diseased muscle. We measured the muscle relaxation rates 1/T-1 and 1/T-2 at 0.1 T and 1/T(1)p at on-resonance locking fields B-1 between 10 and 160 mu T in myositis patients and normal volunteers. 1/T-2 and 1/T(1)p of muscle were lower in the patients than in the volunteers, whereas there was no difference in the 1/T-1 values. The lower relaxation rates 1/T-2 and 1/T(1)p in the diseased muscle may be due to fat and connective tissue infiltrations and edema. 1/T(1)p contrast between muscle and subcutaneous fat was higher than 1/T-2 and 1/T-1 contrast. This may be explained by the different B-1 dispersion behavior of these two tissue types. 1/T(1)p of fat is B-1 field independent, whereas 1/T(1)p of muscle decreases clearly with increasing B-1 field. In conclusion, 1/T(1)p provides a useful tool in manipulating contrast in magnetic resonance imaging of diseased muscle. (C) 1998 Elsevier Science Inc. C1 Univ Turku, Dept Diagnost Radiol, SF-20500 Turku, Finland. Univ Turku, Dept Pathol, SF-20500 Turku, Finland. RP Virta, A (reprint author), NINDS, Neuroimaging Branch, NIH, Bldg 10,Rm 5N 214,10 Ctr Dr, Bethesda, MD 20892 USA. EM anevir@codon.nih.gov NR 24 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 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD MAY PY 1998 VL 16 IS 4 BP 385 EP 391 DI 10.1016/S0730-725X(98)00004-6 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZV953 UT WOS:000074358900005 PM 9665549 ER PT J AU Chen, CN AF Chen, CN TI Generation of depth-perception information in stereoscopic nuclear magnetic resonance imaging by non-linear magnetic field gradients SO MAGNETIC RESONANCE IMAGING LA English DT Article DE stereoscopic MRI; non-linear gradient; depth perception ID DIGITAL SUBTRACTION ANGIOGRAPHY; COIL DESIGN AB Stereoscopic NMR images have been produced in the past. However, because of the gradients are linear, only isometric projections can be produced, i,e., they do not carry correct depth-perception information. The resulting stereoscopic image will not have correct relative sizes at different depths. This paper gives an analysis of what perception information is needed and shows that it can be produced by a non-linear magnetic field gradient. The concept is exemplified by simulations and its implementation is demonstrated successfully tay experiments. The depth-encoding gradient can be generated by static steel pieces or by current loops, The procedure can be incorporated into any existing hardware and pulse sequences, and has potential application in surgery. (C) 1998 Elsevier Science Inc. C1 NIH, Off Res Serv, Biomed Engn & Instrumentat Program, Bethesda, MD 20892 USA. RP Chen, CN (reprint author), NIH, Off Res Serv, Biomed Engn & Instrumentat Program, Bldg 13,Rm 3N-17, Bethesda, MD 20892 USA. EM cnchen@helix.nih.gov NR 24 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD MAY PY 1998 VL 16 IS 4 BP 405 EP 412 DI 10.1016/S0730-725X(97)00309-3 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZV953 UT WOS:000074358900007 PM 9665551 ER PT J AU Jezzard, P Barnett, AS Pierpaoli, C AF Jezzard, P Barnett, AS Pierpaoli, C TI Characterization of and correction for eddy current artifacts in echo planar diffusion imaging SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE diffusion MRI; interleaved EPI; artifacts; eddy currents; navigator echoes ID HUMAN BRAIN; NAVIGATOR ECHOES; IMAGES; COMPENSATION; ANISOTROPY; DISTORTION; STROKE; TENSOR; MOTION AB Magnetic resonance diffusion imaging is potentially an important tool for the noninvasive characterization of normal and pathological tissue. The technique, however, is prone to a number of artifacts that can severely affect its ability to provide clinically useful information. In this study, the problem of eddy current-induced geometric distortions that occur in diffusion images acquired with echo planar sequences was addressed. These geometric distortions produce artifacts in computed maps of diffusion parameters and are caused by misalignments in the individual diffusion-weighted images that comprise the diffusion data set. A new approach is presented to characterize and calibrate the eddy current effects, enabling the eddy current distortions to be corrected in sets of interleaved (or snapshot) echo planar diffusion images. Correction is achieved by acquiring one-dimensional field maps in the read and phase encode direction for each slice and each diffusion step. The method is then demonstrated through the correction of distortions in diffusion images of the human brain. It is shown that by using the eddy current correction scheme outlined, the eddy current-induced artifacts in the diffusion-weighted images are almost completely eliminated. In addition, there is a significant improvement in the quality of the resulting diffusion tensor maps. C1 NIMH, Unit MRI Phys, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. NINDS, Neuroimaging Branch, NIH, Bethesda, MD 20892 USA. RP Jezzard, P (reprint author), John Radcliffe Hosp, FMRIB Ctr, Oxford OX3 9DU, England. RI Pierpaoli, Carlo/E-1672-2011; OI Jezzard, Peter/0000-0001-7912-2251 NR 34 TC 190 Z9 194 U1 0 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD MAY PY 1998 VL 39 IS 5 BP 801 EP 812 DI 10.1002/mrm.1910390518 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZJ612 UT WOS:000073234200017 PM 9581612 ER PT J AU Yang, YH Frank, JA Hou, L Ye, FQ McLaughlin, AC Duyn, JH AF Yang, YH Frank, JA Hou, L Ye, FQ McLaughlin, AC Duyn, JH TI Multislice imaging of quantitative cerebral perfusion with pulsed arterial spin labeling SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; perfusion imaging; cerebral blood flow (CBF); arterial spin labeling ID BLOOD-FLOW; ECHO-PLANAR; INVERSION-RECOVERY; RESONANCE; WATER; F-19; FMRI AB A method is presented for multislice measurements of quantitative cerebral perfusion based on magnetic labeling of arterial spins. The method combines a pulsed arterial inversion, known as the FAIR (Flow-sensitive Alternating Inversion Recovery) experiment, with a fast spiral scan image acquisition. The short duration (22 ms) of the spiral data collection allows simultaneous measurement of up to 10 slices per labeling period, thus dramatically increasing efficiency compared to current single slice acquisition protocols. Investigation of labeling efficiency, suppression of unwanted signals from stationary as well as intraarterial spins, and the FAIR signal change as a function of inversion delay are presented, The assessment of quantitative cerebral blood flow (CBF) with the new technique is demonstrated and shown to require measurement of arterial transit time as well as suppression of intraarterial spin signals. CBF values measured on normal volunteers are consistent with results obtained from H2O15 positron emission tomography (PET) studies acid other radioactive tracer approaches. In addition, the new method allows detection of activation-related perfusion changes in a finger-tapping experiment, with locations of activation corresponding well to those observed with blood oxygen level dependent (BOLD) fMRI. C1 NIH, OIR, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. NIH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Duyn, JH (reprint author), NIH, OIR, Lab Diagnost Radiol Res, Bldg 10,Room B1N-256, Bethesda, MD 20892 USA. RI Duyn, Jozef/F-2483-2010 NR 35 TC 127 Z9 131 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD MAY PY 1998 VL 39 IS 5 BP 825 EP 832 DI 10.1002/mrm.1910390520 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZJ612 UT WOS:000073234200019 PM 9581614 ER PT J AU Peichel, CL Kozak, CA Luyten, FP Vogt, TF AF Peichel, CL Kozak, CA Luyten, FP Vogt, TF TI Evaluation of mouse Sfrp3/Frzb1 as a candidate for the lst, Ul, and Far mutants on Chromosome 2 SO MAMMALIAN GENOME LA English DT Article ID RECEPTOR; GENES; LIMB C1 Princeton Univ, Lewis Thomas Lab, Dept Mol Biol, Princeton, NJ 08544 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NIDR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP Vogt, TF (reprint author), Princeton Univ, Lewis Thomas Lab, Dept Mol Biol, Princeton, NJ 08544 USA. EM tvogt@molbio.princeton.edu FU NICHD NIH HHS [HD-30707] NR 21 TC 6 Z9 6 U1 0 U2 1 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 MAY PY 1998 VL 9 IS 5 BP 385 EP 387 DI 10.1007/s003359900775 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA ZK441 UT WOS:000073321200009 PM 9545497 ER PT J AU de Miguel, M Centanni, JM Gopalan, G Gilbert, DJ Copeland, NG Jenkins, NA Donovan, PJ AF de Miguel, M Centanni, JM Gopalan, G Gilbert, DJ Copeland, NG Jenkins, NA Donovan, PJ TI Cellular apoptosis susceptibility gene Capts maps to mouse Chromosome 2 SO MAMMALIAN GENOME LA English DT Article ID HUMAN HOMOLOG; SEGREGATION; CSE1; CAS C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. Univ Alcala de Henares, Dept Genet & Cell Biol, Alcala De Henares 28871, Madrid, Spain. RP Donovan, PJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, POB B,Bldg 539, Frederick, MD 21702 USA. NR 9 TC 0 Z9 0 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 MAY PY 1998 VL 9 IS 5 BP 411 EP 412 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA ZK441 UT WOS:000073321200018 PM 9545506 ER PT J AU Thamer, M Ray, NF Henderson, SC Rinehart, CS Sherman, CR Ferguson, JH AF Thamer, M Ray, NF Henderson, SC Rinehart, CS Sherman, CR Ferguson, JH TI Influence of the NIH consensus conference on Helicobacter pylori on physician prescribing among a Medicaid population SO MEDICAL CARE LA English DT Article DE peptic ulcer disease; H-pylori; antimicrobials; antibiotics; omeprazole; physician prescribing; Medicaid population; NIH Consensus Development Conference ID PEPTIC-ULCER DISEASE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RANDOMIZED CONTROLLED TRIAL; DUODENAL-ULCER; CAMPYLOBACTER-PYLORI; DEVELOPMENT PROGRAM; ELDERLY PERSONS; TRIPLE THERAPY; INFECTION; ERADICATION AB OBJECTIVES. In February 1994, an National Institutes of Health (NIH) Consensus Development Conference panel unequivocally recommended antimicrobial therapy to eradicate Helicobacter pylori in the treatment of peptic ulcer disease. The goal of this study was to determine if these recommendations resulted in a change in physician prescribing among an underserved population. METHODS. Computerized Pennsylvania Medicaid data from January 1993 through February 1996 were used to evaluate prescribing patterns in the year before and 2 years after the NIH conference. An interrupted time series model, based on 12,737 outpatient peptic ulcer disease encounters, assessed the impact of the conference in influencing physician prescribing. RESULTS. The prescription of antimicrobial agents for the treatment of peptic ulcer disease significantly increased across the study period, from 6.5% in January 1993 to 10.2% in February 1996. Similarly, the prescription rate for the proton pump inhibitor, omeprazole, significantly increased from 9.4% in January 1993 to 25.6% in February 1996. Neither trend, however, could be attributed to the NIH Consensus Development Conference. Stratification by physician specialty, ulcer type, nonsteroidal anti-inflammatory drug use, and patient demographics did not affect these results. The traditional treatment approach, using H-2-receptor antagonists, remained the preferred pharmacotherapy (72% of all prescriptions). CONCLUSIONS. Two years after the highly publicized NIH conference on the eradication of Helicobacter pylori, antimicrobial agents were not widely prescribed among the Pennsylvania Medicaid population. In treating this underserved population, physicians do not appear to be using recommendations developed by an NIH expert panel based on recent scientific advances. C1 Med Technol & Practice Patterns Inst MTPPI, Washington, DC 20007 USA. NIH, Off Med Applicat Res, Bethesda, MD 20892 USA. RP Thamer, M (reprint author), Med Technol & Practice Patterns Inst MTPPI, 2121 Wisconsin Ave NW,Suite 220, Washington, DC 20007 USA. EM thamer@aol.com NR 68 TC 26 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAY PY 1998 VL 36 IS 5 BP 646 EP 660 DI 10.1097/00005650-199805000-00005 PG 15 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA ZM940 UT WOS:000073591600005 PM 9596056 ER PT J AU Brody, LC Biesecker, BB AF Brody, LC Biesecker, BB TI Breast cancer susceptibility genes - BRCA1 and BRCA2 SO MEDICINE LA English DT Review ID EARLY-ONSET BREAST; ASHKENAZI-JEWISH INDIVIDUALS; RADIATION HYBRID MAP; OVARIAN-CANCER; FAMILIAL BREAST; PHYSICAL MAP; HUMAN GENOME; GERMLINE MUTATIONS; PSYCHOLOGICAL DISTRESS; POSITIONAL CLONING C1 Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Brody, LC (reprint author), Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, 49 Convent Dr,Room 3A14, Bethesda, MD 20892 USA. EM lbrody@helix.nih.gov NR 232 TC 94 Z9 97 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD MAY PY 1998 VL 77 IS 3 BP 208 EP 226 DI 10.1097/00005792-199805000-00006 PG 19 WC Medicine, General & Internal SC General & Internal Medicine GA ZV824 UT WOS:000074345000006 PM 9653432 ER PT J AU Nagi, DK Foy, CA Mohamed-Ali, V Yudkin, JS Grant, PJ Knowler, WC AF Nagi, DK Foy, CA Mohamed-Ali, V Yudkin, JS Grant, PJ Knowler, WC TI Angiotensin-1-converting enzyme (ACE) gene polymorphism, plasma ACE levels, and their association with the metabolic syndrome and electrocardiographic coronary artery disease in Pima Indians SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID ANGIOTENSIN-CONVERTING-ENZYME; HEART-DISEASE; MYOCARDIAL-INFARCTION; DIABETES-MELLITUS; INSERTION/DELETION POLYMORPHISM; DELETION POLYMORPHISM; HIGH PREVALENCE; INSULIN; HYPERTENSION; RISK AB In Caucasian subjects, an insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with coronary artery disease (CAD) and fatal myocardial infarction. The underlying mechanism(s) of this association is not fully understood. Pima Indians have a low incidence of nonfatal and fatal CAD despite a high prevalence of diabetes. In Pima Indians, circulating ACE levels are related to ACE genotype, but the frequency of the D allele is significantly lower than in Caucasians. A lower frequency of the D allele may underlie a low risk of CAD in this population. We examined the relationship of the ACE genotype and plasma ACE level with electrocardiographic evidence of CAD (Tecumseh criteria), hypertension, and metabolic variables associated with insulin resistance in 305 (146 men and 159 women aged 47 +/- 9.0 years) Pima Indians characterized for the ACE I/D genotype. The distribution of ACE genotypes was unrelated to diabetes and obesity. Easting plasma insulin, plasminogen activator inhibitor-1 (PAI-1) activity, plasma triglyceride concentrations, and systolic (SBP) and diastolic (DBP) blood pressure were not significantly different between the three ACE genotypes among nondiabetic and diabetic subjects. There was no significant association of ACE genotype with electrocardiographic evidence of CAD or with hypertension. Plasma ACE concentrations were not significantly different between nondiabetic and diabetic subjects (median, 77 [range, 21 to 169] v 83 [7 to 238] IU/mL, P = NS). In all subjects, plasma ACE levels were associated weakly with plasma triglyceride (partial r =.20, P <.01) and total cholesterol (partial r =.13, P <.03) concentrations, but not with fasting plasma insulin or PAI-1 activity. In diabetic subjects, ACE levels were related to fasting plasma glucose concentrations (partial r =.15, P =.07). These findings would suggest that ACE gene I/D polymorphism is unlikely to be a major determinant of susceptibility to CAD in Pima Indians. Plasma ACE levels, but not ACE genotype, correlated with lipids, plasma glucose, and blood pressure, suggesting that elevated plasma ACE levels may contribute to the link between insulin resistance and CAD disease or may be a consequence of it. Copyright (C) 1998 by W.B. Saunders Company. C1 Univ Leeds, Dept Med, Diabet & Thrombosis Res Grp, Leeds, W Yorkshire, England. UCL, Sch Med, Dept Med, London W1N 8AA, England. NIDDKD, NIH, Phoenix, AZ 85016 USA. RP Nagi, DK (reprint author), Pinderfields Hosp Trust, Edna Coates Ctr, Aberford Rd, Wakefield WF1 4DG, England. RI Yudkin, John/C-1988-2008 NR 18 TC 43 Z9 46 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD MAY PY 1998 VL 47 IS 5 BP 622 EP 626 DI 10.1016/S0026-0495(98)90250-5 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZM113 UT WOS:000073506000022 PM 9591757 ER PT J AU Conte, D Barber, E Banerjee, M Garfinkel, DJ Curcio, MJ AF Conte, D Barber, E Banerjee, M Garfinkel, DJ Curcio, MJ TI Posttranslational regulation of Ty1 retrotransposition by mitogen-activated protein kinase Fus3 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE GENOME; VIRUS-LIKE PARTICLES; SIGNAL-TRANSDUCTION; ELEMENT TRANSPOSITION; REVERSE-TRANSCRIPTASE; TRANSFER-RNA; CELL-CYCLE; YEAST; GENE; CASCADE AB Ty1 retrotransposons in Saccharomyces cerevisiae are maintained in a state of transpositional dormancy. We isolated a mutation, rtt100-1, that increases the transposition of genomic Ty1 elements 18- to 56-fold but has little effect on the transposition of related Ty2 elements. rtt100-1 was shown to be a null allele of the FUS3 gene, which encodes a haploid-specific mitogen-activated protein kinase. In fus3 mutants, the levels of Ty1 RNA, protein synthesis, and proteolytic processing were not altered relative to those in FUS3 strains but steady-state levels of TyA integrase, and reverse transcriptase proteins and Ty1 cDNA were all increased. These findings suggest that Fus3 suppresses Ty1 transposition by destabilizing viruslike particle-associated proteins. The Fus3 kinase is activated through the mating-pheromone response pathway by phosphorylation at basal levels in naive cells and at enhanced levels in pheromone-treated cells. We demonstrate that suppression of Ty1 transposition in naive cells requires basal levels of Fus3 activation. Substitution of conserved amino acids required for activation of Fus3 derepressed Ty1 transposition. Moreover, epistasis analyses revealed that components of the pheromone response pathway that act upstream of Fus3, including Ste4, Ste5, Ste7, and Ste11, are required for the posttranslational suppression of Ty1 transposition by Fus3. The regulation of Ty1 transposition by Fus3 provides a haploid-specific mechanism through which environmental signals can modulate the levels of retrotransposition. C1 SUNY Albany, Mol Genet Program, Wadsworth Ctr, Albany, NY 12201 USA. SUNY Albany, Sch Publ Hlth, Albany, NY 12201 USA. NCI, Chromosome Biol Lab, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Ft Detrick, MD 21702 USA. RP Curcio, MJ (reprint author), SUNY Albany, Mol Genet Program, Wadsworth Ctr, POB 22002, Albany, NY 12201 USA. EM joan.curcio@wadsworth.org OI Curcio, M. Joan/0000-0001-5361-3909 FU NIGMS NIH HHS [GM52072, R01 GM052072, R29 GM052072] NR 56 TC 42 Z9 42 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 MAY PY 1998 VL 18 IS 5 BP 2502 EP 2513 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZJ274 UT WOS:000073197600008 PM 9566871 ER PT J AU El Kharroubi, A Piras, G Zensen, R Martin, MA AF El Kharroubi, A Piras, G Zensen, R Martin, MA TI Transcriptional activation of the integrated chromatin-associated human immunodeficiency virus type 1 promoter SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RNA-POLYMERASE-II; LONG TERMINAL REPEAT; NF-KAPPA-B; PROTEIN-DNA INTERACTIONS; HIV-1 GENE-EXPRESSION; HISTONE ACETYLATION; HYPERSENSITIVE SITES; NUCLEOSOMAL TEMPLATES; MUTATIONAL ANALYSIS; LOCATED DOWNSTREAM AB The regulation of human immunodeficiency virus type 1 (HIV-1) gene expression involves a complex interplay between cellular transcription factors, chromatin-associated proviral DNA, and the virus-encoded transactivator protein, Tat. Here we show that Tat transactivates the integrated HIV-1 long terminal repeat (LTR), even in the absence of detectable basal promoter activity and this transcriptional activation is accompanied by chromatin remodelling downstream of the transcription initiation site, as monitored by increased accessibility to restriction endonucleases. However, with an integrated promoter lacking both Sp1 and NF-kappa B sites, Tat was unable to either activate transcription or induce changes in chromatin structure even when it was tethered to the HIV-1 core promoter upstream of the TATA box. Tat responsiveness was observed only when Sp1 or NF-kappa B was bound to the promoter, implying that Tat functions subsequent to the formation of a specific transcription initiation complex. Unlike Tat, NF-kappa B failed to stimulate the integrated transcriptionally silent HIV-1 promoter. Histone acetylation renders the inactive HIV-1 LTR responsive to NF-kappa B, indicating that a suppressive chromatin structure must be remodelled prior to transcriptional activation by NF-kappa B. Taken together, these results suggest that Sp1 and NF-kappa B are required for the assembly of transcriptional complexes on the integrated viral promoter exhibiting a continuum of basal activities, all of which are fully responsive to Tat. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Martin, MA (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Room 315,4 Ctr Dr, Bethesda, MD 20892 USA. EM maln@nih.gov NR 63 TC 100 Z9 100 U1 1 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 MAY PY 1998 VL 18 IS 5 BP 2535 EP 2544 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZJ274 UT WOS:000073197600011 PM 9566873 ER PT J AU Latimer, M Ernst, MK Dunn, LL Drutskaya, M Rice, NR AF Latimer, M Ernst, MK Dunn, LL Drutskaya, M Rice, NR TI The N-terminal domain of I kappa B alpha masks the nuclear localization signal(s) of p50 and c-Rel homodimers SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DNA-BINDING; CYTOPLASMIC RETENTION; ANKYRIN REPEATS; V-REL; ACTIVATION; INHIBITION; SITE; PHOSPHORYLATION; SEQUENCES; PROTEINS AB Members of the Rel/NF-kappa B family of transcription factors are related to each other over a region of about 300 amino acids called the Rel Homology Domain (RHD), which governs DNA binding, dimerization, and binding to inhibitor. At the C-terminal end of the RHD, each protein has a nuclear localization signal (NLS), The crystal structures of the p50 and RelA family members show that the RHD consists of two regions: an N-terminal section which contains some of the DNA contacts and a C-terminal section which contains the remaining DNA contacts and controls dimerization, In unstimulated cells, the homo- or heterodimeric Rel/ NF-kappa B proteins are cytoplasmic by virtue of binding to an inhibitor protein (I kappa B) which somehow masks the NLS of each member of the dimer. The I kappa B proteins consist of an ankyrin-repeat-containing domain that is required for binding to dimers and N- and C-terminal domains that are dispensable for binding to most dimers. In this study, we examined the interaction between I kappa B alpha and Rel family homodimers by mutational analysis. We show that (i) the dimerization regions of p50, RelA, and c-Rel are sufficient for binding to I kappa B alpha, (ii) the NLSs of RelA and c-Rel are not required for binding to I kappa B alpha but do stabilize the interaction, (iii) the NLS of p50 is required for binding to I kappa B alpha, (iv) only certain residues within the p50 NLS are required for binding, and (v) in a p50-I kappa B alpha complex or a c-Rel-I kappa B alpha complex the N terminus of I kappa B alpha either directly or indirectly masks one or both of the dimer NLSs. C1 NCI, Mol Basis Carcinogenesis Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Rice, NR (reprint author), NCI, Mol Basis Carcinogenesis Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, POB B, Ft Detrick, MD 21702 USA. NR 31 TC 56 Z9 58 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 MAY PY 1998 VL 18 IS 5 BP 2640 EP 2649 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZJ274 UT WOS:000073197600021 PM 9566883 ER PT J AU Benard, L Carroll, K Valle, RCP Wickner, RB AF Benard, L Carroll, K Valle, RCP Wickner, RB TI Ski6p is a homolog of RNA-processing enzymes that affects translation of non-poly(A) mRNAs and 60S ribosomal subunit biogenesis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DOUBLE-STRANDED-RNA; L-A-HN; SACCHAROMYCES-CEREVISIAE; MESSENGER-RNA; CAP STRUCTURE; SUPERKILLER MUTATIONS; VIRUS PROPAGATION; PROTEIN-SYNTHESIS; ANTIVIRAL SYSTEM; KILLER SYSTEMS AB We mapped and cloned SK16 of Saccharomyces cerevisiae, a gene that represses the copy number of the L-A double-stranded RNA virus, and found that it encodes an essential 246-residue protein with homolog to a tRNA-processing enzyme, RNase PH. The ski6-2 mutant expressed electroporated non-poly(A) luciferase mRNAs 8- to 10-fold better than did the isogenic wild type. No effect of ski6-2 on expression of uncapped or normal mRNAs was found, Kinetics of luciferase synthesis and direct measurement of radiolabeled electroporated mRNA indicate that the primary effect of Ski6p was on efficiency of translation rather than on mRNA stability. Both ski6 and ski2 mutants show hypersensitivity to hygromycin, suggesting functional alteration of the translation apparatus. The ski6-2 mutant has normal amounts of 40S and 60S ribosomal subunits but accumulates a 38S particle containing 5'-truncated 25S rRNA but no 5.8S rRNA, apparently an incomplete or degraded 60S subunit. This suggests an abnormality in 60S subunit assembly. The ski6-2 mutation suppresses the poor expression of the poly(A)(-) viral mRNA in a strain deficient in the 60S ribosomal protein L4. Thus, a ski6 mutation bypasses the requirement of the poly(A) tail for translation, allotting better translation of non-poly(A) mRNA, including the L-A virus mRNA which lacks poly(A). We speculate that the derepressed translation of non-poly(A) mRNAs is is due to abnormal (but full-size) 60S subunits. C1 NIDDKD, Lab Biochem & Genet, Bethesda, MD 20892 USA. RP Wickner, RB (reprint author), NIH, Bldg 8,Room 225,8 Ctr Dr,MSC 0830, Bethesda, MD 20892 USA. EM wickner@helix.nih.gov NR 64 TC 51 Z9 53 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 MAY PY 1998 VL 18 IS 5 BP 2688 EP 2696 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZJ274 UT WOS:000073197600026 PM 9566888 ER PT J AU Qiu, HF Garcia-Barrio, MT Hinnebusch, AG AF Qiu, HF Garcia-Barrio, MT Hinnebusch, AG TI Dimerization by translation initiation factor 2 kinase GCN2 is mediated by interactions in the C-terminal ribosome-binding region and the protein kinase domain SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSFER-RNA-SYNTHETASES; SACCHAROMYCES-CEREVISIAE; YEAST; GENE; EXPRESSION; PHOSPHORYLATION; ASSOCIATION; MECHANISMS; ACTIVATION; MUTATIONS AB The protein kinase GCN2 stimulates translation of the transcriptional activator GCN4 in yeast cells starved for amino acids by phosphorylating translation initiation factor 2, Several regulatory domains, including a pseudokinase domain, a histidyl-tRNA synthetase (HisRS)-related region, and a C-terminal (C-term) segment required for ribosome association, have been identified in GCN2, We used the yeast two-hybrid assay, coimmunoprecipitation analysis, and in vitro binding assays to investigate physical interactions between the different functional domains of GCN2, A segment containing about two thirds of the protein kinase (PK) catalytic domain and another containing the C-term region of GCN2 interacted with themselves in the two-hybrid assay, and both the PK and the C-term domains could be coimmunoprecipitated with wild-type GCN2 from yeast cell extracts, In addition, in vitro-translated PK and C-term segments showed specific binding in vitro to recombinant glutathione S-transferase (GST)-PK and GST-C-term fusion proteins, respectively. Wild-type GCN2 could be coimmunoprecipitated with a full-length LexA-GCN2 fusion protein from cell extracts, providing direct evidence for dimerization by full-length GCN2 molecules. Deleting the C-term or PK segments abolished or reduced, respectively, the yield of GCN2-LexA-GCN2 complexes. These results provide in vivo and in vitro evidence that GCN2 dimerizes through self-interactions involving the C-term and PK domains, The PK domain showed pairwise in vitro binding interactions with the pseudokinase, HisRS, and C-term domains; additionally, the HisRS domain interacted with the C-term region, We propose that physical interactions between the PK domain and its Banking regulatory regions and dimerization through the PK and C-term domains both play important roles in restricting GCN2 kinase activity to amino acid-starved cells. C1 NICHHD, Lab Eukaryot Gene Regulat, Bethesda, MD 20892 USA. RP Hinnebusch, AG (reprint author), NICHHD, Lab Eukaryot Gene Regulat, Bldg 6A,Room B1A-13A, Bethesda, MD 20892 USA. NR 40 TC 43 Z9 46 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1998 VL 18 IS 5 BP 2697 EP 2711 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZJ274 UT WOS:000073197600027 PM 9566889 ER PT J AU Zhan, QM Chen, IT Antinore, MJ Fornace, AJ AF Zhan, QM Chen, IT Antinore, MJ Fornace, AJ TI Tumor suppressor p53 can participate in transcriptional induction of the GADD45 promoter in the absence of direct DNA binding SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ZINC FINGER PROTEIN; WT1 GENE-PRODUCT; WILMS-TUMOR; GROWTH SUPPRESSION; DAMAGING AGENTS; UV-IRRADIATION; CELL-CYCLE; EXPRESSION; ACTIVATION; REPRESSION AB The GADD45 gene is a growth arrest-associated gene that is induced by certain DNA-damaging agents and other stresses, such as starvation, in all mammalian cells. In addition to a strong p53-binding clement in an intronic sequence, we have recently found that p53, while not required or sufficient alone, may contribute to the stress responsiveness of the promoter. Much of the responsiveness,vas localized to a GC-rich motif in the proximal promoter which contains multiple Egr1 sites and a larger WT1 site; this 20-bp WT1 motif is identical to the WT1-binding site in the PDGF-A gene. In extracts from a human breast carcinoma cell line expressing p53 and WT1, which is known to associate with p53 in vivo, evidence was obtained that these proteins are in a complex that binds this 20-bp element. A combination of p53 and WT1 expression vectors strongly induced a GADD45-reporter construct, while mutation of the WT1-Egr1 site in the promoter pre rented this induction. Abrogation of p53 function by a dominant-negative vector or abrogation of WT1 function by an antisense vector markedly reduced the induction of this promoter. Since p53 does not bind directly to the promoter, these results indicate that p53 can contribute to the positive regulation of a promoter by protein-protein interactions. C1 NIH, NCI, Div Basic Sci, Bethesda, MD 20892 USA. RP Fornace, AJ (reprint author), NIH, NCI, Div Basic Sci, Bldg 37,Rm 5C09, Bethesda, MD 20892 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 65 TC 129 Z9 135 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 MAY PY 1998 VL 18 IS 5 BP 2768 EP 2778 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZJ274 UT WOS:000073197600034 PM 9566896 ER PT J AU Kokoska, RJ Stefanovic, L Tran, HT Resnick, MA Gordenin, DA Petes, TD AF Kokoska, RJ Stefanovic, L Tran, HT Resnick, MA Gordenin, DA Petes, TD TI Destabilization of yeast micro- and minisatellite DNA sequences by mutations affecting a nuclease involved in Okazaki fragment processing (rad27) and DNA polymerase delta (pol3-t) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SIMPLE REPETITIVE DNA; NUCLEOTIDE EXCISION-REPAIR; TRANSPOSON TN5 EXCISION; 5' EXONUCLEASE ACTIVITY; CALF RTH-1 NUCLEASE; SACCHAROMYCES-CEREVISIAE; MISMATCH REPAIR; MICROSATELLITE INSTABILITY; SOMATIC MUTATIONS; GENE CONVERSION AB We examined the effects of mutations in the Saccharomyces cerevisiae RAD27 (encoding a nuclease involved in the processing of Okazaki fragments) and POL3 (encoding DNA polymerase delta) genes on the stability of a minisatellite sequence (20-bp repeats) and microsatellites (1- to 8-bp repeat units). Both the rad27 and pol3-t mutations destabilized both classes of repeats, although the types of tract alterations observed in the two mutant strains were different. The tract alterations observed in rad27 strains were primarily additions, and those observed in pol3-t strains were primarily deletions. Measurements of the rates of repetitive tract alterations in strains with both rad27 and pol3-t indicated that the stimulation of microsatellite instability by rad27 was reduced by the effects of the pol3-t mutation. We also found that rad27 and pol3-01 (an allele carrying a mutation in the "proofreading" exonuclease domain of DNA polymerase delta) mutations were synthetically lethal. C1 Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA. NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. St Petersburg State Univ, Dept Genet, St Petersburg 199034, Russia. RP Petes, TD (reprint author), Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. EM tompetes@email.unc.edu FU NIGMS NIH HHS [F32 GM017879, GM17879, GM52319, R01 GM052319] NR 62 TC 147 Z9 148 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 MAY PY 1998 VL 18 IS 5 BP 2779 EP 2788 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZJ274 UT WOS:000073197600035 PM 9566897 ER PT J AU Zagariya, A Mungre, S Lovis, R Birrer, M Ness, S Thimmapaya, B Pope, R AF Zagariya, A Mungre, S Lovis, R Birrer, M Ness, S Thimmapaya, B Pope, R TI Tumor necrosis factor alpha gene regulation: Enhancement of C/EBP beta-induced activation by c-Jun SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NF-KAPPA-B; DOMINANT-NEGATIVE MUTANT; TRANSCRIPTION FACTOR; NUCLEAR FACTOR; TNF-ALPHA; INSULIN-RESISTANCE; PULMONARY FIBROSIS; EXPRESSION NF-IL6; PROMOTER REGION; FAMILY MEMBERS AB Tumor necrosis factor alpha (TNF alpha) is a key regulatory cytokine whose expression is controlled by a complex set of stimuli in a variety of cell types. Previously, we found that the monocyte/macrophage-enriched nuclear transcription factor C/EBP beta played an important role in the regulation of the TNF alpha gene in myelomonocytic cells. Abundant evidence suggests that other transcription factors participate as well. Here we have analyzed interactions between C/EBP beta and c-Jun, a component of the ubiquitously expressed AP-1 complex. In phorbol myristate acetate (PMA)-treated Jurkat T cells, which did not possess endogenous C/EBP beta, expression of c-Jun by itself had relatively little effect on TNF alpha promoter activity. However, the combination of C/EBP beta and c-Jun was synergistic, resulting in greater than 130-fold activation. This effect required both the leucine zipper and DNA binding domains, but not the transactivation domain, of c-Jun, plus the AP-1 binding site centered 102/103 bp upstream of the transcription start site in the TNF alpha promoter. To determine if C/EBP beta and c-Jun might cooperate to regulate the cellular TNF alpha gene in myelomonocytic cells, U937 cells that possess endogenous C/EBP beta and were stably transfected with either wild-type c-Jun or the transactivation domain deletion mutant (TAM-67) were examined. U937 cells expressing ectopic wild type c-Jun or TAM-67 secreted over threefold more TNF alpha than the control line in response to PMA plus lipopolysaccharide. Transient transfection of the U937 cells expressing TAM-67 suggested that TAM-67 binding to the -106/-99-bp AP-1 binding site cooperated with endogenous C/EBP beta in the activation of the -120 TNF alpha promoter-reporter. DNA binding assays using oligonucleotides derived from the TNF alpha promoter suggested that C/EBP beta and c-Jun interact in vitro and that the interaction may be DNA dependent. Our data demonstrate that the TNF alpha gene is regulated by the interaction of the ubiquitous AP-1 complex protein c-Jun and the monocyte/macrophage-enriched transcription factor C/EBP beta and that this interaction contributes to the expression of the cellular TNF alpha gene in myelomonocytic cells. This interaction was unique in that it did not require the c-Jun transactivation domain, providing new insight into the fell-type-specific regulation of the TNF alpha gene. C1 Northwestern Univ, Sch Med, Dept Med, Div Arthritis, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Med, Div Arthritis, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Vet Adm Lakeside Med Ctr, Chicago, IL 60611 USA. NIH, Dept Cell & Canc Biol, NCI, Rockville, MD 20805 USA. Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA. RP Pope, R (reprint author), Northwestern Univ, Sch Med, Dept Med, Div Arthritis, Ward 3-315,303 E Chicago Ave, Chicago, IL 60611 USA. EM rmp158@nwu.edu FU NCI NIH HHS [R01 CA058443, R01-CA-58443]; NIAMS NIH HHS [P060-AR-30692, P60 AR030692, R01-AR-43642] NR 55 TC 92 Z9 92 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 MAY PY 1998 VL 18 IS 5 BP 2815 EP 2824 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZJ274 UT WOS:000073197600038 PM 9566900 ER PT J AU Gao, XP Sedgwick, T Shi, YB Evans, T AF Gao, XP Sedgwick, T Shi, YB Evans, T TI Distinct functions are implicated for the GATA-4, -5, and -6 transcription factors in the regulation of intestine epithelial cell differentiation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BINDING-PROTEIN GENE; ERYTHROID-DIFFERENTIATION; AMPHIBIAN METAMORPHOSIS; DEVELOPING HEART; TRANSGENIC MICE; XENOPUS-LAEVIS; HT-29 CELLS; EXPRESSION; PROMOTER; FAMILY AB Based on conserved expression patterns, three members of the GATA family of transcriptional regulatory proteins, GATA-4, -5, and -6, are thought to be involved in the regulation of cardiogenesis and gut development. Functions for these factors are known in the heart, but relatively little is understood regarding their possible roles in the regulation of gut-specific gene expression. In this study, we analyze the expression and function of GATA-4, -5, and -6 using three separate but complementary vertebrate systems, and the results support a function for these proteins in regulating the terminal-differentiation program of intestinal epithelial cells, We show that xGATA-4, -5, and -6 can stimulate directly activity of the promoter for the intestinal fatty acid-binding protein (xIFABP) gene, which is a marker for differentiated enterocytes, This is the first direct demonstration of a target for GATA factors in the vertebrate intestinal epithelium. Transactivation by xGATA-4, -5, and -6 is mediated at least in part by a defined proximal IFABP promoter element. The expression patterns for cGATA-4, -5, and -6 are markedly distinct along the proximal-distal villus axis, Transcript levels for cGATA-4 increase along the axis toward the villus tip; likewise, cGATA-5 transcripts are largely restricted to the distal tip containing differentiated cells, In contrast, the pattern of cGATA-6 transcripts is complementary to cGATA-5, with highest levels detected in the region of proliferating progenitor cells. Undifferentiated and proliferating human HT-29 cells express hGATA-6 but not hGATA-4 or hGATA-5. Upon stimulation to differentiate, the transcript levels for hGATA-5 increase, and this occurs prior to increased transcription of the terminal differentiation marker intestinal alkaline phosphatase. At the same time, hGATA-6 steady-state transcript levels decline appreciably. All of the data are consistent with evolutionarily conserved but distinct roles for these factors in regulating the differentiation program of intestinal epithelium. Based on this data, we suggest that GATA-6 might function primarily within the proliferating progenitor population, while GATA-4 and GATA-5 function during differentiation to activate terminal-differentiation genes including IFABP. C1 Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10467 USA. NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Evans, T (reprint author), 1300 Morris Pk Ave,Chanin 503, Bronx, NY 10461 USA. NR 58 TC 182 Z9 185 U1 1 U2 3 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 MAY PY 1998 VL 18 IS 5 BP 2901 EP 2911 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZJ274 UT WOS:000073197600047 PM 9566909 ER PT J AU Lee, YH Sauer, B Gonzalez, FJ AF Lee, YH Sauer, B Gonzalez, FJ TI Laron dwarfism and non-insulin-dependent diabetes mellitus in the Hnf-1 alpha knockout mouse SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID FACTOR-I GENE; SITE-SPECIFIC RECOMBINATION; NUCLEAR FACTOR-I; FUNCTIONAL EXPRESSION; GROWTH; TRANSCRIPTION; MUTATIONS; BINDING; MANIPULATION; COOPERATION AB Mice deficient in hepatocyte nuclear factor 1 alpha (HNF-1 alpha) were produced by use of the Cre-loxP recombination system. HNF-1 alpha-null mice are viable but sterile and exhibit a phenotype reminiscent of both Laron-type dwarfism and non-insulin-dependent diabetes mellitus (NIDDM), In contrast to an earlier HNF-1 alpha-null mouse line that had been produced by use of standard gene disruption methodology (M. Pontoglio, J. Barra, M. Hadchouel, A. Doyen, C. Kress, J.P. Bach, C. Babinet, and M. Yaniv, Cell 84:575-585, 1996), these mice exhibited no increased mortality and only minimal renal dysfunction during the first 6 months of development. Both dwarfism and NIDDM are most likely due to the loss of expression of insulin-like growth factor I (IGF-I) and lower levels of insulin, resulting in stunted grow th and elevated serum glucose levels, respectively, These results confirm the functional significance of the HNF-1 alpha regulatory elements that had previously been shown to reside in the promoter regions of both the IGF-I and the insulin genes. C1 Acad Sinica, Inst Mol Biol, Taipei 115, Taiwan. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. NIDDKD, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. RP Lee, YH (reprint author), Acad Sinica, Inst Mol Biol, Taipei 115, Taiwan. EM mbying@ccvax.sinica.edu.tw NR 45 TC 190 Z9 191 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 MAY PY 1998 VL 18 IS 5 BP 3059 EP 3068 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZJ274 UT WOS:000073197600062 PM 9566924 ER PT J AU Sundaresan, V Roberts, I Bateman, A Bankier, A Sheppard, M Hobbs, C Xiong, JY Minna, J Latif, F Lerman, M Rabbitts, P AF Sundaresan, V Roberts, I Bateman, A Bankier, A Sheppard, M Hobbs, C Xiong, JY Minna, J Latif, F Lerman, M Rabbitts, P TI The DUTT1 gene, a novel NCAM family member is expressed in developing murine neural tissues and has an unusually broad pattern of expression SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID CELL-ADHESION MOLECULES; AXON GUIDANCE; IMMUNOGLOBULIN SUPERFAMILY; PROTEIN; FRAGMENTS; SEQUENCES; ENCODES; BIOLOGY AB A new member of the NCAM family mapping to 3p12 has been isolated and predicted to be arranged in five immunoglobulin-like domains and three fibronectin-like domains which are particularly homologous to L1. There is a transmembrane domain and a long cytoplasmic region with no detectable homology to other sequences. Although less closely related to DCC, another family member, both share a loop of positively charged amino acids within the first immunoglobulin domain, unique to these two members of this very large gene family. Preliminary studies of expression in mouse embryos support an inferred role in neural development, but the observation of widespread gene expression in adult human tissues indicates that this protein has additional functions to those performed in neural cells. C1 United Med & Dent Sch Guys & St Thomas Hosp, MRC Ctr, London SE1 9RT, England. United Med & Dent Sch Guys & St Thomas Hosp, Dept Histopathol & Expt Pathol, London SE1 9RT, England. Mol Biol Lab, Cambridge CB2 2QH, England. Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol, Dallas, TX 75235 USA. NCI, Immunobiol Lab, Frederick, MD 21701 USA. RP Rabbitts, P (reprint author), United Med & Dent Sch Guys & St Thomas Hosp, MRC Ctr, Guys Hosp Campus, London SE1 9RT, England. RI Bateman, Alex/E-6518-2011; OI Bateman, Alex/0000-0002-6982-4660 NR 31 TC 47 Z9 53 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell Neurosci. PD MAY PY 1998 VL 11 IS 1-2 BP 29 EP 35 DI 10.1006/mcne.1998.0672 PG 7 WC Neurosciences SC Neurosciences & Neurology GA ZN094 UT WOS:000073609300004 PM 9608531 ER PT J AU Castillo, SO Baffi, JS Palkovits, M Goldstein, DS Kopin, IJ Witta, J Magnuson, MA Nikodem, VM AF Castillo, SO Baffi, JS Palkovits, M Goldstein, DS Kopin, IJ Witta, J Magnuson, MA Nikodem, VM TI Dopamine biosynthesis is selectively abolished in substantia nigra ventral tegmental area but not in hypothalamic neurons in mice with targeted disruption of the Nurr1 gene SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID FLOOR PLATE; RECEPTOR SUPERFAMILY; NUCLEAR RECEPTORS; SONIC HEDGEHOG; INDUCTION; RAT; DISEASE AB To ascertain the function of an orphan nuclear receptor Nurr1, a transcription factor belonging to a large gene family that includes receptors for steroids, retinoids, and thyroid hormone, we generated Nurr1-null mice by homologous recombination. Mice, heterozygous for a single mutated Nurr1 allele, appear normal, whereas mice homozygous for the null allele die within 24 h after birth. Dopamine (DA) was absent in the substantia nigra (SN) and ventral tegmental area (VTA) of Nurr1-null mice, consistent with absent tyrosine hydroxylase (TH), L-aromatic amino acid decarboxylase, and other DA neuron markers. TH immunoreactivity and mRNA expression in hypothalamic, olfactory, and lower brain stem regions were unaffected. I-Dihydroxyphenylalanine treatments, whether given to the pregnant dams or to the newborns, failed to rescue the Nurr1-null mice. We were unable to discern differences between null and wild-type mice in the cellularity, presence of neurons, or axonal projections to the SN and VTA. These findings provide evidence for a new mechanism of DA depletion in vivo and suggest a unique role for Nurr1 in fetal development and/or postnatal survival. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. NIMH, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Sch Med, Nashville, TN 37232 USA. RP Castillo, SO (reprint author), NIDDKD, NIH, 10-8N317,10 Ctr Dr,MSC 1766, Bethesda, MD 20892 USA. RI Palkovits, Miklos/F-2707-2013; Magnuson, Mark/B-1335-2009; OI Magnuson, Mark/0000-0002-8824-6499; Palkovits, Miklos/0000-0003-0578-0387 NR 22 TC 215 Z9 220 U1 2 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell Neurosci. PD MAY PY 1998 VL 11 IS 1-2 BP 36 EP 46 DI 10.1006/mcne.1998.0673 PG 11 WC Neurosciences SC Neurosciences & Neurology GA ZN094 UT WOS:000073609300005 PM 9608532 ER PT J AU Rabin, O Drieu, K Grange, E Chang, MCJ Rapoport, SI Purdon, AD AF Rabin, O Drieu, K Grange, E Chang, MCJ Rapoport, SI Purdon, AD TI Effects of EGb 761 on fatty acid reincorporation during reperfusion following ischemia in the brain of the awake gerbil SO MOLECULAR AND CHEMICAL NEUROPATHOLOGY LA English DT Article DE ischemia; fatty acid metabolism; phospholipid metabolism; Ginkgo biloba extract (EGb 761); brain; gerbil; arachidonic acid; reincorporation; recovery; damage ID PLATELET-ACTIVATING-FACTOR; GINKGO-BILOBA EXTRACT; ACYL-COA CONCENTRATIONS; DELAYED NEURONAL DEATH; ARACHIDONIC-ACID; ELECTROCONVULSIVE SHOCK; CEREBRAL-CORTEX; RAT-BRAIN; FREE-RADICALS; GLIAL-CELLS AB Transient cerebral ischemia (5 min) releases unesterified fatty acids from membrane phospholipids, increasing brain concentrations of fatty acids for up to 1 h following reperfusion. To understand the reported anti-ischemic effect of Ginkgo biloba extract (EGb 761), we monitored its effect on brain fatty acid reincorporation in a gerbil-stroke model. Both common carotid arteries in awake gerbils were occluded for 5 min, followed by 5 min of reperfusion. Animals were infused intravenously with labeled arachidonic (AA) or palmitic acid (Pam), and rates of incorporation of unlabeled fatty acid from the brain acyl-CoA pool were calculated by the model of Robinson et al. (1992), using quantitative autoradiography and biochemical analysis of brain acyl-CoA. Animals were treated for 14 d with 50 or 150 mg/kg/d EGb 761 or vehicle. Ischemia-reperfusion had no effect on the rate of unlabeled Pam incorporation into brain phospholipids from palmitoyl-CoA; this rate also was unaffected by EGb 761. In contrast, ischemia-reperfusion increased the rate of incorporation of unlabeled AA from brain arachidonoyl-CoA by a factor of 2.3-3.3 compared with the control rate; this factor was further augmented to 3.6-5.0 by pretreatment with EGb 761. There is selective reincorporation of AA compared with Pam into brain phospholipids following ischemia. EGb 761 further accelerates AA reincorporation, potentially reducing neurotoxic effects of prolonged exposure of brain to high concentrations of AA and its metabolites. C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. Inst Henri Beaufour, F-75116 Paris, France. RP Purdon, AD (reprint author), NIA, Neurosci Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 54 TC 11 Z9 11 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1044-7393 J9 MOL CHEM NEUROPATHOL JI Mol. Chem. Neuropathol. PD MAY PY 1998 VL 34 IS 1 BP 79 EP 101 DI 10.1007/BF02815137 PG 23 WC Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 119UH UT WOS:000075915800005 PM 9778647 ER PT J AU Mitsuhata, C Kitayama, S Morita, K Vandenbergh, D Uhl, GR Dohi, T AF Mitsuhata, C Kitayama, S Morita, K Vandenbergh, D Uhl, GR Dohi, T TI Tyrosine-533 of rat dopamine transporter: involvement in interactions with 1-methyl-4-phenylpyridinium and cocaine SO MOLECULAR BRAIN RESEARCH LA English DT Article DE dopamine transporter; MPP+; cocaine; mutagenesis ID UPTAKE SITES; BINDING; NEUROTOXICITY AB To improve our understanding of structure-function relationships for neurotransmitter transporters, we performed site-directed mutagenesis of the rat dopamine transporter (DAT) and assessed the functions of the mutants in transiently-expressing COS cells. Tyrosine-533 of rat DAT lies in the 11th transmembrane region, where the corresponding amino acid of human DAT is phenylalanine. Alanine substitution of tyrosine-533 (Y533A) conferred an increased affinity for 1-methyl-4-phenylpyridinium (MPP+). Phenylalanine substitution of tyrosine-533 (Y533F) increased the velocity of MPP+ uptake but decreased DAT's affinity for MPP+. Cocaine's potency in inhibiting dopamine uptake was unchanged with Y533A, but increased with Y533F. Differences in the uptake kinetics and inhibitory potency of cocaine between rat and human DATs were similar to the differences observed between the wild-type and Y533F mutants DATs. Tyrosine-533 may be important for the DAT function and for species differences in transporter functions, including differential sensitivities to cocaine and 1-methyl-1,2,3,6-tetrahydropyridine (MPTP) in humans and rats. (C) 1998 Elsevier Science B.V. C1 Hiroshima Univ, Sch Dent, Dept Pharmacol, Minami Ku, Hiroshima 734, Japan. NIDA, Mol Neurobiol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21224 USA. RP Kitayama, S (reprint author), Hiroshima Univ, Sch Dent, Dept Pharmacol, Minami Ku, Kasumi 1-2-3, Hiroshima 734, Japan. NR 12 TC 25 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD MAY PY 1998 VL 56 IS 1-2 BP 84 EP 88 DI 10.1016/S0169-328X(98)00032-1 PG 5 WC Neurosciences SC Neurosciences & Neurology GA ZW232 UT WOS:000074388900010 ER PT J AU Biro, T Brodie, C Modarres, S Lewin, NE Acs, P Blumberg, PM AF Biro, T Brodie, C Modarres, S Lewin, NE Acs, P Blumberg, PM TI Specific vanilloid responses in C6 rat glioma cells SO MOLECULAR BRAIN RESEARCH LA English DT Article DE capsaicin; vanilloid receptor; resiniferatoxin; glial cell; apoptosis; differentiation ID H-3 RESINIFERATOXIN BINDING; ROOT GANGLION MEMBRANES; GLIAL-CELLS; CAPSAICIN RECEPTORS; RUTHENIUM RED; NADH-OXIDASE; CA-45 UPTAKE; NEURONS; CULTURE; CAPSAZEPINE AB Capsaicin and its ultrapotent analog resiniferatoxin (RTX) act through specific vanilloid receptors on sensory neurons. Here, we describe specific vanilloid responses in rat C6 glioma cells. Capsaicin and RTX stimulated Ca-45 uptake in a similar fashion to that found for cultured rat dorsal root ganglion neurons (DRGs); this response was antagonized by the antagonists capsazepine and ruthenium red. As in DRGs, pretreatment of C6 cells with capsaicin or RTX produced desensitization to subsequent stimulation of Ca-45 uptake. The potency for desensitization by RTX in the C6 cells corresponded to that for Ca-45 uptake, whereas in DRGs it occurred at significantly lower concentrations corresponding to that for the high affinity [H-3]RTX binding site. Consistent with this difference, in C6 cells we were unable to detect [H-3]RTX binding. These characteristics suggest the presence of C-type but not R-type vanilloid receptors on C6 cells. After 2 day treatment, capsaicin but not RTX inhibited the proliferation and altered the differentiation of the cells and produced apoptosis. In the long term experiments, capsazepine, instead of antagonizing the effect of capsaicin, acted as an agonist. Moreover, capsazepine displayed these effects with higher potency than that of capsaicin. The different potencies and structure activity relations suggest a distinct mechanism for these long-term vanilloid effects. Our finding that C6 cells can respond directly to capsaicin necessitates a reevaluation of the in vivo pathway of response to vanilloids, and highlights the importance of the neuron-glial network. (C) 1998 Elsevier Science B.V. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, MMTP, Mol Mechanisms Tumor Promot Sect,NIH, Bethesda, MD 20892 USA. RP Blumberg, PM (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, MMTP, Mol Mechanisms Tumor Promot Sect,NIH, Bldg 37,Room 3A01,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. EM blumberp@dc37a.nci.nih.gov NR 41 TC 46 Z9 49 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD MAY PY 1998 VL 56 IS 1-2 BP 89 EP 98 DI 10.1016/S0169-328X(98)00033-3 PG 10 WC Neurosciences SC Neurosciences & Neurology GA ZW232 UT WOS:000074388900011 ER PT J AU Brodie, C Kuperstein, I Acs, P Blumberg, PM AF Brodie, C Kuperstein, I Acs, P Blumberg, PM TI Differential role of specific PKC isoforms in the proliferation of glial cells and the expression of the astrocytic markers GFAP and glutamine synthetase SO MOLECULAR BRAIN RESEARCH LA English DT Article DE astrocytic differentiation; protein kinase C (PKC); GFAP; glutamine synthetase; proliferation ID PROTEIN-KINASE-C; FIBRILLARY ACIDIC PROTEIN; CYCLIC-AMP; MESSENGER-RNA; GLIOMA-CELLS; SIGNAL-TRANSDUCTION; NERVOUS-SYSTEM; PHORBOL ESTERS; BETA-II; CULTURE AB In this study, we explored the role of specific protein kinase C (PKC) isoforms in glial cell proliferation and on the expression of the astrocytic markers GFAP and,glutamine synthetase using C6 cells as a model. Analysis of the expression of the various PKC isoforms in control and differentiated C6 cells revealed differences in the expression of specific PKC isoforms. Undifferentiated C6 cells, which express low levels of GFAP and glutamine synthetase (GS), have high levels of PKC alpha and delta, whereas differentiated C6 cells, which express higher levels of both GFAP and GS have lower levels of PKC alpha and delta and higher levels of PKC gamma, theta and eta. Using C6 cells overexpressing specific PKC isoforms, we examined the role of these isoforms on the proliferation and differentiation of C6 cells. Cells overexpressing PKC alpha displayed a reduced level of GFAP, whereas GS expression was not affected. On the other hand, cells overexpressing PKC delta showed reduced GS expression but little effect on GFAP. Finally, cells expressing PKC gamma displayed a marked increase in the levels of both GFAP and GS. The proliferation of C6 cells was increased in cells overexpressing PKC alpha and epsilon and decreased in cells overexpressing PKC gamma, delta and eta. The results of this study suggest that glial cell proliferation and astrocytic differentiation can be regulated by specific PKC isoforms that selectively affect cell proliferation and the expression of the two astrocytic markers GFAP and GS. (C) 1998 Elsevier Science B.V. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, MMTP, Mol Mechanisms Tumor Promot Sect,NIH, Bethesda, MD 20892 USA. Bar Ilan Univ, Dept Life Sci, IL-52900 Ramat Gan, Israel. RP Brodie, C (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, MMTP, Mol Mechanisms Tumor Promot Sect,NIH, Bldg 37,Room 3A01,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. NR 51 TC 41 Z9 41 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD MAY PY 1998 VL 56 IS 1-2 BP 108 EP 117 DI 10.1016/S0169-328X(98)00035-7 PG 10 WC Neurosciences SC Neurosciences & Neurology GA ZW232 UT WOS:000074388900013 ER PT J AU Akar, CA Wallace, WC AF Akar, CA Wallace, WC TI Amyloid precursor protein modulates the interaction of nerve growth factor with p75 receptor and potentiates its activation of trkA phosphorylation SO MOLECULAR BRAIN RESEARCH LA English DT Article DE amyloid precursor protein; nerve growth factor; receptor; neurotrophic activity ID CHOLINE-ACETYLTRANSFERASE ACTIVITY; AFFINITY NGF BINDING; ALZHEIMERS-DISEASE; MESSENGER-RNA; PROTOONCOGENE PRODUCT; NEURITE OUTGROWTH; SECRETED FORM; NEXIN-II; CELL; DOMAIN AB We have recently shown that the secreted form of amyloid precursor protein (APP(s)) potentiates the neurotrophic actions of nerve growth factor (NGF). The combined presence of NGF and APP(s) in low concentrations resulted in a synergistic potentiation of NGF neuritogenic activity on PC12 cells. Therefore, the effect of APP(s) on NGF receptor-binding has been examined. In the presence of APP(s), the apparent affinity of NGF' s low affinity binding site increased by a factor of 2.5. In addition, a 2- to 2.5-fold decrease in the number of sites was observed, although APP(s) did not compete with NGF for the same binding sites. These effects of APP(s) were not caused by direct interaction with NGF itself. In addition, APP(s) synergistically potentiated the tyrosine phosphorylation of trkA due to NGF. These results suggest that an increased affinity of p75 for NGF may underlie the potentiation of neurotrophic actions of NGF by APP(s), and that increase may be caused by an indirect interaction between APP(s) and p75. (C) 1998 Elsevier Science B.V. C1 NIA, Gerontol Res Ctr, Mol & Cellular Biol Lab, Baltimore, MD 21224 USA. RP Wallace, WC (reprint author), NIA, Gerontol Res Ctr, Mol & Cellular Biol Lab, 4940 Eastern Ave, Baltimore, MD 21224 USA. NR 49 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD MAY PY 1998 VL 56 IS 1-2 BP 125 EP 132 DI 10.1016/S0169-328X(98)00037-0 PG 8 WC Neurosciences SC Neurosciences & Neurology GA ZW232 UT WOS:000074388900015 ER PT J AU Tamaoka, A Fraser, PE Ishii, K Sahara, N Ozawa, K Ikeda, M Saunders, AM Komatsuzaki, Y Sherrington, R Levesque, G Yu, G Rogaeva, E Shoji, S Nee, LE Pollen, DA Hendriks, L Martin, JJ Van Broeckhoven, C Roses, AD Farrer, LA St George-Hyslop, PH Mori, H AF Tamaoka, A Fraser, PE Ishii, K Sahara, N Ozawa, K Ikeda, M Saunders, AM Komatsuzaki, Y Sherrington, R Levesque, G Yu, G Rogaeva, E Shoji, S Nee, LE Pollen, DA Hendriks, L Martin, JJ Van Broeckhoven, C Roses, AD Farrer, LA St George-Hyslop, PH Mori, H TI Amyloid-beta-protein isoforms in brain of subjects with PS1-linked, beta APP-linked and sporadic Alzheimer disease SO MOLECULAR BRAIN RESEARCH LA English DT Article DE Alzheimer's disease; presenilin-1; APP717; amyloid deposition; insoluble ID A-BETA; APOLIPOPROTEIN-E; MISSENSE MUTATIONS; PRESENILIN-1; DEPOSITION; PEPTIDE; A-BETA-1-42/43; A-BETA-42(43); CHROMOSOME-1; AGGREGATION AB To determine whether similar abnormalities of various soluble full-length and N-terminal truncated A beta peptides occur in postmortem cerebral cortex of affected PS1 mutation carriers, we examined the amounts of two amyloid species ending at residue 40 or at residues 42(43) using sandwich ELISA systems. Our results indicate that PS1 mutations effect a dramatic accumulation in brain of the highly insoluble potentially neurotoxic long-tailed isoforms of the A beta peptide such as A beta 1-42(43) and A beta x-42(43). This enhancing effect of PS1 mutation on A beta x-42(43) deposition was highly similar to that of a beta APP mutation (Val717IIe) but the effects on A beta x-40 production were significantly different between these two causal genes. In contrast to previous studies of soluble AP in plasma and in supernatants from cultured fibroblasts of subjects with PS1 mutations, our studies also show that there is an increase in insoluble A beta x-40 peptides in brain of subjects with PS1 mutations. (C) 1998 Elsevier Science B.V. C1 Tokyo Inst Psychiat, Dept Mol Biol, Setagaya Ku, Tokyo 156, Japan. Univ Tsukuba, Inst Clin Med, Dept Neurol, Tsukuba, Ibaraki 305, Japan. Univ Toronto, Dept Med Neurol & Med Biophys, Ctr Res Neurodegenerat Dis, Toronto, ON M5S 1A8, Canada. Toronto Hosp, Div Neurol, Dept Med, Toronto, ON M5S 1A8, Canada. Tokyo Inst Psychiat, Dept Mol Biol, Setagaya Ku, Tokyo 156, Japan. Duke Univ, Joseph & Kathleen Bryan Alzheimer Dis Res Ctr, Med Ctr, Dept Med Neurol, Durham, NC USA. Duke Univ, Joseph & Kathleen Bryan Alzheimer Dis Res Ctr, Med Ctr, Dept Neurobiol, Durham, NC USA. Hatsuishi Hosp, Kashiwa, Chiba 277, Japan. NINDS, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. Univ Massachusetts, Med Ctr, Dept Neurol, Worcester, MA 01655 USA. Univ Antwerp VIB, Born Bunge Fdn, Dept Biochem, Lab Neurogenet, B-2020 Antwerp, Belgium. Univ Antwerp, Born Bunge Fdn, Dept Med, Neuropathol Lab, B-2020 Antwerp, Belgium. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Neurol, Neurogenet Lab, Boston, MA 02118 USA. RP Mori, H (reprint author), Tokyo Inst Psychiat, Dept Mol Biol, Setagaya Ku, 2-1-8 Kamikitazawa, Tokyo 156, Japan. EM mori@prit.go.jp OI Farrer, Lindsay/0000-0001-5533-4225 FU NIA NIH HHS [AG05128, AG09029] NR 42 TC 16 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD MAY PY 1998 VL 56 IS 1-2 BP 178 EP 185 DI 10.1016/S0169-328X(98)00044-8 PG 8 WC Neurosciences SC Neurosciences & Neurology GA ZW232 UT WOS:000074388900020 PM 9602117 ER PT J AU Galdzicki, Z Coan, EJ Rapoport, SI Stoll, J AF Galdzicki, Z Coan, EJ Rapoport, SI Stoll, J TI Increased expression of voltage-activated calcium channels in cultured hippocampal neurons from mouse trisomy 16, a model for Down syndrome SO MOLECULAR BRAIN RESEARCH LA English DT Article DE calcium current; L-type channel; trisomy 16; Down syndrome; Na+/myo-inositol transporter; hippocampal neuron; mouse ID ROOT GANGLION NEURONS; LONG-TERM DEPRESSION; PROTEIN-KINASE-C; ALZHEIMERS-DISEASE; SODIUM-CHANNELS; CA2+ CHANNELS; MAMMALIAN CNS; RAT; CELLS; BRAIN AB Calcium is an important second messenger that affects metabolic and physiological activities of developing and mature neurons. It has been reported that electrical activity is abnormal in cultured hippocampal and DRG neurons from the trisomy 16 (Ts16) mouse, a model for Down syndrome (trisomy 21-Ts21 in human). Whole-cell voltage-clamp, radiolabeled ligand binding techniques and mRNA measurements were used to study the effect of Ts16 on voltage-dependent calcium currents in cultured fetal hippocampal neurons from the Ts16 mouse. In neither Ts16 nor control diploid neurons were low-voltage-activated calcium currents detected. However, a high-voltage-activated (HVA) calcium current was identified and shown to be dihydropyridine sensitive. The density of this HVA calcium current was 80% greater in Ts16 neurons than in control. This difference correlated with a 70% increase in binding of radiolabeled dihydropyridine, PN200-110, a marker of L-type calcium channels. However, mRNA levels encoding the ct,, and ct,, subunits were unchanged in the Ts16 neurons. In contrast, mRNA level of the myo-inositol transporter, the gene for which is located on mouse chromosome 16, was elevated in Ts16 neurons due to a gene-dosage effect. Therefore, it is likely that posttranscriptional regulation of dihydropyridine-sensitive voltage-dependent calcium channels is abnormal in Ts16. As dihydropyridine sensitive HVA Ca channels are implicated in heterosynaptic long-term depression and long-term potentiation, the differences reported here, if also present in the Down syndrome brain, may contribute to mental retardation in that disorder. (C) 1998 Elsevier Science B.V. C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. Texas Tech Sch Pharm, Dept Pharmaceut Sci, Amarillo, TX 79106 USA. RP NIA, Neurosci Lab, NIH, Bldg 10,Room 6C103, Bethesda, MD 20892 USA. EM zyga@helix.nih.gov NR 49 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD MAY PY 1998 VL 56 IS 1-2 BP 200 EP 206 DI 10.1016/S0169-328X(98)00046-1 PG 7 WC Neurosciences SC Neurosciences & Neurology GA ZW232 UT WOS:000074388900023 ER PT J AU Rabin, SJ Tornatore, C Baker-Cairns, B Spiga, G Mocchetti, I AF Rabin, SJ Tornatore, C Baker-Cairns, B Spiga, G Mocchetti, I TI TrkA receptors delay C6-2B glioma cell growth in rat striatum SO MOLECULAR BRAIN RESEARCH LA English DT Article DE TrkA; NGF; p75NTR; glioblastoma multiforme ID BRAIN-TUMORS; EXPRESSION; DIFFERENTIATION; PROTOONCOGENE AB Nerve growth factor (NGF) acts as an anti-mitogenic factor in C6-2B glioma cells stably expressing TrkA (C6trk(+)). To study the effect of TrkA on cell growth in vivo, we grafted mock and C6trk+ cells into the striatum of ACI nude rats. Thy 1.1 and p75NTR immunohistochemistry revealed that wild type C6-2B cells formed a tumor mass in the striatum by 14 days. In contrast, C6trk(+) transplanted rats did not show the presence of a significant tumor mass until 71 days. Analysis of this tumor showed that expression of TrkA was retained, but the synthesis of NGF was abolished. Our data encourage the speculation that expression of TrkA in glioblastoma in vivo will attenuate tumor progression. (C) 1998 Elsevier Science B.V. C1 Georgetown Univ, Dept Cell Biol, Washington, DC 20007 USA. Georgetown Univ, Dept Neurol, Washington, DC 20007 USA. NIH, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. RP Mocchetti, I (reprint author), Georgetown Univ, Dept Cell Biol, 3900 Reservoir Rd, Washington, DC 20007 USA. NR 18 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD MAY PY 1998 VL 56 IS 1-2 BP 273 EP 276 DI 10.1016/S0169-328X(98)00020-5 PG 4 WC Neurosciences SC Neurosciences & Neurology GA ZW232 UT WOS:000074388900030 ER PT J AU Jakowlew, SB Moody, TW You, L Mariano, JM AF Jakowlew, SB Moody, TW You, L Mariano, JM TI Reduction in transforming growth factor-beta type II receptor in mouse lung carcinogenesis SO MOLECULAR CARCINOGENESIS LA English DT Article DE chemical carcinogenesis; gene expression; tumor progression; A/J mouse ID ACCOMPANIES VIRAL TRANSFORMATION; CANCER CELL-LINES; TGF-BETA; MICROSATELLITE INSTABILITY; CARCINOMA-CELLS; EXPRESSION CLONING; PANCREATIC-CANCER; VINYL CARBAMATE; MESSENGER-RNAS; RODENT CELLS AB Transforming growth factor-beta (TGF-beta) is a growth modulator that inhibits the proliferation of many epithelial cells through interaction with its receptors, the type I and type II receptors (TGF-beta RI and RII) by activating their serine/threonine kinase activities. Loss of growth inhibition by TGF-beta is thought to contribute to the development of many types of tumors. To examine the roles of TGF-beta 1, -beta 2, and -beta 3 and TGF-beta RI and RII in chemically induced mouse lung tumorigenesis, we used immunohistochemical and in situ hybridization analyses to measure the expression of their proteins and mRNAs in A/J mice treated with the carcinogen urethane to induce lung adenomas. Immunostaining for the TGF-beta ligands and receptors was detected in the epithelia of the bronchioles of untreated and treated A/J mice at similar levels. Immunostaining for the TGF-beta ligands and receptors was also detected in adenomas by 2 mo. While immunostaining for TGF-beta 1, -beta 2, and -beta 3 and TGF-beta RI in adenomas was detected at levels comparable to those in bronchioles, immunostaining for TGF-beta RII was less intense in adenomas than in bronchioles. Decreased immunostaining for TGF-beta RII in adenomas persisted for at least 8 mo after exposure to urethane, whereas immunostaining for TGF-beta 1, -beta 2, and -beta 3 and TGF-beta RI persisted at levels comparable to those in normal bronchioles. In situ hybridization studies conducted with TGF-beta receptor riboprobes showed a corresponding reduction in expression of TGF-beta RII mRNA but not of TGF-beta RI mRNA in adenomas compared with expression in bronchioles. Expression of TGF-beta RII mRNA was also examined in non-tumorigenic and tumorigenic mouse lung cells; expression of TGF-beta RII mRNA was lower in the tumorigenic cells derived from urethane-induced lung tumors. These data suggest that a decrease in expression of TGF-beta RII may contribute to autonomous cell growth and may play an important role in mouse lung carcinogenesis induced by urethane. (C) 1998 Wiley-Liss, Inc. C1 NCI, Dept Cell & Canc Biol, Med Branch, Rockville, MD 20850 USA. RP Jakowlew, SB (reprint author), NCI, Dept Cell & Canc Biol, Med Branch, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. NR 43 TC 27 Z9 27 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD MAY PY 1998 VL 22 IS 1 BP 46 EP 56 DI 10.1002/(SICI)1098-2744(199805)22:1<46::AID-MC6>3.0.CO;2-J PG 11 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA ZP895 UT WOS:000073799400005 PM 9609100 ER PT J AU Smith, RD Baukal, AJ Zolyomi, A Gaborik, Z Hunyady, L Sun, L Zhang, M Chen, HC Catt, KJ AF Smith, RD Baukal, AJ Zolyomi, A Gaborik, Z Hunyady, L Sun, L Zhang, M Chen, HC Catt, KJ TI Agonist-induced phosphorylation of the endogenous AT(1) angiotensin receptor in bovine adrenal glomerulosa cells SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PROTEIN-KINASE-C; II RECEPTOR; DEPENDENT PHOSPHORYLATION; MOLECULAR-CLONING; EXPRESSION; DESENSITIZATION; IDENTIFICATION; INVOLVEMENT; MECHANISM AB A polyclonal antibody was raised in rabbits against a fusion protein immunogen consisting of bacterial maltose-binding protein coupled to a 92-amino acid C-terminal fragment of the rat AT(1b) angiotensin II (Ang II) receptor. The antibody immunoprecipitated the photoaffinity-labeled bovine AT(1) receptor (AT(1)-R), but not the rat AT(2) receptor, and specifically stained bovine adrenal glomerulosa cells and AT(1a) receptor-expressing Cos-7 cells, as well as the rat adrenal zona glomerulosa and renal glomeruli. The antibody was employed to analyze Ang II-induced phosphorylation of the endogenous AT(1)-R immunoprecipitated from cultured bovine adrenal glomerulosa cells. Receptor phosphorylation was rapid, sustained for up to 60 min, and enhanced by pretreatment of the cells with okadaic acid. Its magnitude was correlated with the degree of ligand occupancy of the receptor. Activation of protein kinase A and protein kinase C (PKC) also caused phosphorylation of the receptor, but to a lesser extent than Ang II. Inhibition of PKC by staurosporine augmented Ang II-stimulated AT(1)-R phosphorylation, suggesting a negative regulatory role of PKC on the putative G protein-coupled receptor kinase(s) that mediates the majority of AT(1)-R phosphorylation. The antibody should permit further analysis of endogenous AT(1)-R phosphorylation in Ang II target cells. C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. Semmelweis Univ Med, Sch Med, Dept Physiol, H-1444 Budapest, Hungary. RP Catt, KJ (reprint author), NICHHD, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Room 6A-36,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 30 TC 40 Z9 40 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAY PY 1998 VL 12 IS 5 BP 634 EP 644 DI 10.1210/me.12.5.634 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZL146 UT WOS:000073403400003 PM 9605926 ER PT J AU Ooi, GT Hurst, KR Poy, MN Rechler, MM Boisclair, YR AF Ooi, GT Hurst, KR Poy, MN Rechler, MM Boisclair, YR TI Binding of STAT5a and STAT5b to a single element resembling a gamma-interferon-activated sequence mediates the growth hormone induction of the mouse acid-labile subunit promoter in liver cells SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID DNA-BINDING; TYROSINE PHOSPHORYLATION; PROTEIN COMPLEX; FACTOR-I; GENE-EXPRESSION; FACTOR IGF; MAMMARY TISSUE; INSULIN; TRANSCRIPTION; SERUM AB After birth, the endocrine actions of insulin-like growth factor (IGF)-I and -II become increasingly important. In postnatal animals, most of circulating IGFs occur in 150-kDa complexes formed by association of an acid-labile subunit (ALS) with complexes of IGF and IGF-binding protein-3. ALS is synthesized almost exclusively in liver. GH stimulates the transcription of the ALS gene, resulting in increased hepatic mRNA and circulating ALS levels. To map the GH response element, a series of 5'-deletion fragments of the mouse ALS promoter (nt -2001 to -49, A(+1)TG) were inserted in the luciferase reporter plasmid pGL3 and transfected into the H4-II-E rat hepatoma cell line. GH stimulated the activity of promoter fragments with 5'-ends between nucleotide (nt) -2001 and nt -653 by 1.9- to 2.7-fold. This stimulation was abolished by deletion of the region located between nt -653 and nt -483. This region contains two sites, ALS-GAS1 and ALS-GASP, that resemble the gamma-interferon activated sequence (GAS). Mutation of the ALS-GAS1 site, but not of the ALS-GASP site, eliminated the response to GH when assessed in the context of a GH-responsive promoter fragment, indicating that ALS-GAS1 was necessary for GH induction. Three tandem copies of ALS-GAS1 were sufficient to confer GH inducibility to the minimal promoter of the thymidine kinase gene. In electrophoretic mobility shift assays, ALS-GAS1 formed a specific, GH-dependent protein-DNA complex with nuclear extracts from H4-II-E cells. Using antibodies directed against members of the family of signal transducers and activators of transcription (STAT), this complex was shown to be composed of STAT5a and STAT5b. Identical results were obtained when transfections and mobility shift assays were performed in primary rat hepatocytes in which the endogenous ALS gene is expressed. Thus, the transcriptional activation of the mouse ALS gene by GH is mediated by the binding of STAT5 isoforms to a single GAS-like element. C1 Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA. NIDDKD, Growth & Dev Sect, Mol & Cellular Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Boisclair, YR (reprint author), Cornell Univ, Dept Anim Sci, 259 Morrison Hall, Ithaca, NY 14853 USA. EM yrb1@cornell.edu FU NIDDK NIH HHS [DK-51624-01A1] NR 59 TC 52 Z9 53 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAY PY 1998 VL 12 IS 5 BP 675 EP 687 DI 10.1210/me.12.5.675 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZL146 UT WOS:000073403400007 PM 9605930 ER PT J AU Lee, L Irani, K Finkel, T AF Lee, L Irani, K Finkel, T TI Bcl-2 regulates nonapoptotic signal transduction: Inhibition of c-jun N-terminal kinase (JNK) activation by IL-1 beta and hydrogen peroxide SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE bcl-2; JNK; rac1; calcium ID INTRACELLULAR CALCIUM; DEPENDENT ACTIVATION; INDUCED APOPTOSIS; PROTEIN-KINASE; CELL-DEATH; PATHWAY; GTPASES; RAF-1; RAC1 AB We have explored the role of bcl-2 as a potential modulator of intracellular signal transduction. Stable expression of bcl-2 in fibroblasts inhibited the activation of the c-jun amino terminal kinase (JNK) by the nonapoptotic cytokine interleukin-1 beta (IL-1 beta) This effect appeared to be selective for JNK activation as bcl-2 did not appear to alter other aspects of IL-1 beta signal transduction. Similarly, bcl-2 did not inhibit all activators of JNK as it had no effect on JNK activation by the protein synthesis inhibitor anisomycin. Treatment with nonlethal concentrations of H2O2, which resulted in the simultaneous stimulation of mitogen-activated protein kinase (MAPK) and JNK, demonstrated that bcl-2 appeared to alter the balance of activation of these two kinase cascades. The pathway by which bcl-2 inhibits JNK activation is demonstrated to be independent of the rad GTPase. In contrast, the reduction in JNK activity in cells expressing bcl-2 can be restored by costimulation with a calcium ionophore. This suggests that bcl-2 can regulate certain nonapoptotic signaling pathways. Such results therefore expand the functions of bcl-2 and may have important implication in the understanding of the role of this protein in a variety of human diseases. (C) 1998 Academic Press. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD 21205 USA. RP Finkel, T (reprint author), NHLBI, Cardiol Branch, NIH, 10 Ctr Dr,10-7B-15, Bethesda, MD 20892 USA. EM finkelt@gwgate.nhlbi.nih.gov NR 31 TC 22 Z9 22 U1 0 U2 1 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 MAY PY 1998 VL 64 IS 1 BP 19 EP 24 DI 10.1006/mgme.1998.2704 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 102LK UT WOS:000074925700004 PM 9682214 ER PT J AU Lin, T Orrison, BM Suchy, SF Lewis, RA Nussbaum, RL AF Lin, T Orrison, BM Suchy, SF Lewis, RA Nussbaum, RL TI Mutations are not uniformly distributed throughout the OCRL1 gene in Lowe syndrome patients SO MOLECULAR GENETICS AND METABOLISM LA English DT Article ID INOSITOL AB Lowe syndrome (OCRL) is an X-linked disorder involving the eyes, kidney, and nervous system that is caused by loss of function in the OCRL1 gene. OCRL1 contains 24 exons (23 of which are coding) and encodes a 105-kDa enzyme with phosphatidylinositol 4,5 bisphosphate (PtdIns[4,5]P-2) 5-phosphatase activity. We published previously (1,2) 13 different mutations in 15 patients. Here we report another 8 mutations in 10 families. Four are missense mutations in highly conserved PtdIns(4,5)Pz 5-phosphatase domains, two are premature terminations caused by nonsense mutations, and three others are premature terminations caused by frameshift mutations. One frameshift, a GT deletion in exon 21, has been observed previously in two unrelated Lowe syndrome patients, suggesting that it may be a relative "hotspot" for mutation in a disorder marked otherwise by allelic heterogeneity. We have also seen two other recurrent mutations. One is a nonsense mutation <(C)under bar GA> > <(T)under bar GA> in exon 22 observed in two patients and the second is a missense mutation CGA > CA in exon 15 present in two unrelated patients. These 21 distinct mutations we have found in 25 Lowe syndrome patients occur in only 9 of the 24 exons: 10, 12, 13, 14, 15, 18, 19, 21, and 22. interestingly missense mutations have occurred only in exons 12 through 15 in highly conserved residues among the phosphatidylinositol 5-phosphatases, These observations suggest useful strategies for mutation screening in OCRL, (C) 1998 Academic Press. C1 NIH, Lab Genet Dis Res, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Ophthalmol & Mol & Human Genet, Houston, TX 77030 USA. RP Nussbaum, RL (reprint author), NIH, Lab Genet Dis Res, NIH, 49 Convent Dr,MSC4472, Bethesda, MD 20892 USA. NR 9 TC 34 Z9 39 U1 0 U2 0 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 MAY PY 1998 VL 64 IS 1 BP 58 EP 61 DI 10.1006/mgme.1998.2687 PG 4 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 102LK UT WOS:000074925700009 PM 9682219 ER PT J AU Gaudenz, K Roessler, E Vainikka, S Alitalo, K Muenke, M AF Gaudenz, K Roessler, E Vainikka, S Alitalo, K Muenke, M TI Analysis of patients with craniosynostosis syndromes for a Pro246Arg mutation in FGFR4 SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE fibroblast growth factor receptor; FGFR4; craniosynostosis ID GROWTH-FACTOR RECEPTOR; SIGNAL-TRANSDUCTION; EXPRESSION PATTERN; FIBROBLAST; MOUSE; GENE; ORGANOGENESIS; MEMBER; FAMILY; KINASE AB An identical amino acid substitution in fibroblast growth factor receptors (FGFR) 1, 2 and 3 occurs in patients with different craniosynostosis syndromes. We tested 113 patients with various craniosynostosis syndromes for the analogous Pro246Arg mutation in FGFR4 by a PCR-restriction enzyme assay. None of the patients displayed this change nor other mutations in the conserved linker region, as tested by SSCP analysis. Mutations in this domain of FGFR4 are unlikely to contribute significantly to craniosynostosis in humans, (C) 1998 Academic Press. C1 Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Human Genet & Mol Biol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. Univ Helsinki, Haartman Inst, Mol Canc Biol Lab, SF-00014 Helsinki, Finland. RP Muenke, M (reprint author), Natl Human Genome Res Inst, Med Genet Branch, 10 Ctr Dr,MSC 1852,Bldg 10,Room 10C101, Bethesda, MD 20892 USA. EM mmuenke@nhgri.nih.gov RI Alitalo, Kari/J-5013-2014 OI Alitalo, Kari/0000-0002-7331-0902 FU NICHD NIH HHS [5T32HD07107, HD28732, HD29862] NR 22 TC 10 Z9 10 U1 0 U2 1 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 MAY PY 1998 VL 64 IS 1 BP 76 EP 79 DI 10.1006/mgme.1998.2694 PG 4 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 102LK UT WOS:000074925700012 PM 9682222 ER PT J AU Dasgupta, S Fernandez, L Kameyama, L Inada, T Nakamura, Y Pappas, A Court, DL AF Dasgupta, S Fernandez, L Kameyama, L Inada, T Nakamura, Y Pappas, A Court, DL TI Genetic uncoupling of the dsRNA-binding and RNA cleavage activities of the Escherichia coli endoribonuclease RNase III - the effect of dsRNA binding on gene expression SO MOLECULAR MICROBIOLOGY LA English DT Article ID DOUBLE-STRANDED-RNA; T7 EARLY RNAS; RIBONUCLEASE-III; BACTERIOPHAGE-LAMBDA; PROCESSING SIGNAL; PROTEIN-KINASE; HELICASE-A; OPERON; DOMAIN; TERMINATION AB RNase III, a double-stranded RNA-specific endonuclease, is proposed to be one of Escherichia coli's global regulators because of its ability to affect the expression of a large number of unrelated genes by influencing post-transcriptional control of mRNA stability or mRNA translational efficiency. Here, we describe the phenotypes of bacteria carrying point mutations in me, the gene encoding RNase III. The substrate recognition and RNA-processing properties of mutant proteins were analysed in vivo by measuring expression from known RNase III-modulated genes and in vitro from the proteins' binding and cleavage activities on known double-stranded RNA substrates, Our results show that although the point mutation rnc70 exhibited all the usual me null-like phenotypes, unlike other mutations, it was dominant over the wild-type allele, Multicopy expression of rnc70 could suppress a lethal phenotype of the wild-type me allele in a certain genetic background; it could also inhibit the RNase III-mediated activation of lambda N gene translation by competing for the RNA-binding site of the wild-type endonuclease. The mutant protein failed to cleave the standard RNase III substrates in vitro but exhibited an affinity for double-stranded RNA when passed through poly(rl):poly(rC) columns. Filter binding and gel-shift assays with purified Rnc70 showed that the mutant protein binds to known RNase III mRNA substrates in a site-specific manner. In vitro processing reactions with purified enzyme and labelled RNA showed that the in vivo dominant effect of the mutant enzyme over the wild-type was not necessarily caused by formation of mixed dimers. Thus, the rnc70 mutation generates a mutant RNase III with impaired endonucleolytic activity but without blocking its ability to recognize and bind double-stranded RNA substrates. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. Univ Tokyo, IMSUT Inst Med Sci, Dept Tumor Biol, Minato Ku, Tokyo 108, Japan. RP Court, DL (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Gene Regulat & Chromosome Biol Lab, POB B, Frederick, MD 21702 USA. EM court@ncifcrf.gov NR 47 TC 66 Z9 67 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD MAY PY 1998 VL 28 IS 3 BP 629 EP 640 DI 10.1046/j.1365-2958.1998.00828.x PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA ZP880 UT WOS:000073797900019 PM 9632264 ER PT J AU Greenberg, BD McMahon, FJ Murphy, DL AF Greenberg, BD McMahon, FJ Murphy, DL TI Serotonin transporter candidate gene studies in affective disorders and personality: promises and potential pitfalls SO MOLECULAR PSYCHIATRY LA English DT Editorial Material ID BIPOLAR AFFECTIVE-DISORDER; LINKAGE DISEQUILIBRIUM; CODING REGION; ASSOCIATION; SUSCEPTIBILITY; POLYMORPHISM; DEPRESSION C1 NIMH, Clin Sci Lab, Adult OCD Unit, NIH,Clin Ctr, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21218 USA. RP Greenberg, BD (reprint author), NIMH, Clin Sci Lab, Adult OCD Unit, NIH,Clin Ctr, Bldg 10-3D-41, Bethesda, MD 20892 USA. RI McMahon, Francis/A-7290-2009; OI McMahon, Francis/0000-0002-9469-305X NR 34 TC 41 Z9 41 U1 3 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAY PY 1998 VL 3 IS 3 BP 186 EP 189 DI 10.1038/sj.mp.4000415 PG 4 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA ZR702 UT WOS:000074005200001 PM 9672885 ER PT J AU Zhang, YL Akmal, KM Tsuruta, JK Shang, Q Hirose, T Jetten, AM Kim, KH O'Brien, DA AF Zhang, YL Akmal, KM Tsuruta, JK Shang, Q Hirose, T Jetten, AM Kim, KH O'Brien, DA TI Expression of germ cell nuclear factor (GCNF/RTR) during spermatogenesis SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article DE spermatogenesis; germ cell nuclear factor; nuclear orphan receptor; gene expression; transcription factors ID MESSENGER-RNA DEGRADATION; RECEPTOR SUPERFAMILY; GENE-EXPRESSION; MOLECULAR-CLONING; SERTOLI CELLS; RAT TESTIS; MOUSE; ACID; SPERMIOGENESIS; MEMBER AB Germ cell nuclear factor (GCNF/RTR), a novel orphan receptor in the nuclear receptor superfamily of ligand-activated transcription factors, is expressed predominantly in developing germ cells. In several mammalian species two GCNF/RTR mRNAs ave present in the testis, with the smaller 2.3-kb transcript generally expressed at higher levels than the larger 7.4- or 8.0-kb transcript. In both the mouse and rat, the 2.3- and 7.4-kb GCNF/RTR transcripts were detected in isolated spermatogenic cells, but not in Sertoli cells. Expression of these transcripts is differentially regulated, with the larger 7.4-kb mRNA appearing earlier during testicular development. The major 2.3-kb transcript is expressed predominantly in round spermatids in the mouse and vat. In situ hybridization studies in the rat demonstrated that GCNF/RTR transcripts reach maximal steady-state levels in round spermatids at stages VII and VIII of the spermatogenic cycle, and then decline abruptly as spermatids begin to elongate. RNase protection assays were used to predict the 3' termination site of the 2.3-kb transcript. An alternative polyadenylation signal (AGUAAA) was identified just upstream of this termination site. These studies suggest that GCNF/RTR may regulate transcription during spermatogenesis, particularly in round spermatids just prior to the initiation of nuclear elongation and condensation. (C) 1998 Wiley-Liss, Inc. C1 Univ N Carolina, Dept Pediat, Chapel Hill, NC 27514 USA. Univ N Carolina, Dept Cell Biol & Anat, Reprod Biol Lab, Chapel Hill, NC 27514 USA. Chinese Acad Sci, Shanghai Inst Biochem, State Key Lab Mol Biol, Shanghai 200031, Peoples R China. Washington State Univ, Dept Genet & Cell Biol, Dept Biochem & Biophys, Pullman, WA 99164 USA. Osaka Univ, Sch Med, Dept Med 3, Osaka, Japan. NIEHS, Pulm Pathobiol Lab, Cell Biol Sect, Res Triangle Pk, NC 27709 USA. RP O'Brien, DA (reprint author), Univ N Carolina, Dept Pediat, CB 7090, Chapel Hill, NC 27514 USA. EM dao@med.unc.edu RI Hirose, Takahisa /E-6117-2011; OI Jetten, Anton/0000-0003-0954-4445 FU FIC NIH HHS [TW00627]; NCI NIH HHS [CA16806]; NICHD NIH HHS [U54 HD035041, U54 HD35041] NR 43 TC 44 Z9 49 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 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD MAY PY 1998 VL 50 IS 1 BP 93 EP 102 DI 10.1002/(SICI)1098-2795(199805)50:1<93::AID-MRD12>3.3.CO;2-N PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA ZD296 UT WOS:000072671000012 PM 9547515 ER PT J AU Metman, LV Blanchet, PJ van den Munckhof, P Del Dotto, P Natte, R Chase, TN AF Metman, LV Blanchet, PJ van den Munckhof, P Del Dotto, P Natte, R Chase, TN TI A trial of dextromethorphan in parkinsonian patients with motor response complications SO MOVEMENT DISORDERS LA English DT Article DE NMDA; glutamate; motor complications ID NMDA RECEPTOR BLOCKADE; METHYL-D-ASPARTATE; SIGMA-LIGANDS; LEVODOPA; DISEASE; FLUCTUATIONS; PATHOGENESIS; DYSKINESIAS; ANTAGONISTS; MECHANISMS AB The effects of the NMDA antagonist dextromethorphan (DM) on levodopa-associated dyskinesias and motor fluctuations were studied in patients with advanced Parkinson's disease. During initial open-label dose escalation, 6 of 18 patients reported a beneficial effect at their individually determined optimal DM dose (range, 60-120 mg/day). The 12 remaining patients either experienced reversible side effects, particularly mild drowsiness, or decreased levodopa efficacy, and were therefore excluded from the study. The six responders entered the double-blind. placebo-controlled, crossover study with two 2-week arms separated by 1 week wash-out. On the last day of each arm, motor ratings were performed every 20 minutes for g consecutive hours. In addition, motor complications and Activities of Daily Living (ADL) were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and patient diaries. With Dh?, dyskinesias improved by 25% according to physician's ratings and by 40% according to UPDRS interviews, without compromising the anti-Parkinson effect of Ievodopa. Motor fluctuations and ADL scores also improved significantly. Although the narrow therapeutic index of DM limits its clinical usefulness, these findings support the view that drugs acting to inhibit glutamatergic transmission at the NMDA receptor can ameliorate levodopa-associated motor complications. C1 NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Chase, TN (reprint author), NINDS, Expt Therapeut Branch, NIH, Bldg 10,Room 5C104,10 Ctr Dr MSC 1406, Bethesda, MD 20892 USA. NR 21 TC 46 Z9 47 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAY PY 1998 VL 13 IS 3 BP 414 EP 417 DI 10.1002/mds.870130307 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA ZV257 UT WOS:000074286100006 ER PT J AU Pranzatelli, MR Huang, YY Tate, E Goldstein, DS Holmes, CS Goldstein, EM Ketner, K Kinast, M Lange, BM Sanz, A Shevell, MI Stanford, RE Taff, IP AF Pranzatelli, MR Huang, YY Tate, E Goldstein, DS Holmes, CS Goldstein, EM Ketner, K Kinast, M Lange, BM Sanz, A Shevell, MI Stanford, RE Taff, IP TI Monoaminergic effects of high-dose corticotropin in corticotropin-responsive pediatric opsoclonus-myoclonus SO MOVEMENT DISORDERS LA English DT Article DE ACTH; CSF 5-HIAA; HVA; myoclonus; opsoclonus; OMS; paraneoplastic ID INFANTILE SPASMS; ACTH; METABOLITES; RECEPTORS; SEROTONIN; PLASMA; BRAIN; CSF AB Children with the opsoclonus-myoclonus syndrome (OMS) usually respond to corticotropin (adrenocorticotrophic hormone, ACTH) treatment but the mechanism of benefit is unknown. We previously showed that both cerebrospinal fluid (CSF) homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations are low in pediatric OMS. In this study, we measured levels of CSF Dopa, catecholamines, deaminated metabolites of catecholamines, as well as HVA and 5-HIAA in eight patients before and during treatment with ACTH. All the children were ACTH-responsive with 50-70% improvement in multiple clinical features of OMS. ACTH treatment reduced the HVA concentration in every child by a mean of 21% (p < 0.001). Treatment with ACTH was associated with significant correlations between dopaminergic markers such as HVA, dihydroxyphenylacetic acid (DOPAC), and Dopa, There were no significant changes in the CSF concentrations of the noradrenergic markers norepinephrine (NE) and dihydroxyphenylglycol (DHPG): or the serotonergic marker 5-HIAA. The only child with a marked inflammatory pattern in CSF, which was reversed by ACTH, was atypical for a large increase in NE and decrease in 5-HIAA during ACTH treatment. Beneficial effects of ACTH in OMS are not associated with normalization of HVA or 5-HIAA levels. The pattern of decreased HVA and unchanged DOPAC levels could reflect decreased extraneuronal uptake of catecholamines (which steroids inhibit) or decreased O-methylation of catecholamines in nonneuronal cells. C1 Natl Pediat Myoclonus Ctr, Washington, DC 20036 USA. New York State Psychiat Inst, Dept Neurosci, New York, NY 10032 USA. Columbia Univ, Dept Psychiat, New York, NY 10032 USA. NINDS, Clin Neurosci Branch, NIH, Bethesda, MD USA. Scottish Rite Childrens Ctr, Atlanta, GA USA. UCSF Stanford Med Ctr, Dept Pediat, Palo Alto, CA USA. Arkansas Childrens Hosp, Div Child Neurol, Little Rock, AR 72202 USA. St Josephs Hosp, Dept Pediat, Paterson, NJ USA. Montreal Childrens Hosp, Montreal, PQ, Canada. Baptist Med Ctr, Dept Pediat, Oklahoma City, OK 73112 USA. RP Pranzatelli, MR (reprint author), Natl Pediat Myoclonus Ctr, 1828 L St,NW,Ste 402, Washington, DC 20036 USA. FU FDA HHS [FD-U-000955, FD-U-000746] NR 17 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAY PY 1998 VL 13 IS 3 BP 522 EP 528 DI 10.1002/mds.870130323 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA ZV257 UT WOS:000074286100022 PM 9613746 ER PT J AU Floeter, MK Gerloff, C Kouri, J Hallett, M AF Floeter, MK Gerloff, C Kouri, J Hallett, M TI Cutaneous withdrawal reflexes of the upper extremity SO MUSCLE & NERVE LA English DT Article DE flexor reflex; cutaneomuscular reflex; interlimb coordination; spinal cord; human ID AFFERENT STIMULATION; SILENT PERIOD; RESPONSES AB We characterized reflexes of the upper limb elicited by electrical stimulation of the fingers. Surface electromyogram (EMG) was recorded from several upper extremity muscles, and a finger was stimulated through paired ring electrodes. A train of 4-10 shocks at a frequency of 300 Hz and an intensity 4-6 times the perceptual threshold was the most effective stimulus for evoking EMG activity in relaxed arm muscles. Habituation was prominent. Latencies of EMG activity were <100 ms for most proximal and forearm muscles, and at least 40 ms prior to voluntary withdrawal movements. The timing of EMC; activity in arm muscles was similar to that of the E2 component of the cutaneomuscular reflex evoked in these same muscles during contraction, and coincided with a silent period in active hand muscles. We conclude that cutaneous stimuli to the fingers activate a complex motor pattern that tends to withdraw the hand at the same time the grasp is released. (C) 1998 John Wiley & Sons, Inc. C1 NINDS, EMG Sect, NIH, Bethesda, MD 20892 USA. RP Floeter, MK (reprint author), NINDS, EMG Sect, NIH, 10 Ctr Dr MSC 1404, Bethesda, MD 20892 USA. NR 18 TC 57 Z9 57 U1 1 U2 3 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD MAY PY 1998 VL 21 IS 5 BP 591 EP 598 DI 10.1002/(SICI)1097-4598(199805)21:5<591::AID-MUS5>3.0.CO;2-3 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA ZJ453 UT WOS:000073217200005 PM 9572238 ER PT J AU Gejman, PV Cao, QH Guedj, F Sommer, S AF Gejman, PV Cao, QH Guedj, F Sommer, S TI The sensitivity of denaturing gradient gel electrophoresis: A blinded analysis SO MUTATION RESEARCH-GENOMICS LA English DT Article DE denaturing gradient gel electrophoresis (DGGE); mutation; detection; analysis; method; control ID DNA FRAGMENTS; GC-CLAMP; MUTATIONS; ATTACHMENT; SEQUENCE; SSCP AB Denaturing gradient gel electrophoresis (DGGE) is considered one of the most sensitive and specific of the mutational scanning techniques, yet blinded analyses have not been reported. We report the results of a blinded study of the efficiency of DGGE to detect mutations in the Human Coagulation Factor IX. Two overlapping genomic DNA sequences from exon 8 of Factor IX (290 bp and 539 bp length) with an unknown number of mutations were amplified with a 40 bp GC-clamp and tested blindly by DGGE. DGGE detected all mutations in the 290 bp genomic DNA segment. DGGE detected all but one mutation in the 539 bp genomic segment after experimental conditions were fully optimized but missed multiple mutations in an initial blinded experiment. These results demonstrate the utility of blinded analyses and confirm the exquisite power of DGGE for detecting mutations. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NIMH, Unit Mol Clin Invest, Clin Neurogenet Branch, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Dept Biochem & Mol Biol, Rochester, MN 55905 USA. RP Gejman, PV (reprint author), NIMH, Unit Mol Clin Invest, Clin Neurogenet Branch, 10 Ctr Dr MSC 1384, Bethesda, MD 20892 USA. NR 11 TC 21 Z9 23 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5726 J9 MUTAT RES-GENOMICS JI Mutat. Res.-Genomics PD MAY PY 1998 VL 382 IS 3-4 BP 109 EP 114 DI 10.1016/S1383-5726(98)00002-8 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 128LN UT WOS:000076407900006 PM 9691991 ER PT J AU Yang, T Adamson, TE Resnick, JL Leff, S Wevrick, R Francke, U Jenkins, NA Copeland, NG Brannan, CI AF Yang, T Adamson, TE Resnick, JL Leff, S Wevrick, R Francke, U Jenkins, NA Copeland, NG Brannan, CI TI A mouse model for Prader-Willi syndrome imprinting-centre mutations SO NATURE GENETICS LA English DT Article ID ANGELMAN SYNDROME; SNRPN GENE; UNIPARENTAL DISOMY; PARENTAL ORIGIN; EXPRESSED GENE; POLYPEPTIDE-N; PROTEIN-N; DELETIONS; REGION; HUMAN-CHROMOSOME-15 AB Imprinting in the 15q11-q13 region involves an 'imprinting centre' (IC), mapping in part to the promoter and first exon of SNRPN. Deletion of this IC abolishes local paternally derived gene expression and results in Prader-Willi syndrome (PWS). We have created two deletion mutations in mice to understand PWS and the mechanism of this IC. Mice harbouring an intragenic deletion in Snrpn are phenotypically normal, suggesting that mutations of SNRPN are not sufficient to induce PWS. Mice with a larger deletion involving both Snrpn and the putative PWS-IC lack expression of the imprinted genes Zfp127 (mouse homologue of ZNF127) Ndn and Ipw, and manifest several phenotypes common to PWS infants. These data demonstrate that both the position of the IC and its role in the coordinate expression of genes is conserved between mouse and human, and indicate that the mouse is a suitable model system in which to investigate the molecular mechanisms of imprinting in this region of the genome. C1 Univ Florida, Coll Med, Dept Microbiol & Mol Genet, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Ctr Mammalian Genet, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Inst Brain, Gainesville, FL 32610 USA. Cell Genesys Inc, Foster City, CA 94404 USA. Univ Alberta, Heritage Med Res Ctr 659, Dept Med Genet, Edmonton, AB T6G 2S2, Canada. Stanford Univ, Sch Med, Dept Genet, Beckman Ctr Mol & Genet Med, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Howard Hughes Med Inst, Beckman Ctr Mol & Genet Med, Stanford, CA 94305 USA. NCI, Frederick Canc Res & Dev Ctr, Mammalian Genet Lab, ABL Basic Res Program, Frederick, MD 21702 USA. RP Brannan, CI (reprint author), Univ Florida, Coll Med, Dept Microbiol & Mol Genet, Gainesville, FL 32610 USA. OI Wevrick, Rachel/0000-0002-3343-5794 FU NIGMS NIH HHS [GM55272] NR 44 TC 214 Z9 217 U1 1 U2 7 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 MAY PY 1998 VL 19 IS 1 BP 25 EP 31 DI 10.1038/ng0598-25 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA ZK651 UT WOS:000073346700012 PM 9590284 ER PT J AU Folkers, GK Fauci, AS AF Folkers, GK Fauci, AS TI The role of US Government agencies in vaccine research and development SO NATURE MEDICINE LA English DT Editorial Material ID STATES C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Folkers, GK (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 22 TC 11 Z9 11 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 MAY PY 1998 VL 4 IS 5 SU S BP 491 EP 494 DI 10.1038/nm0598supp-491 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA ZL625 UT WOS:000073453500011 PM 9585193 ER PT J AU Miller, LH Hoffman, SL AF Miller, LH Hoffman, SL TI Research toward vaccines against malaria SO NATURE MEDICINE LA English DT Review ID PLASMODIUM-FALCIPARUM; PROTECTIVE IMMUNITY; VACCINATION; PROTEINS; PEPTIDE; DOMAINS; IDENTIFICATION; ERYTHROCYTES; INDUCTION; EFFICACY C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. USN, Med Res Inst, Malaria Program, Bethesda, MD 20889 USA. RP Miller, LH (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. EM louis_miller@nih.gov NR 40 TC 87 Z9 87 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 MAY PY 1998 VL 4 IS 5 SU S BP 520 EP 524 DI 10.1038/nm0598supp-520 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA ZL625 UT WOS:000073453500021 PM 9585203 ER PT J AU Heilman, CA Baltimore, D AF Heilman, CA Baltimore, D TI HIV vaccines - where are we going? SO NATURE MEDICINE LA English DT Review ID IMMUNODEFICIENCY-VIRUS TYPE-1; ANTIBODY-RESPONSES; NEUTRALIZING ANTIBODIES; INFECTION; AIDS; ENV C1 NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. CALTECH, Pasadena, CA 91125 USA. RP Heilman, CA (reprint author), NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. NR 38 TC 50 Z9 50 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 MAY PY 1998 VL 4 IS 5 SU S BP 532 EP 534 DI 10.1038/nm0598supp-532 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA ZL625 UT WOS:000073453500023 PM 9585205 ER PT J AU Ioannidis, JPA O'Brien, TR Rosenberg, PS Contopoulos-Ioannidis, DG Goedert, JJ AF Ioannidis, JPA O'Brien, TR Rosenberg, PS Contopoulos-Ioannidis, DG Goedert, JJ TI Genetic effects on HIV disease progression SO NATURE MEDICINE LA English DT Letter C1 NIAID, HIV Res Branch, Div Aids, NIH, Bethesda, MD 20852 USA. NCI, Viral Epidemiol Branch, NIH, Bethesda, MD 20852 USA. NCI, Biostat Branch, NIH, Bethesda, MD 20852 USA. Childrens Natl Med Ctr, Dept Pediat Infect Dis, Washington, DC 20010 USA. RP Ioannidis, JPA (reprint author), NIAID, HIV Res Branch, Div Aids, NIH, Bethesda, MD 20852 USA. RI Ioannidis, John/G-9836-2011 NR 6 TC 48 Z9 48 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 1998 VL 4 IS 5 BP 536 EP 536 DI 10.1038/nm0598-536 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA ZL111 UT WOS:000073399900002 PM 9585207 ER PT J AU Jacobson, S Soldan, SS Berti, R AF Jacobson, S Soldan, SS Berti, R TI HHV-6 and multiple sclerosis - Soldan et al. reply SO NATURE MEDICINE LA English DT Letter C1 NIH, Viral Immunol Sect, Bethesda, MD 20892 USA. RP Jacobson, S (reprint author), NIH, Viral Immunol Sect, Bldg 10,Room 5B-16, Bethesda, MD 20892 USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 1998 VL 4 IS 5 BP 538 EP 538 DI 10.1038/nm0598-538 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA ZL111 UT WOS:000073399900005 ER PT J AU Zhan, S Helman, LJ AF Zhan, S Helman, LJ TI Glimpsing the cause of rhabdomyosarcoma SO NATURE MEDICINE LA English DT Editorial Material ID ALVEOLAR RHABDOMYOSARCOMA; GENE; EXPRESSION; FUSION; CELLS C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Zhan, S (reprint author), NCI, Pediat Oncol Branch, Bldg 10,10 Ctr Dr,Room 13N240, Bethesda, MD 20892 USA. EM helmanl@pbmac.nci.nih.gov NR 13 TC 14 Z9 14 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 1998 VL 4 IS 5 BP 559 EP 560 DI 10.1038/nm0598-559 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA ZL111 UT WOS:000073399900024 PM 9585226 ER PT J AU Cairns, JS D'Souza, MP AF Cairns, JS D'Souza, MP TI Chemokines and HIV-1 second receptors: The therapeutic connection SO NATURE MEDICINE LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; SINGLE-CHAIN ANTIBODY; SELECTIVE-INHIBITION; TYPE-1 GP120; INFECTION; ENTRY; PROGRESSION; REPLICATION; POTENT; CCR5 AB The discovery that HIV requires a chemokine co-receptor to invade host cells has prompted many investigations into therapeutic strategies that target these receptors in an attempt to block HIV entry. In this review, Scott Cairns and Patricia D'Souza discuss these potentially powerful approaches and how they complement existing antiretroviral drug therapy. C1 NIAID, Targeted Intervent Branch, Div Aids, Bethesda, MD 20892 USA. NIAID, Pathogenesis & Basic Res Branch, Div Aids, Bethesda, MD 20892 USA. RP D'Souza, MP (reprint author), NIAID, Targeted Intervent Branch, Div Aids, Solar Bldg 2C34, Bethesda, MD 20892 USA. NR 76 TC 100 Z9 101 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 MAY PY 1998 VL 4 IS 5 BP 563 EP 568 DI 10.1038/nm0598-563 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA ZL111 UT WOS:000073399900027 PM 9585229 ER PT J AU Hahn, H Wojnowski, L Zimmer, AM Hall, J Miller, G Zimmer, A AF Hahn, H Wojnowski, L Zimmer, AM Hall, J Miller, G Zimmer, A TI Rhabdomyosarcomas and radiation hypersensitivity in a mouse model of Gorlin syndrome SO NATURE MEDICINE LA English DT Article ID CELL CARCINOMA SYNDROME; NEVUS SYNDROME; HUMAN HOMOLOG; GENE AB Gorlin (or nevoid basal cell carcinoma) syndrome is characterized by a variety of clinical problems including generalized overgrowth of the body, cysts, developmental abnormalities of the skeleton and a predisposition to benign and malignant tumors(1,2). The syndrome results from germline mutations of the human homolog of the drosophila segment polarity gene patched (ptc)(3,4). Here we report that mice heterozygous for ptc develop many of the features characteristic of Gorlin syndrome and that they exhibit a high incidence of rhabdomyosarcomas (RMS), the most common soft-tissue sarcoma in children(5). The downstream signalling partner of ptc, gli1, was overexpressed in all RMSs analyzed, indicating that abnormal signalling of the ptc-gli1 pathway may be common for the various tumors(6,7) associated with the syndrome. igf2, implicated in the formation of RMSs(8), was also overexpressed, suggesting cross-talk between the ptc and igf2 pathways in tumorigenesis. Developemental defects in Gorlin syndrome resemble those induced by ionizing radiation(9). We show that ptc heterozygous mice exhibit increased incidence of radiation-induced teratogenesis. This suggests a role for ptc in the response to ionizing radiation and provides a model for both the systemic (developmental) and stochastic (cancer) abnormalities observed in Gorlin syndrome. C1 NIMH, Genet Sect, Bethesda, MD 20892 USA. Natl Inst Res Resources, Vet Resources Program, NIH, Bethesda, MD 20892 USA. RP Zimmer, A (reprint author), NIMH, Genet Sect, 36 Convent Dr,Room 3006, Bethesda, MD 20892 USA. RI Zimmer, Andreas/B-8357-2009 NR 20 TC 290 Z9 295 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 MAY PY 1998 VL 4 IS 5 BP 619 EP 622 DI 10.1038/nm0598-619 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA ZL111 UT WOS:000073399900037 PM 9585239 ER PT J AU Optican, LM AF Optican, LM TI Low rates yield big returns SO NATURE NEUROSCIENCE LA English DT News Item ID CEREBELLUM; NEURONS; MODEL AB The function of cerebellar climbing fibers is controversial, one puzzle being their very low firing rates. The application of information theory is now providing some answers. C1 NEI, Sect Neural Modeling, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Optican, LM (reprint author), NEI, Sect Neural Modeling, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. NR 15 TC 1 Z9 1 U1 0 U2 0 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 MAY PY 1998 VL 1 IS 1 BP 8 EP 9 DI 10.1038/204 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 127QA UT WOS:000076361000006 PM 10195099 ER PT J AU Choi, HJ Kang, SW Yang, CH Rhee, SG Ryu, SE AF Choi, HJ Kang, SW Yang, CH Rhee, SG Ryu, SE TI Crystal structure of a novel human peroxidase enzyme at 2.0 angstrom resolution SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID THIOL-SPECIFIC ANTIOXIDANT; SELENOENZYME GLUTATHIONE-PEROXIDASE; CYSTEINE-SULFENIC ACID; REFINED STRUCTURE; NADH PEROXIDASE; REDOX CENTER; THIOREDOXIN; REDUCTASE; PROGRAM; H2O2 AB Hydrogen peroxide (H2O2) has been implicated recently as an intracellular messenger that affects cellular processes including protein phosphorylation, transcription and apoptosis, A set of novel peroxidases, named peroxiredoxins (Prx), regulate the intracellular concentration of H2O2 by reducing it in the presence of an appropriate electron donor. The crystal structure of a human Prx enzyme, hORF6, reveals that the protein contains two discrete domains and forms a dimer, The N-terminal domain has a thioredoxin fold and the C-terminal domain is used for dimerization. The active site cysteine (Cys 47), which exists as cysteine-sulfenic acid in the crystal, is located at the bottom of a relatively narrow pocket. The positively charged environment surrounding Cys 47 accounts for the peroxidase activity of the enzyme, which contains no redox cofactors. C1 KIST, Korea Res Inst Biosci & Biotechnol, Div Prot Engn, Taejon 305600, South Korea. NHLBI, Lab Cell Singaling, NIH, Bethesda, MD 20892 USA. Seoul Natl Univ, Coll Nat Sci, Dept Chem, Seoul 151742, South Korea. RP Ryu, SE (reprint author), KIST, Korea Res Inst Biosci & Biotechnol, Div Prot Engn, POB 115, Taejon 305600, South Korea. NR 34 TC 259 Z9 278 U1 1 U2 15 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 MAY PY 1998 VL 5 IS 5 BP 400 EP 406 DI 10.1038/nsb0598-400 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA ZL597 UT WOS:000073450300018 PM 9587003 ER PT J AU Veneman, TF Tack, CJJ van Haeften, TW AF Veneman, TF Tack, CJJ van Haeften, TW TI The newly developed sulfonylurea glimepiride: a new ingredient, an old recipe SO NETHERLANDS JOURNAL OF MEDICINE LA English DT Article DE glimepiride; SU derivatives; diabetes mellitus; hypoglycemia ID DEPENDENT DIABETES-MELLITUS; STIMULATED INSULIN RELEASE; POTASSIUM CHANNELS; ADIPOSE-TISSUE; NIDDM; GLUCOSE; GLIBENCLAMIDE; RECEPTOR; PATHOGENESIS; IMPROVEMENT AB Disturbances in insulin secretion and insulin action are both involved in the pathophysiology of type 2 (or non-insulin-dependent) diabetes mellitus. The newly developed sulfonylurea (SU) derivative glimepiride has a marked insulin secretory effect both in vitro and in vivo, and is capable of increasing plasma insulin levels with approximately 50% in type 2 diabetes subjects. Glimepiride improves metabolic control comparable but not superior to other (second generation) SU derivatives. Although it has been advocated for once-daily use, maximum effect is presumably achieved by twice-daily dosing. One of the most important side-effects of SU remains hypoglycemia in some patients, which may last for several hours. Although there is some indication that the use of glimepiride leads to fewer hypoglycemic episodes than glibenclamide, the differences reported sofar are not statistically significant. (C) 1998 Elsevier Science B.V. C1 Univ Utrecht Hosp, Dept Internal Med G02 228, NL-3508 GA Utrecht, Netherlands. NINDS, Clin Neurosci Branch, Dept Hlth, Bethesda, MD 20892 USA. RP van Haeften, TW (reprint author), Univ Utrecht Hosp, Dept Internal Med G02 228, POB 85500, NL-3508 GA Utrecht, Netherlands. RI Tack, Cees/A-2368-2014 NR 50 TC 1 Z9 2 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0300-2977 J9 NETH J MED JI Neth. J. Med. PD MAY PY 1998 VL 52 IS 5 BP 179 EP 186 DI 10.1016/S0300-2977(98)00048-5 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA ZU963 UT WOS:000074254100005 PM 9652156 ER PT J AU Axelrod, J Felder, CC AF Axelrod, J Felder, CC TI Cannabinoid receptors and their endogenous agonist, anandamide SO NEUROCHEMICAL RESEARCH LA English DT Article DE marijuana; anandamide; fatty acid ethanolamide; cannabinoids; receptors; G proteins; signal transduction; adenylate cyclase ID MEDIATED SIGNAL-TRANSDUCTION; CEREBRAL-CORTEX SLICES; ARACHIDONIC-ACID; RAT-BRAIN; ADENYLATE-CYCLASE; MOLECULAR CHARACTERIZATION; ENZYMATIC-SYNTHESIS; IN-VIVO; INHIBITION; LIGAND AB Cannabinoids are a class of compound found in marijuana which have been known for their therapeutic and psychoactive properties for at least 4000 years. Isolation of the active principle in marijuana, Delta 9-THC, provided the lead structure in the development of highly potent congeners which were used to probe for the mechanism of marijuana action. Cannabinoids were shown to bind to selective binding sites in brain tissue thereby regulating second messenger formation. Such studies led to the cloning of three cannabinoid receptor subtypes, CB1, CB2, and CB1A all of which belong to the superfamily of G protein-coupled plasma membrane receptors. Analogous to the discovery of endogenous opiates, isolation of cannabinoid receptors provided the appropriate tool to isolate an endogenous cannabimimetic eicosanoid, anandamide, from porcine brain. Recent studies indicate that anandamide is a member of a family of fatty acid ethanolamides that may represent a novel class of lipid neurotransmitters. This review discusses recent progress in cannabinoid research with a focus on the receptors for Delta 9-THC, their coupling to second messenger responses, and the endogenous lipid cannabimimetic, anandamide. C1 Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. NIMH, Bethesda, MD 20892 USA. RP Axelrod, J (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. EM felder@lilly.com NR 49 TC 58 Z9 59 U1 0 U2 3 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD MAY PY 1998 VL 23 IS 5 BP 575 EP 581 DI 10.1023/A:1022418217479 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA ZG369 UT WOS:000072994700002 PM 9566594 ER PT J AU Barbieri, D Abbracchio, MP Salvioli, S Monti, D Cossarizza, A Ceruti, S Brambilla, R Cattabeni, F Jacobson, KA Franceschi, C AF Barbieri, D Abbracchio, MP Salvioli, S Monti, D Cossarizza, A Ceruti, S Brambilla, R Cattabeni, F Jacobson, KA Franceschi, C TI Apoptosis by 2-chloro-2 '-deoxy-adenosine and 2-chloro-adenosine in human peripheral blood mononuclear cells SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article ID NECROSIS-FACTOR-ALPHA; HUMAN-LYMPHOCYTES; HUMAN THYMOCYTES; LEUKEMIA-CELLS; ADENOSINE; 2-CHLORO-2'-DEOXYADENOSINE; DEOXYADENOSINE; DEATH; 2-CHLORODEOXYADENOSINE; 2-CHLOROADENOSINE AB Adenosine has profound effects on immune cells and has been implicated in the intrathymic apoptotic deletion of T-cells during development. In order to characterize adenosine effects on quiescent peripheral blood mononuclear cells (PBMC), we have evaluated the ability of the previously characterized adenosine receptor agonist 2-chloro-adenosine (2CA; Ceruti, Barbieri et al., 1997) and of the antineoplastic drug 2-chloro-2'-deoxy-adenosine (2CdA, cladribine) to trigger apoptosis of PBMC. Apoptosis was assessed by morphological changes, DNA fragmentation by agarose gel electrophoresis and appearance of hypodiploid DNA peak by flow cytometry. 2CA (10 mu M) and 2CdA (1 mu M) induced apoptosis in human PBMC, which are relatively insensitive to apoptosis. For both agents, the effect was concentration- and time-dependent, although 2CdA induced apoptosis more potently than 2CA. Evaluation of mitochondrial function in parallel samples using the mitochondrial membrane-potential-specific dye JC-1 showed that mitochondrial damage followed the same kinetics as apoptosis, hence an early damage of mitochondria is likely not responsible for adenosine-induced death of PBMC. The effect of 2CA was partially prevented by addition of dipyridamole (DP), a nucleoside transport inhibitor, hence some of the apoptotic effect of this nucleoside is, at least in part, due to intracellular action. Alternatively, DP did not affect 2CdA-induced apoptosis, suggesting that 2CdA may enter cells via a DP-insensitive transporter. 5-Iodotubercidin (5-Itu), a nucleoside kinase inhibitor, was also able to partially prevent the action of 2CA and was not able to affect 2CdA-induced apoptosis, suggesting a different role for phosphorylation in 2CA- vs 2CdA-induced apoptosis. To test the role of P1 receptors, agonists and antagonists selective at various P1 receptor subtypes were used. Data suggest that, for 2CA, apoptosis is partially sustained by activation of the A,, receptor subtype, whereas no role is exerted by P1 receptors in 2CdA-dependent apoptosis. Moreover, in these cells, apoptosis could also be triggered through intense activation of the A(3) receptor via selective agonists such as 2-chloro-N-6-(3-iodobenzyl)adenosine-5'-N-methyluronamide (CI-IB-MECA), but this mechanism plays no role in either 2CA- or 2CdA-induced apoptosis. On the whole, our results suggest that 2CA and 2CdA follow different pathways in inducing apoptosis of immune cells. Moreover, our data also suggest that there are at least three different ways by which adenosine derivatives may induce apoptosis of human PBMC: (i) through an A(2A)-like extracellular membrane receptor; (ii) through entry of nucleosides into cells and direct activation of intracellular events involved in the apoptotic process; or (iii) through activation of the A(3) receptor. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Univ Milan, Inst Pharmacol Sci, I-20133 Milan, Italy. Univ Modena, Dept Biomed Sci, Sect Gen Pathol, I-41100 Modena, Italy. NIDDK, Mol Recogn Sect, Bioorgan Chem Lab, NIH, Bethesda, MD USA. INRCA, I-60100 Ancona, Italy. RP Abbracchio, MP (reprint author), Univ Milan, Inst Pharmacol Sci, Via Balzaretti 9, I-20133 Milan, Italy. RI Ceruti, Stefania/A-6376-2008; Jacobson, Kenneth/A-1530-2009; Abbracchio, Maria Pia/B-9342-2014; Monti, Daniela/G-9556-2012; Salvioli, Stefano/K-6663-2016; OI Ceruti, Stefania/0000-0003-1663-4211; Jacobson, Kenneth/0000-0001-8104-1493; Abbracchio, Maria Pia/0000-0002-7833-3388; Monti, Daniela/0000-0001-8651-8123; Salvioli, Stefano/0000-0002-6191-1225; Cossarizza, Andrea/0000-0002-5381-1558 FU NIMH NIH HHS [N01MH30003] NR 43 TC 57 Z9 57 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD MAY-JUN PY 1998 VL 32 IS 5-6 BP 493 EP 504 DI 10.1016/S0197-0186(97)00129-0 PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA ZX493 UT WOS:000074521700014 PM 9676749 ER PT J AU Mezey, E Eisenhofer, G Hansson, S Hunyady, B Hoffman, BJ AF Mezey, E Eisenhofer, G Hansson, S Hunyady, B Hoffman, BJ TI Dopamine produced by the stomach may act as a paracrine/autocrine hormone in the rat SO NEUROENDOCRINOLOGY LA English DT Article DE stomach; sympathectomy; monoamine transporters; parietal cells; catecholamines; peripheral neuroendocrinology ID MUCOSAL BLOOD-FLOW; VESICULAR MONOAMINE TRANSPORTER; GASTRIC-ACID SECRETION; GASTROINTESTINAL-TRACT; DIFFERENTIAL EXPRESSION; BICARBONATE SECRETION; MOLECULAR-CLONING; UPTAKE INHIBITOR; PORCINE JEJUNUM; NERVOUS-SYSTEM AB Dopamine (DA) has been suggested to be a protective factor in the gastrointestinal tract but neither a source of DA nor its exact targets of action have been identified. In this study, we demonstrate high levels of DA (and DOPA) which persist after chemical sympathectomy in the gastric juice of rats. Immunostaining and in situ hybridization histochemistry reveal the presence of tyrosine hydroxylase (TH), DA transporter and vesicular monamine transporters in the acid-producing parietal cells. Like DA, TH enzyme activity remains after chemical sympathectomy. We also demonstrate active reuptake and storage of DA that indicates a regulated release of this neurohormone from parietal cells. DA Dib receptor mRNA is the most abundant DA receptor subtype in gastric and duodenal epithelium. Therefore, we suggest that selective DA Dib receptor agonists may be useful adjuncts in the treatment of duodenal and gastric ulcers. Gastric epithelia possess the hallmarks of functional DA neuroendocrine cells, suggesting that DA has an important role in self-protective mechanisms of the gastrointestinal tract. These findings should allow elucidation of DA role in normal and disease states in the stomach and duodenum. C1 NINDS, Basic Neurosci Branch, Bethesda, MD 20892 USA. NINDS, Clin Neurosci Branch, Bethesda, MD 20892 USA. NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. NIMH, People Investigating Genes, Bethesda, MD 20892 USA. Dept Med 1, Pecs, Hungary. RP Mezey, E (reprint author), NINDS, Basic Neurosci Branch, Bldg 36,3D06, Bethesda, MD 20892 USA. NR 87 TC 27 Z9 27 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD MAY PY 1998 VL 67 IS 5 BP 336 EP 348 DI 10.1159/000054332 PG 13 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA ZR389 UT WOS:000073970100007 PM 9641616 ER PT J AU Goldberg, TE Berman, KF Fleming, K Ostrem, J Van Horn, JD Esposito, G Mattay, VS Gold, JM Weinberger, DR AF Goldberg, TE Berman, KF Fleming, K Ostrem, J Van Horn, JD Esposito, G Mattay, VS Gold, JM Weinberger, DR TI Uncoupling cognitive workload and prefrontal cortical physiology: A PET rCBF study SO NEUROIMAGE LA English DT Article DE PET; cognition; humans; working memory; dual task; frontal lobe ID POSITRON EMISSION TOMOGRAPHY; WORKING-MEMORY; COMPREHENSION; SCHIZOPHRENIA; PERFORMANCE; CEREBELLUM; ACTIVATION; CORTEX; WORDS AB Working memory is a fundamental cognitive building block, involved in the short-term maintenance and transformation of information. In neuropsychological studies, working memory has been shown to be of limited capacity; however, the neurophysiological concomitants of this capacity limitation have not been explored. In this study we used the [O-15]water PET rCBF technique and statistical parametric mapping to examine normal subjects while they performed two cognitive basks, both individually and simultaneously, One task was the Wisconsin Card Sorting Test, a complex reasoning task involving working memory, and the other was a rapidly paced auditory verbal shadowing task. When both tasks were performed simultaneously, there were significant decrements in performance compared with the individual task performance scores, indicating that cognitive workload had been increased. Analysis of the rCBF maps showed that when the two tasks were performed together, in contrast to when they were performed separately, there was less prefrontal activation. These results suggest that increases in cognitive workload do not necessarily recruit and then sustain cortical neurophysiological resources to a maximum, but rather may actually be accompanied by a diminution in cortical activity. (C) 1998 Academic Press. C1 St Elizabeth Hosp, Ctr Neurosci, NIMH,Intramural Res Program, Clin Brain Disorders Branch,NIH, Washington, DC 20032 USA. RP Goldberg, TE (reprint author), St Elizabeth Hosp, Ctr Neurosci, NIMH,Intramural Res Program, Clin Brain Disorders Branch,NIH, Washington, DC 20032 USA. NR 32 TC 95 Z9 102 U1 1 U2 6 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY PY 1998 VL 7 IS 4 BP 296 EP 303 DI 10.1006/nimg.1998.0338 PN 1 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA ZT101 UT WOS:000074048500003 PM 9626670 ER PT J AU Metman, LV Del Dotto, P van den Munckhof, P Fang, J Mouradian, MM Chase, TN AF Metman, LV Del Dotto, P van den Munckhof, P Fang, J Mouradian, MM Chase, TN TI Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson's disease SO NEUROLOGY LA English DT Article ID TARDIVE-DYSKINESIA; NMDA; ANTAGONIST; BLOCKADE; LEVODOPA; BRAIN; SITE AB Objective: To determine the effects of the N-methyl-D-aspartate (NMDA) antagonist amantadine on levodopa-associated dyskinesias and motor fluctuations in Parkinson's disease (PD). Background: NMDA receptor blockade can ameliorate levodopa-induced dyskinesias in primates and PD patients. Amantadine, a well-tolerated and modestly effective antiparkinsonian agent, was recently found to possess NMDA antagonistic properties. Methods: Eighteen patients with advanced PD participated in a double-blind, placebo-controlled, cross-over study. At the end of each 3-week treatment arm, parkinsonian and dyskinesia scores were obtained during a steady-state intravenous levodopa infusion. Motor fluctuations and dyskinesias were also documented with patient-kept diaries and Unified Parkinson's Disease Rating Scale (UPDRS) interviews. Results: In the 14 patients completing this trial, amantadine reduced dyskinesia severity by 60% (p = 0.001) compared to placebo, without altering the antiparkinsonian effect of levodopa. Motor fluctuations occurring with patients' regular oral levodopa regimen also improved according to UPDRS and patient-kept diaries. Conclusions: These findings suggest that amantadine given as adjuvant to levodopa can markedly improve motor response complications and support the view that hyperfunction of NMDA receptors contributes to the pathogenesis of levodopa-associated motor complications. C1 NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Chase, TN (reprint author), NINDS, Expt Therapeut Branch, NIH, Bldg 10,Room 5C104,10 Ctr Dr MSC 1406, Bethesda, MD 20892 USA. OI Mouradian, M. Maral/0000-0002-9937-412X NR 24 TC 211 Z9 214 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1998 VL 50 IS 5 BP 1323 EP 1326 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA ZN179 UT WOS:000073617800025 ER PT J AU Gorell, JM Johnson, CC Rybicki, BA Peterson, EL Richardson, RJ AF Gorell, JM Johnson, CC Rybicki, BA Peterson, EL Richardson, RJ TI The risk of Parkinson's disease with exposure to pesticides, farming, well water, and rural living SO NEUROLOGY LA English DT Article ID YOUNG-ONSET; EPIDEMIOLOGY; IRON AB We assessed exposure to pesticides, farming, well water use, and rural living as risk factors for Parkinson's disease (PD) in a population-based case-control study consisting of men and women greater than or equal to 50 years of age who had primary medical care at Henry Ford Health System in metropolitan Detroit. Enrolled PD patients (n = 144) and control subjects (n = 464) were frequency-matched for age, race, and sex. When adjusted for these variables and smoking status, there was a significant association of occupational exposure to herbicides (odds ratio [OR], 4.10; 95% CI, 1.37, 12.24) and insecticides (OR, 3.55; 95% CI, 1.75, 7.18) with PD, but no relation was found with fungicide exposure. Farming as an occupation was significantly associated with PD (OR, 2.79; 95% CI, 1.03, 7.55), but there was no increased risk of the disease with rural or farm residence or well water use. The association of occupational exposure to herbicides or insecticides with PD remained after adjustment for farming. The association of farming with PD was maintained after adjustment for occupational herbicide exposure and was of borderline significance after adjustment for occupational insecticide exposure. These results suggest that PD is associated with occupational exposure to herbicides and insecticides and to farming and that the risk, of farming cannot be accounted for by pesticide exposure alone. C1 Henry Ford Hlth Syst, Dept Neurol, Detroit, MI USA. Henry Ford Hlth Syst, Dept Biostat & Res Epidemiol, Detroit, MI USA. Wayne State Univ, NIEHS, Ctr Mol & Cellular Toxicol Human Applicat, Detroit, MI USA. Univ Michigan, Sch Publ Hlth, Dept Environm & Ind Hlth, Toxicol Program, Ann Arbor, MI 48109 USA. RP Gorell, JM (reprint author), Henry Ford Hosp & Hlth Sci Ctr, Dept Neurol, 2799 W Grand Blvd, Detroit, MI 48202 USA. OI Richardson, Rudy/0000-0002-2028-5723; Johnson, Christine Cole/0000-0002-6864-6604 FU NIEHS NIH HHS [ES 06418] NR 27 TC 410 Z9 424 U1 7 U2 36 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1998 VL 50 IS 5 BP 1346 EP 1350 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA ZN179 UT WOS:000073617800029 PM 9595985 ER PT J AU Shoulson, I Penney, J Kieburtz, K Oakes, D Chase, T Choi, D Marder, K Moskowitz, C Zubin, N Ventura, P Feigin, A Hickey, C Como, P Richard, IH Goldstein, J Hersch, S Bissey-Black, C Jones, R Swenson, M Bell, J Paulsen, JS Swenson, A Tawfik-Reedy, Z Orme, C Plumb, S Rudolph, A Claude, K McMullen, N Day, D Marshall, FJ Bourgeois, K Watts, A Tariot, PN Jackson, WJ Hall, WJ Maddrey, W Biziere, K Jaffe, M AF Shoulson, I Penney, J Kieburtz, K Oakes, D Chase, T Choi, D Marder, K Moskowitz, C Zubin, N Ventura, P Feigin, A Hickey, C Como, P Richard, IH Goldstein, J Hersch, S Bissey-Black, C Jones, R Swenson, M Bell, J Paulsen, JS Swenson, A Tawfik-Reedy, Z Orme, C Plumb, S Rudolph, A Claude, K McMullen, N Day, D Marshall, FJ Bourgeois, K Watts, A Tariot, PN Jackson, WJ Hall, WJ Maddrey, W Biziere, K Jaffe, M CA Huntington Study Grp TI Safety and tolerability of the free-radical scavenger OPC-14117 in Huntington's disease SO NEUROLOGY LA English DT Article ID LIQUID-CHROMATOGRAPHY; QUINOLINIC ACID; LESIONS; INHIBITION; DISORDERS; MALONATE; CHOREA AB Oxidative damage due to free-radical generation in the setting of underlying defects of neuronal energy metabolism has been implicated as a pathogenetic mechanism for Huntington's disease (HD). The authors conducted a randomized, double-blind, placebo-controlled, multicenter trial of the tolerability of OPC-14117, a lipophilic free-radical scavenger that concentrates in the brain. Ambulatory patients with HD received OPC-14117 60 mg/d, 120 mg/d, 240 mg/d, or placebo and were assessed by the Unified Huntington's Disease Rating Scale (UHDRS) for 20 weeks, including 12 or 16 weeks of assigned treatment and 8 or 4 weeks of blinded withdrawal of the study drug. Tolerability was measured by the proportion of patients completing the initial 12-week course of treatment on their originally assigned regimen. Sixty-four patients were enrolled in the study, 56 of whom completed the 12 weeks of treatment. Treatment was discontinued in four patients (1 placebo, 1 60 mg/d, 2 240 mg/d) due to asymptomatic but persistent serum elevations of liver transaminase. Two patients (1 60 mg/d and 1 120 mg/d) withdrew because of increased involuntary movements, one patient (60 mg/d) withdrew due to persistent dry eyes, and one patient (120 mg/d) withdrew because of persistent vomiting. There were no significant differences between treatment arms in the primary measures of tolerability, the frequency and types of clinical adverse events, or the clinical/functional features of HD. OPC-14117 was safe and generally well tolerated; however, elevations of liver transaminase suggested that continued surveillance monitoring is warranted in conducting more long-term studies of this antioxidant therapy. C1 Univ Rochester, Dept Neurol, Clin Trials Coordinat Ctr, Rochester, NY 14620 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NINDS, NIH, Bethesda, MD USA. Washington Univ, St Louis, MO 63130 USA. Columbia Univ, New York, NY 10027 USA. Emory Univ, Atlanta, GA 30322 USA. Univ Calif San Diego, Med Ctr, La Jolla, CA 92093 USA. UMDNJ, Robert Wood Johnson Med Sch, Newark, NJ 07103 USA. Univ Texas, SW Med Ctr, Austin, TX 78712 USA. Otsuka Amer Pharmaceut Inc, Rockville, MD USA. RP Marshall, FJ (reprint author), Univ Rochester, Dept Neurol, Clin Trials Coordinat Ctr, 1351 Mt Hope Ave,Suite 216, Rochester, NY 14620 USA. NR 43 TC 26 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1998 VL 50 IS 5 BP 1366 EP 1373 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA ZN179 UT WOS:000073617800032 ER PT J AU Ling, W Shoptaw, S Majewska, D AF Ling, W Shoptaw, S Majewska, D TI Baclofen as a cocaine anti-craving medication: A preliminary clinical study SO NEUROPSYCHOPHARMACOLOGY LA English DT Letter ID RELEASE C1 Los Angeles Addict Treatment Res Ctr, Los Angeles, CA USA. NIDA, Medicat Dev Div, Bethesda, MD USA. RP Ling, W (reprint author), Los Angeles Addict Treatment Res Ctr, Los Angeles, CA USA. FU NIDA NIH HHS [P50 DA09260] NR 8 TC 119 Z9 123 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 1998 VL 18 IS 5 BP 403 EP 404 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA ZC201 UT WOS:000072551600010 PM 9536455 ER PT J AU Du, J Tao-Cheng, JH Zerfas, P McBain, CJ AF Du, J Tao-Cheng, JH Zerfas, P McBain, CJ TI The K+ channel, Kv2.1, is apposed to astrocytic processes and is associated with inhibitory postsynaptic membranes in hippocampal and cortical principal neurons and inhibitory interneurons SO NEUROSCIENCE LA English DT Article DE electron microscopy; astrocytes; interneurons; spatial buffering; subsurface cistern; postsynaptic density ID DEPOLARIZATION-INDUCED SUPPRESSION; RAT-BRAIN; PLASMA-MEMBRANES; PYRAMIDAL CELLS; SUBUNIT KV3.1B; EXPRESSION AB A variety of voltage-gated ion channels are expressed on principal cell dendrites and have been proposed to play a pivotal role in the regulation of dendritic excitability. Previous studies at the light microscopic level demonstrated that the K+ channel subunit Kv2.1 expression was polarized to the cell soma and dendrites of principal neurons throughout the central nervous system. Here, using double immunostaining we now show that Kv2.1 protein is similarly expressed in the majority of cortical and hippocampal parvalbumin, calbindin and somatostatin-containing inhibitory interneurons. At the electron microscopic level Kv2.1 immunoreactivity was primarily observed on the plasma membrane of the somata and proximal dendrites of both principal neurons and inhibitory interneurons; expression was low on smaller dendritic branches, and absent on axons and presynaptic terminals. Kv2.1 subunit expression was highly concentrated on the cell surface membrane immediately facing astrocytic processes. Kv2.1 expression was also concentrated in specific cytoplasmic compartments and on the subsurface cisterns underlying the plasma membrane facing astrocytes. In addition, Kv2.1 subunit immunoreactivity was associated with postsynaptic densities of a fraction of inhibitory symmetric synapses; while expression at asymmetric synapses was rare. These data demonstrate that channels formed by Kv2.1 subunits are uniquely positioned on the soma and principal dendrites of both pyramidal cells and inhibitory interneurons at sites immediately adjacent to astrocytic processes. This close apposition to astrocytes will ensure a rapid removal and limit the influence of K+ released into the extracellular space. This expression pattern suggests that channels formed by Kv2.1 are poised to provide a role in the regulation of neuronal dendritic excitability. (C) 1998 IBRO. Published by Elsevier Science Ltd. C1 NICHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. NINDS, Electron Microscopy Facil, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP McBain, CJ (reprint author), NICHD, Lab Cellular & Mol Neurophysiol, NIH, 49 Convent Dr, Bethesda, MD 20892 USA. RI Du, Jing/A-9023-2012 NR 29 TC 97 Z9 100 U1 2 U2 5 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 MAY PY 1998 VL 84 IS 1 BP 37 EP 48 DI 10.1016/S0306-4522(97)00519-8 PG 12 WC Neurosciences SC Neurosciences & Neurology GA ZA353 UT WOS:000072355000005 PM 9522360 ER PT J AU Friedman, WJ Black, IB Kaplan, DR AF Friedman, WJ Black, IB Kaplan, DR TI Distribution of the neurotrophins brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5 in the postnatal rat brain: An immunocytochemical study SO NEUROSCIENCE LA English DT Article DE neurotrophin; immunocytochemistry; BDNF; NT3; NT4/5 ID NERVE GROWTH-FACTOR; FACTOR MESSENGER-RNA; SEPTAL CHOLINERGIC NEURONS; MOLECULAR-CLONING; FACTOR FAMILY; REGIONAL DISTRIBUTION; PERIPHERAL-TISSUES; SENSORY NEURONS; TRK FAMILY; FACTOR NGF AB The neurotrophin family of trophic factors influences survival and function of neurons in both the peripheral and central nervous systems. Critical information regarding physiological function of these factors may be gained by examining their localization in the brain. Here we report the immunocytochemical characterization of antisera directed against brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin 4/5. These antisera provide important tools to localize the bioactive neurotrophin proteins. Correspondence between protein distribution and previously determined messenger RNA expression was observed in some brain regions, such as hippocampus and cortex. However, neurotrophin proteins were also detected in neurons which have no apparent corresponding messenger RNA, indicating that the proteins may be transported from the sites of synthesis in certain populations. Immunocytochemical double-labelling analysis also indicated that a sub-population of neurotrophin-positive cells were labelled with an astrocyte marker (glial fibrillary acidic protein) as well, demonstrating that trophic molecules are localized to glial cells as well as neurons in vivo. Thus, the use of antisera specific for individual neurotrophic factors has indicated potential cellular sites of action. (C) 1998 IBRO. Published by Elsevier Science Ltd. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Eukaryot Signal Transduct Sect, Frederick, MD 21702 USA. RP Friedman, WJ (reprint author), Columbia Univ Coll Phys & Surg, Dept Pathol, Taub Ctr Alzheimer Dis Res, 630 W 168th St, New York, NY 10032 USA. FU NCI NIH HHS [N01-CO-4600]; NINDS NIH HHS [NS 31357] NR 56 TC 104 Z9 104 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 MAY PY 1998 VL 84 IS 1 BP 101 EP 114 DI 10.1016/S0306-4522(97)00526-5 PG 14 WC Neurosciences SC Neurosciences & Neurology GA ZA353 UT WOS:000072355000011 PM 9522366 ER PT J AU Schafer, MKH Eiden, LE Weihe, E AF Schafer, MKH Eiden, LE Weihe, E TI Cholinergic neurons and terminal fields revealed by immunohistochemistry for the vesicular acetylcholine transporter. I. Central nervous system SO NEUROSCIENCE LA English DT Article DE acetylcholine; vesicular acetylcholine transporter (VAChT); choline acetyltransferase (ChAT); cholinergic; aminergic; central nervous system ID RAT CEREBRAL-CORTEX; ACETYLTRANSFERASE MESSENGER-RNA; VASOACTIVE INTESTINAL POLYPEPTIDE; PIG PINEAL-GLAND; SPINAL-CORD; GUINEA-PIG; BRAIN-STEM; IMMUNOCYTOCHEMICAL LOCALIZATION; CAENORHABDITIS-ELEGANS; INSITU HYBRIDIZATION AB Antibodies directed against the C-terminus of the rat vesicular acetylcholine transporter mark expression of this specifically cholinergic protein in perinuclear regions of the soma and on secretory vesicles concentrated within cholinergic nerve terminals. In the central nervous system, the vesicular acetylcholine transporter terminal fields of the major putative cholinergic pathways in cortex, hippocampus, thalamus, amygdala, olfactory cortex and interpeduncular nucleus were examined and characterized. The existence of an intrinsic cholinergic innervation of cerebral cortex was confirmed by both in situ hybridization histochemistry and immunohistochemistry for the rat vesicular acetylcholine transporter and choline acetyltransferase. Cholinergic interneurons of the olfactory tubercle and Islands of Calleja, and the major intrinsic cholinergic innervation of striatum were fully characterized at the light microscopic level with vesicular acetylcholine transporter immunohistochemistry. Cholinergic staining was much more extensive for the vesicular acetylcholine transporter than for choline acetyltransferase in all these regions, due to visualization of cholinergic nerve terminals not easily seen with immunohistochemistry for choline acetyltransferase in paraffin-embedded sections. Cholinergic innervation of the median eminence of the hypothalamus, previously observed with vesicular acetylcholine transporter immunohistochemistry, was confirmed by the presence of vesicular acetylcholine transporter immunoreactivity in extracts of median eminence by western blotting. Cholinergic projections to cerebellum, pineal gland, and to the substantia nigra were documented by vesicular acetylcholine transporter-positive punctate staining in these structures. Additional novel localizations of putative cholinergic terminals to the subependymal zone surrounding the lateral ventricles, and putative cholinergic cell bodies in the sensory mesencephalic trigeminal nucleus, a primary sensory afferent ganglion located in the brainstem, are documented here. The cholinergic phenotype of neurons of the sensory mesencephalic trigeminal nucleus was confirmed by choline acetyltransferase immunohistochemistry. A feature of cholinergic neurons of the central nervous system revealed clearly with vesicular acetylcholine transporter immunohistochemistry in paraffin-embedded sections is the termination of cholinergic neurons on cholinergic cell bodies. These are most prominent on motor neurons of the spinal cord, less prominent but present in some brainstem motor nuclei, and apparently absent from projection neurons of the telencephalon and brainstem, as well as from the preganglionic vesicular acetylcholine transporter-positive sympathetic and parasympathetic neurons visualized in the intermediolateral and intermediomedial columns of the spinal cord. In addition to the large puncta decorating motor neuronal perikarya and dendrites in the ventral horn, vesicular acetylcholine transporter-positive terminal fields are distributed in lamina X surrounding the central canal, where additional small vesicular acetylcholine transporter-positive cell bodies are located, and in the superficial layers of the dorsal horn. Components of the central cholinergic nervous system whose existence has been controversial have been confirmed, and the existence of new components documented, with immunohistochemistry for the vesicular acetylcholine transporter. Quantitative visualization of terminal fields of known cholinergic systems by staining for vesicular acetylcholine transporter will expand the possibilities for documenting changes in synaptic patency accompanying physiological and pathophysiological changes in these systems. (C) 1998 IBRO. Published by Elsevier Science Ltd. C1 Univ Marburg, Dept Anat & Cell Biol, D-35033 Marburg, Germany. NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Univ Marburg, Dept Anat & Cell Biol, Robert Koch Str 6, D-35033 Marburg, Germany. OI Eiden, Lee/0000-0001-7524-944X NR 82 TC 126 Z9 126 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD MAY PY 1998 VL 84 IS 2 BP 331 EP 359 DI 10.1016/S0306-4522(97)00516-2 PG 29 WC Neurosciences SC Neurosciences & Neurology GA ZB378 UT WOS:000072466100002 PM 9539209 ER PT J AU Schafer, MKH Eiden, LE Weihe, E AF Schafer, MKH Eiden, LE Weihe, E TI Cholinergic neurons and terminal fields revealed by immunohistochemistry for the vesicular acetylcholine transporter. II. The peripheral nervous system SO NEUROSCIENCE LA English DT Article DE vesicular acetylcholine transporter; choline acetyltransferase; cholinergic; aminergic; sympathetic and parasympathetic innervation; autonomic nervous system ID VASOACTIVE INTESTINAL POLYPEPTIDE; GUINEA-PIG; ACETYLTRANSFERASE-IMMUNOREACTIVITY; MONOAMINE TRANSPORTER; SYNAPTIC VESICLES; ENDOCRINE-CELLS; RAT; INNERVATION; PEPTIDE; SPHENOPALATINE AB The peripheral sympathetic and parasympathetic cholinergic innervation was investigated with antibodies directed against the C-terminus of the rat vesicular acetylcholine transporter. Immunohistochemistry for the vesicular acetylcholine transporter resulted in considerably more detailed visualization of cholinergic terminal fields in the peripheral nervous system than reported previously and was well suited to also identify cholinergic perikarya. Vesicular acetylcholine transporter immunoreactivity completely delineated the preganglionic sympathetic terminals in pre-and paravertebral sympathetic ganglia, and in the adrenal medulla as well as postganglionic cholinergic neurons in the paravertebral chain. Cholinergic terminals of sudomotor and vasomotor nerves of skeletal muscle were optimally visualized. Mixed peripheral ganglia, including periprostatic and uterovaginal ganglia, exhibited extensive preganglionic cholinergic innervation of both noradrenergic and cholinergic postganglionic principal neurons which were intermingled in these ganglia. Varicose vesicular acetylcholine transporter-positive fibres and terminals, representing the cranial parasympathetic innervation of the cerebral vasculature, of salivary and lacrimal glands, of the eye, of the respiratory tract and of the upper digestive tract innervated various target structures including seromucous gland epithelium and myoepithelium, respiratory epithelium, and smooth muscle of the tracheobronchial tree. The only macrovascular elements receiving vesicular acetylcholine transporter-positive innervation were the cerebral arteries. The microvasculature throughout the viscera, with the exception of lymphoid tissues, the liver and kidney, received vesicular acetylcholine transporter-positive innervation while the microvasculature of limb and trunk skeletal muscle appeared to be the only relevant somatic target of vesicular acetylcholine transporter innervation. Vesicular acetylcholine transporter immunoreactivity was particularly useful for identification of parasympathetic intrinsic ganglia, and their terminal fields, in heart, uterus, and other peripheral organs receiving parasympathetic innervation. Extensive vesicular acetylcholine transporter-positive terminal fields were apparent in both atrial and ventricular tissues of the heart targeting cardiomyocytes as well as cardiac microvessels. Pericardiac brown adipose tissue was also supplied by vesicular acetylcholine transporter-positive varicose fibres. The enteric ganglia of the myenteric and submucous plexus, their synaptic junctions with circular and longitudinal smooth muscle, and terminal fields of the lamina propria of the stomach and intestine and of the local microvasculature were intensely vesicular acetylcholine transporter positive. Vesicular acetylcholine transporter-positive innervation was delivered to the exocrine and endocrine pancreas originating from vesicular acetylcholine transporter-positive intrapancreatic ganglia. Vesicular acetylcholine transporter immunoreactivity in urogenital organs revealed the patterns of terminal cholinergic fields arising from the sacral parasympathetic innervation of these structures. Components of the cholinergic nervous system in the periphery whose existence has been controversial have been confirmed, and the existence of new components of the cholinergic nervous system has been documented, with vesicular acetylcholine transporter immunohistochemistry. Visualization of vesicular acetylcholine transporter will allow documentation of changes in synaptic patency during development, in disease, and during changes in neurotransmission accompanying injury and dystrophy, in the peripheral nervous system. (C) 1998 IBRO. Published by Elsevier Science Ltd. C1 Univ Marburg, Dept Anat & Cell Biol, D-35033 Marburg, Germany. NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Univ Marburg, Dept Anat & Cell Biol, Robert Koch Str 6, D-35033 Marburg, Germany. OI Eiden, Lee/0000-0001-7524-944X NR 30 TC 126 Z9 134 U1 3 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD MAY PY 1998 VL 84 IS 2 BP 361 EP 376 DI 10.1016/S0306-4522(97)80196-0 PG 16 WC Neurosciences SC Neurosciences & Neurology GA ZB378 UT WOS:000072466100003 PM 9539210 ER PT J AU Kobayashi, H Han, ES Kim, IS Le, N Rajagopal, V Kreitman, RJ Pastan, I Paik, CH Carrasquillo, JA AF Kobayashi, H Han, ES Kim, IS Le, N Rajagopal, V Kreitman, RJ Pastan, I Paik, CH Carrasquillo, JA TI Similarities in the biodistribution of iodine-labeled anti-Tac single-chain disulfide-stabilized Fv fragment and anti-Tac disulfide-stabilized Fv fragment SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE IL-2R alpha; Fv fragment; I-125; radioimmunodetection; monoclonal antibody ID IMMUNOGLOBULIN FORMS; NUDE-MICE; PROTEIN; RADIOIMMUNOTHERAPY; CELL AB We evaluated the biodistribution and pharmacokinetics of two different iodine-labeled Fv fragments of anti Tac monoclonal antibody (MAb) in normal and tumor bearing nude mice. One was a disulfide stabilized Fv fragment (dsFv), and the other was a single-chain disulfide-stabilized Fv fragment (scdsFv). The scdsFv is a newly developed type of Fv fragment superior to the dsFv in which the V-H and V-L are linked by covalent bonds through a spacer arm and by an internal disulfide bond. These modifications increase the yield of scdsFv. Both reagents recognize the alpha subunit of the interleukin-2 receptor (IL-2R alpha). The biodistribution of the Fv fragments was evaluated in normal mice co injected with 50 mg of L-lysine and in a no lysine control group. Biodistribution was also evaluated in nude mice bearing subcutaneous tumor xenografts derived from IL-2R alpha-positive ATAC4 cells and receptor-negative A431 cells. These mice were co injected with I-125-labeled anti-Tac scdsFv (6 mu Ci/0.7 mu g) and I-131-labeled anti-Tac dsFv (2 mu Ci/0.7 mu g) or with I-131-labeled anti-Tac scdsFv (6 mu Ci/0.7 mu g) and I-125-labeled anti Tac dsFv (4 mu Ci/0.7 mu g). The biodistribution of I-125-labeled anti-Tac scdsFv and I-131 labeled anti-Tac dsFv was very similar in all organs and the tumors. The renal uptake of both reagents was blocked effectively (<93%) and similarly by lysine. The scdsFv cleared slightly faster from the circulation than did the dsFv because there were more aggregates of dsFv than of scdsFv (3% vs. 1%, respectively). The scdsFv to dsFv ratio ranged from 0.79 to 1.20 in all organs at all time points we examined. In conclusion, the first biodistribution study of an scdsFv molecule shows that the scdsFv had a biodistribution very similar to that of the dsFv and seems to be a good alternative to the dsFv because of its higher production yield. Published by Elsevier Science Inc. C1 NCI, Dept Nucl Med, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, Div Basic 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 16 TC 8 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD MAY PY 1998 VL 25 IS 4 BP 387 EP 393 DI 10.1016/S0969-8051(97)00228-X PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZL789 UT WOS:000073471700011 PM 9639301 ER PT J AU Jaiswal, M Lipinski, LJ Bohr, VA Mazur, SJ AF Jaiswal, M Lipinski, LJ Bohr, VA Mazur, SJ TI Efficient in vitro repair of 7-hydro-8-oxodeoxyguanosine by human cell extracts: involvement of multiple pathways SO NUCLEIC ACIDS RESEARCH LA English DT Article ID FORMAMIDOPYRIMIDINE DNA GLYCOSYLASE; COLI FPG PROTEIN; BLUE PLUS LIGHT; EXCISION-REPAIR; IONIZING-RADIATION; ESCHERICHIA-COLI; SINGLET OXYGEN; ABASIC SITE; SUBSTRATE-SPECIFICITY; HUMAN-FIBROBLASTS AB To investigate the repair of oxidative damage in DNA, we have established an in vitro assay utilizing human lymphoblastoid whole cell extracts and plasmid DNA damaged by exposure to methylene blue and visible light. This treatment has been shown to produce predominantly 7-hydro-8-oxodeoxyguanosine (8-oxodG) in double-stranded DNA at low levels of modification. DNA containing 1.6 lesions per plasmid is substrate for efficient repair synthesis by cell extracts. The incorporation of dGMP is 2.7 +/- 0.5 times greater than the incorporation of dCMP, indicating an average repair patch of 3-4 nucleotides. Damage-specific nicking occurs within 15 min, while resynthesis is slower, The incorporation of dGMP increases linearly, while the incorporation of dCMP exhibits a distinct lag. Extracts from xeroderma pigmentosum (XP) complementation groups A and B exhibit 25 and 40%, respectively, of the incorporation of dCMP compared with normal extracts, but extracts from an XP-D cell line exhibit twice the activity. These data suggest that the efficient repair of 8-oxodG lesions observed in human cell extracts involves more than one pathway of base excision repair. C1 NIA, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. American Univ, Dept Chem, Washington, DC 20016 USA. RP Mazur, SJ (reprint author), NIA, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. NR 47 TC 39 Z9 39 U1 0 U2 0 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 MAY 1 PY 1998 VL 26 IS 9 BP 2184 EP 2191 DI 10.1093/nar/26.9.2184 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZL462 UT WOS:000073435300024 PM 9547279 ER PT J AU Ikeda, H Fernandez, R Wilk, A Barchi, JJ Huang, XL Marquez, VE AF Ikeda, H Fernandez, R Wilk, A Barchi, JJ Huang, XL Marquez, VE TI The effect of two antipodal fluorine-induced sugar puckers on the conformation and stability of the Dickerson-Drew dodecamer duplex [d(CGCGAATTCGCG)](2) SO NUCLEIC ACIDS RESEARCH LA English DT Article ID YEAST TFIIA/TBP/DNA COMPLEX; TRANSCRIPTION FACTOR-IIIA; DOUBLE-HELIX FORMATION; CRYSTAL-STRUCTURE; ANTIVIRAL NUCLEOSIDES; DNA DODECAMER; BINDING-SITE; MINOR-GROOVE; B-FORM; X-RAY AB UV thermal melting studies, CD and NMR spectroscopies were employed to assess the contribution of antipodal sugar conformations on the stability of the canonical B-DNA conformation of the Dickerson-Drew dodecamer duplex {[d(CGCGAATTCGCG)](2), (ODN 1)}. Different oligodeoxynucleotide versions of ODN 1 were synthesized with modified thymidine units favoring distinct sugar conformations by using a 3'-endo (north) 2'-fluoro-2'-deoxyribofuranosyl thymine (1) or a 2'-endo (south) 2'-fluoro-2'-deoxyarabinofuranosyl thymine (2). The results showed that two south thymidines greatly stabilized the double helix, whereas two north thymidines destabilized it by inducing a more A-like conformation in the middle of the duplex. Use of combinations of north and south thymidine conformers in the same oligo destabilized the double helix even further, but without inducing a conformational change. The critical length for establishing a detectable A-like conformation in the middle of a B-DNA ODN appears to be 4 bp. Our results suggest that manipulation of the conformation of DNA in a sequence-independent manner is possible. C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. US FDA, Div Hematol Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Marquez, VE (reprint author), NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. EM marquezv@dc37a.nci.nih.gov RI Barchi Jr., Joseph/N-3784-2014 NR 52 TC 56 Z9 56 U1 1 U2 8 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 MAY 1 PY 1998 VL 26 IS 9 BP 2237 EP 2244 DI 10.1093/nar/26.9.2237 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZL462 UT WOS:000073435300031 PM 9547286 ER PT J AU Wysocki, AB AF Wysocki, AB TI Launching your research career through postdoctoral training opportunities SO NURSING RESEARCH LA English DT Editorial Material C1 NIH, Natl Inst Nursing Res, Div Intramural Res, Bethesda, MD 20892 USA. RP Wysocki, AB (reprint author), NIH, Natl Inst Nursing Res, Div Intramural Res, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER J NURSING CO PI NEW YORK PA 555 W 57TH ST, NEW YORK, NY 10019-2961 USA SN 0029-6562 J9 NURS RES JI Nurs. Res. PD MAY-JUN PY 1998 VL 47 IS 3 BP 127 EP 128 DI 10.1097/00006199-199805000-00001 PG 2 WC Nursing SC Nursing GA ZN358 UT WOS:000073637900001 PM 9610645 ER PT J AU Xu, TS Soares, JH AF Xu, TS Soares, JH TI Molecular aspects of tibial dyschondroplasia in the chicken: II. Effects of 1,25(OH)(2)D-3, on the expression of type X collagen and alkaline phosphatase activity in growth plate chondrocytes SO NUTRITION RESEARCH LA English DT Article DE tibial dyschondroplasia; 1,25(OH)(2)D-3; alkaline phosphatase; type X collagen mRNA; chondrocytes ID GENE-EXPRESSION; EPIPHYSEAL CARTILAGE; BROILER-CHICKENS; VITAMIN-D; CALCIUM; 1,25-DIHYDROXYCHOLECALCIFEROL; INVITRO; CELLS; 25-HYDROXYCHOLECALCIFEROL; LOCALIZATION AB The present study investigated the regulation of type X collagen expression in normal and dyschondroplastic (TD) growth plate chondrocytes by vitamin D metabolites. Type X collagen mRNA transcription was 20% lower in vitamin D deficient growth plate cartilage as compared to normal chondrocytes obtained from chicks fed a diet supplemented with 5 mu g vitamin D-3/kg diet. Administration of 1,25(OH)(2)D-3 to rachitic chicks increased type X collagen mRNA levels. Higher concentrations of 1,25(OH)(2)D-3 (10(-10) versus 10(-12) M) and lower levels of extracellular calcium (5 mM versus 20 mM) were required to stimulate type X collagen gene expression in cultured chondrocytes from TD chicks compared to normal chicks. The growth of chondrocytes from normal chicks was reduced by high concentrations (greater than or equal to 10(-8) M) of 1,25(OH)(2)D-3, whereas the inhibitory effect was not observed in chondrocytes from TD chicks. While low concentrations (10(-13) 10(-11)M) of 1,25(OH)(2)D-3 had no effect on the alkaline phosphatase (AP) activity of chondrocytes from normal chicks, the activity was increased in TD chicks. Although high concentrations (greater than or equal to 10(-10)M) of 1,25(OH)(2)D-3 inhibited AP activity in normal chondrocytes, even higher levels (greater than or equal to 10(-8)M) were required to produce an inhibitory effect in TD chondrocytes. These results indicate that TD chondrocytes are more resistant to vitamin D-3 action than normal chondrocytes. (C) 1998 Elsevier Science Inc. C1 Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. NIDR, Bone Res Grp, NIH, Bethesda, MD 20817 USA. RP Soares, JH (reprint author), Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. NR 35 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD MAY PY 1998 VL 18 IS 5 BP 809 EP 822 DI 10.1016/S0271-5317(98)00066-9 PG 14 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZP788 UT WOS:000073788500005 ER PT J AU Lichtenstein, AH Kennedy, E Barrier, P Danford, D Ernst, ND Grundy, SM Leveille, GA Van Horn, L Williams, CL Booth, SL AF Lichtenstein, AH Kennedy, E Barrier, P Danford, D Ernst, ND Grundy, SM Leveille, GA Van Horn, L Williams, CL Booth, SL TI Dietary fat consumption and health SO NUTRITION REVIEWS LA English DT Article; Proceedings Paper CT Tufts-University Dialogue Conference on the Role of Fat-Modified Foods in Dietary Change CY DEC 07-09, 1997 CL TUFTS UNIV, BOSTON, MASSACHUSETTS SP Proctor & Gamble Co HO TUFTS UNIV ID NUTRITION EXAMINATION SURVEYS; DEPENDENT DIABETES-MELLITUS; AMERICAN-HEART-ASSOCIATION; HIGH-CARBOHYDRATE DIETS; BREAST-CANCER; RISK-FACTORS; PHYSICAL-ACTIVITY; NATIONAL-HEALTH; ENERGY-INTAKE; COLON-CANCER C1 Tufts Univ, Boston, MA 02111 USA. USDA, Res Educ & Econ, Washington, DC 20250 USA. Amer Diabet Assoc, Alexandria, VA USA. US FDA, Washington, DC USA. NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Leveille Associates, Denville, NJ USA. Northwestern Univ, Chicago, IL 60611 USA. Amer Hlth Fdn, Valhalla, NY 10595 USA. RP Booth, SL (reprint author), Tufts Univ, 711 Washington St, Boston, MA 02111 USA. NR 143 TC 99 Z9 103 U1 0 U2 19 PU INT LIFE SCIENCES INST PI LAWRENCE PA 810 EAST 10TH ST SUBSCRIPTION OFFICE, LAWRENCE, KS 66044 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD MAY PY 1998 VL 56 IS 5 BP S3 EP S19 PN 2 PG 17 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZR336 UT WOS:000073963900002 PM 9624878 ER PT J AU Roberts, SB Pi-Sunyer, FX Dreher, M Hahn, R Hill, JO Kleinman, RE Peters, JC Ravussin, E Rolls, BJ Yetley, E Booth, SL AF Roberts, SB Pi-Sunyer, FX Dreher, M Hahn, R Hill, JO Kleinman, RE Peters, JC Ravussin, E Rolls, BJ Yetley, E Booth, SL TI Physiology of fat replacement and fat reduction: Effects of dietary fat and fat substitutes on energy regulation SO NUTRITION REVIEWS LA English DT Article; Proceedings Paper CT Tufts-University Dialogue Conference on the Role of Fat-Modified Foods in Dietary Change CY DEC 07-09, 1997 CL TUFTS UNIV, BOSTON, MASSACHUSETTS SP Proctor & Gamble Co HO TUFTS UNIV ID HIGH-CARBOHYDRATE DIETS; EATING AD-LIBITUM; FREE-LIVING MEN; FOOD-INTAKE; WEIGHT-LOSS; SUCROSE POLYESTER; COVERT MANIPULATION; MACRONUTRIENT INTAKE; SUBSTRATE OXIDATION; CONTROLLED TRIAL C1 Tufts Univ, Boston, MA 02111 USA. Columbia Univ, St Lukes Roosevelt Hosp, New York, NY USA. Nabisco Foods Grp, E Hanover, NJ USA. Publ Voice Food & Hlth Policy, Washington, DC USA. Univ Colorado, Denver, CO 80202 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Procter & Gamble Co, Cincinnati, OH USA. NIH, Phoenix, AZ USA. Penn State Univ, University Pk, PA 16802 USA. US FDA, Washington, DC 20204 USA. RP Booth, SL (reprint author), Tufts Univ, 711 Washington St, Boston, MA 02111 USA. NR 102 TC 35 Z9 36 U1 4 U2 5 PU INT LIFE SCIENCES INST PI LAWRENCE PA 810 EAST 10TH ST SUBSCRIPTION OFFICE, LAWRENCE, KS 66044 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD MAY PY 1998 VL 56 IS 5 BP S29 EP S41 PN 2 PG 13 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZR336 UT WOS:000073963900004 PM 9624879 ER PT J AU Taylor Marshall Astrup Kennedy Nestle Mela Liebman Leveille Denke Kristal Milner Lichtenstein Roberts Foreman Sims Clark Birch Hill Pi-Sunyer Haas Bieber Berg Hubbard Rapaille Rosenberg Wing Sigman-Grant Kris-Etherton AF Taylor Marshall Astrup Kennedy Nestle Mela Liebman Leveille Denke Kristal Milner Lichtenstein Roberts Foreman Sims Clark Birch Hill Pi-Sunyer Haas Bieber Berg Hubbard Rapaille Rosenberg Wing Sigman-Grant Kris-Etherton TI Dietary fat consumption and health - Discussion SO NUTRITION REVIEWS LA English DT Editorial Material C1 King & Spalding, Washington, DC USA. Royal Vet & Agr Univ, Dept Human Nutr, Frederiksberg, Denmark. Best Foods, Somerset, NJ USA. Penn State Univ, University Pk, PA 16802 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Foreman Heiedepriem & Mager Inc, Washington, DC USA. Georgetown Univ, Ctr Food & Nutr, Washington, DC USA. Univ Colorado, Denver, CO 80202 USA. NIH, Bethesda, MD 20892 USA. USDA, Ctr Nutr Policy & Promot, Washington, DC 20250 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Leveille Associates, Denville, NJ USA. Tufts Univ, Boston, MA 02111 USA. Ctr Sci Publ Interest, Washington, DC USA. Inst Food Res, Reading RG2 9AT, Berks, England. NYU, New York, NY USA. Arizona Canc Ctr, Tucson, AZ USA. Columbia Univ, St Lukes Roosevelt Hosp Ctr, New York, NY USA. Archetype Discoveries World Wide, Boca Raton, FL USA. Univ Nevada, Las Vegas, NV 89154 USA. Univ Maryland, College Pk, MD 20742 USA. Western Psychiat Sch Med, Pittsburgh, PA USA. RP Taylor (reprint author), King & Spalding, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU INT LIFE SCIENCES INST PI LAWRENCE PA 810 EAST 10TH ST SUBSCRIPTION OFFICE, LAWRENCE, KS 66044 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD MAY PY 1998 VL 56 IS 5 BP S19 EP S28 PN 2 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZR336 UT WOS:000073963900003 ER PT J AU Tarone, RE Kaune, WT Linet, MS Hatch, EE Kleinerman, RA Robison, LL Boice, JD Wacholder, S AF Tarone, RE Kaune, WT Linet, MS Hatch, EE Kleinerman, RA Robison, LL Boice, JD Wacholder, S TI Residential wire codes: reproducibility and relation with measured magnetic fields SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article DE childhood acute lymphoblastic leukaemia; magnetic fields; exposure assessment; wire codes; misclassification ID ELECTRICAL WIRING CONFIGURATIONS; POWER-LINE CONFIGURATIONS; CHILDHOOD-CANCER; SELECTION BIAS; EXPOSURE; LEUKEMIA AB Objectives-To investigate the reproducibility of wire codes to characterise residential power line configurations and to determine the extent to which wire codes provide a proxy measure of residential magnetic field strength in a case-control study of childhood leukaemia conducted in nine states within the United States. Methods-Misclassification of wire codes was assessed with independent measurements by two technicians for 187 residences. The association between categories of wire code and measured level of magnetic field was evaluated in 858 residences with both a wire code measurement and a 24 hour measurement of the magnetic field in the bedroom. The strength of the association between category of wire code and risk of leukaemia was examined in two regions with different average levels of magnetic field in homes with high categories of wire code. Results-The reproducibility of any of three different classifications of wire codes was excellent (kappa greater than or equal to 0.89). Mean and median magnetic fields, and the percentage of homes with high magnetic fields increased with increasing category for each of the wire code classification schemes. The size of the odds ratios for risk of leukaemia and high categories of wire code did not reflect the mean levels of the magnetic field in those categories in two study regions. Conclusion-Misclassification of categories of wire code is not a major source of bias in the study. Wire codes provide a proxy measure of exposure to residential magnetic fields. If magnetic fields were a risk factor for leukaemia, however, there would be some attenuation of risk estimates based on wire codes because of misclassification of exposure to magnetic fields at both extremes of the wire code range. The lack of an association between high categories of wire code and risk of leukaemia cannot be explained by a failure of the wire code classification schemes to estimate exposure to magnetic fields in the study area. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM Factors, Richland, WA USA. Univ Minnesota, Sch Med, Div Pediat Epidemiol & Clin Res, Minneapolis, MN 55455 USA. RP Tarone, RE (reprint author), NCI, Div Canc Epidemiol & Genet, EPN 403, Bethesda, MD 20892 USA. OI Kleinerman, Ruth/0000-0001-7415-2478 NR 25 TC 16 Z9 16 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD MAY PY 1998 VL 55 IS 5 BP 333 EP 339 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZU860 UT WOS:000074242900006 PM 9764111 ER PT J AU Danforth, DN AF Danforth, DN TI Pregnancy after breast cancer: From psychosocial issues through conception - The Collichio/Agnello/Staltzer article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Danforth, DN (reprint author), NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI HUNTINGTON PA 17 PROSPECT ST, HUNTINGTON, NY 11743 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD MAY PY 1998 VL 12 IS 5 BP 770 EP + PG 2 WC Oncology SC Oncology GA ZM514 UT WOS:000073547800024 ER PT J AU Grem, JL Steinberg, SM Chen, AP McAtee, N Cullen, E Hamilton, JM Allegra, CJ AF Grem, JL Steinberg, SM Chen, AP McAtee, N Cullen, E Hamilton, JM Allegra, CJ TI The utility of monitoring carcinoembyronic antigen during systemic therapy for advanced colorectal cancer SO ONCOLOGY REPORTS LA English DT Article DE tumor markers; prognostic indicators; colon cancer; rectal cancer; carcinoembryonic antigen ID METASTATIC GASTROINTESTINAL ADENOCARCINOMA; PLUS CALCIUM LEUCOVORIN; CARCINOEMBRYONIC ANTIGEN; CONTINUOUS-INFUSION; INTERFERON ALFA-2A; TUMOR-MARKERS; PHASE-II; FLUOROURACIL; CHEMOTHERAPY; CARCINOMA AB To determine if pre-treatment serum carcinoembryonic antigen (CEA) levels or changes in CEA values during treatment have prognostic value, we reviewed five prior fluorouracil/leucovorin-based trials and identified 125 colorectal cancer patients with no prior chemotherapy for metastatic disease in whom CEA values were available. Although pre-treatment serum CEA values did not predict for clinical response or time to progression, serial monitoring of CEA appeared to be useful in patients with an elevated pretreatment CEA, particularly when a decrease in CEA occurred in concert with radiographic evidence of disease response. The CEA nadir was a strong prognostic variable with respect to time to disease progression. A consistent rise in CEA values over the minimum value signals the need for radiographic reassessment of the patient's disease status to rule out disease progression. C1 NCI, Med Branch, NNMC, Div Clin Sci, Bethesda, MD 20889 USA. NCI, Biostat & Data Management Sect, Div Clin Sci, Bethesda, MD 20892 USA. RP Grem, JL (reprint author), NCI, Med Branch, NNMC, Div Clin Sci, 8901 Wisconsin Ave,Bldg 8,Room 5101, Bethesda, MD 20889 USA. NR 28 TC 11 Z9 11 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD MAY-JUN PY 1998 VL 5 IS 3 BP 559 EP 567 PG 9 WC Oncology SC Oncology GA ZJ094 UT WOS:000073178900004 PM 9538153 ER PT J AU White, EL Ross, LJ Schmid, SM Kelloff, GJ Steele, VE Hill, DL AF White, EL Ross, LJ Schmid, SM Kelloff, GJ Steele, VE Hill, DL TI Screening of potential cancer-preventing chemicals for inhibition of induction of ornithine decarboxylase in epithelial cells from rat trachea SO ONCOLOGY REPORTS LA English DT Article DE chemoprevention; ornithine decarboxylase; alpha difluoromethyl ornithine; N-(2-carboxyphenyl)-all-trans retinamide; ZK 119010; curcumin; 18-alpha-olean-12-ene-3 beta,23,28-triol; genistein; phenethyl isothiocyanate ID SUPPRESSES MAMMARY-CANCER; PHENETHYL ISOTHIOCYANATE; GLAND DIFFERENTIATION; POLYAMINE METABOLISM; DIETARY CURCUMIN; CARCINOGENESIS; RETINOIDS; GENISTEIN; PROMOTER; CHEMOPREVENTION AB Sixty-one selected chemicals were evaluated in rat tracheal epithelial (2C5) cells for their capacity to inhibit induction (or inhibit directly) the enzyme ornithine decarboxylase, the activity of which is associated with cell growth and division. alpha-Difluoromethylornithine (DFMO) was used as a positive control. At non-toxic concentrations, six test compounds had substantial activity (values for IC50 DFMO/IC50 compound >1): N-(2-carboxyphenyl)-all-trans-retinamide, ZK 119010 (2-(4-hydroxyphenyl)-3-methyl-1-[6-(1-pyrrolidinyl)hexyl]-1H-ind-ol-5-ol), curcumin, 18-alpha-olean-12-ene-3B,23,28-triol, genistein and phenethyl isothiocyanate. These should be considered for further development as cancer preventive agents. C1 So Res Inst, Birmingham, AL 35255 USA. NCI, Div Canc Prevent & Control, Bethesda, MD 20892 USA. RP Hill, DL (reprint author), So Res Inst, POB 55305, Birmingham, AL 35255 USA. FU NCI NIH HHS [N01-CN-45587] NR 38 TC 6 Z9 6 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD MAY-JUN PY 1998 VL 5 IS 3 BP 717 EP 722 PG 6 WC Oncology SC Oncology GA ZJ094 UT WOS:000073178900034 PM 9538183 ER PT J AU Sperduto, RD Hiller, R Chew, E Seigel, D Blair, N Burton, TC Farber, MD Gragoudas, ES Haller, J Seddon, JM Yannuzzi, LA AF Sperduto, RD Hiller, R Chew, E Seigel, D Blair, N Burton, TC Farber, MD Gragoudas, ES Haller, J Seddon, JM Yannuzzi, LA TI Risk factors for hemiretinal vein occlusion: Comparison with risk factors for central and branch retinal vein occlusion - The eye disease case-control study SO OPHTHALMOLOGY LA English DT Article ID ALCOHOL-CONSUMPTION; CLINICAL-FEATURES; NATURAL-HISTORY; PATHOGENESIS AB Objective: Possible risk factors for hemiretinal vein occlusion were identified and compared with risk factor profiles for central and branch retinal vein occlusion. Design: The design was a multicenter case-control study. Methods: The authors identified 79 patients with hemiretinal vein occlusion (HRVO), 258 patients with central retinal vein occlusion (CRVO), 270 patients with branch retinal vein occlusion (BRVO), and 1142 control subjects at 5 clinical centers. Risk factor data were obtained through interviews, clinical examinations, and laboratory analyses of blood specimens. Results: Systemic hypertension and history of diabetes mellitus were associated with increased risk of HRVO. Risk of CRVO increased with history of diabetes, systemic hypertension, and higher erythrocyte sedimentation rate (females only); risk of CRVO decreased with increasing amounts of physical activity and increasing amounts of alcohol consumption. Systemic hypertension, higher body mass index, and higher alpha(2)-globulin levels were associated with increased risk of BRVO, whereas higher high-density lipoprotein levels and increasing levels of alcohol consumption were associated with decreased risk of BRVO. Glaucoma history was associated with all three types of retinal vein occlusion. Conclusion: Patients presenting with retinal vein occlusion should be evaluated for cardiovascular disease, diabetes, and glaucoma. C1 NEI, Div Biometry & Epidemiol, Bethesda, MD 20892 USA. Univ Illinois, Chicago, IL USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Wilmer Eye Inst, Baltimore, MD USA. Manhattan Eye Ear & Throat Hosp, New York, NY 10021 USA. RP Sperduto, RD (reprint author), NEI, Div Biometry & Epidemiol, Bldg 31,Room 6A52,31 Center Dr,MSC 2510, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 EY999999]; NEI NIH HHS [N01-EY-5-2111, N01-EY-5-2109, N01-EY-5-2110] NR 21 TC 82 Z9 87 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 1998 VL 105 IS 5 BP 765 EP 771 DI 10.1016/S0161-6420(98)95012-6 PG 7 WC Ophthalmology SC Ophthalmology GA ZL595 UT WOS:000073450100013 PM 9593373 ER PT J AU Cardinali, M Jakus, J Shah, S Ensley, JF Robbins, KC Yeudall, WA AF Cardinali, M Jakus, J Shah, S Ensley, JF Robbins, KC Yeudall, WA TI p21(WAF1/Cip1) retards the growth of human squamous cell carcinomas in vivo SO ORAL ONCOLOGY LA English DT Article DE oral cancer; gene therapy; tumour suppressor; cell cycle; p21; WAF1; Cip1; sdi1 ID WILD-TYPE P53; CYCLIN-DEPENDENT KINASES; TGF-BETA; GENE-TRANSFER; DNA-REPLICATION; NECK-CANCER; TUMOR-CELLS; IN-VITRO; RETROVIRAL VECTORS; MEDIATED TRANSFER AB The excessive proliferation exhibited by cancer cells is frequently a result of their failure to adequately regulate cell cycle progression, In the present study, we developed a xenograft model of oral cancer in athymic mice, using squamous carcinoma cell lines and examined the ability of the cyclin-dependent kinase inhibitor p21 (WAF1/Cip1) to retard tumour growth in vivo, using a retroviral delivery system. Human p21 cDNA was cloned by polymerase chain reaction, expressed, and the encoded protein shown to have biological activity in in vitro kinase assays. Amphotropic retrovirus cultures which expressed recombinant p21 were generated and used to treat established squamous cell carcinoma xenografts. Two weeks following onset of treatment, tumours injected with p21 virus producer cells showed a reduction in size between 3- and 10-fold compared with tumours which received control cells which produced control virus alone. The data indicate that recombinant p21 may be of future use for therapeutic intervention in oral cancer. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NIDR, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. Wayne State Univ, Div Hematol Oncol, Detroit, MI 48201 USA. RP Cardinali, M (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Clin Trials Design & Anal, Oncol Branch, 1401 Rockville Pike,WOC I HFM-573, Rockville, MD 20852 USA. EM cardinali@al.cber.fda.gov NR 71 TC 30 Z9 31 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0964-1955 J9 ORAL ONCOL JI Oral Oncol. PD MAY PY 1998 VL 34 IS 3 BP 211 EP 218 DI 10.1016/S1368-8375(97)00083-3 PG 8 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA ZU714 UT WOS:000074226900009 PM 9692056 ER PT J AU Sternberg, WF Bailin, D Grant, M Gracely, RH AF Sternberg, WF Bailin, D Grant, M Gracely, RH TI Competition alters the perception of noxious stimuli in male and female athletes SO PAIN LA English DT Article DE noxious stimuli; athletic competition; gender difference; pain assessment ID SKIN TEMPERATURE; PAIN THRESHOLD; DENTAL PAIN; EXERCISE; ANALGESIA; SENSITIVITY; NALOXONE; STRESS AB The ability of athletes to continue to compete despite sustaining painful injury is often interpreted as evidence for the activation of endogenous analgesia mechanisms. However, alterations in perception of noxious stimuli during competition have not yet been systematically investigated. This experiment evaluated experimental pain sensitivity in male and female athletes 2 days before, immediately following, and 2 days after competition. Non-athlete controls were evaluated at the same intervals. Competition dramatically reduced pain report on the cold-presser test in all athletes. Withdrawal latencies to noxious heat also were altered by competition, with finger withdrawal latency decreasing and arm withdrawal latency increasing in most athletes. No changes in pain report were observed across time in nonathlete controls. Competition induces both hyperalgesic and analgesic states that are dependent on the body region tested and pain assessment methodology used. (C) 1998 International Association for the Study of Pain. Published by Elsevier Science B.V. C1 Haverford Coll, Dept Psychol, Haverford, PA 19041 USA. NIDR, PNMB, NIH, Bethesda, MD 20892 USA. RP Sternberg, WF (reprint author), Haverford Coll, Dept Psychol, 370 Lancaster Ave, Haverford, PA 19041 USA. NR 21 TC 39 Z9 39 U1 4 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD MAY PY 1998 VL 76 IS 1-2 BP 231 EP 238 DI 10.1016/S0304-3959(98)00050-5 PG 8 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA ZW322 UT WOS:000074398700027 PM 9696478 ER PT J AU Lu, J Li, Q Donadel, G Notkins, AL Lan, MS AF Lu, J Li, Q Donadel, G Notkins, AL Lan, MS TI Profile and differential expression of protein tyrosine phosphatases in mouse pancreatic islet tumor cell lines SO PANCREAS LA English DT Article DE protein tyrosine phosphatase; insulinoma; glucagonoma; IA-2; pancreatic islets ID CYTOSKELETAL-ASSOCIATED PROTEINS; DEPENDENT DIABETES-MELLITUS; R-PTP-KAPPA; TRANSMEMBRANE PROTEIN; EXTRACELLULAR REGION; MOLECULAR-CLONING; SEQUENCE; IDENTIFICATION; IA-2; DOMAIN AB Protein tyrosine phosphatases (PTPs) play important roles in cell growth and differentiation of normal and tumor cells. In this study, we analyzed the PTP profile in two pancreatic islet tumor cell lines. Transcripts were isolated from alpha TC-1 (glucagon-secretin,) and PTC-I (insulin-secreting) cell lines for templates. A pair of degenerative primers, based on the conserved regions of known PTPs, was used to amplify the transcripts by polymerase chain reaction. A total of 1,620 clones was examined by restriction enzyme analysis and cDNA sequencing. Twenty-one PTPs were identified, including nine cytosolic PTPs (TcPTP, P19PTP, PTP1B, PTPMEG. PTP1C, SYP, PTPH1, PTPL1, and PTPD1), nine transmembrane PTPs (PTP delta, PTP gamma, PTP kappa, DEP-1, IA-2, LAR, PTP alpha, PTPNE3, and PTP epsilon), and three new PTPs-PTP mu-like PTP kappa-like, and IA-2 beta. An RNase protection assay demonstrated that some of these PTPs were expressed predominantly in glucagonoma (i.e., PTP delta and IA-2) and others in insulinoma (i.e., PTP1C, PTP kappa, and PTPNE3) cells. In this report, we present the first profile of PTPs in alpha and beta tumor cell lines. C1 NIDR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Lan, MS (reprint author), NIDR, Oral Infect & Immun Branch, NIH, Bldg 30,Room 124,30 Convent Dr,MSC 4322, Bethesda, MD 20892 USA. NR 36 TC 6 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD MAY PY 1998 VL 16 IS 4 BP 515 EP 520 DI 10.1097/00006676-199805000-00010 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZJ969 UT WOS:000073271900010 PM 9598814 ER PT J AU Read, JS Frasch, CE Rich, K Fitzgerald, GA Clemens, JD Pitt, J Pelton, SI Hanson, IC Handelsman, E Diaz, C Fowler, MG AF Read, JS Frasch, CE Rich, K Fitzgerald, GA Clemens, JD Pitt, J Pelton, SI Hanson, IC Handelsman, E Diaz, C Fowler, MG CA Women Infants Transmission Study Grp TI The immunogenicity of Haemophilus influenzae type b conjugate vaccines in children born to human immunodeficiency virus-infected women SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Academic-Society/Ambulatory-Pediatric-Association CY MAY 01-05, 1998 CL NEW ORLEANS, LOUISIANA SP Pediat Acad Soc, Ambulatory Pediat Assoc DE Haemophilus vaccines; bacterial antibodies; acquired immunodeficiency syndrome-related opportunistic infections ID CAPSULAR POLYSACCHARIDE; ANTIBODY-RESPONSES; INFANTS; VACCINATION; IMMUNITY AB Background. Immunocompromise caused by HIV-1 infection increases the importance of receipt of routine childhood vaccines to prevent infections such as invasive Haemophilus influenzae type B (Hib) disease. The objectives of the study were to evaluate the immunogenicity of Hib conjugate vaccines among HIV-infected children according to clinical and immunologic disease progression as well as viral load. Methods. The concentration of antibody to polyribosylribitol phosphate (PRP) was measured at similar to 9 and 24 months of age in plasma specimens from children of HIV-infected women enrolled in the Women and Infants Transmission Study. Results. Among 227 children (35 HIV-infected, 192 uninfected) at the 9-month study visit who were known to have received age-appropriate immunization with CRM197 mutant Corynebacterium diphtheriae protein-conjugated Hib vaccine, geometric mean antibody concentrations were lower among HIV-infected children (1.64 mu g/ml) than among uninfected children (2.70 mu g/ml), although the difference was not statistically significant. Anti-PRP antibody concentrations did not vary significantly among these HIV-infected children with predominantly mild-moderate disease progression according to clinical category, immunologic stage or viral load (P greater than or equal to 0.48). The proportion of children with antibody concentrations greater than or equal to 1.0 mu g/ml did not vary significantly according to HIV infection status (73% uninfected, 74% infected) or, if infected, clinical or immunologic disease progression or viral load. Similar results were obtained among 127 children (17 HIV-infected, 110 uninfected) eligible for analysis at the 24-month study visit. Changes in antibody concentrations over time (between 9 and 24 months of age) did not differ significantly among 10 HIV-infected as compared with 72 uninfected children (P = 0.81). Conclusions. These results suggest that HIV-infected children with predominantly mild-moderate disease progression respond reasonably well in terms of a quantitative antibody response to Hib conjugate vaccines during the first 2 years of life. Research to further characterize the immune response to Hib conjugate vaccines and to further delineate the "durability" of anti-PRP antibody concentrations beyond 2 years of life should be pursued. C1 NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA. US FDA, Div Bacterial Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Univ Illinois, Chicago, IL USA. New England Res Inst, Watertown, MA 02172 USA. NICHHD, Epidemiol Branch, Bethesda, MD 20892 USA. NICHHD, WHO Int Collaborating Ctr Clin Evaluat Vaccines D, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. Columbia Univ, New York, NY USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Baylor Coll Med, Houston, TX 77030 USA. SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. Univ Puerto Rico, San Juan, PR 00936 USA. NIAID, Bethesda, MD 20892 USA. RP Read, JS (reprint author), NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Execut Bldg,Room 4B11F,6100 Execut Blvd MSC 751, Bethesda, MD 20892 USA. EM jr92o@nih.gov NR 29 TC 20 Z9 20 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD MAY PY 1998 VL 17 IS 5 BP 391 EP 397 DI 10.1097/00006454-199805000-00009 PG 7 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA ZN324 UT WOS:000073634500008 PM 9613652 ER PT J AU Lehrnbecher, T Greissinger, S Navid, F Pfuller, H Jeschke, R AF Lehrnbecher, T Greissinger, S Navid, F Pfuller, H Jeschke, R TI Albumin, IgG, retinol-binding protein, and alpha(1)-microglobulin excretion in childhood SO PEDIATRIC NEPHROLOGY LA English DT Article DE protein excretion; albumin; IgG; alpha(1)-microglobulin; retinol-binding protein; reference values ID HEALTHY-CHILDREN; URINE; ALPHA-1-MICROGLOBULIN; AGE AB Urine concentrations of two high molecular weight proteins, albumin and IgG, and two low molecular weight proteins, alpha(1)-microglobulin (A1M) and retinol-binding protein (RBP), were measured in 657 healthy children from birth to 18 years of age. The urinary levels of REP and A1M suggest an age-dependent decline, whereas the levels of albumin and IgG show an uneven distribution. Reference values for albumin, IgG, A1M, and REP for each group are reported. C1 Univ Wurzburg, Dept Pediat, D-97080 Wurzburg, Germany. RP Lehrnbecher, T (reprint author), NCI, Pediat Oncol Branch, NIH, Bldg 10 Room 13N240,10-13N240, Bethesda, MD 20892 USA. NR 14 TC 21 Z9 21 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD MAY PY 1998 VL 12 IS 4 BP 290 EP 292 PG 3 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA ZT561 UT WOS:000074100200006 PM 9655359 ER PT J AU Tayebi, N Reissner, KJ Lau, EK Stubblefield, BK Klineburgess, AC Martin, BM Sidransky, E AF Tayebi, N Reissner, KJ Lau, EK Stubblefield, BK Klineburgess, AC Martin, BM Sidransky, E TI Genotypic heterogeneity and phenotypic variation among patients with type 2 Gaucher's disease SO PEDIATRIC RESEARCH LA English DT Article ID HUMAN GLUCOCEREBROSIDASE GENE; BETA-GLUCOSIDASE GENE; HYDROPS-FETALIS; TARGETED DISRUPTION; MOUSE MODEL; FUSION GENE; MUTATIONS; PSEUDOGENE; DIFFERENTIATION; NUCLEOTIDE AB Gaucher's disease, the inherited deficiency of glucocerebrosidase, manifests with vast phenotypic variation. Even among patients with type 2 (acute neuronopathic) Gaucher's disease, there is a spectrum of clinical presentations. DNA samples from 14 patients with type 2 Gaucher's disease with a course ranging from intrauterine death at 22 wk of gestation to survival until age 30 mo were studied. L444P was the only common mutation identified, found in 15 patients' alleles. Sequencing of genomic DNA amplified by long template PCR revealed that mutation L444P occurred as a single point mutation in seven mutant alleles and as part of a recombinant allele in eight mutant alleles. Two patients had a deletion of 55 bp in exon 9; in one patient the deletion was part of a recombinant allele, and in a second the deletion occurred alone. Direct sequencing identified R120W on one allele, P415R on another, and one fetus was homoallelic for a deletion of a C nucleotide at codon 139 in exon 5. Eight of the mutant alleles remain unidentified. Northern blots revealed an appropriately sized mRNA in all except one of the patients studied. Of the 14 type 2 Gaucher patients, three had hydrops fetalis and died in utero or at birth, five had congenital ichthyosis, and seven survived 5 mo or more. Patients who died in the neonatal period had decreased protein detected by Western blot, regardless of genotype observed. These studies demonstrate that genotypic heterogeneity exists in patients with type 2 Gaucher's disease, even among infants with the most severe phenotypes. C1 NIMH, Clin Neurosci Branch, IRP, NIH, Bethesda, MD 20892 USA. RP Sidransky, E (reprint author), NIMH, Clin Neurosci Branch, IRP, NIH, Bldg 49,Room B1EE16,49 Convent Dr MSC 4405, Bethesda, MD 20892 USA. NR 52 TC 43 Z9 43 U1 1 U2 2 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD MAY PY 1998 VL 43 IS 5 BP 571 EP 578 DI 10.1203/00006450-199805000-00003 PG 8 WC Pediatrics SC Pediatrics GA ZK262 UT WOS:000073301600003 PM 9585001 ER PT J AU Wexler, ID Kerr, DS Du, YF Kaung, MM Stephenson, W Lusk, MM Wappner, RS Higgins, JJ AF Wexler, ID Kerr, DS Du, YF Kaung, MM Stephenson, W Lusk, MM Wappner, RS Higgins, JJ TI Molecular characterization of pyruvate carboxylase deficiency in two consanguineous families SO PEDIATRIC RESEARCH LA English DT Article ID AMINO-ACID-SEQUENCE; DEHYDROGENASE COMPLEX; DOMAIN-STRUCTURE; POINT MUTATION; BIOTIN; CDNA; CLONING; FIBROBLASTS; MECHANISM; PROTEIN AB Pyruvate carboxylase (PC) is a biotinylated mitochondrial enzyme that catalyzes the conversion of pyruvate to oxaloacetate. Children with inborn errors of PC metabolism have lactic acidosis, hypoglycemia, and mental retardation. The variable severity of the clinical phenotype is dependent on both genetic and environmental factors. Two consanguineous families with moderate forms of PC deficiency were characterized at the biochemical and molecular levels. In both families, the probands were found to have low PC activity (range, 2-25% of control) in blood lymphocytes and skin fibroblasts associated with either diminished or normal protein levels. In the first case, sequencing of patient-specific PC cDNA demonstrated a T to C substitution at nucleotide 434, which causes a valine to alanine change at amino acid residue 145. Direct sequencing of the parents showed that they are heterozygous for this mutation. In the second family, a brother and sister had mental retardation and episodes of severe lactic/ketoacidosis in early childhood. In these cases, a C to T substitution at nucleotide 1351 results in a cysteine for arginine substitution at amino acid residue 451; the parents were also found to be heterozygous for this mutation. In both families, no other mutations were found, and both substitutions occurred in relatively conserved amino acid residues. These mutations, located in the biotin carboxylase domain, provide a unique opportunity to analyze how natural occurring mutations affect PC function. C1 Case Western Reserve Univ, Sch Med, Dept Pediat, Cleveland, OH 44118 USA. Indiana Univ, Dept Pediat, Indianapolis, IN 46202 USA. Indiana Univ, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. NINDS, Clin Neurogenet Unit, Med Neurol Branch, Bethesda, MD 20892 USA. RP Wexler, ID (reprint author), Univ Hosp Cleveland, Dept Pediat, RB&C, 11100 Euclid Ave, Cleveland, OH 44106 USA. FU NICHD NIH HHS [HD-32434]; NIDDK NIH HHS [DK20478] NR 27 TC 19 Z9 20 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD MAY PY 1998 VL 43 IS 5 BP 579 EP 584 DI 10.1203/00006450-199805000-00004 PG 6 WC Pediatrics SC Pediatrics GA ZK262 UT WOS:000073301600004 PM 9585002 ER PT J AU Clark, NM Gong, M Schork, A Evans, D Roloff, D Hurwitz, M Maiman, L Mellins, RB AF Clark, NM Gong, M Schork, A Evans, D Roloff, D Hurwitz, M Maiman, L Mellins, RB TI Impact of education for physicians on patient outcomes SO PEDIATRICS LA English DT Article DE patient outcomes; continuing education; asthma; quality of care; patient satisfaction ID ASTHMA; TRIAL AB Objectives. This study was conducted to assess the impact of an interactive seminar based on self-regulation theory on 1) the treatment practices and communications and education behavior of physicians, 2) the health status and medical care utilization of their pediatric patients with asthma, and 3) the satisfaction with care of the subjects' parents. Methods. A total of 74 general practice pediatricians were assigned to either a program or a control group in a randomized controlled study. Data were collected from physicians at baseline, and 69 (93%) provided follow-up data 5 months after the program. Data were also collected from 637 of their patients at baseline, and in a 22-month window after the intervention, 472 (74%) of this number provided follow-up data. Results. After the seminar, physicians in the program group were more likely than were control group physicians to address patients' fears about medicines, review written instructions, provide a sequence of educational messages, write down how to adjust the medicines at home when symptoms change, and report that they spent less time with their patients. Parents of the children treated by program physicians were significantly more likely than were control group parents to report that the physician had been reassuring, described as a goal that the child be fully active, and gave information to relieve specific worries. After a visit with the physician, these parents were also more likely to report that they knew how to make management decisions at home. After the intervention compared to controls, patients of physicians in the program group were more likely to have received a prescription for inhaled antiinflammatory medicine and to have been asked by the physician to demonstrate how to use a metered-dose inhaler. After the intervention, children seen by program physicians made significantly fewer nonemergency office visits and visits for follow-up of an episode of symptoms; however, there were no differences in emergency department visits and hospitalizations. Among children who were placed on inhaled corticosteroids during this study, however, children treated by physicians who had received education had significantly fewer symptoms and fewer follow-up office visits, nonemergency physician office visits, emergency department visits, and hospitalizations. Conclusions. The interactive seminar based on theories of self-regulation led to patient-physician encounters that were of shorter duration, had significant impact on the prescribing and communications behavior of physicians, led to more favorable patient responses to physicians' actions, and led to reductions in health care utilization. C1 Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Publ Hlth, Dept Publ Hlth, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Pediat & Communicable Dis, Ann Arbor, MI USA. Columbia Univ, Dept Clin Publ Hlth, Coll Phys & Surg, New York, NY USA. Columbia Univ, Dept Pediat, Coll Phys & Surg, New York, NY USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Clark, NM (reprint author), Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, 1420 Washington Heights, Ann Arbor, MI 48109 USA. FU NHLBI NIH HHS [HL-44976] NR 21 TC 219 Z9 220 U1 2 U2 14 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 MAY PY 1998 VL 101 IS 5 BP 831 EP 836 DI 10.1542/peds.101.5.831 PG 6 WC Pediatrics SC Pediatrics GA ZL376 UT WOS:000073426700004 PM 9565410 ER PT J AU Munoz, KA Krebs-Smith, SM Ballard-Barbash, R Cleveland, LE AF Munoz, KA Krebs-Smith, SM Ballard-Barbash, R Cleveland, LE TI Errors in food intake article SO PEDIATRICS LA English DT Letter C1 Merck & Co Inc, Blue Bell, PA 19422 USA. NCI, Appl Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. USDA ARS, Food Surveys Res Grp, Beltsville Human Nutr Res Ctr, Riverdale, MD USA. RP Munoz, KA (reprint author), Merck & Co Inc, Blue Bell, PA 19422 USA. NR 1 TC 13 Z9 13 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 MAY PY 1998 VL 101 IS 5 BP 952 EP 953 DI 10.1542/peds.101.5.952 PG 2 WC Pediatrics SC Pediatrics GA ZL376 UT WOS:000073426700048 PM 9599129 ER PT J AU Leickly, FE Wade, SL Crain, E Kruszon-Moran, D Wright, EC Evans, R AF Leickly, FE Wade, SL Crain, E Kruszon-Moran, D Wright, EC Evans, R TI Self-reported adherence, management behavior, and barriers to care after an emergency department visit by inner city children with asthma SO PEDIATRICS LA English DT Article DE asthma; adherence; inner city children ID MEDICATION COMPLIANCE; INHALED MEDICATION; DRUG-THERAPY; PATIENT; MORTALITY; PATTERNS; USAGE AB Objective. The inability to adhere to a prescribed therapeutic program for the treatment of a chronic disease may be responsible in part for continued disease activity. This problem may be more of an issue in the treatment of asthma, a common, potentially lethal chronic condition in which the lack of symptoms may be interpreted as remission. Adherence was one of the key areas of interest for the National Cooperative Inner-City Asthma Study. The focus of this study was to identify those issues reported by families that could adversely affect their adherence to an asthma care program. The identification of barriers to adherence could then form the basis of a successful intervention program. This study describes barriers to adherence, asthma management behavior, and self-reported adherence. Methods. Patients presenting during an acute attack of asthma at an emergency department (ED) were recruited for this study. The medical record of the ED encounter was abstracted and compared with information that was obtained during a baseline interview 3 to 5 weeks later. During the baseline interview, parents were asked about health care behaviors related to adherence. Results. There were 344 children 4 to 9 years of age living in inner city census tracts in the study. Pour areas of adherence (medicine use, appointment-keeping emergency actions, and asthma attack prevention) were investigated. The parental report of medications prescribed at the ED and the information on the abstracted ED report agreed 94.9% of the time for the beta-agonists, 86.8% for steroids, and 69.4% for cromolyn. Among respondents, 85.4% of parents reported that they are able to follow the ED recommendations almost ail of the time; side effects of medicines were a concern for 81.1% of caretakers who were adherent and for 89.5% of caretakers who were nonadherent. Doubts regarding the usefulness of medications occurred in 34.4% of those considered adherent and 54.2% who admitted nonadherence. Medications were forgotten some of the time by 45.2% of the children, and 52.8% tried to get out of taking medicine. Appointments for follow-up care were kept by 69% of those given an appointment in the ED, by an estimated 60.0% of those who were told specifically to call for an appointment, and by an estimated 25.2% of those who were neither given an appointment nor told specifically to make one. Only one third of parents report that they were able to keep the child away from known asthma triggers nearly all of the time. Approximately half avoided allergens; however, only 37.5% reported avoidance of cigarette smoke. The use of preventive medicines occurred in 23.5%. Using a medicine and taking the child to a physician were reported as the first or second action during an acute attack of asthma by 72.1% of respondents. Conclusions. Adherence to an asthma-management program involves a number of areas: medication, appointment-keeping, prevention, and applying an emergency plan of action. Barriers to adherence may exist in one or all four of these areas, leading to ineffective control of asthma. Recommendations are made for improving the patient-physician partnership to improve adherence. C1 Indiana Univ, James Whitcomb Riley Hosp Children, Indianapolis, IN 46202 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. NIAID, NIH, Bethesda, MD 20892 USA. New England Res Inst, Watertown, MA 02172 USA. Childrens Mem Hosp, Chicago, IL 60614 USA. RP Leickly, FE (reprint author), Indiana Univ, James Whitcomb Riley Hosp Children, 2750,702 Barnhill Dr, Indianapolis, IN 46202 USA. FU PHS HHS [A1-30752, A1-30756, U01 A1-30751] NR 32 TC 63 Z9 63 U1 2 U2 3 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 MAY PY 1998 VL 101 IS 5 BP art. no. EP e8 DI 10.1542/peds.101.5.e8 PG 8 WC Pediatrics SC Pediatrics GA ZL376 UT WOS:000073426700026 PM 9565441 ER PT J AU Player, MR Torrence, PF AF Player, MR Torrence, PF TI The 2-5A system: Modulation of viral and cellular processes through acceleration of RNA degradation SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE double-stranded RNA; 2-5A; interferons; ribonuclease L; virus; host defense ID DOUBLE-STRANDED-RNA; TREATED HELA-CELLS; 2'-5' OLIGOADENYLATE SYNTHETASE; HUMAN-IMMUNODEFICIENCY-VIRUS; BLOOD MONONUCLEAR-CELLS; TUMOR NECROSIS FACTOR; POTENTIAL ANTIVIRAL AGENTS; INTERFERON-INDUCED ENZYME; FREE PROTEIN-SYNTHESIS; HUMAN 2',5'-OLIGOADENYLATE SYNTHETASE AB The 2-5A system is an RNA degradation pathway that can be induced by the interferons (IFNs), Treatment of cells with IFN activates genes encoding several double-stranded RNA (dsRNA)-dependent synthetases. These enzymes generate 5'-triphosphorylated, 2',5'-phosphodiester-linked oligoadenylates (2-5A) from ATP. The effects of 2-5A in cells are transient since 2-5A is unstable in cells due to the activities of phosphodiesterase and phosphatase, 2-5A activates the endoribonuclease 2-5A-dependent RNase L, causing degradation of single-stranded RNA with moderate specificity. The human 2-5A-dependent RNase is an 83.5 kDa polypeptide that has little, if any, RNase activity, unless 2-5A is present. 2-5A binding to RNase L switches the enzyme from its off-state to its on-state. At least three 2',5'-linked oligoadenylates and a single 5'-phosphoryl group are required for maximal activation of the RNase. Even though the constitutive presence of 2-5A-dependent RNase is observed in nearly all mammalian cell types, cellular amounts of 2-5A-dependent mRNA and activity can increase after IFN treatment. One well-established role of the 2-5A system is as a host defense against some types of viruses. Since virus infection of cells results in the production and secretion of IFNs, and since dsRNA is both a frequent product of virus infection and an activator of 2-5A synthesis, the replication of encephalomyocarditis virus, which produces dsRNA during its life cycle, is greatly suppressed in IFN treated cells as a direct result of RNA decay by the activated 2-5A dependent RNase. This review covers the organic chemistry, enzymology, and molecular biology of 2-5A and its associated enzymes, Additional possible biological roles of the 2-5A system, such as in cell growth and differentiation, human immunodeficiency virus replication, heat shock, atherosclerotic plaque, pathogenesis of Type I diabetes, and apoptosis, are presented. (C) 1998 Elsevier Science Inc. C1 NIDDKD, Sect biomed Chem, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Torrence, PF (reprint author), NIDDKD, Sect biomed Chem, Med Chem Lab, NIH, Bldg 8,Room B2A02, Bethesda, MD 20892 USA. NR 546 TC 223 Z9 232 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD MAY PY 1998 VL 78 IS 2 BP 55 EP 113 DI 10.1016/S0163-7258(97)00167-8 PG 59 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZJ481 UT WOS:000073220000001 PM 9623881 ER PT J AU Stadtman, TC Walker, H AF Stadtman, TC Walker, H TI Selenophosphate: Biological roles and studies on mechanism of biosynthesis SO PHOSPHORUS SULFUR AND SILICON AND THE RELATED ELEMENTS LA English DT Article DE biological selenium donor; isotope exchange C1 NHLBI, NIH, Biochem Lab, Bethesda, MD 20892 USA. RP Stadtman, TC (reprint author), NHLBI, NIH, Biochem Lab, Bldg 3,Room 108, Bethesda, MD 20892 USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU GORDON BREACH PUBLISHING, TAYLOR & FRANCIS GROUP PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1042-6507 J9 PHOSPHORUS SULFUR JI Phosphorus Sulfur Silicon Relat. Elem. PD MAY-JUL PY 1998 VL 136 BP 367 EP 372 PG 6 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA V3230 UT WOS:000171897600034 ER PT J AU Chignell, CF Sik, RH AF Chignell, CF Sik, RH TI The effect of static magnetic fields on the photohemolysis of human erythrocytes by ketoprofen SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID MECHANISM AB Ultraviolet irradiation (lambda > 300 nm) of the nonsteroidal anti-inflammatory agent ketoprofen (KP, 3-benzoyl-alpha-methylbenzoacetic acid) in aqueous solution, pH 7.4, results in heterolytic decarboxylation of the drug to give 3-ethylbenzophenone (EtBP). Ketoprofen caused the photohemolysis of human erythrocytes probably as a result of lipid peroxidation. Application of a static magnetic field (250-1500 G) during UV (>300 nm) irradiation of KP and erythrocytes significantly decreased the time required for photohemolysis. This observation suggests that KP-induced photohemolysis involves the initial generation of a triplet radical pair derived from the reaction of triplet state KP (or 3-EtBP) with erythrocyte component(s) probably lipids. The magnetic field increases the concentration and/or lifetime of free radicals that escape from the radical pair so that the critical radical concentration needed to initiate membrane damage and cause cell lysis is reached sooner. Spin-trapping studies with 2,6-dibromo-1-nitrosobenzene-4-sulfonate confirmed that the application of an external static magnetic field increased the concentration of radicals released during the photolysis of either KP or 3-EtBP dissolved in organized media such as sodium dodecylsulfate micelles. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Chignell, CF (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM chignell@niehs.nih.gov NR 12 TC 24 Z9 24 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 MAY PY 1998 VL 67 IS 5 BP 591 EP 595 DI 10.1111/j.1751-1097.1998.tb09098.x PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZP864 UT WOS:000073796300020 PM 9613243 ER PT J AU Roberts, RL Cushing, BS Carter, CS AF Roberts, RL Cushing, BS Carter, CS TI Intraspecific variation in the induction of female sexual receptivity in prairie voles SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE Microtus ochrogaster; prairie vole; induced estrus; lordosis; intraspecific variation ID HOME-RANGE SIZE; MICROTUS-OCHROGASTER; PREGNANCY SUCCESS; VAGINAL ESTRUS; MEADOW VOLES; BEHAVIOR; OVULATION; PENNSYLVANICUS; IMPLANTATION; MONOGAMY AB Prairie voles (Microtus ochrogaster) are monogamous New World rodents which show geographic variation in social behavior. In this study, parameters of female reproduction which might be related to mating system were compared in prairie voles from eastern Kansas (KAN) versus central Illinois (ILL). KAN females showed a more rapid onset of natural estrus following exposure to a male and were more likely to respond to injections of a low dose (0.5 mu g) of exogenous estradiol benzoate than ILL females. Neither mating duration nor pregnancy success-after mate removal differed in KAN versus ILL females. These results suggest that ILL voles are less sensitive than KAN voles to the estrus-inducing effects of either endogenous or exogenous estrogen, supporting the hypothesis that variations in reproductive strategy occur among geographically discrete populations of prairie voles. (C) 1998 Elsevier Science Inc. C1 Univ Maryland, Dept Zool, College Pk, MD 20742 USA. RP Roberts, RL (reprint author), NICHHD, Comparat Ethol Lab, POB 529, Poolesville, MD 20837 USA. EM roberts1@1ce.nichd.nih.gov FU NICHD NIH HHS [HD 32675]; NIMH NIH HHS [MH 01050] NR 34 TC 24 Z9 27 U1 4 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD MAY PY 1998 VL 64 IS 2 BP 209 EP 212 DI 10.1016/S0031-9384(98)00042-0 PG 4 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA ZW318 UT WOS:000074398200014 PM 9662088 ER PT J AU Pratley, RE AF Pratley, RE TI Gene-environment interactions in the pathogenesis of type 2 diabetes mellitus: lessons learned from the Pima Indians SO PROCEEDINGS OF THE NUTRITION SOCIETY LA English DT Article; Proceedings Paper CT Summer Meeting of the Nutrition-Society CY JUL 09-11, 1997 CL UNIV NEWCASTLE UPON TYNE, NEWCASTLE TYNE, ENGLAND SP Nutr Soc HO UNIV NEWCASTLE UPON TYNE ID ACID-BINDING PROTEIN; INSULIN-RESISTANCE; OBESITY; NIDDM; CAUCASIANS; MUTATIONS; PREVALENCE; INCREASES; LINKAGE; WEIGHT C1 NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. RP Pratley, RE (reprint author), NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Clin Res Branch, NIH, 4212 N 16Th St, Phoenix, AZ 85016 USA. NR 35 TC 40 Z9 40 U1 0 U2 3 PU C A B INTERNATIONAL PI WALLINGFORD PA C/O PUBLISHING DIVISION, WALLINGFORD OX10 8DE, OXON, ENGLAND SN 0029-6651 J9 P NUTR SOC JI Proc. Nutr. Soc. PD MAY PY 1998 VL 57 IS 2 BP 175 EP 181 DI 10.1079/PNS19980029 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZV132 UT WOS:000074272600001 PM 9656318 ER PT J AU Zhang, BX Tsai, S Shih, JWK Wear, DJ Lo, SC AF Zhang, BX Tsai, S Shih, JWK Wear, DJ Lo, SC TI Absence of mycoplasmal gene in malignant mammalian cells transformed by chronic persistent infection of mycoplasmas SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; DNA; IDENTIFICATION; INCOGNITUS; SEQUENCES; PENETRANS; BACTERIA; VIRUS AB Chronic persistent infections by mycoplasmas induced malignant transformation of C3H mouse embryo cells that normally had never been reported to undergo spontaneous transformation, This mycoplasma-mediated oncogenic process had a long latency (more than 7 weeks of continuous mycoplasmal infection) and showed a multistage progression characterized by reversibility (at least up to 11 weeks of mycoplasmal infection) and irreversibility of malignant properties upon removal of the mycoplasma from culture, Further prolonged infections (18 weeks) by Mycoplasma fermentans or M. penetrans resulted in permanent transformation of these C3H cells that no longer required the continued presence of the transformation-inducing mycoplasmas in cultures to retain their malignant properties, Previous studies of viral oncogenesis revealed that virus-transformed cells always had viral gene(s) present, Integration of viral gene(s) apparently played an important role in the process of oncogenesis, In this study, we examined if the continued presence of any mycoplasmal gene(s) in mammalian cells, in whatever form, was also crucial in causing malignant cell transformation, Representational difference analysis (RDA) was a recently developed powerful technique to compare differences between two complex genomes, In the RDA system, subtractive and kinetic enrichment was used to purify and isolate restriction endonuclease gene fragment(s) of mycoplasmal origin, presumably present only in mycoplasma-transformed C3H cells, but not in nonmycoplasma-exposed control C3H cells. After three rounds of subtractive hybridization following PCR enrichment for each of three different restriction enzymes DNA digests, no gene fragment of mycoplasmal origin was amplified or identified in the permanently transformed C3H cells, Differing from tumorigenesis in animal cells induced by most oncogenic viruses or in plant cells induced by Agrobacteria, mycoplasmas evidently did not cause malignant transformation by integrating their gene(s) into the mammalian cell genome. C1 Armed Forces Inst Pathol, Dept Infect & Parasit Dis Pathol, Amer Registry Pathol, Washington, DC 20306 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Lo, SC (reprint author), Armed Forces Inst Pathol, Dept Infect & Parasit Dis Pathol, Amer Registry Pathol, Bldg 54,Room 4091,14th & Alaska Ave NW, Washington, DC 20306 USA. NR 25 TC 13 Z9 14 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD MAY PY 1998 VL 218 IS 1 BP 83 EP 89 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZJ485 UT WOS:000073220400010 PM 9572156 ER PT J AU Salgaller, ML Lodge, PA McLean, JG Tjoa, BA Loftus, DJ Ragde, H Kenny, GM Rogers, M Boynton, AL Murphy, GP AF Salgaller, ML Lodge, PA McLean, JG Tjoa, BA Loftus, DJ Ragde, H Kenny, GM Rogers, M Boynton, AL Murphy, GP TI Report of immune monitoring of prostate cancer patients undergoing T-cell therapy using dendritic cells pulsed with HLA-A2-specific peptides from prostate-specific membrane antigen (PSMA) SO PROSTATE LA English DT Article DE dendritic cells; T-cell; immunotherapy; prostate cancer; phase II trial; monitoring ID SIGNAL-TRANSDUCTION MOLECULES; ACTIVE SPECIFIC IMMUNOTHERAPY; POLYVALENT MELANOMA VACCINE; TUMOR-BEARING MICE; METASTATIC MELANOMA; MONOCLONAL-ANTIBODY; ELISPOT ASSAY; RESPONSES; IMMUNIZATION; CARCINOMA AB BACKGROUND. In this paper we describe our program for the immune monitoring of phase II participants given dendritic cell (DC)/prostate-specific membrane antigen (PSMA)-based immunotherapy, and we also present some initial findings. METHODS. Phase II subjects received six administrations of autologous dendritic cells exogenously pulsed with two peptides derived from PSMA. Prior to the initial infusion, and following each treatment, peripheral blood mononuclear cells (PBMC) were collected for the generation of dendritic cells as well as for comprehensive immune monitoring. RESULTS. Thus far, an increase in PSMA-peptide-specific as well as overall cellular reactivity has been observed in several patients receiving DC plus PSM-P1 and -P2, as measured by delayed-type hypersensitivity (DTH) test and enzyme-linked immunosorbant assay (ELISA). CONCLUSIONS. Our initial observations using an ELISA and DTH test indicate that we are enhancing cellular immunity in prostate cancer patients following infusion with DC plus PSMA-derived peptides. Several methods are underway to comprehensively monitor both cell-mediated and humoral immune responsiveness, including: determining anti-PSMA serum antibody titers, testing immunogen-restricted responder-cell proliferation and cytotoxicity, assessing aberrations in signal transduction, antigen processing, and presentation, and measuring soluble factors that may promote tumor outgrowth. (C) 1998 Wiley-Liss, Inc. C1 Pacific NW Canc Fdn, NW Biotherapeut LLC, Seattle, WA 98125 USA. Northwest Hosp, Canc Res Div, Seattle, WA USA. NCI, NIH, Bethesda, MD 20892 USA. Northwest Hosp, Dept Mol Med, Seattle, WA USA. RP Salgaller, ML (reprint author), Pacific NW Canc Fdn, NW Biotherapeut LLC, 120 Northgate Plaza,Suite 219, Seattle, WA 98125 USA. EM mls@nwbio.org NR 40 TC 89 Z9 93 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 0270-4137 J9 PROSTATE JI Prostate PD MAY 1 PY 1998 VL 35 IS 2 BP 144 EP 151 DI 10.1002/(SICI)1097-0045(19980501)35:2<144::AID-PROS8>3.0.CO;2-J PG 8 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA ZJ114 UT WOS:000073180900008 PM 9568678 ER PT J AU Qu, KB Martin, DL Lawrence, CE AF Qu, KB Martin, DL Lawrence, CE TI Motifs and structural fold of the cofactor binding site of human glutamate decarboxylase SO PROTEIN SCIENCE LA English DT Article DE Bayesian statistics; Gibbs sampling; human glutamate decarboxylase; multiple sequence alignment; structural prediction by homology ID MITOCHONDRIAL ASPARTATE-AMINOTRANSFERASE; ORNITHINE DECARBOXYLASE; ACID DECARBOXYLASE; CRYSTAL-STRUCTURE; GOLGI-COMPLEX; BRAIN; REGION; ALIGNMENT; ANGSTROM; ENZYMES AB The pyridoxal-P binding sites of the two isoforms of human glutamate decarboxylase (GAD65 and GAD67) were modeled by using PROBE (a recently developed algorithm for multiple sequence alignment and database searching) to align the primary sequence of GAD with pyridoxal-P binding proteins of known structure. GAD's cofactor binding site is particularly interesting because GAD activity in the brain is controlled in part by a regulated interconversion of the apo-and holoenzymes. PROBE identified six motifs shared by the two GADs and four proteins of known structure: bacterial ornithine decarboxylase, dialkylglycine decarboxylase, aspartate aminotransferase, and tyrosine phenol-lyase. Five of the motifs corresponded to the alpha/beta elements and loops that form most of the conserved fold of the pyridoxal-P binding cleft of the four enzymes of known structure; the sixth motif corresponded to a helical element of the small domain that closes when the substrate binds. Eight residues that interact with pyridoxal-P and a ninth residue that lies at the interface of the large and small domains were also identified. Eleven additional conserved residues were identified and their functions were evaluated by examining the proteins of known structure. The key residues that interact directly with pyridoxal-P were identical in ornithine decarboxylase and the two GADs, thus allowing us to make a specific structural prediction of the cofactor binding site of GAD. The strong conservation of the cofactor binding site in GAD indicates that the highly regulated transition between apo-and holoGAD is accomplished by modifications in this basic fold rather than through a novel folding pattern. C1 New York State Dept Hlth, Wadsworth Ctr Labs & Res, Biometr Lab, Albany, NY 12201 USA. New York State Dept Hlth, Wadsworth Ctr Labs & Res, Lab Nervous Syst Disorders, Albany, NY 12201 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Lawrence, CE (reprint author), New York State Dept Hlth, Wadsworth Ctr Labs & Res, Biometr Lab, POB 509,Empire State Plaza, Albany, NY 12201 USA. FU NHGRI NIH HHS [5R01HG0125702]; NIMH NIH HHS [MH35664] NR 41 TC 29 Z9 29 U1 0 U2 1 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 MAY PY 1998 VL 7 IS 5 BP 1092 EP 1105 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZL552 UT WOS:000073445800003 PM 9605314 ER PT J AU Almog, O Benhar, I Vasmatzis, G Tordova, M Lee, B Pastan, I Gilliland, GL AF Almog, O Benhar, I Vasmatzis, G Tordova, M Lee, B Pastan, I Gilliland, GL TI Crystal structure of the disulfide-stabilized Fv fragment of anticancer antibody B1: Conformational influence of an engineered disulfide bond SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE antibody; antitumor; single chain Fv; variable domains; X-ray crystallography; protein structure; protein stability ID SINGLE-CHAIN ANTIBODY; RECOMBINANT IMMUNOTOXIN; ANTIGEN-BINDING; NUDE-MICE; PROTEIN; CRYSTALLIZATION; IMMUNOGLOBULIN; EXPRESSION; COMPLEX; FAB AB A recombinant Fv construct of the B1 monoclonal antibody that recognizes the Lewis(Y)-related carbohydrate epitope on human carcinoma cells has been prepared, The Fv is composed of the polypeptide chains of the V-H and V-L domains expressed independently and isolated as inclusion bodies. The Fv is prepared by combining and refolding equimolar amounts of guanidine chloride solubilized inclusion bodies. The Fv is stabilized by an engineered interchain disulfide bridge between residues V(L)100 and V(H)44. This construct has a similar binding affinity as that of the single-chain construct (Benhar and Pastan, Clin. Cancer Res. 1:1023-1029, 1995). The B1 disulfide-stabilized Fv (B1dsFv) crystallizes in space group P6(1)22 with the unit cell parameters a = b = 80.1 Angstrom, and c = 138.1 Angstrom. The crystal structure of the B1dsFv has been determined at 2.1-Angstrom resolution using the molecular replacement technique, The final structure has a crystallographic R-value of 0.187 with a root mean square deviation in bond distance of 0.014 Angstrom and in bond angle of 2.74 degrees, Comparisons of the B1dsFv structure with known structures of Fv regions of other immunoglobulin fragments shows closely related secondary and tertiary structures. The antigen combining site of B1dsFv is a deep depression 10-Angstrom wide and 17-Angstrom long with the walls of the depression composed of residues, many of which are tyrosines, from complementarity determining regions L1, L3, H1, H2, and H3. Model building studies indicate that the Lewis(Y) tetrasaccharide, Fuc-Gal-Nag-Fuc, can be accommodated in the antigen combining site in a manner consistent with the epitope predicted in earlier biochemical studies (Pastan, Lovelace, Gallo, Rutherford, Magnani, and Willingham, Cancer Res. 51:3781-3787, 1991). Thus, the engineered disulfide bridge appears to cause little, if any, distortion in the Fv structure, making it an effective substitute for the B1 Fab, Proteins 31:128-138, 1998. (C) 1998 Wiley-Liss, Inc.dagger C1 Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. Natl Inst Stand & Technol, Rockville, MD USA. Tel Aviv Univ, George S Wise Fac Life Sci, Dept Mol Microbiol & Biotechnol, IL-69978 Tel Aviv, Israel. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Gilliland, GL (reprint author), Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, 9600 Gudelsky Dr, Rockville, MD 20850 USA. RI Lee, Byungkook/E-4564-2011 OI Lee, Byungkook/0000-0002-3339-4582 NR 39 TC 13 Z9 13 U1 0 U2 6 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 MAY 1 PY 1998 VL 31 IS 2 BP 128 EP 138 DI 10.1002/(SICI)1097-0134(19980501)31:2<128::AID-PROT3>3.0.CO;2-I PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZJ661 UT WOS:000073239400003 PM 9593187 ER PT J AU Bassett, SS Chase, GA Folstein, MF Regier, DA AF Bassett, SS Chase, GA Folstein, MF Regier, DA TI Disability and psychiatric disorders in an urban community: measurement, prevalence and outcomes SO PSYCHOLOGICAL MEDICINE LA English DT Article ID DSM-III; HEALTH-SERVICES; MENTALLY-ILL; PRIMARY CARE; DEPRESSION; DIAGNOSIS; ANXIETY; WORK AB Background. The purpose of this analysis was to examine: (1) the prevalence of psychiatric disorders among disabled people, using seven different measures of disability; (2) variation in disability between and within psychiatric diagnostic categories; and (3) relationship of diagnosis and disability to health service utilization. Method. Data were drawn from Phase I and Phase II of the Eastern Baltimore Mental Health Survey, part of the Epidemiologic Catchment Area Program (ECA) conducted in 1980-1 to survey mental morbidity within the adult population. A total of 810 individuals received both a household interview and a standardized clinical psychiatric evaluation. Estimated prevalence rates were computed using appropriate survey sampling weights. Results. Prevalence of disability ranged from 2.5 to 19.5%, varying with specific disability measure. Among those classified as disabled by any of the measures examined, 56 to 92% had a psychiatric disorder and serious chronic medical conditions were present in the majority of these cases (54 to 78%). Disability was expressed differently among the various diagnostic groups. Diagnostic category and disability were significant independent predictors of medical service utilization and receipt of disability payments. Conclusions. The majority of disabled adults living in the community have diagnosable psychiatric disorders, with the majority of these individuals suffering from significant chronic medical conditions as well, thus making co-morbidity the norm. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21287 USA. Georgetown Med Ctr, Dept Biostat & Biomath, Washington, DC 20007 USA. New England Med Ctr, Dept Psychiat, Boston, MA 02111 USA. NIMH, Div Epidemiol & Serv Res, Bethesda, MD 20892 USA. RP Bassett, SS (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat, 600 N Wolfe St,Osler 320, Baltimore, MD 21287 USA. NR 33 TC 21 Z9 21 U1 2 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD MAY PY 1998 VL 28 IS 3 BP 509 EP 517 DI 10.1017/S0033291798006606 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA ZP839 UT WOS:000073793600002 PM 9626708 ER PT J AU Goldberg, TE Patterson, KJ Taqqu, Y Wilder, K AF Goldberg, TE Patterson, KJ Taqqu, Y Wilder, K TI Capacity limitations in short-term memory in schizophrenia: tests of competing hypotheses SO PSYCHOLOGICAL MEDICINE LA English DT Article ID PERFORMANCE; ATTENTION; DEFICITS; INTERFERENCE; DYSFUNCTION; DISORDERS AB Background. Capacity limitation theories have proved to be surprisingly resilient in characterizing some of the cognitive deficits in schizophrenia. However, this perspective has not generally been applied to short-term verbal memory tasks. We explored this issue by first attempting to ascertain if gross misallocations of processing resources might explain impairments in short-term memory in schizophrenia on a classic digit span task and in a second study by attempting to determine what effects delay and memory set size had on a divided attention short-term verbal memory paradigm. Methods. In the first study 16 patients with schizophrenia and 21 normal controls received 40 trials of a three digit task and 20 trials of a six digit span task. As the absolute number of digits presented and duration of presentation in two conditions were identical, subjects thus had equivalent 'opportunities' to make errors if distraction, in the sense of misallocation of cognitive resources, were at the root of poor performance. In the second study 15 patients with schizophrenia and 15 normal controls were tested in conditions in which two, four or six words were presented and in which rehearsal was prevented by an interference task (colour naming) for delays of 5, 10 or 15 s. Results. Patients had disproportionate difficulty on the six digit rather than the three digit condition, suggesting that deficits in the verbal working memory short-term store may not be the result of attentional factors. In the second study, patients' performance was differentially worsened by the interference task, by memory set size (i.e. a capacity limitation) and by delay, a measure of decay rate. Conclusions. In concert, these studies demonstrate that schizophrenia patients have difficulties on verbal short-term memory span tasks not because of misallocation of resources, but rather because of limitations in 'representational capacity' and maintenance of information over delays. C1 NIMH, St Elizabeths Hosp, Ctr Neurosci,Intramural Res Program, Clin Brain Disorders Branch, Washington, DC 20032 USA. RP Goldberg, TE (reprint author), NIMH, St Elizabeths Hosp, Ctr Neurosci,Intramural Res Program, Clin Brain Disorders Branch, Washington, DC 20032 USA. NR 34 TC 59 Z9 59 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD MAY PY 1998 VL 28 IS 3 BP 665 EP 673 DI 10.1017/S0033291797006429 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA ZP839 UT WOS:000073793600016 PM 9626722 ER PT J AU Tran, TT de Costa, BR Matsumoto, RR AF Tran, TT de Costa, BR Matsumoto, RR TI Microinjection of sigma ligands into cranial nerve nuclei produces vacuous chewing in rats SO PSYCHOPHARMACOLOGY LA English DT Article DE sigma receptors; DTG; haloperidol; dyskinesia; facial nucleus; spinal trigeminal nucleus; movement disorders ID GUINEA-PIG BRAIN; ANTIPSYCHOTIC-DRUGS; AUTORADIOGRAPHIC LOCALIZATION; TARDIVE-DYSKINESIA; RECEPTOR LIGANDS; HALOPERIDOL; DOPAMINE; BINDING; CLOZAPINE; SCHIZOPHRENIA AB Many typical neuroleptics carry a high risk for producing motor side effects in humans, and have significant affinities for sigma (sigma) receptors. Sigma receptors are densely concentrated in cranial nerve nuclei that comprise the final common pathways for lingual, facial and masticatory movements; thus, they may serve as important substrates for some of the unwanted movements that can accompany neuroleptic treatment, Therefore, the purpose of this study was to evaluate whether microinjection of sigma ligands into the facial nucleus or spinal trigeminal nucleus, oralis would cause orofacial dyskinesias, and whether these effects could be attenuated with sigma receptor antagonists. Microinjection of the high affinity sigma ligands, di-o-tolyl-guanidine or haloperidol (0-10 nmol/0.5 mu l), produced a marked increase in vacuous chewing and facial tremors in rats, while coadministration of the functional a antagonists, BD1047 or BD1063 (5 nmol), greatly attenuated these drug-induced movements. Sulpiride and clozapine (10 nmol/0.5 mu l), sigma inactive/ dopamine active atypical antipsychotic drugs with a much reduced risk for producing motor side effects in humans; were unable to elicit orofacial dyskinesias when microinjected into the facial or spinal trigeminal nucleus, oralis. These studies indicate that sigma receptors may contribute to some f'orms of motor side effects resulting from antipsychotic drug treatment. C1 Univ Oklahoma, Hlth Sci Ctr, Dept Pharmacol & Toxicol, Oklahoma City, OK 73190 USA. Univ Calif Irvine, Dept Neurol, Irvine, CA 92697 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Matsumoto, RR (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Pharmacol & Toxicol, POB 26901, Oklahoma City, OK 73190 USA. FU NIMH NIH HHS [MH50564] NR 42 TC 15 Z9 17 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAY PY 1998 VL 137 IS 2 BP 191 EP 200 DI 10.1007/s002130050609 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA ZZ522 UT WOS:000074737800011 PM 9630006 ER PT J AU Cuthbert, BN Schupp, HT Bradley, M McManis, M Lang, PJ AF Cuthbert, BN Schupp, HT Bradley, M McManis, M Lang, PJ TI Probing affective pictures: Attended startle and tone probes SO PSYCHOPHYSIOLOGY LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 17-20, 1996 CL VANCOUVER, CANADA SP Soc Psychophysiol Res DE event-related potentials; P300; startle; emotion; attention ID REFLEX AB Reflexive eyeblinks to a startle probe vary with the pleasantness of affective pictures, whereas the corresponding P300 varies with emotional arousal. The impact of attention to the probe on these effects was examined by varying task and probe type. Probes were either nonstartling tones or startling noises presented during affective picture viewing. Half the participants performed a task requiring attention to the probes; the other participants were told to ignore the probes. Blinks to the startle probe varied with picture pleasantness for both task and nontask conditions. In contrast, P300 magnitudes for both startle and tone probes were reduced during emotionally arousing pictures, irrespective of pleasantness, in task and nontask conditions. Further attending to the startle probe prompted an augmentation of N100 during unpleasant pictures. The data suggest that affective modulation of probe responses reflects obligatory processes in picture perception. C1 Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL USA. RP Cuthbert, BN (reprint author), NIMH, Ctr Study Emot & Attent, Box 100165 HSC, Gainesville, FL 32610 USA. EM brucec@nervm.nerdc.ufl.edu FU NIMH NIH HHS [MH43975, MH41950, MH37757] NR 13 TC 84 Z9 88 U1 1 U2 14 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD MAY PY 1998 VL 35 IS 3 BP 344 EP 347 DI 10.1017/S0048577298970536 PG 4 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA ZF856 UT WOS:000072940100013 PM 9564755 ER PT J AU Suomi, SJ AF Suomi, SJ TI Compelling retrospective results call for creative prospective investigations SO PSYCHOSOMATIC MEDICINE LA English DT Editorial Material ID RHESUS-MONKEYS; HEART-RATE; CORTISOL; MACAQUES; RESPONSES; STRESS C1 NICHHD, Comparat Ethol Lab, Bethesda, MD 20892 USA. RP Suomi, SJ (reprint author), NICHHD, Comparat Ethol Lab, Bethesda, MD 20892 USA. NR 19 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD MAY-JUN PY 1998 VL 60 IS 3 BP 245 EP 246 PG 2 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA ZP508 UT WOS:000073760500002 PM 9625209 ER PT J AU Losonczy, KG White, LR Brock, DB AF Losonczy, KG White, LR Brock, DB TI Prevalence and correlates of dementia: Survey of the Last Days of Life SO PUBLIC HEALTH REPORTS LA English DT Article ID ALZHEIMERS-DISEASE; MORTALITY; AGE AB Objectives, To estimate the prevalence and correlates of dementia at death and to assess the usefulness of death certificate data in the reporting of dementia. Methods, The authors analyzed next-of-kin interviews for 599 male and 628 female decedents using data from the National Institute on Aging's Survey of the Last Days of Life. Results. Death certificate data in this population show the prevalence of dementia to be less than 1%, consistent with previous reports based on death certificates but a substantial underestimate compared to the 11.9% reported in a national survey. Using a dementia index based on the informant's report of whether the decedent had been diagnosed with a dementing illness and the extent of her or his cognitive and functional limitations, this study found a prevalence of dementia of 8.5%. A high score on the dementia index was significantly associated with older age, Parkinson's disease, and incontinence. Lower relative odds for dementia at death were found for people with either a lifetime history or a death certificate report of cancer. Similarly, people with a lifetime history of coronary heart disease were found to have lower relative odds for dementia at death. Conclusion, These results suggest that informant interviews may be a useful source of data to examine factors associated with dementia and to estimate the prevalence of dementi; in the last year of life. C1 NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. RP Brock, DB (reprint author), NIA, Epidemiol Demog & Biometry Program, NIH, Gateway Bldg,Suite 3C309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. NR 22 TC 12 Z9 13 U1 2 U2 2 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD MAY-JUN PY 1998 VL 113 IS 3 BP 273 EP 280 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZQ313 UT WOS:000073845800026 PM 9633876 ER PT J AU Fail, PA George, JD Grizzle, TB Heindel, JJ AF Fail, PA George, JD Grizzle, TB Heindel, JJ TI Formamide and dimethylformamide: Reproductive assessment by continuous breeding in mice SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE formamide; dimethylformamide; toxicity; mice; continuous breeding protocol ID SWISS CD-1 MICE; DEVELOPMENTAL TOXICITY; N-METHYLFORMAMIDE; INHALATION EXPOSURE; DOSE LEVELS; RATS; N,N-DIMETHYLFORMAMIDE; TOXICOLOGY; METABOLISM; PROTOCOL AB Reproductive toxicity in Swiss mice, during chronic exposure to formamide (FORM) or dimethylformamide (DMF), was evaluated using the Reproductive Assessment by Continuous Breeding Protocols. FORM administered in drinking water at 0, 100, 350, and 750 ppm (similar to 20 to 200 mg/kg/d) reduced fertility and litter size in F-0 animals without generalized toxicity at 750 ppm FORM. Crossover matings suggested that females were the affected sex. After F-1 mating, FORM reduced F-2 litter size, increased days to litter, reduced relative ovarian weight, and lengthened estrous cycles at 750 ppm, The No-Observed-Adverse-Effect-Level for generalized toxicity was 750 ppm for the F-0 and 350 ppm for the F-1 generation. Reproductive performance was normal at 350 ppm for both F-0 and F-1 mice. Chronic exposure to DMF in drinking water at 0, 1000, 4000, and 7000 ppm (similar to 200 to 1300 mg/kg/d) reduced fertility by the first litter at 4000 ppm, reduced body weight in F-0 females at 7000 ppm, and increased liver weights at all doses in both sexes. A crossover mating at 7000 ppm identified F-0 females as the affected sex. F-1 postnatal survival was reduced at greater than or equal to 4000 ppm DMF, F-1 mating reduced F-2 litter size and live pup weight at greater than or equal to 1000 ppm. At necropsy, body weight of F-1 males and females was reduced at greater than or equal to 4000 ppm. DMF-treated pups (both F-1 and F-2) and F-1 adults had cranial and sternebral skeletal malformations. Only DMF caused overt developmental toxicity. A No-Observed-Adverse-Effect-level for DMF was not established. (C) 1998 Elsevier Science Inc. C1 Dreyfus Lab, Res Triangle Inst, Ctr Life Sci & Toxicol, Chem & Life Sci Div, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Natl Toxicol Program, Dev & Reprod Toxicol Grp, Res Triangle Pk, NC USA. RP Fail, PA (reprint author), Dreyfus Lab, Res Triangle Inst, Ctr Life Sci & Toxicol, Chem & Life Sci Div, POB 12194, Res Triangle Pk, NC 27709 USA. FU NIEHS NIH HHS [N01-ES-45061, N01-ES-65141, N01-ES-45060] NR 56 TC 20 Z9 22 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD MAY-JUN PY 1998 VL 12 IS 3 BP 317 EP 332 DI 10.1016/S0890-6238(98)00011-2 PG 16 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA ZR507 UT WOS:000073984500010 PM 9628555 ER PT J AU Moorman, WJ Skaggs, SR Clark, JC Turner, TW Sharpnack, DD Murrell, JA Simon, SD Chapin, RE Schrader, SM AF Moorman, WJ Skaggs, SR Clark, JC Turner, TW Sharpnack, DD Murrell, JA Simon, SD Chapin, RE Schrader, SM TI Male reproductive effects of lead, including species extrapolation for the rabbit model SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE lead; rabbit model; semen quality; blood lead ID SEMEN QUALITY; ENDOCRINE; FERTILITY; DYSFUNCTION; TOXICITY; EXPOSURE; RISKS; MEN AB The effects of elevated blood lead on semen quality were evaluated in the rabbit model and compared to published effects in humans. Mature, male rabbits were given lead acetate by subcutaneous injection in the dose range of 0 to 3.85 mg/kg on a Monday-Wednesday-Friday basis. In each of eight treatment groups, a dosing regimen was developed to produce blood lead levels of 0, 20, 40, 50, 70, 80, 90, and 110 mu g/dL. A 5-week pre-exposure period was followed by a 15-week exposure testing period allowing for response through six cycles of the seminiferous epithelium, Semen analyses revealed that increased blood lead levels were associated with adverse changes in the sperm count, ejaculate volume, percent motile sperm, swimming velocities, and morphology. Hormonal responses were minimal. Testicular pathology revealed a dose-dependent inhibition of spermiation, For six measures of semen quality, threshold estimates ranged from 16 to 24 mu g/dL. Using the species extrapolation factor derived in this study, a rabbit dose would have to be divided by 1.56 to obtain the equivalent human dose for an equal percentage decrease in sperm concentration; however, rabbits are 3.75 more sensitive in terms of absolute decrease in sperm count for a given blood lead level. Published by Elsevier Science Inc. C1 NIOSH, Cincinnati, OH 45226 USA. Analyt Sci Inc, Durham, NC USA. Childrens Mercy Hosp, Kansas City, KS USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Moorman, WJ (reprint author), 4676 Columbia Pkwy,MS C23, Cincinnati, OH 45215 USA. RI Schrader, Steven/E-8120-2011; OI Chapin, Robert/0000-0002-5997-1261 FU NIEHS NIH HHS [IA YO1-ES-40266] NR 27 TC 26 Z9 27 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD MAY-JUN PY 1998 VL 12 IS 3 BP 333 EP 346 DI 10.1016/S0890-6238(98)00010-0 PG 14 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA ZR507 UT WOS:000073984500011 PM 9628556 ER PT J AU Deepe, GS Seder, RA AF Deepe, GS Seder, RA TI Molecular and cellular determinants of immunity to Histoplasma capsulatum SO RESEARCH IN IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; MOUSE SPLENIC MACROPHAGES; HEAT-SHOCK PROTEIN-60; CD4+ T-CELLS; FACTOR-ALPHA; IFN-GAMMA; PULMONARY HISTOPLASMOSIS; FUNGISTATIC ACTIVITY; HOST-DEFENSE; STIMULATED MACROPHAGES C1 Univ Cincinnati, Coll Med, Div Infect Dis, Cincinnati, OH 45267 USA. NIAID, Clin Invest Lab, Lymphokine Regulat Unit, Bethesda, MD 20892 USA. RP Deepe, GS (reprint author), Univ Cincinnati, Coll Med, Div Infect Dis, Cincinnati, OH 45267 USA. NR 77 TC 18 Z9 18 U1 0 U2 1 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0923-2494 J9 RES IMMUNOL JI Res. Immunol. PD MAY-JUN PY 1998 VL 149 IS 4-5 BP 397 EP 406 DI 10.1016/S0923-2494(98)80763-3 PG 10 WC Immunology SC Immunology GA 112HL UT WOS:000075488000013 PM 9720957 ER PT J AU Roilides, E Katsifa, H Walsh, TJ AF Roilides, E Katsifa, H Walsh, TJ TI Pulmonary host defences against Aspergillus fumigatus SO RESEARCH IN IMMUNOLOGY LA English DT Review ID COLONY-STIMULATING FACTOR; CHRONIC GRANULOMATOUS-DISEASE; TUMOR-NECROSIS-FACTOR; ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS; MACROPHAGE OXIDATIVE BURST; MONOCYTE-MEDIATED DAMAGE; RHIZOPUS-ORYZAE HYPHAE; NITRIC-OXIDE SYNTHASE; SURFACTANT PROTEIN-A; ALVEOLAR MACROPHAGES C1 Aristotelian Univ Salonika, Hippokratio Gen Hosp, Dept Pediat 3, GR-54642 Thessloniki, Greece. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Roilides, E (reprint author), Aristotelian Univ Salonika, Hippokratio Gen Hosp, Dept Pediat 3, Konstantinoupoleos 49, GR-54642 Thessloniki, Greece. NR 105 TC 50 Z9 51 U1 0 U2 1 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0923-2494 J9 RES IMMUNOL JI Res. Immunol. PD MAY-JUN PY 1998 VL 149 IS 4-5 BP 454 EP 465 DI 10.1016/S0923-2494(98)80769-4 PG 12 WC Immunology SC Immunology GA 112HL UT WOS:000075488000019 PM 9720963 ER PT J AU Agostini, HT Ryschkewitsch, CF Stoner, GL AF Agostini, HT Ryschkewitsch, CF Stoner, GL TI Rearrangements of archetypal regulatory regions in JC virus genomes from urine SO RESEARCH IN VIROLOGY LA English DT Article DE polyomavirus; progressive multifocal leukoencephalopathy; JC virus; genomes; rearrangements; kidney; DNA sequence; urine; archetypal regulatory regions; AIDS; multiple sclerosis ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; RENAL-TRANSPLANT PATIENTS; PROMOTER ENHANCER; HUMAN BRAIN; POLYOMAVIRUS; AMPLIFICATION; INDIVIDUALS; TANZANIA; VARIANTS; SEQUENCE AB The regulatory region of progressive multifocal leukoencephalopathy-type JC virus (JCV) is rearranged in each host by a process of deletion and duplication. Of the more than 40 that have been examined, no two regulatory regions have been rearranged identically in the brain. The substrate for this rearrangement appears to be a highly stable archetypal regulatory region excreted in the urine. Its role as the transmissible form of the virus, although inferred, has never been proven. We have now amplified by PCR and cycle-sequenced the regulatory regions from 48 urinary strains of the virus. We find that the urinary form of the regulatory region is not entirely stable. Short deletions and duplications in the range of 2-16 bp were observed in seven of these strains. One of these, an inverted repeat, is a pattern of rearrangement not yet found in the brain. Two others (#208 and 230) showed a 2-bp deletion at position nos. 221 and 222, and an unusual mutation at position no. 219. These two urines were collected in different states of the USA at different times and analysed months apart. It is very unlikely that these unusual changes represent sample contamination or that they arose independently. This finding indicates that archetypal forms of the JCV regulatory region are infectious, despite their relative inactivity in tissue culture. While changes in the archetypal structure can be found, it is clear that rearrangements in the kidney are rare or rarely infectious. C1 NINDS, Neurotoxicol Sect, NIH, Bethesda, MD 20892 USA. RP Stoner, GL (reprint author), NINDS, Neurotoxicol Sect, NIH, Bethesda, MD 20892 USA. NR 23 TC 19 Z9 19 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0923-2516 J9 RES VIROLOGY JI Res. Virol. PD MAY-JUN PY 1998 VL 149 IS 3 BP 163 EP 170 DI 10.1016/S0923-2516(98)80034-4 PG 8 WC Virology SC Virology GA 103LT UT WOS:000075158000004 PM 9711540 ER PT J AU Velichutina, IV Rogers, MJ McCutchan, TF Liebman, SW AF Velichutina, IV Rogers, MJ McCutchan, TF Liebman, SW TI Chimeric rRNAs containing the GTPase centers of the developmentally regulated ribosomal rRNAs of Plasmodium falciparum are functionally distinct SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE development; malaria parasite; ribosome; Saccharomyces cerevisiae; translation ID ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; TRANSLATIONAL FIDELITY; THIOSTREPTON INTERACT; RNA; YEAST; MUTATIONS; ANTIBIOTICS; RESISTANCE; BINDING AB The human malaria parasite, Plasmodium falciparum, maintains at least two distinct types, A and S, of developmentally controlled ribosomal RNAs. To investigate specific functions associated with these rRNAs, we replaced the Saccharomyces cerevisiae GTPase domain of the 25S rRNA with GTPase domains corresponding to the Plasmodium A-and S-type 28S rRNAs, The A-type rRNA differs in a single nonconserved base pair from the yeast GTPase domain, The S-type rRNA GTPase domain has three additional changes in highly conserved residues, making it unique among all known rRNA sequences. The expression of either A-or S-type chimeric rRNA in yeast increased translational accuracy, Yeast containing only A-type chimeric rRNA and no wild-type yeast rRNA grew at the wild-type level. In contrast, S-type chimeric rRNA severely inhibited growth in the presence of wild-type yeast rRNA, and caused lethality in the absence of the wild-type yeast rRNA, We show what before could only be hypothesized, that the changes in the GTPase center of ribosomes present during different developmental stages of Plasmodium species can result in fundamental changes in the biology of the organism. C1 Univ Illinois, Dept Biol Sci, Mol Biol Lab, Chicago, IL 60607 USA. NIAID, Growth & Dev Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Liebman, SW (reprint author), Univ Illinois, Dept Biol Sci, Mol Biol Lab, Mol Biol Res Bldg,900 S Ashland Ave,Room 4079, Chicago, IL 60607 USA. FU NIGMS NIH HHS [GM 51412] NR 33 TC 24 Z9 24 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD MAY PY 1998 VL 4 IS 5 BP 594 EP 602 DI 10.1017/S1355838298980049 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZL363 UT WOS:000073425400009 PM 9582100 ER PT J AU Kaiser, J AF Kaiser, J TI Clues to unsolved arsenic case (vol 280, pg 1850, 1998) SO SCIENCE LA English DT Correction C1 NCI, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAY 1 PY 1998 VL 280 IS 5364 BP 659 EP 659 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZL268 UT WOS:000073415600011 ER PT J AU Duesbery, NS Webb, CP Leppla, SH Gordon, VM Klimpel, KR Copeland, TD Ahn, NG Oskarsson, MK Fukasawa, K Paull, KD Vande Woude, GF AF Duesbery, NS Webb, CP Leppla, SH Gordon, VM Klimpel, KR Copeland, TD Ahn, NG Oskarsson, MK Fukasawa, K Paull, KD Vande Woude, GF TI Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor SO SCIENCE LA English DT Article ID BACILLUS-ANTHRACIS; PROTECTIVE ANTIGEN; ADENYLATE-CYCLASE; MAMMALIAN-CELLS; TOXIN; PROTEIN; INHIBITORS; TRANSFORMATION; COMPONENTS; INVITRO AB Anthrax lethal toxin, produced by the bacterium Bacillus anthracis, is the major cause of death in animals infected with anthrax. One component of this toxin, lethal factor (LF), is suspected to be a metalloprotease, but no physiological substrates have been identified. Here it is shown that LF is a protease that cleaves the amino terminus of mitogen-activated protein kinase kinases 1 and 2 (MAPKK1 and MAPKK2) and that this cleavage inactivates MAPKK1 and inhibits the MAPK signal transduction pathway. The identification of a cleavage site for LF may facilitate the development of LF inhibitors. C1 NCI, Adv Biosci Lab, Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NIDR, NIH, Bethesda, MD 20892 USA. Univ Colorado, Dept Chem & Biochem, Howard Hughes Med Inst, Boulder, CO 80309 USA. Univ Cincinnati, Coll Med, Dept Cell Biol, Cincinnati, OH 45267 USA. NCI, Div Canc Res, NIH, Bethesda, MD 20892 USA. RP Vande Woude, GF (reprint author), NCI, Adv Biosci Lab, Basic Res Program, Frederick Canc Res & Dev Ctr, POB B, Frederick, MD 21702 USA. RI Webb, Craig/I-8123-2012; OI DUESBERY, NICK/0000-0002-4258-5655 NR 31 TC 762 Z9 784 U1 2 U2 24 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 MAY 1 PY 1998 VL 280 IS 5364 BP 734 EP 737 DI 10.1126/science.280.5364.734 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZL268 UT WOS:000073415600047 PM 9563949 ER PT J AU Dada, AJ Diamondstone, L Quinn, TC Blattner, WA Biggar, RJ AF Dada, AJ Diamondstone, L Quinn, TC Blattner, WA Biggar, RJ TI A serosurvey of Haemophilus ducreyi, syphilis, and herpes simplex virus type 2 and their association with human immunodeficiency virus among female sex workers in Lagos, Nigeria SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID SEXUALLY-TRANSMITTED DISEASES; INFECTION; HIV-2 AB Background and Objectives: To determine the prevalence rates of serological reactivity of Haemophilus (H.) ducreyi, Treponema pallidum, and herpes simplex virus type 2 (HSV-2) antibodies among female sex workers (FSWs) and their association with human immunodeficiency virus (HIV) antibody status. Study Design: Cross-sectional, standard serological assays were used for syphilis, HSV-2 and HIV; a modified enzyme-linked immunosorbent assay (ELISA) was used to detect specific anti-H. ducreyi immunoglobulin (Ig) G and IgA antibodies. Results: Seroprevalence rates were 86% for anti-H. ducreyi IgG and 69% for anti-H. ducreyi IgA; 4% for rapid plasma reagin (RPR) and Treponema palladium hemagglutination assay (TPHA) confirmed syphilis; 59% for HSV-2; 12% for HIV-1 and 2% for HIV-2. Lower-class FSWs were significantly more likely than upper-class FSWs to be H. ducreyi seropositive (IgG: OR = 42.7; IgA: OR = 7.6) and have current or past syphilis infection (RPR: OR = 3.5; RPR and TPHA: OR = 4.5). The presence of syphilis increased significantly with older age (P-trend < 0.001). Non-Nigerian FSWs had significantly higher reactivity to chancroid (IgG: OR = 3.5; IgA: OR = 1.8) and borderline reactivity to syphilis (RPR: OR = 1.6; TPHA: OR = 2.0). A history of sex with non-Nigerian Africans was significantly associated with chancroid reactivity and borderline significant with syphilis serostatus. H. ducreyi seropositivity was significantly more likely in FSWs with HSV-2 (OR = 2.4) and syphilis (OR = 5.6). Chancroid and HSV-2 antibodies were also more common in HIV-infected FSWs. C1 NCI, VEB, NIH, Viral Epidemiol Branch,Div Canc Etiol & Genet, Rockville, MD 20852 USA. Fed Minist Hlth, Cent Publ Hlth Lab, Lagos, Nigeria. Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD USA. Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. RP Dada, AJ (reprint author), NCI, VEB, NIH, Viral Epidemiol Branch,Div Canc Etiol & Genet, 6130 Execut Blvd, Rockville, MD 20852 USA. EM dadaa@epndce.nci.nih.gov FU NCI NIH HHS [N01-CP-95612, N01-CP-85603] NR 21 TC 44 Z9 44 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD MAY PY 1998 VL 25 IS 5 BP 237 EP 242 DI 10.1097/00007435-199805000-00004 PG 6 WC Infectious Diseases SC Infectious Diseases GA ZL094 UT WOS:000073398200004 PM 9587174 ER PT J AU Barbato, G Wehr, TA AF Barbato, G Wehr, TA TI Homeostatic regulation of REM sleep in humans during extended sleep SO SLEEP LA English DT Article DE NREM sleep; REM sleep; NREM-REM cycle, extended sleep ID EEG POWER-DENSITY; BODY-TEMPERATURE; CYCLE; INTERRUPTION; PATTERNS; NIGHT; DELTA; CONSERVATION; ALTERNATION; PROPENSITY AB Benington and Heller (1994) recently proposed a sleep-dependent model for the homeostatic control of REM sleep in which the amount of REM sleep propensity discharged in each bout of REM sleep affects the timing of the subsequent REM episode. Consistent with their hypothesis, they reported that in rats the duration of a REM episode was positively correlated with the duration of the succeeding NREM episode and not with the duration of the preceding NREM episode. To assess this hypothesis in humans, we used 308 sleep records from 11 subjects who remained at bedrest in the dark and slept ad libitum during 14-hour periods each night for 4 weeks. The timing of the onset of the first REM episode of the long night was linked to the timing of sleep onset. NREM-REM cycle duration decreased progressively throughout the night as a result of a progressive decrease in duration of the NREM component. Durations of REM sleep episodes correlated significantly with durations of subsequent NREM episodes in three out of the eight rank cycles analyzed (p<.0031, Bonferroni corrected); positive correlation coefficients were found for all the remaining cycles, but were not statistically significant when the conservative Bonferroni correction of the alpha level was applied. With the exception of the first sleep cycle, durations of REM sleep episodes did not correlate with durations of preceding NREM sleep episodes. According to the present results, the amount of REM sleep in one episode controls the time of occurrence of the next REM episode when the impact of other possible regulating factors are at a low level. We hypothesize that the extended dark/rest period, by increasing the time window allowed for sleep, provided a condition under which the systems governing REM sleep expression were free of the masking imposed by the conventional 16 hours light/8 hours dark schedule that consolidates and compresses sleep. C1 NIMH, Clin Psychobiol Branch, Bethesda, MD 20892 USA. RP Barbato, G (reprint author), Sez Psichiatria, Dipartimento Neurosci & Comunicaz Interumana, Via Pansini 5, I-80131 Naples, Italy. OI Barbato, Giuseppe/0000-0001-6523-5327 NR 55 TC 22 Z9 22 U1 1 U2 6 PU AMER SLEEP DISORDERS ASSOC PI ROCHESTER PA 1610 14TH STREET NW SUITE 300, ROCHESTER, MN 55806 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAY 1 PY 1998 VL 21 IS 3 BP 267 EP 276 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA ZT942 UT WOS:000074143800005 PM 9595605 ER PT J AU Wiener, LS AF Wiener, LS TI Telephone support groups for HIV-positive mothers whose children have died of AIDS SO SOCIAL WORK LA English DT Article ID DISABLED ADULTS C1 NCI, Pediat HIV Psychosocial Support Program, NIH, Bethesda, MD 20892 USA. RP Wiener, LS (reprint author), NCI, Pediat HIV Psychosocial Support Program, NIH, Bethesda, MD 20892 USA. NR 11 TC 5 Z9 5 U1 1 U2 1 PU NATL ASSOC SOCIAL WORKERS PI WASHINGTON PA 750 FIRST ST, NE, STE 700, WASHINGTON, DC 20002-4241 USA SN 0037-8046 J9 SOC WORK JI Soc. Work PD MAY PY 1998 VL 43 IS 3 BP 279 EP 285 PG 7 WC Social Work SC Social Work GA ZM150 UT WOS:000073509700009 PM 9597947 ER PT J AU Migliaccio, S Bernardini, S Wetsel, WC Korach, KS Faraggiana, T Teti, A AF Migliaccio, S Bernardini, S Wetsel, WC Korach, KS Faraggiana, T Teti, A TI Protein kinase C modulates estrogen receptors in differentiated osteoblastic cells in vitro SO STEROIDS LA English DT Article; Proceedings Paper CT XVIII Meeting of the International-Study-Group-for-Steroid-Hormones CY NOV 29-DEC 02, 1997 CL ROME, ITALY SP Int Study Grp Steroid Hormones ID RESPONSIVENESS; ACTIVATION AB Several reports have shown an interaction between the estrogen receptor (ER) and the protein kinase C (PKC) intracellular pathways. Data from our laboratory showed that PKC activation can modulate ER levels and responsiveness in estrogen target tissues such as uterus and bone. In particular, ROS.SMER #14 osteoblastic cells, stably transfected with the mouse ER, undergo specific morphological changes in vitro. ROS.SMER #14 cells at postconfluence express a differentiated phenotype and become unresponsive to estrogenic stimulation. Interestingly, ER mRNA and protein levels were not modified by post-confluence, but ER building sites/cell (2500-3000/cell at subconfluence) were undetectable. Moreover PKC activity was significantly increased in post-confluent cells. Inhibition of PKC by H7 or staurosporin in (PKC inhibitors) or down-regulation by long-term treatment with 12-O-tetradecanoylphorbol-13-acetate enchanced ER binding capacity in a dose-dependent manner. Since the PKC family includes several different isoforms that play different roles in cell homeostasis, we evaluated,whether specific isoenzymes were involved in this event. To address this question, Western blotting analysis was performed on both sub-and post-confluent ROS.SMER #14 cells using antibodies against different PKC isoforms. in conclusion, our preliminary data indicate that estrogen responsiveness of osteoblastic cells can be highly regulated by PKC. Finally, these data suggest that this intracellular interaction might play an important role in modulating hormonal and pharmacological responsiveness of bone tissue. (C) 1998 by Elsevier Science Inc. C1 Univ Rome La Sapienza, Histol & Med Embryol Dept, I-00161 Rome, Italy. Univ Rome La Sapienza, Dept Expt Med, I-00161 Rome, Italy. Univ Aquila, Dept Expt Med, I-67100 Laquila, Italy. Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, Receptor Biol Sect, Res Triangle Pk, NC USA. Duke Univ, Dept Psychiat, Durham, NC 27706 USA. RP Migliaccio, S (reprint author), Univ Rome La Sapienza, Histol & Med Embryol Dept, Via Antonio Scarpa 14, I-00161 Rome, Italy. OI Migliaccio, Silvia/0000-0002-4563-6630; Korach, Kenneth/0000-0002-7765-418X; Teti, Anna Maria/0000-0002-5887-4419 NR 9 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0039-128X J9 STEROIDS JI Steroids PD MAY-JUN PY 1998 VL 63 IS 5-6 BP 352 EP 354 DI 10.1016/S0039-128X(98)00040-3 PG 3 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA ZQ452 UT WOS:000073863500026 PM 9618801 ER PT J AU Kronmal, RA Hart, RG Manolio, TA Talbert, RL Beauchamp, NJ Newman, A AF Kronmal, RA Hart, RG Manolio, TA Talbert, RL Beauchamp, NJ Newman, A CA CHS Collaborat Res Grp TI Aspirin use and incident stroke in the Cardiovascular Health Study SO STROKE LA English DT Article DE aspirin; cerebral infarction; cerebral hemorrhage; elderly; risk factors; stroke ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; NITRIC-OXIDE SYNTHASE; HEMORRHAGE; RABBITS AB Background and Purpose-Randomized clinical trials testing aspirin in relatively low-risk, middle-aged people have consistently shown small increases in stroke associated with aspirin use. We analyzed the relationship between the regular use of aspirin and incident ischemic and hemorrhagic stroke among people aged 65 years or older participating in the Cardiovascular Health Study. Methods-We conducted a multivariate analysis of incident stroke rates in a prospectively assessed, observational cohort of 5011 elderly people followed for a mean of 4.2 years. Results-Participants had a mean age of 72 years, and 58% were women. Twenty-three percent used aspirin frequently, and 17% used aspirin infrequently at study entry. Frequent aspirin use was associated with an increased rate of ischemic stroke compared with nonusers (relative risk=1.6; 95% confidence interval [CI], 1.2 to 2.2; P=0.001). After adjustment for other stroke risk factors, women who used aspirin frequently or infrequently at study entry had a 1.8-fold (95% CI, 1.2 to 2.8) and 1.6-fold (95% CI, 0.9 to 3.0) increased risk of ischemic stroke, respectively (P<0.01, test for trend), compared with nonusers. In men, aspirin use was not statistically significantly associated with stroke risk. Findings were similar when aspirin use in the years before the incident stroke was used in the modeling. Aspirin use at entry was also associated with a 4-fold (95% CI, 1.6 to 10.0) increase in risk of hemorrhagic stroke for both infrequent and frequent users of aspirin (P=0.003). Conclusions-Aspirin use was associated with increased risks of ischemic stroke in women and hemorrhagic stroke overall in this elderly cohort, after adjustment for other stroke predictors. The possibility exists of-confounding by reasons for aspirin use rather than cause and effect. Whether regular aspirin use increases stroke risk for elderly people without cardiovascular disease can only be determined by randomized clinical trials. C1 Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Texas, Dept Med, Div Neurol, San Antonio, TX 78285 USA. Univ Texas, Dept Clin Pharmacol, San Antonio, TX 78285 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Johns Hopkins Univ, Neuroradiol Div, Baltimore, MD USA. Univ Pittsburgh, Dept Geriatr Med, Pittsburgh, PA USA. RP Kronmal, RA (reprint author), Cardiovasc Hlth Study, 1501 4th Ave,Suite 2105, Seattle, WA 98101 USA. EM kronmal@biostat.washington.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NHLBI NIH HHS [N01-HC-85079, N01-HC-85080, N01-HC-85081] NR 25 TC 44 Z9 45 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 1998 VL 29 IS 5 BP 887 EP 894 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA ZN073 UT WOS:000073606000002 PM 9596230 ER PT J AU Howard, G Wagenknecht, LE Cai, JW Cooper, L Kraut, MA Toole, JF AF Howard, G Wagenknecht, LE Cai, JW Cooper, L Kraut, MA Toole, JF TI Cigarette smoking and other risk factors for silent cerebral infarction in the general population SO STROKE LA English DT Article DE cerebral ischemia; cigarette smoking; diabetes mellitus; hypertension; magnetic resonance imaging; risk factors ID TRANSIENT ISCHEMIC ATTACK; CARDIOVASCULAR HEALTH; COMPUTED-TOMOGRAPHY; STROKE; ATHEROSCLEROSIS; LESIONS AB Background and Purpose-Silent cerebral infarctions (SCIs) have a prevalence between 10% and 40% in the transient ischemic attack population and have been associated with increased mortality and morbidity; however, little is known about the prevalence and risk factors for SCI in the general population. This report focuses on the role of cigarette smoking and other risk factors for SCI in the general population, Methods-MRI scans were performed on 1737 participants selected from the general population as part of the Atherosclerosis Risk in Communities Study. Smoking status and other major cerebrovascular risk factors were assessed, and associations between smoking status and SCIs were established with the use of ANCOVA. Results-Overall, the prevalence of SCI in this population aged 55 to 70 years was 11%. Cigarette smoking had an ordered association (P=0.029) with the presence of SCI, with the odds ratio (OR) of nonsmoking participants exposed to environmental tobacco smoke being 1.06 (95% confidence interval [CI], 0.64 to 1.75) times as great as for nonsmokers not exposed; the OR of past smokers was 1.16 (95% CI, 0.74 to 1.83) times greater, and the OR of current smokers was 1.88 (95% CI, 1.13 to 3.13) times greater. An increased prevalence was also noted among black, older, and hypertensive participants. Conclusions-This report is among the first to examine the risk factors for SCI in the general population and finds a relatively high overall prevalence (11%). There is an ordered relationship between increasing exposure to cigarette smoke and the presence of SCI that parallels the relationship between smoking and carotid atherosclerosis. The magnitude of the association with smoking is substantial compared with the effect of hypertension and other traditional cerebrovascular risk factors. The reduction in prevalence of SCI between current and past smokers and the trend that increased pack-years of smoking is related to increased prevalence of SCI are both additional arguments for smoking avoidance and cessation. C1 Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27157 USA. Wake Forest Univ, Sch Med, Dept Neurol, Winston Salem, NC 27157 USA. Wake Forest Univ, Sch Med, Ctr Stroke Res, Winston Salem, NC 27157 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. NHLBI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Radiol & Radiol Sci, Baltimore, MD 21205 USA. RP Howard, G (reprint author), Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27157 USA. EM ghoward@rc.phs.wfubmc.edu FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55018, N01-HC-55016] NR 30 TC 144 Z9 150 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 1998 VL 29 IS 5 BP 913 EP 917 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA ZN073 UT WOS:000073606000006 PM 9596234 ER PT J AU Koch, CA Moore, JL Krahling, KH Palm, DG AF Koch, CA Moore, JL Krahling, KH Palm, DG TI Fenestration of porencephalic cysts to the lateral ventricle: Experience with a new technique for treatment of seizures SO SURGICAL NEUROLOGY LA English DT Article DE porencephalic cyst; seizures; fenestration; West syndrome; Lennox-Gastaut Syndrome; uncapping; brain malformation ID INFANTILE SPASMS; ARACHNOID CYSTS; WEST SYNDROME; BRAIN; EPILEPSY; CHILDREN; SURGERY AB BACKGROUND Porencephalic cysts are brain cavities resulting from perinatal vascular occlusion and are commonly associated with severe neurological deficits and medically intractable epilepsy, Thirty-seven children presenting to the University of Munster with intractable seizures because of a porencephalic cyst were treated by uncapping and fenestration of these cysts to the lateral ventricle between 1978 and 1992. We conducted the following study to determine the efficacy and safety of the uncapping and fenestration procedure for the treatment of seizures. METHODS We reviewed all cases retrospectively and assessed the outcome of these patients with regard to seizures, paresis, and perioperative complications. RESULTS Of 37 children, 23 (62%) were seizure-free postoperatively. Nine patients (24%) had a reduction of seizures and five children (14%) remained unchanged. Of 30 patients with preoperative hemiparesis, 11 (30%) improved after the operation. The leading postoperative problem was a subcutaneous/subgaleal cushion of CSF, which affected 12 children (12 of 37). A dural patch covering the iatrogenic dural defect could not prevent or reduce postoperative CSF leakage, but prolonged the postoperative fever period. Postoperative fever occurred in 36 children (36 of 37) and was caused by an aseptic meningitis. CONCLUSIONS Children with intractable seizures and porencephalic cysts benefit from uncapping and cyst fenestration to the lateral ventricle. Concomitant perioperative complications are mild and are easily treated. (C) 1998 by Elsevier Science Inc. C1 Ohio State Univ, Med Ctr, Dept Med, Columbus, OH 43210 USA. Ohio State Univ, Med Ctr, Dept Neurol, Columbus, OH 43210 USA. Univ Munster, Med Ctr, Dept Neurosurg, D-4400 Munster, Germany. Univ Munster, Med Ctr, Dept Neuropediat, D-4400 Munster, Germany. RP Koch, CA (reprint author), NICHHD, NIH, Bldg 10,Room 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 58 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PD MAY PY 1998 VL 49 IS 5 BP 524 EP 532 DI 10.1016/S0090-3019(97)00288-7 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA ZM171 UT WOS:000073511800021 PM 9586931 ER PT J AU Shields, MJ Ribaudo, RK AF Shields, MJ Ribaudo, RK TI Mapping of the monoclonal antibody W6/32: sensitivity to the amino terminus of beta(2)-microglobulin SO TISSUE ANTIGENS LA English DT Article DE beta(2)-microglobulin; HLA; mAb; MHC ID CLASS-I MOLECULES; BOVINE BETA-2-MICROGLOBULIN; 3-DIMENSIONAL STRUCTURE; ANTIGENIC PEPTIDES; HEAVY-CHAINS; HLA; DETERMINANTS; IDENTIFICATION; ASSOCIATION; EXPRESSION AB The monoclonal antibody W6/32 is one of the most commonly used pan-HLA-ABC antibodies in studying human MHC I structure and function. We have discovered that the reactivity of W6/32 is absolutely sensitive to the amino terminus of human beta(2)-microglobulin (h beta(2)m). Bacterially expressed recombinant forms of h beta(2)m that have been extensively used in structural and biochemical studies of MHC I molecules often have an additional methionine at their amino terminus. Cell surface MHC I molecules reconstituted with allele-specific peptides and recombinant h beta(2)m are reactive with Various HLA-specific mAbs, but not W6/32. In contrast, cell surface HLA molecules reconstituted with peptide and native h beta(2)m, which has no amino terminal methionine, are recognized by W6/32 as well as other HLA-specific mAbs. Thus, the specificity of W6/32 includes the amino terminus of h beta(2)m. C1 NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. RP Ribaudo, RK (reprint author), NCI, Lab Immune Cell Biol, NIH, Bldg 10,Room 1B43, Bethesda, MD 20892 USA. NR 26 TC 19 Z9 20 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD MAY PY 1998 VL 51 IS 5 BP 567 EP 570 DI 10.1111/j.1399-0039.1998.tb02994.x PG 4 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA ZV100 UT WOS:000074269100010 PM 9672158 ER PT J AU Trukhanova, LS Hong, HHL Sills, RC Bowser, AD Gaul, B Boorman, GA Turusov, VS Devereux, TR Dixon, D AF Trukhanova, LS Hong, HHL Sills, RC Bowser, AD Gaul, B Boorman, GA Turusov, VS Devereux, TR Dixon, D TI Predominant p53 G -> A transition mutation and enhanced cell proliferation in uterine sarcomas of CBA mice treated with 1,2-dimethylhydrazine SO TOXICOLOGIC PATHOLOGY LA English DT Article DE tumor suppressor gene; ras proto-oncogene; malignant fibrous histiocytoma; stromal sarcoma; undifferentiated sarcoma; estrogen receptor; desmin ID TUMOR-SUPPRESSOR GENE; ETHYL-N-NITROSOUREA; INDUCED LUNG-TUMORS; RAS MUTATIONS; PROTOONCOGENE ACTIVATION; ENDOMETRIAL CARCINOMA; ALKYLATING-AGENTS; ESCHERICHIA-COLI; B6C3F1 MICE; SKIN TUMORS AB Mouse uterine tumors were examined for genetic alterations in the ras proto-oncogene and p53 tumor suppressor gene and for other biologically relevant immunohistochemical markers that may increase our understanding of the events that occur in uterine cancer. Fourteen dimethylhydrazine (DMH)-induced uterine sarcomas, including 3 primary malignant fibrous histiocytomas (MFH), 7 transplanted MFH, 3 stromal sarcomas, and 1 undifferentiated sarcoma, were first screened by immunohistochemistry for p53 missense mutations, followed by single strand conformation polymorphism analysis and DNA sequencing for the identification of point mutations. There was 100% correlation between p53 protein immunopositivity and subsequent detection of p53 mutations in DMH-induced malignant fibrous histiocytomas. All MFH had a characteristic p53 G:C-->A:T transition mutation, consistent with O-6-methylguanine mispairing with thymine, the most common DNA lesion caused by alkylating agents. DMH-induced uterine MFH with p53 mutations also had a higher proliferative rate (qualitatively evaluated by immunohistochemical detection of proliferating cell nuclear antigen) when compared with other DMH-induced sarcomas. Uterine sarcomas were further evaluated for biological end points, such as estrogen receptor and desmin. Neoplastic cells from stromal sarcomas (SS), undifferentiated sarcomas (US), and MFH did not stain for desmin. The estrogen receptor was detected in normal uteri and a small portion of MFH, SS, and US. Our data suggest that DMH-induced uterine sarcomas are not consistent with smooth muscle cell origin and that a subset of these tumors, specifically DMH-induced malignant fibrous histiocytomas, have unique p53 G:C-->A:T transitions and a high proliferative rate. C1 Russian Acad Med Sci, Canc Res Ctr, Moscow, Russia. RP Sills, RC (reprint author), NIEHS, Environm Toxicol Program, POB 12233,MD B3-08, Res Triangle Pk, NC 27709 USA. NR 42 TC 18 Z9 18 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAY-JUN PY 1998 VL 26 IS 3 BP 367 EP 374 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA ZN733 UT WOS:000073676500010 PM 9608642 ER PT J AU Abdo, KM Wenk, ML Harry, GJ Mahler, J Goehl, TJ Irwin, RD AF Abdo, KM Wenk, ML Harry, GJ Mahler, J Goehl, TJ Irwin, RD TI Glycine modulates the toxicity of benzyl acetate in F344 rats SO TOXICOLOGIC PATHOLOGY LA English DT Article DE benzyl acetate; glycine; rats; brain; neurodegeneration ID ZERO DOSE CONTROL; BENZYL ACETATE; AVAILABILITY; DISPOSITION; METABOLISM; MICE AB The influence of supplemental glycine on benzyl acetate (BA; a compound metabolized via the hippurate pathway)-induced toxicity was investigated. Groups of male F344 rats were fed NIH-07 diet containing 0, 20,000, 35,000, or 50,000 ppm BA for up to 28 days. Two additional groups were fed NIH-07 diet with 50,000 ppm BA and 27,000 ppm glycine or 50,000 ppm BA and 32,000 ppm L-alanine; supplemental glycine and L-alanine were equimolar. The L-alanine group served as an amino nitrogen control. A third group was fed NIH-07 diet with 32,000 ppm L-alanine and served as an untreated isonitrogenous control. BA caused increase in mortality, body weight loss, the incidence of abnormal neurobehavioral signs such as ataxia and convulsions, along with astrocyte hypertrophy and neuronal necrosis in the cerebellum, hippocampus, and pyriform cortex of the brain. These effects were reduced significantly by supplementation with glycine but not with L-alanine. These results suggest that the neurodegeneration induced by BA is mediated by a depletion of the glycine pool and the subsequent excitotoxicity. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Abdo, KM (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 23 TC 7 Z9 7 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAY-JUN PY 1998 VL 26 IS 3 BP 395 EP 402 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA ZN733 UT WOS:000073676500014 PM 9608646 ER PT J AU Haseman, JK Hailey, JR Morris, RW AF Haseman, JK Hailey, JR Morris, RW TI Spontaneous neoplasm incidences in Fischer 344 rats and B6C3F(1) mice in two-year carcinogenicity studies: A National Toxicology Program update SO TOXICOLOGIC PATHOLOGY LA English DT Article DE tumor incidence; historical control data; F344 rats; B6C3F(1) mice; National Toxicology Program ID CHRONIC ACTIVE HEPATITIS; HISTORICAL CONTROL DATA; BODY-WEIGHT; F344/N RATS; CORN-OIL; NONNEOPLASTIC LESIONS; DIETARY RESTRICTION; SPONTANEOUS TUMORS; SURVIVAL; VARIABILITY AB Spontaneous neoplasm rates were determined for control Fischer 344 (F344) rats and B6C3F(1) mice from 2-yr rodent carcinogenicity studies carried out by the National Toxicology Program (NTP). The most frequently occurring neoplasms in untreated male F344 rats were testicular adenoma (89.1%), mononuclear cell leukemia (50.5%), adrenal gland pheochromocytoma (31.9%), and pituitary gland neoplasms (30.4%). For untreated female F344 rats, the most frequently occurring neoplasms were pituitary gland neoplasms (54.2%); mammary gland fibroadenoma (41.2%), and mononuclear cell leukemia (28.1%). The: most frequently occurring neoplasms in untreated male B6C3F, mice were liver adenoma/carcinoma (42.2%), lung adenoma/carcinoma (20.5%), and malignant lymphoma (8.3%). For untreated female B6C3F, mice, the most frequently occurring neoplasms were liver adenoma/carcinoma (23.6%), malignant lymphoma (20.9%), and pituitary gland adenoma/carcinoma (14.8%). The tumor rates observed in feeding study (untreated) and inhalation study (chamber) control rats were generally similar. The major exceptions were pituitary gland tumors and testicular adenoma in male F344 rats. The overall incidence of testicular adenoma was much lower in chamber controls (69.4%) than in feeding study controls (89.1%), whereas pituitary gland neoplasms showed the opposite trend (60.7% vs 30.4%). The most likely explanation for this difference is related to the individual housing of chamber controls and the group housing of feeding study controls. Differences in diagnostic criteria may influence reported tumor rates. To ensure consistency and comparability of tumor diagnosis from study to study, the NTP uses rigorous histopathology quality assurance and peer review procedures. Biological factors such as body weight may also affect tumor incidence. For example, increased body weights are associated with increased incidences of certain site-specific neoplasms, especially pituitary gland and mammary gland neoplasms in rats and liver tumors in mice. The presence of Helicobacter hepaticus has been associated with an increased incidence of liver neoplasms in male B6C3F, mice. Other factors that may produce differences in control tumor rates from study to study include diet, environmental factors, genetic drift, study duration, and survival differences. The NTP database provides historical control data that may be useful in the evaluation of possible chemically related changes in tumor incidence. However, it is essential that the study being evaluated be comparable to those in the NTP database with respect to those factors that are known to influence tumor occurrence. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Haseman, JK (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. NR 46 TC 173 Z9 178 U1 1 U2 8 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAY-JUN PY 1998 VL 26 IS 3 BP 428 EP 441 PG 14 WC Pathology; Toxicology SC Pathology; Toxicology GA ZN733 UT WOS:000073676500018 PM 9608650 ER PT J AU Thomas, RS Gustafson, DL Ramsdell, HS El-Masri, HA Benjamin, SA Yang, RSH AF Thomas, RS Gustafson, DL Ramsdell, HS El-Masri, HA Benjamin, SA Yang, RSH TI Enhanced regional expression of glutathione S-transferase P1-1 with colocalized AP-1 and CYP 1A2 induction in chlorobenzene-induced porphyria SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID RAT-LIVER; P GENE; BENZYL ISOTHIOCYANATE; RESPONSIVE ELEMENT; HEPATIC PORPHYRIA; LEUCINE ZIPPER; CUTANEA-TARDA; HEXACHLOROBENZENE; FOS; JUN AB A distinct, nonfocal expression pattern was observed for glutathione S-transferase PP-P (rGSTP1-1) in rats exposed to either hexachloro- (HCB) or pentachlorobenzene (PeCB). The nonfocal expression was localized to the centrilobular region with the most intense staining nearest the central vein. A Western blot analysis revealed a 5- and 15-fold induction of rGSTP1-1 with PeCB and HCB treatment on an equal molar basis, respectively. Evaluation of porphyrin fluorescence also revealed a centrilobular accumulation with average porphyrin measurements of 0.319, 0.590, and 0.206 mu g/g tissue for PeCB, HCB, and corn-oil controls, respectively. Due to the role of Activator Protein-1 (AP-1) in rGSTP1-1 expression and CYP 1A2 in the pathogenesis of porphyria cutanea tarda, immunohistochemical localization of c-jun, c-fos, and CYP 1A2 was also performed. increased expression and colocalization within the liver lobule was observed for c-jun, c-fos, CYP 1A2, rGSTP1-1, and areas of porphyrin accumulation. These observations are consistent with studies that have associated the induction of GST-P with jun-and fos-related gene products. (C) 1998 Academic Press. C1 Colorado State Univ, Ctr Environm Toxicol & Technol, Dept Environm Hlth, Ft Collins, CO 80523 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Colorado State Univ, Dept Pathol, Ft Collins, CO 80523 USA. RP Thomas, RS (reprint author), Colorado State Univ, Ctr Environm Toxicol & Technol, Dept Environm Hlth, Ft Collins, CO 80523 USA. OI Thomas, Russell/0000-0002-2340-0301 FU NIEHS NIH HHS [P42 ES05949] NR 49 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAY PY 1998 VL 150 IS 1 BP 22 EP 31 DI 10.1006/taap.1998.8385 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA ZT328 UT WOS:000074073800003 PM 9630449 ER PT J AU Hall, PD Kreitman, RJ Willingham, MC Frankel, AE AF Hall, PD Kreitman, RJ Willingham, MC Frankel, AE TI Toxicology and pharmacokinetics of DT388-GM-CSF, a fusion consisting of a truncated diphtheria toxin (DT388) linked to human granulocyte-macrophage colony-stimulating factor (GM-CSF) in C57BL/6 mice SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; RECEPTOR; CELLS; BINDING; CHEMOTHERAPY; EXPRESSION; FRAGMENT; PROTEIN; CLONING AB Because the majority of acute myeloid leukemia (AML) blasts express the granulocyte-macrophage colony-stimulating factor (GMCSF) receptor, we are developing a fusion toxin consisting of a truncated diphtheria toxin (DT388) linked to human GM-CSF for multi-drug resistant AML, Our goal was to determine the toxicity and pharmacokinetics of DT388-GM-CSF in C57BL/6 mice, Because human GM-CSF does not cross-react with the mouse GM-GSF receptor, the toxicity observed should be nonspecific toxicity of DT388, We injected C57BL/6 mice ip with 0.1, 0.5, 1.0, 1.5, 175, 2.0, 3.5, 5.0, or 10 mu g/day of DT388-GM-CSF for 5 consecutive days. For pharmacokinetics, blood samples were drawn at 20, 40, 60, 120, and 180 min after ip administration of 81 mu g/kg of DT388-GM-CSF. In mice, the LD10 of DT388-GM-CSF is between 84.4 (1.5) and 104.4 (1.75) mu g/kg (mu g) when administered for 5 consecutive days. AU mice receiving greater than or equal to 201 mu g/kg (3.5 mu g) for 5 consecutive days died, Histopathologic examination of morbid animals showed only renal toxicity with acute proximal tubular necrosis, DT388-GM-CSF is stable in vivo based on nonreducing SDS-PAGE gel of plasma samples of I-125-labeled DT388-GM-CSF injected ip, The peak concentration of DT388-GM-CSF was 3.3 x 10(-8) M at 40 min and exhibited a t 1/2 of 24 min. Based on its half-life, DT388-GM-CSF concentrations in :he plasma are above the concentration inhibiting 50% protein synthesis and inducing apoptosis in 50% of HL-60 cells (AML cell line) for 5.2 h. Only four of 17 mice developed a weak immune response (0.9-160 ng/mL) 3 weeks after treatment. DT388-GM-CSF exhibits a short t 1/2, but concentrations exceed those required in vitro to inhibit AML cell lines. (C) 1998 Academic Press. C1 Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. Med Univ S Carolina, Coll Pharm, Charleston, SC 29425 USA. Bowman Gray Sch Med, Dept Pathol, Charleston, SC 29425 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD USA. RP Frankel, AE (reprint author), Med Univ S Carolina, Hollings Canc Ctr, Room 311,86 Jonathan Lucas St, Charleston, SC 29425 USA. EM frankela@musc.edu NR 31 TC 12 Z9 13 U1 0 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 MAY PY 1998 VL 150 IS 1 BP 91 EP 97 DI 10.1006/taap.1998.8389 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA ZT328 UT WOS:000074073800011 PM 9630457 ER PT J AU Alter, HJ AF Alter, HJ TI Science, lawyers, and "the Europeans": Testing requirements in transfusion medicine - Reply SO TRANSFUSION LA English DT Letter C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. RP Alter, HJ (reprint author), NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 1998 VL 38 IS 5 BP 507 EP 507 PG 1 WC Hematology SC Hematology GA ZU086 UT WOS:000074159800015 ER PT J AU McCullough, J Herr, G Lennon, S Stroncek, D Clay, M AF McCullough, J Herr, G Lennon, S Stroncek, D Clay, M TI Factors influencing the availability of umbilical cord blood for banking and transplantation SO TRANSFUSION LA English DT Letter ID BONE-MARROW RECONSTITUTION; PLACENTAL BLOOD C1 Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. Orphan Med, Clin Serv, Minnetonka, MN USA. NIH, Lab Serv, Bethesda, MD 20892 USA. Univ Minnesota, Dept Lab Med & Pathol, St Paul, MN 55108 USA. Amer Red Cross, Dept Res & Dev, St Paul, MN USA. RP McCullough, J (reprint author), Univ Minnesota, Dept Lab Med & Pathol, Box 198,420 Delaware St SE, Minneapolis, MN 55455 USA. NR 5 TC 20 Z9 20 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 1998 VL 38 IS 5 BP 508 EP 510 DI 10.1046/j.1537-2995.1998.38598297222.x PG 3 WC Hematology SC Hematology GA ZU086 UT WOS:000074159800016 PM 9633566 ER PT J AU Conry-Cantilena, C Melpolder, JC Alter, HJ Gorlin, JB Mascotti, K AF Conry-Cantilena, C Melpolder, JC Alter, HJ Gorlin, JB Mascotti, K TI Intranasal drug use among volunteer whole-blood donors: results of survey C SO TRANSFUSION LA English DT Letter C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. RP Conry-Cantilena, C (reprint author), NIH, Dept Transfus Med, 10 Ctr Dr,MSC-1184,Bldg 10,Room 1C711, Bethesda, MD 20892 USA. NR 2 TC 5 Z9 5 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 1998 VL 38 IS 5 BP 512 EP 513 DI 10.1046/j.1537-2995.1998.38598297225.x PG 2 WC Hematology SC Hematology GA ZU086 UT WOS:000074159800020 PM 9633569 ER PT J AU Wang, JM Shen, WP Su, SB AF Wang, JM Shen, WP Su, SB TI Chemokines and their role in cardiovascular diseases SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; SMOOTH-MUSCLE CELLS; LOW-DENSITY-LIPOPROTEIN; ENDOTHELIAL-CELLS; CHEMOTACTIC PROTEIN-1; INTERLEUKIN-8; EXPRESSION; CYTOKINE; INDUCTION; MIGRATION AB Leukocyte infiltration into inflammatory or injured tissues requires a variety of cell-associated and soluble factors that mediate the communications between circulating leukocytes and vascular cells. During the past decade, a superfamily of polypeptide leukocyte chemoattractants known as chemokines has been identified and demonstrated to selectively induce rapid endothelial cell adhesion and transmigration of leukocyte subpopulations. Chemokines are produced by virtually every mammalian somatic cell type in response to inflammatory and immunologic stimuli and have been detected in tissues of numerous disease states characterized by infiltration of distinct leukocyte subsets. Chemokines bind and activate cell surface receptors that belong to the seven transmembrane, G protein-coupled receptor superfamily. Several chemokine receptors have been identified as fusion cofactors for human immunodeficiency virus type 1 (HIV-1). Chemokines have also been shown to play a critical role in atherosclerosis and ischemic reperfusion injury. As chemokine research is a rapidly expanding area, it is the purpose of this brief review to summarize recent progress in the field and to focus on the involvement of chemokines in cardiovascular diseases. Published 1998, Elsevier Science Inc. C1 NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Div Basic Sci, Frederick, MD 21702 USA. RP Wang, JM (reprint author), NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Div Basic Sci, Bldg 560,Room 31-19, Frederick, MD 21702 USA. NR 45 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD MAY PY 1998 VL 8 IS 4 BP 169 EP 174 DI 10.1016/S1050-1738(98)00006-1 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZN731 UT WOS:000073676300005 PM 21235929 ER PT J AU Shafer, WS AF Shafer, WS TI Careers-perspective interview SO TRENDS IN CELL BIOLOGY LA English DT Editorial Material C1 NIGMS, NIH, Bethesda, MD 20892 USA. RP Shafer, WS (reprint author), NIGMS, NIH, 2AN-32C Natcher Bldg, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD MAY PY 1998 VL 8 IS 5 BP 213 EP 213 PG 1 WC Cell Biology SC Cell Biology GA ZK971 UT WOS:000073386000013 ER PT J AU Kubbutat, MHG Vousden, KH AF Kubbutat, MHG Vousden, KH TI New HPV E6 binding proteins: Dangerous liaisons? SO TRENDS IN MICROBIOLOGY LA English DT Review ID P53 C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Basic Res Program, Frederick, MD 21702 USA. RP Kubbutat, MHG (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Basic Res Program, POB B, Frederick, MD 21702 USA. NR 12 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD MAY PY 1998 VL 6 IS 5 BP 173 EP 175 DI 10.1016/S0966-842X(98)01267-0 PG 3 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA ZN420 UT WOS:000073644100003 PM 9614337 ER PT J AU Jacobson, KA AF Jacobson, KA TI Adenosine A(3) receptors: novel ligands and paradoxical effects SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID MAST-CELL; TISSUE DISTRIBUTION; MOLECULAR-CLONING; IN-VIVO; RAT; ACTIVATION; DERIVATIVES; EXPRESSION; SUBTYPE AB The physiological role of the adenosine A(3) receptor is being investigated using newly synthesized, selective ligands. Recently, in addition to agonists, selective antagonists have been developed that belong to three distinct, non-purine chemical classes: flavonoids, 1,4-dihydropyridine derivatives (e.g. MRS1191, which is 1300-fold selective for human adenosine A(3) vs A(1)/A(2A) receptors, with a K-i value of 31 nM) and the triazoloquinazolines (e.g. MRS1220, which has a K-i value of 0.65 nM). The A(3) receptor has proven enigmatic in terms of antagonist tig and specificity, coupling to second messengers, and biological effects in the CNS, inflammatory system and cardiovascular system. A(3) receptors are also potentially involved in apoptosis. It appears that intense, a cute activation of A(3) receptors acts as a lethal input to cells, while low concentrations of A(3) receptor agonists protect against a poptosis. Here, Kenneth Jacobson describes how A(3) receptor agonists might be useful in treating inflammatory conditions, possibly through their inhibition of tumour necrosis factor alpha (TNF-alpha) release, which has been shown in macrophages, A(3) receptor antagonists might be useful in treating asthma or acute brain ischaemia. Recently, the versatility of A(3) receptor agonists, administered either before or during ischaemia, in eliciting potent cardioprotection has been shown. C1 NIDDK, Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Jacobson, KA (reprint author), NIDDK, Recognit Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20] NR 49 TC 252 Z9 253 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD MAY PY 1998 VL 19 IS 5 BP 184 EP 191 DI 10.1016/S0165-6147(98)01203-6 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZT578 UT WOS:000074101900007 PM 9652191 ER PT J AU Keddy, KH Klugman, KP Robbins, JB AF Keddy, KH Klugman, KP Robbins, JB TI Efficacy of Vi polysaccharide vaccine against strains of Salmonella typhi: reply SO VACCINE LA English DT Letter ID CAPSULAR POLYSACCHARIDE; FEVER C1 S African Inst Med Res, ZA-2000 Johannesburg, South Africa. NIH, Bethesda, MD 20892 USA. RP Keddy, KH (reprint author), S African Inst Med Res, POB 1038, ZA-2000 Johannesburg, South Africa. NR 9 TC 3 Z9 3 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 MAY-JUN PY 1998 VL 16 IS 9-10 BP 871 EP 872 DI 10.1016/S0264-410X(98)80024-8 PG 2 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA ZV083 UT WOS:000074266800001 PM 9682329 ER PT J AU Haines, DC Gorelick, PL Battles, JK Pike, KM Anderson, RJ Fox, JG Taylor, NS Shen, Z Dewhirst, FE Anver, MR Ward, JM AF Haines, DC Gorelick, PL Battles, JK Pike, KM Anderson, RJ Fox, JG Taylor, NS Shen, Z Dewhirst, FE Anver, MR Ward, JM TI Inflammatory large bowel disease in immunodeficient rats naturally and experimentally infected with Helicobacter bilis SO VETERINARY PATHOLOGY LA English DT Article DE colitis; Helicobacter; nude rats; typhlitis ID CHRONIC ACTIVE HEPATITIS; SP-NOV; CAMPYLOBACTER-CINAEDI; BACTERIAL-INFECTION; MACACA-NEMESTRINA; GASTRIC-CARCINOMA; PYLORI GASTRITIS; HOMOSEXUAL MEN; ANIMAL-MODEL; SCID MICE AB Proliferative and ulcerative typhlitis, colitis, and proctitis were found incidentally in a breeding colony of male athymic nude (Cr:NIH-rnu) rats. Within the crypts of the large intestine, modified Steiner's silver stain revealed spiral organisms that were identified by culture, polymerase chain reaction, and sequencing to be Helicobacter bills. The large bowel disease was reproduced in H. bilis-free male athymic nude rats that were injected intraperitoneally with a culture of H. bilis from the affected colony. The organism was isolated from the feces and cecum of the experimentally infected rats. H. bilis should be considered a potential pathogen in immunocompromised rats. The infection in immunocompromised rats may serve as an animal model for inflammatory large bowel disease. C1 NCI, Vet & Tumor Pathol Sect, Anim Sci Branch, Off Lab Anim Resources,Div Basic Sci,FCRDC, Frederick, MD 21702 USA. NCI, Pathol Histotechnol Lab, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. NCI, Lab Anim Sci Program, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. NCI, Lab Cell & Mol Struct, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. MIT, Div Comparat Med, Cambridge, MA 02139 USA. Forsyth Dent Ctr, Dept Mol Genet, Boston, MA 02115 USA. RP Ward, JM (reprint author), NCI, Vet & Tumor Pathol Sect, Anim Sci Branch, Off Lab Anim Resources,Div Basic Sci,FCRDC, Fairview 201,POB B, Frederick, MD 21702 USA. EM ward@mail.ncifcrf.gov FU NCI NIH HHS [R01CA67529]; NCRR NIH HHS [RR07036] NR 46 TC 51 Z9 53 U1 0 U2 1 PU AMER COLL VET PATHOLOGIST PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD MAY PY 1998 VL 35 IS 3 BP 202 EP 208 PG 7 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA 167FJ UT WOS:000078621600005 PM 9598583 ER PT J AU Beason-Held, LL Purpura, KP Van Meter, JW Azari, NP Mangot, DJ Optican, LM Mentis, MJ Alexander, GE Grady, CL Horwitz, B Rapoport, SI Schapiro, MB AF Beason-Held, LL Purpura, KP Van Meter, JW Azari, NP Mangot, DJ Optican, LM Mentis, MJ Alexander, GE Grady, CL Horwitz, B Rapoport, SI Schapiro, MB TI PET reveals occipitotemporal pathway activation during elementary form perception in humans SO VISUAL NEUROSCIENCE LA English DT Article DE positron emission tomography; visual; striate; extrastriate; hippocampus; frontal lobe ID POSITRON EMISSION TOMOGRAPHY; HUMAN EXTRASTRIATE CORTEX; HUMAN VISUAL-CORTEX; RECOGNITION MEMORY; CORTICAL AREAS; STRIATE CORTEX; TEMPORAL-LOBE; BRAIN-REGIONS; ORGANIZATION; TEXTURES AB To define brain regions involved in feature extraction or elementary form perception, regional cerebral blood flow (rCBF) was measured using positron emission tomography (PET) in subjects viewing two classes of achromatic textures. Textures composed of local features (e.g, extended contours and rectangular blocks) produced activation or increased rCBF along the occipitotemporal pathway relative to textures with the same mean luminance, contrast, and spatial-frequency content but lacking organized form elements or local features. Significant activation was observed in striate, extrastriate, lingual, and fusiform cortices as well as the hippocampus and brain stem. On a scan-by-scan basis, increases in rCBF shifted from the occipitotemporal visual cortices to medial temporal (hippocampus) and frontal lobes with increased exposure to only those textures containing local features. These results suggest that local feature extraction occurs throughout the occipitotemporal (ventral) pathway during extended exposure to visually salient stimuli, and may indicate the presence of similar receptive-field mechanisms in both occipital and temporal visual areas of the human brain. C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. Cornell Univ Med Coll, Dept Neurol & Neurosci, New York, NY USA. NEI, Sect Neural Modeling, NIH, Bethesda, MD 20892 USA. RP Beason-Held, LL (reprint author), NIA, Neurosci Lab, NIH, Bldg 10,Rm 6C414,9000 Rockville Pike, Bethesda, MD 20892 USA. FU NINDS NIH HHS [NS-01677] NR 61 TC 40 Z9 40 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0952-5238 J9 VISUAL NEUROSCI JI Visual Neurosci. PD MAY-JUN PY 1998 VL 15 IS 3 BP 503 EP 510 PG 8 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA ZL180 UT WOS:000073406800011 PM 9685203 ER PT J AU Flessner, MF Dedrick, RL AF Flessner, MF Dedrick, RL TI Tissue-level transport mechanisms of intraperitoneally-administered monoclonal antibodies SO JOURNAL OF CONTROLLED RELEASE LA English DT Article; Proceedings Paper CT 8th International Symposium on Recent Advances in Drug Delivery Systems CY FEB 24-27, 1997 CL SALT LAKE CITY, UTAH SP Univ Utah, Ctr Controlled Chem Delivery, Alza Corp, Becton Dickinson & Co, Chugai Pharm Co Ltd, Emisphere Technol Inc, Labopharm Inc, MacroMed Inc, Meiji Milk Prod Co Ltd, Pacific Corp, Pharmacia Upjohn Inc, Sam Yang Corp, Shiseido, Theratech Inc, 3M Co, Baxter Healthcare Corp, Boston Sci, Cygnus Therapeut Syst, Focal Inc, Genentech Inc, Hisamitsu Pharm Co Inc, Hoffman La Roche Inc, Novartis, Pfizer Inc, Sankyo Co Ltd, Schering Plough Res Inst, Teikoku Seiyaku Co Ltd, DuPont Merck Pharm Co, VivoRx Inc DE diffusion; convection; immunoglobulin; antibody binding ID BINDING-SITE BARRIER; QUANTITATIVE AUTORADIOGRAPHY; INTERSTITIAL PRESSURE; TUMORS; RATS; MACROMOLECULES; ALBUMIN AB Monoclonal antibodies (MAbs), produced for specific tumor antigens, can be linked with radioisotopes or metabolic toxins and administered intraperitoneally (i.p.) to treat metastatic cancer located on the peritoneum. Despite their specific binding properties, these proteins distribute to the serosal surface of all tissues surrounding the cavity in the same manner as other serum proteins. Recent data have raised a problem of access of the solution containing the MAb to significant portions of the peritoneal surface. If the MAb does arrive at the surface of the tumor, it penetrates via diffusion and convection. The rapidity and depth of penetration of the MAb are very dependent on the binding characteristics of the MAb to the tumor cells. Current data indicate that tumors often have a large interstitial space relative to normal muscle, and this can accelerate both diffusion and convection. However, a highly permeable tumor vasculature in the absence of lymphatic drainage has also been shown to produce interstitial pressure gradients from the center toward the periphery of the tumor, setting up a potential outward flow which may be a significant barrier to the movement of MAbs into the nodule. While theoretical mechanisms of diffusion, convection, and binding are well established, there is still a great need for in vivo data. (C) 1998 Elsevier Science B.V. C1 Univ Rochester, Med Ctr, Dept Med, Rochester, NY 14642 USA. NIH, Biomed Engn & Instrumentat Program, Bethesda, MD 20892 USA. RP Flessner, MF (reprint author), Univ Rochester, Med Ctr, Dept Med, Box 675,601 Elmwood Ave, Rochester, NY 14642 USA. FU NIDDK NIH HHS [R29-DK48479-01] NR 24 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD APR 30 PY 1998 VL 53 IS 1-3 BP 69 EP 75 DI 10.1016/S0168-3659(97)00238-1 PG 7 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA ZM279 UT WOS:000073522600008 PM 9741914 ER PT J AU Cool, DR Loh, YP AF Cool, DR Loh, YP TI Carboxypeptidase E is a sorting receptor for prohormones: Binding and kinetic studies SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE proinsulin; proenkephalin; carboxypeptidase H; chromogranin A; prohormone sorting ID REGULATED SECRETORY PATHWAY; TRANS-GOLGI NETWORK; C-TERMINAL REGION; ATT-20 CELLS; MEMBRANE-PROTEINS; INTERMEDIATE LOBE; DISULFIDE BOND; CHROMOGRANIN-B; PC12 CELLS; PH AB The binding of pro-opiomelanocortin,(POMC), pro-insulin, pro-enkephalin and chromogranin A (CGA) to the regulated secretory pathway sorting receptor, carboxypeptidase E (CPE), in bovine pituitary secretory granule (SG) membranes was investigated. N-POMC1-26, which contains the POMC sorting signal, bound to CPE in the SG membranes with low affinity and the binding was ion independent. Pro-insulin bound CPE with similar kinetics. Pro-enkephalin, but not CGA bound to CPE with similar IC50 as pro-insulin and N-POMC1-26. Crosslinking studies showed that pro-insulin and pro-enkephalin bound specifically to SG membrane CPE, similar to N-POMC1-26 reported previously. CPE was extracted from the SG membranes with NaHCO3 or KSCN, but not Triton X-100/1 M NaCl. The results show that CPE is tightly associated with SG membranes and binds several prohormones, but not CGA, with similar kinetics, providing further evidence that membrane CPE has the characteristics to function as a common sorting receptor for targeting prohormones to the regulated secretory pathway. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 NICHHD, Cellular Neurobiol Sect, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Loh, YP (reprint author), NICHHD, Cellular Neurobiol Sect, Dev Neurobiol Lab, NIH, Bldg 49,Room 5A38, Bethesda, MD 20892 USA. NR 28 TC 45 Z9 45 U1 0 U2 1 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 APR 30 PY 1998 VL 139 IS 1-2 BP 7 EP 13 DI 10.1016/S0303-7207(98)00081-1 PG 7 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA ZZ412 UT WOS:000074726800002 PM 9705069 ER PT J AU Eberstadt, M Huang, BH Chen, ZH Meadows, RP Ng, SC Zheng, LX Lenardo, MJ Fesik, SW AF Eberstadt, M Huang, BH Chen, ZH Meadows, RP Ng, SC Zheng, LX Lenardo, MJ Fesik, SW TI NMR structure and mutagenesis of the FADD (Mort1) death-effector domain SO NATURE LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; CELL-DEATH; PROTEINS; PROTEASE; FAS; INTERACTS; C-13 AB When activated, membrane-bound receptors for Fas and tumour-necrosis factor initiate programmed cell death by recruiting the death domain of the adaptor protein FADD(1) (Mort1; ref, 2) to the membrane. FADD then activates caspase 8 (ref. 3) (also known as FLICE4 or MACH(5)) through an interaction between the death-effector domains of FADD and caspase 8. This ultimately leads to the apoptotic response. Death-effector domains and homologous protein modules known as caspase-recruitment domains(6) have been found in several proteins(1-14) and are important regulators of caspase (FLICE) activity and of apoptosis. Here we describe the solution structure of a soluble, biologically active mutant of the FADD death-effector domain. The structure consists of six antiparallel, amphipathic alpha-helices and resembles the overall fold of the death domains of Fas(15) and p75 (ref. 16). Despite this structural similarity, mutations that inhibit protein-protein interactions involving the Fas death domain have no effect when introduced into the FADD death-effector domain. Instead, a hydrophobic region of the FADD death-effector domain that is not present in the death domains is vital for binding to FLICE and for apoptotic activity. C1 Abbott Labs, Div Pharmaceut Discovery, Abbott Pk, IL 60064 USA. NIH, Immunol Lab, Bethesda, MD 20892 USA. RP Fesik, SW (reprint author), Abbott Labs, Div Pharmaceut Discovery, Abbott Pk, IL 60064 USA. NR 28 TC 180 Z9 183 U1 1 U2 10 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD APR 30 PY 1998 VL 392 IS 6679 BP 941 EP 945 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZK759 UT WOS:000073359900054 PM 9582077 ER PT J AU Gahl, WA Brantly, M Kaiser-Kupfer, MI Iwata, F Hazelwood, S Shotelersuk, V Duffy, LF Kuehl, EM Troendle, J Bernardini, I AF Gahl, WA Brantly, M Kaiser-Kupfer, MI Iwata, F Hazelwood, S Shotelersuk, V Duffy, LF Kuehl, EM Troendle, J Bernardini, I TI Genetic defects and clinical characteristics of patients with a form of oculocutaneous albinism (Hermansky-Pudlak syndrome) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PULMONARY FIBROSIS; GRANULOMATOUS COLITIS; POPULATION; CHILDREN; GROWTH; CT AB Background Hermansky-Pudlak syndrome is characterized by oculocutaneous albinism, a storage-pool deficiency, and lysosomal accumulation of ceroid lipofuscin, which causes pulmonary fibrosis and granulomatous colitis in some cases. All identified affected patients in northwest Puerto Rico are homozygous for a 16-bp duplication in exon 15 of a recently cloned gene, HPS. We compared the clinical and laboratory characteristics of these patients with those of patients without the 16-bp duplication. Methods Forty-nine patients - 27 Puerto Ricans and 22 patients from the mainland United States who were not of Puerto Rican descent - were given a diagnosis on the basis of albinism and the absence of platelet dense bodies. We used the polymerase chain reaction to determine which patients carried the 16-bp duplication. Results Twenty-five of the Puerto Rican patients were homozygous for the 16-bp duplication, whereas none of the non-Puerto Rican patients carried this mutation. Like the patients without the duplication, the patients with the 16-bp duplication had a broad variation in pigmentation. Nine of 16 adults with the duplication, but none of the 10 without it, had a diffusing capacity for carbon monoxide that was less than 80 percent of the predicted value. High-resolution computed tomography in 12 patients with the 16-bp duplication revealed minimal fibrosis in 8, moderate fibrosis in 1, severe fibrosis in 1, and no fibrosis in 2. Computed tomography in eight patients without the duplication revealed minimal fibrosis in three and no fibrosis in the rest. Inflammatory bowel disease developed in eight patients (four in each group) between 3 and 25 years of age. Conclusions The 16-bp duplication in exon 15 of HPS, which we found only in Puerto Rican patients, is associated with a broad range of pigmentation and an increased risk of restrictive lung disease in adults. (C)1998, Massachusetts Medical Society. C1 NICHHD, Heritable Disorders Branch, Bethesda, MD 20892 USA. NICHHD, Biometry & Math Stat Branch, Bethesda, MD 20892 USA. NHLBI, Pulm Crit Care Med Branch, Bethesda, MD 20892 USA. NEI, Ophthalm Genet & Clin Serv Branch, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. Gastroenterol Associates No Virginia, Fairfax, VA USA. RP Gahl, WA (reprint author), NICHD, Sect Human Biochem Genet, NIH, 10 Ctr Dr,MSC 1830,Bldg 10,Rm 9S-241, Bethesda, MD 20892 USA. NR 36 TC 156 Z9 159 U1 0 U2 5 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 30 PY 1998 VL 338 IS 18 BP 1258 EP 1264 DI 10.1056/NEJM199804303381803 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA ZK547 UT WOS:000073335800003 PM 9562579 ER PT J AU Yu, KF AF Yu, KF TI Confidence limits based on the first occurrence of an event by V. T. George and R. C. Elston, Statistics in Medicine, 12, 685-690 (1993) SO STATISTICS IN MEDICINE LA English DT Letter C1 NICHD, BMSB, DESPR, NIH, Bethesda, MD 20892 USA. RP Yu, KF (reprint author), NICHD, BMSB, DESPR, NIH, Bldg 6100,Room 7B13, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 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 APR 30 PY 1998 VL 17 IS 8 BP 945 EP 945 DI 10.1002/(SICI)1097-0258(19980430)17:8<945::AID-SIM835>3.0.CO;2-P PG 1 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 ZJ496 UT WOS:000073221800009 PM 9595620 ER PT J AU Kozma, C Blancato, J Meck, J Jiang, Y AF Kozma, C Blancato, J Meck, J Jiang, Y TI Characterization of a supernumerary marker derived from chromosome 17 by microdissection in an adult with MR/MCA SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE partial trisomy 17; marker chromosome; microdissection; centromere; proximal 17q trisomy; ring chromosome; 17q duplication ID UNIPARENTAL DISOMY; PRENATAL-DIAGNOSIS; FISH AB We describe a 38-year-old adult who has a supernumerary marker chromosome in 10% of metaphase cells which was identified by reverse in situ hybridization with a DNA probe made by microdissection to be derived from chromosome 17, The breakpoints are estimated by G-banding and fluorescence in situ hybridization (FISH) to consist of the region from 17p11.1 to proximal 17q21. The propositus displayed severe growth retardation, kyphoscoliosis, bilateral cataracts, severe calcaneovalgus deformity of the feet, dysmorphic facies, profound mental retardation, and multiple medical problems requiring ongoing medical management, These problems included a mitral valve prolapse with regurgitation, recurrent upper and lower respiratory tract infections, and severe respiratory insufficiency. The relatively long survival of this patient enabled us to describe the natural history of this rare chromosomal mutation. (C) 1998 Wiley-Liss, Inc. C1 Georgetown Univ, Med Ctr, Child Dev Ctr, Washington, DC 20007 USA. ONCOR, Gaithersburg, MD USA. Natl Ctr Human Genome Res, Bethesda, MD USA. RP Kozma, C (reprint author), Georgetown Univ, Med Ctr, Child Dev Ctr, 3307 M St,NW Suite 401, Washington, DC 20007 USA. NR 18 TC 9 Z9 9 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 APR 28 PY 1998 VL 77 IS 1 BP 19 EP 22 DI 10.1002/(SICI)1096-8628(19980428)77:1<19::AID-AJMG5>3.3.CO;2-W PG 4 WC Genetics & Heredity SC Genetics & Heredity GA ZF472 UT WOS:000072900900005 PM 9557888 ER PT J AU Tomarev, SI Tamm, ER Chang, B AF Tomarev, SI Tamm, ER Chang, B TI Characterization of the mouse Myoc/Tigr gene SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MURINE GENE; PROTEIN AB Mutations in the myocilin (MYOC), also known as Trabecular meshwork-Inducible Glucocorticoid Response (TIGR) gene can lead to juvenile open-angle glaucoma in human and may be responsible for at least 3% of primary open-angle glaucoma. To develop a mouse model of primary open angle glaucoma, and to get deeper insight into the mechanisms of the MYOC/TIGR gene regulation and function, we have isolated and characterized full size mouse Myoc/Tigr cDNA and genomic clones. The mouse and human MYOC/TIGR genes have the same exon-intron structure and contain 3 exons, although the mouse gene is 6 kb shorter than the human gene (10 kb versus 16 kb) due to differences in the length of introns. The MYOC/TIGR gene encodes a moderately conserved protein, which is 82% identical between human and mouse. The encoded protein is 14 amino acids shorter at the N-terminus in the mouse than in the human (490 versus 504 amino acids). Mouse and human MYOC/TIGR genes show a similar pattern of expression in adult ocular and nonocular tissues. The mouse Myoc/Tigr gene was mapped to Chromosome 1 at position 82.8 cM from the centromere. All residues, which were identified in the human MYOC/TIGR protein as critical for glaucoma development, are conserved in the mouse Myoc/Tigr. (C) 1998 Academic Press. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RP Tomarev, SI (reprint author), NEI, Mol & Dev Biol Lab, NIH, Bldg 6,Room 203, Bethesda, MD 20892 USA. FU NEI NIH HHS [EY05578, EY07757] NR 28 TC 52 Z9 55 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 APR 28 PY 1998 VL 245 IS 3 BP 887 EP 893 DI 10.1006/bbrc.1998.8541 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZL947 UT WOS:000073489500043 PM 9588210 ER PT J AU Wyatt, MK Overby, LH Lawton, MP Philpot, RM AF Wyatt, MK Overby, LH Lawton, MP Philpot, RM TI Identification of amino acid residues associated with modulation of flavin-containing monooxygenase (FMO) activity by imipramine: Structure/function studies with FMO1 from pig and rabbit SO BIOCHEMISTRY LA English DT Article ID CONTAINING MONO-OXYGENASE; TRYPANOTHIONE REDUCTASE; ESCHERICHIA-COLI; SUBSTRATE-SPECIFICITY; GLUTATHIONE-REDUCTASE; PRIMARY ALKYLAMINES; HALF-REACTION; LIVER; LUNG; EXPRESSION AB The activity of the flavin-containing monooxygenase (EMO) can be modulated by a number of nitrogen-containing compounds in a manner that is both isoform and modulator-dependent. We now show that the direction (activation or inhibition) and extent of modulation can also be dependent on substrate concentration. Imipramine activates methimazole metabolism catalyzed by rabbit FMO1 or FMO2 at methimazole concentrations greater than 50 or 100 mu M, respectively, and inhibits at lower methimazole concentrations. The extent of the activation increases as the substrate concentration increases, and the extent of inhibition increases as the substrate concentration decreases. With either inhibition or activation, the magnitude of the effect shows a similar, direct dependency on imipramine concentration. In contrast, imipramine inhibits the metabolism of methimazole catalyzed by pig FMO1 at all substrate concentrations. The structural basis for this unique ortholog difference between the responses of rabbit and pig FMO1 to imipramine was studied by random chimeragenesis and site-directed mutagenesis. Results with chimeras indicated that modulation of FMO1 activity by imipramine is controlled to a great extent by two areas of the FMO primary structure (residues 381-432 and 433-465). Four amino acids in these regions (positions 381, 400, 420 and 433) and one additional residue (position 186) were identified by site-directed mutagenesis as primary determinants of the imipramine response. When the residues at these positions in rabbit FMO1 are exchanged for the corresponding residues of pig FMO1, a mutant with the functional properties of pig FMO1 is produced. Our results suggest that the response of FMO1 to imipramine involves a distribution between two sites that is regulated by structural features that do not alter the overall binding. The inhibition observed, although it appears to be competitive, likely does not involve competition for a binding site since alteration of imipramine metabolism has no effect on the parameters of methimazole metabolism. C1 NIEHS, Lab Signal Transduct, Mol Pharmacol Sect, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Toxicol, Raleigh, NC 27695 USA. RP Philpot, RM (reprint author), NIEHS, Lab Signal Transduct, Mol Pharmacol Sect, POB 12233, Res Triangle Pk, NC 27709 USA. NR 39 TC 12 Z9 12 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 APR 28 PY 1998 VL 37 IS 17 BP 5930 EP 5938 DI 10.1021/bi972622b PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZL949 UT WOS:000073489700018 PM 9558327 ER PT J AU Heller, PF AF Heller, PF TI Paclitaxel and Arterial Smooth Muscle Cell Proliferation SO CIRCULATION LA English DT Letter C1 NIH, Cardiovasc Sci Lab, Baltimore, MD USA. RP Heller, PF (reprint author), NIH, Cardiovasc Sci Lab, Baltimore, MD USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 28 PY 1998 VL 97 IS 16 BP 1651 EP 1651 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ZJ597 UT WOS:000073232700022 PM 9593574 ER PT J AU Weber, HC Hampton, LL Jensen, RT Battey, JF AF Weber, HC Hampton, LL Jensen, RT Battey, JF TI Structure and chromosomal localization of the mouse bombesin receptor subtype 3 gene SO GENE LA English DT Article DE gene structure; mouse X-chromosome; human X-chromosome; genomic clones; mammalian; G protein-coupled receptors ID LOWE OCULOCEREBRORENAL SYNDROME; GASTRIN-RELEASING PEPTIDE; CANCER-CELLS-INVITRO; LUNG-CARCINOMA CELLS; X-CHROMOSOME; MOLECULAR-CLONING; SMOOTH-MUSCLE; GROWTH; XQ24-Q26; MARKERS AB Bombesin (BN)-like peptides/neurotransmitters mediate a broad range of physiological funtions in the gastrointestinal tract and the central nervous system through binding to their specific, high-affinity mammalian bombesin receptors. This family of heptahelical, G protein-coupled receptors includes the gastrin-releasing peptide receptor (GRP-R, or bb2), neuromedin B receptor (NMB-R, or bbl), and the bombesin receptor subtype 3 (BRS-3, or bb3). The tissue distribution of BRS-3 is quite dissimilar compared to the other two BN receptors, GRP-R and NMB-R, and a natural ligand for BRS-3 is currently unknown. Nothing is known about mechanisms regulating BRS-3 gene expression and possible association with disease. To gain insight into the underlying structure and chromosomal localization of the BRS-3 genes, bacteriophage P1 genomic clones, harboring the genes for the human and mouse BRS-3, respectively, were isolated and their structure and chromosomal localizations determined. The protein-coding region of both genes is divided into three exons and spans approximately 5 kb. The loci of the BRS-3 genes were mapped to a syntenic region of the human (Xq25) and mouse (XA7.1-7.2) X-chromosome, respectively. The structural data of the BRS-3 genes derived from this study will permit future investigations of the mechanisms regulating their expression. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Boston Univ, Sch Med, Gastroenterol Sect, Boston, MA 02118 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD 20850 USA. NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Weber, HC (reprint author), Boston Univ, Sch Med, Gastroenterol Sect, 88 E Newton St, Boston, MA 02118 USA. EM christian.weber@bmc.org NR 30 TC 12 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD APR 28 PY 1998 VL 211 IS 1 BP 125 EP 131 DI 10.1016/S0378-1119(98)00050-X PG 7 WC Genetics & Heredity SC Genetics & Heredity GA ZM749 UT WOS:000073572000016 PM 9573346 ER PT J AU Lubkowski, J Yang, F Alexandratos, J Wlodawer, A Zhao, H Burke, TR Neamati, N Pommier, Y Merkel, G Skalka, AM AF Lubkowski, J Yang, F Alexandratos, J Wlodawer, A Zhao, H Burke, TR Neamati, N Pommier, Y Merkel, G Skalka, AM TI Structure of the catalytic domain of avian sarcoma virus integrase with a bound HIV-1 integrase-targeted inhibitor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; DNA-BINDING DOMAIN; RETROVIRAL INTEGRASE; ACTIVE-SITE; PROTEIN; TYPE-1 AB The x-ray structures of an inhibitor complex of the catalytic core domain of avian sarcoma virus integrase (ASV IN) were solved at 1.9- to 2.0-Angstrom resolution at two pH values, with and without Mn2+ cations. This inhibitor (Y-3), originally identified in a screen for inhibitors of the catalytic activity of HIV type 1 integrase (HIV-1 IN), was found in the present study to be active against ASV IN as well as HIV-1 IN. The Y-3 molecule is located in close proximity to the enzyme active site, interacts with the flexible loop, alters loop conformation, and affects the conformations of active site residues. As crystallized, a Y-3 molecule stacks against its symmetry-related mate. Preincubation of IN with metal cations does not prevent inhibition, and Y-3 binding does not prevent binding of divalent cations to IN. Three compounds chemically related to Y-3 also were investigated, but no binding was observed in the crystals. Our results identify the structural elements of the inhibitor that likely determine its binding properties. C1 NCI, Macromol Struct Lab, Adv BioSci Labs, Basic Res Program,Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. Fox Chase Canc Ctr, Inst Canc Res, Philadelphia, PA 19111 USA. RP Wlodawer, A (reprint author), NCI, Macromol Struct Lab, Adv BioSci Labs, Basic Res Program,Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RI Burke, Terrence/N-2601-2014 NR 36 TC 80 Z9 83 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 APR 28 PY 1998 VL 95 IS 9 BP 4831 EP 4836 DI 10.1073/pnas.95.9.4831 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZL269 UT WOS:000073415700011 PM 9560188 ER PT J AU Iwai, K Drake, SK Wehr, NB Weissman, AM LaVaute, T Minato, N Klausner, RD Levine, RL Rouault, TA AF Iwai, K Drake, SK Wehr, NB Weissman, AM LaVaute, T Minato, N Klausner, RD Levine, RL Rouault, TA TI Iron-dependent oxidation, ubiquitination, and degradation of iron regulatory protein 2: Implications for degradation of oxidized proteins SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SITE-SPECIFIC PHOSPHORYLATION; KAPPA-B-ALPHA; GLUTAMINE-SYNTHETASE; BINDING PROTEIN; MESSENGER-RNA; ACTIVE-SITE; PROTEASOME; PATHWAY; METABOLISM; GENERATION AB The ability of iron to catalyze formation of reactive oxygen species significantly contributes to its toxicity In cells and animals. Iron uptake and distribution is regulated tightly in mammalian cells, in part by iron regulatory protein 2 (IRP2), a protein that is degraded efficiently by the proteasome in iron-replete cells. Here, me demonstrate that IRP2 is oxidized and ubiquitinated in cells before degradation. Moreover, iron-dependent oxidation converts IRP2 into a substrate for ubiquitination in vitro. A regulatory pathway is described in which excess iron is sensed by its ability to catalyze site-specific oxidations in IRP2, oxidized IRP2 is ubiquitinated, and ubiquitinated IRP2 subsequently is degraded by the proteasome, Selective targeting and removal of oxidatively modified proteins may contribute to the turnover of many proteins that are degraded by the proteasome. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Biochem Lab, Bethesda, MD 20892 USA. NCI, Lab Immune Cell Biol, Div Basic Sci, Bethesda, MD 20892 USA. Kyoto Univ, Grad Sch Med, Dept Immunol & Cell Biol, Sakyo Ku, Kyoto 6068501, Japan. RP Rouault, TA (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bldg 18T,Room 101, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 27 TC 226 Z9 229 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 APR 28 PY 1998 VL 95 IS 9 BP 4924 EP 4928 DI 10.1073/pnas.95.9.4924 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZL269 UT WOS:000073415700027 PM 9560204 ER PT J AU Ogryzko, VV AF Ogryzko, VV TI Hot papers - Genetics - The transcriptional coactivators p300 and CBP are histone acetyltransferases by V.V. Ogryzko, R.L. Schiltz, V. Russanova, B.H. Howard, Y. Nakatani - Comments SO SCIENTIST LA English DT Editorial Material AB HOT papers: Investigator Vasily V. Ogryzko discusses the acetylation of chromatin and its role in genetic processes. C1 NICHHD, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. RP Ogryzko, VV (reprint author), NICHHD, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. NR 5 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 APR 27 PY 1998 VL 12 IS 9 BP 11 EP 11 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA ZK427 UT WOS:000073319800011 ER PT J AU Fetsch, PA Abati, A Hijazi, YM AF Fetsch, PA Abati, A Hijazi, YM TI Utility of the antibodies CA 19-9, HBME-1, and thrombomodulin in the diagnosis of malignant mesothelioma and adenocarcinoma in cytology SO CANCER CYTOPATHOLOGY LA English DT Article DE CA 19-9; HBME-1; thrombomodulin; mesothelioma; adenocarcinoma; immunocytochemistry ID PLEURAL MESOTHELIOMA; PULMONARY ADENOCARCINOMA; DIFFERENTIAL-DIAGNOSIS; LUNG ADENOCARCINOMA; MONOCLONAL-ANTIBODY; EXTRAPULMONARY MALIGNANCIES; LOGISTIC-REGRESSION; CELL-LINES; MARKER; IMMUNOCYTOCHEMISTRY AB BACKGROUND. The distinction between malignant mesothelioma (MM) and adenocarcinoma (ACA) in cytologic specimens frequently is difficult, often requiring immunocytochemistry to support the diagnosis. Recent reports have proposed the utilization of antibodies to mesothelial cell clone HBME-1 and thrombomodulin (TM), because they are immunoreactive in MM and less commonly reactive in ACA. Immunoreactivity for the monoclonal antibody CA 19-9 has been observed in many ACAs and reportedly is absent in MM. METHODS. In this study, immunostaining was performed on formalin fixed, paraffin embedded cell blocks from effusions or fine-needle aspirations using the avidin-biotin-peroxidase method. Thirty-eight MMs and 49 ACAs were tested using antibodies to CA 19-9, HBME-1, and TM. RESULTS. Anti-CA 19-9 stained only 1 of the 37 cases of MM tested (3%), but stained 24 of the 49 cases of ACA (49%). Anti-HBME-1 stained 34 of 38 cases of MM (89%), and 28 of 43 cases of ACA tested (65%). Anti-TM stained 24 of 36 cases of MM (67%), and 21 of 40 cases of ACA tested (53%). CONCLUSIONS. CA 19-9 has utility as part of an immunocytochemical panel for distinguishing ACA from MM, because a positive staining reaction would make the diagnosis of MM unlikely. Although HBME-1 and TM can identify MM positively, each frequently is detected in ACA, thus limiting the utility of these antibodies in cytologic specimens. (C) 1998 American Cancer Society. C1 NIH, Pathol Lab, Cytopathol Sect, NCI, Bethesda, MD 20892 USA. RP Abati, A (reprint author), NIH, Pathol Lab, Cytopathol Sect, NCI, Bldg 10,Room 2A19,10 Ctr Dr MSC 1500, Bethesda, MD 20892 USA. NR 39 TC 38 Z9 42 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD APR 25 PY 1998 VL 84 IS 2 BP 101 EP 108 DI 10.1002/(SICI)1097-0142(19980425)84:2<101::AID-CNCR6>3.0.CO;2-S PG 8 WC Oncology; Pathology SC Oncology; Pathology GA ZJ043 UT WOS:000073173800006 PM 9570213 ER PT J AU Wolffe, EJ Weisberg, AS Moss, B AF Wolffe, EJ Weisberg, AS Moss, B TI Role for the vaccinia virus A36R outer envelope protein in the formation of virus-tipped actin-containing microvilli and cell-to-cell virus spread SO VIROLOGY LA English DT Article ID EXTRACELLULAR VIRUS; MEMBRANE; DISSEMINATION; DELETION; FUSION; EGRESS AB A small-plaque-forming vaccinia virus mutant with a deletion in the A36R gene encoding an outer envelope protein (Parkinson and Smith, Virology, 204, 376-390, 1994) was shown to assemble wrapped forms of intra-and extracellular virus particles and to mediate acid-induced polykaryon formation. The intracellular virions, however, did not acquire actin tails and those on the cell surface were not associated with specialized microvilli. This phenotype is similar to that of the A34R (E. J. Wolffe, E. Katz, A. Weisberg, and a. Moss, J. Virol. 71, 3904-3915, 1997) and A33R (R. Roper, E.J. Wolffe, A Weisberg, and a. Moss, J. Virol., in press) deletion mutants. Taken together, these data support a model in which the envelope proteins encoded by the A33R, A34R, and A36R genes are all required for nucleation of actin tails, which facilitate dissemination rather than egress of virus particles. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr, Bethesda, MD 20892 USA. NR 20 TC 102 Z9 103 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 APR 25 PY 1998 VL 244 IS 1 BP 20 EP 26 DI 10.1006/viro.1998.9103 PG 7 WC Virology SC Virology GA ZM346 UT WOS:000073529300003 PM 9581774 ER PT J AU Yanagi, M St Claire, M Shapiro, M Emerson, SU Purcell, RH Bukh, J AF Yanagi, M St Claire, M Shapiro, M Emerson, SU Purcell, RH Bukh, J TI Transcripts of a chimeric cDNA clone of hepatitis C virus genotype 1b are infectious in vivo SO VIROLOGY LA English DT Article ID GENETIC ORGANIZATION; CELL-CULTURES; GENOME; RNA; SEQUENCE; 3'-TERMINUS; HCV; GLYCOPROTEIN; SELECTION; DIVERSITY AB We constructed a chimeric cDNA clone of hepatitis C virus (HCV) that is infectious. The chimeric genome encodes the polyprotein of a genotype Ib strain (HC-J4) of HCV and replicates via 5' and 3' untranslated regions of a genotype la strain. The infectivity of three full-length cDNA clones was tested by direct injection of RNA transcripts into the liver of a chimpanzee. The chimpanzee became infected with HCV and the viral titer increased over time from 10(2) genome equivalents (GE)/ml at week 1 postinoculation (p.i.) to 10(4)-10(5) GE/ml during weeks 3-11 p.i. Antibodies to HCV were detected from week 18 p.i. However, the chimpanzee did not develop hepatitis. Sequence analysis of PCR products amplified from the serum of the chimpanzee demonstrated that only one of the three clones was infectious. Sequence comparisons with the cloning source, an acute-phase infectious plasma pool derived from an experimentally infected chimpanzee, showed that this infectious clone had three amino acids that differed from the consensus sequence of HC-J4, whereas the two noninfectious clones had seven and nine amino acid differences, respectively. Together, genotype Ib, represented by the infectious molecular clone described herein, and genotype la, represented by the two cDNA clones previously shown to be infectious for chimpanzees, account for the majority of HCV infections in the United States, Europe, and Japan. (C) 1998 Academic Press. C1 NIAID, LID, Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA. Bioqual Inc, Rockville, MD USA. RP Bukh, J (reprint author), NIAID, LID, Hepatitis Viruses Sect, NIH, Bldg 7,Room 201,7 Ctr Dr,MSC 0740, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CO-56000]; NIAID NIH HHS [N01-AI-45180, N01-AI-52705] NR 42 TC 180 Z9 187 U1 0 U2 5 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 APR 25 PY 1998 VL 244 IS 1 BP 161 EP 172 DI 10.1006/viro.1998.9092 PG 12 WC Virology SC Virology GA ZM346 UT WOS:000073529300017 PM 9581788 ER PT J AU Townsend, AJ Fields, WR Haynes, RL Doss, AJ Li, Y Doehmer, J Morrow, CS AF Townsend, AJ Fields, WR Haynes, RL Doss, AJ Li, Y Doehmer, J Morrow, CS TI Chemoprotective functions of glutathione S-transferases in cell lines induced to express specific isozymes by stable transfection SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article; Proceedings Paper CT International Conference on Glutathione and Glutathione-Linked Enzymes in Human Cancer and Other Diseases CY OCT 31-NOV 03, 1996 CL HILTON HEAD ISL, SC DE glutathione S-transferase; chemoprevention; carcinogenesis; mutagenesis; cytotoxicity; transfection ID CHINESE-HAMSTER-CELLS; BREAST-CANCER-CELLS; CATALYTIC ACTIVITY; RAT-LIVER; AFLATOXIN-B1; RESISTANCE; OLTIPRAZ; MOUSE; GENE; BIOTRANSFORMATION AB The authors have shown that expression of mGSTM1-1 or hGSTP1-1 in MCF-7 cells protects against DNA alkylation by 4-nitroquinoline-1-oxide (NQO) in an isozyme-specific manner and is commensurate with relative specific activity. Expression of GSTs also conferred protection against both DNA strand breaks and sister-chromatid exchange induced by NQO. Interestingly, GST expression did not protect against NQO cytotoxicity in transfected MCF-7 cell lines, although resistance to NQO cytotoxicity was observed in a T47D pi transfectant line, expressing much higher specific activity of the transfected hGSTP1-1. However, high level expression of hGSTP1-1 or mGSTM1-1 in V79 transfectants did not confer resistance to cytotoxicity, indicating that expression of GST alone is not sufficient. The authors have also shown protection against AFB(1) in cell lines expressing transfected rat CYP2B1 (V79MZr2B1) and transfected mGST-Yc (mGSTA3-3). Protection was observed against both alkylation of DNA (3-fold) by [H-3]AFB(1) and against AFB, cytotoxicity (7-fold). Similarly, V79MZr1A1 cells that express CYP1A1 and either transfected human or murine GSTP1-1 (> 5000 mIU/mg, CDNB) exhibited > 70% decrease in covalent labeling of total nucleic acids by [H-3]BPDE. However, no protection against the cytotoxicity of BPDE was conferred by expression of hGSTP1-1. Overall, these results indicate that in some (NQO or BPDE), but not all (AFB(1)) cases, protection by GST expression against DNA damage is more effective than protection against cytotoxicity. In addition, there is evidence to indicate that additional factor(s) other than high GST isozyme expression level and good substrate efficacy affect the degree of protection against cytotoxicity of reactive electrophiles. This includes the differential protection against NQO cytotoxicity in T47D pi, but not V79 Xh pi-33 cells and also the recent studies which showed that expression of the MRP GS-X conjugate efflux transporter confers synergistic protection against NQO cytotoxicity when co-expressed with transfected human GSTP1-1 in MCF-7 cells. Thus, protective efficacy conferred by GST expression can vary with different cellular targets and/or experimental end-points, as well as with variations in relative specific activity or in different cellular phenotypic contexts. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Wake Forest Univ, Sch Med, Ctr Comprehens Canc, Dept Biochem, Winston Salem, NC 27157 USA. RJ Reynolds Tobacco Co, Res & Dev, Cellular & Mol Biol Div, Winston Salem, NC 27102 USA. NIH, Bethesda, MD 20892 USA. Tech Univ Munich, Inst Toxikol & Umwelthyg, D-80636 Munich, Germany. RP Townsend, AJ (reprint author), Wake Forest Univ, Sch Med, Ctr Comprehens Canc, Dept Biochem, Med Ctr Blvd, Winston Salem, NC 27157 USA. RI Haynes, Robin/M-4401-2016 OI Haynes, Robin/0000-0003-4909-9585 NR 42 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-2797 EI 1872-7786 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD APR 24 PY 1998 VL 112 BP 389 EP 407 PG 19 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA ZV735 UT WOS:000074335800033 ER PT J AU Segal, JA Skolnick, P AF Segal, JA Skolnick, P TI Polyamine-like actions of aminoglycosides and aminoglycoside derivatives at NMDA receptors SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE NMDA receptor; polyamine; aminoglycoside; aminocyclitol; aminosugar; ototoxicity ID D-ASPARTATE RECEPTOR; H-3 IFENPRODIL; RAT-BRAIN; RECOGNITION SITE; MODULATORY SITE; MK-801 BINDING; CONANTOKIN-G; COMPLEX; ANTAGONIST; GLYCINE AB Recent pharmacological studies indicate that aminoglycoside-induced hearing loss may be an excitotoxic process modulated by a polyamine-like activation of cochlear NMDA receptors. Aminoglycoside antibiotics are constituted by a series of glycosidically linked aminocyclitols and aminosugars. We report here on the actions of these individual aminocyclitols and aminosugars on wild type NMDA receptors from rat brain. Compared to the parent molecules, neither aminocyclitols (e.g., 2-deoxystreptamine, streptamine, and streptidine) nor aminosugars (e.g., D-glucosamine and kanosamine) were effective at enhancing [H-3]dizocilpine ([H-3]MK-801) binding or inhibiting [3H]ifenprodil at NMDA receptors. Moreover, the appropriate combinations of aminosugars and aminocyclitols did not reconstitute the activity of the parent aminoglycoside at NMDA receptors. These data indicate that the polyamine-like actions of aminoglycosides are attributable to the conformation of the parent molecule rather than a particular amine containing constituent. Thus, it may be possible to synthesize or isolate aminoglycoside antibiotics devoid of ototoxicity. Published by Elsevier Science B.V. C1 NIDDK, Neurosci Lab, Bethesda, MD 20892 USA. RP Segal, JA (reprint author), Eli Lilly & Co, Lilly Res Labs, CNS Discovery, Bldg 48,Drop Code 0510, Indianapolis, IN 46285 USA. EM segalj@lilly.com NR 31 TC 25 Z9 26 U1 0 U2 2 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 APR 24 PY 1998 VL 347 IS 2-3 BP 311 EP 317 DI 10.1016/S0014-2999(98)00108-3 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZP727 UT WOS:000073782400025 PM 9653898 ER PT J AU Witkin, J Gasior, M Acri, J Beekman, M Thurkauf, A Yuan, J DeBoer, P Wikstrom, H Dijkstra, D AF Witkin, J Gasior, M Acri, J Beekman, M Thurkauf, A Yuan, J DeBoer, P Wikstrom, H Dijkstra, D TI Atypical antipsychotic-like effects of the dopamine D-3 receptor agonist, (+)-PD 128,907 SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE dopamine D-3 receptor; antipsychotic; (+)-PD 128,907 AB Anti-schizophrenia agents with improved efficacy and side-effect profiles are required. A dopamine D-3 receptor agonist, R-(+)-trans-3,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4,3-b]-1,4-oxazin-9-ol HCl ((+)-PD 128,907), displayed an atypical antipsychotic profile comparable to that of clozapine. (+)-PD 128,907 blocked stereotypy produced by dizocilpine (MK-801) at 12-fold lower doses than those affecting apomorphine-induced stereotypes in mice and did not produce catalepsy. These effects of(+)-PD 128,907 were stereospecific and were blocked by a D-3 antagonist. These data suggest a role for D-3 receptors in antipsychotic drug action. Published by Elsevier Science B.V. C1 NIDA, Addict Res Ctr, Drug Dev Grp, NIH, Baltimore, MD 21224 USA. Neurogen Corp, Branford, CT USA. Univ Groningen, Dept Med Chem, NL-9713 AW Groningen, Netherlands. RP Witkin, J (reprint author), NIDA, Addict Res Ctr, Drug Dev Grp, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jwitkin@irp.nida.nih.gov NR 8 TC 19 Z9 20 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 APR 24 PY 1998 VL 347 IS 2-3 BP R1 EP R3 DI 10.1016/S0014-2999(98)00174-5 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZP727 UT WOS:000073782400033 PM 9741997 ER PT J AU Ahmad, F Wang, LM Resjo, S Degerman, E Pierce, JH Manganiello, VC AF Ahmad, F Wang, LM Resjo, S Degerman, E Pierce, JH Manganiello, VC TI Regulation of cyclic nucleotide phosphodiesterases PDE3 and PDE4 by cytokines in FDCP2 myeloid cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, PCCMB, NIH, Bethesda, MD USA. NCI, LCMB, NIH, Bethesda, MD USA. Univ Lund, S-22100 Lund, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 360 BP A1372 EP A1372 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500512 ER PT J AU Altschul, S Madden, T Schaffer, A Zhang, JH Zhang, Z Miller, W Lipman, D AF Altschul, S Madden, T Schaffer, A Zhang, JH Zhang, Z Miller, W Lipman, D TI Gapped BLAST and PSI-BLAST: A new generation of protein database search programs SO FASEB JOURNAL LA English DT Meeting Abstract C1 Natl Ctr Biotechnol Informat, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. Natl Lib Med, Bethesda, MD 20894 USA. NR 0 TC 35 Z9 35 U1 12 U2 120 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 102 BP A1326 EP A1326 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500256 ER PT J AU Angus, CW Klivington, D Wyman, J Kovacs, JA AF Angus, CW Klivington, D Wyman, J Kovacs, JA TI Nucleic acid vaccination against Toxoplasma gondii in mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 512 BP A1399 EP A1399 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500668 ER PT J AU Bera, TK Onda, M Brinkmann, U Pastan, I AF Bera, TK Onda, M Brinkmann, U Pastan, I TI A bivalent disulfide-stabilized Fv with improved antigen binding to erbB2. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 682 BP A1428 EP A1428 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500837 ER PT J AU Bertelsen, EB Zhou, HJ Flynn, GC Dahlquist, FW AF Bertelsen, EB Zhou, HJ Flynn, GC Dahlquist, FW TI NMR characterization of the C-terminal 10 kDa domain of DnaK SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Oregon, Inst Mol Biol, Eugene, OR 97403 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 633 BP A1420 EP A1420 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500789 ER PT J AU Beuron, F Steven, AC Kessel, M Buoy, FB Wickner, S Maurizi, MR AF Beuron, F Steven, AC Kessel, M Buoy, FB Wickner, S Maurizi, MR TI Clp-AP : substrate interactions studied by cryo-electron microscopy. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAMS, NIH, Bethesda, MD USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 644 BP A1422 EP A1422 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500798 ER PT J AU Bhagwat, M Nossal, N AF Bhagwat, M Nossal, N TI Control of DNA degradation during lagging strand processing by bacteriophage T4 proteins SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 124 BP A1331 EP A1331 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500278 ER PT J AU Bortner, CD Cidlowski, JA AF Bortner, CD Cidlowski, JA TI Caspase independent activation of cell shrinkage and altered mitochondrial potential during apoptosis SO FASEB JOURNAL 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 FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 174 BP A1340 EP A1340 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500330 ER PT J AU Casas-Finet, JR Morcock, D Kane, BP AF Casas-Finet, JR Morcock, D Kane, BP TI Nucleic acid binding properties of HTLV-1 nucleocapsid protein p15. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, SAIC Frederick, FCRDC, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 829 BP A1453 EP A1453 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500983 ER PT J AU Chen, HX Centola, M AF Chen, HX Centola, M TI Gene expression profiles in resting and stimulated mast cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAMS, ARB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 876 BP A1461 EP A1461 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501028 ER PT J AU Chowdhury, PS Vasmatzis, G Beers, R Lee, B Pastan, I AF Chowdhury, PS Vasmatzis, G Beers, R Lee, B Pastan, I TI Improvement of the stability and yield of scFv immunotoxins by molecular modeling and protein engineering SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 681 BP A1428 EP A1428 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500834 ER PT J AU Daugherty, AL Silva, J Fryling, CM FitzGerald, DJ Mrsny, RJ AF Daugherty, AL Silva, J Fryling, CM FitzGerald, DJ Mrsny, RJ TI Mucosal administration of a non-toxic pseudomonas exotoxin-gp120 V3 loop chimera elevates gp120 specific IgG and IgA in the serum and saliva of BALB/c mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 Genentech Inc, S San Francisco, CA 94080 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 939 BP A1472 EP A1472 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501094 ER PT J AU Drohat, AC Tjandra, N Baldisseri, DM Weber, DJ AF Drohat, AC Tjandra, N Baldisseri, DM Weber, DJ TI Refinement of the solution structure of rat apo-S100B(beta beta) using internuclear magnetic dipolar couplings measured by NMR in a dilute liquid crystalline medium SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 814 BP A1451 EP A1451 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500970 ER PT J AU Erlenbach, I Wess, J AF Erlenbach, I Wess, J TI Identification of structural elements that determine the G protein coupling selectivity of the V2 vasopressin receptor SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 855 BP A1458 EP A1458 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501011 ER PT J AU Fisher, A Shi, Y Ritter, A Ferretti, JA Shah, M Shiloach, J Taniuchi, H AF Fisher, A Shi, Y Ritter, A Ferretti, JA Shah, M Shiloach, J Taniuchi, H TI Cooperativity of hydrophobic core residues in structure, function and thermodynamics of yeast iso-2 cytochrome c. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 738 BP A1438 EP A1438 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500891 ER PT J AU FitzGerald, DJ Fryling, CM McKee, M Daugherty, AL Mrsny, RJ AF FitzGerald, DJ Fryling, CM McKee, M Daugherty, AL Mrsny, RJ TI Development of V3-loop pseudomonas exotoxin chimeras: candidate vaccines for human immunodeficiency virus-1. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Mol Biol Lab, DBS, Bethesda, MD 20892 USA. Genentech Inc, S San Francisco, CA 94080 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 944 BP A1473 EP A1473 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501097 ER PT J AU Foley, TD Linnoila, M AF Foley, TD Linnoila, M TI Low concentrations of the Na+, K+-ATPase ligand ouabain activate intracellular signaling enzymes SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA, Rockville, MD 20852 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 837 BP A1455 EP A1455 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500993 ER PT J AU Gerschenson, M Quan, H Erhart, SW Poirier, MC AF Gerschenson, M Quan, H Erhart, SW Poirier, MC TI Oxidative phosphorylation (OXPHOS) enzyme activities are effected in fetal Erythrocebus patas monkeys exposed transplacentally to 3 '-azido-2 ',3 '-dideoxythymidine (AZT). SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 292 BP A1361 EP A1361 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500446 ER PT J AU Gladyshev, V Diamond, A Factor, V Wootton, J Moustafa, M Jeang, KT Berry, M Parodi, A Lee, BJ Hatfield, D AF Gladyshev, V Diamond, A Factor, V Wootton, J Moustafa, M Jeang, KT Berry, M Parodi, A Lee, BJ Hatfield, D TI Association between a novel mammalian 15 kDa selenoprotein and cancer SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Univ Nebraska, Lincoln, NE USA. Univ Chicago, Chicago, IL 60637 USA. Harvard Univ, Sch Med, Boston, MA USA. Fdn Campomar, RA-1405 Buenos Aires, DF, Argentina. SNU, Seoul, South Korea. NIH, Bethesda, MD 20892 USA. Univ Nebraska, Lincoln, NE USA. Univ Chicago, Chicago, IL 60637 USA. Harvard Univ, Sch Med, Boston, MA USA. RI Jeang, Kuan-Teh/A-2424-2008; Gladyshev, Vadim/A-9894-2013 NR 0 TC 1 Z9 1 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 700 BP A1431 EP A1431 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500855 ER PT J AU Gorlatov, SN Stadtman, TC AF Gorlatov, SN Stadtman, TC TI Properties of two forms of thioredoxin reductase from HeLa cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 645 BP A1422 EP A1422 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500799 ER PT J AU Greene, LE Zhao, X Greener, T Eisenberg, E AF Greene, LE Zhao, X Greener, T Eisenberg, E TI Expression of the clathrin assembly protein, AP-180, in tissue culture cells inhibits endocytosis. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 923 BP A1469 EP A1469 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501075 ER PT J AU Greener, T Nojima, H Eisenberg, E Greene, LE AF Greener, T Nojima, H Eisenberg, E Greene, LE TI Cyclin G associated kinase (GAK) has kinase and auxilin domains that are active in vitro. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. Osaka Univ, Inst Microbiol Dis, Osaka, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 631 BP A1419 EP A1419 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500785 ER PT J AU Griffith, CE Zhang, WG Wange, RL AF Griffith, CE Zhang, WG Wange, RL TI Peroxide-induced MAPK activation in Jurkat requires ZAP-70 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA, Biol Chem Lab, NIH, Baltimore, MD 21224 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 593 BP A1413 EP A1413 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500747 ER PT J AU Gupta, R Hamasaki, N Tabor, CW Tabor, H AF Gupta, R Hamasaki, N Tabor, CW Tabor, H TI Studies on the degradation of ornithine decarboxylase (ODC) in Saccharomyces cerevisiae SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 723 BP A1435 EP A1435 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500878 ER PT J AU Hamasaki-Katagiri, N Katagiri, Y Tabor, CW Tabor, H AF Hamasaki-Katagiri, N Katagiri, Y Tabor, CW Tabor, H TI Spermine is not essential for growth of Saccharomyces cerevisiae: Study of a SPE4 (spermine synthase) deletion mutant SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 599 BP A1414 EP A1414 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500753 ER PT J AU Hamid, EH Dickson, LA Egan, MF AF Hamid, EH Dickson, LA Egan, MF TI Drug withdrawal after short-term neuroleptic treatment causes a rapid increase in Cu/Zn superoxide dismutase mRNA expression in rat striatum SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH, Neuropsychiat Res Hosp, IRP, Washington, DC 20032 USA. Howard Univ, Dept Biol, Washington, DC 20059 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA S16 BP A1294 EP A1294 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500097 ER PT J AU Hoffmann, C Moro, S Nicholas, RA Harden, TK Jacobson, KA AF Hoffmann, C Moro, S Nicholas, RA Harden, TK Jacobson, KA TI Conformational constraints of extracellular loop 2 are essential for activation of human P2Y1 receptors. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. RI Moro, Stefano/A-2979-2012; Jacobson, Kenneth/A-1530-2009 OI Moro, Stefano/0000-0002-7514-3802; Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 856 BP A1458 EP A1458 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501009 ER PT J AU Huang, S Angus, W Turner, R Sorial, V Kovacs, JA AF Huang, S Angus, W Turner, R Sorial, V Kovacs, JA TI Identification and characterization of a novel major surface glycoprotein like gene family in rat Pneumocystis carinii SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 223 BP A1349 EP A1349 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500377 ER PT J AU Huang, STJ Cidlowski, JA AF Huang, STJ Cidlowski, JA TI Glucocorticoids inhibit serum depletion-induced apoptosis in T-lymphocytes expressing Bcl-2 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RI Huang, Se-Te/F-6881-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 172 BP A1339 EP A1339 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500326 ER PT J AU Hunyady, L Zhang, M Gaborik, Z Catt, KJ AF Hunyady, L Zhang, M Gaborik, Z Catt, KJ TI An intramolecular interaction between conserved amino acids is required for activation of the angiotensin AT(1) receptor SO FASEB JOURNAL LA English DT Meeting Abstract C1 Semmelweis Univ Med, Dept Physiol, H-1085 Budapest, Hungary. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 912 BP A1467 EP A1467 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501066 ER PT J AU Ibeanu, GC Blaisdell, J Benhamou, S Bouchardy, C Dayer, P Ghanayem, B Goldstein, JA AF Ibeanu, GC Blaisdell, J Benhamou, S Bouchardy, C Dayer, P Ghanayem, B Goldstein, JA TI New genetic defects in human CYP2C19 result in decreased catalytic activity towards S-mephenytoin. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, NC 27709 USA. INSERM, U351, Villejuif, France. Univ Hosp Geneva, Geneva, Switzerland. Geneva Canc Registry, Geneva, Switzerland. RI Benhamou, Simone/K-6554-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 670 BP A1426 EP A1426 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500825 ER PT J AU Jacobson, KA Moro, S AF Jacobson, KA Moro, S TI Molecular recognition in purine receptors: Ligand development aided by molecular modeling and mutagenesis. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. RI Moro, Stefano/A-2979-2012; Jacobson, Kenneth/A-1530-2009 OI Moro, Stefano/0000-0002-7514-3802; Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA D13 BP A1304 EP A1304 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500148 ER PT J AU Jagannath, SB Jaffe, H Quarles, RH Stebbins, JW AF Jagannath, SB Jaffe, H Quarles, RH Stebbins, JW TI Cloning and heterologous expression of bovine brain specific protein P25 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINCDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 798 BP A1448 EP A1448 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500953 ER PT J AU Jakowlew, SB Cuttitta, F Mariano, JM Montuenga, LM AF Jakowlew, SB Cuttitta, F Mariano, JM Montuenga, LM TI Coordinate expression of transforming growth factor-beta 1 and adrenomedullin in rodent embryogenesis. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 883 BP A1463 EP A1463 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501037 ER PT J AU Jaworski, C Putilina, T Gentleman, S AF Jaworski, C Putilina, T Gentleman, S TI Elimination of a LIM domain by tissue-specific alternative splicing SO FASEB JOURNAL LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 758 BP A1441 EP A1441 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500912 ER PT J AU Jeng, J Kallarakal, A Eriksson, P Goldman, D Wang, T Weiner, H Song, BJ AF Jeng, J Kallarakal, A Eriksson, P Goldman, D Wang, T Weiner, H Song, BJ TI Characterization of transgenic mice carrying the human ALDH2(2) (oriental variant) allele SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA, Rockville, MD 20852 USA. Finnish State Alcohol Co, Res Lab, Helsinki, Finland. NCI, Frederick, MD 21701 USA. Purdue Univ, W Lafayette, IN 47907 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 270 BP A1357 EP A1357 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500423 ER PT J AU Jiang, R Gao, B Eisenberg, E Greene, LE AF Jiang, R Gao, B Eisenberg, E Greene, LE TI An HSC70-clathrin complex formed during uncoating may be involved in rebinding of clathrin to uncoated clathrin vesicles. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 632 BP A1420 EP A1420 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500786 ER PT J AU Johnson, A Murphy, B Proctor, K Rubinstein, Y AF Johnson, A Murphy, B Proctor, K Rubinstein, Y TI Characterization of a repressor of epidermal growth factor receptor gene expression SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 466 BP A1390 EP A1390 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500618 ER PT J AU Kakuta, Y Petrotchenko, EV Pedersen, LC Negishi, M AF Kakuta, Y Petrotchenko, EV Pedersen, LC Negishi, M TI Structure-based analysis of catalysis in estrogen sulfotransferase SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Reprod & Dev Toxicol Lab, Pharmacogenet Sect, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 306 BP A1363 EP A1363 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500459 ER PT J AU Kenan, Y Murata, T Shakur, Y Manganiello, VC AF Kenan, Y Murata, T Shakur, Y Manganiello, VC TI Characterization of N-terminal deletion mutants of cyclic nucleotide phosphodiesterase 3 (PDE 3) isoforms. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, PCCMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 999 BP A1482 EP A1482 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501153 ER PT J AU Kim, JR Kwon, KS Yoon, HW Lee, SR Rhee, SG AF Kim, JR Kwon, KS Yoon, HW Lee, SR Rhee, SG TI Identification of proteins that contain cysteine susceptible to oxidation by dopamine-derived H2O2 in PC12 cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 177 BP A1340 EP A1340 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500329 ER PT J AU King, MT Veech, RL AF King, MT Veech, RL TI Feeding a rich fat ketogenic diet reduces mitochondrial W/QH(2) in brain while pure ketones oxidize Q/QH(2) in heart. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA, LMBB, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 379 BP A1375 EP A1375 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500533 ER PT J AU Kohama, T Olivera, A Tu, Z Milstien, S Spiegel, S AF Kohama, T Olivera, A Tu, Z Milstien, S Spiegel, S TI Purification and characterization of rat kidney sphingosine kinase SO FASEB JOURNAL LA English DT Meeting Abstract C1 Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 1020 BP A1486 EP A1486 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501173 ER PT J AU Kohn, KW AF Kohn, KW TI Functional capabilities of molecular network components controlling the G1/S cell cycle phase transition. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 161 BP A1337 EP A1337 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500315 ER PT J AU Kostenis, E Zeng, FY Wess, J AF Kostenis, E Zeng, FY Wess, J TI Functional characterization of a series of mutant G protein alpha(q) subunits displaying promiscuous receptor coupling properties SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 333 BP A1368 EP A1368 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500487 ER PT J AU Kutty, RK Kutty, G Samuel, W Duncan, T Wiggert, B AF Kutty, RK Kutty, G Samuel, W Duncan, T Wiggert, B TI Characterization of an activin gene from Drosophila melanogaster SO FASEB JOURNAL LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 900 BP A1465 EP A1465 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501054 ER PT J AU Lacourciere, GM Stadtman, TC AF Lacourciere, GM Stadtman, TC TI Catalytic properties of selenophosphate synthetase enzymes SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 755 BP A1441 EP A1441 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500908 ER PT J AU Landsman, D McEntyre, J Madden, TL AF Landsman, D McEntyre, J Madden, TL TI Data mining and analysis tools at the NCBIWWW site. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RI Landsman, David/C-5923-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA T23 BP A1490 EP A1490 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501195 ER PT J AU Lebowitz, J Schuck, P Ott, R Teale, M AF Lebowitz, J Schuck, P Ott, R Teale, M TI Band centrifugation for the characterization of proteins and protein complexes. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Alabama, Birmingham, AL USA. Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 500 BP A1396 EP A1396 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500654 ER PT J AU Lee, BJ Park, JM Kim, MJ Kwon, SY Carlson, BA Hatfield, D AF Lee, BJ Park, JM Kim, MJ Kwon, SY Carlson, BA Hatfield, D TI Purification and characterization of Xenopus RNA polymerase III and its transcription initiation factors SO FASEB JOURNAL LA English DT Meeting Abstract C1 Seoul Natl Univ, Inst Mol Biol & Genet, Seoul 151742, South Korea. NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 469 BP A1391 EP A1391 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500625 ER PT J AU Lee, HY Nam, SW Jeong, EM Kang, YJ Chang, KC Hong, SY Clair, T Liotta, LA Stracke, ML AF Lee, HY Nam, SW Jeong, EM Kang, YJ Chang, KC Hong, SY Clair, T Liotta, LA Stracke, ML TI Role of ATP binding in the stimulation of cancer cell motility by autotaxin SO FASEB JOURNAL LA English DT Meeting Abstract C1 Gyeongsang Natl Univ, Dept Pharmacol, Chinju, South Korea. Sung Kyun Kwan Univ, Dept Genet Engn, Suwon 440746, South Korea. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 894 BP A1464 EP A1464 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501048 ER PT J AU Lee, SR Kwon, KS Kim, SR Rhee, SG AF Lee, SR Kwon, KS Kim, SR Rhee, SG TI Reversible inactivation of protein tyrosine phosphatase 1B in A431 cells stimulated with epidermal growth factor SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S BP A1405 EP A1405 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500704 ER PT J AU Li, J Pak, JH Huang, FL Huang, KP AF Li, J Pak, JH Huang, FL Huang, KP TI Oxidation of rat brain neurogranin in brain slices by nitric oxide and oxidants. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD 20854 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 985 BP A1480 EP A1480 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501140 ER PT J AU Li, JJ Cao, Y Rhim, J Colburn, NH AF Li, JJ Cao, Y Rhim, J Colburn, NH TI Expression of a dominant negative c-jun under constitutive or inducing conditions inhibits AP-1 and NFkB, and reverses tumor phenotype in transformed human keratinocytes. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Lab Biochem Physiol, NIH, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 464 BP A1390 EP A1390 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500617 ER PT J AU Lubas, WA Hanover, JA AF Lubas, WA Hanover, JA TI Functional expression of recombinant human O-linked GlcNAc transferase. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDKD, Lab Cell Biochem & Biol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 230 BP A1350 EP A1350 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500386 ER PT J AU Makar, TK Accili, D Milstien, S AF Makar, TK Accili, D Milstien, S TI Suppression of nitric oxide and cytokine-induced apoptotic cell death by IGF-1 in insulin receptor knockout hepatocyes SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH, LCMR, NIH, Bethesda, MD 20892 USA. NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 995 BP A1482 EP A1482 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501151 ER PT J AU McKay, LI Cidlowski, JA AF McKay, LI Cidlowski, JA TI Mechanisms of mutual antagonism between glucocorticoid receptor and the p65 subunit of NF-kappa B SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 907 BP A1467 EP A1467 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501061 ER PT J AU McKee, M FitzGerald, D AF McKee, M FitzGerald, D TI Reduction of furin-nicked Pseudomonas exotoxin A by mammalian cells: an unfolding story. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, LMB, DBS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 946 BP A1473 EP A1473 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501098 ER PT J AU Moody, TW Badamchian, M Goldstein, AL AF Moody, TW Badamchian, M Goldstein, AL TI Thymosin alpha one prevents lung carcinogenesis. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Dept Cell & Canc Biol, Med Branch, Rockville, MD 20850 USA. George Washington Univ, Dept Biochem & Mol Biol, Med Ctr, Washington, DC 20037 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 851 BP A1457 EP A1457 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501006 ER PT J AU Moskovitz, J Berlett, BS Poston, JM Stadtman, ER AF Moskovitz, J Berlett, BS Poston, JM Stadtman, ER TI Overexpression of methionine sulfoxide reductase (MsrA) in yeast and its antioxidant activity. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 705 BP A1432 EP A1432 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500860 ER PT J AU Moustafa, ME Lee, BJ Kandeel, KM El-Saadani, MA Hatfield, DL Diamond, AM AF Moustafa, ME Lee, BJ Kandeel, KM El-Saadani, MA Hatfield, DL Diamond, AM TI Transfection of CHO cells in culture with increasing mouse selenocysteine tRNA gene copy numbers. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, BRL, NIH, Bethesda, MD 20892 USA. SNU, IMBG, LMG, Seoul, South Korea. Univ Alexandria, Fac Sci, Dept Biochem, Alexandria, Egypt. Univ Chicago, DRCO, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 463 BP A1390 EP A1390 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500619 ER PT J AU Nambiar, MP Vasmatzis, G Lee, BK FitzGerald, DJ Pastan, IH AF Nambiar, MP Vasmatzis, G Lee, BK FitzGerald, DJ Pastan, IH TI Production of stable scFv by mutation of the unusual amino acids at the framework region SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 683 BP A1428 EP A1428 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500835 ER PT J AU Neiditch, BR Dewar, C Hosfield, T Callahan, M Kobrin, M Bauer, JC Emmert-Buck, M Krizman, DB Lu, Q AF Neiditch, BR Dewar, C Hosfield, T Callahan, M Kobrin, M Bauer, JC Emmert-Buck, M Krizman, DB Lu, Q TI Construction of directional cDNA libraries from limited amounts of RNA using LIC-PCR. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Stratagene Cloning Syst Inc, La Jolla, CA USA. NCI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 517 BP A1400 EP A1400 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500671 ER PT J AU Newcomb, FM Davis, DA Wingfield, PT Stahl, SJ Kaufman, JD Fales, HM Moskovitz, J Levine, RL Yarchoan, R AF Newcomb, FM Davis, DA Wingfield, PT Stahl, SJ Kaufman, JD Fales, HM Moskovitz, J Levine, RL Yarchoan, R TI Reversible inactivation of both HIV-1 and HIV-2 proteases by oxidative modification of an amino acid located at the dimer interface SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, HAMB, Bethesda, MD 20892 USA. PEL, Bethesda, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 830 BP A1454 EP A1454 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500984 ER PT J AU Pak, M Singh, SK Maurizi, M Wickner, S AF Pak, M Singh, SK Maurizi, M Wickner, S TI Molecular chaperone function of ClpA in plasmid P1 RepA activation SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 639 BP A1421 EP A1421 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500795 ER PT J AU Pan, CJ Annabi, B Chou, JY AF Pan, CJ Annabi, B Chou, JY TI Transmembrane topology of glucose-6-phosphatase SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHD, HDB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 794 BP A1447 EP A1447 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500948 ER PT J AU Polakis, P Porfiri, E Albert, I Robbins, P Rubinfeld, B AF Polakis, P Porfiri, E Albert, I Robbins, P Rubinfeld, B TI The adenomatous polyposis coli (APC) tumor suppressor, catenins and cancer SO FASEB JOURNAL LA English DT Meeting Abstract C1 Onyx Pharmaceut, Richmond, CA 94806 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA D4 BP A1302 EP A1302 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500138 ER PT J AU Prasad, R Beard, WA Chyan, JY Maciejewski, MW Mullen, GP Wilson, SH AF Prasad, R Beard, WA Chyan, JY Maciejewski, MW Mullen, GP Wilson, SH TI Residues required for dRP lyase activity in the N-terminal 8-kDa domain of DNA Polymerase beta SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, LSB, Res Triangle Pk, NC 27709 USA. USAM, Mobile, AL USA. UCHC, Farmington, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 244 BP A1352 EP A1352 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500398 ER PT J AU Prasad, R Beard, W Strauss, PP Wilson, SH AF Prasad, R Beard, W Strauss, PP Wilson, SH TI Studies of human DNA polymerase beta dRP lyase activity on abasic site DNA and AP endonuclease-incised abasic site DNA SO FASEB JOURNAL LA English DT Meeting Abstract C1 NEU, Boston, MA USA. NIEHS, LSB, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 241 BP A1352 EP A1352 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500394 ER PT J AU Rabinovitz, M AF Rabinovitz, M TI Uncharged tRNA-phosphofructokinase interaction in amino acid deficiency: One inhibition, several consequences SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 1006 BP A1484 EP A1484 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501160 ER PT J AU Rivera-Nieves, J Moss, J AF Rivera-Nieves, J Moss, J TI Thiols stimulate the nitric oxide-independent linkage of NADH to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 989 BP A1481 EP A1481 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501145 ER PT J AU Romanova, L Alexandrov, L Nguyen, M Nordan, R Trepel, J Mushinski, F AF Romanova, L Alexandrov, L Nguyen, M Nordan, R Trepel, J Mushinski, F TI PKC- and IL-3 regulate actin cytoskeleton rearrangements associated with the effects on cell cycle by two distinct pathways: PKC-delta dominates over IL-3 signal. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. US FDA, CBER, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 543 BP A1404 EP A1404 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500696 ER PT J AU Russian, DA Andrawis-Sorial, V Vogel, P Turner, RE Klivington, DL Angus, CW Kovacs, JA AF Russian, DA Andrawis-Sorial, V Vogel, P Turner, RE Klivington, DL Angus, CW Kovacs, JA TI A surface expressed serine protease is encoded by a multicopy gene family in Pneumocystis carinii. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 704 BP A1432 EP A1432 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500857 ER PT J AU Ruvinov, SB Thompson, J Sackett, DL Ginsburg, A AF Ruvinov, SB Thompson, J Sackett, DL Ginsburg, A TI N-5-(L-1-carboxyethyl)ornithine synthase: Stability and unfolding of a tetrameric enzyme SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NIDR, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 736 BP A1438 EP A1438 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500890 ER PT J AU Santos, AD Padlan, EA AF Santos, AD Padlan, EA TI Does mRNA translation using an alternative initiation site cause Huntington's disease? SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 13 Z9 13 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 81 BP A1322 EP A1322 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500234 ER PT J AU Sata, M Donaldson, JG Moss, J Vaughan, M AF Sata, M Donaldson, JG Moss, J Vaughan, M TI Brefeldin A-sensitive guanine nucleotide-exchange activity of Sec7 domain of yeast Sec7 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 335 BP A1368 EP A1368 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500488 ER PT J AU Schrager, JA Marsh, JW AF Schrager, JA Marsh, JW TI Hiv-1 Nef increases signal of T cell co-stimulatory pathway SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 833 BP A1454 EP A1454 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500988 ER PT J AU Schultz, CJ Noggle, WJ Londos, C AF Schultz, CJ Noggle, WJ Londos, C TI A murine adipose cell cDNA containing the CDP-aminoalcoholphosphotransferase (CDP-AAPT) signature sequence of phospholipid synthesizing enzymes. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 399 BP A1379 EP A1379 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500555 ER PT J AU Sekiya, F Bae, YS Rhee, SG AF Sekiya, F Bae, YS Rhee, SG TI Activation of phospholipase C-gamma by the concerted action of AHNAK-related protein and arachidonic acid in the absence of tyrosine-phosphorylation SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Lab Cell Signaling, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 432 BP A1384 EP A1384 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500584 ER PT J AU Smith, PB Crespi, C Philpot, RM Tiano, H Langenbach, R AF Smith, PB Crespi, C Philpot, RM Tiano, H Langenbach, R TI Flavin dependent monooxygenase expression in mammalian cell lines. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Wake Forest Univ, Med Ctr, Winston Salem, NC USA. Gentest Co, Woburn, MA USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 840 BP A1455 EP A1455 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500992 ER PT J AU Song, BJ Jeong, KS Lee, IJ Soh, Y AF Song, BJ Jeong, KS Lee, IJ Soh, Y TI Cytochrome P450 2E1-dependent formation of acetaldehyde protein adducts SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA, Lab Membrane Biochem & Biophys, Rockville, MD 20852 USA. Korea Res Inst Biosci & Biotechnol, Taejon, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 648 BP A1422 EP A1422 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500802 ER PT J AU Stevens, LM Hanley-Hyde, J Rainey, GJ Taylor, C Henderson, DW Mai, S Mushinski, JF AF Stevens, LM Hanley-Hyde, J Rainey, GJ Taylor, C Henderson, DW Mai, S Mushinski, JF TI MYC-dependent genomic instability at the murine cyclin D2 locus resulting in increased cyclin D2 mRNA and protein. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Genet Lab, NIH, Bethesda, MD USA. Univ Maryland, Cell & Mol Biol Program, College Pk, MD 20742 USA. Univ Manitoba, Manitoba Inst Cell Biol, Winnipeg, MB, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 185 BP A1342 EP A1342 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500341 ER PT J AU Sudhakar, K Sowder, RC Casas-Finet, JR AF Sudhakar, K Sowder, RC Casas-Finet, JR TI Characterization of nucleic acid binding by EIAV nucleocapsid (NC) protein p11 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, SAIC Frederick, FCRDC, Frederick, MD 21702 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 826 BP A1453 EP A1453 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500979 ER PT J AU Suzuki, YJ Shi, SS Day, RM Chedid, M Blumberg, JB AF Suzuki, YJ Shi, SS Day, RM Chedid, M Blumberg, JB TI Homocysteine and other biothiols activate serum response factor. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 1010 BP A1484 EP A1484 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501162 ER PT J AU Sweitzer, SM Hinshaw, JE AF Sweitzer, SM Hinshaw, JE TI GTP hydrolysis induces membrane vesiculation by dynamin SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 348 BP A1370 EP A1370 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500503 ER EF